The safety of isotretinoin in patients with lupus nephritis: a comprehensive review.

Oral isotretinoin (13-cis-retinoinc acid) is a derivative of vitamin A and belongs to the first generation of retinoids, which act as synthetic isomers of retinoic acid (RA). It is a very effective agent in a treatment of acne vulgaris; however, multiple side effects related to therapy with retinoids preclude the use of isotretinoin in less severe acne vulgaris. A significant limitation for the administration of isotretinoin appears in case of concomitant kidney disease with a special attention regarding the safety of the agent in patients with lupus nephritis (LN). The aim of this review is an assessment of the safety of isotretinoin for the treatment of acne vulgaris in patients with LN. We searched both MEDLINE and SCOPUS databases, as well as several dermatological textbooks, to present all limitations and benefits of therapy with isotretinoin or its isomer (ATRA) for patients with kidney diseases. Several mouse models of SLE revealed a significant modulatory influence of retinoids on autoimmune injury of the glomerular unit. Retinoids were demonstrated to affect mononuclear cell infiltrations of renal tissue allowing for a reduction in the overall glomerular damage. Presumptively, they can affect a synthesis of autoantibodies significantly limiting their deposition in the glomerular unit. Moreover, retinoids were also shown to affect the synthesis of different cytokines specific both for lymphocytes Th1 (IL-2, IL-12, INFγ) ant Th2 (IL-4, IL-10). The influence of retinoids on the course of LN seems to be more multidimensional than only restricted to immune aspects and these synthetic RA isomers manifest also antiproteinuric activity in comparable extent to steroidal agents. The agents were demonstrated to counteract a loss of podocytes after the injury of the glomerular unit. They can promote a differentiation of renal progenitor cells (RPCs) within the Bowman capsule into mature podocytes leading to regeneration of podocyte number. Additionally, retinoids can probably protect podocytes from injury limiting their apoptosis, as well as reducing foot process effacement. Although, an endogenous production of RA isomers increases after the injury of the glomerular unit aiming to the restoration of podocyte number, it can be significantly impaired by a loss of albumins into urine. RA isomers are progressively sequestered by albumin within the Bowman's space and therefore, they are quickly eliminated with urine. It was demonstrated that the administration of exogenous RA isomers (retinoids) can bypass the activity of albumins enhancing the regeneration of podocytes. Finally, retinoids can regulate the production of vasoactive substances influencing on different vascular functions in the kidney. They can beneficially change a balance of angiotensin metabolites through by down-regulation of angiotensin-converting enzyme type 1 and the enhancement of an expression of angiotensin-converting enzyme type 2. Another studies revealed that retinoids could also alter the activity of renal endothelin pathway; however, the significance of this effect requires further elucidation. Taken all these presented effects of retinoids in the kidney into consideration, we can conclude that isotretinoin can be the safe treatment option of acne vulgaris in patients with LN.