Medullary Cystic Disease Workup

Updated: Mar 16, 2020
  • Author: Prasad Devarajan, MD, FAAP; Chief Editor: Craig B Langman, MD  more...
  • Print

Laboratory Studies

Urinalysis may be helpful in patients with nephronophthisis (NPH)–medullary cystic kidney disease (MCKD) complex. A low specific gravity in the first morning voiding sample, which should be concentrated, is a characteristic feature of this disease. The concentrating ability rarely exceeds 800 mOsm/kg of water. Hematuria, proteinuria, and bacteriuria are uncommon. Proteinuria, if present, is mild and of tubular origin. Significant proteinuria develops late in the course of the disease, reflecting secondary glomerular sclerosis.

Metabolic acidosis, elevated serum blood urea nitrogen (BUN) and creatinine concentrations, hypocalcemia, and hyperphosphatemia are indicators of renal failure.

The complete blood cell (CBC) count frequently reveals profound normocytic normochromic anemia. Approximately one third of patients develop anemia before renal insufficiency occurs. Low erythropoietin (EPO) levels have been found in patients with NPH.

Liver function tests are used to detect congenital hepatic fibrosis.

Hyperuricemia with hypouricosuria is characteristic of MCKD patients with UMOD or REN gene mutations. The fractional excretion of uric acid is often below 4% (normal values, 8-13%).


Imaging Studies

Contrast-enhanced thin-section computed tomography (CT) scanning is the modality of choice. The kidneys are imaged with 1-mm to 2-mm-thick sections. Multiple cysts are typically seen in the medulla and corticomedullary region. The cysts range from smaller than 0.5 mm to 2 cm in diameter.

Renal ultrasonography may be helpful in assessing NPH-MCKD. The kidneys are of normal or moderately reduced size, with a smooth outline. Typically, corticomedullary differentiation is lost, and echogenicity is increased. Cysts may or may not be present at the corticomedullary border. These findings are distinct from those of autosomal dominant or autosomal recessive polycystic kidney disease (PKD), in which the kidneys are enlarged and the cysts are uniformly distributed throughout the entire kidney. Patients with end-stage renal disease (ESRD) have multiple small and large cysts that can be seen in the corticomedullary area. No cysts are located in organs other than the kidney.

The absence of cysts on the sonogram does not exclude the diagnosis of NPH–MCKD. Patients with UMOD mutations frequently do not exhibit renal cysts that are detectable by ultrasound.

Hepatic ultrasonography is used to detect congenital hepatic fibrosis.

Skeletal radiography is used to identify dysplastic lesions.


Other Tests

Ophthalmoscopy and electroretinography are used to determine the presence of tapetoretinal degeneration.

Molecular genetic analysis is the only diagnostic procedure with which the diagnosis of NPH or MCKD can be confirmed with certainty. Details are available at Renal Genes.

Before genetic counseling is given, a thorough pedigree analysis should be performed to distinguish recessive (early-onset) disease from dominant (late-onset) disease, and extrarenal involvement should be excluded.

Blood may be obtained from a patient with clinical and renal ultrasonographic findings suggestive of NPH-MCKD complex or from an affected parent. DNA is extracted from this blood and amplified by using the polymerase chain reaction (PCR) to detect the homozygous deletion in the NPH1 gene. Approximately 66% of children with NPH type 1 have this large homozygous deletion. However, because of the additional loci for NPH, the disease cannot be excluded if mutations in the NPH1 gene are not detected.


Histologic Findings

On renal biopsy findings, the characteristic histologic triad is identical in the findings in childhood and adult forms of NPH. First, tubular basement membrane disintegration with irregular thickening is present with membrane attenuation. In later stages, biopsy findings include distal tubular atrophy and cystic formation predominantly at the corticomedullary junction. Second, the interstitium shows round cell infiltration and fibrosis. Third, periglomerular fibrosis is observed. These histologic changes are characteristic of but not pathognomonic for the disease complex.

NPH type 3 should be considered if the histologic features are consistent with NPH in the absence of molecular defects in NPH type 1.

Early histologic findings reveal peritubular lymphohistiocytic infiltrations. As renal failure progresses, diffuse tubulointerstitial fibrosis occurs, with tubular atrophy and dilatation. Light microscopy and electron microscopy reveal periglomerular and peritubular basement membrane thickening and splitting.

The renal architecture is characterized by a uniformly thinned cortex and a segmental distribution of variably sized cysts in the medulla and corticomedullary junction. Cysts can be barely visible to several centimeters in size, and they vary in number from fewer than 5 to more than 50 in a segmental distribution. The cysts do not communicate with nephrons. The presence of cysts is not a diagnostic requirement because it is a late finding, and cysts may not be detected at biopsy.