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 appears similar to other cystic kidney diseases; therefore a renal biopsy must be done for a definitive diagnosis. Examples of renal biopsy findings include mild proliferation of mesangial cells and matrixes, and 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 antihypertensives, diabetes medication and surgery, 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. 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 glomerularcystic kidney cases.

Figure 1.

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

Table I.

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

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

What is the evidence?

Ecder, T, Godelam, FM, Schrier, RW, Schrier, RW. "Polycystic kidney disease". Diseases of the kidney & urinary tract. Lippincott Williams & Wilkins. 2007. pp. 502-540.

(A textbook chapter covers polycystic kidney diseases)

Borges Oliva, MR, Hsing, J, Rybicki, FJ, Fennessy, F, Mortele, KJ, Ros, PR. "Glomerulocystic kidney disease: MRI findings". Abdom Imaging. vol. 28. 2003. pp. 889-892.

(An earlier imaging study of glomerulocystic kidney disease)

Sharp, CK, Bergman, SM, Stockwin, JM, Robbin, ML, Galliani, C, Guay-Woodford, LM. "Dominantly transmitted glomerulocystic kidney disease: a distinct genetic entity". J Am Soc Nephrol. vol. 8. 1997. pp. 77-84.

(The first known genetic linkage study conducted in GCKD family)

Gusmano, R, Caridi, G, Marini, M, Perfumo, F, Ghiggeri, GM, Piaggio, G, Ceccherini, I, Seri, M. "Glomerulocystic kidney disease in a family". Nephrol Dial Transplant. vol. 17. 2002. pp. 813-818.

(A cases report distinguishing GCKD from ADPKD)

Fitch, SJ, Stapleton, FB. "Ultrasonographic features of glomerulocystic disease in infancy: similarity to infantile polycystic kidney disease". Pediatr Radiol. vol. 16. 1986. pp. 400-402.

(An earlier ultrasound study in GCKD, which authors emphasize that appeared similar to other infantile polycystic diseases)

Hotta, O, Sato, M, Furuta, T, Taguma, Y. "Pathogenic role of glomerulo-tubular junction stenosis in glomerulocystic disease". Clin Nephrol. vol. 51. 1999. pp. 177-180.

(A histological observation suggested that the glomerular cystic lesion develops as a consequence of glomerulo-tubular junctional stenosis and peri-glomerular fibrosis.)

Bingham, C, Bulman, MP, Ellard, S, Allen, LI, Lipkin, GW, Hoff, WG, Woolf, AS, Rizzoni, G, Novelli, G, Nicholls, AJ, Hattersley, AT. "Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease". Am J Hum Genet. vol. 68. 2001. pp. 219-224.

(Authors suggested that mutations in the HNF-1ß gene are associated with familial cases of GCKD.)

Miyazaki, K, Miyazaki, M, Yoshizuka, N, Sasaki, O, Furusu, A, Horita, Y, Taguchi, T, Harada, T, Ozono, Y, Kohno, S. "Glomerulocystic kidney disease (GCKD) associated with Henoch-Schoenlein purpura: a case report and a review of adult cases of GCKD". Clin Nephrol. vol. 57. 2002. pp. 386-391.

(A case report on sporadic GCKD and associated Henoch-Schoenlein purpura (HSP))

Obata, Y, Furusu, A, Miyazaki, M, Nishino, T, Kawazu, T, Kanamoto, Y, Nishikido, M, Taguchi, T, Kohno, S. "Glomerulocystic kidney disease in an adult with enlarged kidneys: a case report and review of the literature". Clin Nephrol. vol. 75. 2011. pp. 158-164.

(Another case report on sporadic GCKD with enlarged kidneys)

Rizzoni, G, Loirat, C, Levy, M, Milanesi, C, Zachello, G, Mathieu, H. "Familial hypoplastic glomerulocystic kidney. A new entity?". Clin Nephrol. vol. 18. 1982. pp. 263-268.

(An earlier description of the GCKD disease with urographic abnormalities)

Bernstein, J. "Glomerulocystic kidney disease--nosological considerations". Pediatr Nephrol. vol. 7. 1993. pp. 464-470.

(In the early publication, author describes glomerulocystic disease as a group of diseases share the common symptom and attempted on categorizing.)

Lennerz, JK, Spence, DC, Iskandar, SS, Dehner, LP, Liapis, H. "Glomerulocystic kidney: one hundred-year perspective". Arch Pathol Lab Med. vol. 134. 2010. pp. 583-605.

(Authors suggested the term GCK disease (GCKD) should be reserved for the recognized/inherited subtypes of GCK (not to include PKD) and a classification scheme. Authors also summarized up Table 1 from reviewing more than two hundred cases.)

Bissler, JJ, Siroky, BJ, Yin, H. "Glomerulocystic kidney disease". Pediatr Nephrol. vol. 25. 2010. pp. 2056-2049.

(Another review that describes glomerulocystic diseases as a group of diseases shares the common feature and suggested classifications.)
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