No Nephrons: Nephronophthisis in an Asymptomatic Patient with Advanced CKD

Introduction: Nephronophthisis (NPHP), literally translated as “disappearance of nephrons,” is a group of autosomal recessive cystic kidney disorders that affect the function of primary cilia, basal bodies, and centrosomes, leading to early-onset end-stage renal disease (ESRD). NPHP is the most common genetic cause of ESRD in the first three decades of life. Here we have a case of juvenile nephronophthisis, diagnosed in a 27-year-old. Case Description: A 27-year-old Caucasian male, with past medical history significant for asthma controlled with as-needed albuterol, was referred to the nephrology clinic by his primary care provider for worsening renal function on routine labs. His creatinine was 3.49 mg/dL with eGFR 24 mL/minute/1.73m2; his labs were also significant for anemia, uremia, and metabolic acidosis. On review of systems, the patient denied lower extremity edema, periorbital puffiness, rash, and joint pain; he did endorse chronic cough. He was not sure if he had a family history of kidney disease. He worked in the fiberglass industry and previously worked as a cashier at a hardware store with exposure to sawdust. He was diagnosed with chronic kidney disease (CKD) stage 4, perhaps due to occupational silica exposure, although his chest radiograph was normal. Urinalysis was negative for proteinuria and hematuria. Kidney ultrasound showed bilateral renal cysts with increased echogenicity. Renal biopsy showed advanced non-specific chronic glomerular and tubulointerstitial nephritis without evidence of immune complex mediated disease or paraprotein-associated disease. No active glomerular or tubulointerstitial process was identified. Pulmonology evaluation ruled out silicosis. Kidney gene panel was also completed and was positive for homozygous whole-gene deletion of the NPHP1 gene. The patient was referred for renal transplant evaluation. Discussion: This patient had an unexplained, asymptomatic decline in kidney function. He had no known family history of kidney disease; however, genetic testing was essential to his diagnosis. This case highlights the importance of obtaining a kidney gene panel, especially in younger patients, when history and exam do not present a clear etiology and when kidney biopsy is not revealing. Genetic testing is emerging as a diagnostic tool and should be considered when evaluating causes of kidney disease.