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Original ArticlesChronic Kidney Disease
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Discontinuation of RAAS Inhibition in Children with Advanced CKD

Sophie M. van den Belt, Hiddo J.L. Heerspink, Marietta Kirchner, Valentina Gracchi, Daniela Thurn-Valsassina, Aysun K. Bayazit, Anna Niemirska, Nur Canpolat, Ipek Kaplan Bulut, Karolis Azukaitis, Ali Duzova, Justine Bacchetta, Rukshana Shroff, Dusan Paripovic, Zeynep Birsin Özçakar, Kibriya Fidan, Hakan Erdogan, Jutta Gellermann, Elke Wühl, Dick de Zeeuw, Anette Melk, Uwe Querfeld and Franz Schaefer
CJASN May 2020, 15 (5) 625-632; DOI: https://doi.org/10.2215/CJN.09750819
Sophie M. van den Belt
1Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Hiddo J.L. Heerspink
1Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Marietta Kirchner
2Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
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Valentina Gracchi
3Department of Pediatric Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Daniela Thurn-Valsassina
4Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
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Aysun K. Bayazit
5Department of Pediatric Nephrology, Cukurova University School of Medicine, Adana, Turkey
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Anna Niemirska
6Department of Nephrology, Kidney Transplantation and Arterial Hypertension, The Children’s Memorial Health Institute, Warsaw, Poland
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Nur Canpolat
7Department of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey
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Ipek Kaplan Bulut
8Division of Pediatric Nephrology, Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey
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Karolis Azukaitis
9Clinic of Pediatrics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
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Ali Duzova
10Division of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey
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Justine Bacchetta
11Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France
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Rukshana Shroff
12Department of Pediatric Nephrology, Great Ormond Street Hospital for Children and Institute of Child Health, London, United Kingdom
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Dusan Paripovic
13Department of Pediatric Nephrology, University Children’s Hospital, Belgrade, Serbia
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Zeynep Birsin Özçakar
14Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Ankara University, Ankara, Turkey
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Kibriya Fidan
15Department of Pediatric Nephrology, Gazi University, Ankara, Turkey
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Hakan Erdogan
16Department of Nephrology, Bursa Yuksek Ihtisas Teaching and Researching Hospital, Bursa, Turkey
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Jutta Gellermann
17Division of Gastroenterology, Nephrology, and Metabolic Medicine, Department of Pediatrics, Charité Universitätsmedizin Berlin, Berlin, Germany
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Elke Wühl
18Division of Pediatric Nephrology, University Hospital Heidelberg, Heidelberg, Germany
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Dick de Zeeuw
1Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Anette Melk
4Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
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Uwe Querfeld
17Division of Gastroenterology, Nephrology, and Metabolic Medicine, Department of Pediatrics, Charité Universitätsmedizin Berlin, Berlin, Germany
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Franz Schaefer
18Division of Pediatric Nephrology, University Hospital Heidelberg, Heidelberg, Germany
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Abstract

Background and objectives Although renin-angiotensin-aldosterone system inhibition (RAASi) is a cornerstone in the treatment of children with CKD, it is sometimes discontinued when kidney function declines. We studied the reasons of RAASi discontinuation and associations between RAASi discontinuation and important risk markers of CKD progression and on eGFR decline in the Cardiovascular Comorbidity in Children with CKD study.

Design, setting, participants, & measurements In this study, 69 children with CKD (67% male, mean age 13.7 years, mean eGFR 27 ml/min per 1.73 m2) who discontinued RAASi during prospective follow-up were included. Initial change in BP, albuminuria, and potassium after discontinuation were assessed (median time 6 months). Rate of eGFR decline (eGFR slope) during a median of 1.9 years before and 1.2 years after discontinuation were estimated using linear mixed effects modeling.

Results Physician-reported reasons for RAASi discontinuation were increase in serum creatinine, hyperkalemia, and symptomatic hypotension. After discontinuation of RAASi, BP and albuminuria increased, whereas potassium decreased. eGFR declined more rapidly after discontinuation of RAASi (−3.9 ml/min per 1.73 m2 per year; 95% confidence interval, −5.1 to −2.6) compared with the slope during RAASi treatment (−1.5 ml/min per 1.73 m2 per year; 95% confidence interval, −2.4 to −0.6; P=0.005). In contrast, no change in eGFR slope was observed in a matched control cohort of patients in whom RAASi was continued.

Conclusions Discontinuation of RAASi in children with CKD is associated with an acceleration of kidney function decline, even in advanced CKD.

  • RAAS inhibition
  • pediatric nephrology
  • chronic renal disease
  • Hyperkalemia
  • albuminuria
  • Renin-Angiotensin System
  • creatinine
  • blood pressure
  • Potassium
  • Prospective Studies
  • Follow-Up Studies
  • glomerular filtration rate
  • Renal Insufficiency, Chronic
  • Cohort Studies
  • Blood Pressure Determination
  • hypotension
  • Comorbidity
  • Acceleration
  • Received August 21, 2019.
  • Accepted February 28, 2020.
  • Copyright © 2020 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 15 (5)
Clinical Journal of the American Society of Nephrology
Vol. 15, Issue 5
May 07, 2020
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Discontinuation of RAAS Inhibition in Children with Advanced CKD
Sophie M. van den Belt, Hiddo J.L. Heerspink, Marietta Kirchner, Valentina Gracchi, Daniela Thurn-Valsassina, Aysun K. Bayazit, Anna Niemirska, Nur Canpolat, Ipek Kaplan Bulut, Karolis Azukaitis, Ali Duzova, Justine Bacchetta, Rukshana Shroff, Dusan Paripovic, Zeynep Birsin Özçakar, Kibriya Fidan, Hakan Erdogan, Jutta Gellermann, Elke Wühl, Dick de Zeeuw, Anette Melk, Uwe Querfeld, Franz Schaefer
CJASN May 2020, 15 (5) 625-632; DOI: 10.2215/CJN.09750819

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Discontinuation of RAAS Inhibition in Children with Advanced CKD
Sophie M. van den Belt, Hiddo J.L. Heerspink, Marietta Kirchner, Valentina Gracchi, Daniela Thurn-Valsassina, Aysun K. Bayazit, Anna Niemirska, Nur Canpolat, Ipek Kaplan Bulut, Karolis Azukaitis, Ali Duzova, Justine Bacchetta, Rukshana Shroff, Dusan Paripovic, Zeynep Birsin Özçakar, Kibriya Fidan, Hakan Erdogan, Jutta Gellermann, Elke Wühl, Dick de Zeeuw, Anette Melk, Uwe Querfeld, Franz Schaefer
CJASN May 2020, 15 (5) 625-632; DOI: 10.2215/CJN.09750819
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Keywords

  • RAAS inhibition
  • pediatric nephrology
  • chronic renal disease
  • Hyperkalemia
  • albuminuria
  • Renin-Angiotensin System
  • creatinine
  • blood pressure
  • Potassium
  • Prospective Studies
  • Follow-Up Studies
  • glomerular filtration rate
  • renal insufficiency, chronic
  • Cohort Studies
  • Blood Pressure Determination
  • hypotension
  • Comorbidity
  • Acceleration

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