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Immunoglobulin A nephropathy and ischemic heart disease: a nationwide population-based cohort study
Örebro University, School of Medical Sciences. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0001-8754-8463
Department of Nephrology, Danderyd Hospital, Stockholm, Sweden; Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden; The George Institute for Global Health, University of New South Wales, Sydney, Australia.
Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
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2021 (English)In: BMC Nephrology, E-ISSN 1471-2369, Vol. 22, no 1, article id 165Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chronic kidney disease has been linked to cardiovascular disease and specifically ischemic heart disease (IHD), but large-scale population data in patients with immunoglobulin A nephropathy (IgAN) are missing.

OBJECTIVE: To examine absolute and relative risks for IHD in patients with IgAN.

METHODS: Population-based register-based cohort study in Sweden. We identified 3945 patients with biopsy-verified IgAN, and 19,272 age- and sex-matched reference individuals from the general population. To reduce residual confounding from genetic factors and early environmental factors we carried out secondary analyses, where we compared 3039 IgAN patients with 6729 siblings, whereas a spousal analysis consisted of 2377 married couples where one of the spouses had IgAN. Data on IHD and end-stage renal disease (ESRD) were retrieved from the nationwide Patient Register. Cox regression estimated hazard ratios (HRs) adjusted for matching variables, education, country of birth, cancer, diabetes mellitus, and other systemic inflammatory diseases.

RESULTS: During a follow-up of 55,527 person-years (py; mean follow-up 14.1 years), 371 patients (9.4%) with IgAN developed IHD (6.7/1000 py), compared with 1070 (5.6%) in 287,677 py in reference individuals (3.7/1000 py). The corresponding adjusted HR was 1.86 (95%CI = 1.63-2.13), equivalent to one extra case of IHD per 34 IgAN patients followed-up for 10 years. HRs were similar in men and women with IgAN, but higher in the first year after diagnosis and in patients born outside the Nordic countries. Patients with IgAN were at increased risk of IHD also compared to siblings (HR = 2.07; 95%CI = 1.62-2-64) and spouses (HR = 1.91; 95%CI = 1.40-2.61).

CONCLUSIONS: In this nationwide population-based study, patients with IgAN were at an 86% increased risk of future IHD.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2021. Vol. 22, no 1, article id 165
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:oru:diva-91714DOI: 10.1186/s12882-021-02353-7ISI: 000656150100001PubMedID: 33952193Scopus ID: 2-s2.0-85105496628OAI: oai:DiVA.org:oru-91714DiVA, id: diva2:1553603
Funder
The Karolinska Institutet's Research FoundationAvailable from: 2021-05-10 Created: 2021-05-10 Last updated: 2024-07-04Bibliographically approved
In thesis
1. Immunoglobulin A nephropathy and disease complications: register-based studies
Open this publication in new window or tab >>Immunoglobulin A nephropathy and disease complications: register-based studies
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Immunoglobulin A nephropathy (IgAN) is the commonest primary glomerular disease worldwide. A kidney biopsy is required for the diagnosis. IgA immune-complex depositions sets off a cascade leading to renal scarring, proteinuria and hypertension. Peaking in young adults, IgAN contributes significantly to the burden of chronic kidney disease, which in turn may lead to cardiovascular disease and death. As IgAN peaks in childbearing age, its effect on pregnancy outcomes is of interest. 

All studies use the same cohort of 4126 patients with a biopsy diagnosis of IgAN, identified through the combination of computerized andmanual search in biopsy reports from all Swedish kidney pathology labs. In study I, a random subset of 127 patients from the biopsy cohort were selected for diagnosis validation by patient chart review. IgAN was confirmed or likely in 121 cases (positive predictive value > 95 %). Mean age at diagnosis was 39.6 years, 74 % were male. 

Study II compared mortality in IgAN patients and an individuallymatched reference population by survival analysis. IgAN was associated with an increase of 53 % in all-cause and 59 % in cardiovascular mortality, with an absolute excess death rate of in 310 person years. Mortality before end-stage renal disease was not significantly increased.

Study III used a similar design to examine incident fatal and non-fatal ischemic heart disease (IHD) in IgAN patients and the same reference populations. We found an 86 % increase in IHD hazard and an absolute excess IHD risk of one per 340 person-years. 

In study IV, outcomes of 327 pregnancies in 208 women with IgAN were compared to reference pregnancies without IgAN, indicating increased odds of preterm birth < 37 weeks gestation, but not for very preterm birth < 34 weeks. Preeclampsia odds were quadrupled. Stillbirth and neonatal death were both uncommon and not increased in IgAN.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2023. p. 90
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 275
Keywords
immunoglobulin A nephropathy, nephrology, validation studies, register studies, cohort studies, mortality, ischemic heart disease, pregnancy, preterm birth
National Category
General Practice Urology and Nephrology
Identifiers
urn:nbn:se:oru:diva-102261 (URN)9789175294834 (ISBN)
Public defence
2023-01-20, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:00 (English)
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Available from: 2022-11-17 Created: 2022-11-17 Last updated: 2023-01-26Bibliographically approved

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Jarrick, SimonLudvigsson, Jonas F.

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