BACKGROUND

The relative impact on renal allograft outcome of specific histological diseases (e.g. acute T-cell mediated rejection [TCMR], acute and chronic antibody-mediated rejection [aABMR and cABMR], polyomavirus nephropathy [PVAN], de novo/recurrent glomerular pathology [GN]) vs. non-specific histological injury, remains unclear.

METHODS

We followed all 1197 renal allograft recipients transplanted at a single center between 1991 and 2001. During follow-up (mean 14.5±2.80 years post-transplant), 1365 post-transplant renal allograft indication biopsies were performed in 738 recipients. All biopsies were rescored according to the current Banff classification. Risk models for graft loss were calculated using multivariate Cox proportional hazards analysis.

RESULTS

During follow-up, 664 grafts were lost: 351 due to recipient death with a functioning graft and 313 due to loss of graft function. In multivariate Cox proportional hazards analysis, the presence of a specific disease significantly predicted loss of graft function (HR for aABMR 3.00 [1.70-5.30], p=0.0001; for borderline changes 1.74 [1.02-2.97], p=0.04; for TCMR 3.41 [2.14-5.43], p<0.0001; for cABMR 2.01 [1.27-3.20], p=0.003; for PVAN 3.17 [1.34-7.51], p=0.009; and for GN 1.92 [1.12-3.29], p=0.02). These specific diseases were present in the large majority of kidneys that ultimately lost function (69% of graft losses). In 31% of patients, grafts were lost without specific disease process prior to graft loss. Chronic histological injury (interstitial fibrosis/tubular atrophy [IF/TA] and glomerulosclerosis) and interstitial inflammation (after the first post-transplant year) accounted for these losses. Importantly, these non-specific lesions were highly significant and independent risk factors for graft loss (HR 2.33, p<0.0001 for IF/TA; HR 3.40, p<0.0001 for interstitial inflammation) in all biopsies, including biopsies with a specific disease. In the absence of scarring, the outcome of specific diseases was good on long term, while extensive scarring portended a bad prognosis on short term.

CONCLUSION

The current study demonstrates that renal allograft loss is multifactorial, and most often secondary to a combination of specific disease processes and non-specific injury. Non-specific chronic histological damage and non-specific inflammation should be taken into account in prognostication of graft outcome, and likely also in treatment algorithms, irrespective of whether a specific disease is present or not.

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