Specific Nutritional Supplements for Dialysis Patient 2023

Specific Nutritional Supplements for Dialysis Patient Sirin Jiwakanon, MD. Nephrologist, Hat yai hospital 14th Jan 2023

Case scenario “PD Patients Problem” • A 38-Thai male with CKD stage 5 from diabetes nephropathy. • He had started peritoneal dialysis with 1.5% CAPD 1.5 L x 4 Ex/day with UF 200-300 ml/day and urine output 1.5 L/day. • 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 2.7 g/dl, serum potassium 3 mmol/L, serum Mg 1.5 mg/dl, pitting edema 3+ • Problem: • Hypoalbuminemia: kwashiorkor-like protein malnutrition • 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

*

Composition of PD fluid “No” Potassium Saxena R, West C. J Am Board Fam Med 2006; 19: 380–9

Nutritional problems in PD • Peritoneal solutions with a high glucose content are standard, CAPD is associated with a high glucose uptake. • PD leads to the absorption of glucose, the calorific value of which can range from 300-450 kcals/day (approximately 8 kcal/kg/day) or mean daily glucose absorption 27.98 to 110.35 grams depending on the type of PD undertaken, dwell time, and peritoneal membrane transport status. • An excess of energy over protein net intake can ensue, and obesity can develop that can conceal a dangerous kwashiorkor-like protein malnutrition. • The high glucose intake can cause: – Obesity – Hypertriglyceridemia – Increased LDL and VLDL cholesterols – Hyperglycemia – Induction or aggravation of diabetes N Cano, E Fiaccadori, et al. Clinical Nutrition, 2006; 25: 295–310 NJM Cano et al. Clinical Nutrition, 2009; 28: 401–414 Johansson L. PDI, 2015; 35(6): 655–658 G Toigo, M Aparicio, et al. Clinical Nutrition, 2000; 19(4): 281-291 Kotla SK, Saxena A, Saxena Kidney360. 2020 Dec 31; 1(12): 1373–1379

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 & 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 & 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)

Case scenario “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. • His HD prescribe is 4-hours x3/weeks, after 3 months of HD he became enjoyed eating again with high BP, high potassium level, high interdialytic weight gain, and hyperphosphatemia. • 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: • Hypertension: Salt & water retention • Hyperkalemia & hyperphosphatemia • Hypoalbuminemia in acutely illness

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.

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 & 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

www.spent.or.th

X X X

Nutritional recommendation Nutrition SPENT 2018 K/DOQI 2000 ESPEN 2006 KDOQI 2020 HD PD HD PD HD PD 35 HD PD Total calories At least 35 < 60 y.: 35 (kcal/kg IBW/D) (depend on activities) > 60 y.: 30-35 25-35 *include energy > 60 y: at least 30 (based on age, from PD fluid gender, level of physical activity, body composition, weight status goals, CKD stage, and concurrent illness or presence of inflammation) Total protein 1.1-1.4 1.2-1.3 1.2 1.2-1.3 1.2-1.4 1.2-1.5 1-1.2 In acutely ill: In peritonitis: Insufficient evidence (g/kg IBW/D) In peritonitis: At least 1.3 additional to recommend a 0.1-0.2 particular protein HBV protein >50% 1.5-1.7 type (plant vs animal) IBW: male = Height (cm.) – 100 female = Height (cm.) – 105

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 )

Recommendation 3 “In malnourished non-critically ill hospitalized patients with AKI/AKD or CKD with or without KF and those patients at risk for malnutrition who can safely feed orally but cannot reach their nutritional requirements with a regular diet alone, ONS shall be offered.” Grade of recommendation A - Strong consensus (100% agreement) • ONS, and especially those with higher energy and protein content, can add up to 10-12 kcal/kg and 0.3-0.5 g of protein/kg daily over the spontaneous intake in a 70 kg patient if provided 2 times a day at least 1 h after a meal, thus facilitating the achievement of nutritional targets. Fiaccadori E, Sabatino A, et al. Clinical Nutrition (40): 2021; 1644-1668

Nutritional recommendation SPENT 2018 K/DOQI 2000 ESPEN 2006 KDOQI 2020 Nutrition HD PD HD PD HD PD HD PD 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.

Guideline 4: Nutritional Supplementation • ONS should be prescribed 2 - 3 times daily & patients should be advised to take ONS preferably 1 hour after meals rather than as a meal replacement to maximize benefit. • Monitored in-center provision of high-protein meals/ONS during MHD may be a useful strategy to increase total protein & energy intake. • Many of the perceived negative effects of intradialytic feeding such as postprandial hypotension, aspiration risk, infection control, and hygiene, as well as diabetes & phosphorus control, can be avoided with careful monitoring. • ONS prescription should take into account patient preference. • The acceptability of ONS in terms of appearance, smell, taste, texture, & 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 & energy intake & avoid fluid overload & electrolyte derangements. KDOQI CLINICAL PRACTICE GUIDELINE FOR NUTRITION IN CKD: 2020 UPDATE, AJKD, 76, ISSUE 3, SUPPLEMENT 1, S1-S107, SEPTEMBER 01, 2020

Decisional Algorithm for Management of PEW in HD N.J.M. Cano et al. Clinical Nutrition 28 (2009) 401–414

Recommended IDPN formulations Dextrose (infusion rates) Lipid (infusion rates) Protein Moderate to high dextrose 4 mg/kg/min or AA 0.6-0.8 g/kg/HD Carbohydrate controlled; 4-6 mg d-glucose/kg/min 12-12.5 g/hr or IDPN bag Noncarbohydrate controlled; 6-8 mg d-glucose/kg/min Low dextrose; < 3 mg/kg/min 4 mg/kg/min or AA 0.6-0.8 g/kg/HD 12-12.5 g/hr or IDPN bag Low dextrose, no lipids; < 3 mg/kg/min No lipids AA 0.6-0.8 g/kg/HD or IDPN bag Glucose 50-100 g/HD Lipid 50 g/HD AA 30-40 g/HD (200-400 kcal/HD) (450 kcal/HD) (120-160 kcal/HD) 400-900 kcal/HD Dukkipati R, Nutritional management of renal disease, 3rd edition, 2013



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.

Inclusion criteria Exclusion criteria • Age 18-75 years • Inadequate dialysis • Regular HD 4 hrs, 3 times/wk > 3 months • Life expectancy < 6 months • Serum albumin level < 3.8 g/dl • Non-adherence to dialysis • Dietary protein intake < 1 g/kg/day • Dietary energy intake < 25 kcal/kg/day regimen • Active infection, malignancy Record dietary intake 3 days (before start study) and severe heart, lung or liver disease 370 kcal/Day for 30 days Lab / Nutrition assessment MIS, SF-36 (Baseline) Record dietary intake 3 days (within study) Lab / Nutrition assessment MIS, SF-36 (End of study) Limwannata P, Satirapoj B, et aI. Int Urol Nephrol.2021 Aug;53(8):1675-1687

Limwannata P, Satirapoj B, et aI. Int Urol Nephrol.2021 Aug;53(8):1675-1687

* Limwannata P, Satirapoj B, et aI. Int Urol Nephrol.2021 Aug;53(8):1675-1687

* * Limwannata P, Satirapoj B, et aI. Int Urol Nephrol.2021 Aug;53(8):1675-1687

* * ** * Limwannata P, Satirapoj B, et aI. Int Urol Nephrol.2021 Aug;53(8):1675-1687

Conclusion • Short-term ONS were associated with increased energy, protein, fat, fiber & magnesium intake. • Oral-specific ODF treatment may be an effective method of improving the nutritional status among dialysis patients. • ONCE Dialyze supplementation ameliorates low dietary energy and nutrient intakes as well as improves serum prealbumin & BW in patients with long-term CAPD. • ONCE dialyze supplement significantly improved nutritional status score & serum albumin level in malnourished patients undergoing maintenance HD without abnormal electrolyte disturbance. • Compliance of patients in our study was extremely good; 96% of patients complied with the ONS supplement for 30 days Satirapoj B, Limwannata P, et al. International Journal of Nephrology and Renovascular Disease 2017:10 145–151 Limwannata P, Satirapoj B, et aI. Int Urol Nephrol.2021 Aug;53(8):1675-1687

ONCE Dialyze • 400 g Powder • Nutrition following dialysis guideline • Caloric distribution 18 : 42 : 40 (High protein formula) • Preserve lean body mass • Control blood sugar • Control lipid profile • Suitable minerals for both PD/HD dialysis patients • Suitable total fiber (13.52 g/1000 kcal) • Use for meal supplement