Combined and simultaneous use of Nefecon and irbesartan in treatment-naïve primary IgA nephropathy: A retrospective study

Nefecon is a targeted-release formulation of the corticosteroid budesonide. It is specifically engineered to selectively target the ileal gut-associated lymphoid tissue to reduce galactose-deficient IgA1 (Gd-IgA1) production and IgA immune complex formation. Irbesartan is an angiotensin II receptor blocker that is widely used to reduce proteinuria in chronic kidney disease. The study aimed to investigate the effects of the concomitant administration of both drugs in treatment-naïve patients with primary IgA nephropathy (IgAN). We conducted a retrospective study of 12 patients with primary IgAN at a single institution who received a 6-month combination therapy with Nefecon and irbesartan. Irbesartan was administered at a fixed dose of 150 mg/day, and Nefecon was given at a dosage of 16 mg/day. Treatment effectiveness was assessed by evaluating the alterations in 24-hour urinary protein and estimated glomerular filtration rate (eGFR). We measured the levels of Gd-IgA1 and analyzed the correlations between Gd-IgA1 and clinical outcomes. Linear mixed models assessed urinary protein, albumin, creatinine, and eGFR over time. Estimated mean urinary protein reductions from baseline were -28.28% (1 month), -32.78% (3 months), and -51.46% (6 months) (P < .001). eGFR was stable at 1 month (+4.08 mL/min/1.73 m2) but rose significantly at 3 months (+10.40) and 6 months (+8.80) (P = .009). Gd-IgA1 levels before and 1 month after treatment were 15.81 ± 1.43 and 15.16 ± 1.71 U/mL. Changes in Gd-IgA1 at 1 month correlated with changes in urinary protein (r = 0.664, P = .018). Urinary dysmorphic red blood cells decreased from 108.5 (37.5, 308.8) to 14 (6, 74.2) cells/μL at 6 months (P = .012). In treatment-naïve patients with primary IgAN, combined use of Nefecon and irbesartan was associated with reduced proteinuria and stable kidney function. However, given the single-arm design, these changes cannot be attributed to the combination itself and may reflect the effects of either agent alone, natural fluctuation of proteinuria, or regression to the mean. Although early changes in Gd-IgA1 correlated with reduced proteinuria, this exploratory finding requires confirmation. In addition, subgroup findings - such as the sex-based difference in proteinuria reduction - are exploratory and hypothesis-generating. These retrospective observational findings require confirmation in adequately powered controlled studies.