You are here: Urology Textbook > Kidneys > Nephronophthisis

Nephronophthisis: Juvenile and Infantile Form

Definition of Nephronophthisis

Nephronophthisis is an autosomal recessive group of diseases, which lead to a tubulointerstitial nephritis and the formation of multiple renal cysts. Depending on the genetic defect, currently nine different forms are known, nephronophthisis leads to end-stage renal disease in different ages (Solomon et al, 2009).

Epidemiology:

• 10% of children with end-stage renal disease are suffering from nephronophthisis
• Nephronophthisis is the most common form of inherited renal failure before the age of 30 years.

Causes, Pathology and Sign and Symptoms of Nephronophthisis

Known Gen Mutations

Known genetic defects of nephronophthisis cause a defect of the primary cilium, which leads to the disruption of cell polarity, tubular atrophy, disruption of the basement membrane and interstitial fibrosis. The juvenile nephronophthisis is caused by the gene NPHP1, which encodes a defective form of nephrocystin-1. The infantile form is caused by mutations of the gene NPHP2. Seven other gene defects with partially different onset of disease have been discovered (NPHP3–9).

Juvenile Nephronophthisis

Children with juvenile nephronophthisis have normal-sized kidneys at birth. The disease starts with 6–20 years of age with polydipsia and polyuria. Interstitial nephritis with tubular dilation and atrophy develops. In end stage disease, small-sized kidneys have multiple cysts of 1&ndash10 mm in size. The electrolyte loss prevents hypertension. End-stage renal disease occurs 5–10 years after onset of symptoms.

Infantile nephronophthisis

Infantile nephronophthisis leads to end-stage renal disease before the age of 5 years.

Associated Diseases:

• Retinitis pigmentosa (Senior-Løken syndrome)
• Laurence-Moon-Bardet-Biedl syndrome (obesity, debility, polydactyly, retinitis pigmentosa and hypogenitalism)
• Orthopedic diseases
• Liver fibrosis

Diagnosis Work-Up of Nephronophthisis

Ultrasound of the kidneys:

Small sized kidneys, cysts are often seen only in the later disease stages. Hyper-echogenic parenchyma.

Genetic diagnosis:

Mutations in the NPHP gene family.

Renal biopsy:

in unclear cases.

Treatment of juvenile Nephronophthisis

Sodium replacement in early stages of the disease. Later in the course of the disease, dialysis and renal transplantation is necessary.

References

Salomon, R.; Saunier, S. & Niaudet, P.

Nephronophthisis.
Pediatr Nephrol, 2009, 24, 2333-2344

  Deutsche Version: Nephronophthise