1. Section 4: Managing progression of CKD

2. Glomerulosclerosis Reduction in number of functioning glomeruli Increased blood flow to remaining nephrons Intraglomerular hypertension RENAL FUNCTION The downward spiral

3. MAP Renal disease: dilated afferent arteriole allows transmission of high systemic pressure leading to glomeular capillary hypertension ACEI/ARBs dilate the efferent arteriole – the downstream pressure valve – thus controlling glomerular capillary hypertension GCP Anti-hypertensives reduce MAP

4. Hypertension and Progression

5. Blood Pressure and Progression of CKD AIPRD Study Meta-analysis of 11 RCTs of ACEIs 1860 patients with non-diabetic kidney disease RR Systolic BP (mmHg) Jafar et al Ann Intern Med 2003;139:244-252

6. Number of Medications to reach target blood pressure Bakris et al AJKD 2001

7. 70% RRR* Irbesartan 300 mg vs Placebo, p < 0.001 Incidence of diabetic nephropathy (%) 0 5 10 15 20 0 3 6 1218 24 201 195 194 Placebo Irbesartan 150 mg Irbesartan 300 mg 201 195 194 164 167 180 154 161 172 139 148 159 36 45 49 No. at Risk 129 142 150 Months of Follow-up 22 Adapted from Parving H-H, et al. N Engl J Med 2001;345:870-878 IRMA 2 - primary endpoint *RRR = relative risk reduction

9. AIPRI: Reduction of Risk with ACE-I Maschio G, et al. N Engl J Med. 1996;334(15):939-945. Creatinine Clearance Proteinuria

10. Cardiovascular mortality risk in the general population Impact of microalbuminuria 1.Adapted from Hallan et al. Archives Internal Medicine 2007 167;22;2490-2496 2.K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease Am J Kidney Dis 2002; 39 (2 Suppl 1):S1-246 3.Edinburgh Consensus Conference on Early Chronic Kidney Disease, February 2007 (http://www.rcpe.ac.uk/Whats_New/consensus-statements/final-early-chronic-kidney-disease.pdf; date last accessed 30/04/08) * P<0.05 †P<0.01 ‡P<0.001 * † ‡ ‡ Adjusted incidence rate ratios (IRR) UACR Category of eGFR, mL/min/1.73 m 2 ‡ Corresponding CKD stage 1 & 2 22 3a 3 3b 3 & 4 2

11. Urine Protein Excretion and CKD Progression AIPRD study group Meta-analysis of 11 RCTs of ACEIs 4685 records with non-diabetic kidney disease RR Urine protein excretion (g/day) Jafar et al 2003

12. Proteinuria and ESRF 10,000 38 86,253 185 4007 55 1072 76 357 55 Proteinuria Screened ESRF Iseki et al KI 2003

13. Urine Protein Excretion and Progression of CKD AIPRD Study Group Meta-analysis of 11 RCTs of ACEIs 4685 records with non-diabetic kidney disease RR Urine protein excretion (g/day) Jafar et al, Ann Intern Med 2003;139:244-252

14. Proteinuria and Progression of CKD: REIN Study

16. Optimal Management Saves Patients from Dialysis Renoprotective strategies that decrease the rate of GFR decline also delay ESRD Adapted from Trivedi et al. Am J Kidney Dis 2002; 17:371-375 Comparison is with expected rate of GFR decline (7.56 mL/min/1.73m 2 ) Slowing of GFR decline Years delay for GFR 60 (Stage 3) Years delay for GFR 30 (Stage 4) 30 %2.941.24 20 %1.720.72 10 %0.980.32