THE USE OF A NOVEL MONITORING APPARATUS AND MODIFIED BELZER HYDROXYETHYL STARCH PERFUSATE FOR ANALYSIS OF GLOMERULAR FILTRATION DURING HYPOTHERMIC PERFUSION PRESERVATION1

Abstract

The present study describes an experimental model for measurement of glomerular filtration during hypothermic perfusion preservation (HPP). To facilitate glomerular filtration during HPP, perfusate oncotic pressure was reduced by lowering the concentration of hydroxyethyl starch. Lewis rats underwent HPP at a mean perfusion pressure of 40-46 mmHg. An isograft model was used to demonstrate that retrieval and preparation for HPP did not impact adversely on renal function. Total cold ischemic time (CIT) consisted of the time from retrieval and preparation for perfusion (2 hr) added to the time of HPP. Tubular function studies demonstrated identical concentrations of Na+ and iohexol in ureteral effluent (UE) compared with circulating perfusate and, as such, established that UE flow represented a direct measure of glomerular filtration. Glomerular filtration rate (GFR) was then monitored during HPP by collecting UE in a beaker housed within a computerized Mettler balance system. GFR evolved in a characteristic, biphasic pattern during HPP, increasing from baseline values to reach a peak level at 4.8+/-0.3 hr of CIT and declining progressively thereafter. At 2.5 hr, time of peak values, 10 hr, 19.5 hr, and 24 hr of CIT, GFR values were 29+/-6 microl/min, 39+/-7 microl/min, 20+/-4 microl/min (n=15; P<0.01), 7+/-2 microl/min (n=14; P<0.001), and 14+/-6 microl/min (n=5), respectively. Intrarenal perfusate flows at the same time intervals were 4180+/-292 microl/min, 4083+/-290 microl/min, 3577+/-294 microl/min (P=NS), 1948+/-393 microl/min (P<0.001), and 2175+/-743 microl/min, respectively. Filtration fraction (FF) initially changed in parallel to glomerular filtration. Thereafter, FF either declined at a disproportionately slow rate compared with GFR (n=8) or increased rapidly (n=7). The data suggest that (1) primary change(s) in glomerular dynamics occur during HPP and (2) declining perfusate flow during the later stages of HPP reflects increasing renal vascular resistance localized at a postglomerular level. The data provide an experimental basis for investigating the clinical utility of monitoring glomerular filtration during HPP.