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Acute rejection of rat renal allografts is influenced by the presence of a native kidney
ELSEVIER
Acute Rejection of Rat Renal Allografts of a Native Kidney
Is Influenced
by the Presence
V. Grau, B. Herbst, and B. Steiniger
P
REVIOUS bilateral native nephrectomy in humans results in a better outcome of primary renal allografts.’ In spite of its clinical relevance, the mechanism resulting in an improved allograft outcome is still unknown and has not been investigated experimentally. MATERIALS
AND
METHODS
We performed a sequential daily analysis of orthotopically transplanted’ isogencic (LEW-,LEW, n = 1 per day) and allogeneic (DA+LEW, n = 3 per day) rat kidneys. Graft recipients were either unilaterally or bilaterally nephrectomised. Total ischemic times remained below 40 min. Paraffin sections were stained with hematoxylin-eosin. Immunohistochemical staining was performed on cryostat sections fixed in 100% isopropanol. Graft morphology and infiltration by ED1 (CDhR-like)-positive and ol//3 T cell reccptor-positive positive lymphocytes (mAb R73) were analyzed. Unilaterally nephrectomised allograft recipients survived in good health, whereas bilaterally nephrectomised allograft recipients died between day 6 and day 8 posttransplantation (7.4 + 0.7, mean + SD).
RESULTS
AND
DISCUSSION
During the first four days, histologic sections of allografts showed increasing atrophic changes of the renal tubules and infiltrates of mononuclear cells, irrespective of the presence or absence of a native contralateral kidney. Later, differences in the onset and the histologic pattern of allograft necrosis were obvious. On day 6 posttransplantation allografts of unilaterally nephrectomised recipients became abruptly and completely necrotic. In contrast, after bilateral nephrectomy, allograft necrosis occurred on day 5 and was incomplete: Necrotic regions in the allogeneic kidney were intermingled with viable but atrophic regions from day 5 until death. Isograft morphology in totally nephrectomised recipients was well preserved from day 1 to day 10 posttransplantation. In contrast, in the presence of a native contralateral kidney, numerous dilated and slightly atrophic renal tubules were observed in isografts from day 3 to day 10. The
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Transplantation Proceedings, 29, 1723 (1997)
infiltration of allografts by macrophages and T cells was altered in the presence of a native kidney: ( 1) infiltration of the renal interstitium by EDl-positive macrophages and T lymphocytes started on day 2, one day earlier than in bilaterally nephrectomised animals; (2) the number of macrophages and T cells was higher in the presence of a native kidney; and (3) Similar numbers of infiltrating macrophages and T cells were counted in allografts of unilaterally nephrectomised animals, whereas macrophages outnumbered T cells after bilateral nephrectomy. An influence of a native healthy kidney on graft infiltration was also observed in the isogeneic rat strain combination: From day 3 to day 10 after transplantation the number of infiltrating leukocytes was increased in comparison to isografts in totally nephrectomised recipients. In conclusion, we demonstrated that the presence or absence of a native contralateral kidney had a strong effect on allograft rejection. The recovery of isogeneic kidneys from ischemic stress during transplantation has been shown to be negatively influenced by a healthy contralateral kidney.” We suggest then, that a difference in the recovery from an initial ischemic damage eventually resulted in a changed allograft infiltration and in a different histologic pattern of allograft rejection in our experimental system.
REFERENCES 1. Advisory Committee plant Proc 9:9, 1977 2. Fabre
to the Renal Transplant
J, Lim SH, Morris
3. Coffman 1986
TM, Sanfilippo
Registry:
Trans-
PJ: Aust NZ J Surg 41:6Y, 1971 FP, Brazy PC, et al: Kidney Int 30:20,
From the Institute of Anatomy and Cell Biology, Marburg, Germany. Address reprint requests to Veronika Grau, Institute of Anatomy and Cell Biology, Robert-Koch Str. 6, D-35033, Marburg, Germany. This study was supported by the Stiftung P.E. Kempkes.
0041-l 345/97/$17.00 PII soo41-1345(97)00030-4
1723
Acute Rejection of Rat Renal Allografts of a Native Kidney
Is Influenced
by the Presence
V. Grau, B. Herbst, and B. Steiniger
P
REVIOUS bilateral native nephrectomy in humans results in a better outcome of primary renal allografts.’ In spite of its clinical relevance, the mechanism resulting in an improved allograft outcome is still unknown and has not been investigated experimentally. MATERIALS
AND
METHODS
We performed a sequential daily analysis of orthotopically transplanted’ isogencic (LEW-,LEW, n = 1 per day) and allogeneic (DA+LEW, n = 3 per day) rat kidneys. Graft recipients were either unilaterally or bilaterally nephrectomised. Total ischemic times remained below 40 min. Paraffin sections were stained with hematoxylin-eosin. Immunohistochemical staining was performed on cryostat sections fixed in 100% isopropanol. Graft morphology and infiltration by ED1 (CDhR-like)-positive and ol//3 T cell reccptor-positive positive lymphocytes (mAb R73) were analyzed. Unilaterally nephrectomised allograft recipients survived in good health, whereas bilaterally nephrectomised allograft recipients died between day 6 and day 8 posttransplantation (7.4 + 0.7, mean + SD).
RESULTS
AND
DISCUSSION
During the first four days, histologic sections of allografts showed increasing atrophic changes of the renal tubules and infiltrates of mononuclear cells, irrespective of the presence or absence of a native contralateral kidney. Later, differences in the onset and the histologic pattern of allograft necrosis were obvious. On day 6 posttransplantation allografts of unilaterally nephrectomised recipients became abruptly and completely necrotic. In contrast, after bilateral nephrectomy, allograft necrosis occurred on day 5 and was incomplete: Necrotic regions in the allogeneic kidney were intermingled with viable but atrophic regions from day 5 until death. Isograft morphology in totally nephrectomised recipients was well preserved from day 1 to day 10 posttransplantation. In contrast, in the presence of a native contralateral kidney, numerous dilated and slightly atrophic renal tubules were observed in isografts from day 3 to day 10. The
0 1997 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Transplantation Proceedings, 29, 1723 (1997)
infiltration of allografts by macrophages and T cells was altered in the presence of a native kidney: ( 1) infiltration of the renal interstitium by EDl-positive macrophages and T lymphocytes started on day 2, one day earlier than in bilaterally nephrectomised animals; (2) the number of macrophages and T cells was higher in the presence of a native kidney; and (3) Similar numbers of infiltrating macrophages and T cells were counted in allografts of unilaterally nephrectomised animals, whereas macrophages outnumbered T cells after bilateral nephrectomy. An influence of a native healthy kidney on graft infiltration was also observed in the isogeneic rat strain combination: From day 3 to day 10 after transplantation the number of infiltrating leukocytes was increased in comparison to isografts in totally nephrectomised recipients. In conclusion, we demonstrated that the presence or absence of a native contralateral kidney had a strong effect on allograft rejection. The recovery of isogeneic kidneys from ischemic stress during transplantation has been shown to be negatively influenced by a healthy contralateral kidney.” We suggest then, that a difference in the recovery from an initial ischemic damage eventually resulted in a changed allograft infiltration and in a different histologic pattern of allograft rejection in our experimental system.
REFERENCES 1. Advisory Committee plant Proc 9:9, 1977 2. Fabre
to the Renal Transplant
J, Lim SH, Morris
3. Coffman 1986
TM, Sanfilippo
Registry:
Trans-
PJ: Aust NZ J Surg 41:6Y, 1971 FP, Brazy PC, et al: Kidney Int 30:20,
From the Institute of Anatomy and Cell Biology, Marburg, Germany. Address reprint requests to Veronika Grau, Institute of Anatomy and Cell Biology, Robert-Koch Str. 6, D-35033, Marburg, Germany. This study was supported by the Stiftung P.E. Kempkes.
0041-l 345/97/$17.00 PII soo41-1345(97)00030-4
1723