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Effect of Statins on Recurrence of IgA Nephropathy and Graft Loss in Renal Transplant Recipients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Smerud Medical Research International AS.
Haukeland University Hospital.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
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(English)Manuscript (preprint) (Other academic)
Keyword [en]
IgA nephropathy, pharmacological treatment, recurrence, statin, transplantation
National Category
Clinical Medicine Urology and Nephrology
Identifiers
URN: urn:nbn:se:uu:diva-168629OAI: oai:DiVA.org:uu-168629DiVA: diva2:500875
Available from: 2012-02-13 Created: 2012-02-13 Last updated: 2015-06-15
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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 744
Keyword
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
Identifiers
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)
Opponent
Supervisors
Available from: 2012-03-09 Created: 2012-02-13 Last updated: 2012-03-29Bibliographically approved

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Lorant, TomasTufveson, Gunnar

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