CARD9, VAV3, and infection risk in IgA nephropathy

The risk of opportunistic infection reported from trials of systemic immunosuppression for IgA nephropathy (IgAN) is higher than the risk expected in a general rheumatology population. 1 Park J.W. Curtis J.R. Moon J. et al. Prophylactic effect of trimethoprim-sulfamethoxazole for pneumocystis pneumonia in patients with rheumatic diseases exposed to prolonged high-dose glucocorticoids. Ann Rheum Dis. 2018; 77: 644-649 Crossref PubMed Scopus (160) Google Scholar In Part A of the Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy (NefIgArd) trial, Barratt et al. report no increased risk of infection with the use of local gut-targeting corticosteroids that have minimal systemic absorption, while still achieving reductions in proteinuria similar to those seen with systemic therapy. 2 Barratt J. Lafayette R. Kristensen J. et al. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney Int. 2023; 103: 391-402 Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathyKidney InternationalVol. 103Issue 2PreviewThe therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965 ). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. Full-Text PDF Open AccessThe authors replyKidney InternationalVol. 103Issue 5PreviewWe read with interest the correspondence from Gleeson and colleagues discussing the potential genetic predisposition of patients with IgA nephropathy (IgAN) to opportunistic infections, especially during treatment with systemic glucocorticoids.1 A takeaway from these observations is that prior to treating IgAN patients with a systemic glucocorticoid, stratifying by genetic risk, to avoid serious complications, may be a good idea. One of the main motivations for developing Nefecon for IgAN treatment has been to provide a new tool for effective treatment that has far less toxicity than the immunomodulatory agents typically used, especially prednisone/prednisolone. Full-Text PDF