Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
IgA Nephropathy – Mucosal Immunity and Treatment Options
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
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 [en]
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: urn:nbn:se:uu:diva-168631ISBN: 978-91-554-8286-2 (print)OAI: oai:DiVA.org:uu-168631DiVA: diva2:501020
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
List of papers
1. Gluten sensitivity in patients with IgA nephropathy
Open this publication in new window or tab >>Gluten sensitivity in patients with IgA nephropathy
Show others...
2009 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 24, no 8, 2476-2481 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Coeliac disease is more frequent in IgA nephropathy (IgAN) patients compared to the healthy population. Several hypotheses postulate that food antigens like gluten may be involved in the onset of IgAN. METHODS: In this study, we used a recently developed mucosal patch technique to evaluate the rectal mucosal inflammatory reaction to gluten in patients with IgAN (n = 27) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analysed for IgA and IgG antigliadin antibodies (AGA), IgA antibodies against tissue transglutaminase and IgA endomysium antibodies. RESULTS: Gluten reactivity, defined as increase in MPO and/or NO after gluten exposure, was observed in 8 of 27 IgAN patients. The prevalence of HLA-DQ2 and DQ8 was not increased among gluten-sensitive patients, and the total prevalence among IgAN patients was the same as for the normal population. An elevated serum IgA AGA response was seen in 9 of 27 IgAN patients. The increase in IgA AGA did not correlate with the gluten sensitivity as measured by NO and/or MPO. A specific serum IgG AGA response was seen in one patient only. Antibodies against tissue transglutaminase and endomysium were not observed. CONCLUSION: It is concluded that approximately one-third of our IgAN patients have a rectal mucosal sensitivity to gluten, but without signs of coeliac disease, and we hypothesize that such sub-clinical inflammation to gluten might be involved in the pathogenesis of IgAN in a subgroup of patients.

Keyword
food antigens, gluten sensitivity, IgA nephropathy, myeloperoxidase, nitric oxide
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-123172 (URN)10.1093/ndt/gfp133 (DOI)000268115400031 ()19332868 (PubMedID)
Available from: 2010-04-26 Created: 2010-04-26 Last updated: 2017-12-12Bibliographically approved
2. Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy
Open this publication in new window or tab >>Gastrointestinal sensitivity to soy and milk proteins in patients with IgA nephropathy
Show others...
2010 (English)In: Clinical Nephrology, ISSN 0301-0430, Vol. 74, no 5, 364-371 p.Article in journal (Refereed) Published
Abstract [en]

Background Sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN) Methods In this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18) The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (M PO) and eosinophil cationic protein (ECP) were measured Serum samples were analyzed for IgA and IgG antibodies to a-lactalbumin, P-lactoglobulin, casein and soy Results 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins The levels of IgG antibodies to a-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar No differences were seen in serum levels of IgA or IgG antibodies to soy Conclusion It is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients

Keyword
IgA nephropathy, food antigens, milk sensitivity, soy sensitivity, nitrogen oxide
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-140051 (URN)000285040100007 ()20979945 (PubMedID)
Available from: 2011-01-03 Created: 2011-01-03 Last updated: 2017-12-11Bibliographically approved
3. New Treatment of IgA nephropathy: Enteric Budesonide Targeted to the Ileocaecal Region Ameliorates Proteinuria
Open this publication in new window or tab >>New Treatment of IgA nephropathy: Enteric Budesonide Targeted to the Ileocaecal Region Ameliorates Proteinuria
Show others...
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.

Keyword
budesonide, clinical trial, corticosteroid, IgA nephropathy, prospective
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-124580 (URN)10.1093/ndt/gfr052 (DOI)000296349200030 ()
Available from: 2010-05-05 Created: 2010-05-05 Last updated: 2017-12-12Bibliographically approved
4. Effect of Statins on Recurrence of IgA Nephropathy and Graft Loss in Renal Transplant Recipients
Open this publication in new window or tab >>Effect of Statins on Recurrence of IgA Nephropathy and Graft Loss in Renal Transplant Recipients
Show others...
(English)Manuscript (preprint) (Other academic)
Keyword
IgA nephropathy, pharmacological treatment, recurrence, statin, transplantation
National Category
Clinical Medicine Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-168629 (URN)
Available from: 2012-02-13 Created: 2012-02-13 Last updated: 2015-06-15

Open Access in DiVA

fulltext(6133 kB)1726 downloads
File information
File name FULLTEXT01.pdfFile size 6133 kBChecksum SHA-512
b7161650735301ebd6cde3d283fe97f5658f12710cd318c8224ac96efefb2392f933a0d0602ef2bfacfb7db7826194fabea80295c01d72c05437286382fc4df5
Type fulltextMimetype application/pdf
Buy this publication >>

Search in DiVA

By author/editor
Smerud, Hilde Kloster
By organisation
Department of Medical Sciences
Clinical MedicineUrology and Nephrology

Search outside of DiVA

GoogleGoogle Scholar
Total: 1726 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 817 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf