Abstract: FR-PO0118
A Rare Combination: Coexistence of Dent Disease and Autosomal Dominant Alport Syndrome
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Borghol, Abdul Hamid, Cleveland Clinic, Cleveland, Ohio, United States
- Cavanaugh, Corey J., Cleveland Clinic, Cleveland, Ohio, United States
- Wang, Xiangling, Cleveland Clinic, Cleveland, Ohio, United States
Introduction
Concurrent hereditary glomerular and tubular nephropathies are rarely reported and may produce atypical yet complex clinical phenotypes. We describe a patient with progressive chronic kidney disease (CKD) found to have concurrent autosomal dominant Alport syndrome and Dent disease type 1.
Case Description
A 38-year-old man with hypertension was referred for evaluation of worsening kidney function and proteinuria. He initially presented in 2017 with acute decompensated heart failure, microscopic hematuria, and nephrotic-range proteinuria. Serologic workup including ANA, ANCA, anti-GBM antibodies, hepatitis B/C, HIV, SPEP/UPEP, and cryoglobulins was negative. Kidney biopsy was deferred. Kidney function progressively declined from an eGFR >60 mL/min/1.73m^2 in 2017 to 21 mL/min/1.73m^2 by 2024 despite RAAS and SGLT2 inhibition. Persistent microscopic hematuria was present throughout follow-up. Urine studies demonstrated mixed proteinuria with urine albumin-creatinine ratio increasing from 853 mg/g in 2017 to 1938 mg/g in 2024, while urine protein-creatinine ratio increased from 1.3 g/g to 5.77 g/g. Genetic testing identified a heterozygous likely pathogenic COL4A3 splice-site variant consistent with autosomal dominant Alport syndrome and a hemizygous likely pathogenic CLCN5 variant consistent with Dent disease type 1. Both variants were maternally inherited; the patient’s mother carried both variants, and the maternal grandmother had a history of proteinuria and CKD. Additional evaluation demonstrated marked low-molecular-weight proteinuria. Notably, nephrolithiasis, nephrocalcinosis, hypercalciuria, and hearing loss were absent.
Discussion
This case highlights a blended hereditary glomerular and tubular nephropathy resulting from concurrent COL4A3- and CLCN5-associated disease. Persistent hematuria and albuminuria supported Alport syndrome, whereas disproportionate non-albumin and low molecular weight proteinuria suggested concomitant proximal tubular dysfunction from Dent disease. The absence of classic Dent manifestations such as nephrocalcinosis and hypercalciuria illustrates the phenotypic variability of CLCN5-associated disease. Concurrent Dent disease may also have accelerated CKD progression. This case emphasizes the importance of expanded genetic testing and proteinuria characterization in atypical kidney disease presentations and how genetic diagnosis may obviate the need for kidney biopsy.