. 2022 Dec 17;8(3):596-605.

doi: 10.1016/j.ekir.2022.12.007. eCollection 2023 Mar.

Exome-First Strategy in Adult Patients With CKD: A Cohort Study

Alice Doreille^{1

2}, Yannis Lombardi^{1

2}, Marine Dancer³, Radoslava Lamri³, Quentin Testard³, Xavier Vanhoye³, Anne-Sophie Lebre^{4

5}, Hugo Garcia¹, Cédric Rafat¹, Nacera Ouali¹, Yosu Luque^{1

2}, Hassan Izzedine⁶, Emmanuel Esteve^{2

7}, Alexandre Cez⁷, Camille Petit-Hoang¹, Hélène François^{1

2

8}, Armance Marchal^{2

7}, Emmanuel Letavernier^{2

7

8}, Véronique Frémeaux-Bacchi⁹, Jean-Jacques Boffa^{2

7

8}, Eric Rondeau^{1

2

8}, Laure Raymond³, Laurent Mesnard^{1

2

8

10

11}

Affiliations

¹ Soins Intensifs Néphrologiques et Rein Aigu, hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.
² Faculté de médecine, Sorbonne Université, Paris, France.
³ Laboratoire Eurofins Biomnis, Lyon, France.
⁴ Service de génétique, Pole de biologie, Hôpital Maison Blanche, CHU Reims, Reims, France.
⁵ Département de Génétique, hôpital Pité Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁶ Department of Nephrology, Peupliers Private Hospital, Ramsay Générale de Santé, Paris, France.
⁷ Department of Nephrology, hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁸ Inserm UMR_S1155, Paris, France.
⁹ Immunology Department, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, Paris, France.
¹⁰ Institut des Sciences du Calcul et des Données, Sorbonne Université, Paris, France.
¹¹ Centre Maladie Rare MAHREA, hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.

PMID: 36938085
PMCID: PMC10014383
DOI: 10.1016/j.ekir.2022.12.007

Exome-First Strategy in Adult Patients With CKD: A Cohort Study

Alice Doreille et al. Kidney Int Rep. 2022.

. 2022 Dec 17;8(3):596-605.

doi: 10.1016/j.ekir.2022.12.007. eCollection 2023 Mar.

Authors

Affiliations

¹ Soins Intensifs Néphrologiques et Rein Aigu, hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.
² Faculté de médecine, Sorbonne Université, Paris, France.
³ Laboratoire Eurofins Biomnis, Lyon, France.
⁴ Service de génétique, Pole de biologie, Hôpital Maison Blanche, CHU Reims, Reims, France.
⁵ Département de Génétique, hôpital Pité Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁶ Department of Nephrology, Peupliers Private Hospital, Ramsay Générale de Santé, Paris, France.
⁷ Department of Nephrology, hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁸ Inserm UMR_S1155, Paris, France.
⁹ Immunology Department, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, Paris, France.
¹⁰ Institut des Sciences du Calcul et des Données, Sorbonne Université, Paris, France.
¹¹ Centre Maladie Rare MAHREA, hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Paris, France.

PMID: 36938085
PMCID: PMC10014383
DOI: 10.1016/j.ekir.2022.12.007

Abstract

Introduction: Exome sequencing (ES) has widened the field of nephrogenomics in adult nephrology. In addition to reporting the diagnostic yield of ES in an adult cohort study, we investigated the clinical implications of molecular diagnosis and developed a clinical score to predict the probability of obtaining positive result.

Methods: From September 2018 we have used ES to prospectively perform a first-tier liberal exploration of adult nephropathies of unknown origin and/or when a genetic kidney disease was clinically suggested. We also analyzed copy number variant using the same assay.

Results: Molecular diagnosis was made in 127 of 538 patients sequenced (diagnostic yield: 24%), comprising 47 distinct monogenic disorders. Eight of these monogenic disorders (17% [8/47]) accounted for 52% of genetic diagnoses. In 98% (n = 125/127) of the patients, the genetic information was reported to have major clinical implications. We developed a 4-value clinical score to predict the probability of obtaining a molecular diagnosis (area under the receiver operating characteristics curve [AUC] 0.726 [95% confidence interval: 0.670-0.782]) (available at http://allogenomics.com/score).

Conclusion: This study reinforces the role of ES as a first-tier exploration for adult chronic kidney disease patients in whom phenotypes are often poor and atypical. Although external validation is required, our clinical score could be a useful tool for the implementation of nephrogenomics in adults.

Keywords: CKD of unknown origin; exome sequencing; nephrogenomics.

PubMed Disclaimer

Figures

**Figure 1**
Genetic diagnosis. ADPKD, autosomal dominant polycystic kidney disease; ADTKD, autosomal dominant tubulo-interstitial kidney disease; ARPKD, autosomal recessive polycystic kidney disease.

**Figure 2**
Genetic diagnoses and clinical presentation. ADPKD, autosomal dominant polycystic kidney disease; ADTKD, autosomal dominant tubulo-interstitial kidney disease; ARPKD, autosomal recessive polycystic kidney disease.

See this image and copyright information in PMC

Cited by

Novel COL4A3-COL4A5 variants and digenic inheritance in pediatric Alport syndrome from Southwestern China.
Chen JY, Jiang XM, Liao YB, Zhang YH, Yang MF, Cui JJ, Wang J, Zhang J, Wang HY, Zhao B. Chen JY, et al. Sci Rep. 2025 Aug 25;15(1):31313. doi: 10.1038/s41598-025-17027-9. Sci Rep. 2025. PMID: 40855356 Free PMC article.
Exome Sequencing in Pacific Islanders With Nephropathies of Unknown Origin.
de Saint Gilles D, Quirin N, Lombardi Y, Lamy T, Butté Y, Biron A, Dancer M, Raymond L, Mesnard L, Doreille A. de Saint Gilles D, et al. Kidney Int Rep. 2025 Mar 10;10(6):2054-2057. doi: 10.1016/j.ekir.2025.03.005. eCollection 2025 Jun. Kidney Int Rep. 2025. PMID: 40630292 Free PMC article. No abstract available.
The Promise of Exome Sequencing for the Differential Diagnosis of Late-Onset End-Stage Renal Disease in Turkish Cypriots.
Kazan HH, Ozadali S, Oygar DD, Neild GH, Gurkan C. Kazan HH, et al. Cureus. 2025 Jun 26;17(6):e86797. doi: 10.7759/cureus.86797. eCollection 2025 Jun. Cureus. 2025. PMID: 40718208 Free PMC article.
MUC1-associated autosomal dominant tubulointerstitial kidney disease: prevalence in kidney failure of undetermined aetiology and clinical insights from Danish families.
Granhøj J, Lildballe DL, Pedersen KV, Tougaard BG, Sokol M, Aagaard MM, Petersen AH, Kristensen T, Djursby M, Birn H, Rasmussen M. Granhøj J, et al. Clin Kidney J. 2024 Nov 18;18(1):sfae355. doi: 10.1093/ckj/sfae355. eCollection 2025 Jan. Clin Kidney J. 2024. PMID: 39781475 Free PMC article.
Systematic Screening of Autosomal Dominant Tubulointerstitial Kidney Disease- MUC1 27dupC Pathogenic Variant through Exome Sequencing.
Bensouna I, Robert T, Vanhoye X, Dancer M, Raymond L, Delaugère P, Hilbert P, Richard H, Mesnard L. Bensouna I, et al. J Am Soc Nephrol. 2025 Feb 1;36(2):256-263. doi: 10.1681/ASN.0000000503. Epub 2024 Sep 26. J Am Soc Nephrol. 2025. PMID: 39325540

See all "Cited by" articles

References

1. GBD Chronic Kidney Disease Collaboration Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (Lond Engl) 2020;395:709–733. doi: 10.1016/S0140-6736(20)30045-3. - DOI - PMC - PubMed
1. McClellan W.M., Satko S.G., Gladstone E., et al. Individuals with a family history of ESRD are a high-risk population for CKD: implications for targeted surveillance and intervention activities. Am J Kidney Dis. 2009;53(Suppl 3):S100–S106. doi: 10.1053/j.ajkd.2008.07.059. - DOI - PubMed
1. Connaughton D.M., Bukhari S., Conlon P., et al. The Irish Kidney gene project--prevalence of family history in patients with kidney disease in Ireland. Nephron. 2015;130:293–301. doi: 10.1159/000436983. - DOI - PubMed
1. Wühl E., van Stralen K.J., Wanner C., et al. Renal replacement therapy for rare diseases affecting the kidney: an analysis of the ERA-EDTA Registry. Nephrol Dial Transplant. 2014;29(Suppl 4) doi: 10.1093/ndt/gfu030. - DOI - PubMed
1. Groopman E.E., Marasa M., Cameron-Christie S., et al. Diagnostic utility of exome sequencing for kidney disease. N Engl J Med. 2019;380:142–151. doi: 10.1056/NEJMoa1806891. - DOI - PMC - PubMed

LinkOut - more resources

Full Text Sources

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Exome-First Strategy in Adult Patients With CKD: A Cohort Study

Affiliations

Exome-First Strategy in Adult Patients With CKD: A Cohort Study

Authors

Affiliations

Abstract

Figures

Similar articles

Cited by

References

LinkOut - more resources

Full Text Sources

Abstract

Figures

Similar articles

Cited by

References

Related information

LinkOut - more resources

Full Text Sources