Second and Third Generational Advances in Therapies of the Immune-Mediated Kidney Diseases in Children and Adolescents

Abstract

Therapy of immune-mediated kidney diseases has evolved during recent decades from the non-specific use of corticosteroids and antiproliferative agents (like cyclophosphamide or azathioprine), towards the use of more specific drugs with measurable pharmacokinetics, like calcineurin inhibitors (cyclosporine A and tacrolimus) and mycophenolate mofetil, to the treatment with biologic drugs targeting detailed specific receptors, like rituximab, eculizumab or abatacept. Moreover, the data coming from a molecular science revealed that several drugs, which have been previously used exclusively to modify the upregulated adaptive immune system, may also exert a local effect on the kidney microstructure and ameliorate the functional instability of podocytes, reducing the leak of protein into the urinary space. The innate immune system also became a target of new therapies, as its specific role in different kidney diseases has been de novo defined. Current therapy of several immune kidney diseases may now be personalized, based on the detailed diagnostic procedures, including molecular tests. However, in most cases there is still a space for standard therapies based on variable protocols including usage of steroids with the steroid-sparing agents. They are used as a first-line treatment, while modern biologic agents are selected as further steps in cases of lack of the efficacy or toxicity of the basic therapies. In several clinical settings, the biologic drugs are effective as the add-on therapy.

Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy

“…It has been observed that oral glucocorticoid therapy in children with nephrotic syndrome may encounter issues of resistance, with approximately 50% of affected children eventually progressing to end-stage kidney disease if unresponsive after five years of treatment ( 149 ). Consequently, the implementation of specific immunosuppressive therapies, including drugs such as cyclophosphamide, has become necessary ( 150 ). The combination of alkylating agents with steroids has demonstrated high efficacy in managing high-risk podocyte-associated proteinuric kidney diseases such as MN ( 151 ).…”