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Achieving remission of proteinuria in childhood CKD

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Abstract

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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Acknowledgments

The Authors thank Nadia Rubis for monitoring the study data and the staff of the Outpatient Clinics of ASST Ospedale Papa Giovanni XXIII of Bergamo for the help in patient monitoring and care.

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Author notes

    Authors and Affiliations

    1. Centro di Ricerche Cliniche per le Malattie Rare “Aldo e Cele Daccò”, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy

      Piero Ruggenenti, Antonietta Chianca & Giuseppe Remuzzi

    2. Unit of Nephrology, Azienda Socio Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy

      Piero Ruggenenti, MariaRosa Caruso & Giuseppe Remuzzi

    3. Department of Medicine, Recanati Miller Transplant Institute and Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

      Paolo Cravedi

    4. Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy

      Giuseppe Remuzzi

    5. Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy

      Giuseppe Remuzzi

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    1. Piero Ruggenenti
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    Correspondence to Giuseppe Remuzzi.

    Ethics declarations

    The research ethics boards of all participating hospitals approved the study. Written informed consent was obtained from the parents and/or the patients.

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    All authors declare that they have no conflicts of interest regarding this work.

    Additional information

    Piero Ruggenenti, Paolo Cravedi and Antonietta Chianca contributed equally to this work.

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    Figure S1

    Algorithm describing the key steps of the Remission Clinic intervention protocol. Hydrochlorothiazide (2 mg/kg, if eGFR > 40 ml/min/1.73 m2) or furosemide (1 mg/kg, if eGFR < 40 ml/min/1.73 m2) could be added at any time as deemed clinically appropriate to control edema and hyperkalemia and maximize the antihypertensive and antiproteinuric effect of RAS inhibition. (JPG 35 kb)

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    Ruggenenti, P., Cravedi, P., Chianca, A. et al. Achieving remission of proteinuria in childhood CKD. Pediatr Nephrol 32, 321–330 (2017). https://doi.org/10.1007/s00467-016-3495-1

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    • DOI: https://doi.org/10.1007/s00467-016-3495-1

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