Nutritional Management of Chronic Renal Failure

1. Nutritional Management of Chronic RenalFailure

2. Chronic Renal Disease • Importance • Rationale for nutritional intervention • Key nutritional factors • Feeding management • Results of a clinical trial

3. Importance • Prevalence of renal disease • Aging associated renal changes • Rationale for nutritional intervention

4. Kidney Disease Cancer Feline Leukemia Virus Heart Problems Prevalence of Renal Disease Leading Causes of Death Cats Dogs Percent of Response MAF Health Survey (2000)

5. Prevalence of Renal Disease • Renal disease second most common cause of death in a series of 2,002 dogs necropsied at Angell Memorial Animal Hospital Bronson RT, Am J Vet Res 1982; 43:205 7-59

6. Aging Associated Renal Changes • Kidneys susceptible to aging • Functional and morphologic alterations

7. Aging Associated Renal Changes • Survey 1600 dogs > 5 years of age • 22.4% azotemic (SUN>40mg/dland creatinine>1.2 mg/dl after 12 h fast) Leibetseder J, Neufeld K. Proceedings WSVA World Congress, Vienna, 1991 p. 271-274

8. Aging Associated Renal Changes Early Changes Are Not Detectable By Routine Tests Percent Functioning Nephrons Serum Creatinine (mg/dl) 88 264 440 616 792 Serum Creatinine (mmol/L) Utilize urine protein determinations for earlier detection of renal insufficiency

9. Rationale for Nutritional Intervention • Natural history of clinical renal disease • Controversy - when to institute nutritional management Normal renal function Renal insufficiency Azotemia Uremia Death

10. Rationale for Nutritional Intervention • Progression of renal disease occurs at an early stage of renal dysfunction • Early - may slow progression of renal disease • Late - may slow progression, reduces clinical signs of uremia • No risk for the patient

11. Rationale for Nutritional Intervention • Rationale - avoid excess of key nutrients • Requirements not reduced • Tolerance reduced • More is not always better • Prevent malnutrition

12. Potential Mechanisms Responsible for Progression • Glomerular hyperfiltration • Tubular deterioration • Hyperparathyroidism • Others ?

13. Potential Mechanisms Responsible for Progression • Initially beneficial, ultimately maladaptive • Changes occur regardless of underlying etiology

14. Glomerular Hyperfiltation “Vicious Cycle”

15. Glomerular Hyperfiltration • Nutritional goals • Improve renal hemodynamics • ( hyperfiltration) • Avoid excess dietary protein • Avoid excess dietary sodium & chloride • Increase n-3 fatty acids

16. Glomerular Hyperfiltration Influence of Diet on Renal Function in Induced Renal Failure GlomerularFiltration Rate(ml/min) 16.28 304 Urine protein (mg/24 h) 128 Low protein High protein 10.88 Polzin, et al. J Vet Int Med 1988; 2:15

17. Tubular Deterioration • Chronic acid load → • Increased ammonia excretion per nephron • Activates alternate complement pathway • Membrane attack complex • Tubulo-interstitial damage Nath, et al. J Clin Invest 1985; 76:667

18. Tubular Deterioration • Dietary acid load (including protein)

19. Tubular Deterioration • Nutritional goals • Reduce acid load • Avoid excess dietary protein • Increase buffering capacity of diet • Do not feed urine acidifying diets

20. Hyperparathyroidism Chronic Renal Failure Phosphate retention Low levels 1,25(OH)2 Vit D Resistance of bone to PTH Hypocalcemia Hyperparathyroidism Decreased sensitivity to calcium Modified from Delmex JA, Slatopolsky E. Pathogensis and treatment of uremic hyperparathyroidism. AKF Nephrology letter volume 10, no 2. May 1993

21. Hyperparathyroidism • Renal osteodystrophy

22. Hyperparathyroidism • Other manifestations of the uremic syndrome • Cardiac • Hematologic • Neurologic • Nephro-calcinosis

23. Hyperparathyroidism • Nutritional goal • Avoid excess dietary phosphorus • May also use phosphorus binding agents or calcitriol(grade 4 evidence)

24. Hyperparathyroidism Influence of phosphorus restriction on serum PTH 600 500 PTH µl equiv. /ml 400 High P Diet 300 200 Low P Diet 100 24 12 18 6 • TIME (mo) Rutherford, et al. J Clin Invest 1977, 60:332

25. Mechanisms Responsible for Progression Glomerular hyperfiltration Tubular deterioration Hyperparathyroidism Progressive nephron Loss Renal failure

26. Nutritional Management • Nutritional factors slow progression by altering pathophysiologic mechanisms Phosphorus Hyperparathyroidism Lipid (n3)Na & Cl Glomerular hyperfiltration Protein Buffer Tubular deterioration

27. 1. 2. Nutritional Management • Controversy - when to institute nutritional management Normal renal function Renal insufficiency Azotemia Uremia Death 1. Churchill J, Polzin D, Osborne C, Adams L. The influence of dietary protein on progression of chronic renal failure in dogs. Seminars in Vet Med and Surg (Small Animal) 1992; 7(3):244-250. 2. Bovee KC, Kronfeld DS, Ramberg, et al. Long-term measurement of renal function in partially nephrectomized dogs fed 56, 27, or 19% protein. Invest Urol 1979; 16:378-384.

28. Nutritional Management • Reduces clinical signs of uremia • Decreases vomiting, anorexia and lethargy • Decreases azotemia, acidosis and hyperphosphatemia

29. Key Nutritional Factors • Water • Energy • Protein/AA • Na, Cl, K • Phosphorus • Fatty acids • Vitamins • Acid load • Soluble fiber

30. Key Nutritional Factors - Water • Correct fluid, acid base and electrolyte deficits before feeding • Avoid dehydration and renal hypoperfusion • Oral, subcutaneous or IV administration of fluids • Fresh water • Canned foods

31. Key Nutritional Factors - Protein • Influence of Diet on Urea Nitrogen in Induced Renal Failure Urea nitrogen(mg/dl) Weeks of Renal Failure Source: Polzin, et al. Am J Vet Res 1984, 45:506

32. Key Nutritional Factors - Protein • Protein recommendation in renal failure may be as much as 2 X’s minimum requirement • Biologic value important when protein intake is restricted • Provide adequate energy to prevent endogenous protein catabolism

33. Key Nutritional Factors - Protein Dogs • Phos. % DMB • Prot. % DMB 1.0-1.3 40 30 20 10 1.0 0.75 0.5 0.25 25-50 15 0.2 8-9 0.15 Regular Commercial Foods Minimum Requirement Renal Failure Recommendation

34. Key Nutritional Factors - Protein • Phos. % DMB • Prot. % DMB Cats 36-60 1.2-1.5 50 40 30 20 10 1.0 0.5 0 28 0.4 0.3 14 Regular Commercial Foods Renal Failure Recommendation Minimum Requirement

35. Feline Protein Requirement • Feline CRF trial* • Mild-moderate CRF (n=10) vs. controls (n=9) • Provided 3 practical dry diets containing 16, 20 & 24% protein (ME) • Randomized, block design x 4 months/diet • Monitored PCV, BUN, ALB, TP, CRE, LBM, BW and N-balance (7d) * Kirk, Hickman. ACVIM, 2000

36. Feline Protein Requirement • CRF requirement similar to that of healthy cats • Provide 20% ME as high quality protein (28-30% DM)

37. Key Nutritional Factors - Protein • Protein adequacy • [AA] exceed requirements • Levels support growth of puppies • N balance studies - feline • N balance studies - canine & feline dialysis patients • Experimental (nephrectomy) trials - short & long term • Spontaneous (congenital) renal failure trials

38. Key Nutritional Factor - Protein • Individual assessment of protein intake, serially monitor: • Urea nitrogen - reduced • Creatinine – constant • Albumin – WNL • Body condition score – ideal • Acid-base status - WNL • Urine protein – constant or

39. Key Nutritional Factor - Protein • Conundrum • In many cases food intake rather than protein intake is the issue • Poor food intake malnutrition protein catabolism

40. 100 p < 0.01 Survival % 75 • Group 1, 0.44% P 50 25 • Group 2, 1.4% P Time (months) 4 8 12 16 20 24 Key Nutritional Factor - Phosphorus • Survival Improved in Dogs Fed Low Protein and Low Phosphorus Diet Brown SA, et al. J Am Soc Nephrol 1991; 1:1169-1179

41. Key Nutritional Factor - Phosphorus • Cats - Influence of phosphorus restriction on histopathology • 1.56% phosphorus diet mineralization, fibrosis & mononuclear infiltrates • 0.42% phosphorus diet kidney remnants normal histology Ross, et al A J Vet Res 1982; 43:1023

42. 8 7 6 5 4 3 2 0 4 8 12 16 20 Key Nutritional Factor – n3 Fatty Acids Survival in Dogs Influenced by Lipid Source Fish oil Tallow Number of dogs Safflower oil Time (months) Brown SA, et al. Proceedings ACVIM, 1995.

43. Key Nutritional Factor - Fatty Acids • n-3 supplementation increases exogenous CC, ST and decreases UP/C ratios as compared to n-6 • Recommend n-6:n-3 ratio< 2.5:1

44. Key Nutritional Factors - Vitamins • Replete B vitamins • Antioxidant vitamins?

45. Feeding Management • Feeding method • Small, frequent meals • Avoid food aversion • Uremic crisis • Consider assisted feeding techniques

46. Feeding Management • Patient factors affecting appetite • Uremia nausea • Oral ulcerations • Altered taste acuity • Learned food aversions • K, vitamin B, Zn depletion

47. Feeding Management • Diet factors affecting intake • Palatability • Form/texture • Timing/presentation

48. Increased Appetite Clinical Improvement Increased Energy Weight Gain Increased Strength Eats Therapeutic Diet More Playful Better Grooming 0 20 10 30 40 50 60 70 80 90 100 Feeding Managment Percentage of Cats with Reported Clinical Attributes After Treatment with r-HuEPO Cowgill, 1992

49. Feeding Management • Protein • Lipids • CHO • Phosphorus • Calcium • Sodium • Potassium • Acid load • Vitamins Optimal nutritional management requires more than protein restriction Renal Diet

50. Renal Diet - Typical Characteristics • Reduced protein content • Reduced phosphorus content • Increased lipid/calorie content • Modified n6:n3 ratio • Reduced sodium/chloride content • Neutral to alkalinizing • Feline diets may be K+ supplemented