BACKGROUND/AIMS: Alport syndrome (AS) is a renal disorder caused by a genetic abnormality of type IV collagen α3 and α4, or α5 genes and shows a poor prognosis. Since the defect of type IV collagen synthesis disturbs the maturation process of the glomerular capillary loop, residual immature glomeruli persist after birth. The therapeutic efficacy of cyclosporin A (CyA) for AS patients seems to be controversial. We recently noted that renal specimens obtained from a child with AS who was treated with CyA and then developed CyA nephropathy included an increased number of undifferentiated embryonic-type glomeruli. METHODS: We analyzed renal histologic and immunohistologic findings in children with AS who did (n = 3) or did not (n = 2) develop CyA-induced nephropathy despite appropriately low serum CyA concentrations (<100 ng/mL) being maintained over a period of 2 years. To discriminate embryonic-type from mature glomeruli, staining for type IV collagen α1, laminin β1, and laminin β2 accompanied by light microscopic observation were employed. Staining patterns were used to semiquantitatively assess glomerular immaturity (glomerular immaturity index, or GII). RESULTS: In initial biopsy specimens, residual embryonic-type glomeruli were observed in each patient. Patients with early-onset CyA nephropathy had a high GII (median value 2.91 vs 1.23 ± 0.62 normal kidney tissues). In the follow-up biopsy after CyA treatment, surviving embryonic-type, collapsing embryonic-type, and sclerotic glomeruli that had failed to differentiate were observed. Taken together, the number of these glomeruli essentially equaled the total number of embryonic-type glomeruli in specimens obtained before CyA treatment. CONCLUSIONS: Our findings indicate a need for caution in CyA therapy for patients with AS, even for a relatively short course of administration, because some patients may have an unexpected number of embryonic-type glomeruli that predispose to CyA nephropathy.
BACKGROUND/AIMS: Alport syndrome (AS) is a renal disorder caused by a genetic abnormality of type IV collagen α3 and α4, or α5 genes and shows a poor prognosis. Since the defect of type IV collagen synthesis disturbs the maturation process of the glomerular capillary loop, residual immature glomeruli persist after birth. The therapeutic efficacy of cyclosporin A (CyA) for AS patients seems to be controversial. We recently noted that renal specimens obtained from a child with AS who was treated with CyA and then developed CyAnephropathy included an increased number of undifferentiated embryonic-type glomeruli. METHODS: We analyzed renal histologic and immunohistologic findings in children with AS who did (n = 3) or did not (n = 2) develop CyA-induced nephropathy despite appropriately low serum CyA concentrations (<100 ng/mL) being maintained over a period of 2 years. To discriminate embryonic-type from mature glomeruli, staining for type IV collagen α1, laminin β1, and laminin β2 accompanied by light microscopic observation were employed. Staining patterns were used to semiquantitatively assess glomerular immaturity (glomerular immaturity index, or GII). RESULTS: In initial biopsy specimens, residual embryonic-type glomeruli were observed in each patient. Patients with early-onset CyAnephropathy had a high GII (median value 2.91 vs 1.23 ± 0.62 normal kidney tissues). In the follow-up biopsy after CyA treatment, surviving embryonic-type, collapsing embryonic-type, and sclerotic glomeruli that had failed to differentiate were observed. Taken together, the number of these glomeruli essentially equaled the total number of embryonic-type glomeruli in specimens obtained before CyA treatment. CONCLUSIONS: Our findings indicate a need for caution in CyA therapy for patients with AS, even for a relatively short course of administration, because some patients may have an unexpected number of embryonic-type glomeruli that predispose to CyAnephropathy.
Authors: N Kuroda; N Yoshikawa; K Nakanishi; K Iijima; K Hanioka; Y Hayashi; Y Imai; Y Sado; M Nakayama; H Itoh Journal: Pediatr Nephrol Date: 1998-09 Impact factor: 3.714