Changes in levels of matrix metalloproteinase-2 and-9, pregnancy-associated plasma protein-A in patients with various nephropathies
Abstract
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.