Autosomic Dominant Tubulo Interstitial Kidney Disease: Case Report of a New Variant of the UMOD Gene


Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a low-prevalence pathology mainly associated with pathogenic variants of the UMOD gene. It is characterized by the progressive deterioration of renal function, associated with hyperuricemia and accompanied by a family history of gout or hyperuricemia. Often, clinical variability and a lack of molecular testing results in diagnostic failure to determine the ADTKD-UMOD association.

Case presentation: We describe the case of a 14-year-old male who presented to the nephrology service with hyperuricemia, renal ultrasonographic changes, and progression to chronic kidney disease in 4 years. He had a family history of hyperuricemia. A probable genetic disease with an autosomal dominant inheritance pattern was considered, confirmed by the presence of a probably pathogenic variant of the UMOD gene, not previously reported in the literature.

Conclusion: The investigation of this case led to the identification of a new variant in the UMOD gene, broadening the spectrum of known variants for ADTKD-UMOD. In addition, in this case, a comprehensive anamnesis, that takes into account family history, was the key point to carry out genetic tests that confirmed the diagnosis suspicion. Directed Genetic tests are currently an essential diagnostic tool and should be performed as long as they are available and there is an indication to perform them.

Keywords: UMOD, Uromodulin, hyperuricemia, Uric acid, Familial Juvenile Hyperuricemic Nephropathy, case report


Interstitial nephropathies (IN) compromise not only the interstitial tissue of the kidney, but also the renal parenchyma, affecting the glomerulus, tubules and blood vessels at the renal level [1, 2]. Autosomal dominant tubulointerstitial kidney disease (ADTKD) was recently introduced in the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines [3], and includes genetic disorders with high penetrance (~100%); however, few cases have been reported in unaffected heterozygous individuals [4]. To date (April 2023), five genes associated with the disease have been described: UMOD (ADTKD-UMOD), REN (ADTKD-REN), MUC1 (ADTKD-MUC1), HNF1B (ADTKD-HNF1B) and SEC61A1, the last one still without clear clinical relevance and defined outcome [13, 5].

Regarding frequency, the main cause of ADTKD is secondary to pathogenic variants in the MUC-1 gene (Spain 42.5% and Ireland 64%), followed by the UMOD gene (35%), and in third place HNF1B gene variants (13.9%). So far, only 14 affected families have been reported in the literature with REN gene-related ADTKD [6, 7].

The clinical profile can be heterogeneous according to the variant and age group, even within the same families. Different levels of proteinuria, urinary sediment, and microscopic hematuria could be present [2]; despite this, the progressive decrease in renal function that leads to end-stage chronic kidney disease (ESKD) seems to be a characteristic sign [1, 7], which could be; depending on the genetic variant [3, 7, 8], also accompanied by bilateral renal hypoplasia [1]. 

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