Sophie M van den Belt1, Hiddo J L Heerspink2, Marietta Kirchner3, Valentina Gracchi4, Daniela Thurn-Valsassina5, Aysun K Bayazit6, Anna Niemirska7, Nur Canpolat8, Ipek Kaplan Bulut9, Karolis Azukaitis10, Ali Duzova11, Justine Bacchetta12, Rukshana Shroff13, Dusan Paripovic14, Zeynep Birsin Özçakar15, Kibriya Fidan16, Hakan Erdogan17, Jutta Gellermann18, Elke Wühl19, Dick de Zeeuw2, Anette Melk5, Uwe Querfeld18, Franz Schaefer19. 1. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands s.m.van.den.belt@umcg.nl. 2. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3. Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany. 4. Department of Pediatric Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 5. Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany. 6. Department of Pediatric Nephrology, Cukurova University School of Medicine, Adana, Turkey. 7. Department of Nephrology, Kidney Transplantation and Arterial Hypertension, The Children's Memorial Health Institute, Warsaw, Poland. 8. Department of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey. 9. Division of Pediatric Nephrology, Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. 10. Clinic of Pediatrics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 11. Division of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey. 12. Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France. 13. Department of Pediatric Nephrology, Great Ormond Street Hospital for Children and Institute of Child Health, London, United Kingdom. 14. Department of Pediatric Nephrology, University Children's Hospital, Belgrade, Serbia. 15. Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Ankara University, Ankara, Turkey. 16. Department of Pediatric Nephrology, Gazi University, Ankara, Turkey. 17. Department of Nephrology, Bursa Yuksek Ihtisas Teaching and Researching Hospital, Bursa, Turkey. 18. Division of Gastroenterology, Nephrology, and Metabolic Medicine, Department of Pediatrics, Charité Universitätsmedizin Berlin, Berlin, Germany. 19. Division of Pediatric Nephrology, University Hospital Heidelberg, Heidelberg, Germany.
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.
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.
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