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Section 4: Managing progression of CKD. The downward spiral. Glomerulosclerosis. RENAL FUNCTION. Intraglomerular hypertension. Reduction in number of functioning glomeruli. Increased blood flow to remaining nephrons.
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The downward spiral Glomerulosclerosis RENAL FUNCTION Intraglomerular hypertension Reduction in number of functioning glomeruli Increased blood flow to remaining nephrons
Renal disease: dilated afferent arteriole allows transmission of high systemic pressure leading to glomeular capillary hypertension MAP Anti-hypertensives reduce MAP GCP ACEI/ARBs dilate the efferent arteriole – the downstream pressure valve – thus controlling glomerular capillary hypertension
1860 patients with non-diabetic kidney disease Meta-analysis of 11 RCTs of ACEIs RR Systolic BP (mmHg) Jafar et alAnn Intern Med 2003;139:244-252 Blood Pressure and Progression of CKD AIPRD Study
Number of Medications to reach target blood pressure Bakris et al AJKD 2001
20 15 Incidence of diabetic nephropathy (%) 10 5 0 22 24 0 3 12 18 6 No. at Risk Months of Follow-up 201 195 194 201 195 194 164 167 180 154 161 172 139 148 159 129 142 150 36 45 49 Placebo Irbesartan 150 mg Irbesartan 300 mg IRMA 2 - primary endpoint 70% RRR* Irbesartan 300 mg vs Placebo, p < 0.001 *RRR = relative risk reduction Adapted from Parving H-H, et al.N Engl J Med 2001;345:870-878
AIPRI: Reduction of Risk with ACE-I Proteinuria Creatinine Clearance Maschio G, et al. N Engl J Med. 1996;334(15):939-945.
Cardiovascular mortality risk in the general populationImpact of microalbuminuria ‡ *P<0.05 †P<0.01 ‡P<0.001 Adjusted incidence rate ratios (IRR) Category of eGFR, mL/min/1.73 m2 Corresponding CKD stage 1 & 22 22 3a3 3b3 & 42 ‡ ‡ † * * UACR • Adapted from Hallan et al. Archives Internal Medicine 2007 167;22;2490-2496 • K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease Am J Kidney Dis 2002; 39 (2 Suppl 1):S1-246 • 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)
Urine Protein Excretion and CKD ProgressionAIPRD study group RR 4685 records with non-diabetic kidney disease Meta-analysis of 11 RCTs of ACEIs Urine protein excretion (g/day) Jafar et al 2003
Proteinuria and ESRF Proteinuria Screened ESRF 86,253 185 10,000 38 4007 55 1072 76 357 55 Iseki et al KI 2003
Urine Protein Excretion and Progression of CKDAIPRD Study Group 4685 records with non-diabetic kidney disease Meta-analysis of 11 RCTs of ACEIs RR Urine protein excretion (g/day) Jafar et al, Ann Intern Med 2003;139:244-252
Optimal ManagementSaves Patients from Dialysis Renoprotective strategies that decrease the rate of GFR decline also delay ESRD Comparison is with expected rate of GFR decline (7.56 mL/min/1.73m2) Adapted from Trivedi et al.Am J Kidney Dis 2002; 17:371-375