Adalat, S;
Hayes, WN;
Bryant, WA;
Booth, J;
Woolf, AS;
Kleta, R;
Subtil, S;
... Bockenhauer, D; + view all
(2019)
HNF1B Mutations Are Associated With a Gitelman-like Tubulopathy That Develops During Childhood.
Kidney International Reports
, 4
(9)
pp. 1304-1311.
10.1016/j.ekir.2019.05.019.
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Abstract
Background: Mutations in the transcription factor hepatocyte nuclear factor 1B (HNF1B) are the most common inherited cause of renal malformations, yet also associated with renal tubular dysfunction, most prominently magnesium wasting with hypomagnesemia. The presence of hypomagnesemia has been proposed to help select appropriate patients for genetic testing. Yet, in a large cohort, hypomagnesemia was discriminatory only in adult, but not in pediatric patients. We therefore investigated whether hypomagnesemia and other biochemical changes develop with age. Methods: We performed a retrospective analysis of clinical, biochemical, and genetic results of pediatric patients with renal malformations tested for HNF1B mutations, separated into 4 age groups. Values were excluded if concurrent estimated glomerular filtration rate (eGFR) was <30 ml/min per 1.73 m2 , or after transplantation. Results: A total of 199 patients underwent HNF1B genetic testing and mutations were identified in 52 (mutþ). The eGFRs were comparable between mutþ and mut in any age group. Although median plasma magnesium concentrations differed significantly between mutþ and mut patients in all age groups, overt hypomagnesemia was not present until the second half of childhood in the mutþ group. There was also a significant difference in median potassium concentrations in late childhood with lower values in the mutþ cohort. Conclusions: The abnormal tubular electrolyte handling associated with HNF1B mutations develops with age and is not restricted to magnesium, but consistent with a more generalized dysfunction of the distal convoluted tubule, reminiscent of Gitelman syndrome. The absence of these abnormalities in early childhood should not preclude HNF1B mutations from diagnostic considerations.
| Type: | Article |
|---|---|
| Title: | HNF1B Mutations Are Associated With a Gitelman-like Tubulopathy That Develops During Childhood |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ekir.2019.05.019 |
| Publisher version: | https://doi.org/10.1016/j.ekir.2019.05.019 |
| Language: | English |
| Additional information: | ª 2019 Published by Elsevier, Inc., on behalf of the International Society of Nephrology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | alkalosis; children; HNF1B; hypokalemia; hypomagnesemia; renal tubular function |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10080102 |
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