The diagnostic value of uromodulin protein measurement in autosomal dominant tubulointerstitial kidney disease due to uromodulin mutation (ADTKD-UMOD): serum or urine?

BACKGROUND

Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutation (ADTKD-UMOD) is a hereditary condition characterized by progressive renal dysfunction, often requiring renal replacement therapy by middle age. A notable feature is a strong family history of chronic kidney disease (CKD) and hyperuricemia; however, the absence of urinary abnormalities often delays diagnosis. To facilitate early CKD management, a diagnostic method that is simpler than genetic analysis yet strongly indicative of ADTKD-UMOD is needed.

METHODS

Serum and urinary UMOD levels were measured in patients with ADTKD-UMOD, healthy controls, and patients with other diseases. We investigated whether reduced UMOD levels are a distinctive feature of ADTKD-UMOD.

RESULTS

In 13 cases of ADTKD-UMOD, the serum UMOD (sUMOD) was 24.5 ± 13.9 ng/ml, the serum UMOD/GFR (sUMOD/GFR) was 1.23 ± 0.96, and the urinary UMOD/Cr (uUMOD/Cr) was 1.8 ± 0.9 mg/gcr. In the ADTKD-UMOD dataset, the sUMOD values were significantly lower than those in the other disease datasets. The UMOD/Cr and sUMOD/eGFR values also tended to be lower, although statistically significant differences were observed only in limited comparisons. The ROC analysis revealed that a serum UMOD concentration of < 56.4 ng/ml or sUMOD/GFR of < 1.71 is strongly suggestive of ADTKD-UMOD.

CONCLUSIONS

Measurement of UMOD protein levels is a useful tool for the diagnosis of　ADTKD-UMOD. Considering the stability of the procedure, serum UMOD may be more reliable than urinary UMOD measurement.