PVP-sieving curves as an estimate of glomerular hemodynamics in HgCl2 acute renal failure in the dog.

Abstract

In the present study, the pathophysiologic role of glomerular hemodynamic factors in the early phase of HgCl 2 -induced acute renal failure is evaluated in the dog. This model of moderate ARF is characterized by a parallel fall in glomerular filtration rate (AGFR, -43%) and renal blood flow (ARBF, -38%) within the first three hours after HgCl 2 administration. Glomerular hemodynamics were studied by analysis of PVP-sieving curves. There was a significant shift of these curves upward and to the right during the 3 hours that followed the injection of HgCl 2 . From this analysis, no arguments for tubular back-leak could be found. Mathematical analysis of the curves revealed a fall in effective filtration pressure ( If a glomerular hemodynamic factor was involved in the initiation of ARF, then the fall in GFR should be mediated by either a decrease in intraglomerular effective nitration pressure (EFP) and/or by a decrease in glomerular ultrafiltration coefficient (Kf). Direct estimations of both glomerular parameters in experimental ARF are scarce, and the reported results are often inconsistent. 5 " 9 In human forms of ARF, evaluation of glomerular dynamics is necessarily indirect, and the only available technique that has been applied is the analysis of macromolecular glomerular sieving curves. Myers and coworkers, using this method in forms of postoperative ischemic ARF, were able to observe remarkable shifts of the macromolecular sieving curves compatible with either tubular back-leak in severe ARF or a fall in This work was supported in part by a grant of the NFWGO n°3 .0015.82.Address for correspondence: R. Vanholder, Nephrology Department, University Hospital, De Pintelaan, 185, B-9000, GENT, (Belgium).Received July 7, 1986; accepted April 10, 1987. filtration pressure in milder forms. l0~13 Similar data on experimental ARF are as yet unavailable.Therefore, in the present study of early phase toxic ARF, macromolecular glomerular sieving curves were obtained to determine whether a change in EFP or Kf accompanied the fall in GFR after HgCl 2 in the experimental dog model. The results indicate that, at least in the early phase, this model is characterized by an important fall of EFP without substantial changes in glomerular permeability. Materials and MethodsThe studies were performed in 15 mongrel dogs. After anesthesia with pentobarbital (30 mg/kg i.v.), surgical preparation and clearance studies were performed as previously reported. 4 Clearance StudiesAfter 3 control clearance collections had been obtained, HgCl 2 (3 mg/kg bolus i.v.) was administered. Experimental clearances were collected 1,2, and 3 hours after the HgCl 2 administration. Exogenous creatinine and inulin clearances were obtained as an estimation of GFR. RBF was calculated from paraaminohippurate (PAH) clearances and renal venous blood PAH extractions obtained via a small catheter, introduced into the renal vein through the gonadal vein. Filtration fraction (FF), fractional sodium excretion (FE Na ), and urinary osmolar excretion (UV...