Medullary Cystic Disease Clinical Presentation

Updated: Mar 16, 2020
  • Author: Prasad Devarajan, MD, FAAP; Chief Editor: Craig B Langman, MD  more...
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A family history of consanguinity, early death, or renal disease is present in 67% of patients with nephronophthisis (NPH). [5]

In juvenile NPH (the most common form), the first symptoms usually develop around age 5 years and consist of polyuria and polydipsia. These symptoms are related to a reduced urinary concentrating capacity and loss of sodium conservation and occur early in the course of the disease, well before a reduction in glomerular filtration rate. Typically, the urine osmolarity is less than 400 mOsm/kg in the first morning sample.

Children exhibit decreased growth velocity, initially related to chronic dehydration and subsequently confounded by renal insufficiency.

Features that distinguish NPH from medullary cystic kidney disease (MCKD) include the following:

  • The inheritance pattern is autosomal recessive.

  • The median age of onset of end-stage renal disease (ESRD) is 13 years in juvenile NPH, 1-3 years in infantile NPH, and 19 years in adolescent NPH.

Extrarenal associations of NPH include the following:

  • Cogan syndrome: Oculomotor apraxia

  • Senior-Loken syndrome: Retinitis pigmentosa

  • Mainzer-Saldino syndrome: Liver fibrosis and bone dysplasia

  • Joubert syndrome: Coloboma or retinal degeneration, nystagmus, ptosis, aplasia of cerebellar vermis with ataxia and psychomotor retardation, polydactyly, and neonatal tachypnea or dyspnea

  • Sensenbrenner syndrome: Cranioectodermal dysplasia and electroretinal abnormalities

Distinguishing features of MCKD include the following:

  • The inheritance pattern is autosomal dominant.

  • The median onset of ESRD for MCKD type 1 is age 62 years and for MCKD type 2 is age 32 years.

  • Extrarenal associations are restricted to hyperuricemia and gout.

The following conditions have renal histologic features similar to those of NPH:

  • Jeune syndrome or asphyxiating thoracic dysplasia: Small thorax, short limbs, and hypoplastic iliac wings

  • Ellis-van Creveld syndrome: Chondroectodermal dysplasia

  • RHYNS syndrome: Retinitis pigmentosa, hypopituitarism, NPH, and skeletal dysplasia

  • Laurence-Moon-Bardet-Biedl syndrome: Retinitis pigmentosa, obesity, polydactyly, and mental retardation

In the case of MCKD, there is usually a family history of hyperuricemia and progressive kidney disease. Patients with MCKD type 2 (the more common form) present as adolescents or young adults with gout and chronic kidney disease, with a relatively bland urinalysis. Patients with MUC1 mutations typically present with slowly progressive chronic kidney disease and usually develop hyperuricemia later in life. Patients with REN mutations present with features similar to those of UMOD mutations but additionally have manifestations of low renin and angiotensin (anemia out of proportion to the kidney disease, low blood pressure, hyperkalemia, and increased risk of volume depletion).


Physical Examination

The clinical findings are related to tubular injury that leads to a reduction in urinary concentrating capacity, renal sodium loss, and insidious but inevitable progression to renal failure. The tubular defects precede the decline in renal function and may be present in asymptomatic siblings with the disease.

Nephronophthisis and medullary cystic kidney disease share several clinical features. In most patients, the signs associated with decreased urinary concentration capacity are present by age 5 years. The signs include polyuria, polydipsia, enuresis, and dehydration. Common findings include a failure to thrive and weakness. Anorexia, nausea, pruritus, bone pain, and neurologic symptoms herald end-stage renal disease. Because of salt wasting, hypertension is rare, except in the infantile form of nephronophthisis.

Pallor is another characteristic finding. In contrast to other renal diseases in which the degree of anemia depends on the stage of renal insufficiency, in nephronophthisis, the severity of the anemia exceeds the degree of renal insufficiency. Anemia may occur before renal insufficiency develops. This normocytic and normochromic anemia is more severe than that of other chronic renal diseases and does not result from iron deficiency or hemolysis.

In patients with nephronophthisis, the serum erythropoietin (EPO) concentration is lower than that of patients with other progressive renal diseases. EPO is a glycoprotein hormone that controls the differentiation of erythroid progenitor cells in the bone marrow and the production of erythrocytes. After birth, EPO is produced mainly in the kidneys, specifically in the peritubular fibroblasts. In patients with nephronophthisis, the synthesis of EPO is decreased.