Atypical histological abnormalities in an adult patient with nephronophthisis harboring NPHP1 deletion: a case report.

BACKGROUND: Nephronophthisis (NPHP) is a chronic tubular interstitial disorder that exhibits an autosomal recessive genetic form and causes progressive renal failure in children. Patients with NPHP rarely show urinary abnormalities, edema, or hypertension. Thus, NPHP is often detected only when renal failure becomes advanced. NPHP can be divided into three types based on the age of end-stage renal failure, i.e., infant type (approximately 5 years old), juvenile type (approximately 13-14 years old), and adolescent type (approximately 19 years old). Here, we report a case of NPHP diagnosed by genetic analysis at 26 years of age with atypical histological abnormalities. CASE PRESENTATION: A 26-year-old woman showed no growth disorders or urinary abnormalities in annual school physical examinations. However, at a check-up at 26 years old, she exhibited renal dysfunction (eGFR 26 mL/min/1.73 m2). Urine tests indicated low specific gravity of urine, but not proteinuria or microscopic hematuria. Urinary ß2-microglobulin was high (805 µg/L), and renal biopsy was performed for definitive diagnosis. Histological findings showed no significant findings in glomeruli. However, moderate fibrosis was observed in the interstitial area, and moderate atrophy was observed in the tubules. There were no significant findings in immunofluorescence analysis, and no electron dense deposits were detected by electron microscopy. Although cyst-like expansion of the tubules was unclear, tubular atrophy was dominantly found in the distal tubule by cytokeratin 7 staining. Genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP. CONCLUSIONS: NPHP is not merely a pediatric disease and is relatively high incidence in patients with adult onset end-stage of renal disease. In this case, typical histological abnormalities, such as cyst-like expansion of the tubular lesion, were not observed, and diagnosis was achieved by genetic analysis of the NPHP1 gene, which is responsible for the onset of NPHP. In patients with renal failure with tubular interstitial disease dominantly in the distal tubules, it is necessary to discriminate NPHP, even in adult cases.

Exercise-Induced Acute Kidney Injury in a Police Officer with Hereditary Renal Hypouricemia.

Hereditary renal hypouricemia is characterized by hypouricemia with hyper-uric acid clearance due to a defect in renal tubular transport. Patients with hereditary renal hypouricemia have a higher risk of exercise-induced acute kidney injury (EAKI) and reduced kidney function. Although the best preventive measure is avoiding exercise, there are many kinds of jobs that require occupational exercise. A 27-year-old male police officer suffered from stage 3 AKI after performing a 20-m multistage shuttle run test. His mother had previously been diagnosed as having renal hypouricemia at another facility. The patient had reported having hypouricemia during a health check at a previous police station, but his serum uric acid concentration was within the normal range at our hospital. After treatment, he recovered from EAKI and exhibited low serum uric acid and hyper-uric acid clearance. Since the patient desired to continue his career requiring strenuous exercise, it was difficult to establish a preventive plan against the recurrence of EAKI. Patients with hereditary renal hypouricemia who must undergo strenuous occupational anaerobic exercise are at higher risk of developing EAKI than other workers. The risks of EAKI among patients with hypouricemia should be considered when undergoing physical occupational training.