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[Intraglomerular coagulation and fibrinolysis in human primary glomerular diseases]
Insights
Reduced levels of urinary urokinase (UK) and tissue plasminogen activator (t-PA), along with diminished intraglomerular plasminogen activator activity (PAA), are linked to the progression of primary glomerular diseases, indicating impaired fibrinolysis.
Area of Science:
- Nephrology
- Hematology
- Biochemistry
Context:
- Intraglomerular coagulation is implicated in human primary glomerular diseases.
- The precise mechanisms of intraglomerular coagulation and fibrinolysis remain unclear.
Purpose:
- To investigate the roles of intraglomerular coagulation and fibrinolysis in primary human glomerular diseases.
Summary:
- This study measured urinary urokinase (UK), tissue plasminogen activator (t-PA), fibrinopeptide A (FPA), B beta 15-42, fibrin/fibrinogen degradation products (FDP), and intraglomerular plasminogen activator activity (PAA) in patients with various glomerular diseases and healthy controls.
- Results showed significantly lower urinary UK and t-PA levels in patients compared to controls, with further decreases correlating with mesangial proliferation and fibrin deposition.
- PAA was also reduced in specific conditions like mesangial proliferative glomerulonephritis (mesPGN) and focal glomerular sclerosis (FGS), and correlated with coagulation and fibrinolysis markers.
Impact:
- Findings suggest that decreased urinary UK and t-PA, and reduced PAA contribute to the progression of primary glomerular diseases.
- This research highlights the importance of the coagulation and fibrinolysis balance in kidney disease pathogenesis.
Abstract:
It is a well known fact that intraglomerular coagulation plays an important role in the development of human primary glomerular diseases. However, the precise mechanism of intraglomerular coagulation, and intraglomerular coagulability and/or fibrinolytic activity remains obscure. The present study was aimed to elucidate the role of the intraglomerular coagulation and fibrinolysis in human primary glomerular diseases. Subjects enrolled in this study were 27 patients with minimal change nephrotic syndrome (MCNS), 14 patients with focal glomerular sclerosis (FGS), 36 patients with membranous nephropathy (MN), 161 patients with mesangial proliferative glomerulonephritis (mesPGN), 9 patients with membranoproliferative glomerulonephritis (MPGN), and 40 healthy volunteers as controls. Normal human renal cortex as controls of isolated intraglomerular plasminogen activator activity (PAA) was obtained at the time of nephrectomy from the normal pole of kidneys removed because of an opposite pole tumor. Urinary urokinase (UK), fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (B beta 15-42) antigens were measured by RIA. Urinary tissue plasminogen activator (t-PA) antigen was measured by ELISA. Urinary fibrin/fibrinogen degradation products (FDP) were measured by latex agglutination method. Moreover, PAA was measured by 125I-fibrin films. The following results were obtained: 1) In primary glomerular diseases, levels of urinary UK and t-PA were significantly lower than those in healthy volunteers, 2) Urinary UK and t-PA showed gradual decrease along with the development of mesangial proliferation, 3) Urinary UK and t-PA were significantly correlated with both the urinary FPA and B beta 15-42, 4) In mesPGN and FGS, PAA was significantly lower than that in normal controls, 5) PAA was significantly correlated with urinary UK, t-PA, FPA and B beta 15-42, 6) Urinary UK and t-PA in the patients with urinary FDP were significantly lower than those in patients without urinary FDP, 7) Urinary UK, t-PA and PAA were significantly lower in patients with intraglomerular fibrin deposition than those in patients without fibrin depositions. These findings suggest that the decrease of urinary UK and t-PA levels and the diminution of isolated intraglomerular plasminogen activator activity contribute to the progression of primary glomerular diseases.