Glomerulocystic Kidney Disease and its rare associations: an autopsy report of two unrelated cases
© Gupta et al; licensee BioMed Central Ltd. 2007
Received: 19 March 2007
Accepted: 25 April 2007
Published: 25 April 2007
Glomerulocystic kidney disease is an uncommon type of cystic renal disease. It is characterized by cortical microsysts, which are represented by cystic dilatation of Bowman's spaces.
We describe a case of glomerulocystic disease in a neonate and another in an abortus associated with tracheo-oesophageal fistula and megacystic-megaureter syndrome. The kidney on autopsy was sponge-like and revealed presence of cysts corresponding to dilatations of Bowman's space microscopically. In these two cases, the Glomerulocystic Kidney Disease in one case corresponded to a sporadic form and, in the other, to a syndromic, non-heritable form of glomerulocystic kidney disease.
The associated anomalies in Glomerulocystic Kidney disease are well described in the literature. Two more new unrelated associations are described in this article.
Glomerulocystic kidney disease (GCKD) was characterized as a distinct histopathological entity in 1976 by Taxy and Filmer, who described this as a heterogeneous group of disorders with a common link being a variable degree of cystic dilatation of Bowman's spaces . These cortical cysts seen grossly are mostly located in the subcapsular area of the renal cortex. It occurs in both sporadic and familial forms. Glomerular cysts have been observed in various renal cystic diseases such as autosomal dominant polycystic kidney disease (ADPKD), cystic renal dysplasia, autosomal recessive polycystic kidney disease (ADPKD), Zellweger's cerebral-renal-hepatic syndrome, and tuberous sclerosis . Familial GCKD can be associated either with hypoplastic or normal sized kidneys. Hence, GCKD must be diagnosed by excluding other cystic renal disorders.
About one half of the examples of GCKD described in infants appear to be an expression of ADPKD with unusually early clinical onset, but not all cases of infantile-onset ADPKD have predominantly glomerular cysts. The exact significance of this morphologic expression in relation to ADPKD is yet not established. GCKD is also known to be encountered as sporadic condition in infants and young children who present in renal failure .
Case summary 1
Case summary 2
Glomerulocystic kidney disease is an uncommon type of cystic renal disease. Roos first described it as an isolated abnormality in 1941 . However, Taxy and Filmer proposed the term of GCKD in 1976 , which is widely used to describe the characteristic morphological features of dilatation of Bowman's space often without quantitative criteria. Bernstein defined glomerular cyst as dilatation of Bowman's space 2–3 times in the plane of section . He also considered that the occurrence of glomerular tufts, within atleast 5 % of otherwise identifiable cysts, defines glomerulocystic kidney. However the definition does not exclude the presence of associated tubular dilatation. GCKD can be categorized into five major groups :
1. Familial GCKD,
2. GCKD associated with heritable diseases such as ADPKD/ARPKD and tuberous sclerosis,
3. Syndromic, non-hereditary GCKD,
4. Sporadic GCKD and
5. Acquired GCKD.
The first group includes autosomal dominantly transmitted GCKD (ADGCKD). The second group comprises of diffusely glomerulocystic kidneys in newborns and young children, many of whom have family histories positive for classical polycystic kidney disease. It also includes sporadic and familial disease in older children and adults. No differences between familial and sporadic cases have been identified, apart from the family histories. The sporadic cases conceivably represent new mutations of the same disease. It also includes glomerulocystic kidneys as major component of heritable syndromes such as tuberous sclerosis, trisomy 13 and others. The third group includes glomerulocystic kidneys as components of diffuse cystic dysplasia and renal-hepatic-pancreatic dysplasia syndrome. The fourth group comprises all the sporadically occurring GCKD. Acquired GCKD (group 5) has been described following hemolytic-uremic syndrome .
The mechanism of cyst formation in GCKD is poorly understood. Various factors that may be involved in the pathogenesis of GCKD include tubular obstruction due to renal medullary inflammation in neonates, increased intraglomerular pressure when the fetal glomeruli become functional and maternal intake of drugs such as phenacetin during pregnancy . Baxter et al suggested that GCKD is produced late in gestation, by malformation in nephrogenic zone or tubular obstruction . Ischemia, an acquired factor, may be involved in the genesis of glomerular cysts and explain sporadic forms observed in adults . Evidence for the glomerular origin of the cysts was first provided by Baxter. Vernani et al in a study have shown that, the cysts showed negative staining with markers of proximal and distal tubular epithelium, thereby suggesting a glomerular origin of cysts . Although no microdissection studies were performed in our cases, the morphometric findings also support glomerular origin of GCKD . Recent studies have also suggested stenosis at glomerulo-tubular junction to be the main cause of glomerular cyst development. However, three-dimensional imaging analysis has excluded stenosis or obstruction at the level of the glomerulo-tubular neck . Recently, mutation in the hepatocyte nuclear factor-1beta (HNF-1β) gene has been identified in hypoplastic GCKD variant . The genetic studies could not be carried out in our cases. However there was no history of any cystic disease/or renal function derangement in the siblings in both the families.
Dilatation of the bladder and ureters can be seen with any obstructive lesion of lower urinary tract, but in the megacystic-megaureter syndrome, no anatomic obstruction is present . Severe vesicoureteric reflux leads to the constant recycling of large volumes of refluxed urine, which in turn results in an enlarged bladder and massively dilated ureters . There was no evidence of posterior uretheral valves, thus the plausible explanation for megacystic-megaureter in abortus appears to be a functional defect, which must also have contributed partly to development of dysplasia and glomerular cysts. Evidence for such a mechanism derives from experimental ureteral ligation in neonatal animals .
The above two cases illustrates the sporadic form of GCKD (group 4) occurring in term baby and syndromic, non-heritable GCKD (group 3) in a 17-week abortus according to the above classification. A recent literature review failed to show a link between this rare association of GCKD with TEF, and megacystic-megaureter syndrome. Glomerular cysts are considered to be the basic and predominant lesions of GCKD. No dilatation of tubules is present; the absence of tubular dilatation excludes the diagnosis of ADPKD. Dysplastic elements were noted in the kidney sections of abortus, however were absent in term baby.
In conclusion, the above two cases highlight the rare associations with which this heterogeneous entity is associated.
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