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The challenge of renal function in heart transplant children

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Abstract

Renal dysfunction may occur after pediatric heart transplantation and impacts on long-term prognosis. This study aims to review the incidence and mechanisms of chronic nephropathy following heart transplantation, and suggest therapeutic directions. The proportion of pediatric heart-transplant recipients with impaired renal function varies from 22 to 57%, and end-stage renal failure from 3 to 10%, depending on the method used for estimating the glomerular filtration rate. The pathophysiology of renal dysfunction is in part due to calcineurin inhibitor-induced renal vasoconstriction, through activation of the intrarenal renin-angiotensin system, TGF-β1 upregulation and TGF-β1 gene polymorphisms. Overproduction of angiotensin II, associated with angiotensin-converting-enzyme genotype, might be associated with poor prognosis and pharmacological factor gene polymorphisms, and may contribute to variation of calcineurine inhibitor exposure in the kidney. Strategies to prevent renal dysfunction include reducing calcineurine inhibitor exposure or delaying calcineurine inhibitor administration from the early post-transplant period. Calcium channel blockers and angiotensin-converting-enzyme inhibitors, blockade of angiotensin II, or anti-TGF-β1 antibodies might limit nephrotoxicity. No accurate marker can predict the potential of renal lesions to develop. Lowering calcineurine inhibitors levels with immunosuppressive agents that are either less nephrotoxic or non-nephrotoxic should be formally studied. Of high interest is the impact of genetic polymorphism on the development of renal dysfunction.

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  1. Department of Pediatric Cardiology, Hopital Cardiologique de Lyon, 28 Avenue Doyen Lepine, 69677, Bron Cedex, France

    Sylvie Di Filippo & André Bozio

  2. Pediatric Nephrology, Hopital Edouard Herriot, 8 Place d’Arsonval, 69008, Lyon, France

    Pierre Cochat

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  1. Sylvie Di Filippo
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Di Filippo, S., Cochat, P. & Bozio, A. The challenge of renal function in heart transplant children. Pediatr Nephrol 22, 333–342 (2007). https://doi.org/10.1007/s00467-006-0229-9

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