International Journal of Nephrology and Renovascular Disease (Dec 2021)
Mechanism of Action and Efficacy of Immunosupressors in Lupus Nephritis
Abstract
Mario E Alamilla-Sanchez,1 Miguel A Alcala-Salgado,1 Cesar D Alonso-Bello,2 Gandhy T Fonseca-Gonzalez1 1Department of Nephrology, Centro Medico Nacional “ 20 de Noviembre”, Mexico City, Mexico; 2Department of Immunology, Centro Medico Nacional “ 20 de Noviembre”, Mexico City, MexicoCorrespondence: Mario E Alamilla-SanchezDepartment of Nephrology, Centro Medico Nacional “ 20 de Noviembre”, Mexico City, MexicoTel +52 5541334931Email [email protected]: Approximately 70% of the patients with systemic lupus erythematosus will have clinical evidence of kidney damage during their evolution. Patients with impaired renal function at onset and those with recurrent flares have a poor prognosis. Understanding the mechanism of action of immunosuppressants is essential for proper prescription. Steroids inhibit the DNA sequence that promotes the release of inflammatory cytokines. Phosphoramide mustard, metabolite of cyclophosphamide, cross-link with the DNA, causing the aggregation of an alkyl group, causing cell death. Mycophenolate inhibits inosine monophosphate dehydrogenase, prevents de novo synthesis of guanine, inducing cell arrest in S phase. Azathioprine blocks the synthesis of purines and induces apoptosis. Calcineurin inhibitors prevent the dephosphorylation of NFAT and reduce the production of interleukin 2. Antimalarials alter the enzymatic release of lysosomes by increasing intravesicular pH. The mechanism of action of rituximab is related to complement-dependent cytotoxicity and the elimination of anti-CD20-labeled B cells. Progress in the knowledge and management of low doses of steroids may change the current paradigm and reduce the frequency of related adverse events. Mycophenolate seems to be a better choice than cyclophosphamide for induction, it is also preferred over azathioprine as a maintenance immunosuppressive agent, although azathioprine is preferred in women with a desire for conception, those pregnant, or with low resources. For treatment-resistant cases, tacrolimus, rituximab or belimumab may be effective. Ongoing clinical trials with new drugs offer promising results.Keywords: systemic lupus erythematosus, lupus nephritis, mechanism of action, therapeutics, clinical pharmacology
