When should we start and stop ACEi/ARB in paediatric chronic kidney disease?

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EDUCATIONAL REVIEW

When should we start and stop ACEi/ARB in paediatric chronic kidney disease? Eugene Yu-hin Chan 1,2

&

Alison Lap-tak Ma 1,2 & Kjell Tullus 1

Received: 21 July 2020 / Revised: 19 August 2020 / Accepted: 15 September 2020 # IPNA 2020

Abstract Renin-angiotensin-aldosterone inhibitors (RAASi) are the mainstay therapy in both adult and paediatric chronic kidney disease (CKD). RAASi slow down the progression of kidney failure by optimization of blood pressure and reduction of proteinuria. Despite recommendations from published guidelines in adults, the evidence related to the use of RAASi is surprisingly scarce in children. Moreover, their role in advanced CKD remains controversial. Without much guidance from the literature, paediatric nephrologists may discontinue RAASi in patients with advanced CKD due to apparent worsening of kidney function, hyperkalaemia and hypotension. Current data suggest that this strategy may in fact lead to a more rapid decline in kidney function. The optimal approach in this clinical scenario is still not well defined and there are varying practices worldwide. We will in this review describe the existing evidence on the use of RAASi in CKD with particular focus on paediatric data. We will also address the use of RAASi in advanced CKD and discuss the potential benefits and harms. At the end, we will suggest a practical approach for the use of RAASi in children with CKD based on current state of knowledge. Keywords Angiotensin-converting enzyme inhibitor . Angiotensin receptor blocker . RAAS inhibition . Blood pressure . Proteinuria . Chronic kidney disease . Children

Introduction Chronic kidney disease (CKD) in children is often characterized by gradual deterioration of kidney function, resulting in kidney failure and the need of kidney replacement therapy (KRT). Over the years, a number of strategies have been shown to slow CKD progression in children, including strict blood pressure control, reducing proteinuria, optimizing anaemia and achieving normal 25-hydroxyvitamin D levels [1–4]. Renin-angiotensin-aldosterone-system inhibitors (RAASi), consisting of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), lower blood pressure and also urinary protein excretion by reducing intra-glomerular pressure and enhancing the barrier-size

* Eugene Yu-hin Chan [email protected] 1

Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, London, UK

2

Paediatric Nephrology Centre, Hong Kong Children’s Hospital, Ngau Tau Kok, Hong Kong

selection function in the slit pore membrane [5]. To date, RAASi is the mainstay therapy to attenuate kidney progression in both adult and paediatric CKD by attaining desirable blood pressure and proteinuria control [6–15]. The antifibrotic and anti-inflammatory properties of RAASi provide additional benefits to preserve kidney function [6]. Despite an undisputed efficacy in delaying disease progression in multiple adult studies, evidence supporting the renoprotective e