Chronic Kidney Disease (CKD)
Nutri&on Dilemmas, Controversies & Issues
Objec&ves
• To discuss the role of nutri&on in clinical outcomes of chronic kidney disease (CKD)
• To discuss and update on the nutri&on management of CKD
• To iden&fy problem areas in nutri&on management of CKD
Prevalence of malnutri&on
• United States: Prevalence of CKD Stage 3-‐5: 2.6% 1
• Philippines: In hemodialysis pa8ents:2,3 – Prevalence of malnutri8on: 75%2 – Severe malnutri8on: 56.8%2; 36%3
1. NNHeS 2003-‐2004 Renal Report 2. Divina R et al. Nutri&onal status of hemodialysis pa&ents in the Philippines: a cross sec&onal
survey in four out-‐pa&ent dialysis centers. PhilSPEN Online J Paren Ent Nutr Jan 2010 -‐ Jan 2012: 82-‐89. hXp://www.dpsys120991.com/POJ_0010.html
3. Boado JA et al. Nutri&onal assessment of pa&ents on maintenance hemodialysis using Dialysis Malnutri&on Score (DMS). PhilSPEN Online J Paren Ent Nutr Feb 2012 -‐ Dec 2014: 74-‐88. 2013. hXp://www.dpsys120991.com/POJ_0018.html
Morbidity and mortality in CKD
Tonelli M et al. Chronic Kidney Disease and Mortality Risk: A Systema&c Review. J Am Soc Nephrol 2006; 17: 2034–2047
Malnutri&on and survival
Qureshi AR et al. Inflamma&on, Malnutri&on, and Cardiac Disease as Predictors of Mortality in Hemodialysis Pa&ents. J Am Soc Nephrol 2002; 13: S28–S36.
HGS = Hand Grip Strength SGA
Pathophysiology of PEW in CKD
PEW: Protein Energy Was&ng; ESRD: End Stage Renal Disease
Very Low Protein prescrip8on
LBM Loss and Mortality
• LBM loss leads to: – ä Physical strength – ä ADL (ac&vi&es of daily living)
– ä Organ func&on – ä Whole body protein metabolism
– ä Wound healing – ä Immune func&on Demling R. ePlasty
2009;9:65-‐94 LBM = Lean Body Mass/Muscle Mass = PEW PEW = Protein Energy Was&ng
The MDRD Study* • Study period: 1989-‐1993 • 550 trial par&cipants with
predominantly stage 4 nondiabe&c chronic kidney disease
• Compared results of these diets: – Low-‐protein diet (0.58 g/kg/d) – Very low-‐protein diet (0.28 g/
kg/d) supplemented with a mixture of essen8al ketoacids and amino acids
• Median &me to death = 10.6 years
• THERE ARE MORE DEATHS IN VERY LOW PROTEIN DIET GRP
Outcome
Low protein
Very low protein
Hazard Ra8o
Developed kidney failure
117 (90.7%)
110 (87.3%) 0.83
Died 30
(23.3%) 49
(38.9%) 1.95
Reached composite outcome
124 (96.1%)
120 (95.2%) 0.89
Menon V. Effect of a Very Low-‐Protein Diet on Outcomes: Long-‐term Follow-‐up of the Modifica&on of Diet in Renal Disease (MDRD) Study. Am J Kidney Dis, 2009.
(*MDRD = Modifica&on of Diet in Renal Disease)
Malnutri&on diagnosis
• Subjec&ve global assessment – Validated in Philippine semng 1,2
• Is serum albumin a good marker of nutri&onal status? 3 – Unwarranted; it is a marker of illness – Strategy of supplying expensive nutri&onal supplements as a reflexive first step in managing hypoalbuminemia should be discouraged
1. Lacuesta-‐Corro et al. PhilSPEN Online Journal. hXp://www.dpsys120991.com/POJ_0002.html 2. Boado JR et al. PhilSPEN Online Journal. hXp://www.dpsys120991.com/POJ_0018.HTML 3. Friedman, Reassessment of Albumin as a Nutri&onal Marker in Kidney Disease. Journal of
American Society of Nephrology. 2010
Nutri&onal Assessment in CKD
ASPEN Core Curriculum, 2012. p. 497
• Required data: – Subjec&ve global assessment – Anthropometric measures – Per&nent laboratory data (crea&nine, serum visceral protein concentra&ons, inflammatory markers)
– Diet History – Physical Examina&on
• Addi&onal data that will help: – Cause of CKD and associated complica&ons. – Evalua&on of medica&ons (nephrotoxic, need for renal adjustment).
Goals of nutri&on in CKD
• Nutri&onal status – Maintain or further improve lean body mass and func&on
• Kidney status and func&on – To sustain what is leq of the normal func&ons of the kidney
– To slow down the deteriora&on caused by the disease process
Goal: maintain/improve nutri&on status
• Strategies: – Adequate calories (=carbohydrate and fat) – Adequate protein to maintain protein balance with minimum stress on kidney func&on
– Adequate micronutrient balance
Energy requirements Energy recommenda8ons ESPEN ASPEN
Conserva&ve/Predialysis state > 35 kcal/kg 35-‐38 kcal/kg
Hemodialysis state 30-‐35 35-‐38 Peritoneal dialysis state >35 35-‐38 x (1.1 -‐ 1.2)*
ESPEN: European Society of Parenteral and Enteral Nutri&on ASPEN: American Society of Parenteral and Enteral Nutri&on * Stress factor added when using the Harris-‐Benedict formula
Protein requirements Energy recommenda8ons ESPEN ASPEN
Conserva&ve/Predialysis state 0.6-‐0.8 g/kg 0.6-‐0.8 g/kg
Hemodialysis (HD) 1.1-‐1.4 1.2-‐1.3 CRRT >1 -‐ 2.5 Peritoneal dialysis (PD) 1.2-‐1.5
1.2-‐1.3 to 1.5-‐1.8
ESPEN: European Society of Parenteral and Enteral Nutri&on ASPEN: American Society of Parenteral and Enteral Nutri&on
CKD Stage 1-‐3 CKD G4 (severe) CKD G5 (failure)
Energy Variable 22-‐35 kcal/kg 30-‐35 kcal/kg
Protein DM: 0.8-‐1 g/kg/d, ≥50% high biologic value Non-‐DM: 0.8 g/kg
DM: 0.8-‐1 g/kg Non-‐DM: 0.6-‐0.8 g/kg
≥ 1.2 g/kg (HD) 1.2-‐1.3 kg.kg (PD)
CKD specific recommenda&ons 1,2,3
1. Kopple, 2001; Mitch 2010; Na&onal Kidney Disease Educa&on Program (NKDEP), 2010; 2. American Diete&c Associa&on, 2010; Uhlig, 2010; Byham-‐Gray and Wiesen, 2004); 3. Na&onal Kidney Founda&on, 2009
DM = Diabetes Mellitus HD = Hemodialysis PD = Peritoneal dialysis
Clinical pathway to feeding: CKD
Micronutrient losses
Issues/dilemmas/controversies
• CKD pa&ents are at risk of malnutri8on, however the amount of protein needed to upbuild might be in excess of the amount that the diseased kidney can handle which may lead to uremia.
• In the hospital semng, it is common that a low albumin level is aXributed with malnutri&on hence Clinical Nutri&on physicians are expected to give the maximum protein level allowable in cases of hypoalbuminemia even in renal pa&ents.
Issues/dilemmas/controversies
• How low should the protein intake be? – The MDRD study review showed very low protein intake is harmful (=death)
• Are there indica&ons for increasing protein intake?
• When the serum albumin is low, do I have to correct it immediately with albumin infusion?
• Can eggs provide all protein needs? What is meant by high biological value protein?
What is the value of achieving adequate protein intake?
• Anabolic resistance requires more amino acids to achieve adequate muscular synthesis rate.
• The inflammatory status and its effects on the rest of the organ systems require more amino acids for the synthesis of acute phase response proteins.
• The need for cysteine, the rate limi&ng step of glutathione synthesis, in order to limit oxida&ve stress.
• Preven&on in glutamine deple&on in muscle and plasma.
• Increased u&liza&on in both increased metabolic rate and requirements.
Preiser et. Al. Cri&cal Care (2015) 19:35
What is the value of achieving adequate protein intake?
• Effects of achieving a zero protein balance: – Efficient use of non-‐protein calories for both metabolic and inflammatory requirements
– When the amino acid mix (in both EN or PN) is close to requirements: • Urea synthesis is reduced • Nitrogen balance improves • Amino acid catabolism is minimized and whole-‐body protein turnover decreases.
EN: Enteral Nutri&on PN: Parenteral Nutri&on
Preiser et. Al. Cri&cal Care (2015) 19:35
What are the factors causing protein loss in CKD?
• Kidney disease – Reduced oral intake of nutrients
(anorexia, depression, restric&ve diets, low social status) – most important
– Effects on gastric mo&lity and rest of the gut
– Endocrine factors (growth factor abnormali&es, deficiency in erythropoie&n and male hormones, insulin resistance, hyperparathyroidism)
• Inadequate blood purifica8on – Uremia; metabolic acidosis
• Dialysis associated factors – Loss of macro and micro
nutrients, inflammatory response
• Others: – Diabetes mellitus and
inflammatory state – Reduced physical ac&vity
What is the role of protein restric&on in CKD?
• Preserve renal func&on by reducing: – intraglomerular pressure – solute load – mesangial stretch – toxic products of metabolism – overall nephron ac&vity
• Dietary protein restric&on – decreases the severity of uremic symptoms – can delay the onset of dialysis need – and preserves GFR
ASPEN Core Curriculum Chapter 29, p 495
What do the evidence(s) say for low protein restric&on?
Nutri&on therapy in Chronic Kidney Disease. 2012. p. 125
• Studies exploring the long term risks and benefits of an LPD (=Low Protein Diet) have yielded mixed results.
• Shorualls in many of the studies include: – Poor assessment of adherence to prescribed protein intake levels – Limited long term follow-‐up – Exclusion of diabe&cs
• Given that restric8ng protein intake has the poten8al to preserve renal func8on and reduce the symptoms of uremia with minimal impact on nutri8onal status, many feel that this recommenda8on should be u8lized more frequently with close monitoring by a die88an
Is there evidence for increasing the protein dose for CKD?
How to achieve adequate to high protein dose in CKD
• Formula&on: – Oral supplementa&on – EN (Enteral Nutri&on) like tube feeding – PN (Parenteral Nutri&on)
• IDPN (Intradialy&c Parenteral Nutri&on) – Combina&ons – Micronutrients should be given daily
• Close monitoring – Calorie and protein coun&ng – Die&&an or a nutri&on team
Biological value of protein source
• HIGH • contains the essen&al amino acids in a propor&on similar to that required by humans
• animal sources of protein, such as meat, poultry, fish, eggs, milk, cheese and yogurt
• LOW • one or more essen&al amino acids are scarce
• Plant sources of protein like legumes, grains, nuts, seeds and vegetables
European Food Informa&on Council. hXp://www.eufic.org/
Egg white
70 gm protein/day = 23 pieces of eggs/day
If serum albumin is low Low serum albumin
History, PE, laboratory
• Extreme dietary protein deficiency (
If serum albumin is low
• Factors causing low serum albumin – Reduced hepa&c synthesis and secre&on due to inflamma&on, malnutri&on or poor intake
– Exchanges between the intra-‐ and extravascular compartments
– Increased lympha&c uptake – Altera&ons in volume of distribu&on (including hemodilu&on)
– Body losses Friedman AN , Fadem SZ. Reassessment of albumin as a nutri&onal marker in kidney disease. J
Am Soc Nephrol 2010; 21: 223–230
Mechanism of kidney injury
• Increased workload of remaining nephrons.
• Increased GFR results in intraglomerular hypertension, stretching of the mesangial suppor&ng cells, and an increase in oxygen-‐free radicals and other inflammatory metabolic products
• progressive scarring of the remaining glomeruli.
ASPEN Core Curriculum Chapter 29, p 494
Goal: improve kidney status and/or func&on
• Special nutri&on that intervene in the kidney disease process – An&-‐inflammatory nutri&on
• Fish oils • Glutamine
– Keto-‐analogs
Fish Oils (w3 FaXy Acids)
Glutamine
Ketoanalogs • Background:
– CKD > endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are elevated and may contribute to vascular complica8ons
• Methodology: prospec&ve randomized; obese pa&ents; 36 mos ff-‐up – Diet: 0.6 g/kg protein; 28-‐30 kcal/kg – Study group: keto-‐amino acids at 100 mg/kg
• Results: Study group > significant changes – êBMI – ê in the plasma level of ADMA – ê in pentosidine (marker for AGEs = advanced glyca+on end
products), proteinuria, glycated Hb and LDL-‐cholesterol
Teplan V et al. Reduc&on of plasma asymmetric dimethylarginine in obese pa&ents with chronic kidney disease aqer three years of a low-‐protein diet supplemented with keto-‐amino acids: a
randomized controlled trial. Wien Klin Wochenschr. 2008;120(15-‐16):478-‐85
What are we doing?
• Ins&tu&on: – Nutri&on Screening and Assessment
• Prac&ce: – Evidence-‐based guidelines and clinical pathways* – For pa&ents not on dialysis: 0.8 – 1.0 g/kg/day – For pa&ents on dialysis: 1.2 – 1.5 g/kg/day – Request for serum prealbumin and CRP to rule out inflamma&on (if available)
– If inflamma&on is ruled out, upper protein limit may be used.
*Once you have logged in as PhilSPEN member: . . ./ClinicalNutriGuidelines.php
What can we say?
• Recommenda&on: – Always coordinate with aXending nephrologist – Refer to available evidence based clinical guidelines*
– Evaluate the cause of hypoalbuminemia (inflammatory status/cri&cal illness?)
– Clinical experience/judgment
*Once you have logged in as PhilSPEN member: . . ./ClinicalNutriGuidelines.php
THANK YOU