1 / 16

Dick de Zeeuw Department of Clinical Pharmacology University Medical Center Groningen The Netherlands

Albuminuria; a tool for measuring non-blood pressure related renal protection. Data from the RENAAL trial. Dick de Zeeuw Department of Clinical Pharmacology University Medical Center Groningen The Netherlands. RENAAL.

gayle
Download Presentation

Dick de Zeeuw Department of Clinical Pharmacology University Medical Center Groningen The Netherlands

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Albuminuria; a tool for measuring non-blood pressure related renal protection. Data from the RENAAL trial Dick de Zeeuw Department of Clinical Pharmacology University Medical Center Groningen The Netherlands

  2. RENAAL • Trial design: Rand control trial, double dummy intervention placebo vs losartan with conventional therapy background (without ACEi or ARB) • Population: 1513 type 2 diabetic nephropathy • Serum creatinine: 1.3 to 3 mg/dl • Albuminuria: > 300 mg/g • Dosing: 50 mg losartan or 100 mg if blood pressure >140/90 • Measurements: • Albuminuria: morning void ACR; 24 hour Albumin and ACR in subgroup (n=710) • Proteinuria: 24 hour proteinuria, in subgroup (n=710) • Change in albuminuria: • Individual ACR change comparing baseline to 6 months • End-points: • Combined endpoint: Doubling serum creatinine, ESRD, Death • Single of each

  3. 160 P Systolic L 140 120 Blood Pressure (mmHg) MAP 100 Diastolic 80 Pulse Pressure 60 0 12 24 36 48 Mo RENAAL; AII-antagonist more renal protective than placebo in type 2 diabetes; similar blood pressure, different albuminuria Placebo Risk Reduction: 16% 50 p=0.024 40 Losartan 30 % with event 20 40 10 20 P 0 0 Albuminuria (Change,%) 0 12 24 36 48 -20 35% Overall Reduction p=<0.001 -40 L -60 0 12 24 36 48Mo Brenner et al; New Engl J Med 2001

  4. Questions • Is Albuminuria a predictor of outcome? • Is it independent from other risk markers? • Is proteinuria different than albuminuria • Is spot sampling different than 24 hour • Is Albuminuria lowering predictive of outcome? • Is it independent from blood pressure lowering? • Is residual albuminuria predicting outcome?

  5. RENAAL; Baseline proteinuria as a determinant for renal events in type 2 diabetic nephropathy 30 20 10 Primary composite Endpoint ESRD 15 10 Hazard ratio Hazard ratio 5 0 0 ³ ³ ³ ³ ³ ³ ³ ³ <.5 2.0 2.95 4.4 5.25 ³ <.5 2.0 2.95 4.4 5.25 Baseline Albuminuria (g/g) Baseline Albuminuria (g/g) De Zeeuw et al; Kidney Int 2004

  6. RENAAL; Model for independent renal risk factors during (optimal) blood pressure treatment in type 2 diabetic nephropathy (n=1300) 95% Conf Interval p-Value Hazard Ratio* 6.2 Urine albumin:creatinine (log, mg/g) 4.4 - 8.7 <0.0001 2.1 1.7 – 2.5 <0.0001 Serum creatinine (mg/dL) 0.70 0.61 - 0.80 <0.0001 Serum albumin (per 0.5 g/dL) 0.89 0.84 - 0.95 =0.0001 Hemoglobin (g/dL) RENAAL RISK SCORE: (1.96 log [urinary albumin:creatinine ratio]) *(0.78 serum albumin [g/dl]) *(1.28 serum creatinine [mg/dl]) *(0.11 hemoglobin [g/dl]). Keane et al, Kidney Int 2003; and Keane et al, Clin J Am Soc Nephrol 2006

  7. Questions • Is Albuminuria a predictor of outcome? • Is it independent from other risk markers? • Is proteinuria different than albuminuria • Is spot sampling different than 24 hour • Is Albuminuria lowering predictive of outcome? • Is it independent from blood pressure lowering? • Is residual albuminuria predicting outcome?

  8. <0% 60 60 50 50 >30% 40 40 <0% % with ESRD 30 30 % with composite endpoint 20 20 >30% 10 10 0 0 0 12 24 36 48 0 12 24 36 48 Month Month RENAAL; Albuminuria Reduction (<0% versus >30%) at Month 6 determines the renal outcome ESRD Renal Endpoint De Zeeuw et al; Kidney Int 2004

  9. ESRD Renal Endpoint 2.5 2.5 2.0 2.0 1.5 1.5 Hazard ratio 1.0 1.0 0.5 0.5 0.0 0.0 -90 -25 0 25 50 72 -90 -25 0 25 50 72 Albuminuria reduction (%) Albuminuria reduction (%) RENAAL; Initial anti-albuminuric response predicts renal outcome De Zeeuw et al; Kidney Int 2004

  10. RENAAL; Antialbuminuric effect of losartan expIains the renal protective effect De Zeeuw et al; Kidney Int 2004

  11. RENAAL; Response variability discordant for blood pressure and albuminuria Eijkelkamp et al; JASN 2007

  12. RENAAL; Differential effect of antihypertensive treatment on albuminuria and BP has differential effect on ESRD Eijkelkamp et al; JASN 2007

  13. Questions • Is Albuminuria a predictor of outcome? • Is it independent from other risk markers? • Is proteinuria different than albuminuria • Is spot sampling different than 24 hour • Is Albuminuria lowering predictive of outcome? • Is it independent from blood pressure lowering? • Is residual albuminuria predicting outcome?

  14. RENAAL; High residual albuminuria levels 300 300 272 264 252 247 250 250 230 196 189 200 200 169 165 160 158 155 150 150 123 106 99 100 100 79 47 43 50 50 37 35 0 0 <.5 .5-1.5 1.5-3.5 3.5-5.0 >5.0 <.5 .5-1.5 1.5-3.5 3.5-5.0 >5.0 Losartan 0 mo (n=751) Placebo 0 mo (n=762) Losartan 6 mo (n=751) Placebo 6 mo (n=762) De Zeeuw et al; Kidney Int 2004

  15. RENAAL: Residual high albuminuria and not residual high blood pressure determines risk for ESRD Eijkelkamp et al; JASN 2007

  16. Summary • Is Albuminuria a predictor of outcome? YES • Is it independent from other risk markers? YES • Is proteinuria different than albuminuria NO • Is spot sampling different than 24 hour NO • Is Albuminuria lowering predictive of outcome? YES • Is it independent from blood pressure lowering? YES • Is residual albuminuria predicting outcome? YES

More Related