This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Herrero-Fresneda, I. Articles by Grinyo, J. M. Search for Related Content PubMed PubMed Citation Articles by Herrero-Fresneda, I. Articles by Grinyo, J. M.

(American Journal of Pathology. 2003;162:127-137.)
© 2003 American Society for Investigative Pathology

Regular Articles

Do Alloreactivity and Prolonged Cold Ischemia Cause Different Elementary Lesions in Chronic Allograft Nephropathy?

Immaculada Herrero-Fresneda^*, Joan Torras^*, Josep M. Cruzado^*, Enric Condom, August Vidal, Marta Riera^*, Nuria Lloberas^*, Jeroni Alsina and Josep M. Grinyo^*

From the Department of Medicine,^* Laboratory of Nephrology, University of Barcelona, Barcelona; and the Nephrology and Pathology Services, Hospital de Bellvitge, Ciutat Sanitària i Universitària de Bellvitge, Barcelona, Spain

This study assesses the individual contributions of the nonalloreactive factor, cold ischemia (CI), and alloreactivity to late functional and structural renal graft changes, and examines the effect of the association of both factors on the progression of chronic allograft nephropathy. Lewis rats acted as receptors of kidneys from either Lewis or Fischer rats. For CI, kidneys were preserved for 5 hours. The rats were divided into four groups: Syn, syngeneic graft; SynI, syngeneic graft and CI; Allo, allogeneic graft; AlloI, allogeneic graft and CI. Renal function was assessed every 4 weeks for 24 weeks. Grafts were evaluated for acute inflammatory response at 1 week and for chronic histological damage at 24 weeks. Only when CI and allogenicity were combined did immediate posttransplant mortality occur, while survivors showed accelerated renal insufficiency that induced further mortality at 12 weeks after transplant. Solely ischemic rats developed renal insufficiency. Renal structural damage in ischemic rats was clearly tubulointerstitial, while significant vasculopathy and glomerulosclerosis appeared only in the allogeneic groups. There was increased infiltration of macrophages and expression of mRNA-transforming growth factor-ß1 in the ischemic groups, irrespective of the allogeneic background. The joint association of CI plus allogenicity significantly increased cellular infiltration at both early and late stages, aggravating tubulointerstitial and vascular damage considerably. In summary, CI is mainly responsible for tubulointerstitial damage, whereas allogenicity leads to vascular lesion. The association of both factors accelerates and aggravates the progression of experimental chronic allograft nephropathy.

This article has been cited by other articles:

				A. Nakao, G. Faleo, M. A. Nalesnik, J. Seda-Neto, J. Kohmoto, and N. Murase Low-dose carbon monoxide inhibits progressive chronic allograft nephropathy and restores renal allograft function Am J Physiol Renal Physiol, July 1, 2009; 297(1): F19 - F26. [Abstract] [Full Text] [PDF]

				H. Wu, M. L. Craft, P. Wang, K. R. Wyburn, G. Chen, J. Ma, B. Hambly, and S. J. Chadban IL-18 Contributes to Renal Damage after Ischemia-Reperfusion J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2331 - 2341. [Abstract] [Full Text] [PDF]

				N. Lloberas, J. Torras, G. Alperovich, J. M. Cruzado, P. Gimenez-Bonafe, I. Herrero-Fresneda, M.{m. d.}l. Franquesa, I. Rama, and J. M. Grinyo Different renal toxicity profiles in the association of cyclosporine and tacrolimus with sirolimus in rats Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3111 - 3119. [Abstract] [Full Text] [PDF]

				N. Lloberas, J. M. Cruzado, M. Franquesa, I. Herrero-Fresneda, J. Torras, G. Alperovich, I. Rama, A. Vidal, and J. M. Grinyo Mammalian Target of Rapamycin Pathway Blockade Slows Progression of Diabetic Kidney Disease in Rats J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1395 - 1404. [Abstract] [Full Text] [PDF]

				H. Patel, R. A.G. Smith, S. H. Sacks, and W. Zhou Therapeutic Strategy with a Membrane-Localizing Complement Regulator to Increase the Number of Usable Donor Organs after Prolonged Cold Storage J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1102 - 1111. [Abstract] [Full Text] [PDF]

				J. M. Cruzado, N. Lloberas, J. Torras, M. Riera, C. Fillat, I. Herrero-Fresneda, J. M. Aran, G. Alperovich, A. Vidal, and J. M. Grinyo Regression of Advanced Diabetic Nephropathy by Hepatocyte Growth Factor Gene Therapy in Rats Diabetes, April 1, 2004; 53(4): 1119 - 1127. [Abstract] [Full Text] [PDF]

				C. Ponticelli, J. Torras, I. Herrero-Fresneda, J. M. Grinyo, M. Pietrzyk, U. Hoffmann, B. K. Kramer, B. J. Nankivell, and J. R. Chapman Chronic Allograft Nephropathy N. Engl. J. Med., March 18, 2004; 350(12): 1254 - 1256. [Full Text] [PDF]

				P. A. Marsden Predicting Outcomes after Renal Transplantation -- New Tools and Old Tools N. Engl. J. Med., July 10, 2003; 349(2): 182 - 184. [Full Text] [PDF]