Chronic proteinuric nephropathies: Outcomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury

Piero Ruggenenti, Annalisa Perna, Giulia Gherardi, Roberto Benini, Giuseppe Remuzzi

Research output: Contribution to journalArticle

Abstract

The Ramipril Efficacy in Nephropathy (REIN) study found that angiotensin-converting enzyme (ACE) inhibitors effectively decreased proteinuria, glomerular filtration rate (GFR) decline (ΔGFR), and incidence of end-stage renal disease (ESRD) in patients with proteinuric chronic nephropathies. In this study, we prospectively investigated the main clinical determinants-of progression and response to treatment in the 352 patients enrolled into the REIN study. Mean ΔGFR (0.56 ± 0.05 [SEM] versus 0.21 ± 0.05 mL/min/1.73 m 2/mo; P = 0.0001) and incidence of ESRD (30% and 10%; P = 0.0001) were more than twice that in patients with proteinuria of 2 g/24 h or greater of protein compared with those with protein less than 2 g/24 h (relative risk [RR], 4.07; 95% confidence interval [CI], 2.20 to 7.52), as well as in patients with hypertension compared with normotension (mean ΔGFR, 0.48 ± 0.05 versus 0.22 ± 0.05 mL/min/1.73 m 2/mon; P = 0.0006; ESRD, 25% versus 10%; P = 0.004; RR, 3.18; 95% CI, 1.38 to 7.32). Hypertension at study entry (P = 0.038), greater mean blood pressure on follow-up (P = 0.002), and urinary protein excretion rate (P = 0.0001) were independent predictors of faster ΔGFR. ΔGFR was approximately twofold faster in patients with type 2 diabetes than in those with primary glomerular disease (P = 0.002; including immunoglobulin A [IgA] nephropathy, P = 0.009); nephrosclerosis (P = 0.03), adult polycystic kidney disease (APKD), or chronic interstitial nephritis (P = 0.006). Diabetes at study entry (P = 0.02) and greater mean blood pressure (P = 0.0001) and urinary protein excretion rate (P= 0.0001) on follow-up were independent predictors of faster ΔGFR. After correction for baseline covariates, diabetes was also associated with an increased risk for progression to ESRD (RR, 2.39; 95% CI, 1.01 to 5.68; P <0.05). At multivariate analyses ramipril significantly decreased ΔGFR (regression coefficient, -0.23 ± 0.11 [SEM]; P = 0.036) and ESRD (RR, 2.08; 95% CI, 1.21 to 3.57; P = 0.008) in patients with baseline proteinuria of 2 g/24 h or greater of protein, and the renoprotective effect increased for increasing levels of proteinuria. Ramipril decreased ΔGFR to a similar extent in normotensive and hypertensive patients (-0.14 ± 0.11 versus -0.14 ± 0.09) and significantly limited ESRD in hypertensive patients (RR, 2.03; 95% CI, 1.26 to 3.26; P = 0.004). ΔGFR was decreased by 42% in primary glomerular disease (P = 0.017), by 35% in IgA nephropathy, and by 37% in nephrosclerosis, but was not improved in type 2 diabetes, APKD, or interstitial nephritis. At multivariate analyses, ramipril significantly slowed ΔGFR (-0.24 ± 0.08; P = 0.004) and progression to ESRD (RR, 2.32; 95% CI, 1.36 to 3.96; P = 0.002) in patients without diabetes, but not in patients with diabetes, who tended to have a faster ΔGFR (+0.62 ± 0.44) on ramipril therapy. In summary, patients with proteinuria of 2 g/24 h or greater of protein, preexisting hypertension, or type 2 diabetes were faster progressors. Greater blood pressure and degree of proteinuria were the strongest determinants of faster GFR decline. The renoprotective effect of ramipril was similar in patients with normotension and hypertension. Hypertensive patients and those with proteinuria of 2 g/24 h or greater of protein, primary glomerular disease, or nephrosclerosis gained the most from ACE inhibitor treatment. During the study period, those with proteinuria less than 2 g/24 h of protein, type 2 diabetes, or polycystic kidney disease did not benefit by treatment to an appreciable extent. (C) 2000 by the National Kidney Foundation, Inc.

Original languageEnglish
Pages (from-to)1155-1165
Number of pages11
JournalAmerican Journal of Kidney Diseases
Volume35
Issue number6
Publication statusPublished - 2000

Keywords

  • Angiotensin- converting enzyme (ACE) inhibitors
  • Diabetic nephropathy
  • Hypertension
  • Nephroprotection
  • Proteinuric nephropathies
  • Renal disease progression

ASJC Scopus subject areas

  • Nephrology

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