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Achieving remission of proteinuria in childhood CKD
Piero Ruggenenti1,2, Paolo Cravedi3, Antonietta Chianca1
1Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò", IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
Insights
Combination therapy using maximum doses of ACE inhibitors and ARBs effectively reduces proteinuria in children with kidney disease. This safe treatment strategy can stabilize or improve kidney function, offering a promising approach for pediatric nephropathies.
Area of Science:
- Nephrology
- Pediatric Nephrology
- Pharmacology
Background:
- A multidrug strategy combining angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) at maximum tolerated doses, along with intensive blood pressure (BP) control, is known to prevent renal function loss in adults with proteinuric nephropathies.
- This study investigated the efficacy and safety of this combined therapeutic approach in pediatric patients with proteinuric nephropathies.
Purpose of the Study:
- To evaluate the effects of a combined ACE inhibitor and ARB treatment protocol on proteinuria and renal function in children with chronic nephropathies.
- To assess the safety and efficacy of up-titrating ramipril and losartan to maximum approved and tolerated doses in pediatric patients.
Main Methods:
- An observational, longitudinal cohort study included 20 children with chronic nephropathies and significant proteinuria (>200 mg/24 h).
- Patients received ramipril and losartan, up-titrated to maximum approved and tolerated doses.
- Primary efficacy endpoint was >50% reduction in proteinuria to <200 mg/24 h (remission); secondary outcomes included changes in proteinuria, serum albumin, BP, and glomerular filtration rate (GFR).
Main Results:
- Proteinuria significantly decreased by month 6, and serum albumin levels increased over a median follow-up of 78 months.
- Nine children achieved remission, with sustained proteinuria reduction throughout follow-up.
- Glomerular filtration rate (GFR) improved in children who achieved remission and worsened in those who did not, with significant differences in GFR slopes between the groups. Two children experienced hyperkalemia.
Conclusions:
- Combination therapy with maximum approved doses of ACE inhibitors and ARBs is a safe strategy for pediatric proteinuric nephropathies.
- This approach can achieve proteinuria remission and stabilize or improve kidney function in a substantial proportion of children.
- The findings support the use of this intensified treatment protocol for managing chronic nephropathies in pediatric populations.
Background:
A multidrug treatment strategy that targets urinary proteins with an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) up-titrated to the respective maximum tolerated dose combined with intensified blood pressure (BP) control has been found to prevent renal function loss in adults with proteinuric nephropathies. Herein, we investigated the effects of this treatment protocol in the pediatric patient population.
Methods:
From May 2002 to September 2014 we included in this observational, longitudinal, cohort study 20 consecutive children with chronic nephropathies and 24-h proteinuria of >200 mg who had received ramipril and losartan up-titrated to the respective maximum approved and tolerated doses [mean (standard deviation) dose:2.48 (1.37) mg/m2 and 0.61 (0.46) mg/kg daily, respectively]. The primary efficacy endpoint was a >50 % reduction in 24-h proteinuria to <200 mg (remission). Secondary outcomes included changes in proteinuria, serum albumin, BP, and glomerular filtration rate (GFR).
Results:
Mean (± standard deviation) patient age at inclusion was 13.8 ± 2.8 years, and the median [interquartile range (IQR)] serum creatinine level and proteinuria were 0.7 (0.6-1.0) mg/dl and 690 (379-1270) mg/24 h or 435 (252-711) mg/m2/24 h, respectively. Proteinuria significantly decreased by month 6 of follow-up, and serum albumin levels increased over a median follow-up period of 78 (IQR 39-105) months. In the nine children who achieved remission, proteinuria reduction persisted throughout the whole follow-up without rebounds. The GFR improved in those children who achieved remission and worsened in those who did not. The mean GFR slopes differed significantly between these two groups (p < 0.05), being positive in those children with remission and negative in those without remission (+0.023 ± 0.15 vs.-0.014 ± 0.23 ml/min/1.73 m2/month, respectively), whereas BP control was similar between the two groups. Hyperkalemia was observed in two children.
Conclusions:
Combination therapy with maximum approved doses of ACE inhibitors and ARBs is a safe strategy which may achieve proteinuria remission with kidney function stabilization or even improvement in a substantial proportion of children with proteinuric nephropathies.
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