Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis

Abstract

The study sought a diagnostic clue to identify the group of pediatric patients with apparent minimal change disease who subsequently develop focal glomerular sclerosis (FGS). Review of all renal biopsy material at our institutions identified 42 pediatric patients who met the standard criteria for minimal change disease (MCD) on initial biopsies. Of those, 10 deteriorated clinically and on rebiopsy showed focal glomerular sclerosis (FGS). The initial renal biopsies of these 10 patients were analyzed morphometrically to determine the mean glomerular tuft area (GA). The results were compared to those of the remaining 32 patients whose subsequent benign clinical course was consistent with MCD, and to randomly selected, age-matched autopsy controls without renal disease (CONT, N = 10). The mean age was comparable among the three groups studied. Separate groups of adult (N = 12) and pediatric (N = 18) patients with initial biopsies with FGS were also studied. The initial biopsy of pediatric patients who subsequently showed FGS (rebiopsy performed on average 3.3 years later) had an average GA of 13.5 x 10(-3) mm2, 76% larger than glomeruli from children with MCD (7.7 x 10(-3) mm2, P less than 0.0005) and 62% larger than CONT (8.4 x 10(-3) mm2, P less than 0.005). Patients with FGS on initial biopsy, whether adult or pediatric, also had significantly larger GA than the age-matched MCD or CONT groups. Evaluation of GA in all the 42 pediatric biopsies with initial MCD further showed that in 23 patients GA was equal to or smaller than the CONT average.(ABSTRACT TRUNCATED AT 250 WORDS)

ECM homeostasis in renal diseases: a genomic approach

“…Although MCD and FSGS can often be differentiated on the basis of clinical course, discrimination of the two entities merely based on clinical symptoms at time of biopsy and histopathology is difficult [94], especially in the case of a small biopsy sample with only non-sclerosed glomeruli. Evidence has been found that glomerular size is relatively high in patients with FSGS [95] and in patients having MCD with an unfavourable prognosis [96]. Molecular research has shown that levels of podocyte-associated components such as dystroglycans [97] and α-actinin 4 532 M Eikmans et al [98] differ between MCD and FSGS in non-hereditary cases.…”

Dystroglycan in the Diagnosis of FSGS

“…Furthermore, most recurrent cases showed fidelity of histologic phenotype, further supporting inherent pathogenetic mechanisms leading to specific types of FSGS (25). The presence of glomerular hypertrophy in patients with initial diagnosis of apparent MCD predicts an increased risk of subsequently developing overt FSGS (18). More recent molecular studies also support that MCD and FSGS differ from the onset (26).…”

“…In some patients, large biopsies may show apparent MCD, i.e., lack of segmental sclerosis at first biopsy. However, subsequent course and rebiopsy showed that the ultimate process indeed is FSGS in some of these patients (18). Whether this represents a sclerosing process from the onset or transition from MCD to FSGS is controversial.…”

“…Cases with hilar or cellular FSGS were not included. Cases without segmental sclerosis but with significant glomerular hypertrophy, a feature we have previously linked to evolution to overt FSGS, were not included (18). Primary FSGS was defined by exclusion of other primary glomerular diseases and absence of other morphologic signs of a secondary cause of segmental sclerosis, such as disproportional severe vascular sclerosis, periglomerular fibrosis, surrounding nonsclerotic glomeruli, lamina rara interna expansion (a sign of hypertension-associated and/or chronic endothelial injury) by electron microscopy, limited FPE; lesions indicative of arterionephrosclerosis; or geographic pattern scarring with periglomerular fibrosis, lesions indicative of chronic pyelonephritis/ reflux nephropathy).…”

Glomerular stereology: Why, what and how to measure glomerular structure

“…In the second phase, the continued glomerular growth was not due to capillary lengthening but, rather, was probably due to an increase in mesangial matrix volume. 28, the kidneys were perfusion-fixed and samples taken for embedding in glycolmethacrylate as described above. Glomerular number and volume were determined using the methods described above.…”