AUGMENTING KIDNEY MASS AT TRANSPLANTATION ABROGATES CHRONIC RENAL-ALLOGRAFT INJURY IN RATS

Conventional renal transplantation, which substitutes a single allogra ft for two native kidneys, imposes an imbalance between nephron supply and the metabolic and excretory demands of the recipient. This discre pancy, which stimulates hyperfunction and hypertrophy of viable allogr aft nephrons, may be intensified by nephron loss through ischemia-repe rfusion injury or acute rejection episodes occurring soon after transp lantation. In other settings where less than 50% of the total renal ma ss remains, progressive glomerular injury develops through mechanisms associated with compensatory nephron hyperfiltration and hypertrophy. To determine whether responses to nephron loss contribute to chronic i njury in renal allografts, nephron supply was restored to near-normal levels by transplanting Lewis recipients with two Fisher 344 kidneys ( group 2A! compared with the standard single allograft F344-->LEW rat m odel of late renal allograft failure (group 1A). At 20 weeks, indices of injury were observed in 1A but not 2A rats. These indices included proteinuria (1A: 45 +/- 13; 2A: 4.0 +/- 0.29 mg/day) and glomeruloscle rosis (1A: 23 +/- 4.9%, 2A: 0.7 +/- 0.3%) (p < .05). Double-allograft recipients maintained near normal renal structure and function, wherea s 1A rats showed evidence of compensatory hyperfiltration (single-neph ron glomerular filtration rate of 63 +/- 10 versus 44 +/- 2.0 nl/min i n 2A rats) and hypertrophy (mean glomerular volume of 2.64 +/- 0.15 ve rsus 1.52 +/- 0.05 mu m(3) x 10(6) in 2A rats) (p < .05). Thus, we con clude that a major component of late allograft injury is attributable to processes associated with inadequate transplanted renal mass, a fin ding that has major implications for kidney transplantation biology an d policy.