Functional tests to guide management in an adult with loss of function of type-1 angiotensin II receptor

Daan H.H.M. Viering, Anneke P. Bech, Jeroen H.F. de Baaij, Eric J. Steenbergen, A. H.Jan Danser, Jack F.M. Wetzels, René J.M. Bindels, Jaap Deinum*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Genetic loss of function of AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), or AGTR1 (type-1 angiotensin II receptor) leads to renal tubular dysgenesis (RTD). This syndrome is almost invariably lethal. Most surviving patients reach stage 5 chronic kidney disease at a young age. Methods: Here, we report a 28-year-old male with a homozygous truncating mutation in AGTR1 (p.Arg216*), who survived the perinatal period with a mildly impaired kidney function. In contrast to classic RTD, kidney biopsy showed proximal tubules that were mostly normal. During the subsequent three decades, we observed evidence of both tubular dysfunction (hyperkalemia, metabolic acidosis, salt-wasting and a urinary concentrating defect) and glomerular dysfunction (reduced glomerular filtration rate, currently ~30 mL/min/1.73 m2, accompanied by proteinuria). To investigate the recurrent and severe hyperkalemia, we performed a patient-tailored functional test and showed that high doses of fludrocortisone induced renal potassium excretion by 155%. Furthermore, fludrocortisone lowered renal sodium excretion by 39%, which would have a mitigating effect on salt-wasting. In addition, urinary pH decreased in response to fludrocortisone. Opposite effects on urinary potassium and pH occurred with administration of amiloride, further supporting the notion that a collecting duct is present and able to react to fludrocortisone. Conclusions: This report provides living proof that even truncating loss-of-function mutations in AGTR1 are compatible with life and relatively good GFR and provides evidence for the prescription of fludrocortisone to treat hyperkalemia and salt-wasting in such patients.

Original languageEnglish
Pages (from-to)2731-2737
Number of pages7
JournalPediatric Nephrology
Issue number9
Publication statusPublished - 25 Mar 2021

Bibliographical note

Funding Information:
We thank Pedro San-Cristobal for his contributions to the genetic investigations.

Publisher Copyright:
© 2021, The Author(s).


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