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Mortality in IgA Nephropathy: 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 University Hospital, Stockholm, Sweden; Department of Clinical Sciences, Danderyd Hospital, Stockholm, Sweden.
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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2019 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 30, no 5, p. 866-876Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The clinical course of IgA nephropathy (IgAN) varies from asymptomatic nonprogressive to aggressive disease, with up to one in four patients manifesting ESRD within 20 years of diagnosis. Although some studies have suggested that mortality appears to be increased in IgAN, such studies lacked matched controls and did not report absolute risk.

METHODS: We conducted a population-based cohort study in Sweden, involving patients with biopsy-verified IgAN diagnosed in 1974-2011; main outcome measures were death and ESRD. Using data from three national registers, we linked 3622 patients with IgAN with 18,041 matched controls; we also conducted a sibling analysis using 2773 patients with IgAN with 6210 siblings and a spousal analysis that included 2234 pairs.

RESULTS: During a median follow-up of 13.6 years, 577 (1.1%) patients with IgAN died (10.67 per 1000 person-years) compared with 2066 deaths (0.7%) in the reference population during a median follow-up of 14.1 years (7.45 per 1000 person-years). This corresponded to a 1.53-fold increased risk and an absolute excess mortality of 3.23 per 1000 person-years (equaling one extra death per 310 person-years) and a 6-year reduction in median life expectancy. Similar increases in risk were seen in comparisons with siblings and spouses. IgAN was associated with one extra case of ESRD per 54 person-years. Mortality preceding ESRD was not significantly increased compared with controls, spouses, or siblings. Overall mortality did not differ significantly between patients with IgAN-associated ESRD and patients with ESRD from other causes.

CONCLUSIONS: Patients with IgAN have an increased mortality compared with matched controls, with one extra death per 310 person-years and a 6-year reduction in life expectancy.

Place, publisher, year, edition, pages
American Society of Nephrology , 2019. Vol. 30, no 5, p. 866-876
Keywords [en]
Epidemiology and outcomes, IgA nephropathy, end-stage renal disease, mortality risk
National Category
Gastroenterology and Hepatology Urology and Nephrology
Identifiers
URN: urn:nbn:se:oru:diva-74205DOI: 10.1681/ASN.2018101017ISI: 000467401000011PubMedID: 30971457Scopus ID: 2-s2.0-85065508250OAI: oai:DiVA.org:oru-74205DiVA, id: diva2:1315633
Note

Funding Agency:

Research Committee of Örebro County Council 

Available from: 2019-05-14 Created: 2019-05-14 Last updated: 2023-01-26Bibliographically 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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