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A 40-year-old man presented for evaluation from his primary care doctor with an elevated serum creatinine level. Of note, his grandmother died from kidney failure, and his father suffered from kidney failure and underwent a kidney transplant at age 50 years. No family members suffer from gout. The patient’s only medication is a multivitamin. Physical examination reveals a BP of 130/70 mm Hg. Other findings are unremarkable. Laboratory studies reveal a normal urinalysis and no urinary protein. Renal ultrasonography revealed a small cyst in each kidney, with kidney lengths of 9.2 and 9.5 cm.
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The case was prepared by Anthony J. Bleyer, MD, Professor of Internal Medicine/Nephrology at Wake Forest University School of Medicine in Winston-Salem, North Carolina. He also is a member of the Renal & Urology News editorial advisory board.
In renal genetic syndromes, the most important steps in the initial evaluation are to identify the inheritance pattern and interpret the urinalysis results.
Autosomal recessive conditions require an individual to have two mutant alleles – having inherited 1 from each patient. Parents typically have 1 normal and 1 mutant allele and are carriers who do not suffer from disease. Thus, the presence of clinical disease in both parent and child almost always rules out autosomal recessive disease. In X-linked diseases, the mutated gene occurs on the X-chromosome. Since sons inherit a Y chromosome from their fathers, father-to-son transmission rules out an X-linked recessive disorder. In autosomal dominant disorders, 1 mutated allele is all that is required for the disease to be evident. Thus, an affected individual has one mutant and one normal allele. This individual has a 50% chance of passing on the mutated allele (and the disease) to his children. Therefore, there are many affected family members, as in this case. Thus, this condition is most consistent with autosomal dominant inheritance.
The absence of proteinuria or hematuria rules out hereditary FSGS and IgA nephropathy. The presence of a bland urinary sediment suggests a tubulo-interstitial process. The absence of many cysts on renal ultrasound rules out autosomal dominant polycystic kidney disease. The findings of a bland urinary sediment and small kidneys (once chronic kidney disease [CKD] is advanced) are characteristic of autosomal dominant tubulo-interstitial kidney disease (ADTKD). ADTKD due to a UMOD mutation is usually associated with gout in adolescence or early adulthood, while ADTKD due to a MUC1 mutation is not associated with any clinical findings except CKD. Thus, ADTKD due to a MUC1 mutation is the most likely diagnosis. To make the diagnosis, genetic mutational analysis for the MUC1 gene can be performed.
(Contact Dr. Bleyer at [email protected] for information on genetic testing.)