Autosomal Dominant Tubulointerstitial Kidney Disease-UMOD: Case Report and Disease Update

Background and Clinical Significance: Autosomal dominant tubulointerstitial kidney disease caused by mutation in uromodulin gene (ADTKD-UMOD) is a rare kidney disorder characterized by progressive tubulointerstitial damage and slowly progressive loss of renal function. ADTKD is often under-recognized in the clinical setting. In fact, diagnosis of ADTKD-UMOD can be challenging due to its nonspecific symptoms, being confirmed by genetic testing only. Case presentation: We report the case of a 42-years-old male patient referred for evaluation of renal dysfunction, incidentally discovered in routine laboratory checks. He had no significant medical history and no known familiarity for kidney disease or gout. Physical examination was unremarkable. Renal dysfunction was confirmed, with serum creatinine 1.44 mg/dl and eGFR 59.5 ml/min/1.73 m2. Urinalysis was within physiological limits, with proteinuria of 75 mg/day. Uric acid was mildly elevated (7.5 mg/dl) without gout history. Other laboratory findings including autoantibodies were in normal range. Patient underwent kidney biopsy, which however was not diagnostic showing mild focal tubular atrophy and interstitial fibrosis without glomeruli involvement. Immunofluorescence staining was negative for complement and immunoglobulins. Based on above nonspecific findings, the patient was suspected of a possible diagnosis of ADTKD. Genetic investigation using a clinical exome next-generation sequencing approach identified a novel heterozygous missense variant in the UMOD gene (c.409T>C; p.Cys137Arg). Patient is in regular clinical-laboratory monitoring. After one year, his overall health is good, renal function stable with no proteinuria, uric acid mildly increased without gout attacks. Conclusions: Increased clinical awareness is crucial for detecting ADTKD-UMOD. Genetic testing can help to solve clinical diagnostic challenges in patients with unexplained decreased kidney function.