# Histopathological analysis of the skin of renal transplant recipients submitted to three different immunosuppression regimens

## TL;DR

This study compares skin changes in kidney transplant patients using different immunosuppressive drugs, finding that mTOR inhibitors cause significant epidermal thinning.

## Contribution

The study identifies specific histopathological effects of mTOR inhibitors on skin in renal transplant recipients.

## Key findings

- Patients on mTOR inhibitors showed significant epidermal thinning in both sun-exposed and protected skin.
- Only the mTOR inhibitor group showed interruption of epidermal proliferation.
- The study highlights potential links between immunosuppressive regimens and skin cancer risk.

## Abstract

Renal transplant recipients (RTRs) use a combination of immunosuppressive agents: a corticosteroid; a calcineurin inhibitor (cyclosporine or tacrolimus) and an antimetabolic agent (azathioprine [AZA] or a mycophenolic acid precursor [MPA] ‒ Mycophenolate mofetil or sodium) or an mTOR inhibitor (mTORi) ‒ sirolimus or everolimus. These treatments increase the incidence of various neoplasms, especially non-melanoma skin cancers (NMSCs).

To evaluate the histopathological alterations in the skin of the RTRs under three different immunosuppressive regimens: one mTORi (sirolimus or everolimus); or one antimetabolic agent (MPA or AZA), comparing them by groups and with healthy controls.

This was a cross-sectional comparative study of 30 patients selected from the Renal Transplant Service and divided into three groups: mTORi (n = 10), MPA (n = 10), and AZA (n = 10). The control group consisted of 10 immunocompetent non-transplanted volunteers. All RTRs were using tacrolimus and prednisone. Each participant underwent two biopsies of intact skin: one in a sun-protected and another in a sun-exposed area. The specimens were analyzed without previous information on which group they belonged to.

The most significant histopathological change was thinning of the epidermis in the mTORi group, both in photoexposed and photoprotected skin.

The study was conducted on a limited number of patients, which may influence the representativeness of the results.

Only RTRs treated with mTORi presented interruption of epidermal proliferation. These findings help to understand the influence of these different types of immunosuppressive regimens and their subsequent potential effects on carcinogenesis.