Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (553 page)

This congenital condition is characterized by cystic dilation and malformation of the collecting tubules as well as cyst formation in the medulla. The evidence for genetic transmission is little, and a positive family history is usually absent.

   Who Should Be Suspected?

Most patients are asymptomatic, and the condition may be discovered incidentally after a radiologic testing. Symptomatic patients often present with hematuria, kidney stones, and UTI.

Diagnosis is confirmed by imaging studies.

NEPHRONOPHTHISIS

   Definition

Nephronophthisis (NPHP) is inherited in an autosomal recessive fashion and characterized by decreased urine concentration ability, chronic nephritis, and progression to ESRD at an early age (typically <20 years). It is the most common genetic cause of ESRD in the first two decades of life.

   Who Should Be Suspected?

Patients typically present with polyuria, polydipsia, anemia, and mild proteinuria. Urine sediment is typically bland. Depending on the specific gene defect, patients may also have extrarenal symptoms such as retinal defects, liver problems, and skeletal defects.

   Laboratory Findings

Depending on the median age of onset of ESRD, three clinical variants have been described: infantile (median age 4 years), juvenile (the most common variant; median age 13 years), and adolescent (median age 19 years).

   Eleven different mutations in the genes encoding components of the primary cilia or renal epithelial cells have been identified (
NPHP1–NPHP11
). Mutations of the
NPHP1
gene are most common (20% of cases) and characterized by ESRD at a mean age of 13 years (juvenile NPHP). Mutations in the other genes contribute to only <3% of cases each. The main causative gene is still unknown in approximately 70% of individuals with NPHP. Mutations in the
NPHP2
gene are associated with the infantile form and those in the
NPHP3
gene are rare and associated with the adolescent form. The juvenile form is associated with mutations in all the
NPHP
genes except
NPHP2
.

   Pathologic studies demonstrate sever tubular damage and a thickened basement membrane. NPHP histology findings are similar to those found in MCKD.

Suggested Reading

Wolf MT, Hildebrandt F. Nephronophthisis.
Pediatr Nephrol.
2011;26(2):181–194.

POLYCYSTIC KIDNEY DISEASE

Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous cysts in the kidney and has two major forms—autosomal dominant and autosomal recessive.

   Autosomal Dominant Polycystic Kidney Disease (ADPKD)

   It is the most common hereditary kidney disease affecting 1–2:1,000 live births.

   Approximately 85–90% of ADPKD mutations occur in the
PKD1
gene located on chromosome 16, whereas the remaining mutations (10–15%) occur in the
PKD2
gene located on chromosome 4. Patients with
PKD2
gene mutations generally have a less severe phenotype.

   Symptoms usually develop during the fourth decade of life, but can start earlier. ADPKD leads to progressive renal failure due to continued enlargement of the cysts and replacement of normal kidney tissue. In addition, patients suffer from other complications such as hypertension, hematuria, renal infarction, kidney stones, and renal infections.

   Diagnosis is based on a family history of ADPKD and imaging studies demonstrating the presence of kidney cysts. Cysts can also be found in other organs such as the liver and pancreas. Genetic testing can distinguish between
PKD1
and
PKD2
mutations.