Nephrology Hypertension

Hereditary Renal Cystic Diseases: Glomerulocystic Kidney Disease

Does this patient have glomerulocystic kidney disease (GCKD)?

Glomerulocystic kidney disease (GCKD) is a rare form of hereditary renal cystic disease characterized by cystic dilation of Bowman's capsule and the initial proximal convoluted tubule. The dilated Bowman spaces are lined by a flattened epithelium and contain rudimentary glomerular tufts. On ultrasonographic imaging, the kidneys can appear enlarged with increased echogenicity and loss of corticomedullary junction differentiation.

Familial GCKD is typically identified with hypoplastic or normal-sized kidneys. However, in both sporadic and familial forms, the kidneys can be either hypoplastic, normal-sized, or enlarged. Punctate cysts can be seen and will differentiate this from the classical ARPKD findings on ultrasound. On computed tomography (CT) and magnetic resonance imaging (MRI), GCKD appears as numerous small cortical cysts. These do not enhance with gadolinium during MRI. Unlike other cystic kidney diseases, the tubules in GCKD usually remain unaffected. Given the inconsistent nature of GCKD, it is clinically difficult to diagnose and can only be established by renal biopsy.

What tests to perform?

Lab testing

Management of GCKD includes ordering complete blood count (CBC) diff platelets and comprehensive chemistry panels with phosphorus. For those with advanced renal insufficiency (chronic kidney disease [CKD] Stage 3 or 4) PTH, Vit D 25 and Vit D 1,25 would also be included. All patients with underlying renal disease will need a lipid panel since they are at higher risk for cardiovascular disease.

Imaging

Ultrasonographic (US) imaging, MRI, and CT are all acceptable forms of imaging modalities. On US imaging, kidneys can appear enlarged with increased echogenicity and loss of cortico-medullary junction differentiation. Familial GCKD can also be associated with hypoplastic or normal-sized kidneys. In order to obtain a more accurate determination of cystic involvement in the kidneys, a CT or MRI should be utilized.

Biopsy

GCKD may appear similar to other cystic kidney diseases; therefore, a renal biopsy may be needed for a definitive diagnosis. Examples of renal biopsy findings include mild proliferation of mesangial cells and matrix, tubular atrophy, interstitial fibrosis, cystic dilation of Bowman's capsule and atrophy of the glomerular tuft.

How should patients with GCKD be managed?

A combination of medical modalities, such as anti-hypertensives, diabetes management if needed and surgery (for an anatomical abnormality), may be necessary for the management of GCKD. End stage renal failure is best treated with renal transplantation or dialysis.

What happens to patients with GCKD?

GCKD can be a sporadic or hereditary disease; an autosomal dominant transmission (Figure 1) usually suggests a genetic link. It has been suggested that mutations in the HNF-1ß gene are associated with familial cases of GCKD. Recent studies have suggested an association with mutations in Col4a1 and other genes in mouse models. GCKD can also occur in conjunction with tuberous sclerosis complex (TSC), juvenile nephronopthisis, Meckel-Gruber syndrome, Jeune’s syndrome, Zellweger’s syndrome, trisomy 13, orofaciodigital syndrome type 1, and early-onset autosomal dominant polycystic kidney disease (ADPKD). Jochen K. Lennerz and colleagues summarized up various circumstances in Table 1 from reviewing more than two hundred glomerulocystic kidney cases.

Figure 1.

The pedigree of a family affected with autosomal dominant glomerulocystic kidney disease.

Table 1.

Categories of glomerular cystic disease. (From Lennertz et al, Pathol Lab Med 134: 583-605, 2010, with permission.)

In a large-scale review of 234 cases, the most common forms of GCKD were sporadic or occurred with TSC or Zellweger’s syndrome. The disease can also occur in neonatal and adult forms. Neonates can present with hypertension, abdominal masses, early onset diabetes, and variable degrees of renal failure, while adults typically present with flank pain, hematuria, and hypertension. Mutations in the HNF-1ß gene are associated with maturity-onset diabetes in the young.

Since the protein produced by HNF-1ß is critical for embryonic development of the kidney, pancreas, liver, and Mullerian duct, affected individuals will typically present with hypoplastic kidneys and early-onset diabetes or impaired glucose tolerance. Hepatic cysts may also develop. The natural history of GCKD is not entirely known, but it is suggested that it is associated with a slow progression to end-stage renal disease (ESRD).

How to utilize team care?

Specialty consultations: Families of GCKD patients should receive patient education on the risk for inheritance of the disease (50% in an at-risk individual) and potential progression of endocrine and renal disease for the individual if possible. Nephrologic consultation is necessary for individuals with ESRD.

  • Pediatric and adult endocrinologists for the maintenance of early-onset diabetes in children and adults.

  • Nurses administer blood pressure checks and oral or IV medications; collect urine for urinalysis. Nurses must also educate pediatric and adult patients about adequate water intake and appropriate sodium supplementation

  • Pharmacists dispense blood pressure medications and diabetes medication.

  • Dietitians assist in the institution and maintenance of a renal and diabetic diet, which reduces the amount of phosphate, protein, sodium, acid, and sugar intake.

Are there clinical practice guidelines to inform decision making?

Applications

It is imperative for clinicians to be aware of the similarities between GCKD and other cystic kidney diseases. Extreme attention should be given to the imaging and biopsy criteria, in order to ensure a proper diagnosis.

Other considerations

  • ICD-9 Codes: 753.3 (other specified anomalies of kidney); 585.1-585.5 (chronic kidney disease stages I-V); 585.6 (end stage renal disease); 403 (hypertensive chronic kidney disease); 250. (diabetes with renal manifestations); 599.7 (hematuria)

  • MIMs code: #137920 (renal cysts and diabetes syndrome)

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