Correlation between the expression of DNA topoisomerases I and II alpha and clinical parameters in kidney disease

Multiple factors interact during the evolution of renal diseases. In the pr esent study, we examined the expression of DNA topoisomerases type I and II alpha, which reflect gene transcription and DNA replication, respectively. Enzyme content was assessed by immunohistochemistry using two specific mon oclonal antibodies, C21 and Ki-S4, on 81 archival punch-biopsy specimens fr om patients with renal diseases, including minimal change disease (MCD; n = 10), focal segmental glomerular sclerosis (FSGS; n = 6), mesangial prolife rative glomerulonephritis (MPGN; n = 11), membranous glomerulonephritis (MG N; n = 10), mesangial capillary glomerulonephritis (MCGN; n = 7), rapidly p rogressive glomerulonephritis (RPGN; n = 12), lupus nephritis (LN; n = 15), and tubulointerstitial nephritis (TIN; n = 10). Both enzymes were strongly expressed. in diseases tending to rapid progression, notably RPGN and LN, whereas MCD and MGN showed low protein levels in both the glomerular and tu bular compartments. Moreover, topoisomerase expression was significantly as sociated with the density of monocytogenic infiltrates (monitored by means of the monoclonal antibody Ki-M1p), such pathogenesis-associated factors as antinuclear antibodies, and paranuclear antineutrophilic antibodies, and s erum immunoglobulin levels. There also was a positive correlation with seru m creatinine levels and an inverse association with proteinuria and nephrot ic syndrome. We conclude that the expression of DNA topoisomerases may be l inked to pathogenetic mechanisms and may provide prognostic information. Be cause of their comparatively low nephrotoxicity, topoisomerase inhibitors m ight prove to be useful therapeutic agents In the treatment of renal diseas es. (C) 2001 by the National Kidney Foundation, Inc.