Section 4: Managing progression of CKD

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

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

Hypertension and Progression

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:

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

70% RRR* Irbesartan 300 mg vs Placebo, p < Incidence of diabetic nephropathy (%) Placebo Irbesartan 150 mg Irbesartan 300 mg No. at Risk Months of Follow-up 22 Adapted from Parving H-H, et al. N Engl J Med 2001;345: IRMA 2 - primary endpoint *RRR = relative risk reduction

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

Cardiovascular mortality risk in the general population Impact of microalbuminuria 1.Adapted from Hallan et al. Archives Internal Medicine ;22; K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease Am J Kidney Dis 2002; 39 (2 Suppl 1):S Edinburgh Consensus Conference on Early Chronic Kidney Disease, February 2007 ( 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 & a 3 3b 3 & 4 2

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

Proteinuria and ESRF 10, , Proteinuria Screened ESRF Iseki et al KI 2003

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:

Proteinuria and Progression of CKD: REIN Study

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: 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 % % %