1. Total Nutrition Management in CKD 2022

Insulin resistance & Hypertriglyceridemia Figure. Insulin resistance is associated with an expanded adipose tissue mass. In this setting, many of the metabolic effects of insulin are reduced, including increases in basal lipolysis and less suppression of lipolysis by feeding and insulin. In addition, there is a reduc- tion in the intrahepatic effects of insulin action that relate to apolipoprotein metabolism. Under physiological conditions, insulin sup- presses apolipoprotein C-III (apo C-III) gene transcription and increases apolipoprotein B-100 (apo B-100) degradation, whereas in insulin-resistant states, both effects of insulin are reduced. However, the ability of insulin to increase sterol regulatory element-binding protein-1c gene transcription is preserved. Thus, with increased free fatty acid (FFA) flux and esterification to triglycerides (TG) and increased lipogenesis, hepatic steatosis frequently occurs. Moreover, in the presence of more TG, the increased availability of apo C-III and apo B-100 enhances the synthesis and secretion of very-low- density lipoprotein (VLDL). In addition, in the circulation the inhibitory effect of VLDL apo C-III on lipoprotein lipase (LPL) reduces the fractional catabolic rate of VLDL and contributes to the burden of the hypertriglyceridemia. Eckel RH .Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31:1946–1948

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Composition of PD fluid Saxena R, West C. J Am Board Fam Med 2006; 19: 380–9

* • Small size study, plan to extend the study to include entire cohort of 150 patients. • Plan to develop website-based and smart phone applications for easy use by physicians, advanced practice providers, dietitians, and patients. • Hopefully, the accurate estimation of caloric load & the incorporation of it into the daily caloric intake of the individual will help to reduce metabolic consequences of hyperglycemia, hyperlipidemia, and weight gain and improve overall outcomes of PD. Kotla SK, Saxena A, Saxena Kidney360. 2020 Dec 31; 1(12): 1373–1379

https://www.spent.or.th/index.php/publication/category/gl/2020 KDOQI CLINICAL PRACTICE GUIDELINE FOR NUTRITION IN CKD: 2020 UPDATE, AJKD, 76, ISSUE 3, SUPPLEMENT 1, S1-S107, SEPTEMBER 01, 2020 ESPEN Guidelines on Enteral Nutrition: Adult Renal Failure, Clinical Nutrition (2006) 25, 295–310

Nutritional recommendation in PD Nutrition Nephrothai 2017** SPENT 2018 K/DOQI 2000 ESPEN 2006 KDOQI 2020 Total calories < 60 y.:35 At least 35 < 60 y.: 35 35 25-35 (kcal/kg > 60 y.: 30 (depend on > 60 y.: 30-35 (based on age, IBW/D) < 18 y.: depending activities) gender, level of *include upon age and > 60 y: at least 30 physical activity, body energy from physical activity composition, weight PD fluid status goals, CKD stage, and concurrent illness or presence of inflammation) Total protein 1.2-1.3 1.2-1.3 1.2-1.3 1.2-1.5 1-1.2 (g/kg IBW/D) < 18 y. depending In peritonitis: In acutely ill: In peritonitis: Insufficient evidence HBV protein upon age 1.5-1.7 At least 1.3 additional to recommend a >50% (Not < 0.8) 0.1-0.2 particular protein type (plant vs animal) **Advice increase energy requirement in illness, high fever, or peritonitis IBW: male = Height (cm.) – 100 female = Height (cm.) – 105

Nutritional recommendation in PD Nutrition Nephrothai 2017 SPENT 2018 ESPEN KDOQI 2020 2006 Therapeutic lifestyle changes Not routinely prescribing LC Fat >18 y.: 25-30 :Saturated fat <7% n-3 PUFA, including those (% of total 4-18 y.: 25-35 :Polyunsaturated fat <10% derived from fish or energy) 1-3 y.: 30-40 :Trans fat <1% flaxseed and other oils, to lower risk of mortality or CVD events. 1.3-4 g/d long-chain n-3 PUFA may be prescribed to improve the lipid profile. Sodium 2-3, restricted in HT <2 1.8-2.5 < 2.3 (<100 mmol/day) (g/d) < 18 y.: need more if salt losing



* แสดงปริมาณโซเดยี มในเคร่ืองปรุงรสต่างๆและ ปริมาณทแ่ี นะนาในการปรุงต่อมื้อ * * • โดยปกติหากรับประทานอาหารที่มาจากธรรมชาติไม่ปรุง * รสครบตามท่ีธงโภชนาการสาหรับโรคไตเร้ือรังแนะนา จะไดร้ ับโซเดียมเฉลี่ยประมาณ 600 – 800 มิลลิกรัม • ดงั น้นั ผทู้ ่ีเป็ นโรคไตเร้ือรังจะเหลือปริมาณโซเดียมที่ใช้ ในการปรุงอาหารอีกไมเ่ กิน 1,200 มิลลิกรัมต่อวนั ชนิดา ปโชติการ, สุนาฎ เตชางาม. โภชนาการสาหรับผเู้ ป็นโรคไตเร้ือรัง. พฤศจิกายน 2560





Case scenario Case II : PD Patients Problem • After run CAPD for 3 years, despite very good controlled of BP & BS, his PD treatment is 2.5% CAPD 2 L x 3 Ex/day & 1.5% 2 L x 1 Ex/day with UF 800 ml/day without urine output. He has abdominal pain with cloudy effluent, infected CAPD was diagnosis • Lab: BUN 58 mg/dl, Cr 5.8 mg/dl, albumin 3 g/dl, serum potassium 3 mmol/L, serum Mg 1.5 mg/dl, pitting edema 3+ • Problem: • Hypokalemia & Hypomagnesaemia • Malnutrition during peritonitis

Causes of Protein-energy wasting in PD Seung-Hyeok Han, Dae-Suk Han. Nature Reviews Nephrology (8) 2012, 163–175

Assessment & Management of nutritional status in a PD patient Kiebale T, Holotka J et al. Nutrients. Jun 8;12(6):1715, 2020 ESPEN LLL programme 2013

Nutritional recommendation in PD Nutrition Nephrothai 2017** SPENT 2018 K/DOQI 2000 ESPEN 2006 KDOQI 2020 Total calories < 60 y.:35 At least 35 < 60 y.: 35 35 25-35 (kcal/kg > 60 y.: 30 (depend on > 60 y.: 30-35 (based on age, gender, IBW/D) < 18 y.: depending activities) 1.2-1.5 level of physical activity, *include upon age and > 60 y: at least 30 In peritonitis: body composition, energy from physical activity additional weight status goals, PD fluid 0.1-0.2 CKD stage, and 1.8-2.5 concurrent illness or Total protein 1.2-1.3 1.2-1.3 1.2-1.3 presence of (g/kg IBW/D) < 18 y. depending In peritonitis: In acutely ill: inflammation) HBV protein upon age 1.5-1.7 At least 1.3 >50% (Not < 0.8) 1-1.2 Insufficient evidence to Sodium 2-3, restricted in HT <2 recommend a particular (g/d) < 18 y.: need more protein type (plant vs if salt losing animal) Potassium (mg/d) < 2.3 (<100 mmol/day) Depending upon Keep normal 2000-2500 serum level IBW: male = Height (cm.) – 100 **Advice increase energy requirement in illness, high fever, or peritonitis female = Height (cm.) – 105

Additional causes of malnutrition in Peritoneal dialysis patients • Protein losses have been reported to be approximately 10 g/day, amino acid losses from 3-4 g/day including 30% of EAAs, and approximately 5.7 g/day of albumin is lost into the dialysate. • The loss of protein can increase by 50-100% if mild peritonitis supervenes, but it can be much higher if the infection is severe, about 15 g/day in moderate peritonitis, and can reach 100 g/d in severe peritonitis. • Acute peritonitis is characterized by an increased endothelial exchange area, with increased transport of small solutes and glucose, loss of proteins into the dialysate, and dissipation of the osmotic gradient, leading to UF failure. • Physical inactivity is frequent, mainly because of the time-consuming dialysis procedures. Clinical Nutrition (2000) 19(4): 281-291 Westra WM, et al. PDI 2007; 27:192-5 NJM Cano et al, Clinical Nutrition 28 (2009) 401–414 Stegmayr B. Nutrients (2017) 9, 548

Nutritional Complications of PD • Hyperglycemia • Hyperlipidemia • Obesity • Protein loss • Hypokalemia • Hypomagnesemia • Hyponatremia Saxena R, West C. J Am Board Fam Med 2006; 19: 380–9 CM. Rhee, et al. Kidney Int Rep (2019) 4, 769–780

Mechanisms of Potassium Controlling Bansal S, Pergola PE. Kidney Int Rep. 2020 Feb 26;5(6):779-789

Hypokalemia in PD • Hypokalemia (10-36%) is responsible for a rather common complication and independent prognostic factor leading to the higher cardiovascular mortality than normokalemic CAPD patients. • Intracellular K shift by mostly insulin hormone stimulated by the continuous glucose peritoneal infusion in CAPD, was proposed as a contributory factor for the development of hypokalemia even in the context of a low K excretion. • In CAPD, most dialysate solutions contain no potassium and patients dialyzed with such solutions lose 25-30 mEq of K/day via CAPD, this amount is relatively small when compared to the normal daily uptake (70-80 mEq), hypokalemia secondary to low potassium ingestion usually occurs only after an extended period of low oral potassium intake. • Hypokalemia levels were associated with poor nutritional indicators such as lower PNA, BMI, LBMcr, and serum albumin level. • Low levels of serum potassium were associated to lower survival in PD patients and it seems to be related to malnutrition. Kim HJ. Electrolyte Blood Press. 2006 Mar; 4(1): 47–52. Tziviskou E, Musso C, et al. Int Urol Nephrol 2003, 35: 429-434 Kim HW, Chang JH, et al. Electrolyte & Blood Pressure. 2007, 5:102-110 Vavruk AM, et al. J Bras Nefrol 2012;34(4):349-354

Nakai et al. Renal Replacement Therapy (2017) 3:43

Magnesium & CVD in CKD Kanbay M, Goldsmith D, et al. Blood Purif 2010;29:280–292

Hypomagnesemia in PD • The prevalence of hypomagnesemia about 8.9 to 64% in PD patients. • Baseline serum Mg <1.8 mg/dL is associated with a significantly higher risk for hospitalization, particularly in individuals with serum albumin < 3.5 g/dl. • Hypomagnesemia may be associated with higher rate of hospitalization by several mechanistic pathways. (1) Hypomagnesemia is a recognized risk for cardiac rhythm disturbances & associated with a higher risk for cardiovascular events, dyslipidemia, metabolic syndrome, endothelial dysfunction, atherosclerosis, and vascular calcification. (2) Infection is an ongoing threat to the successful execution of PD, due to low serum Mg levels in PD patients are associated with poorer nutritional status, deteriorating cellular health, increased inflammation, lower BUN, albumin, PO4 & K, which are consistent with a higher prevalence of PEW, an important risk factor for infectious complications in PD patients. • Numerous studies now provide strong suggestive evidence for a protective role of Mg in vascular calcification, a 0.1 mmol/L increase in serum Mg is associated with a 1.1-point decrease in abdominal aortic calcification (AAC) score, arrhythmias & atherosclerosis in ESRD included APD patients. Ye H, et al. Perit Dial Int. 2013 Jul-Aug; 33(4): 450–454 Yang X, Soohoo M, et al. Am J Kidney Dis. 2016 October ; 68(4): 619–627 Molnar AO, et al. BMC Nephrology. 2017; 18 (129)

Diet supplement for K & Mg

Peritoneal Dialysis Solutions * ** * Bonomini M, Masola V, Procino G, et al. Int J Mol Sci. 2021 Aug; 22(15): 7955.

• 4.2 Statement on Nutrition Supplementation–Dialysate • Dialysate Protein-Energy Supplementation • 4.2.1 In adults with CKD 5D on PD with protein-energy wasting, we suggest not substituting conventional dextrose dialysate with amino acid dialysate as a general strategy to improve nutritional status, although it is reasonable to consider a trial of amino acid dialysate to improve and maintain nutritional status if nutritional requirements cannot be met with existing oral and enteral intake (OPINION).

Nutritional recommendation in PD Nutrition Nephrothai SPENT 2018 K/DOQI 2000 ESPEN 2006 KDOQI 2020 2017 Water Depending 30-35 1000 ml + Urine ONS upon physical ml/kgIBW/D volume activity depend on urine output, UF, volume status If oral nutrition Use standard ONS in Minimum 3-months (including nutritional conscious patients. trial of ONS Should apply supplements) is Consider EN before ONS/EN before inadequate, TF Formulae with a IDPN, TPN, IPPN IDPN or PN should be offered if higher protein but medically lower carbohydrate appropriate. content are to be preferred.

Guideline 4: Nutritional Supplementation • ONS should be prescribed 2 - 3 times daily and patients should be advised to take ONS preferably 1 hour after meals rather than as a meal replacement to maximize benefit. • ONS prescription should take into account patient preference. • The acceptability of ONS in terms of appearance, smell, taste, texture, and type of preparation (milkshake type, juice type, pudding type, protein/energy bar, or fortification powder) should be carefully considered. • The tolerability of ONS should also be carefully monitored because some patients may develop GI symptoms with ONS. • Energy-dense and low-electrolyte renal-specific ONS may be necessary to increase protein and energy intake and avoid fluid overload and electrolyte derangements. KDOQI CLINICAL PRACTICE GUIDELINE FOR NUTRITION IN CKD: 2020 UPDATE, AJKD, 76, ISSUE 3, SUPPLEMENT 1, S1-S107, SEPTEMBER 01, 2020



Screening Exclusion criteria • Inadequate dialysis Inclusion criteria • Active CHF, malignancy, advance liver disease • Stable patients with CAPD at least 3 months • Active/chronic inflammation disease • Serum albumin level < 3.8 g/dl • Recent peritonitis/hospitalization within 3 mo. • Dietary protein intake < 1 g/kg/day • Pregnancy • Dietary energy intake 20-25 kcal/kg/day Enrollment N =30 Lab / Nutrition Take ONCE Dialyze 80 g Lab / Nutrition assessment (370 kcal) supplement assessment (Baseline) 1 meal for 15 days (after 15 days) Satirapoj B, Limwannata P, et al. International Journal of Nephrology and Renovascular Disease 2017:10 145–151.

* Satirapoj B, Limwannata P, et al. International Journal of Nephrology and Renovascular Disease 2017:10 145–151.

Satirapoj B, Limwannata P, et al. International Journal of Nephrology and Renovascular Disease 2017:10 145–151.

* * * * * * Satirapoj B, Limwannata P, et al. International Journal of Nephrology and Renovascular Disease 2017:10 145–151.

Conclusion • This prospective study indicated that consuming special renal nutritional formula produces more energy, protein, nutrients, fiber, and appropriate electrolyte intake among patients with CAPD. • This oral supplementation was associated with a trend toward improved modified SGA scores. • Oral-specific ODF treatment may be an effective method of improving the nutritional status among peritoneal dialysis patients. • Further large-scale studies using longer periods will be needed to clarify related issues. • ONCE Dialyze supplementation ameliorates low dietary energy and nutrient intakes as well as improves serum prealbumin and body weight in patients with long-term CAPD. Satirapoj B, Limwannata P, et al. International Journal of Nephrology and Renovascular Disease 2017:10 145–151.



Case scenario Case III : HD Patients Problem • After run CAPD for 5 years, due to loss of his residue renal function overtime, his PD treatment is 2.5% CAPD 2 L x 4 Ex/day with UF 400 ml/day without urine output with PET show high transport (4-hr D/Pcr 0.9) with clinical pitting edema 2+, with uncontrolled BP despite good controlled diet intake, he has asked for shift mode for hemodialysis. • During his first months of HD treatment he still has high BP and volume overload. His HD prescribe is 4-hours x3/weeks, after 3 months of HD he became enjoyed eating again with high BS, high potassium level, high interdialytic weight gain, and hyperphosphatemia. • Problem: • Hypertension: Salt & water retention • Hyperkalemia & hyperphosphatemia

Chou JA, Kalantar-Zadeh K. Curr Heart Fail Rep. 2017 Oct;14(5):421-427.

Chou JA, Kalantar-Zadeh K. Curr Heart Fail Rep. 2017 Oct;14(5):421-427.

Mechanisms of Potassium Controlling Bansal S, Pergola PE. Kidney Int Rep. 2020 Feb 26;5(6):779-789

Physiology of Potassium removal during HD Bansal S, Pergola PE. Kidney Int Rep. 2020 Feb 26;5(6):779-789

Bansal S, Pergola PE. Kidney Int Rep. 2020 Feb 26;5(6):779-789 Pirklbauer M. Hemodial Int. 2020 Jul;24(3):282-289

Hyperphosphatemia in CKD • Chronic renal failure results in reduced synthesis of vitamin D by the kidneys and increased retention of phosphorus. • Disturbances in calcium and phosphorous metabolism in patients with CKD can result in secondary hyperparathyroidism, along with ensuing bone disease, soft tissue and vascular calcification, as well as arterial stiffness and artherosclerosis. • The most effective means of controlling hyperphosphatemia is managing dietary phosphorous intake. • However, dietary phosphorous restriction and HD are often not effective in adequately controlling serum phosphorous, and phosphate binders have been routinely prescribed to reduce the intestinal absorption of phosphorous Friedman EA. Kidney Int Suppl. 2005 Jun;(95):S1-7

Hyperphosphatemia and Hyperparathyroidism in CKD Friedman EA. Kidney Int Suppl. 2005 Jun;(95):S1-7

Nutritional recommendation SPENT 2018 ESPEN 2006 KDOQI 2020 Nutrition HD PD HD PD HD PD Sodium (g/d) 1.8-2.5 <2 1.8-2.5 < 2.3 (<100 mmol/day) Potassium 2000-2500 Keep normal 2000-2500 Keep normal range with dietary or (mg/d) supplemental potassium intake be based on a patient’s individual Calcium Keep normal needs and clinician judgment. :1.5-2 g/D include all source (PD, Adjust calcium intake (dietary foods, drugs) calcium, calcium supplements/calcium- based binders) with consideration of Phosphorous 800-1000 Keep normal 800-1000 concurrent use of vit D analogs & (mg/d) calcimimetics in order to avoid :5-10 mg/kgIBW/D hypercalcemia (<800 mg/D) Keep normal range with consider the bioavailability of phosphorus Trace element In deficiency In deficiency sources (e.g. animal, vegetable, :Zinc 15 mg/D :Zinc 15 mg/D additives) :Se 50-70 mcg/D :Se 50-70 mcg/D Not routinely supplement selenium or Zinc ( little evidence that it improves nutritional, inflammatory or micronutrient status )

Nutritional recommendation SPENT 2018 K/DOQI 2000 ESPEN 2006 KDOQI 2020 Nutrition HD PD HD PD HD PD HD PD Acid load Serum HCO3 Maintain serum Water should be HCO3 at 24-26 Fiber maintained mmol/L at or > 22 mmol/L. 1000 ml + Urine volume 30-35 ml/kgIBW/D depend on urine output, UF, volume status 25-30 g/D ONS Should apply ONS/EN If oral nutrition Use standard ONS in conscious Minimum 3-months before IDPN or PN (including patients. trial of ONS nutritional For TF prefer HD- Formulae with a Consider EN before supplements) is specific formulae. higher protein but IDPN, TPN, IPPN inadequate, TF The formula lower should be offered if content in P & K carbohydrate medically should be content are to be appropriate. checked preferred.





Case scenario Case III : HD Patients Problem • Unfortunately, he get COVID-19 pneumonia and has admitted. He lose appetite and lose his weight from 50 to 48 kgs in 1 week with his serum albumin 2.8 g/dl • Problem: • Hypoalbuminemia

PEW in Hemodialysis • Malnutrition, PEW, and cachexia are frequently undiagnosed & untreated up to 75% of HD patients. • Hypoalbuminemia is the strongest predictor of CVD & mortality in dialysis patients. • Low serum prealbumin is also a recognized predictor of mortality in dialysis patients. • A drop of 1 g/dl in serum albumin was associated with an increased mortality risk of 47% in HD patients. • A drop of 10 mg/dL in dialysis patients with serum prealbumin between 20 and 40 mg/dL was also associated with a 37% increase of death risk independent of serum albumin & inflammatory markers. • Annual death rates in dialysis patients with wasting/cachexia are close to 20%. • The wasting/cachexia syndrome was clearly associated as an independent predictor of morbidity & mortality in incident HD patients during the subsequent 2 years on dialysis. Ruperto M, Sanchez-Muniz FJ, Barril G. Nutr Hosp 2014 Kovesdy CP, Kalantar-Zadeh K. Semin Nephrol 2009 De MR, Grootendorst DC, Indemans F, et al. J Ren Nutr 2009 Chertow GM, Goldstein-Fuchs DJ, Lazarus JM, et al. KI 2005 Rambod M, Kovesdy CP, Bross R, et al. Am J Clin Nutr 2008

Nutrient losses in Hemodialysis • The studies have suggested that the dietary energy failure is more on dialysis treatment days than non dialysis treatment days. • When dialysis fluid not containing glucose is used for 4 hours, 28 g glucose is lost in HD, when 11 mmol/L glucose was added to the dialysis fluid, the patient gained approximately 23 g of glucose. • There are 0.2-0.3 g/kg or 6-8 g/day of protein, AAs and peptide losses with the dialysis fluid during HD which increase 30% of loss in high flux. • Metabolic acidosis in HD patients increases protein catabolism, the BCAA degradation and muscle glutamine release. • Protein catabolized approximately 25-30 g/D F. Esra Güneş. Licensee InTech. 2013 Ikizler TA, Hakim RM: Renal Failure and Parenteral Nutrition, Parenteral Nutrition 3rd: 366-391,2001

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