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Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis
INTRODUCTION: Previous studies have suggested that genetic kidney diseases in adults are often overlooked, representing up to 10% of all cases of chronic kidney disease (CKD). We present data obtained from exome sequencing (ES) analysis of patients with biopsy-proven undetermined kidney disease (UKD...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577324/ https://www.ncbi.nlm.nih.gov/pubmed/37850010 http://dx.doi.org/10.1016/j.ekir.2023.07.003 |
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author | Robert, Thomas greillier, Sophie Torrents, Julia Raymond, Laure Dancer, Marine Jourde-Chiche, Noémie Halimi, Jean-Michel Burtey, Stéphane Béroud, Christophe Mesnard, Laurent |
author_facet | Robert, Thomas greillier, Sophie Torrents, Julia Raymond, Laure Dancer, Marine Jourde-Chiche, Noémie Halimi, Jean-Michel Burtey, Stéphane Béroud, Christophe Mesnard, Laurent |
author_sort | Robert, Thomas |
collection | PubMed |
description | INTRODUCTION: Previous studies have suggested that genetic kidney diseases in adults are often overlooked, representing up to 10% of all cases of chronic kidney disease (CKD). We present data obtained from exome sequencing (ES) analysis of patients with biopsy-proven undetermined kidney disease (UKD). METHODS: ES was proposed during routine clinical care in patients with UKD from January 2020 to December 2021. We used in silico custom kidney genes panel analysis to detect pathological variations using American College of Medical Genetics guidelines in 52 patients with biopsy-proven UKD with histological finding reassessment. RESULTS: We detected 12 monogenic renal disorders in 21 (40.4%) patients. The most common diagnoses were collagenopathies (8/21,38.1%), COL4A3 and COL4A4 accounting for 80% of these diagnoses, and ciliopathies (5/21, 23.8%). The diagnostic yield of ES was higher in female patients and patients with a family history of kidney disease (57.1% and 71%, respectively). Clinical nephropathy categories matched with the final genetic diagnoses in 72.7% of cases, whereas histological renal lesions matched with the final diagnoses in 92.3% of cases. The genetics diagnoses and histopathological findings were in complete agreement for both glomerular and tubulointerstitial cases. Interstitial inflammation without tubulitis was only observed in tubulopathies or ciliopathies. Isolated CKD, CKD with proteinuria or hematuria, and isolated proteinuria or hematuria yielded the highest diagnostic yields (54.6%, 52.6%, and 42.9%, respectively). CONCLUSION: ES done in patients with biopsy-proven UKD should be considered as a first-line tool for CKD patients with a family history of kidney disease. Combination of ES and kidney biopsy may have major impacts on kidney disease ontology. |
format | Online Article Text |
id | pubmed-10577324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-105773242023-10-17 Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis Robert, Thomas greillier, Sophie Torrents, Julia Raymond, Laure Dancer, Marine Jourde-Chiche, Noémie Halimi, Jean-Michel Burtey, Stéphane Béroud, Christophe Mesnard, Laurent Kidney Int Rep Clinical Research INTRODUCTION: Previous studies have suggested that genetic kidney diseases in adults are often overlooked, representing up to 10% of all cases of chronic kidney disease (CKD). We present data obtained from exome sequencing (ES) analysis of patients with biopsy-proven undetermined kidney disease (UKD). METHODS: ES was proposed during routine clinical care in patients with UKD from January 2020 to December 2021. We used in silico custom kidney genes panel analysis to detect pathological variations using American College of Medical Genetics guidelines in 52 patients with biopsy-proven UKD with histological finding reassessment. RESULTS: We detected 12 monogenic renal disorders in 21 (40.4%) patients. The most common diagnoses were collagenopathies (8/21,38.1%), COL4A3 and COL4A4 accounting for 80% of these diagnoses, and ciliopathies (5/21, 23.8%). The diagnostic yield of ES was higher in female patients and patients with a family history of kidney disease (57.1% and 71%, respectively). Clinical nephropathy categories matched with the final genetic diagnoses in 72.7% of cases, whereas histological renal lesions matched with the final diagnoses in 92.3% of cases. The genetics diagnoses and histopathological findings were in complete agreement for both glomerular and tubulointerstitial cases. Interstitial inflammation without tubulitis was only observed in tubulopathies or ciliopathies. Isolated CKD, CKD with proteinuria or hematuria, and isolated proteinuria or hematuria yielded the highest diagnostic yields (54.6%, 52.6%, and 42.9%, respectively). CONCLUSION: ES done in patients with biopsy-proven UKD should be considered as a first-line tool for CKD patients with a family history of kidney disease. Combination of ES and kidney biopsy may have major impacts on kidney disease ontology. Elsevier 2023-07-22 /pmc/articles/PMC10577324/ /pubmed/37850010 http://dx.doi.org/10.1016/j.ekir.2023.07.003 Text en © 2023 International Society of Nephrology. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Clinical Research Robert, Thomas greillier, Sophie Torrents, Julia Raymond, Laure Dancer, Marine Jourde-Chiche, Noémie Halimi, Jean-Michel Burtey, Stéphane Béroud, Christophe Mesnard, Laurent Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis |
title | Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis |
title_full | Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis |
title_fullStr | Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis |
title_full_unstemmed | Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis |
title_short | Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis |
title_sort | diagnosis of kidney diseases of unknown etiology through biopsy-genetic analysis |
topic | Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10577324/ https://www.ncbi.nlm.nih.gov/pubmed/37850010 http://dx.doi.org/10.1016/j.ekir.2023.07.003 |
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