Plasma matrix metalloproteinase-9 [MMP-9], urinary type IV collagen and urinary podocytes as markers of incipient diabetic nephropathy

Increased albumin excretion in diabetes is known to be an early marker of diabetic nephropathy, which mostly progress to renal failure. Early start of treatment is important to delay or prevent late complications. Early markers are important in case of diabetic nephropathy. In this study we investigate urinary collagen type IV [u c IV], matrix metalloproteinase 9 [MMP-9] and urinary podocytes as indicators of incipient [early] diabetic nephropathy and their role as a prognostic factors for deterioration in renal function. The study is a cross sectional case control study. It was carried out on 60 diabetic patients classified into three equal groups according to urinary albumin. The fourth group was 20 healthy control subjects. for all groups in addition to history and clinical examination urinary albumin and creatinine clearance, the level of urinary collagen type IV using immunoassay, plasma MMP-9 using enzyme immunoassay, and urinary podocytes was measured. The diabetic groups were compared with each other and with the control group. Plasma MMP-9 and urinary collagen type IV are significantly higher [p<0.001 for each] in diabetic normoalbuminuric group than healthy control group. Level of both markers increase significantly with the progress of albuminurea. Urinary podocytes is absent in normoalbuminuric diabetics and in healthy control group and its level increases with the progress of proteinurea. MMP-9, Collagen IV excretion and urinary podocytes showed a significant correlation [p <0.001, p <0.001, p =0.002 respectively] with the urinary albumin excretion. ROC curve study showed that MMP-9, Collagen IV excretion but not urinary podocytes can predict [sensitivity 100%, 100%, 33.3% respectively] a decline in creatinine clearance. Because not all patients with microalbuminuria progress to declining renal function and some patients who develop nephropathy do not manifest albuminuria. The findings in this cross-sectional analysis suggest that measurement of urine collagen IV, plasma MMP-9, may be a useful noninvasive indicator to detect diabetic renal disease before the stage of microalbuminuria, and can predicts patients liable to enter a phase of compromised renal function

Diagnostic and Prognostic Significance of urine type IV Collagen in type II diabetes mellitus

This study included 45 Type II diabetic patients diagnosed for more than 5 years, 10 normal control subjects [c]. 6 patients with IgA nephropathy [IgAN], 10 cases of membranoproliferative glomerulonephritis [MCGN], and 6 cases of membranous glomerulonephritis [MGN]. The aim of this work is to find out if there is a discrepancy in the urinary appearance of Type IV collagen [u-IV Col] in these frequently encountered glomerular diseases in comparison to patients with diabetic nephropathy [DN] and to study the rate of excretion of this compound in the different stages of DN. The 45 diabetic patients were selected to include 15 with normal kidney function, blood pressure and 24 hours urine albumin excretion [UAE] [DNO]. Another 15 had UAE between 30 and 300 mg/24 hours and retinal changes of diabetic retinopathy [DNI]. The remaining 15 were selected to have UAE > 300 mg/24 hours, systemic hypertension, normal kidney function and retinal changes of diabetic retinopathy [DNII]. AII groups were matched in age, gender and level of serum creatinine. All cases were tested for fasting blood sugar [FBS], glycsylated haemoglobin [HbA 1c], serum creatinine [Scr], serum albumin [Salb], 24hours urine protein [Uprot], UAE, creatinine clearance [CC], u-IV Col and serum level of type IV Col]. FBS and HbA 1c were significantly higher in the DN groups, however, there was no significant difference in these parameters in between these group. There were no significant differences in Scr and Salb between the different groups. Uprot was significantly lower in C, DN0 and DNI than in DNII, lgAN, MCGN and MGN [P<0.01]. UAE was significantly lower in c and DN0 than in DNI and in any these groups compared to DNII, lgAN, MCGN and MGN [P<0.001 in either]. CC was significantly higher in C, DN0 and DNI than in DNII, lgAN, MCGN and MGN [P<0.01]. u-IV Col was significantly higher in DNI, DNII and MGN than all other groups [p<0.01] There was no significant difference in s-IV Col between the different group [P>0.05]. u-IV Col showed a significant negative corrlation to CC only in DN groups [r=-0.562.p<0.005], but no significant correlation to Uprot, UAE or s-IV Col could be detected in these groups or in the other studied groups. Conclusion:1] u-IV Col could be used as a non- invasive diagnostic tool for DN in type II diabetes. 2] Increased u-IV Col is likely due to local renal over-production. 3] Rate of u-IV Col excretion could give an idea about the severity of DN