Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?

Abstract

SummaryIgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (DGFR < 1Á5 ml/min/year) or mild (DGFR 1Á5-5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (DGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high-dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (DGFR). Mycophenolic acid provided further maintenance in non-randomized trials. Differentiated, precise, larger, randomized, placebo-controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN.

Corticosteroid therapy in IgA nephropathy with minimal proteinuria and high renal pathological score: A single‑center cohort study

“…The circulating immune complexes are mainly composed of Gd-IgA1 and IgG anti-Gd-IgA1 antibodies (19). Microscopic hematuria and proteinuria are the most common presentations of IgAN (20). Renal biopsy is considered to be the gold standard for the diagnosis of IgAN.…”

Integrated analysis of B‑cell and T‑cell receptors by high‑throughput sequencing reveals conserved repertoires in IgA nephropathy

“…IgAN is widely defined as a human autoimmune disease, and certain studies have indicated that a cytokine-mediated switch of naive B cells to antibody-secreting cells or Toll-like receptor ligation pathways in T-cells may be important in the pathogenesis of IgAN ( 6 , 24 ). In the clinical setting, certain classical immunosuppressive drugs that exhibit pleiotropic effects, including cyclophosphamide and azathioprine, have been used for the treatment of IgAN ( 25 , 26 ). With the development of next-generation sequencing, it is possible to analyze the human immune repertoires in different physiological and pathological conditions with a high depth, which was not achievable previously ( 27 , 28 ).…”

Using Routine Laboratory Markers and Immunological Indicators for Predicting Pneumocystis jiroveci Pneumonia in Immunocompromised Patients

“…For individuals without HIV infection, immunosuppressive therapies are the main cause of low immunity and the subsequent PJP occurs ( 5 , 6 ). Previous studies have reported that patients with autoimmune diseases and organ transplantation are the main users of immunosuppressive agents, and these patients are at high risk of PJP due to the status of treatment-related immunosuppression ( 7 – 9 ).…”