ESPEN Congress Nice 2010

1 Nutritional management in chronic kidney diseases and after transplantationBengt LindholmESPEN Congress nice 2010 Nutrition in chronic kidney disease BengtLindholmDiv of Baxter Novum& Renal Medicine, Dept of Clinical Science, Intervention and Technology, KarolinskaInstitutetKarolinska University Hospital, Stockholm, SwedenNutritional management in chronic kidney diseases and after transplantation32nd ESPEN Congress , nice , France5 - 8 September 2010 Nutrition in chronic kidney disease - Educational SessionSunday 5 September 2010 17:00-18:30 chronic kidney disease stages 1-5 Nutritional challenges in CKD The kidneys play a key role in maintaining fluid and electrolyte homeostasis, excretion of metabolic waste products, and regulation of various hormonal and metabolic pathways. Patients with chronic kidney disease (CKD) therefore display a variety of metabolic and nutritional abnormalitiesSimplified flow schedule of uremia and its complicationsThe internist knows everything but doesn t do anythingThe surgeon does everything but doesn t know anything- but too late!

2 !The nephrologist knows everything and does everythingFunction of KidneyMetabolic effect of Kidney Disease Excretion:Waste, fluid, excess minerals, metabolitesAccumulation:Fluid, waste products (uremic toxins) eg urea, and minerals eg K+Regulation:Maintain homeostasis -fluid, acid- base & electrolytes balancelAcidosislDisturbed BP controlled/ Uncontrolled HTlLipid abnormalityEndocrine:lVitamin D/Ca2 +Phosphate MetabolismlHb Synthesis/ErythropoietinlRenal bone disease-OsteodystrophylAnaemiaSlide courtesy of Maria Chan, Sydney, AustraliaAccumulation of Na, P, K, H+ and H2O Metabolic acidosis is a major factor for net protein catabolism due to protein breakdown and subsequent muscle wasting via stimulation of the ATP-ubiquitin-proteasome pathway. Correction of metabolic acidosis improves nitrogen balance. Metabolic acidosis - and in general accumulation of Na, P, K, H+and H2O -should always be monitored and corrected in CKD patients!

3 In renal transplant patients, often need to supply PLipid disorders inCKD:Hypertriglyceridemia, often normal cholesterol but low HDL cholesterol Chmielewski M et al. J Nephrol 21: 635-44, 2008 Therapeutic lifestyle changesReduced intake of saturated fat and cholesterolIncreased physical activityWeight controlBut beware of malnutrition!!!Slide courtesy of Michal ChmielewskiCarbohydrate metabolism is a major issue in CKD Insulin resistance Glucose intolerance Metabolic syndrome Overt diabetes mellitus Plus: Diabetes is the most common cause of CKDG lucose intolerance/ Insulin resistance Hypertension Atherogenic dyslipidemiaProinflammatory/Prothromboti c stateObesityMultiple similarities andmultiple interactions between metabolic syndrome and CKDM etabolicsyndromeCKDC ourtesy of Jonas AxelssonHowever, some of these risk factors may paradoxically be associatedwith improved survival in ESRD patientsCauses and consequences of insulin resistance in CKDC auses Insulin secretion abnormalities Hyperparathyrodism Vitamin D deficiency Insulin resistance Uremic toxins Anemia Metabolic acidosis Inflammation Oxidative stress Muscle Loss Fructose Increased fat mass Physical inactivityConsequences Dyslipidemia Sodium retention Vascular calcification Muscle wasting Hyperuricemia Renin activation Ultimately hypertension and cardiovascular diseaseTreatment targeting Hyperparathyroidism Vit D deficiency ACEIs/ARBs?

4 Glitazones? Metabolic acidosis Carbohydrate imbalance UremiaJuan Jes s Carrero, Peter Stenvinkel and Bengt LindholmENDOCRINE ASPECTS OF chronic KIDNEY DISEASE. Chapter in Brenner & Rector s The Kidney 2010 in press Endocrine and hormonal alterations in CKD: Nutritional consequences Insulin resistance Muscle wasting Erythropoetin deficience - Anemia GH and IGF-1 resistance-Muscle wasting Testosteron deficiency Muscle wasting Low thyroid hormones- ? Vitamin D deficiency- Bone disease etc Hyperparathyroidism-Bone diseaseGH/IGF-1 axis in chronic Kidney DiseaseHypothalamusPituitary glandLiverMuscle CKD is a state of GH resistance because of: Reduced IGF-1 synthesis Reduced IGF-1 bioavailability, due to: impaired renal clearance and increased synthesis of IGFBPP owell et al. Endocrinology 1997; 138:938-946 Blum et al. Pediatr Nephrol 1991; 5:539-544reduced IGF-1 receptor synthesis in the muscle Wang et al.

5 Kidney Int. 2005 Jul;68(1):352-61 Sun et al. JASN 2004;15:2630-2646 Slide courtesy of Juan Jesus Carrero IodineNegative feedbackInflammationMetabolic acidosisInactiveActiveTSH usually normalT4 normal or slightly lowT3 usually low: Low T3 syndromeCKD, a nonthyroideal illnessSlide courtesy of Juan Jesus Carrero As many as 50-70% of CKD stage-5 men have been reported to be hypogonadal. Testosterone deficiency (44%)At risk of deficiency (33%)Normal testosterone (23%)Carrero et al. Nephrol Dial Transplant. 2010 Out of 260 male Swedish ESRD patients, 44% suffered from hypogonadism. Only 23% had normal testosterone levelsHypogonadism is highly prevalentAbnormally low testosterone values increase mortality risk in male dialysis et al. J Am Soc Nephrol. 2009 Mar;20(3):613-20. All-causesCVD-causesMalnutrition in CKD - is often preventableIdentify patients at riskORRoutine monitoring by dietitianScreening by: nDoctornNursenNutrition assistantAssessment & diagnosis Intervention Prevention and Early InterventionSlide courtesy of Maria Chan, Sydney, AustraliaEvaluation of Malnutrition/Wasting.

6 No singlemarker is enoughClinical Weight loss Anorexia Fatigue Muscle wasting SGAA nthropometrics BMI Skinfolds Midarm circumference Handgrip strength Waist circumferenceBiochemical markers S-albumin Prealbumin IGF-1, IGFBP-1 S-creat, S-chol nPNA More advanced Bioimpedance DEXA Total body K or N CT or MR Robust clinical nutritional indices in CKD Subjective global assessment of nutritional status (SGA) Appetite scoring (at SGA) Presence of muscle wasting (at SGA) Handgrip strength Biomarkers such as CRP and IL-6 add some information whereas serum albumin is a poor indicator of nutritional is not a good marker of malnutrition Correlates well with poor prognosis. Correlates poorly with other markers of nutrition. Serum albumin is a negative acute phase reactant. Fluid overload, urinary losses and dialysate losses also result in valueU-albumin84, , , ,2NS5101520253035404550S-albumin (g/l)0500010000150002000025000U-albumin (mg/24h)R= < courtesy ofPeter StenvinkelFig 4 Serum albumin levelwas notrelated toHand grip strength Serum albumin levelwas notrelated to leanbody mass (DEXA)Serum albumin levelwas related tourinary albumin lossHeimburger et al Am J Kidney Dis.

7 2000 Dec;36(6):1213-25 Serum albumin is not a good nutritional marker 115 incident ESRD pts(69 men, 46 women).Age 52 +/- 12 48%. Figure1De Mutsert et al J Renal Nutrition 2009; 19:127-135 NECOSAD: 700 incident dialysis patients starting HD or PDat 38 dialysis centers in The Netherlands. Mean age, 59 [+/-15] years;serum albumin, ( ) g/dL; 60% men; 454 starting HD, and 246 starting of albumin as a nutritional marker in kidney AN, Fadem SZJ Am Soc Nephrol. 2010 Feb;21(2):223-30. Epub 2010 Jan 14. The decision by nephrologists, renal dietitians, federal agencies, health care payers, large dialysis organizations, and the research community to embrace serum albumin as an important index of nutrition and clinical performance is based on numerous misconceptions. Patients with analbuminemia are not malnourished and individuals with simple malnutrition are rarely hypoalbuminemic. Furthermore, nutritional supplementation has not been clearly shown to raise levels of serum albumin.

8 Serum albumin is an unreliable marker of nutritional status in albumin in CKD patients: Why measure it? Surrogate marker of inflammation? Yes Reveals well being of the patient? Probably Predicts mortality? Yes Predicts nutritional status? NoProtein-energy wasting is common in CKD, HD and PD patients0255075100%307 HD patsCurtin et al. 2002238 CKD 5 predialysis patsCurtis et al. 2002106 PD patsMerkus et al. 199973 HD patsVirga et al. 199866 CKD 5 predialysis patsMurtagh et al. 20071846 HD pats (HEMO)Burrowes et al. 2005223 HD patsCarrero et al. 2007331 HD patsKalantar-Zadeh et al. 2004120 HD pats14406 HD pats (DOPPS)Lopes et al. 200734 HD patsMuscaritoli et al. 200735-60%Courtesy of Juan Jesus >5050-2524-10<10 Creatinine clearance, ml/minDat a #1 Creatinine excetion, g/dDPI, g/kg/dIkizler et al. 1995, J Am Soc Nephrol; 6: 1386-9n=90 Spontaneous decrease of dietary protein intake29 Protein and energy intakes decrease as appetite decreasesduring the course of CKD progressionCarrero JJ: J Renal Nutr 19: 10-15, 20090246810 GFR <90 mL/minGFR <60 mL/minGFR <30 mL/minGFR <15 mL/minRRTT ransplantationGFR less than 10-25% of normalRetention of appetite depressants?

9 Increased dialysis dose improves feeding behaviorCourtesy of Juan Jesus CarreroAccumulation of Anorectic Factors in UremiaAguilera et al Sem Dial 17: 44-52, 2004 Anorexigens-CCK-Leptin-CRF-NO deficiency-Insulin-Glucagon -C-peptide-TNF- -IL-1-GIP-PYY-FTRPO rexigens-NPY a-GhrelinbMetabolic disordersRetainedsubstancesCentralmodula torsCulturalaspectsSocialaspectsPeripher almodulatorsa NPY negative correlation to TNF- in PD pts (Aguilera et al NDT 1998)bGhrelin is reduced by glucose solution (Perez-Fontan M, et al. KI 2005)PD (and inflammation)may accentuate this imbalanceAppetite stimulants?Megestrolacetateimproves the nutritional and inflammatory status, as well as anorexia in maintenance dialysis patients Rammohan et al. J Ren Nutr. 2005 Jul;15(3):345-55 Costero et al. Adv Perit Dial. 2004;20:209-12 Boccanfuso et al. J Ren Nutr. 2000 Jan;10(1) et al. J Ren Nutr. 1999 Apr;9(2):89-94.

10 Testosteronein aged healthy men improve lean body mass and nutritional status in two recent randomized controlles et al. JAMA. 2008 Jan 2;299(1):39-52. Allan et al. J Clin Endocrinol Metab. 2008;93(1) decanoate(alone or in combination with resistance exercise training) has anabolic effects in CKD patients. Eiam-Ong et al. J Ren Nutr. 2007;17(3):173-178. Ferruci et al. Arch Intern Med. 2006;166(13) courtesy of Juan Jesus Carrero RoigFuture approaches9 PD patients with mild intake increased during a single meal test after administration of ghrelin ( nmol/Kg) vs saline placeboWynne K, et al. J Am Soc Nephrol 2005;16:2111-8. Slide courtesy of Juan Jesus Carrero Roig10th March 2009 Slide courtesy of Juan Jesus Carrero Roig33 Ashby et al. Kidney Int. 2009 Jul;76(2) in 12 malnourished (PD and HD) patients1-week intervention with subcutaneous ghrelin increased energy intake by 20%Recommended protein intake in non-dialyzed CKD g/kg/dayESPENGFR 25 70 (2/3 HBV)GFR< 25 (2/3 HVB) +EAA or EAA +KAaNKFGFR 25 70 ml/minN/AGFR< 25 or (intolerance or inadequate energy intake)Cano et al Clinical Nutrition (2006) 25, 295 310; Cano et al Clinical Nutrition 28 (2009) 401 414 ESPEN , European Society for Clinical Nutrition and Metabolism; NKF, NationalKidney Foundation; EAA, essential amino acids; GFR, glomerular filtration rate; HBV,high biological value.