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. 2021;52(3):239-249.
doi: 10.1159/000514578. Epub 2021 Mar 26.

Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Diabetic Kidney Disease

Jose Lazaro-Guevara  1   2 , Julio Fierro-Morales  1   2 , A Hunter Wright  2 , River Gunville  2 , Christopher Simeone  1   2 , Scott G Frodsham  2 , Melissa H Pezzolesi  2 , Courtney A Zaffino  2 , Laith Al-Rabadi  2 , Nirupama Ramkumar  2 , Marcus G Pezzolesi  1   2   3
Affiliations

Targeted Next-Generation Sequencing Identifies Pathogenic Variants in Diabetic Kidney Disease

Jose Lazaro-Guevara et al. Am J Nephrol. 2021.

Abstract

Introduction: Diabetes is the most common cause of chronic kidney disease (CKD). For patients with diabetes and CKD, the underlying cause of their kidney disease is often assumed to be a consequence of their diabetes. Without histopathological confirmation, however, the underlying cause of their disease is unclear. Recent studies have shown that next-generation sequencing (NGS) provides a promising avenue toward uncovering and establishing precise genetic diagnoses in various forms of kidney disease.

Methods: Here, we set out to investigate the genetic basis of disease in nondiabetic kidney disease (NDKD) and diabetic kidney disease (DKD) patients by performing targeted NGS using a custom panel comprising 345 kidney disease-related genes.

Results: Our analysis identified rare diagnostic variants based on ACMG-AMP guidelines that were consistent with the clinical diagnosis of 19% of the NDKD patients included in this study. Similarly, 22% of DKD patients were found to carry rare pathogenic/likely pathogenic variants in kidney disease-related genes included on our panel. Genetic variants suggestive of NDKD were detected in 3% of the diabetic patients included in this study.

Discussion/conclusion: Our findings suggest that rare variants in kidney disease-related genes in a diabetic background may play a role in the pathogenesis of DKD and NDKD in patients with diabetes.

Keywords: Diabetic kidney disease; Genetics; Targeted sequencing.

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Conflict of interest statement

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.. Distribution of Rare Pathogenic or Likely Pathogenic Variants in NDKD and DKD Patients. The distribution of rare (MAF<0.1%) pathogenic or likely pathogenic variants identified in NDKD (blue) and DKD (orange) patients. NDKD, non-diabetic kidney disease; DKD, diabetic kidney disease.
See this image and copyright information in PMC

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