Allograft necrosis

Allograft necrosis is a rare and extremely severe complication. It results from defective distal perfusion occurring immediately after graft implantation (primary non-function) or as a consequence of severe acute tubular necrosis (ATN) or acute rejection. It is most often limited to the cortex (cortical necrosis) or extends into the medulla (total necrosis). 

Eason, ID., S.L. Wee,T. Kawai, H.Z. Hong, I Powelson, M. Widmer, and A.B. Cosimi, Recombinant human dimeric tumor necrosis factor receptor (TNFR Fc) as an immunosuppressive agent in renal allograft recipients. Transplant Proc, 1995. 27(1) 554. 

R. L. (1990). Tumor necrosis factor, macrophage colony-stimulating factor, and interleukin-1 production within sponge matrix allografts. Transplantation 50, 460-466. 

In a 23-year-old woman, a kidney allograft recipient with recurrent lymphoceles treated with povidone-iodine irrigations (50 ml of a 1% solution bd for 6 days), a metabolic acidosis occurred and renal function deteriorated. After a few days, despite suspension of irrigation, the patient developed oliguria, and dialysis was needed. A renal biopsy showed acute tubular necrosis. 

Cyclosporine is a macrolide antibiotic and has been used as an immunosuppressive agent. Cyclosporine can cause both renal and nonrenal toxicity. Clinically renal toxicity consists of four discrete syndromes which include acute reversible renal functional impairment, delayed renal allograft function, acute vasculopathy, and chronic nephropathy with interstitial fibrosis. Proximal tubular epithelium is uniquely sensitive to the toxic effect. The toxic effect is characterized by isometric cytoplasmic vacuolations (several small equally sized vacuoles in cytoplasm), necrosis with or without subsequent mineralization, inclusion bodies (giant mitochondria), and giant lysosomes. Acute vasculopathy consists of vacuolization of the arteriolar smooth muscles and endothelial cells leading to necrosis. In some cases, thrombotic microangiopathy develops, characterized by thrombosis of the renal micro vasculature. Long-term treatment with cyclosporine results in chronic nephropathy with interstitial fibrosis (Chamey et al., 2004). 

Acute ciclosporin-induced nephrotoxicity, causing reduced renal function, develops within the first month, and includes a dose-related rise in serum creatinine concentrations and hyperkalemia. Fatal acute tubular necrosis has also been noted after very high intravenous doses (SEDA-19, 345). Although it is clinically often difficult to differentiate from acute allograft rejection in renal transplant patients, the alteration in renal function promptly resolves on ciclosporin withdrawal or dosage reduction, and initial acute renal insufficiency is not clearly associated with the development of subsequent chronic renal dysfunction (93). Several conditions, such as pre-existing hypovolemia, concomitant diuretic treatment, or renal artery stenosis, are susceptibility factors. 

Debets JM, Leunissen KM, van Hooff HJ, van der Linden CJ, Buurman WA. Evidence of involvement of tumor necrosis factor in adverse reactions during treatment of kidney allograft rejection with antithymocyte globulin. Transplantation 1989 47(3) 487-92. 

Schwartz LM, Smith SW, Jones MEE, Osborne BA (1993) Do all programmed cell deaths occur via apoptosis Proc Nati Acad Sci USA 90 980-984 Searle J, Kerr JFR, Bishop CJ (1982) Necrosis and apoptosis distinct modes of cell death with fiindeunentally different significance. Pathol Ann 17 229-259 Searle J, Harmon BV, Bishop CJ, Kerr JFR (1987) The significance of cell death by apoptosis in hepatobiliary disease. J Gastroenterol Hepatol 2 77-96 Searle JW, Balderson G (1996) Apoptosis as a mechanism of cell death in liver allograft rejection. Transplantation 61 168-169... 

C24. Chollet Martin, S., Depoix, J. P., Hvass, U., Pansard, Y., Vissuzaine, C., and Gougerot Pocidalo, M. A. Raised plasma levels of tumor necrosis factor in heart allograft rejection. Transplant. Proc. 22, 283-286 (1990). 

Imagawa, D. K., Millis, J. M., Olthoff, K. M., Derus, L. J., Chia, D., Sugich, L. R., Ozawa, M., Dempsey, R. A., Iwaki, Y., Levy, P. J., Terasaki, P. I., and Busuttil, R. W. The role of tumor necrosis factor in allograft rejection. I. Evidence that elevated levels of tumor necrosis factor-alpha predict rejection following orthotopic liver transplantation. Transplantation SO, 219-225... 

M14. Maury, C. P., and Teppo, A. M. Raised serum levels of cachectin/tumour necrosis factor alpha in renal allograft rejection. J. Exp. Med. 166, 1132-1137 (1987). 

Noronha, I. L., Daniel, V., Rambausek, M., Waldherr, R., and Opelz, G. Soluble interleukin-2 receptor (sIL-2R) and tumor necrosis factor plasma levels in renal allograft recipients. Transplant. Proc. 22, 1859-1860 (1990). 

Perkins, J. D., Munn, S. R., Barr, D., Ferguson, D. C., and Carpenter, H. A. Evidence that the soluble interleukin-2 receptor level may determine the optimal time for cystoscopically-di-rected biopsy in pancreaticoduodenal allograft recipients. Transplantation 49,363-366 (1990). Pessara, U., and Koch, N. Tumor necrosis factor alpha regulates expression of the major histocompatibility complex class 11-associated invariant chain by binding of an NF-kappa B-like factor to a promoter element. Mol. Cell Biol. 10, 4146-4154 (1990). 

DeMeester SR, Rolfe MW, Kunkel SL, et al. The bimodal expression of tumor necrosis factor-alpha in association with rat lung reimplantation and allograft rejection. J Immunol 1993 150 2494-2505. 

Rolfe MW, Kunkel S, Lincoln P, Deeb M, Lupinetti F, Stricter R. Lung allograft rejection role of tumor necrosis factor-alpha and interleukin-6. Chest 1993 103 ... 

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