New treatment for IgA nephropathy: enteric budesonide targeted to the ileocecal region ameliorates proteinuria

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2011-10, Vol.26 (10), p.3237-3242
• Main Authors: KLOSTER SMERUD, Hilde, BARANY, Peter, LINDSTRÖM, Karin, FERNSTRÖM, Anders, SANDELL, Anna, PAHLSSON, Peter, FELLSTRÖM, Bengt
• Format: Article
• Language: English
• Subjects: Adult; Aged; Albuminuria - prevention & control; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-Inflammatory Agents - therapeutic use; Biological and medical sciences; budesonide; Budesonide - therapeutic use; clinical trial; corticosteroid; Emergency and intensive care: renal failure. Dialysis management; Female; Follow-Up Studies; Glomerular Filtration Rate; Glomerulonephritis; Glomerulonephritis, IGA - drug therapy; Humans; IgA nephropathy; Ileocecal Valve; Intensive care medicine; Kidney Function Tests; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Pilot Projects; Prognosis; prospective; Tablets, Enteric-Coated; Young Adult
• ISSN: 0931-0509; 1460-2385; 1460-2385
• DOI: 10.1093/ndt/gfr052

Systemic corticosteroid treatment has been shown to exert some protection against renal deterioration in IgA nephropathy (IgAN) but is not commonly recommended for long-term use due to the well-known systemic side effects. In this study, we investigated the efficacy and safety of a new enteric formulation of the locally acting glucocorticoid budesonide (Nefecon®), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria. Budesonide 8 mg/day was given to 16 patients with IgAN for 6 months, followed by a 3-month follow-up period. The efficacy was measured as change in 24-h urine albumin excretion, serum creatinine and estimated glomerular filtration rate (eGFR). The median relative reduction in urinary albumin excretion was 23% during the treatment period (interquartile range: -0.36 to -0.04, P = 0.04) with pretreatment values ranging from 0.3 to 6 g/24 h (median: 1.5 g/24 h). The median reduction in urine albumin peaked at 40% (interquartile range: -0.58 to -0.15) 2 months after treatment discontinuation. Serum creatinine was reduced by 6% (interquartile range: -0.12 to -0.02; P = 0.003), and eGFR [Modification of Diet in Renal Disease (MDRD)] increased ∼8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed. In the present pilot study, enteric budesonide targeted to the ileocecal region had a significant effect on urine albumin excretion, accompanied by a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation, while eGFR calculated from Cockcroft-Gault equation and cystatin C was not changed. Enteric budesonide may represent a new treatment of IgAN warranting further investigation.