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Nephronopthisis is an autosomal recessive disease characterized by a chronic tubulointerstitial nephritis. Nephrocystin proteins encoded by NPHP genes localize to the primary cilia, basal bodies, and centrosomes. NPHP variants result in ciliopathy. Nephronopthisis is therefore characterized by impaired urinary concentrating ability, a bland urinalysis, chronic tubulointerstitial disease, and progressed to end-stage kidney disease by 20 years of age. The ciliary dysfunction can also result in extra-renal manifestations which occur in approximately 20 percent of patients with NPHP. There are three clinical variants of nephronopthisis that have been described based upon the median age of onset of ESKD: infantile, juvenile, and adolescent. Here we discuss a case of adolescent-diagnosed nephronopthisis.
A 28 year old male with no known medical problems was referred to outpatient nephrology by his PCP for an elevated serum creatinine of 1.84 on his first annual physical in 12/2020. Of note, his brother was diagnosed with renal disease at age 19 and underwent renal transplant at age 21. No identifiable diagnosis was made. Biopsy on the brother noted extensive scarring, and assumed diagnosis at that time was environmental toxin exposure. Both parents were tested at that time, and results were unremarkable. A kidney biopsy done on the patient in August 2021 found severe cortical scarring, focal micro cysts, and patchy interstitial inflammation. Given the nonspecific biopsy findings and the family history of kidney disease, a Natera/Renasight panel was done which revealed NPHP1 gene mutation, consistent with nephronopthisis 1.
In patients with no clear etiology of renal disease, it is prudent to order genetic testing as this may impact family members. In the case above, had genetic testing been ordered for the patient’s brother at the time of his diagnosis, the patient’s renal function may have been able to be monitored more frequently and the diagnosis could have been made prior to the patient’s development of severe interstitial fibrosis/tubular atrophy. While there is no specific therapy for NPHP, interventions include replacing ongoing water losses to prevent episodes of hypovolemia and providing adequate salt intake. Additionally, these diseases are associated with extra renal manifestations. After diagnosis, the patient was able to be counseled to follow with ophthalmology given the association with retinitis pigmentosa.