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Published on: November 8, 2015
Arteriosclerosis in zero-time biopsy is a risk factor for tacrolimus-induced chronic nephrotoxicity
Takafumi Yagisawa1, Kazuya Omoto1, Tomokazu Shimizu1
1Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
Aim:
Calcineurin inhibitors reduce the acute rejection rate and greatly improve renal allograft survival. However, they are associated with some adverse events, including nephrotoxicity, a risk factor for allograft failure. Chronic calcineurin inhibitor-induced nephrotoxicity causes irreversible damage to renal components, such as arteriolar hyaline thickening. The aim of this study is to investigate the risk factors for tacrolimus-induced chronic nephrotoxicity using zero-time biopsy specimens.
Methods:
Between January 2001 and December 2010, 483 patients who underwent living-related kidney transplantation and had also been placed on a tacrolimus-based regimen were enrolled in this study. There were 1859 specimens evaluated comprising 483 zero-time biopsy specimens and 1376 protocol and for-cause biopsy specimens. De novo arteriolar hyaline thickening due to tacrolimus-induced chronic nephrotoxicity was scored according to the Banff classification aah score. In this study, tacrolimus-induced nephrotoxicity was defined as a positive aah score.
Results:
Of the 483 patients, 108 patients (22.4%) had biopsy-proven tacrolimus-induced chronic nephrotoxicity. Multivariate analysis showed that interlobular arteriosclerosis proven by zero-time biopsy (OR: 2.23, 95%CI: 1.38-3.58, P < 0.01) and acute rejection episodes (OR: 1.58, 95%CI: 1.00-2.47, P = 0.04) were independent risk factors for tacrolimus-induced chronic nephrotoxicity. However, tacrolimus-induced chronic nephrotoxicity did not affect long-term graft survival.
Conclusion:
This is the first report showing that arteriosclerosis in zero-time biopsy specimens is a risk factor for histological tacrolimus-induced chronic nephrotoxicity.
Insights
Arteriosclerosis in early kidney transplant biopsies predicts tacrolimus-induced chronic nephrotoxicity. This finding helps identify patients at risk for this adverse event, even though it doesn't impact long-term graft survival.
Area of Science:
- Nephrology
- Transplantation Immunology
- Pathology
Background:
- Calcineurin inhibitors (CNIs) like tacrolimus are crucial for preventing kidney transplant rejection.
- However, CNIs can cause nephrotoxicity, a significant risk factor for graft failure.
- Chronic CNI-induced nephrotoxicity leads to irreversible kidney damage, including arteriolar hyaline thickening.
Purpose of the Study:
- To identify risk factors for tacrolimus-induced chronic nephrotoxicity.
- To investigate the predictive value of zero-time biopsy specimens for this condition.
Main Methods:
- Analysis of 483 living-related kidney transplant recipients on tacrolimus-based regimens.
- Evaluation of 483 zero-time biopsy specimens and 1376 follow-up biopsies.
- Scoring of de novo arteriolar hyaline thickening (aah score) using the Banff classification.
Main Results:
- 22.4% of patients developed biopsy-proven tacrolimus-induced chronic nephrotoxicity.
- Zero-time biopsy evidence of interlobular arteriosclerosis (OR: 2.23) and acute rejection episodes (OR: 1.58) were independent risk factors.
- Tacrolimus-induced chronic nephrotoxicity did not significantly affect long-term graft survival.
Conclusions:
- Zero-time biopsy arteriosclerosis is a significant risk factor for histological tacrolimus-induced chronic nephrotoxicity.
- This study is the first to establish this association.
- Early identification of arteriosclerosis may aid in managing CNI-related nephrotoxicity.
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