Diabetic nephropathy Diabetes is common in Saudi Arabia
Diabetic nephropathy § Diabetes is common in Saudi Arabia § This mainly related to genetic factors as well as the life style § 40% of patients with ERSD are diabetics
The Kidney’s
Transplantatio n Advantages Pa tient's Kidney v Most like your own kidney v No dialysis needed Tra nspla nt Kidney v No access needed (extra -peritonea lly) v Normal Diet (-sodium) v More “normal” life style Disadvantage v Risks of major surgery v Risk of body rejecting kidney v Possible side effects of drugs Bla dder
Renal impairment: Prevalence § The progression of renal impairment can lead to endstage renal disease which has huge medical, social and financial consequences § End-stage renal disease is particularly prevalent in: § § § The elderly African-Americans Patients with diabetes § Nearly half of the hypertensive population displays some abnormality of renal function
Progression to end-stage renal disease In type 1 diabetes, progression to end-stage renal disease has been sequenced into five stages: l Early hypertrophy of renal tissue and increased glomerular filtration rate (GFR) l Development of glomerular lesions without any clinically appreciable disease (GFR remains increased) l Incipient nephropathy with microalbuminuria (GFR normal or slightly increased) l Clinical nephropathy with marked proteinuria and decreased GFR l GFR continues to decrease and end-stage renal disease develops
Type 1 § Strict glycaemic control can decrease the nephropathy and progression of renal diseases
Type one DM It has been suggested that 25 to 45 percent of these patients will, during their lifetime, develop clinically evident disease
§ Strict blood pressure control is very important § Genetic factors play major role in diabetic nephropathy § Most patients have retinopathy § Most are asymptomatic
Nutrition
Alternatives to Avoid
Nutrition in Patients with CRF Classes of nutrients v - carbohydrates v - fats v - proteins v - vitamins v - minerals v - water Essential nutrients v - amino-acids • Without these, an individual cannot function • Dietary protein provide amino acids - body proteins • Without sufficient dietary protein and energy, no growth or repair
Recommended Protein & Energy Intakes Protein (g/kg BW/day) Healthy adults > 0. 75# Energy (kcal/kg BW/day) >35 CRF patients (non-dialyzed) ? 0. 60 (high quality) >35 HD patients > 1. 2 >35 CAPD patients > 1. 2 >35 # safe for 97. 5 % of the population (WHO 1985) CRF patients with GFR 3020 ml/min reduce protein and energy intake (MDRD study) Protein and energy intake lower than recommended in a large proportion (20 -60%? ) of HD and CAPD patients
Serum albumin alone is neither necessary nor sufficient to indicate malnutrition
Relative Death Risk Serum Albumin and Death Risk Haemodialysis Patients 20 10 0 <=2. 5 -3. 0 -3. 5 -4. 0 -4. 5 Serum Albumin (mg/dl) Lowrie et al, 1990 >4. 5
Urinary albumin excretion Normal excretion <30 mg/24 hrs (<20 µg/min) Microalbuminuria 30– 300 mg/24 hrs (20– 200 µg/min) Clinical proteinuria >300 mg/24 hrs (>200 µg/min) Mogensen CE et al. Lancet 1995; 346: 1080– 1084
Microalbuminuria: Prevalence and predictive power in diabetics § Type 1 diabetes § Prevalence: 50% § Predictive value for the development of nephropathy: 75% § Type 2 diabetes § Prevalence: 25– 60% (depending on ethnic origin) § Predictive value for the development of nephropathy: 25% Savage MW et al. Br J Hosp Med 1995; 54: 429– 435 Viberti GC et al. In: International Textbook of Diabetic Medicine, 1992
Serum creatinine level of 1. 4 mg/dl: What is the renal function? Serum creatinine (mg/dl) 12 Large muscular male Normal male Small female 10 8 6 4 2 0 120 100 60 GFR (ml/min) 30 15 50 25 Fraction of normal renal function (%) 0 Sica DA. Unpublished data
Therapeutic options in hypertension ACE inhibitors Angiotensin II antagonists a 1 -antagonists Hypertensio n b-blockers Diuretics Calcium antagonists
ACE inhibitors in hypertension and heart failure In hypertension, ACE inhibitors § Lower blood pressure § Reduce the progression of end-organ damage In heart failure, ACE inhibitors § Improve cardiovascular hemodynamics § Improve symptomatolgy and exercise capacity § Decrease morbidity and mortality
ACE inhibitors and renal impairment: Considerations ACE inhibitors show renoprotective effects over and above blood pressure control Dose modifications are a consideration in patients with renal impairment (except for fosinopril) Occasional cases of renal impairment and hyperkalemia have been reported with ACE inhibitors
Adrenergic agents and renal impairment: Considerations Adrenergic agents There is no evidence of renoprotective effects over and above blood pressure control Modification of initial dosing is a consideration for hydrophilic b-blockers Post-dose temporary reduction in renal blood flow and GFR
Calcium antagonists and renal impairment: Considerations Calcium antagonists There is no evidence of a class-specific renoprotective effect over and above blood pressure control The effect of renal impairment on metabolism of some active metabolites of calcium antagonists (e. g. diltiazem, verapamil) is unknown
Diuretics and renal impairment: Considerations Diuretics There is no evidence of renoprotective effects over and above blood pressure control Thiazides may decrease renal blood flow and GFR Efficacy may be reduced in renal impairment
Antihypertensive treatment in diabetes: Additional considerations Adapted from Cziraky MJ et al. Ann Pharmacother 1996; 30: 791– 801
Schematic diagram of ACE inhibition and renal function Normotensive Hypertensive Renal function (%) Hypertensive treated with an ACE inhibitor Time (years)
Renoprotection: ACE inhibitors vs. other antihypertensives Calcium antagonists ACE inhibitors Diuretics and/or bblockers Urinary protein Mean systemic blood pressure 0 – 10 – 20 – 30 – 40 Decrease from baseline (%) Böhlen L et al. Am J Hypertens 1994; 7: 84 S– 92 S – 50
ACE inhibitors are renoprotective ACE inhibitors have demonstrated renoprotective potential in: § § Patients with type 2 diabetes Patients with type 1 diabetes Non-diabetic patients with nephropathy Non-diabetic patients with hypertension and nephropathy § Non-diabetic hypertensive patients without pre-existing nephropathy
Initial value of reciprocal creatinine (%) ACE inhibition: Renoprotection in type 2 diabetes 105 Placebo (years 1– 5) and ACE inhibitor (years 6 and 7) ACE inhibitor (years 1– 5) and placebo (years 6 and 7) Placebo (years 1– 7) ACE inhibitor (years 1– 7) 100 95 90 85 80 0 1 2 3 4 Treatment (years) 5 6 7 Ravid M et al. Arch Intern Med 1996; 156: 286– 289
Died or needed dialysis or transplantation (%) ACE inhibition: Renoprotection in type 1 diabetes 50 Placebo Captopril 40 30 20 p=0. 006 10 0 0 Placebo Captopril n=202 n=207 1 198 207 2 Follow-up (years) 192 204 186 201 171 195 3 121 140 103 4 59 64 Lewis EJ et al. N Engl J Med 1993; 329: 1456– 1462 26 37
ACE inhibition: Renoprotection in non-diabetic nephropathy Patients not reaching an endpoint (%) 100 90 80 70 Placebo Benazepril 60 50 0 1 Treatment (years) 2 Adapted from Maschio G et al. N Engl J Med 1996; 334: 939– 945 3
ACE inhibition: Renoprotection in hypertension and nephropathy Cumulative survival rate (%) 100 90 80 70 Placebo ACE inhibitor 60 Log rank test p<0. 05 50 0 5 10 15 20 Treatment (months) 25 30 Hannedouche T et al. Br Med J 1994; 309: 833– 837 3
ACE inhibition: Renoprotection in hypertensive patients Decrease in GFR (ml/min/1. 73 m 2) Time (months) 0 0 6 12 18 24 30 – 1 – 2 – 3 – 4 – 5 – 6 – 7 ACE inhibitor b-blocker Himmelmann A et al. Am J Hypertens 1996; 9: 850– 853 3
Dosing of different ACE inhibitors depending on renal function Sica DA. J Cardiovasc Pharmacol 1992; 20(Suppl 10): S 13–S 20
Microalbuminuria: Prevalence and predictive power in non-diabetics § Non-diabetics § Prevalence: 25– 40% (depending on level of antihypertensive control) § Predictive value for the development of nephropathy: Thought to be lower than in diabetic patients Bigazzi R et al. Nephron 1992; 61: 94– 97 Ljungman S. Am J Hypertens 1990; 3: 956– 960
ACE inhibitors are renoprotective ACE inhibitors have demonstrated renoprotective potential in: § § Patients with type 2 diabetes Patients with type 1 diabetes Non-diabetic patients with nephropathy Non-diabetic patients with hypertension and nephropathy § Non-diabetic hypertensive patients without pre-existing nephropathy
Died or needed dialysis or transplantation (%) ACE inhibition: Renoprotection in type 1 diabetes 50 Placebo Captopril 40 30 20 p=0. 006 10 0 0 Placebo Captopril n=202 n=207 1 198 207 2 Follow-up (years) 192 204 186 201 171 195 3 121 140 103 4 59 64 Lewis EJ et al. N Engl J Med 1993; 329: 1456– 1462 26 37
ACE inhibition: Renoprotection in hypertension and nephropathy Cumulative survival rate (%) 100 90 80 70 Placebo ACE inhibitor 60 Log rank test p<0. 05 50 0 5 10 15 20 Treatment (months) 25 30 Hannedouche T et al. Br Med J 1994; 309: 833– 837 3
Correlation between beneficial renal effects and albuminuria * Change in GFR (ml/min/1. 73 m 2/month) 0. 4 Controls ACE inhibitors 0 – 0. 4 – 0. 8 *p=0. 02 vs. controls <30 30– 300 Baseline albuminuria (mg/day) >300 Lebovitz HE et al. Kidney Int 1994; 45(Suppl 45): S 150–S 155
Dosing of different ACE inhibitors depending on renal function Sica DA. J Cardiovasc Pharmacol 1992; 20(Suppl 10): S 13–S 20
Simplifying antihypertensive treatment in the presence of renal failure If a patient presents with hypertension Consider that the patient may have renal impairment WHY? Measure renal function If some degree of renal dysfunction is found, consider treatment with an ACE inhibitor If you consider treatment with an ACE inhibitor, consider dual and compensatory elimination WHY? Hypertension accelerates the decline in GFR and many hypertensive patients have some degree of renal impairment ACE inhibitors are the only antihypertensives with established renoprotective potential
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