BACKGROUND: Specific changes and imbalanced concentrations of matrix metalloproteinases (MMPs) and pregnancy-associated plasma protein-A (PAPP-A) may reflect the pathophysiology of various nephropathies (GN). We compared MMP-2, MMP-9 and PAPP-A levels in patients with GN, with those found in healthy controls. METHODS: We studied 45 controls and 128 patients with GN, defined by kidney biopsy: IgA nephropathy (IgAN, n=33), membranous glomerulonephritis (MN, n=23), minimal change nephrotic syndrome (MCNS, n=7), focal segmental glomerular sclerosis (FSGS, n=11), lupus nephritis (LN, n=22) and ANCA-associated glomerulonephritis (AAV, n=32). MMP-2 and MMP-9 levels were assessed using enzyme-linked immunosorbent assay; PAPP-A levels were determined with time-resolved amplified cryptate emission, and routine biochemical parameters were measured. RESULTS: Compared with controls, IgAN patients exhibited a significant decrease in levels of MMP-2 contrasted with increased MMP-9 and unchanged PAPP-A levels. LN patients exhibited a parallel decrease in MMP-2, MMP-9 and PAPP-A levels. In the MCNS/FSGS and AAV patients, MMP-2, MMP-9 and PAPP-A levels were unchanged. In MN patients, increased MMP-9 levels contrasted with unchanged MMP-2 and PAPP-A levels (all p<0.05). Both MMP-2 (r=-0.34, p<0.0001) and PAPP-A levels (r=-0.31, p<0.0001) were inversely correlated with estimated glomerular filtration rate in all GN groups. CONCLUSIONS: Serum levels of MMP-2, MMP-9 and PAPP-A significantly differed between various nephropathies. These findings suggest that MMPs and PAPP-A are involved in different underlying mechanisms in the regulation of glomerular and tubulointerstitial fibrosis and scarring in these renal diseases.

Department of Nephrology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Prague Czech Republic

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