Autosomal dominant tubulointerstitial kidney disease in Chinese patients

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is recognized as a significant cause of genetic kidney disease. However, data from Asian populations remain limited.

We evaluated 70 patients meeting KDIGO clinical criteria for ADTKD at Peking University First Hospital between 2010 and 2024. Genetic testing was performed using whole-exome sequencing, with PacBio long-read sequencing employed for cases meeting clinical criteria but lacking identifiable causal variants. Plasma and urinary uromodulin levels were measured and compared between ADTKD, IgA nephropathy, and polycystic kidney disease patients.

In this Chinese cohort of 70 ADTKD patients, ADTKD-UMOD was the most prevalent subtype, accounting for 51% of cases, followed by ADTKD-HNF1B (23%), ADTKD-MUC1 (20%), and ADTKD-REN (6%). A notable 71% of patients had a family history of chronic kidney disease, with de novo variants present in 50% of ADTKD-HNF1B cases. The mean age at diagnosis was 32 ± 11 years, and patients exhibited an average estimated glomerular filtration rate (eGFR) of 46 ± 21 ml/min/1.73 m². Importantly, uromodulin levels proved to be a highly effective biomarker, distinguishing ADTKD-UMOD from other subtypes and kidney diseases with impressive diagnostic accuracy, achieving area under the curve values of 0.85 for plasma, 0.86 for urine, and 0.93 when combined.

This study establishes the first ADTKD cohort in China, revealing distinctive genetic and clinical features, including a high prevalence of UMOD and HNF1B variants. Urine and plasma uromodulin proved to be reliable biomarkers for diagnosing and monitoring ADTKD-UMOD. Incorporating uromodulin testing into clinical practice may improve early diagnosis and management of ADTKD and related kidney diseases.