Mortality in IgA Nephropathy: A Nationwide Population-Based Cohort Study

Abstract

BackgroundThe 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.MethodsWe 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.ResultsDuring 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.ConclusionsPatients 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.

Mortality Risk in IgA Nephropathy

“…These deficiencies may have a bearing on the observation that excess mortality was limited to individuals with IgAN and ESRD, a somewhat paradoxical finding considering that large epidemiologic studies have shown that mortality risk increases as stage of "generic" CKD (as defined by Kidney Disease Improving Global Outcomes [KDIGO] criteria) increases, well before ESRD has developed. 6 A comparison with prior reports may provide some insight into some of the perplexing findings of the study by Jarrick et al 5 Knoop et al 4 conducted a nationwide, registry-based cohort study in Norway involving 663 subjects with biopsyproven IgAN followed for a median of 11.3 years. The subjects were an average age 39 years old, and 74% were men.…”

“…Factors that enhance the likelihood of progression and the risks of ESRD have been well studied, but the risks of mortality after long periods of follow-up are less well understood. 2 The gaps in our understanding of the pattern of mortality associated with a diagnosis of IgAN have been lessened by several large observational cohort studies (single center or registry based) with long-term follow-up, 3,4 including one published in this issue of the Journal of the American Society of Nephrology by Jarrick et al 5 Although each of these studies has varied somewhat in the design, they provide substantial support for the conclusion that a diagnosis of IgAN is associated with shortened life expectancy. Although in and of itself, this is not surprising, the details of these studies provide some interesting insights into the nature of this enhanced mortality risk in IgAN and raise several new questions-all hallmarks of excellent clinical research.…”

“…Jarrick et al 5 studied 3622 patients in Sweden with biopsyproven IgAN (including 227 with IgA vasculitis) with a median follow-up of 13.6 years. The average age at diagnosis was 34.9 years old, and 70% were men.…”

“…The comparisons were with the general population adjusted for age and sex, and therefore, a standardized mortality ratio (SMR) could be calculated. Unlike the study by Jarrick et al, 5 both clinical and histologic data were available to "risk stratify" patients at diagnosis. The overall SMR for patients with IgAN was 1.9, but the risk of mortality was strongly inversely related to eGFR at diagnosis.…”

A Personalized Update on IgA Nephropathy: A New Vision and New Future Challenges

“…It is a very common form of primary glomerulonephritis that affects about 200,000–350,000 people per year globally [3]. Its diagnosis is associated with a reduction in life expectancy between 6 and 10 years [4]. Its incidence has also been associated with poor socioeconomic situations [5].…”