Chronic Allograft Nephropathy

Chronic allograft nephropathy is characterized by slowly progressive graft dysfunction ultimately leading to chronic renal failure. Many patients may develop nephrotic-range proteinuria. Histopathological examination shows varying combinations of lesions, chronic transplant glomerulopathy (cg), ischaemic glomerulopathy, interstitial fibrosis (ci), tubular atrophy (ct), arteriosclerosis (cv) and arteriolar hyalinosis (ah). Splitting and multilayering of the intertubular capillary basement membranes has also been described. These lesions are illustrated in the accompanying figures, and can be quantified by numerical codes formulated at The Third Banff Conference on Allograft Pathology.

The pathogenesis of chronic allograft nephropathy is believed to be a multi-factorial process. Recurrent episodes of acute tubular-interstitial rejection can explain the interstitial fibrosis and tubular atrophy observed in some cases. Cytokines released during episodes of rejection, including interleukin 1, fibroblast growth factor and platelet derived growth factor likely play a role in promoting the fibroblast and smooth muscle proliferation seen in allograft vessels. In cases with prior documented intimal arteritis, vessel thickening can be explained as a direct result of immunologic vascular injury. Graft atherosclerosis leads to ischaemic glomerulopathy. Once glomerulosclerosis occurs, the remaining glomeruli undergo compensatory hypertrophy, increased glomerular capillary hydraulic pressure, and increased glomerular filtration. These hemodynamic forces damage the glomerular capillary endothelium, cause mesangial expansion, and accentuate the evolution of chronic transplant glomerulopathy. In support of this hypothesis it has been shown experimentally that if the increase in glomerular filtration rate is prevented by putting animals on a severely protein restricted diet, the rate of progression of glomerular sclerosis in allograft kidneys is retarded. Arteriolosclerosis and interstitial fibrosis in the allograft may also occur as a result of hypertension, recurrent pyelonephritis and chronic cyclosporine or FK506 toxicity. The relative contribution of these various processes to the ultimate demise of any given allograft may be difficult to determine by pathological evaluation alone. The aetiologically non-committal term "chronic allograft nephropathy" has in fact been coined to accommodate this difficulty.

References

1. Solez K, Benediktsson H, Cavallo T, et al. Report of The Third Banff Conference on Allograft Pathology (July 20-24, 1995) on classification and lesion scoring in renal allograft pathology. Transplant Proc, 1996; 28(1): 441-444.
2. Croker BP, Salomon DR. Pathology of the renal allograft. In: Tisher ED, Tisher CC, Brenner BM eds. Renal Pathology with Clinical Functional Correlations. Philadelphia: JB Lippincott Co., 1989, pp. 1518-1554.
3. Maryniak RK, First MR, Weiss MA. Transplant glomerulopathy: evolution of morphologically distinct changes. Kidney Int, 1985; 27(5): 799-806.
4. Kasiske BL, Kalil RSN, Lee HS, Rao KV. Histopathologic findings associated with a chronic progressive decline in renal allograft function. Kidney Int, 1991; 40(3):514-524.
5. Isoniemi HM, Krogerus L, von Willebrand E, et al. Histopathological findings in well-functioning, long-term renal allografts. Kidney Int, 1992; 41(1):155-160.
6. Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. Mod Pathol, 1992;5(2):125-130.

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