ESPN 50th Annual Meeting

ESPN 2017


 
Early proteinuria lowering by ACE inhibition is predictive of renal survival in children with chronic kidney disease
SOPHIE VAN DEN BELT 1 HIDDO JAN LAMBERS HEERSPINK 1 VALENTINA GRACCHI 2 DICK DE ZEEUW 1 ELKE WUEHL 3 FRANZ SCHAEFER 3

1- UNIVERSITY MEDICAL CENTER GRONINGEN, DEPARTEMENT OF CLINICAL PHARMACY AND PHARMACOLOGY
2- UNIVERSITY MEDICAL CENTER GRONINGEN, DEPARTMENT OF PEDIATRIC NEPHROLOGY
3- HEIDELBERG UNIVERSITY HOSPITAL, DEPARTEMENT OF PEDIATRIC NEPHROLOGY
 
Introduction:

The degree of proteinuria predicts progression of renal failure in adults and children with chronic kidney disease (CKD). While lowering of proteinuria by various interventions has been demonstrated to be nephroprotective in adults with proteinuric nephropathies, pediatric data on the relationship of pharmacotherapeutic proteinuria lowering and long-term renal survival is scarce. Here we have revisited the ESCAPE Trial to investigate a potential quantitative association of the initial antiproteinuric effect of standardized ACE inhibition with subsequent renal disease progression in children with CKD.

Material and methods:

All children were started on a fixed dose of ramipril (6 mg/m2/day) and randomized to aim for conventional or intensified blood pressure control. The initial log-transformed change in proteinuria was assessed from baseline to first measurement after starting ramipril (at 2.6 ± 1.4 months). Cox proportional hazard models were used to estimate the association between initial proteinuria change and risk of reaching the renal endpoint (composite of 50% decline in eGFR or progression to end-stage-renal disease), adjusted for age, gender, CKD diagnosis, baseline proteinuria, blood pressure, eGFR and change in blood pressure. 

Results:

Of 285 eligible patients (59% male, age 11.5±3.9 years), 85 reached the endpoint within 5 years of follow-up. Proteinuria was reduced following start of ramipril treatment by a median of 40% (interquartile range 8-64%).  As compared to a reduction in proteinuria of less than 30%, a 30-60% reduction accounted for a HR of 0.65 (CI 0.38-1.12) and reduction of more than 60% gave a HR of 0.42 (0.22-0.79).  This association was independent of eGFR (HR 0.93, CI 0.91-0.94), proteinuria (HR 1.24, CI 1.13-1.38) and blood pressure (HR 1.21, CI 1.03-1.42).

Conclusions:

 The early antiproteinuric effect of ACE inhibition is independently predictive for long-term preservation of renal function in children with CKD. This finding suggests that proteinuria lowering is an important target in the management of pediatric CKD.