Ped Nephrocon 2023 Souvenir

Annual Conference of IAP Kerala Nephrology Chapter 1

PATRONS Annual Conference of IAP Kerala Nephrology Chapter ORGANIZING COMMITTEE Dr. Kurian Thomas Dr. T.U. Sukumaran Dr. Sushmabai Org Chairman: Org Co. Chairperson: Org. Secretary: Gen. Convenor: Treasurer Scientific Committee IAP Nephrology Chapter Dr. Manu M. Dr. Joseph Pattani Dr. Sunu John Dr. Thomas P.Varghese Dr. Balachander D. Chairperson President Dr. Suresh S. Vadakkedom Dr. Anil Mathew IAP Nephrology Chapter President, IAP Kerala Secretary, IAP Kerala President, IAP Kottayam Secretary,IAPKottayam NEB Member NEB Member Dr. Balachander D. Dr. Ashraf Secretary Dr. Jose O. Dr. Krishna Mohan Dr. Murari K.S. Dr. Anush S. Dr. Radhika C.R. NEB Member NEB Member Advisors Advisors Advisors Advisors Advisors Dr. Susan Uthup Dr. S. Latha Dr. M.N. Vankedeswaran Dr. Anil Vincent Dr. George F. Moolayil Dr. C Jayakumar Dr. Sebastian Leukose Advisors Advisors Advisors Advisors Scientific Committee: Scientific Committee: Scientific Committee: Dr. Savida P. Dr. S. Omana Dr. Soorya K. K. Dr. Darly S. Mammen Dr. Sreelatha P.R. Dr. P.R. Jayakumar Dr. Jiji Mary Registration: Registration: Registration: Registration: Venue: Venue: Venue: Dr. Nisha V. Krishnan Dr. Divya Davis Dr. Preeja S. Dr. Jayadev Dr. Harikumar G. Dr. Jacob George Dr. Sahala 2 Venue: Venue: Venue: Dr. Bini M. Chandy Dr. Bindhu K.P. Dr. Keerthi K.

Annual Conference of IAP Kerala Nephrology Chapter MESSAGE Dear Friends and colleagues ::: Warm greetings from IAP Kerala 2023:::: At the outset I wish all the best for the NEPHROCON 2023, the state conference of Pediatric Nephrology Chapter Kerala jointly organized by IAP Kottayam , Pediatric Nephrology chapter ,IAP Kerala and ICH Kottayam . It is great proud and privilege for me to write a message in NEPHROCON 2023 Souvenir .First of all I take this opportunity to congratulate team NPHROCON 2023 team lead by Dr.Joseph Pattani ,Dr.Sunnu John ,Dr.Thomas P Varghese ,Dr.Balachandar D ,Dr.Manu M ,Dr.Suresh Vadakkedam Dr.Anil Mathew & Dr.Radhika for arranging an excellent conference with very good academic CME .It will be a good learning experience for all the delegates who are attending this conference because the scientific contents are excellent with State and National faculties . Jai Hind Jai IAP Jai NNF Dr. Jose. O President IAP Kerala 2023 3

Annual Conference of IAP Kerala Nephrology Chapter MESSAGE Dear Senior Paediatricians, deligates and friends, As the organizing chairman, I am extremely happy to welcome you all to Kottayam for PED NEPHROCON 2023 on June 4th Sunday. This is the annual conference of IAP Kerala Nephrology Chapter. I am sure all pediatricians are very much interested in nephrology chapter, as it is very useful in our day today practice. The organizing committee is working hard for making this event a grant success and memorable. The topic selected for the conference are very useful and didatic. I cannot but salute Dr. Thomas Varghese the orginizing secretory, for his sinereity, hard work and enthusiasam. I am sure out of his sincere effort more than 100 deligates have already registered. My greetings goes to Chapter President Dr. Anil Mathew, Secretory Dr. Radha C.R. My thanks goes to Dr. T.U. Sukumaran, Dr. Jayakumar, Dr. Balachandran, Dr. Darley Mamman, Dr. Murari, Dr. Anush, Dr. Sahila and all members in the organizing team. My personal respect and greetings goes to each one of you; Enjoy our hospitality; Wishing conference and organizing team very best Dr. Joseph Pattani Organizing Chairman 4

Annual Conference of IAP Kerala Nephrology Chapter MESSAGE Dear colleagues, friends and all IAP members, IAP Kottayam along with Paediatric Nephrology Chapter Kerala, ICH Kottayam proudly presents NEPHROCON-2023. Nephrocon 2023 is an excellent academic fiesta with the best academic topics which is needed for our day to day practice, We assure you a wonderful learning experence and topics dealt by the most eminent faculties. We extend a warm welcome to all the delegates to Kottayam on June 4th 2023. Dr. Sunu John Co-chairperson Nephrocon 5

Annual Conference of IAP Kerala Nephrology Chapter MESSAGE Dear seniors and friends, IAP Kottayam has been organising different subspeciality conferences since 2012. This is the 12th different subspeciality conference happen- ing at Kottayam and that too majority of the conferences at our Paediatric House. I congratu- late Dr Thomas Vargese, who is doing all the work single handedly and making the Ped Nephrocon a grand success. Dept of Pediatrics, ICH Kottayam under the leadership of Dr Darly, Dr Jayaprakash KP, Dr Suresh Vadakkedom and Dr Nisha has been whole heartedly supporting him. I thank the stalwarts of IAP, Dr TU Sukumaran, Dr Jayakumar C, Dr Sushama Bai and Dr George F Moolayil for the guidance. I wish all success for the conference and sure the academics by the senior and young faculty of PedNephrology will enlighten our members. Regards Dr D BALACHANDAR NEBM 2023 Convenor Ped Nephrocon 6

Annual Conference of IAP Kerala Nephrology Chapter MESSAGE Dear Colleagues and Esteemed Members of IAP Kottayam. Pediatric Nephrology holds a significant place in our medical landscape of pediatric care. This Souvenir serves as a testament to the tireless efforts made by our pediatric nephrologists and all healthcare professionals involved in the care of our pediatric patients with renal conditions. Your commitment to advancing the understanding, diagnosis, and treatment of kidney diseases in children has positively impacted countless lives, offering hope and a better future for our young ones. In this rapidly evolving healthcare landscape, it is vital for us to stay updated with the latest advancements, research breakthroughs, and treatment modalities. Let this Souvenir serve as a platform for sharing experiences, presenting cutting-edge research, and fostering collaborations that will further enrich our collective knowledge and drive us towards excellence in pediatric nephrology. On behalf of the Indian Academy of Pediatrics, Kottayam Branch, I extend my deepest gratitude to all the contributors, authors, and organizers who have played a pivotal role in making this Souvenir a reality. Your valuable insights, scientific contributions, and unwavering support have made a lasting impact on the field of pediatric nephrology. I congratulate each and every one of you for your remarkable achievements and encourage you to continue striving for excellence in the field of pediatric nephrology. Together, let us work towards a future where every child receives the best possible care for kidney- related conditions, ensuring a healthier and brighter tomorrow. With warm regards, Dr. Murary K S President Indian Academy of Pediatrics, Kottayam Branch 7

Annual Conference of IAP Kerala Nephrology Chapter MESSAGE The members of the organizing committee and myself are very proud to present the annual conference of IAP Kerala Nephrology Chapter “Ped-Nephrocon-2023” on 4th June 2023 at Paediatric House Panampalam, Kottayam. The hard work and dedication of all the members of the organizing team doing the preparation of the conference is highly appreciated without the event would not have become possible. Thanks and acknowledgment due to each and everyone in the Ped-Nephrocon - 2023 team. My personal respect and greetings goes out to all of you. Dr Anush S. Kudakasseril Secretary, IAP Kottayam 8

Annual Conference of IAP Kerala Nephrology Chapter MESSAGE It gives me immense pleasure to see that Ped Nephrocon 2023 at Kottayam is bringing out a souvenir that contains the conference proceedings and academic information. I thank all the faculty for sharing the much needed academic content. Congratulations to the organizing team, and I wish all the delegates a wonderful learning experience.. With regards.. Dr. Suresh S. Vadakedom Chairperson Scientific Committee 9

Annual Conference of IAP Kerala Nephrology Chapter MESSAGE Greetings from Nephrology Chapter-IAP-Kerala. Pediatric Nephrology as a subspeciality in Kerala is making rapid strides under the expert guidance of our present National President, Dr Susan Uthup. It gives me great pleasure to felicitate the organizers of PED NEPHROCON 2023-State Annual Pediatric Nephrology Conference being held in Kottayam on June 4th 2023. This conference has been arranged thoughtfully to discuss and update the practicing Pediatricians and young residents in Pediatrics, the common problems faced while treating children with diseases of kidney and urinary tract. On behalf of Nephrology Chapter- IAP-Kerala, Dr Radhika C Radhakrishnan and I sincerely thank IAP Kottayam and Institute of Child Health Kottayam for taking the appreciable efforts. We wish all success in this earnest endeavor. Dr Anil Mathew President IAP Nephrology Chapter 10

Annual Conference of IAP Kerala Nephrology Chapter SECRETARY REPORT Dear Friends Greetings from the world of Pediatric Nephrology. It gives me immense pleasure and pride to present to you the annual conference of IAP Pediatric Nephrology chapter at Kottayam on 4th June 2023. Care and outcomes in children with kidney diseases have improved leaps and bounds in recent times. A significant reason for this improvement is the improved knowledge of these diseases among practicing pediatricians. Early detection, prompt institution of treatment measures and availability of dialysis have also been very important. Pediatric Nephrologists, though a small breed, have contributed significantly to better disease outcomes. But, given the rarity of these specialists, it is imperative that pediatricians are also sensitised to management of common nephrology conditions in children. It is for this reason that we have selected commonly encountered problems for discussion in this CME. We hope you enjoy our hospitality and participate actively in the scientific deliberations. I extend my warm regards to all faculty and delegates and gratitude to IAP Kottayam for making this event a success. Radhika C Radhakrishnan Secretary IAP Nephrology Chapter 11

Annual Conference of IAP Kerala Nephrology Chapter CONTENTS Editorial ...................................................................................... 13 Dr. Thomas P. Varghese UTI in Children ............................................................................14 Dr. Jayaprakash K.P. APPROACH TO HEMATURIA IN CHILDREN ........................................ 19 Dr. Anil Mathew ACUTE KIDNEY INJURY (AKI) IN CHILDREN ....................................... 22 Dr. Sabarinath Antenatally detected HYDRONEPHROSIS ......................................... 25 Dr. Naveen Viswanath ENURESIS IN CHILDREN .................................................................28 Dr. Anil Mathew FUNCTIONAL VOIDING ISSUES in children – An overview ................... 31 Dr. Naveen Viswanath NEPHROLITHIASIS in children ......................................................... 34 Dr. Christy Cathreen Thomas Uncomplicated Nephrotic Syndrome in children ................................... 37 Dr. Radhika C.R. RICKETS - EVALUATION AND MANAGEMENT ....................................... 40 Dr. Hareesh.K.G MD,DCH,DM Urinalysis ................................................................................................ 44 Dr. Radhika C.R. 12

Annual Conference of IAP Kerala Nephrology Chapter FROM THE ORGANIZING SECRETARY AND EDITOR On behalf of the organizing team of “Ped Nephrocon - 2023”, I welcome you all for this annual pediatric nephrology conference. I am really honoured to be part of this team as organizing secretary and the editor of the souviner. We have tried our best to select the academic topics which are of importance in the day to day practice. I am thankful to all the members of IAP Kottayam for giving me all possible supports. Special thanks to our great teachers Dr. C. Jayakumar, Dr. T.U. Sukumaran, NEB member Dr. D. Balachander, IAP state president Dr. O. Jose, State Secretary Dr. Krishna Mohan, IAP Kottayam President Dr. Murari K.S., Secretary Dr. Anush S., Organizing Chairperson Dr. Joseph Pattani, Organizing co- chairperson Dr. Sunu John, Dr. Manu M., Dr. Darly Mammen, Dr. Sahala, Dr. Nisha V. and all the faculty of ICH Kottayam. With warm regards Dr. Thomas P. Varghese Organazing Secretary and Editor Ped-Nephrocon - 2023 13

Annual Conference of IAP Kerala Nephrology Chapter Dr. Jayaprakash K.P. Associate Professor Paediatrics ICH, GMC KOTTAYAM UTI in Children U rinary tract infection (UTI) is one of the understood. Most UTIs are ascending infections most common bacterial infectionsin that start with periurethral colonization; childhood. In the first year of life, it is more hematogenous spread occurs primarily in common in boys (3.7%), as compared to girls, (2%) debilitated, and after infancy, it is significantly more prevalent in girls. obstructed, or immunocompromised patients, and these are mostly fungal and staphylococcal The risk of UTI recurrence in the first 6 to12 infections.13 months after the initial UTI is <“12% to 30%.4,5 Besides sex, other significant risk factors for UTI The virulence of uropathogenic E coli is largely are bladder-bowel dysfunction (BBD); congenital influenced by the presence of P fimbriae, also anomalies of kidneys and the urinary tract (CAKUT), known as pyelonephritis associated pili, and including vesicoureteral reflux (VUR); and the lipopolysaccharide.The binding of the P fimbriae circumcision status in young boys. toepithelial cells is mediated by the tip adhesin PapG. Bacterial lipopolysaccharide is important for Approximately 85% to 90% of UTIs are caused the initiation of tissue inflammation. by Escherichia coli. Other common organisms include Klebsiella,Proteus, Enterococcus, and The fibrosis and scarring that follows is initiated Enterobacter species.9–11 Organisms such as by macrophages and conducted by neutrophils. Pseudomonas, group B Streptococcus,and Monocyte chemoattractant protein-1, which is Staphylococcus aureus are usually associated with secreted by kidney epithelial cells,recruits CAKUT, genitourinary surgery, a foreign body (eg, monocytes at the site of infection. Monocytes catheter),or recent antibiotic treatment, whereas differentiate into2 groups of macrophages: infection with urea-splitting organisms (eg, proinflammatory monocytes that kill the pathogen Proteus) is associated with stone formation.8,12. by secreting inflammatory cytokines (such as Prompt diagnosis and treatment are important for interleukins and tumor necrosis factor a) as well as the prevention of acute complications as well as cytotoxic reagents (such as nitric oxide synthase renal scarring. and reactive oxygen species) and anti-inflammatory monocytes that terminate the inflammatory PATHOGENESIS OF ACUTE response. PYELONEPHRITIS AND RENAL SCARRING Depending on the severity of kidney damage, The pathogenesis of acute pyelonephritis (APN) the latter also induces kidney fibrosis through and renal scarring is complex and not fully transforming growth factor b. The proinflammatory response, which is necessary for killing the 14

Annual Conference of IAP Kerala Nephrology Chapter pathogen, also damages the surrounding tissue, insiblings or parents, and recent infections or causing tissue ischemia, tubular cell death, and antibiotic treatment should be ascertained. reperfusion injury. The fibrosis and scarring that Relevant signs on abdominal examination follows is initiated by macrophages include distention, presence of a mass or palpable stool, flank or suprapubic tenderness, RISK FACTORS FOR UTI and/or a palpable bladder, particularly after voiding The important risk factors for UTI in children are Urine specimen: In non–toilet trained children, female sex (or uncircumcised infant boy), younger urine collection method has a profound significance age, high-grade VUR,and instrumentation of the for diagnosis of UTI. Urine specimen in such urinary tract (particularly indwelling bladder children should be collected preferably by ureteral catheterization). Other risk factors for UTI in older catheterization or suprapubic bladder aspiration children andadolescents include the presence of Other methods like touching the the kidney stones, sexual activity, and diabetes. Genetic suprapubic area is stimulated by using a gauze factors also influencethe occurrence of UTI. soaked in cold fluid and the voided midstream urine Administration of an antibiotic may increase the is caught in a sterile cup. Regardless of the risk of UTI by changing periurethralmicroflora. technique, contamination of voided specimens from infants isa significant concern, particularly for A calculator was recently developed to help girls and uncircumcised, young boys. clinicians estimatethe probability of UTI in febrile A microscopic urinalysis has only marginally infant sat the bedside (https://uticalc.pitt.edu). It better accuracy than the dipstick. Until better and is based on risk factors that include age ,12 months more accurate biomarkers for UTI become ,female sex (or uncircumcised boy),maximum available, the limitation of bedside UTI screening temperature .39°C, and the absence of another should be kept in mind and used only in conjunction source for fever. with clinical assessment. Urine culture: The acceptable colony count RISK FACTORS FOR RENAL SCARRING threshold for a urine culture positive for UTI depends onits collection method. It is 50 000 A number of risk factors are associated with colony-forming units(CFUs)/mL for samples acquired renalscarring due to APN. These include obtained by catheterization, 100 000 for samples a high grade of VUR (grades .2 and particularly obtained by clean catch grades 4 and 5), duration of fever of 72 hours before antibiotic initiation, recurrent UTI, and organisms COMMON ERRORS IN THE DIAGNOSIS OF other than E coli. UTI Polymorphisms of the HSPA1B gene of HSP72 • Contaminated urine specimen: A diagnosis of protein were found to be associated with UTI based on contaminated urine specimen renalscarring, whereas variants of thetoll-like may lead to unnecessary antibiotic treatment receptor 4 gene were associated with renal scarring or delayed treatment in those with true UTIs. in another study. The contamination rates of bag urine specimens can be as high as80%.34,54 The 2 most DIAGNOSIS OF UTI commonsources of urine contamination are faeces and skin that it may come in contact with A targeted history and physical examination and while passing through the vagina or under the positive urinary findings are essential for an foreskin. accurate diagnosis of UTI. Presence of 10 per high-power field squamous • History and physical examination: In older, epithelial cells onurinalysis, insignificant bacterial verbal children, important findings include colony count, or the presence of 2pathogens on dysuria, urgency and/or frequency, abdominal urine culture in midstream urine specimen is or flank pain, and new-onset incontinence. In suggestive of contamination. contrast, signs and symptoms of UTI in infancy are nonspecific, and fever may be the only symptom, although neonates may present with hypothermia. History of constipation, UTI 15

Annual Conference of IAP Kerala Nephrology Chapter Growth of non uropathogens such as renal scarring after febrile UTI is <“15% and ranges Lactobacillus, Corynebacterium,viridans from 3% after the first streptococci, or coagulase negative staphylococci such as Staphylococcus epidermidis are considered UTI to 29% after .3 febrile UTIs. In the as contaminants in children.3 Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial, only <“7% of Asymptomatic bacteriuria (ABU): Colonization children developed new scarring during the of the bladder in the absence of an inflammatory reaction occurs at all ages, including infants and study period, and this was primarily among children. ABU is more common in girls and children with grade 4 VUR.29In most children, renal generally involves Gram negative bacteria, such as scarring may not be clinically significant, but it may E coli. Its reported incidence is <“1% to 3%,and it cause hypertension and usually resolves spontaneously in a few months to proteinuria and a progressive decline in renal a couple of years, although in some girls, it may function in those with bilateral significant scarring. persist for much longer Delayed initiation of antibiotic treatment is Antibiotic treatment is not recommended for associated with increased risk of scarring, with the otherwise healthy individuals with ABU because its odds of new renal scarring 74% lower among use promotes antimicrobial resistance and other children whose treatment started within 24 hours adverse effects,including the possibility of an of onset of fever, compared with those whose increased risk of symptomatic UTI treatment started after 72 hours of fever Sterile pyuria: Sterile pyuria may occur in RENAL IMAGING AFTER UTI association with infections such as partially treated UTI,appendicitis, tuberculosis, or fungal, viral, or Renal imaging after UTI is driven primarily by a parasitic infections.It can also occur with need to rule out an underlying renal or urinary tract immunologic conditions, such as acute anomaly or the assessment of renal injury.Renal glomerulonephritis, systemic lupus erythematosus, Bladder Ultrasound and Kawasaki disease, or with a foreign body,kidney stones, interstitial nephritis, analgesic nephropathy, The purpose of renal bladder ultrasound (RBUS) and papillary necrosis is to evaluate for urinary tract anomalies, including obstruction, renal structural anomalies, COMPLICATIONS OF UTI nephrolithiasis or calcification, or an abdominal mass.RBUS is a less sensitive imaging modality for Acute complications of UTI are similar to those the diagnosis of VUR, and normal RBUS does not associated with any febrile illness in a young child. rule out high-grade VUR. Particular findings on These include dehydration, electrolyte RBUS that may indicate a higher probability of VUR abnormalities, and febrile seizures.Renal include ureteral dilation, renal parenchymal complications of APN are uncommon in otherwise changes, and bladder abnormalities. RBUS cannot healthy children but may include renal be used to accurately diagnose patients with APN or renalscarring.76–78 The 2011 AAP guidelines abscess or complete occlusion of a pre existing, recommend RBUS be performed in all infants (2– partial uretero pelvic junction obstruction. Acute 24 months) with febrile UTI.34 Older children with kidney injury may occur because of dehydration or recurrent UTIs may also benefit from an RBUS. The an administration of RBUS can be deferred until after resolution of the UTI but should be considered during the acute a nonsteroidal anti-inflammatory drug, such as episode if the illness seems unusually severe or if ibuprofen. Nonsteroidal anti-inflammatory drugs high fevers persist beyond 48 to 72 hours of may also diminish renal function by causing treatment34; such atypical course suggests papillary necrosis or interstitial nephritis. The latter complications, such as renal abscess or occult can also be caused by the antibiotic that is being obstruction, that are well-seen on RBUS. A deferred used for UTI treatment. Urosepsis may occur, RBUS permits more accurate interpretation of the particularly with Gram negative infections anatomy, without potential for false-positive findings associated with tissue edema or The most consequential long-term complication of APN is renal scarring.The reported relevance of 16

Annual Conference of IAP Kerala Nephrology Chapter endotoxin-induced dilation. organisms are resistant. At present, the vast majority of uropathogens are sensitive to third DMSA Renal Scan generation cephalosporins. DMSA scan is the current gold standard for Most uropathogens are resistant to amoxicillin, assessment of renal parenchymal injury in a child and its use should therefore be avoided. with a history of febrile UTI. It is more sensitive for renal scarring than RBUS, which misses a Many studies have revealed that children aged substantial proportion of such cases.However, most .2 months can be safely managed with oral children with first febrile UTI do not need a DMSA antibiotics;thus, hospital admission for treatment renal scan. should be avoided unless the child is unable to tolerate oral antimicrobial therapy. Fever resolves It may be considered in children with recurrent in 68% of children in the first 24 hours and in 92% febrile UTIs or renal parenchymal abnormalities on by 72 hours. RBUS. Demonstration of renal scarring increases the risk for further renal deterioration. Findings of If fever persists beyond 72 hours, the clinician renal scarring may influence surgical decision- should reevaluate the diagnosis and decide making in patients with surgically correctable whether an RBUS is emergently needed to rule out conditions (eg, VUR). Cortical defects on DMSA scan renal abscess. Antibiotic treatment should be performed during or shortly after APN may be due started within 48 hours of fever onset because to pre-existing lesions (either acquired or delayed treatment increases the risk of renal congenital) or to the acute inflammatory reaction scarring. Oral antibiotic therapy for 7 to 10 days is associated with APN. adequate for uncomplicated febrile UTI presumed to be APN that responds well to the treatment. In A delayed DMSA scan at 4 to 6 months allows a recent study, researchers reported that ininfants the acute inflammatory reaction to subside, at aged ,60 days with bacteremic UTI, #7 days of which point any persistent cortical defects can be parenteral antibiotic therapy may be as safe and assumed to represent permanent renal scarring, effective as conventional,longer-duration treatment. Voiding Cystourethrogram In the last decade, the practice patterns have ROLE OF ANTIMICROBIAL PROPHYLAXIS dramatically shifted A VCUG should be considered after first UTI in children with abnormal RBUS, The effectiveness of antimicrobial prophylaxis atypical causative pathogen, in the prevention of UTI recurrence has been complex clinical course, or known renal studied extensively. The RIVUR trial revealed that scarring.34,81,82,84 Patients with a family history trimethoprim-sulfamethoxazole prophylaxis of VUR or CAKUT can also be considered for VCUG reduced the risk of UTI recurrence by 50%. Similar after first febrile UTI. The inter observer variability results were reported by another placebo in VUR grading must be kept in mind while making controlled,double-blind (PRIVENTstudy) trial. clinical decisions Combined results of the Routine follow-up urinalysis and culture (so- called proof-of-cure tests) after the resolution of RIVUR and the Careful Urinary Tract Infection UTI symptoms are not necessary unless clinically Evaluation (CUTIE) studies revealed that toilet- indicated rained children with VUR and BBD exhibit the greatest benefit from antimicrobial prophylaxis. ANTIBIOTIC TREATMENT Many other studies quote no benefit from prophylaxis The choice of an antimicrobial for empirical therapy should be guided by the local, resistant No study has demonstrated any beneficial effect patterns of uropathogens. However, in general in of antimicrobial prophylaxis for the prevention of young febrile children, in whom the chance of renal renal scarring,although one must add that none of involvement is high, itis prudent to choose an these studies were powered to evaluate renal antimicrobial to which only a small proportion of scarring as a primary study end point, and even a recent meta-analysis was likely underpowered to reveal an effect 17

Annual Conference of IAP Kerala Nephrology Chapter Antibiotic resistance is a major risk of long-term increased oral fluid helps flush bacteria from the prophylaxis and, hence,should be used bladder,prompts frequent urination, and alleviates selectively.106,109,110In cases of febrile UTI and constipation, there is limited evidence that it is VUR, the American Urological Association effective in preventing UTIs. recommends continuous antibiotic prophylaxis in children aged,1 year and a selective approach in In uncircumcised boys, gentle, daily retraction older children based on patient age, severity of and cleaning should be performed; inboys with VUR, recurrence of UTI,presence of BBD, and renal phimosis, topical corticosteroid ointment or cortical anomalies. circumcision may be necessary to prevent UTI recurrence. There is no evidence in children to PREVENTION OF RECURRENT UTI recommend cranberry juice for the prevention of UTIs. In a systematic review of studies in adults, Recurrent UTI can be prevented by preventing researchers concluded that given the evidence, constipation and avoidance of urine withholding cranberry juice cannot currently be recommended behavior in toilet-trained children.Although for the prevention of UTIs. Reference 1. Mattoo TK, Shaikh N, Nelson CP. Contemporary Management of Urinary Tract Infection in Children. Pediatrics. 2021;147(2): e2020012138 2. Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, Keren R.Recurrent urinary tract infections in children: risk factors and association with prophylactic antimicrobials. JAMA. 2007;298(2):179–186 3. Dai B, Liu Y, Jia J, Mei C. Long-term antibiotics for the prevention of recurrent urinary tract infection in children: a systematic review and meta-analysis. Arch Dis Child. 2010; 95(7):499–508 4. Shaikh N, Ewing AL, Bhatnagar S, Hoberman A. Risk of renal scarring in children with a first urinary tract infection: a systematic review. Pediatrics. 2010;126(6):1084–1091 5. Roberts KB; Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics. 2011;128(3):595–610 18

Annual Conference of IAP Kerala Nephrology Chapter Dr. Anil Mathew Ped. Nephrologist AIMS, Kochi APPROACH TO HEMATURIA IN CHILDREN H ematuria is defined by the presence of including postinfectious glomerulonephritis and an increased number of red blood cells IgA nephropathy, malignancies (eg,Wilms (RBCs) in the urine. It can either be tumor), and drug-induced hemorrhagic cystitis. visible to the naked eye (gross) or apparent only upon urinalysis (microscopic). Gross History often provide clues that point toward hematuria although an uncommon occurrence a specific diagnosis. in children, is nevertheless a disturbing finding for both the affected child and his/her family. • Recent vigorous exercise or trauma. However, red or brown urine can be due to • History of new onset of incontinence, causes other than blood including pigments dysuria, frequency, or urgency from drugs (eg, phenazopyridine, rifampicin) or foods (eg, beets), metabolites associated with • Radiation -History of unilateral flank pain that other clinical conditions (eg, porphyria) or free may radiate to the groin suggests obstruction hemoglobin or myoglobin. caused by a calculus or blood clot. In comparison, flank pain without radiation but Urinary dipstick test for blood if positive, may with fever, dysuria, and frequency and/or indicate presence of blood, or free hemoglobin urgency is suggestive of UTI. or myoglobin. A negative test eliminates these etiologies. After urine centrifugation, if sediment • Timing- Initial hematuria (onset of urination) is red/brown, then the etiology is most likely usually suggests urethral bleeding; blood and if the supernatant is red/brown with continuous bleeding throughout urination colourless sediment, it is free hemoglobin or may occur from bleeding in the bladder, myoglobin. Microscopic examination confirms ureter or kidneys; and terminal bleeding (at the presence of red blood cells (RBCs). the end of urination) is indicative of bladder disease. GROSS HEMATURIA • Colour -Glomerulonephritis is associated The most commonly identified etiologies for with brown urine. Bleeding from the lower gross hematuria in children are urinary tract urinary tract is suggested by pink or red urine infection (UTI), irritation of the meatus or and may be accompanied by blood clots. perineum, and trauma. Other less common causes include nephrolithiasis, sickle cell Examination should include disease/trait, coagulopathy, glomerular disease • Measurement of blood pressure (BP) – Hypertension may be seen in glomerular disease and hypotension in patients with significant bleeding due to trauma. 19

Annual Conference of IAP Kerala Nephrology Chapter • Assessment for edema and recent weight Cystoscopy — Rarely indicated for gain may be seen in patients with glomerular hematuria in children. It should be reserved for disease. the rare child with a bladder mass noted on ultrasound, persistent symptoms suggestive of • Skin examination for rash or purpura ;SLEor inflammatory cystitis, or those with urethral IgA vasculitis abnormalities due to trauma. • Examination of the genitals (looking for MICROSCOPIC HEMATURIA penile urethral meatal erosion or female introitus pathology). Can be persistent or transient • Evaluation for abdominal discomfort or Persistent hematuria — The most common masses (eg, Wilms tumor). causes of persistent microscopic hematuria include glomerulopathies, hypercalciuria, and nutcracker Urinalysis syndrome • Glomerular bleeding – Signs of glomerular IgA nephropathy — Immunoglobulin A (IgA) bleeding include red cell casts nephropathy is diagnosed by kidney biopsy with (pathognomonic for glomerular disease), mesangial IgA deposits on immunofluorescence dysmorphic RBCs, and brown, cola-colored study. urine. The presence of more than 30 percent dysmorphic RBCs or of more than 5 percent Alport syndrome — Alport syndrome is a of “acanthocytes” is highly suggestive of hereditary disorder often associated with high- glomerular hematuria. frequency sensorineural hearing loss (SNHL), ocular abnormalities, and progressive kidney failure Symptomatic hematuria further evaluation: The genetic abnormality in these patients involves the genes coding for type IV collagen. Classic X- • Trauma history – Obtain a computed linked Alport syndrome typically affects males. tomography (CT) scan of the abdomen and Hemizygous carrier females can also have pelvis to determine the source of blood. hematuria, but less frequently have progressive kidney disease. • Signs or symptoms of UTI –An appropriately collected urine culture is obtained. Thin basement membrane disease — (benign Adenovirus should be considered as a familial hematuria) is diagnosed in children with a potential etiology if urinary symptoms and family history of hematuria and no history of urinalysis are suggestive of infection, but the progressive kidney disease. TBM disease is an culture is negative. autosomal dominant condition involving genes for type IV collagen and usually, it is the heterozygous • Symptoms of nephrolithiasis –. Renal form of autosomal recessive Alport syndrome. ultrasonography/ Abdominal plain films/ Spiral CT scan Poststreptococcal glomerulonephritis . There is usually an antecedent history of a group A • Signs or symptoms suggestive of glomerular beta-hemolytic streptococcal (GAS) skin or throat disease –evaluation includes serum infection. The diagnosis is based on transient creatinine, complete blood count, lowering of complement C3 levels +/- positivity of complement component 3 (C3), complement anti-factor B antibodies component 4 (C4), and serum albumin. Other tests to consider based upon the Hypercalciuria — Hypercalciuria, defined in history and the physical examination include children as a urine calcium/creatinine ratio >0.2 ASO titer and/or streptozyme testing to (mg/mg) in children older than six years of age, detect poststreptococcal glomerulonephritis, and ANA to look for lupus nephritis. Nephrolithiasis and nephrocalcinosis — # Patient referral to pediatric nephrologist is Nutcracker syndrome — results from the recommended if there is evidence of significant compression of the left renal vein between the aorta renal disease. and proximal superior mesenteric artery often presents in children with asymptomatic hematuria. The diagnostic evaluation depends upon the 20

Annual Conference of IAP Kerala Nephrology Chapter threetypes of clinical presentations of substantial or progressive disease. • Asymptomatic isolated microscopic Symptomatic microscopic hematuria - hematuria Most challenging because it encompasses a wide range of diseases with varying clinical • Asymptomatic microscopic hematuria with presentations. The clinical manifestations may proteinuria be nonspecific (eg, fever, malaise, weight loss), extrarenal (eg, rash, purpura, arthritis), or • Symptomatic microscopic hematuria related to kidney disease (eg, edema, hypertension, dysuria, oliguria). The presence Asymptomatic isolated microscopic of nonspecific or extrarenal manifestations hematuria — The most common presentation suggests a systemic process such as lupus of microscopic hematuria. It is usually transient nephritis or IgA vasculitis. Kidney causes of and not associated with significant clinical symptomatic microscopic hematuria include disease. Evaluation including BP and urinalysis glomerular or interstitial diseases of the kidney, should be performed weekly for two weeks. A lower urinary tract disease, nephrolithiasis, thorough evaluation should be undertaken only tumors, and vascular disease. if the patient becomes symptomatic or develops hypertension, gross hematuria, or proteinuria. If isolated hematuria persists, obtain a urine Indications for kidney biopsy — culture. If the patient remains asymptomatic and the urine culture is negative, continue to • evidence of substantial or progressive observe the patient every three to six months disease as manifested by an elevation in the including physical examination with blood S.creatinine, significant proteinuria, and pressure measurement and urinalysis. hypertension If the asymptomatic isolated hematuria • persistent glomerular hematuria, in whom persists for one year, subsequent evaluation the parents are worried about the diagnosis should be performed including urine and prognosis. calcium:creatinine ratio for hypercalciuria/ testing parents and siblings for hematuria to • microscopic hematuria and a family history detect possible thin basement membrane of kidney failure in early adulthood in a first- disease or hereditary nephritis/ hemoglobin order relative. analysis / Doppler ultrasonography Patients with clear evidence of Asymptomatic microscopic hematuria poststreptococcal glomerulonephritis represent and proteinuria — Significantly less common an exception to these general than isolated hematuria. Evaluation of these recommendations, since gradual spontaneous patients starts with measurement of serum recovery is the rule, although proteinuria may creatinine and quantification of proteinuria. If gradually return to normal over many years. in a first morning urine specimen the UPCR is >0.2 mg protein/mg creatinine, the patient Large centre studies demonstrate that should be referred to a pediatric nephrologist kidney biopsy findings in most cases of isolated since it is likely that there is significant kidney microscopic hematuria are normal or are disease. consistent with TBM disease, a benign condition. Although a significant number of If protein excretion is less than the above patients with isolated microscopic hematuria values, the patient should be reevaluated in have IgA nephropathy, these patients have a two to three weeks. If the hematuria and minimal risk of disease progression as long as proteinuria have resolved, no further evaluation they do not develop proteinuria. In contrast, is needed. If proteinuria is persistent, the patient patients with persistent hematuria and should be referred to a pediatric nephrologist. proteinuria are more likely to have significant Kidney biopsy is considered if there is evidence kidney disease. 21

Annual Conference of IAP Kerala Nephrology Chapter Dr. Sabarinath Ped Nephrologist St. Thomas hospital, Chethipuzha ACUTE KIDNEY INJURY (AKI) IN CHILDREN A cute Kidney Injury(AKI) has supplanted the term acute Renal failure to allow earlier detection of renal dysfunction. Acute Kidney Injury is characterized by abrupt decline in kidney function presumed to have occurred in last 7 days which occurs in 30-40% of children in pediatric intensive care units. It results in decrease in glomerular filtration rate(GFR), inability to regulate acid and electrolyte and excrete wastes and fluid. Pediatric AKI has been associated with higher morbidity and mortality and is a risk factor for hypertension and chronic kidney disease in the long term… Definition AKI definition was standardized using the “Risk, Injury, Failure, Loss, End “ criteria in 2004 based on GFR, creatinine values and urine output. It was later modified in 2007 using Acute Kidney Injury Network criteria( AKIN), in which loss and endstage categories were eliminated. In 2012, The Kidney Disease; Improving Global Outcomes(KDIGO) criteria was established for AKI in adults and children, based on elevation in creatinine levels and/or decrease in urine output. KDIGO CLASSIFICATION FOR AKI IN CHILDREN 22

Annual Conference of IAP Kerala Nephrology Chapter Etiology of pediatric AKI There’s a change in trend from primary kidney diseases to secondary renal diseases as the cause of AKI in children which differed from region to region.. The etiology has been conventionally classified into prerenal, intrinsic renal and postrenal categories. In children, the main risk factors for developing AKI are administration for nephrotoxic drugs, severe sepsis with shock, cardiopulmonary bypass surgery, use of vasopressors with invasive ventilation, fluid overload, stem cell transplant and tumor lysis syndrome. Spurious causes of elevated urea and creatinine like high protein intake, GI bleeding, catabolic states like fever, steroids and burns , extreme exercise and drug intake like trimethoprim and cemitidine should be ruled out. Thorough history taking, physical examination and proper evaluation of blood and urine biochemistry is important to find out the etiology , early detection of complications and to rule out the possibility of chronic processes like growth retardation, anemia, rickets etc…..Prerenal AKI occurs due to inadequate systemic and /or renal circulation.. Both prerenal and post renal categoriies if prolonged can lead to intrinsic renal failure. 23

Annual Conference of IAP Kerala Nephrology Chapter Diagnosis Prerenal AKI can be diagnosed usually when it gets resolved with restoration of renal perfusion.. If renal dysfunction persists or worsens despite this, ischemic acute tubular necrosis should be suspected. A comprehensive review may be needed for the evidence of nephrotoxic agent intake. Risk for pigment induced AKI like excess drug abuse, drug abuse, crush injury etc. may be looked into. Post renal AKI may be symptomatic only when the obstruction is complete and there is anuria. Suprapubic or flank pain may occur due to acute distention of the bladder or renal collecting system. Renal function improves following the relief of obstruction. Laboratory analysis Urine analysis is an inexpensive ,useful and essential diagnostic tool for the diagnosis eventhough there is poor corelation between the severity of AKI and urine analysisfindings. Muddy brown casts and tubular epithelial casts are characteristic of ischemic or nephrotoxic ATN in association with microscopic hematuria and mild proteinuria( < 1 g/day). RBC casts almost always indicate glomerular disease. Urine analysis in prerenal AKI will show FENa< 1%, urine sodium <10 mEq and SG> 1.018 while in ischemic or nephrotoxic renal injury, FENA>1%, urine Na>20 mEq/L, SG 1.010. Biomarkers in AKI In AKI, serum creatinine does not increase until GFR has moderately decreased which provides false sense of security and leads to late detection of renal damage. More sensitive biomarkers will sense realtime kidney damage. Various biomarkers useful for early detection of AKI include: • Serum cystatin C • Neutrophil gelatinase-associated lipocalin • Interleukin 18 • Kidney injury molecule 1 • Liver-type Fattyacids binding protein Treatment of pediatric AKI Real time cause directed interventions are very beneficial. Ongoing damage control measures like treatment of sepsis, avoiding exposure to nephrotoxic agents, optimizing fluid administration, maximizing nutrition etc may be encouraged. Low dose dopamine or fenoldopam use did not show much promising results. Only proper dose of preload fluids administration is necessary and the fluid overload is independently associated with mortality in children. Use of diuretics to enhance urine output did not improve outcome Adequate energy and protein supplementation has been advocated in critically ill children ( 2-3 g/kg /day protein for children aged 0-2 years) Renal replacement therapy in the form of hemodialysis, peritoneal dialysis or CRRT is useful for fluid overload resistant to diuretics, metabolic abnormalities like acidosis and electrolyte abnormalities like hyperkalemia. Prevention Preventive measures include avoiding exposure to nephrotoxic agents, use of hemodynamic monitoring, therapeutic monitoring of nephrotoxic agents, assuring adequate hydration etc….. 24

Annual Conference of IAP Kerala Nephrology Chapter Dr. Naveen Viswanath Ped Surgeon, AIMS Kochi Antenatally detected HYDRONEPHROSIS F etal hydronephrosis is a common finding on There is no consensus on the most appropriate antenatal ultrasound. In most cases, renal grading criteria for the diagnosis of fetal pelvic dilation is a transient physiologic hydronephrosis. In general, the possibility of having state, however, congenital anomalies of the kidney a significant renal anomaly correlates with the and urinary tract (CAKUT) can present with fetal severity of hydronephrosis. Fetal hydronephrosis hydronephrosis due to urinary tract obstruction is diagnosed if renal pelvic diameter is more than and vesicoureteral reflux (VUR). These conditions 4 mm between 18 and 22 weeks gestation and may be associated with impaired renal more than 10 mm during third trimester. Foetuses development and/or cause renal injury. with Renal pelvic diameters more than 15 mm are at an increased risk of having CAKUT. Grading of Antenatal hydronephrosis Aetiology: Transient hydronephrosis is the most The Society of Fetal Urology (SFU) grading common cause of fetal hydronephrosis with a system focuses on the degree of hydronephrosis reported range of 41 to 80 % of cases. It is thought in the kidney without directly assessing the state to be related to a transient narrowing of the of the ureter and bladder: ureteropelvic junction early in development that resolves without clinical implications as the fetus Grade 0 – Normal examination with no matures. Mild hydronephrosis with renal pelvic dilation of the renal pelvis diameter (RPD) <6 mm in the second trimester is usually associated with transient hydronephrosis. Grade I – Mild dilation of the renal pelvis only Pelviureteric junction obstruction forms the Grade II – Moderate dilation of the renal commonest cause of clinically significant pelvis including a few calyces hydronephrosis. Vesico ureteric reflux is the second most commonest cause of antenatally detected Grade III – Dilation of the renal pelvis with hydronephrosis. Other less common causes incluse visualization of all the calyces, which are Primary megaureter, Posterior urethral valve, uniformly dilated, and normal renal Multicystic dysplastic kidney, ureteroceles and parenchyma ectopic ureters. Grade IV – Similar appearance of the renal During the ultrasound examination, the pelvis and calyces as grade III, plus thinning of the renal parenchyma 25

Annual Conference of IAP Kerala Nephrology Chapter appearance of the fetal renal system can vary in towards the signs of CAKUT. A palpable bladder in both normal fetuses without hydronephrosis and a male infant, should always make the clinician in those with hydronephrosis. Therefore, serial think about posterior urethral valve. A palpable measurements should be taken during each kidney indicates obstructive uropathy or multicystic examination. The likelihood of CAKUT increases dysplastic kidney. Presence of ear abnormalities, with the severity of RPD. Repeat ultrasound spinal anomalies or single umbilical artery indicates performed during the third trimester is more the need for urological imaging. Postnatal informative in predicting neonatal CAKUT, which ultrasound should be avoided in the first two or may require further follow up and surgical three days after birth, because hydronephrosis may intervention as well. not be detected due to extracellular fluid shifts that will underestimate the degree of hydronephrosis. Risk factors for CAKUT: Bilateral involvement Important exceptions to this include infants with increases the risk of a significant renal abnormality bilateral hydronephrosis associated with ureteral and the risk of impaired postnatal renal function, dilation and/or a dilated bladder and those with a primarily due to post-bladder obstructive uropathy hydronephrotic solitary kidney because these such as PUV. Dilation of the ureter indicates infants require urgent evaluation followed by vesicoureteral reflux or obstructive uropathy distal possible intervention. to the ureteropelvic junction. Thinning of the parenchyma and/or cortical cysts indicate injury or Severity of hydronephrosis is categorized impaired development of the renal cortex. An according to the findings on postnatal ultrasound. echogenic renal cortex may indicate dysplasia, which may be associated with VUR or obstructive The severity according to RPD and SFU is as uropathy. Abnormalities of the bladder, such as follows: increased thickness and trabeculation of bladder wall, are findings associated with obstructive Mild hydronephrosis RPD <10 mm; SFU uropathy distal to the bladder, most importantly grades 1 and 2 PU Valve. Ureteroceles may be visualized in the bladder and can cause bladder outlet obstruction Moderate hydronephrosis RPD 10 to 15 mm; if they insert ectopically within the urethra. SFU grade 3 Oligohydramnios is consistent with impaired Severe hydronephrosis RPD >15 mm; SFU renal function resulting in a decreased production grade 4 of fetal urine. It is a consistent feature of severe renal disease, affecting either both kidneys or Infants with SFU grades 3 and 4 hydronephrosis solitary kidney. Urinoma is a fluid mass formed by are at greatest risk for significant kidney injury and extravasated urine encapsulated in the perirenal may require surgical correction. These infants with fascia. Urinomas are secondary to urinary a persistent moderate to severe hydronephrosis obstruction such as PUV or ureteropelvic junction (RPD e”10 mm) on postnatal ultrasound generally obstruction. Urinary ascites can be secondary to require additional evaluation. A Micturating spontaneous or iatrogenic rupture of the bladder cystourethrogram is done in these infants to rule and the renal calices due to lower obstruction and out VU Reflux and Posterior urethral valve. A increased pressure cystoscopy and valve ablation is done in those cases with PU Valve. Those with VU Reflux are started on Postnatal Evaluation: The goal of the postnatal prophylactic antibiotic and a DMSA scan is done at evaluation of infants with prenatally diagnosed 6 weeks of age. Further follow up and treatment is hydronephrosis is to identify patients with CAKUT decided as per the severity of reflux and the while avoiding unnecessary testing in patients with presence or absence of renal cortical scars. physiologic or clinically insignificant fetal hydronephrosis. Management: Those children with severe hydronephrosis and no VU Reflux undergo DTPA Physical examination of the neonate is focused scan to assess the severity of PUJ obstruction and differential function. Those with moderate hydronephrosis needs a repeat ultrasound 26

Annual Conference of IAP Kerala Nephrology Chapter evaluation at 6 weeks followed by DTPA renogram reported in infants with prenatally diagnosed if the hydronephrosis worsens or persists. If the hydronephrosis compared with the general hydronephrosis becomes better, they can be pediatric population. The risk of infection rises if followed up by another ultrasonogram 3 months there is underlying VUR and is greater in girls later. The third group of infants, those with mild compared to boys. The risk also rises with the hydronephrosis can wait for 3 months before a severity of hydronephrosis. Interventions used to repeat ultrasound scan. Most of these will improve reduce the risk of UTI include judicious use of and settle by about 18 months of age. antibiotic prophylaxis and treatment of physiologic phimosis in male infants with hydronephrosis. Higher rates of urinary tract infections have been 27

Annual Conference of IAP Kerala Nephrology Chapter Dr. Anil Mathew Ped. Nephrologist AIMS, Kochi ENURESIS IN CHILDREN E nuresis or bedwetting beyond 5 years of age voiding frequency, abnormally low or high daytime is a common medical problem. Twenty voiding frequency). NMNE is suspected to have a percent of 5-year-old children are enuretic. somewhat different pathogenesis and need to be Although there is an annual resolution rate of 10- managed differently than those with MNE. 15%, not all children will ‘grow out’ of this problem and more than 2% of adolescents and young adults, Pathophysiology of MNE involves the following continue to have enuresis. three factors either alone or in combination. 1) Nocturnal polyuria (lack of AVP release) 2) Presence of enuresis results in poor self esteem Reduced nocturnal functional bladder capacity in children and they tend to avoid social activities 3) Impaired arousal response from sleep in like camps and sleep overs in the fear of bed response to full bladder. wetting. Chronically disturbed sleep, interferes with daytime behaviour and executive function. Overall Maintaining and assessing a voiding diary enuresis is a reason for significant parental anxiety. forms an important aspect in the evaluation of any kid with enuresis, especially if there are any LUT In a child with enuresis, decision to intervene is symptoms. This should include the fluid intake, the guided by age of the child, extent of distress to the day time voided volumes of at least two days along child and the family and the practical issues in with assessment of incontinence (day and night) applying one or more interventions in his/her for at least 1 week. Maximum voided volume will situation. usually be the first morning voided one, provided the previous night has been free from enuresis. By International Childrens Continence Society weighing of diapers or sheet covers and adding (ICCS) classify enuresis into primary and the first morning void, the detection of nocturnal secondary. Most children fall into the primary polyuria will be possible (preferably be measured group. Children who have at least 6 consecutive during 1 week.) months of normal urinary control followed by commencement of enuresis have secondary Assessing the storage capacity of the bladder- enuresis and it is associated with underlying a crucial parameter in the evaluation of these pathologies. children. From the amount of urine voided at each micturition, average and maximum voided volumes Enuresis may also be classified as are calculated. Expected Bladder Capacity( EBC) monosymptomatic (MNE- constitutes 80% and in a child 1 to 12 years can be calculated by the do not have any day time symptoms) or non- formula EBC= (age in years +2) x 30ml and reaches monosymptomatic (NMNE- in addition to their the adult value of around 400ml by teenage. bedwetting, have any of the following daytime LUT symptoms like daytime incontinence, urgency, Nocturnal polyuria, a crucial pathogenetic voiding difficulties, abnormally low or high daytime mechanism -currently defined as a nocturnal urine 28

Annual Conference of IAP Kerala Nephrology Chapter production (weight of urine in sheet covers or nights. Cleaning after bedwetting should not be diapers plus first morning void), on a night with performed as a punishment. Motivational therapy enuresis, of >130% of the EBC for the child’s age. completely resolves enuresis in up to 25% of cases, and the number of wet nights reduces in up to 70% There are certain red flags in the history, like of children. On failure of 3–6 months of motivational weight loss, growth retardation, excessive thirst, therapy, different management strategies can be secondary enuresis with recent debut, sleep tried. apnoea or heavy snoring. History of constipation should be checked. Enuresis alarm is device which gives a strong arousal stimulus, usually acoustic, to the child and The physical examination should focus on family at the moment when urine activates a general health and rule out signs of occult spinal detector located in the child’s bed or clothing. Alarm dysraphism (lower back findings, leg and anal cleft is especially effective in children with difficulty asymmetries, abnormal neurology of the lower awakening. It works by conditioning the child to limb). awake for urination before bedwetting occurs. The success rate for alarm is between 50 and 70 per Investigations- may include urinalysis and cent and favourable prognostic indicators include Urine Culture, Ultrasonography- KUB and frequent enuresis and a motivated child and family. Urodynamic Studies (reveal storage problems such In concomitant ADHD, child who wets more than as low bladder capacity and decreased bladder once per night alarm is likely to be less effective. compliance or detrusor overactivity and useful for demonstrating neurogenic bladder or outlet The alarm should only be used by well- obstruction.) motivated, well-informed families and should be thoroughly demonstrated for both child and parents. Treatment -usually starts with Urotherapy It needs to be used continuously, every night without although not evidence based in MNE. Non-surgical interruption. The parents need to be prepared to and non-pharmacological methods involves wake the child immediately when the signal is educating families regarding enuresis and its heard, since very often during the first weeks of treatment, offering suggestions for voiding patterns treatment the child itself will not wake up by the and frequency, and avoidance of drinks with a signal . The healthcare provider should contact the diuretic effect (such as those containing caffeine). family after 1 to 3 weeks to give encouragement For limitation of fluid Intake, though commonly and solve technical problems during this crucial advised, efficiency has not been proven . period. If there is no sign of progress after 6 weeks therapy should be stopped. If there is progress Primary management- include behavioural (smaller wet spot, occasional dry nights) then intervention, including dry-bed training, motivational therapy should be continued until 14 consecutive therapy, classic conditioning therapy using an dry nights have been achieved. enuresis alarm system. Overlearning methods- In children who have Dry-bed training involves waking the child on previously responded to enuresis alarm therapy but a schedule of decreasing intervals over several then have relapsed, to improve the chance of cure nights. The child is made to change clothes and during the next alarm attempt, instruct the child, bedding (if wet), and walk to the toilet if voiding is after 14 consecutive dry nights have been achieved, required. The efficacy of dry-bed training is variable. to drink 1to2 extra glasses of water every evening. Factors favouring a positive outcome for adapted ( Simultaneous Desmopressin –contraindicated ). clinical dry-bed training include female gender, mild When 14 consecutive dry nights have reappeared initial enuresis, current diaper use, no prior in spite of the extra fluid - the chance for long term anticholinergic treatment, and degree of enuresis remission or cure is better. after 6 weeks of training. Desmopressin an analogue of Arginine Motivational therapy involves a combination Vasopressin ( ADH), decreases nocturnal urine of providing reassurance, emotional support, eliminating guilt, and rewarding the child for dry 29

Annual Conference of IAP Kerala Nephrology Chapter production to a level which can be accommodated effects like constipation, increase in PVR, dry within the bladder. Approximately one -third of mouth. enuretic children will be reliably dry as long as they take the drug, whereas one-third will have no Imipramine and other tricyclic benefit and one-third will have an intermediate antidepressants- An evidence based anti-enuretic response. It can be used long-term without therapy and used as third-line alternative if substantial risks. Contraindication for desmopressin desmopressin, the alarm and anticholinergics have is habitual polydipsia. If medication is combined all been unsuccessfully tried. The mode of action with excessive fluid intake, water intoxication with is a combination of noradrenergic, serotoninergic hyponatremia may ensue. The chance of response and anticholinergic action on the bladder, urine is highest in children with MNE who have nocturnal production and arousal mechanisms. Among polyuria and normal daytime voided volumes. therapy-resistant enuretic children- 30 to50% may be expected to benefit from imipramine and Desmopressin is given in the evening, 60 min response increases if desmopressin is added . before bedtime. Oral tablets /oral quick-melting Atomoxetine and Riboxetine are newer agents lyophilizate. Standard dosage is 0.2-0.4mg for the useful in this group. tablets and 120-240 ug for the lyophilizate. The efficacy -will be immediately evident. Do not The crucial limiting factor of tricyclics is continue for more than 1-2 weeks if there are no cardiotoxicity. If overdosed or given to a child with beneficial effects. The chance of continued dryness unstable arrhythmia (long QT-syndrome) fatal after therapy is slightly higher if the drug is reactions may occur. Caution should be taken if discontinued gradually. there is any history of unclear syncope or palpitations in the child or a positive family history In children resistant to first line therapy, focus of sudden cardiac death. The most common side- on co morbidities & reasons for failure like effects are mood swings and nausea. Imipramine Constipation, ADHD, incorrect use of alarm, high (25-50mg) should be given approximately 1 hour salt /protein intake at night(may negatively influence before bedtime. Therapeutic response is evaluated Desmopressin response),spinal dysraphism or after 1 month and Desmopressin may be added if anatomical obstruction/high PVR. the effect is incomplete. Oxybutynin and other Anticholinergic Drugs Recent Alternative Therapies- include a) – can be considered after ruling out high PVR and Transcutaneous Para sacral Electrical Nerve constipation and intended to prevent involuntary Stimulation(-In patients with overactive bladder, has detrusor contractions. They significantly decrease been shown to decrease symptoms by up to 63%.) urge incontinence in children and commonly used b) Functional Magnetic Stimulation (FMS)- c) for the treatment of small capacity bladder and Botulinum toxin injections into detrusor. detrusor overactivity. They have only mild side 30

Annual Conference of IAP Kerala Nephrology Chapter Dr. Naveen Viswanath Ped Surgeon, AIMS Kochi FUNCTIONAL VOIDING ISSUES in children – An overview B ladder dysfunction or voiding dysfunction, (squatting position with the legs crossed to prevent is a term used to describe abnormalities in micturition or leaking), are also seen in some of either the filling and/or emptying of the the affected children. bladder. This results from disruptions of the normal voiding process by any alteration of the innervation Voiding postponement and underactive of the bladder or external sphincter, bladder bladder: This occurs in children who habitually compliance or volume capacity, detrusor muscle postpone micturition, usually in specific settings function, or structure of the bladder or bladder like during school hours. These children commonly outlet. These include neurogenic, anatomic, or have behavioral issues. This group generally has a functional causes. The two major categories of low voiding frequency with long intervals between voiding dysfunction are night time incontinence voids that result in increasing bladder capacity over and daytime incontinence disorders. time. With overdistension of the bladder, the detrusor muscle becomes overstretched and Up to 20 percent of four- to six-year-old children hypoactive leading to a weak or absent contraction experience occasional daytime wetting and 3 referred to as an underactive bladder. They use percent will have wetting accidents two or more Valsalva maneuver to increase abdominal pressure times per week to aid in bladder emptying. Inspite of these efforts, high post-void residual volumes with overflow The following conditions result in daytime incontinence are common in these children. urinary incontinence: Children with underactive bladder are at increased risk for urinary tract infection. Overactive bladder: The overactive bladder is defined as abnormal bladder contraction during the Dysfunctional voiding (defined as detrusor filling phase and is detected by urodynamic contractions during voiding against a closed evaluation. It is the second most common bladder external urinary sphincter) is caused by an inability dysfunction disorder following nocturnal enuresis. to relax the urethral sphincter and/or pelvic floor The most important symptom of this disorder is musculature during voiding. Dysfunctional voiding urgency which is defined as the sudden and in children without a known neurologic lesion is unexpected experience of an immediate need to defined as non-neurogenic dysfunctional voiding. void. Incontinence and increased frequency are In these children, urodynamic studies demonstrate also common features of an overactive bladder. the abnormal contraction of the sphincter and/or Holding maneuvers, such as Vincent’s curtsy pelvic floor musculature during voiding. Urinary 31

Annual Conference of IAP Kerala Nephrology Chapter flow is interrupted, producing a staccato pattern Voiding diary — The use of a three-day voiding and a prolonged voiding time. Patients with non- diary is helpful to obtain an objective record of neurogenic bladder dysfunction are more likely to bowel and urinary voiding patterns. It should have constipation and are at increased risk for include the time and volume of each void, the time urinary tract infection and vesicoureteral reflux. In of each incontinent episode, fluid intake and the more severe cases, imaging studies demonstrate time of each bowel movement. hydronephrosis due to severe VUR and trabeculated bladder due to bladder wall Physical examination is done to exclude any hypertrophy. urologic or neurologic abnormalities including markers of spinal dysraphism. Meatal stenosis in Other conditions which cause daytime boys and labial adhesion in girls are specifically incontinence include vaginal voiding in toilet looked for. Abdominal and rectal examinations trained girls, giggle incontinence and primary exclude constipation with faecal impaction. If bladder neck dysfunction possible, observation of urine stream gives valuable information about the voiding dysfunction. The problems that are seen associated with bladder dysfunction in children are urinary tract The differential diagnosis of bladder dysfunction infection, Vesico ureteric reflux and constipation. includes urinary tract infection, Secondary bladder For children with VUR, when bladder dysfunction overactivity from constipation and polyuria due to is present there is a higher incidence of UTI, longer renal problems. time for VUR resolution, and increased failure rate of surgical correction. Treatment of bladder Further evaluation: This includes Imaging, dysfunction, particularly overactive bladder, has Urinary flow measurements and urodynamic been shown to improve spontaneous VUR studies. These studies are done if there is no resolution rate, suggesting an etiologic component improvement after initial trial of conservative for overactive bladder in the genesis of reflux. management such as timed voiding and treatment Bladder dysfunction may partly be a behavioral or of constipation, if there is a suspicion of neurologic learned process that perpetuates itself when not or anatomic etiology, in children who are not treated. Functional causes of bladder dysfunction responsive to behavioral modification therapy, in are often believed to originate from behavioral those with constant continuous incontinence issues arising from toilet training or limiting pointing to an anatomic abnormality like ectopic bathroom access. ureter, in those with urinary tract infection or vesicoureteral reflux and suspected kidney damage. Initial evaluation of Bladder Dysfunction: This is done to determine whether the child has an Ultrasound is the first and most common abnormality in either filling and/or emptying of the imaging done for evaluation of urinary tract. This bladder and if there is a bladder function can detect presence of hydronephrosis or a duplex abnormality, to determine the underlying cause. collecting system, high post void urine residue in specifically, to distinguish organic (ie, neurogenic bladder and increased bladder wall thickness. A or anatomical) from functional causes of bladder micturating cystourethrogram is done in children dysfunction. with recurrent urinary infections. MR is used to image the sacral spinal cord to rule out any occult Initial evaluation starts with a proper history spinal dysraphisms. which includes voiding schedule (frequency of voids and frequency of incontinent episodes), Bowel Urine flow measurement: A uroflowmetry habits and symptoms of bladder dysfunction. provides useful information regarding the pattern Symptoms of bladder dysfunction include urgency, of urine flow that is often diagnostic of an pain during urination, holding maneuvers, underlying cause, making it unnecessary to do a hesitancy (difficulty in initiation of voiding), more invasive urodynamic testing. Uroflowmetry dribbling, straining, and an intermittent or weak provides information regarding the emptying phase urinary stream. of the bladder, but not the filling phase. During voiding, electromyographic activity of the urethral 32

Annual Conference of IAP Kerala Nephrology Chapter sphincter and pelvic floor musculature can be symptoms of bladder dysfunction, the underlying assessed using pads affixed to the perineum. cause of bladder dysfunction should be identified, Sphincter activity should be absent during voiding. followed by appropriate therapy. The presence of sphincter activity during voiding is indicative of dysfunctional voiding. Anticholinergic agents decrease the frequency of uninhibited detrusor contractions during the Fluoro-urodynamic testing is a specialized filling phase of the bladder and increase bladder invasive study that involves placement of urethral capacity. They are used to treat children with and rectal catheters to study the bladder during overactive and/or small capacity bladders. The filling and voiding in an awake child. Information proposed mechanism of action involves blocking obtained includes evaluation of detrusor instability, the M3 muscarinic receptor subtype, which incontinence, compliance, bladder pressure, primarily mediates detrusor contraction. Alpha bladder capacity, urine flow rate, sphincter activity, adrenergic receptor antagonists, which act as and bladder emptying. The bladder is filled with smooth muscle relaxants at the bladder neck and contrast during a urodynamic test, allowing proximal urethra, have been used in patients with radiographic visualization. Urodynamic testing non-neurogenic dysfunctional voiding and/or detects abnormalities during both the filling and urinary retention. voiding phase and is useful in separating the more common disorder of overactive bladder (filling Biofeedback therapy teaches children how to phase abnormality) from those of dysfunctional identify and control pelvic floor muscle involved in voiding due to abnormal sphincter or pelvic voiding. The child observes real-time visual displays musculature contraction during voiding. of urinary flow and electromyography activity. The visual or auditory feedback allows the child to Management: The management of a child with become aware of and gain control over their bladder dysfunction is primarily directed at bladder. Kegel exercises strengthen the pelvic floor improving symptoms and avoiding kidney damage. musculature which compresses the urethra and A stepped strategy moving from the least to most reflexly relaxes the detrusor muscle. invasive therapy is recommended in these children. Neuromodulation, involves implantation of Conservative management is generally the initial noninvasive devices that can stimulate pelvic approach to treating children with bladder muscle contractions and/or modulate detrusor dysfunction. It primarily involves voiding behavior activity. These electrical stimulation therapies modification including timed voiding schedules, include noninvasive pelvic muscle stimulation via and treatment of constipation, if present. Voiding electrodes in the anus or vagina, sacral nerve behavior modification is very useful to rehabilitate stimulation via implanted or transcutaneous the bladder and sphincter function and return the electrodes, or transcutaneous stimulation of the child to normal voiding habits. The habits which peripheral tibial nerve. This is used in a select group deviate from the normal voiding process are of children with overactive bladder refractory to identified and are discussed with the child and behavioral and anticholinergic therapy. In extreme family. A timed voiding schedule with frequent cases Clean Intermittent catheterization, Botulinum voids scheduled every two to three hours during injection or bladder augment surgeries may have the day will be beneficial to many of these children. to be considered. If conservative management fails to relieve the 33

Annual Conference of IAP Kerala Nephrology Chapter Dr. Christy Cathreen Thomas Ped. Nephrologist SATH, Thiruvananthapuram NEPHROLITHIASIS in children I ntroduction Nephrolithiaisis in children is relatively rare but important cause of morbidity especially in pediatric nephrology care. Proper identification and evaluation is essential to direct therapy. Compared to adults, children may have frequent recurrence rate, the presence of metabolic defects and possible association of major morbidity such as chronic kidney disease Epidemilogy Many factors such as race, geographic area, socio-economic status, and dietary habits can influence the incidence, localization within the urinary tract, and the chemical composition of stones. Risk factors Urinary tract malformations, recurrent UTI, obesity, dietary habits ( high Na, protein, low calcium, decrease fluid), preterm birth, low birth weight ,chronic bowel diseases, use of drugs such as diuretics, anticonvulsants, antibiotics, and vitamin D supplementation. Genetic factors also play a role. Family history of nephrolithiasis is also a risk factor. Clinical presentation Clinical manifestations in young children are different from adults. Stones are incidentally detected in many cases. Renal colic occurs more often in school-aged children and in adolescents.Poorly localised abdominal pain, inconsolable crying and irritability in young children. Non-glomerular gross hematuria and/or micro-hematuria, with or without flank tenderness,dysuria, urgency, frequency, vomiting, recurrent urinary tract infections and the isolated presence of leukocytes in the urine are other modes of presentation. Complete urine retention with acute renal failure is a rare event, which occurs when the stone obstructs the urinary tract. Evaluation A complete systematic diagnostic evaluation (clinical history, laboratory and imaging investigations) is mandatory in every child presenting with a first episode, even if the etiology seems to be obvious, in order to make an adequate diagnosis and establish the appropriate course of medical and/or surgical treatment. 34

Annual Conference of IAP Kerala Nephrology Chapter Lab investigation Blood-Urea, creatinine, uric acid, Na, K, Cl, Ca, P, Mg, Venous bicarbonate. Urine microscopy crystals. 24 hour urine Ca, creat, uric acid, citrate, oxalate, beta2 microglobulin (Quatification of stone formers and preventers) Stone analyisis-Infrared spectroscopy or X-ray diffraction Imaging Stones X-ray feature Uric acid, Ammonium urate, Xanthine, 2,8- Dihydroxy adenine, Radiolucent Drug stones Radiopaque Calcium oxalate monohydrate, Calcium oxalate dihydrate, Calcium phosphate Poor radio opacity Magnesium ammonium phosphate, Apatite, Cystine Ultrasound (US) is the most useful and widely used imaging modality to evaluate the presence, dimension and position of stones in the urinary tract. Computed tomography (CT) scan without contrast represents the gold standard and it is always used for the evaluation of adult patients.Radiation exposure is a concern as it may need to be repeated in young hildren. Genetic study is considered in a selected group of patients. Management • Acute episode – During the acute phase when the stone is being passed, management is directed towards pain control, and facilitating passage or removal of the stone(s). The decision is usually based on clinical and radiographic aspects: pelvic or ureteral obstruction caused by a stone, particularly in a solitary or transplanted kidney or in the presence of fever, pain refractory to oral analgesics, increasing inflammatory index, or sepsis. A medical expulsive therapy (MET) using calcium channel blockers are increasingly ued in children with <10 mm nonobstructive stones in distal part of ureter. • Prevention of recurrent disease –. This includes an evaluation to identify any underlying cause or risk factors for stone formation. Based upon this assessment, interventions are tailored to reduce the risk of recurrent stone formation. Medical Management Hydration 70–100 ml/kg/ especially incase of diarhoea/ fever Children with kidney stones should generally be encouraged to increase water intake, reduce sodium intake, maintain normal unrestricted dietary calcium, and increase consumption ofboth potassium and citrate, preferably through eating more fruits and vegetables. Potassium citrate therapy is often needed except in few cases. Dietary management often tailored to the metabolic abnormality or the stone. Surgical Mangement Surgical indications in children are similar to those in adults. The main difference and disadvantage is that all procedures like extracorporeal shockwave lithotripsy, placement or removal of ureteral stents, have to be performed under general anesthesia. Moreover stones can recur, with the need for repeated surgical procedures over the years.The majority of stones can be successfully managed with ESWL, ureteroscopy/retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), or a combination of these treatments. Open surgery is currently indicated in very few selected cases, in the 35

Annual Conference of IAP Kerala Nephrology Chapter presence of: associated structural abnormalities (pelvi-ureteric or ureterovesical junction obstruction), a large burden of infective and staghorn stones, or large bladder calculus particularly in augmented bladder. For further reading 1. David I. Chu, Gregory E. Tasian, Lawrence Copelovitch Pediatric Kidney Stones – Avoidance and Treatment Curr Treat Options Pediatr. 2016 June 2. EAU guidelines on nephrolithiasis 2018 3. Giuseppina Marra,· Francesca Taroni, · Alfredo Berrettini et al, Pediatric nephrolithiasis: a systematic approach from diagnosis to treatment, 2018 Journal of nephrology 36

Annual Conference of IAP Kerala Nephrology Chapter Dr. Radhika C.R. Ped. Nephrologist SATH, Thiruvananthapuram Uncomplicated Nephrotic Syndrome in children ephrotic syndrome (NS) is the commonest glomerular disease in children. It is characterized by N edema, heavy proteinuria and hypoalbuminemia. The annual incidence of childhood Nephrotic syndrome ranges from 1.2 to 16.9 per 100,000 and prevalence is about 16 cases per 100,000 children. Definition of Nephrotic Syndrome Nephrotic Syndrome is a symptom complex characterised by nephrotic proteinuria,hypoalbuminemia with or without edema. • Nephrotic proteinuria - Urine protein/creatinine ratio (UPCR) e”200 mg/mmol (2 mg/mg) in the first morning void; OR 24-h urine sample e”1000 mg/m2/day; >40 mg/m2/hr corresponding to 3+ or 4+ by urine dipstick. • Hypoalbuminemia - serum albumin <3 g/dL. Definitions pertaining to the disease course and severity is given in table 1- (adapted from ISPN guidelines on Nephrotic syndrome 2022(2). Table1: Definitions of disease course and severity Disease state Definition Remission Urine protein nil or trace (Up/Uc <0.2mg/mg)for 3 consecutive early morning specimens Relapse Urine protein e”3+ (Up/Uc>2mg/mg) for 3 consecutive early morning specimens,having been in remission previously Frequent Relapses 2 or more relapses in the first 6 months after stopping initial therapy; e”3 relapses in any 6 months; or e”4 relapses in 1 year Steroid dependence 2 consecutive relapses while on alternate daily steroid or within 14 days of discontinuation Steroid resistance Lack of complete remission despite therapy with daily prednisolone at a dose of 2 mg/kg (or 60 mg/m2) daily for 6 weeks Stable Remission Sustained remission or infrequent relapse while on immunosuppressive therapy 37

Annual Conference of IAP Kerala Nephrology Chapter Complicated Relapse Relapse associated with life threatening complications (1) hypovolemia requiring inpatient care, (2) severe infections (Peritonitis, cellulitis, meningitis) or (3) thrombosis Significant steroid toxicity Hyperglycemia (fasting glucose > 100 mg/dl,post prandial glucose 140mg/dl or Hb A1C>5.7%,Obesity (BMI equivalent of 27 kg/m2 in adults),short stature (Height -2SD)for age, height velocity <3 SDS for age Raised intraocular pressure, Cataract myopathy, osteonecrosis or psychosis Difficult to treat steroid 1) frequent relapses or significant steroid toxicity with infrequent sensitive disease relapses; and 2) failure of e”2 steroid sparing agents (including Levamisole, Cyclophosphamide ,Mycophenolate Mofetyl) Evaluation & Management First episode of Nephrotic Syndrome Evaluation of a child with first episode of nephrotic syndrome includes tests to confirm the diagnosis, assess for complications and identify underlying aetiology. All patients should be assessed for history of asthma, atopy and other allergies, family history of nephrotic syndrome, renal diseases and deafness. Features that suggest an underlying aetiology include fever, rash, hematuria, arthralgia, abdominal pain, oliguria, and history of drugs or infections. Weight, height, and blood pressure is recorded in the first visit. Weight should be monitored on a daily basis for hospitalised patients as it helps in assessment for edema. Investigations suggested at the initial episode are listed in Table 2. Since the risk of latent tuberculosis infection in childhood is high, tuberculin test is suggested prior to the first course of steroid treatment, especially with history of contact. Chest radiography should be done in children with positive tuberculin test. Isoniazid prophylaxis for 6-month is advised in children with positive tuberculin test without bacteriological or radiological evidence of tuberculosis. Children with features of active tuberculosis infection should be given anti-tuberculous treatment as per the guidelines. Table 2 : Investigations in children with nephrotic syndrome(adapted from reference 2) Essential at Onset Urinalysis: Microscopy,Urine Protein Creatinine Ration Complete Blood Count Blood Urea, Serum Creatinine, Electrolytes ,Total Protein,Albumin,Total CholesterolTuberculin Test Additional Evaluation at Onset or Relapse Chest X Ray : Positive tuberculin test or history of contact; suspected lower respiratory tract infection Renal Ultrasonography: Presence of hematuria,Planned for biopsy,suspected Renal Vein thrombosis Complete hemogram: Suspected systemic infection or hypovolemia Renal Function tests: Blood Urea, Serum Creatinine Serum Total Protein, Albumin, Serum Electrolytes: Severe oedema, hypovolemia/dehydration, Oliguria, anuria, prolonged diuretic therapy > 72 hours Complement C3,C4 ,ANA,ASO: Gross hematuria, persistent microscopic hematuria; sustained hypertension, suspected secondary causes(SLE, IgA Vasculitis,C3 Glomerulopathy)Serum Transaminases: Positive HbSAg /HCV, History of jaundice or liver disease Periodic Monitoring (if relapsing illness) Serum Creatinine, Albumin, Electrolytes Quantitative estimation of urine protein is required if diagnosis of Nephrotic range proteinuria is uncertain 38

Annual Conference of IAP Kerala Nephrology Chapter Subsequent Evaluation Parents should be taught to monitor proteinuria at home, using dipstick or boiling test. They should be educated that relapses are common in this disease and should be taught the features of relapse. The child’s urine should be tested for proteinuria 2-3 times a week during remission, every day during infections, or if edema or frothing of urine is present. Patients should be screened for complications during relapses also. Treatment First episode of Nephrotic Syndrome Prednisolone is given at a dose of 60 mg/m2/day (2 mg/kg/day to a maximum 60 mg in 1-2 divided doses) for 6 weeks, followed by 40 mg/m2 (1.5 mg/kg, maximum 40 mg as single morning dose) on alternate days for the next 6 weeks, and then discontinued. Prednisolone is preferably dosed by body surface area in young children as calculation using body weight results in relative underdosing, particularly in young children. Daily prednisolone is administered in single or divided-doses, with similar time to remission. A single morning dose is preferred by most treating physicians. Relapses Relapses should be treated with prednisolone at 60 mg/m2/day (2 mg/kg/day; maximum 60 mg) in single or divided-doses until remission (protein trace/nil for 3 consecutive days), followed by 40 mg/m2 (1.5 mg/kg, maximum 40 mg) on alternate days for 4-weeks. Management of frequent relapses and steroid dependence A flowchart for management of FRNS/SDNS adapted from ISPN 2022 guideline is given in Figure 1. Alternative drugs used include levamisole, MMF, cyclophosphamide, calcineurin inhibitors (CNI) and finally, rituximab. Levamisole is given at the dose of 2-2.5 mg/kg on alternate days. Therapy with MMF is given in two divided doses, 600 to 1200 mg/m2 (20-30 mg/kg) daily. Oral cyclophosphamide, at 2-2.5 mg/kg daily for 8-12 weeks or 500 mg/m2 monthly IV pulse; 6- doses are equally effective. Leukocyte count is monitored every 2 weeks, and therapy withheld if the count falls below 4000/mm3. Nausea and vomiting is more common with intravenous (IV) dosing. Hemorrhagic Cystitis may also occur following IV Cyclphosphamide .Increased fluid intake and frequent voiding helps to prevents hemorrhagic cystitis. The risk of gonadal toxicity is proportionate to the cumulative dose, and appears to be high in pubertal and post-pubertal boys (Tanner stage 2 or more), and lower in girls. The cumulative dose of cyclophosphamide should be kept below 168 mg/kg to avoid risk of gonadal toxicity. Rituximab, anti-CD 20 monoclonal antibody helps to induce sustained remission in high dose SDNS/ FRNS. It is given at a dose of 375mg/m2 every week for 2-4 doses. Figure1: Treatment of steroid dependent/frequently relapsing nephrotic syndrome -adapted from ISPN Guidelines 2022 39

Annual Conference of IAP Kerala Nephrology Chapter Dr. Hareesh.K.G MD,DCH,DM Ped. Nephrologist Parumala Hospital RICKETS - EVALUATION AND MANAGEMENT R ickets is a bone disease that is associated Regulation of calcium and phosphate homeostasis with decreased serum calcium and/or phosphate levels in the blood, leading primarily to widening and delay of mineralization of growth plates in bones. Rickets is also associated with osteomalacia, which is characterized by a delay in the mineralization of bone matrix . Rickets can be caused by deficiencies of vitamin D, calcium or phosphate attributable to nutritional or environmental causes (that is, nutritional rickets) or by mutations in genes encoding proteins involved in vitamin D activation and function, phosphate homeostasis and/or bone mineralization (that is, heritable rickets); rickets can also be the consequence of acquired defects in vitamin D metabolism (such as in severe liver disease) or renal tubular handling of minerals (which may occur with a number of drugs). Globally nutritional rickets is the most common type of rickets . Calcium and phosphate homeostasis Serum calcium and phosphate levels are regulated by vitamin D, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) through actions on the intestine, kidney and bone . The development of rickets, which is associated with abnormal serum calcium and/ or phosphate levels, is often associated with abnormalities in vitamin D, PTH and FGF23 metabolism or action 40

Annual Conference of IAP Kerala Nephrology Chapter Classification of rickets Clinical presentation The clinical presentation of rickets is heterogeneous, involves skeletal and non-skeletal manifestations and depends on the age of presentation. Many children who present with rickets in early childhood will have progressive bowing deformities of the legs (genu varum) often associated with a characteristic waddling gait. In children who develop rickets in the first year of life, the ability to walk is typically delayed (>18 months of age). When rickets develops in older children (aged >3 years), a knock-knee deformity (genu valgum) or a combination of both genu varum and genu valgum is common. The age dependency of the presentation as genu varum or genu valgum reflects the normal growth pattern of the lower limb in the second year of life when the tibio-femoral angle changes from varus to valgus. Older children with rickets may complain of bone pain and fatigue. Fractures may be a presenting feature in a child with nutritional rickets but only in the presence of clear radiological features of rickets. Loss of height and short stature might occur as a consequence of the progressive leg deformities. Infants with rickets associated with vitamin D deficiency or abnormalities of vitamin D metabolism may also develop seizures owing to hypocalcaemia and life-threatening cardiomyopathy. Additional clinical signs seen in an infant with rickets include craniotabes (softening of the skull bones), widening of the wrists ,frontal bossing, delayed closure of the anterior fontanelle, craniosynostosis and delayed eruption of the teeth with enamel hypoplasia. In XLH, dental abscesses associated with defects in the consolidated mineralization of globular dentin may come to the attention of the family before overt evidence of skeletal disease. Chest deformities include a rachitic rosary and Harrison sulcus. Biochemical investigations The typical biochemical picture of a child with calciopenic rickets is low or normal serum calcium levels with increased serum PTH levels leading to decreased renal tubular reabsorption of phosphate and low serum phosphate levels. By contrast, in typical phosphopenic rickets, normal serum calcium, low serum phosphate and normal serum levels of PTH and 25(OH)D are observed. Serum alkaline phosphatase levels are usually markedly raised in calciopenic rickets owing to the high PTH causing increased bone turnover but are often only modestly raised in phosphopenic rickets (especially in XLH) . Measurement of serum PTH is essential to distinguish between calciopenic and phosphopenic rickets. 41

Annual Conference of IAP Kerala Nephrology Chapter In calciopenic rickets, serum PTH levels will be considerably increased, whereas serum PTH levels are often in the normal range or only slightly increased in phosphopenic rickets. Serum and urinary biochemistry associated with different types of rickets Radiography. Radiographs of the wrist and knee enable the diagnosis of rickets .Typical changes seen in the metaphyseal region are cupping, fraying and lateral widening with expansion of the growth plate. Bones with metaphyseal abnormalities may show evidence of osteopenia in calciopenic rickets owing to bone demineralization as a consequence of the high PTH levels. By contrast, in XLH, the bones may become somewhat sclerotic by adulthood, and dense vertebrae can be a particular feature of ARHR type 1, even in childhood.Occasionally, fractures of long bones may be seen in both calciopenic and phosphopenic (excluding XLH) forms of rickets in conjunction with osteopenic bone and typical metaphyseal changes Management Treatment of nutritional rickets 42

Annual Conference of IAP Kerala Nephrology Chapter Treatment of other causes Conclusion The evaluation and management of rickets are crucial for addressing this complex condition, which is not solely limited to nutritional deficiencies. While vitamin D and calcium deficiencies remain common causes of rickets, it is important to recognize that there are other underlying factors at play. Genetic disorders, renal abnormalities, gastrointestinal disorders, and medication-induced causes can also contribute to the development of rickets. Therefore, a comprehensive approach to evaluation and management is necessary. 43

Annual Conference of IAP Kerala Nephrology Chapter Dr. Radhika C.R. Ped. Nephrologist SATH, Thiruvananthapuram Urinalysis U rinalysis is considered as the liquid biopsy and microscopical. of the kidney . Urinalysis is an ancient • Physical examination describes the volume, diagnostic screening test that has stood the test of time and is still useful in clinical laboratories color, clarity, odor, and specific gravity. since it plays a critical role in the health assessment • Chemical examination identifies pH, red blood process. cells, white blood cells, proteins, glucose, Urine is an unstable fluid; it changes composition urobilinogen, bilirubin, ketone bodies, leukocyte as soon as it is eliminated through esterase, and nitrites. micturition. Accurate collection, storage, and • Microscopic examination encompasses the handling are crucial to maintaining the sample’s detection of casts, cells, crystals, and integrity. microorganisms. Urine samples collected from the first void or Appearance “morning urine” are considered the best representative for testing. The urine accumulated • Normal: Clear or translucent overnight in the bladder is more concentrated, thus • Associations: Bacteria, blood clots, contrast provides an insight into the kidneys’ concentrating capacities and allows for the detection of trace media, a diet high in purine-rich foods, fecal amounts of substances that may not be present in contamination or material (i.e., gastrointestinal- more diluted samples. However, other types of bladder fistula), lipids such as chyluria urine specimens may be ordered according to (chylomicrons in the urine), lymph fluid, mucus, specific purposes (randomly, 2-hours postprandial, precipitation of cells (red blood cells (RBC), white 24-hour collection). Furthermore, urine should be blood cells (WBC), squamous and non- ideally examined within the first hour after the squamous epithelial cells), casts or crystals collection due to the instability of some urinary (calcium phosphate, calcium oxalate, uric acid), components (cells, casts, and crystals). If not pyuria, semen, small calculi, talcum powder, possible, the sample should be refrigerated at vaginal creams or secretions, yeast or non- 4 degrees C for up to 24 hours, which will slow down specific/normal. the decomposition process. Any specimen older than 24 hours cannot be used for urinalysis. Specific Gravity (USG)/Osmolality (O) A complete urinalysis consists of three The urinary specific gravity (USG) and osmolality components or examinations: physical, chemical, are of special importance because they indicate the kidney’s capacity to dilute or concentrate urine. Isosthenuria connotes urine with a fixed specific 44

Annual Conference of IAP Kerala Nephrology Chapter gravity and portends renal disease. High Values: • Myoglobinuria: Muscle trauma eg, Contrast media, dehydration, decreased renal rhabdomyolysis, prolonged coma, convulsions, blood flow (shock, heart failure, renal artery drug abuse, extensive exertion, alcoholism/ stenosis), diarrhea, emesis, excessive sweating, overdose, muscle wasting diseases glycosuria, hepatic failure, syndrome of inappropriate antidiuretic hormone (SIADH) • False-positive: Dehydration, exercise, hemoglobinuria, menstrual blood, Low Values: Acute tubular necrosis, acute myoglobinuria adrenal insufficiency, aldosteronism, diuretic use, diabetes insipidus, excessive fluid intake • False-negative: Captopril, elevated specific (psychogenic polydipsia), impaired renal function, gravity, acid interstitial nephritis, hypercalcemia, hypokalaemia, pyelonephritis Microscopic examination Chemical Examination Casts Casts are a coagulum composed of the trapped pH contents of tubule lumen and Tamm-Horsfall • Normal: 4.5 to 8 (usually 5.5 to 6.5) mucoprotein. They originate in the lumen the distal • Associations: convoluted tubule or collecting duct with pH • High Values (alkaline): Stale/old urine specimens alterations or long periods of urinary concentration or stasis. The casts preserve the cylindrical shape (most common), hyperventilation, presence of of the tubule in which they were formed. Only a urease-producing bacteria, renal tubular few hyaline or finely granular casts may be seen acidosis, vegetarian diet, vomiting. under normal physiological conditions. • Low Values (acid): Cranberry juice, dehydration, • Red Blood Cell Casts diabetes mellitus, diabetic ketoacidosis, • Normal: Absent diarrhea, emphysema, high protein diet, • Associations: Glomerulonephritis, vasculitis, starvation, potassium depletion, medications intrinsic renal disease (tubulointerstitial (methionine, mandelic acid, etc.), and a possible nephritis, acute tubular injury/necrosis), predisposition to the formation of renal or strenuous exercise bladder calculi • White Blood Cell Casts Proteins • Normal: Absent • Associations: Pyelonephritis, interstitial Normal: Proteinuria less than 4 mg/m2/hr Nephrotic proteinuria - >40mg/m2/hr nephritis, glomerulonephritis, renal inflammatory processes (see image attached) Blood Cells • Epithelial Cell Casts • Dipstick test for blood detects primarily the • Normal: Absent peroxidase activity of erythrocytes, but • Associations: Acute tubular injury/necrosis, myoglobin and hemoglobin can also catalyze this reaction. Thus, a positive test result indicates interstitial nephritis, glomerulonephritis, hematuria, myoglobinuria, or hemoglobinuria. eclampsia, nephritic syndrome, transplant rejection, heavy metal ingestion, renal disease • Normal: Negative (usually) or less than or equal to 5 RBCs per mL • Granular Casts • Normal: Absent • Associations: • Associations: Glomerular or tubular disease, • Hematuria: Renal calculi, glomerulonephritis, pyelonephritis, advanced renal disease, viral pyelonephritis, tumors, trauma, anticoagulants, infections, stress/exercise, non-specific strenuous exercise, exposure to toxic chemicals • Hemoglobinuria: Hemolytic anemias, RBC • Waxy (broad) Casts trauma, strenuous exercise, transfusion • Normal: Absent reactions, severe burns, infections (i.e., malaria) • Associations: Advanced renal failure (dilated 45

Annual Conference of IAP Kerala Nephrology Chapter tubules with decreased flow) necrosis • Hyaline Casts • Bacteria, Fungi, or Parasites • Normal: Up to 5 casts/low-power field • Associations: Normal finding in concentrated • Normal: Absent • Associations: UTI, contamination urine, fever, exercise, diuretics, pyelonephritis, chronic renal disease Crystals • Fatty Casts • Uric Acid • Normal: Absent • Yellow to orange-brown, diamond- or barrel- • Associations: Heavy proteinuria (nephrotic shaped crystals • Normal: Absent syndrome), renal disease, hypothyroidism, acute • Associations: Acid urine, hyperuricosuria, uric tubular necrosis, diabetes mellitus, severe crush acid nephropathy, normal injuries • Calcium Oxalate Cells • Most commonly encountered crystal in human urine • Red Blood Cell • Refractile square “envelope” shape • Normal: 0-5 cells/high-power field • Normal: Absent • Associations: UTI, inflammation • Associations: Ethylene glycol poisoning, acid urine, hyperoxaluria, normal • White Blood Cell • Normal: 0-5 cells/high-power field • Amorphous Phosphate (Calcium and • Associations: UTI, inflammation magnesium Phosphate) • Normal: Absent • Eosinophil • Associations: Alkaline urine, decreased urine • Normal: Absent volume, a diet rich in calcium, prolonged • Associations: Interstitial nephritis, acute immobilization, overactive parathyroid tubular necrosis, UTI, kidney transplant glands, bone metastases, normal rejection, hepatorenal syndrome • Triple Phosphate (Struvite) • Epithelial cell • “Coffin lid” appearance crystals • Squamous, transitional, or renal tubular cells • Normal: Absent • Type of cell encountered depends on the • Associations: Alkaline urine, decreased urine location of the disease process volume, UTI from urease-producing bacteria • Normal: Less than or equal to 15-20 (Proteus, Klebsiella) squamous epithelial cells/high-power field • Associations: • Cysteine • Squamous (most common): Contamination • Colorless crystals with a hexagonal shape • Transitional: Normal, UTI • Normal: Absent • Renal Tubular: Heavy metal poisoning, drug- • Associations: Cystinuria induced toxicity, viral infections, pyelonephritis, malignancy, acute tubular 46

Annual Conference of IAP Kerala Nephrology Chapter 47

Annual Conference of IAP Kerala Nephrology Chapter 48