Munger K A, Coffman T M, Griffiths R C, Fogo A, Badr K F
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Transplantation. 1993 Jun;55(6):1219-24. doi: 10.1097/00007890-199306000-00003.
The effects of surgery and acute rejection on glomerular hemodynamics in the transplanted rat kidney are examined. Kidneys were transplanted from Munich-Wistar (MW) rats to syngeneic controls and MHC-incompatible PVG strain recipients. We report on 4 groups of animals: (1) two-kidney control MW rats; (2) unilaterally nephrectomized MW rats (UNX); (3) renal transplantation from MHC-identical MW littermates and removal of native kidneys (SYN); and (4) transplantation from MW donors to MHC-incompatible PVG rats and removal of native kidneys (ALLO). Glomerular filtration rate (GFR), single-nephron (SN)GFR, and glomerular capillary pressure (PGC) in SYN kidneys were depressed as compared to those in UNX (GFR, 1.41 +/- 0.08 vs. 0.80 +/- 0.08 ml/min; SNGFR, 67.2 +/- 4.8 vs. 44.7 +/- 6.6 nl/min; and PGC, 67 +/- 2 vs. 48 +/- 4 mmHg, UNX vs. SYN, respectively, P < 0.05). GFR and SNGFR in ALLO kidneys, however, were depressed even further (GFR, 0.40 +/- 0.05 ml/min; SNGFR, 13.8 +/- 1.8 nl/min; P < 0.05 for UNX vs. ALLO and SYN vs. ALLO). Afferent arteriolar resistance (RA) was increased greater than 4-fold (UNX, 1.01 +/- 0.15 10(10) dyn.sec.cm-5; SYN, 1.37 +/- 0.36 10(10) dyn.sec.cm-5; ALLO, 4.76 +/- 0.74 10(10) dyn.sec.cm-5 [P < 0.05, UNX vs. ALLO and SYN vs. ALLO]). This led to a precipitous fall in initial capillary flow rate in ALLO rats. These studies reveal the presence of moderate reductions in SNGFR and PGC in the nonrejecting transplanted kidney, which may relate to as yet unidentified consequences of the transplant surgery. More significantly, the principal mechanism leading to the reduced GFR characteristic of acute allograft rejection is identified as severe preglomerular vasoconstriction.
研究了手术和急性排斥反应对移植大鼠肾脏肾小球血流动力学的影响。将慕尼黑 - 威斯塔(MW)大鼠的肾脏移植到同基因对照和MHC不相容的PVG品系受体中。我们报告了4组动物:(1)双侧肾脏对照MW大鼠;(2)单侧肾切除的MW大鼠(UNX);(3)来自MHC相同的MW同窝仔鼠的肾移植并切除天然肾脏(SYN);以及(4)从MW供体移植到MHC不相容的PVG大鼠并切除天然肾脏(ALLO)。与UNX相比,SYN肾脏的肾小球滤过率(GFR)、单肾单位(SN)GFR和肾小球毛细血管压力(PGC)降低(GFR,1.41±0.08 vs. 0.80±0.08 ml/min;SNGFR,67.2±4.8 vs. 44.7±6.6 nl/min;PGC,67±2 vs. 48±4 mmHg,分别为UNX与SYN,P <0.05)。然而,ALLO肾脏中的GFR和SNGFR进一步降低(GFR,0.40±0.05 ml/min;SNGFR,13.8±1.8 nl/min;UNX与ALLO以及SYN与ALLO相比,P <0.05)。入球小动脉阻力(RA)增加超过4倍(UNX,1.01±0.15×10(10) dyn.sec.cm-5;SYN,1.37±0.36×10(10) dyn.sec.cm-5;ALLO,4.76±0.74×10(10) dyn.sec.cm-5 [P <0.05,UNX与ALLO以及SYN与ALLO相比])。这导致ALLO大鼠的初始毛细血管流速急剧下降。这些研究揭示了在未发生排斥反应的移植肾脏中SNGFR和PGC有适度降低,这可能与移植手术尚未明确的后果有关。更重要的是,导致急性同种异体移植排斥反应特征性GFR降低的主要机制被确定为严重的肾小球前血管收缩。