Shibata K, Dohi K, Fujii Y, Ishikawa H
First Department of Internal Medicine, Nara Medical University.
Nihon Jinzo Gakkai Shi. 1991 Aug;33(8):719-29.
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.
肾小球内凝血在人类原发性肾小球疾病的发展中起重要作用,这是一个众所周知的事实。然而,肾小球内凝血的确切机制以及肾小球内的凝血能力和/或纤溶活性仍不清楚。本研究旨在阐明肾小球内凝血和纤溶在人类原发性肾小球疾病中的作用。本研究纳入的受试者包括27例微小病变肾病(MCNS)患者、14例局灶性节段性肾小球硬化(FGS)患者、36例膜性肾病(MN)患者、161例系膜增生性肾小球肾炎(mesPGN)患者、9例膜增生性肾小球肾炎(MPGN)患者以及40名健康志愿者作为对照。作为分离的肾小球内纤溶酶原激活物活性(PAA)对照的正常人肾皮质,在因对侧肾极肿瘤而切除的肾脏的正常极进行肾切除时获取。采用放射免疫分析法测定尿中尿激酶(UK)、纤维蛋白肽A(FPA)和纤维蛋白肽Bβ15 - 42(Bβ15 - 42)抗原。采用酶联免疫吸附测定法测定尿组织纤溶酶原激活物(t - PA)抗原。采用乳胶凝集法测定尿纤维蛋白/纤维蛋白原降解产物(FDP)。此外,采用125I - 纤维蛋白膜法测定PAA。获得了以下结果:1)在原发性肾小球疾病中,尿UK和t - PA水平显著低于健康志愿者;2)尿UK和t - PA随着系膜增生的发展呈逐渐下降趋势;3)尿UK和t - PA与尿FPA和Bβ15 - 42均显著相关;4)在mesPGN和FGS中,PAA显著低于正常对照;5)PAA与尿UK、t - PA、FPA和Bβ15 - 42显著相关;6)有尿FDP的患者尿UK和t - PA显著低于无尿FDP的患者;7)有肾小球内纤维蛋白沉积的患者尿UK、t - PA和PAA显著低于无纤维蛋白沉积者。这些发现提示尿UK和t - PA水平的降低以及分离的肾小球内纤溶酶原激活物活性的减弱有助于原发性肾小球疾病的进展。