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Chronic Renal Insufficiency

Chronic Renal Insufficiency. Catherine M Clase Division of Nephrology McMaster University. Objectives. Review the epidemiology of CRI Describe progression of CRI Evidence-based strategies to minimize progression Be aware of the interaction between CRI and CVD

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Chronic Renal Insufficiency

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  1. Chronic Renal Insufficiency Catherine M Clase Division of Nephrology McMaster University

  2. Objectives • Review the epidemiology of CRI • Describe progression of CRI • Evidence-based strategies to minimize progression • Be aware of the interaction between CRI and CVD • Describe reasons for referral to nephrologists • Discuss rationale/evidence

  3. Size of the problem - ESRD • New to ESRD • Canada 1996: 3332 patients • Growing at about 10% annually • In CRI in nephrology clinics • Rate of loss GFR ~ 6 mL/min/y • Initiation of dialysis ~ 8 mL/min

  4. Size of the problem - CRI • 10% of men and 2% of women have Cr>133 µmol/L • 11 million in US • Jones et al. Am J Kidney Dis 1998;32:992 • ~1 million in Canada

  5. Referral is mandatory • Diagnostic uncertainty • Treatment of specific diseases • Rapidly rising creatinine (20% increase over days to months)

  6. Optimization of management • Prevention of progression • Optimization of transition to ESRD • Management of metabolic complications of CRI • Management of comorbidity • cardiac • diabetic • other

  7. Optimization of management • Prevention of progression • Optimization of transition to ESRD • Management of metabolic complications of CRI • Management of comorbidity • cardiac • diabetic • other

  8. Rates of progression in referred populations are variable

  9. Multivariate risks for progression • HTN • Proteinuria

  10. Hypertension • Achieved BP control • Intensive blood pressure control • MDRD 1994 • MAP 92 mmHg vs. 107 mmHg; 98 mmHg vs. 113 mmHg • renal outcomes: no difference • HOT study 1998 • DBP <80 mmHg vs. 85 mmHg vs. 90 mmHg • CV outcomes: no difference

  11. Optimal blood pressure control: diabetics and nondiabetics

  12. Hypertension in patients with diabetes • UKPDS 1998 • 150/85 mmHg vs. 180/105mmHg • significant differences • death • stroke • microvascular disease • HOT study (subgroup) 1998 • DBP <80 mmHg vs. 85 mmHg vs. 90 mmHg • significant differences • CV events • CV death

  13. Tight control of blood pressure in patients with diabetes

  14. Hypertension • Volume control • sodium restriction • diuretics • Drug class • HANE 1997 • hydrochlorothiazide, atenolol, nitrendipine, enalapril • similar efficacy & tolerability • Isolated systolic hypertension • Proteinuria

  15. ACE inhibition • Diabetic nephropathy • Collaborative Study Group 1993 • Any chronic renal failure • REIN study 1997, 1998 • meta-analysis Giatras 1997 • proteinuria • increased effectiveness • Normotensive normoalbuminaemic type II DM • Ravid 1998

  16. ARB in DMN New Engl J Med 2001;345:851 & 861 & 870

  17. ACE inhibition & ARBs • Adverse effects • precipitation of ARF • monitoring • usually reversible • hyperkalaemia • dietary intervention • diuretics • K binding resins

  18. Dietary protein restriction • MDRD 1993 • 1.3 vs. 0.58 g/kg/day; 0.58 vs. 0.28 g/kg/day (+KA) • selected, well-nourished patients • intensive dietary counselling • nutritional parameters •  weight, arm circumference, % body fat •  albumin • no difference in rate of loss GFR

  19. Nutrition • Spontaneous reduction in protein intake, independent of dietary advice, with advancing CRI • Cross-sectional studies • Ikizler et al. J Am Soc Nephrol 1995;6:1386 • Pollock et al. J Am Soc Nephrol 1997;8:777

  20. Nutrition • Malnutrition independent predictor of death in ESRD • Bloembergen et al. Kidney Int 1996;50:557 • Struijk et al. Perit Dial Int 1994;14:121 • Churchill et al. J Am Soc Nephrol 1996;7:198 • Blake et al. J Am Soc Nephrol 1993;3:1501 • Maiorca et al. Nephrol Dial Transplant 1995;10:2295 • Jassal et al. Nephrol Dial Transplant 1996;11:1052

  21. Optimization of management • Prevention of progression • Optimization of transition to ESRD • Management of metabolic complications of CRI • Management of comorbidity • cardiac • diabetic • other

  22. How early are patients referred before ESRD? • 39% of HD patients and 27% of PD patients are referred <4 months prior to ESRD • USRDS Wave 2. Am J Kidney Dis 1997;30:S67

  23. How early are patients referred? • Canada, 1998-1999 • Consecutive patients new to ESRD • Multicentre, N=238 • 35% first saw a nephrologist within 3 months of starting dialysis • Curtis et al. Submitted

  24. Referral time • Effects on • mortality • morbidity • access: Collins 1997 • modality: Bloembergen 1997 • quality of life: Jones 1998

  25. Survival and referral time

  26. How early should patients be referred to observe these benefits?

  27. Canadian Clinical Practice Guidelines Creatinine clearance • Cockcroft-Gault formula • Refer when GFR <30 mL/min • Refer when Cr <300 µmol/L • Whichever is worse • Mendelssohn CMAJ 1999;161:4

  28. Referral to nephrologists in Ontario • Mailed survey, N=728, 41% response rate • Mendelssohn et al. Arch Intern Med 1995;155:2473

  29. Modality selection • Late referrals • less likely to select PD: Bloembergen 1997 • Multidisciplinary education •  time to requirement of dialysis: Binik 1993 • Choice •  HRQoL on PD: Szabo 1997

  30. Access • AVF > PTFE > catheter • 25% access at 30 days prior to initiation: USRDS 1997 • Woods 1997, Collins 1997 • access-related morbidity • cost • mortality • Assessment • Preservation of veins • Creation of fistula at GFR 15 - 25 mL/min

  31. Timing of initiation of dialysis • Early dialysis • Tattersall 1995 • CanUSA 1998 • Bonomini 1979 - 1986 • Results •  morbidity •  mortality •  rehabilitation

  32. Symptoms at initiation in the elderly: Porush & Faubert 1991

  33. Optimization of management • Prevention of progression • Optimization of transition to ESRD • Management of metabolic complications of CRI • Management of comorbidity • cardiac • diabetic • other

  34. Anaemia • Progressive relative erythropoietin deficiency and uraemic resistance to erthropoietin • Cardiac • In ESRD • LV dilatation, CHF, death: Foley 1996 • hospitalization, LoS, death: Collins 1997 • In CRF • LVH: Levin 1996 • Quality of life • SF-36 (ESRD): Merkus 1997 • SIP (CRF): Klang 1996

  35. Treatment of anaemia • Erythropoietin • cost • regulations • monitoring • Iron • p.o. (timing)or i.v. • Benefits • quality of life •  energy, physical functioning • no change in GFR, may  BP • Target Hgb

  36. Calcium homeostasis • Phosphate retention early • not necessarily accompanied by  phosphate • 1, 25 D3 deficiency • Hypocalcaemia • Hyperparathyroidism

  37. Management of calcium homeostasis • Dietary intervention • Phosphate binders • Calcium carbonate • 1-alphacalcidol • decreases  PTH • no effect on GFR • monitoring

  38. Metabolic acidosis • Malnutrition • Metabolic bone disease • Treatment • Sodium bicarbonate

  39. Malnutrition • Progressive spontaneous decline in protein intake • MDRD 1994, Ikizler 1995, Pollock 1996 • Malnutrition at initiation: CanUSA 1996 • morbidity • mortality • Improves with starting dialysis: CanUSA 1996

  40. Malnutrition • Management • dietary intervention • 0.8 - 1.3 g/kg/day protein • adequate calories • control of acidosis • initiation of dialysis

  41. Nutrition in unreferred populations • National Health and Nutrition Examination Survey III database • 5248 participants over 60y • Composite definition of malnutrition • Adjusted OR for malnutrition • GFR 30-60 mL/min 1.2 (0.7 – 2.0) • GFR <30 mL/min 3.6 (2.0 – 6.6) • Garg et al, submitted

  42. Optimization of management • Prevention of progression • Optimization of transition to ESRD • Management of metabolic complications of CRI • Management of comorbidity • cardiac • diabetic • other

  43. Cardiac comorbidity is common • Consecutive prevalent patients with CRI in nephrology clinics, mean GFR 75 mL/min • Previous CVD 38.5% • CVD associated with severity of CRI • 80% hypertension • 43% hyperlipidemia • 38% had diabetes mellitus • 27% were smokers

  44. Renal insufficiency is an independent CV risk factor Garg et al. Submitted.

  45. Cardiac comorbidity • Hypertension control • Lipid-lowering agents • ACE inhibition • Beta-blockers • ASA • Anticoagulation • Smoking cessation

  46. Diabetic comorbidity • Glycaemic control • DCCT 1993 (type I) • UKDPS 1998 (type II) • Hypertension • HOT 1998 (subgroup) • UKPDS 1998 • ACE inhibitors • retinopathy (Euclid 1998)

  47. Formalized care of patients with chronic renal failure

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