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Unknown etiology is usually found in the kidney pre-transplant routine program, which accounts for 25% of our recipients’ database. This missing information is in detriment to the prognosis of these patients. We developed a preliminary screening to detect and study recipients that showed the following characteristics: Hypertension with no clear origin, and biopsies that do not meet with the clinical features of the classical glomerulopathies. The aim of this study is to explore clinical, genealogical and genetic landscape in a 45 years old index case with early hypertension and biopsy that showed global and focal glomerulosclerosis without immune deposits that wait for a non-related living donor kidney transplant.
Demographic and clinical data was obtained from institutional database and genealogical information was registered in the routine outpatient consultation. The pretransplant routine blood and urine laboratory were performed. Genetic tests from blood samples were analyzed by NGS technique through two personalized panels (atypical hemolytic uremic syndrome and focal and segmental glomerulosclerosis) for Illumina HiSeq platform according to clinical presentation.
The family tree exploration showed that his son, auntie and cousin present similar clinical features. Urinalysis showed absence of hematuria and urine protein and no gout nor hyperuricemia were found in the clinical records of 3 out of 4 affected relatives. Since underlying tubulointerstitial disease was suspected, an exome sequencing covering 220 genes found the c.610C>G (p.Arg204Gly) pathogenic variant of uromodulin (UMOD) gene in the index case. The variant was also found in his son, which presents a 1 year-long CKD in II stage with hyperuricemia (10.5 mg/dl, normal value ≤ 7) and the electron microscopy revealed chronic thrombotic microangiopathy, that confirmed the ADTKD-UMOD diagnosis.
The ADTKD-UMOD is a diagnosis challenging the cause of CKD, considering the normal sediment and early onset hypertension without special particularities that require genetic confirmation. The ADTKD-UMOD is a ciliopathy that presents abnormal uromodulin cleavage due to genetic mutation and results in lysosomal accumulation and tubulointerstitial nephritis. Our results indicate that an integrated clinical, genealogical and genetic study unravels the cause of CKD in a pre transplant recipient and facilitates the consanguineous donor election as well as the early diagnosis in the relatives.