Laboratory Investigation

Kidney International (1987) 31, 8–14; doi:10.1038/ki.1987.2

Intrarenal hemodynamic alterations induced by anti-GBM antibody

Neil W Boyce1 and Stephen R Holdsworth1

1Monash University Department of Medicine, Prince Henry's Hospital, St. Kilda Road, Melbourne, Victoria, Australia

Correspondence: Neil W Boyce MD, Monash University Department of Medicine, Prince Henry's Hospital, St. Kilda Road, Melbourne, Victoria, Australia 3004.

Received 19 July 1985; Revised 24 February 1986; Re-revised 9 June 1986.

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Abstract

Intrarenal hemodynamic alterations induced by anti-GBM antibody. An isolated perfused kidney system (IPK) was used to study the direct intrarenal hemodynamic effects of binding of anti-glomerular–basement membrane (anti-GBM) antibody in the absence of all other circulating humoral and cellular inflammatory mediators. Control IPK's (perfused with Krebs–Henseleit buffered 5% albumin solution containing nonimmune globulin) had a renal vascular resistance (RVR) mean plusminus SEM 3.10 plusminus 0.47 mm Hg/ml/min and a GFR mean plusminus SEM 0.63 plusminus 0.8 ml/min/g. Anti-GBM antibody administration raised RVR (4.83 plusminus 0.52 mm Hg/ml/min, P < 0.01) and lowered GFR (0.34 plusminus 0.04 ml/min/g, P < 0.01). Perfusate renin activity was higher after antibody administration (684 plusminus 87 ng AI/ml/hr compared with control 308 plusminus 42 ngAI/ml/hr, P < 0.01). Treatment with Sar1Ala8All (3 times 10-6M) or captopril (10 mg/ml) attenuated antibody–induced vasoconstriction (RVR mm Hg/ml/min, Sara1Ala8All = 3.78 plusminus 0.13 captopril = 3.26 plusminus 0.12, both P < 0.05 compared with anti-GBM alone). Both inhibitors of the renin-angiotensin system (RAS) also aggrevated the decline in GFR seen after antibody administration (GFR ml/min/g, Sara1Ala8All = 0.24 plusminus 0.05, Captopril = 0.18 plusminus 0.03, both P < 0.05 compared with anti-GBM alone). These IPK studies demonstrate that anti-GBM antibody itself may directly induce intrarenal hemodynamic alterations in the absence of complement activation, neutrophil infiltration, neural influences or circulating vasoactive substances. The results from perfusate renin sampling and blockade of the RAS provide evidence that anti-GBM antibody deposition activates the intrarenal RAS and thereby induces significant hemodynamic alterations.

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