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New Treatment of IgA nephropathy: Enteric Budesonide Targeted to the Ileocaecal Region Ameliorates Proteinuria
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Renal Medicine Research Group)
(Renal Medicine Research Group)
(Renal Medicine Research Group)
(Renal Medicine Research Group)
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2011 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 10, 3237-3242 p.Article in journal (Refereed) Published
Abstract [en]

Background. 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 (R)), designed to release the active compound in the ileocecal region. The primary objective was to evaluate the efficacy of targeted release budesonide on albuminuria.

Methods. 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).

Results. 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 similar to 8% (interquartile range: 0.02-0.16, P = 0.003) during treatment. No major corticosteroid-related side effects were observed.

Conclusions. 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.

Place, publisher, year, edition, pages
2011. Vol. 26, no 10, 3237-3242 p.
Keyword [en]
budesonide, clinical trial, corticosteroid, IgA nephropathy, prospective
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-124580DOI: 10.1093/ndt/gfr052ISI: 000296349200030OAI: oai:DiVA.org:uu-124580DiVA: diva2:317711
Available from: 2010-05-05 Created: 2010-05-05 Last updated: 2012-03-29Bibliographically approved
In thesis
1. IgA Nephropathy – Mucosal Immunity and Treatment Options
Open this publication in new window or tab >>IgA Nephropathy – Mucosal Immunity and Treatment Options
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the present studies we have explored the link between food hypersensitivity and IgA nephropathy (IgAN) and evaluated treatment options in primary and recurrent disease.

Approximately one third of our IgAN patients had a rectal mucosal sensitivity to gluten, as demonstrated by increased local mucosal nitric oxide production and/or myeloperoxidase release after gluten challenge. The gluten sensitivity seemed to be an innate immune reaction unrelated to the pathogenesis of celiac disease. Approximately half of the patients had a rectal mucosal sensitivity to soy or cow’s milk (CM). The levels of IgG antibodies to alfa-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, indicating that an adaptive immune response might be involved in addition to the innate immune reaction observed.

With the knowledge of gastrointestinal reactivity enteric treatment was considered as a potential new treatment approach of IgAN. A 6-month prospective trial demonstrated proof-of-concept for the use of enteric budesonide targeted to the ileocaecal region of IgAN patients. We observed a modest, but significant reduction in urine albumin, a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation. eGFR calculated from the Cockcroft-Gault formula and cystatin C was not changed.

In a retrospective study recurrence of IgAN and graft loss was evaluated in Norwegian and Swedish patients having received a primary renal transplant due to IgAN. Adjusting for relevant covariates, a multiple Cox-regression analysis on time to IgAN recurrence showed that use of statins was associated with reduced risk of recurrence and reduced risk of graft loss. The time lag from diagnosis to first transplantation and female gender were also associated with lower risk of recurrence. Improved graft survival was associated with related donor, low donor age and no or low number of acute rejection episodes.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 69 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 744
IgA nephropathy, mucosal immunity, gastrointestinal sensitivity, food allergens, pharmacological treatment, budesonide, statin, clinical trial, renal transplantation, recurrence
National Category
Clinical Medicine Urology and Nephrology
Research subject
Internal Medicine
urn:nbn:se:uu:diva-168631 (URN)978-91-554-8286-2 (ISBN)
Public defence
2012-04-13, Robergsalen, Akademiska sjukhuset, ing 40, Uppsala, 09:15 (English)
Available from: 2012-03-09 Created: 2012-02-13 Last updated: 2012-03-29Bibliographically approved

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