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

Abstract

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.

Keywords: Epidemiology and outcomes; IgA nephropathy; end-stage renal disease; mortality risk.

Figure 1.

Reduced patient and renal survival in IgAN patients compared to reference groups, visualized visualized through standardized Cox survival curves. Top left: patient survival of patients with IgAN compared with matched controls from the general population (TPR); P<0.001. Bottom left: patient survival of patients with IgAN compared with their siblings (Multi-Generation Register); P<0.001. Top right: patient survival of patients with IgAN compared with their spouses (the first person an IgAN patient was married to, according to the TPR); P<0.001. Bottom right: renal survival in patients with IgAN compared with matched controls (TPR); ESRD as outcome variable, death as a censoring event; P<0.001. Emigration and end of follow-up are censoring events in all analyses. Small figures indicate individuals at risk (instances of the outcome of interest within parentheses).

Figure 2.

Adjusted HRs for death and ESRD in patients with IgAN with subgroup stratification, showing increased mortality in IgAN compared to all reference groups, and increased ESRD compared to matched general population controls. First column: HRs for death of patients with IgAN compared with matched controls from the general population (TPR). Second column: HRs for death in of patients with IgAN compared with their siblings (Multi-Generation Register). Third column: HRs for death of patients with IgAN compared with their spouses (the first person an IgAN patient was married to, according to the TPR). Fourth column: HRs for ESRD in patients with IgAN compared with matched controls (TPR). Numbers represent absolute numbers of events in patients with IgAN. Whiskers represent 95% CIs. HSP, Henoch-Schönlein purpura.

Figure 3.

Mortality from cardiovascular disease and other causes was increased in IgAN patients compared with primary and secondary comparison groups, but mortality from cancer was only increased compared with siblings. Figures refer to number of deaths and adjusted HRs (diamonds) with 95% CIs (whiskers), with the respective comparison group in column heading. For definition of cardiovascular disease and cancer, please see Supplemental Table 4. Other cause is death from any cause other than cardiovascular disease or cancer.