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Nephronophthisis

Definition of Nephronophthisis

Nephronophthisis (NPH) is a rare autosomal recessive tubulointerstitial kidney disease belonging to the group of ciliopathies. It is characterized by an early urinary concentrating defect with polyuria and polydipsia, chronic progressive decline in kidney function, and progression to end-stage kidney disease during childhood, adolescence, or young adulthood.

Epidemiology:

Overall rare, accounting for approximately 10% of children with end-stage kidney disease.

Etiology (causes), pathology, and clinical presentation (symptoms) of nephronophthisis

Known gene defects

The known gene defects causing nephronophthisis result in dysfunction of the primary cilium, leading to impaired cell polarity, tubular atrophy, basement membrane abnormalities, and interstitial fibrosis. Juvenile nephronophthisis is caused by the NPHP1 gene, which encodes a defective form of nephrocystin-1. The infantile form is caused by the NPHP2 gene. Numerous additional gene defects with partly differing clinical courses have also been identified.

Clinical presentation

Infantile, juvenile, adolescent, and adult forms are distinguished. Hallmark symptoms are polyuria, polydipsia, secondary enuresis, fatigue, failure to thrive, and anemia. Over time, chronic kidney insufficiency, metabolic acidosis, disturbances of mineral metabolism, and later arterial hypertension develop.

Associated disorders:

Retinitis pigmentosa (Senior-Løken syndrome), orthopedic malformations, liver fibrosis, and Laurence-Moon-Biedl-Bardet syndrome (obesity, intellectual disability, polydactyly, retinitis pigmentosa, and hypogenitalism).

Diagnosis of nephronophthisis

Laboratory testing:

Low urine osmolality, progressive decline in eGFR, anemia, and later metabolic acidosis.

Ultrasonography:

Renal ultrasonography shows hyperechoic parenchyma and rather small kidneys; cysts are often visible only in end-stage disease.

Genetic testing:

Detection of mutations in the NPHP gene family.

Kidney biopsy:

In unclear cases.

Treatment of nephronophthisis

Adequate fluid and electrolyte intake, correction of metabolic acidosis, antihypertensive therapy, treatment of anemia, and management of other consequences of chronic kidney insufficiency. In end-stage kidney disease, dialysis and kidney transplantation are the standard treatment options.

References

Salomon, R.; Saunier, S. & Niaudet, P. Nephronophthisis.
Pediatr Nephrol, 2009, 24, 2333-2344

  Deutsche Version: Nephronophthise

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