To Örebro University

Aims: The aims of this study were to validate the diagnosis of IgA nephropathy (IgAN) in Swedish biopsy registers against patient charts and to describe the clinical characteristics of patients with a biopsy indicating IgAN.

Methods: This is a population-based cohort study. Out of 4,069 individuals with a renal biopsy consistent with IgAN (biopsies performed in 1974-2011), this study reviewed patient charts of a random subset of 127 individuals. Clinical and biopsy characteristics at the time of biopsy were evaluated, and positive predictive values (PPV) were calculated with 95% confidence intervals (CI).

Results: Out of 127 individuals with a renal biopsy consistent with IgAN, 121 had a likely or confirmed clinical diagnosis of IgAN, primary or secondary to Henoch-Schonlein purpura, yielding a PPV of 95% (95% CI =92%-99%). The median age at biopsy was 39 years (range: 4-79 years); seven patients (6%) were <16 years. The male to female ratio was 2.8:1. The most common causes for consultation were macroscopic hematuria (n=37; 29%), screening (n=33; 26%), and purpura (n=14, 11%). In patients with available data, the median creatinine level was 104 mu mol/L (range 26-986 mu mol/L, n=110) and glomerular filtration rate 75 mL/min/1.73m(2) (range 5-173 mL/min/1.73m(2), n=114). Hypertension was noted in 59 (46%) individuals. IgA deposits were reported in 97% of the biopsy records (n= 123), mesangial hypercellularity in 76% (n= 96), C3 deposits in 89% (n=113), and C1q deposits in 12% (n=15). Conclusion: A histologic diagnosis of IgAN has a high PPV for a diagnosis of IgAN confirmed by review of patient charts.

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.

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.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) incidence peaks in childbearing age. Data on pregnancy outcomes in women with IgAN are limited.

METHODS: We performed a register-based cohort study in a nationwide cohort of women with biopsy-verified IgAN in Sweden, comparing 327 pregnancies in 208 women with biopsy-verified IgAN and 1060 pregnancies in a matched reference population of 622 women without IgAN, with secondary comparisons with sisters to IgAN women. Adverse pregnancy outcomes, identified by way of the Swedish Medical Birth Register, were compared through multivariable logistic regression and presented as adjusted odds ratios (aORs). Main outcome was preterm birth (< 37 weeks). Secondary outcomes were preeclampsia, small for gestational age (SGA), low 5-min Apgar score (< 7), fetal or infant loss, cesarean section, and gestational diabetes.

RESULTS: We found that IgAN was associated with an increased risk of preterm birth (13.1% vs 5.6%; aOR = 2.69; 95% confidence interval [CI] = 1.52-4.77), preeclampsia (13.8% vs 4.2%; aOR = 4.29; 95%CI = 2.42-7.62), SGA birth (16.0% vs 11.1%; aOR = 1.84; 95%CI = 1.17-2.88), and cesarean section (23.9% vs 16.2%; aOR = 1.74, 95%CI = 1.14-2.65). Absolute risks were low for intrauterine (0.6%) or neonatal (0%) death and for low 5-min Apgar score (1.5%), and did not differ from the reference population. Sibling comparisons suggested increased risks of preterm birth, preeclampsia, and SGA in IgAN, but not of cesarean section.

CONCLUSION: We conclude that although most women with IgAN will have a favorable pregnancy outcome, they are at higher risk of preterm birth, preeclampsia and SGA. Intensified supervision during pregnancy is warranted.