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Autosomal dominant tubulointerstitial kidney disease-UMOD is the most frequent non polycystic genetic kidney disease

Autosomal dominant tubulointerstitial kidney disease-UMOD is the most frequent non polycystic genetic kidney disease
Autosomal dominant tubulointerstitial kidney disease-UMOD is the most frequent non polycystic genetic kidney disease
Background

Autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by mutations in the UMOD gene (ADTKD-UMOD) is considered rare and often remains unrecognised. We aimed to establish the prevalence of genetic kidney diseases, ADTKD and ADTKD-UMOD in adult chronic kidney disease (CKD) patients, and to investigate characteristic features.

Methods

We sent questionnaires on family history to all patients with CKD stages 3–5 in our tertiary renal centre to identify patients with inherited renal disease. Details on clinical and family history were obtained from patient interviews and clinical records. Sanger sequencing of the UMOD gene was performed from blood or saliva samples.

Results

2027 of 3770 sent questionnaires were returned. 459 patients reported a family history, which was consistent with inherited kidney disease in 217 patients. 182 non-responders with inherited kidney diseases were identified through a database search. Of these 399 individuals, 252 had autosomal dominant polycystic kidney disease (ADPKD), 28 had ADTKD, 25 had Alports, and 44 were unknown, resulting in 11% of CKD 3–5 patients and 19% of end-stage renal disease patients with genetic kidney diseases. Of the unknown, 40 were genotyped, of whom 31 had findings consistent with ADTKD. 30% of unknowns and 39% of unknowns with ADTKD had UMOD mutations. Altogether, 35 individuals from 18 families were found to have ten distinct UMOD mutations (three novel), making up 1% of patients with CKD 3–5, 2% of patients with end-stage renal disease, 9% of inherited kidney diseases and 56% with ADTKD. ADTKD-UMOD was the most common genetic kidney disease after ADPKD with a population prevalence of 9 per million. Less proteinuria and haematuria, but not hyperuricaemia or gout were predictive of ADTKD-UMOD. The main limitations of the study are the single-centre design and a predominantly Caucasian population.

Conclusions

The prevalence of genetic kidney diseases and ADTKD-UMOD is significantly higher than previously described. Clinical features poorly predicted ADTKD-UMOD, highlighting the need for genetic testing guided by family history alone.
1471-2369
1-11
Gast, Christine
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Marinaki, Anthony
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Arenas-Hernandez, Monica
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Campbell, Sara
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Seaby, Eleanor G.
a7290ab8-98ea-4093-9aa7-641d319d6064
Pengelly, Reuben
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Gale, Daniel P.
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Connor, Thomas M.
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Bunyan, David J.
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Hodanova, Katerina
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Zivna, Martina
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Ennis, Sarah
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Venkat-Raman, G.
00de8dd2-d7d3-4ba9-91ae-be6f359908d4
Gast, Christine
4126ea74-b62d-4356-84ed-572fdfb1c5e3
Marinaki, Anthony
616f2fdb-480a-4267-9a00-fad5693395c3
Arenas-Hernandez, Monica
e6cc76fa-b4a4-4241-b9f4-49ae725773fe
Campbell, Sara
79c6d7a5-8b90-4e89-83b1-519a529b5eeb
Seaby, Eleanor G.
a7290ab8-98ea-4093-9aa7-641d319d6064
Pengelly, Reuben
af97c0c1-b568-415c-9f59-1823b65be76d
Gale, Daniel P.
5b1a286f-2c35-454c-8f40-240df50ea051
Connor, Thomas M.
71bf957e-b717-4e75-8160-c219be492553
Bunyan, David J.
dd9134b9-f889-44cc-83cc-a41fc5d74d69
Hodanova, Katerina
83b6466d-b536-4ddc-8d58-4390a52f55a8
Zivna, Martina
84cbec1f-d98a-4990-8abc-8378f2b7ecf9
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Venkat-Raman, G.
00de8dd2-d7d3-4ba9-91ae-be6f359908d4

Gast, Christine, Marinaki, Anthony, Arenas-Hernandez, Monica, Campbell, Sara, Seaby, Eleanor G., Pengelly, Reuben, Gale, Daniel P., Connor, Thomas M., Bunyan, David J., Hodanova, Katerina, Zivna, Martina, Ennis, Sarah and Venkat-Raman, G. (2018) Autosomal dominant tubulointerstitial kidney disease-UMOD is the most frequent non polycystic genetic kidney disease. BMC Nephrology, 19 (301), 1-11. (doi:10.1186/s12882-018-1107-y).

Record type: Article

Abstract

Background

Autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by mutations in the UMOD gene (ADTKD-UMOD) is considered rare and often remains unrecognised. We aimed to establish the prevalence of genetic kidney diseases, ADTKD and ADTKD-UMOD in adult chronic kidney disease (CKD) patients, and to investigate characteristic features.

Methods

We sent questionnaires on family history to all patients with CKD stages 3–5 in our tertiary renal centre to identify patients with inherited renal disease. Details on clinical and family history were obtained from patient interviews and clinical records. Sanger sequencing of the UMOD gene was performed from blood or saliva samples.

Results

2027 of 3770 sent questionnaires were returned. 459 patients reported a family history, which was consistent with inherited kidney disease in 217 patients. 182 non-responders with inherited kidney diseases were identified through a database search. Of these 399 individuals, 252 had autosomal dominant polycystic kidney disease (ADPKD), 28 had ADTKD, 25 had Alports, and 44 were unknown, resulting in 11% of CKD 3–5 patients and 19% of end-stage renal disease patients with genetic kidney diseases. Of the unknown, 40 were genotyped, of whom 31 had findings consistent with ADTKD. 30% of unknowns and 39% of unknowns with ADTKD had UMOD mutations. Altogether, 35 individuals from 18 families were found to have ten distinct UMOD mutations (three novel), making up 1% of patients with CKD 3–5, 2% of patients with end-stage renal disease, 9% of inherited kidney diseases and 56% with ADTKD. ADTKD-UMOD was the most common genetic kidney disease after ADPKD with a population prevalence of 9 per million. Less proteinuria and haematuria, but not hyperuricaemia or gout were predictive of ADTKD-UMOD. The main limitations of the study are the single-centre design and a predominantly Caucasian population.

Conclusions

The prevalence of genetic kidney diseases and ADTKD-UMOD is significantly higher than previously described. Clinical features poorly predicted ADTKD-UMOD, highlighting the need for genetic testing guided by family history alone.

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ADTKD-UMOD paper BMC Nephrology revised - Accepted Manuscript
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More information

Accepted/In Press date: 19 October 2018
e-pub ahead of print date: 30 October 2018
Published date: 30 October 2018

Identifiers

Local EPrints ID: 425488
URI: http://eprints.soton.ac.uk/id/eprint/425488
ISSN: 1471-2369
PURE UUID: ec937757-73e7-4f74-a441-d2b5c5f67ff1
ORCID for Reuben Pengelly: ORCID iD orcid.org/0000-0001-7022-645X
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869

Catalogue record

Date deposited: 22 Oct 2018 16:30
Last modified: 26 Nov 2021 05:31

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Contributors

Author: Christine Gast
Author: Anthony Marinaki
Author: Monica Arenas-Hernandez
Author: Sara Campbell
Author: Eleanor G. Seaby
Author: Reuben Pengelly ORCID iD
Author: Daniel P. Gale
Author: Thomas M. Connor
Author: David J. Bunyan
Author: Katerina Hodanova
Author: Martina Zivna
Author: Sarah Ennis ORCID iD
Author: G. Venkat-Raman

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