Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies

Piero Ruggenenti, Annalisa Perna, Lidia Mosconi, Roberto Pisoni, Giuseppe Remuzzi

Research output: Contribution to journalArticlepeer-review


We investigated the predictors of the rate of glomerular filtration rate decline (ΔGFR) and progression to end-stage renal failure (ESRF) in the 352 patients with proteinuric non-diabetic chronic nephropathies [urinary protein excretion rate (U(Prot)) ≤ 1 g/24 hr, creatinine clearance 20 to 70 ml/min/1.73 m2] enrolled in the Ramipril Efficacy In Nephropathy (REIN) study. Overall the GFR declined linearly by 0.46 ± 0.05 ml/min/1.73 m2/month (mean rate ± SEM) over a median follow-up of 23 months (range 3 to 64 months), and progression to ESRF was 17.3%. Using multivariate analysis, higher U(Prot) and mean arterial pressure (MAP) independently correlated with a faster ΔGFR (P = 0.0001 and P = 0.0002, respectively) and progression to ESRF (P = 0.0001 and P = 0.003, respectively). Mean U(Prot) and systolic blood pressure during follow-up were the only time-dependent covariates that significantly correlated with ΔGFR (P = 0.005 and P = 0.003, respectively) and ESRF (P = 0.006 and P = 0.0001, respectively). After stratification for baseline U(Prot), patients in the lowest tertile (U(Prot) <1.9 g/24 hr) had the slowest ΔGFR (0.16 ± 0.07 ml/min/1.73 m2/month) and progression to ESRF (4.3%) as compared with patients in the middle tertile (U(Prot) 2.0 to 3.8 g/24 hr; ΔGFR, 0.55 ± 0.09 ml/min/1.73 m2/month, P = 0.0002; ESRF, 15.3%, P = 0.0001) and in the highest tertile (U(Prot) 3.9 to 18.8 g/24 hr; ΔGFR, 0.70 ± 0.11 ml/min/1.73 m2/month, P = 0.0001; ESRF, 32.5%, P = 0.0001). Both ΔGFR (P = 0.01) and progression to ESRF (P = 0.01) significantly differed even between the middle and the highest tertiles. On the contrary, stratification in tertiles of baseline MAP failed to segregate subgroups of patients into different risk levels. Patients with the highest proteinuria and blood pressure were those with the fastest progression (ΔGFR, 0.91 ± 0.23; ESRF 34.7%). Of interest, at each level of baseline MAP, a higher proteinuria was associated with a faster ΔGFR and progression to ESRF. On the other hand, at each level of proteinuria, a faster ΔGFR was associated with MAP only in the highest tertile (> 112 mm Hg) and the risk of ESRF was independent of the MAP. Thus, in chronic nephropathies proteinuria is the best independent predictor of both disease progression and ESRF. Arterial hypertension may contribute to the acceleration of renal injury associated with enhanced traffic of plasma proteins. Antihypertensive drugs that most effectively limit protein traffic at comparable levels of blood pressure are those that most effectively slow disease progression and delay or prevent ESRF in proteinuric chronic nephropathies.

Original languageEnglish
Pages (from-to)1209-1216
Number of pages8
JournalKidney International
Issue number5
Publication statusPublished - 1998


  • Blood pressure
  • Chronic nephropathy
  • Glomerular filtration rate
  • Injury
  • Progression of renal disease
  • Proteinuria
  • Survival

ASJC Scopus subject areas

  • Nephrology


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