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

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.

Clinical validation of immunoglobulin A nephropathy diagnosis in Swedish biopsy registers.

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-Schönlein 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 µmol/L (range 26-986 µmol/L, n=110) and glomerular filtration rate 75 mL/min/1.73m2 (range 5-173 mL/min/1.73m2, 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.

A proposed set of metrics for standardized outcome reporting in the management of low back pain.

BACKGROUND AND PURPOSE: Outcome measurement has been shown to improve performance in several fields of healthcare. This understanding has driven a growing interest in value-based healthcare, where value is defined as outcomes achieved per money spent. While low back pain (LBP) constitutes an enormous burden of disease, no universal set of metrics has yet been accepted to measure and compare outcomes. Here, we aim to define such a set. PATIENTS AND METHODS: An international group of 22 specialists in several disciplines of spine care was assembled to review literature and select LBP outcome metrics through a 6-round modified Delphi process. The scope of the outcome set was degenerative lumbar conditions. RESULTS: Patient-reported metrics include numerical pain scales, lumbar-related function using the Oswestry disability index, health-related quality of life using the EQ-5D-3L questionnaire, and questions assessing work status and analgesic use. Specific common and serious complications are included. Recommended follow-up intervals include 6, 12, and 24 months after initiating treatment, with optional follow-up at 3 months and 5 years. Metrics for risk stratification are selected based on pre-existing tools. INTERPRETATION: The outcome measures recommended here are structured around specific etiologies of LBP, span a patient's entire cycle of care, and allow for risk adjustment. Thus, when implemented, this set can be expected to facilitate meaningful comparisons and ultimately provide a continuous feedback loop, enabling ongoing improvements in quality of care. Much work lies ahead in implementation, revision, and validation of this set, but it is an essential first step toward establishing a community of LBP providers focused on maximizing the value of the care we deliver.

Infectious disease at gluten introduction and risk of childhood diabetes mellitus.

OBJECTIVES: To investigate the risk of future diabetes mellitus type 1 (T1D) in children who suffered from infection at time of gluten introduction. STUDY DESIGN: Population-based prospective study. Parents filled out a diary at home. We hereby obtained data on date of gluten introduction, breastfeeding duration, and infections in 9414 children born in the southeast of Sweden from October 1, 1997, through October 1, 1999 (the All Babies in Southeast Sweden cohort). The Cox proportional hazards model was used to investigate the risk of future T1D until February 1, 2012, among children with infection at time of gluten introduction. RESULTS: Forty-six children (0.5%) developed T1D and were compared with 9368 reference children from the general population. Some 10 of 46 children with later T1D had an infection at time of gluten introduction (22%) compared with 2520 reference children (27%, P=.43). Later T1D was not associated with age at end of breastfeeding, age at any infection, or age at gluten introduction. Breastfeeding at time of gluten introduction was not protective against future T1D (hazard ratio 1.2; 95% CI, 0.5-2.7). In our final model, when we adjusted for age at gluten introduction, age at infection, and breastfeeding duration, infection at time of gluten introduction did not influence the risk of future T1D (hazard ratio 0.8; 95% CI, 0.3-1.6). CONCLUSION: Infection at time of gluten introduction is not a major risk factor for future T1D in nonselected children.

Breast-feeding duration and gluten introduction among mothers with celiac disease.

OBJECTIVES: Both breast-feeding duration and age at gluten introduction have been implicated in the pathogenesis of celiac disease (CD). We hypothesized that parental CD affects the feeding pattern of the offspring, mediated by parental health awareness increasing adherence to infant feeding guidelines. METHODS: Prospectively collected infant feeding data were obtained through the All Babies in Southeast Sweden study. Information regarding infant feeding was available in 9414 children. Twenty-two mothers had a history of biopsy-verified CD before delivery of a child in the study, and 9392 mothers had no diagnosis of CD before birth and thus constituted the unexposed or control population. Cox regression was used to compare the risk of early weaning and gluten introduction according to parental CD status, and logistic regression to assess whether mothers with CD were more likely to breast-feed their children at gluten introduction. RESULTS: Some 63% of children were breast-fed for at least 9 months. We found no association between maternal CD and early weaning (adjusted hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.6-1.7), or between paternal CD and early weaning (HR 0.5, 95% CI 0.1-1.9). Sixty percent of children were introduced to gluten in months 5 and 6. Maternal CD was not associated with age at gluten introduction (adjusted HR 0.8, 95% CI 0.6-1.3). There was no statistically significant association between maternal CD and breast-feeding at the time of gluten introduction (odds ratio 1.4, 95% CI 0.4-4.7). CONCLUSIONS: Feeding patterns do not seem to vary between offspring and mothers with CD and those without.

Increased risk of IgA nephropathy among individuals with celiac disease.

GOAL: To determine the risk of future biopsy-verified IgA nephropathy (IgAN) among individuals with biopsy-verified celiac disease (CD). BACKGROUND: Individuals with CD suffer increased risk of end-stage renal disease. An association between CD and IgAN has been suggested; however, results have been inconclusive and no previous study has considered the risk of IgAN in biopsy-verified CD. STUDY: We performed a population-based prospective cohort study. We identified 27,160 individuals with CD (Marsh stage III) and no previous renal disease through small-intestinal biopsy reports obtained between July 1969 and February 2008 in all (n=28) Swedish pathology departments. Individuals with IgAN were identified by biopsy reports acquired at the 4 Swedish pathology departments specialized in renal pathology. Cox regression analysis was used to determine the risk of future IgAN among individuals with CD compared with 133,949 age-matched and sex-matched reference individuals. RESULTS: Seven (0.026%) individuals with CD and 11 (0.008%) reference individuals developed IgAN. We found an increased risk of biopsy-verified IgAN among individuals with CD [hazard ratio, 3.03; 95% confidence interval, 1.22-7.56]. The risk increase remained statistically significant after adjustment for prior liver disease and country of birth. CONCLUSIONS: Individuals with CD suffer a 3-fold increased risk of future IgAN. Our findings warrant awareness of renal function in individuals with CD.

Increased risk of end-stage renal disease in individuals with coeliac disease.

OBJECTIVE: The prevalence of end-stage renal disease (ESRD) is increasing worldwide. Although increased levels of coeliac disease (CD) autoantibodies are often seen in renal disease, the importance of biopsy-verified CD for the risk of future ESRD is unclear. The aim of this study was therefore to investigate the risk of future ESRD in individuals with CD. METHODS: This was a population-based prospective cohort study. 29,050 individuals with CD (Marsh III) were identified through small-intestinal biopsy reports obtained between July 1969 and February 2008 in Sweden's 28 pathology departments. ESRD was defined as the need for renal dialysis or renal transplant in accordance with the international classification of disease and procedure codes in Swedish patient registers. Using Cox regression, the risk of ESRD in individuals with CD compared with age- and sex-matched reference individuals was estimated. RESULTS: During follow-up, 90 individuals with CD developed ESRD (expected count 31). This corresponded to a HR for ESRD of 2.87 (95% CI 2.22 to 3.71, p<0.001). Adjusting for diabetes mellitus had only a marginal effect on the risk estimate (HR 2.52, 95% CI 1.92 to 3.31). Excluding individuals with any urinary/renal disorder before study entry, the HR for ESRD in CD was 2.47 (95% CI 1.80 to 3.40). When restricting the outcome measure to ESRD confirmed by independent data from the Swedish Renal Registry (SRR), the risk estimate increased to 3.20 (95% CI 2.39 to 4.28). CONCLUSION: This study indicates that individuals with biopsy-verified CD suffer increased risk of subsequent ESRD.

Infectious disease and risk of later celiac disease in childhood.

OBJECTIVE: The goal was to examine whether parent-reported infection at the time of gluten introduction increases the risk of future celiac disease (CD). METHODS: Through the population-based All Infants in Southeast Sweden study, parents recorded data on feeding and infectious disease prospectively. Complete data on gluten introduction and breastfeeding duration were available for 9408 children. Those children had 42 826 parent-reported episodes of infectious disease in the first year of life (including 4003 episodes of gastroenteritis). We identified 44 children with biopsy-verified CD diagnosed after 1 year of age, and we used Cox regression to estimate the risk of future CD for children with infection at gluten introduction. RESULTS: Eighteen children with CD (40.9%) had an infection at the time of gluten introduction, compared with 2510 reference individuals (26.8%; P = .035). Few children had gastroenteritis at the time of gluten introduction (1 child with CD [2.3%] vs 166 reference individuals [1.8%]; P = .546). With adjustment for age at gluten introduction and breastfeeding duration, we found no association between a future diagnosis of CD and either any infection (adjusted hazard ratio: 1.8 [95% confidence interval: 0.9-3.6]) or gastroenteritis (adjusted hazard ratio: 2.6 [95% confidence interval: 0.2-30.8]) at the time of gluten introduction. We found no associations between breastfeeding duration, age at gluten introduction, and future CD. CONCLUSION: These results indicate that parent-reported infection at the time of gluten introduction is not a major risk factor for CD.

Risk of thromboembolism in 14,000 individuals with coeliac disease.

The risk of venous thromboembolism (VTE) was examined in individuals with coeliac disease (CD). The Swedish national inpatient register was used to identify 14 207 individuals with a diagnosis of CD (1964-2003). These individuals were matched for age, sex, calendar year and county with 69 048 reference individuals. Cox regression was used to estimate hazard ratios (HRs) for subsequent thromboembolism in individuals with more than 1 year of follow-up and no prior VTE. CD was associated with an increased risk of subsequent VTE (HR = 1.86; 95% confidence interval (CI) 1.54-2.24). The risk increase was restricted to individuals with CD diagnosed in adulthood. Risk estimates were not affected by the presence of diabetes mellitus or concomitant surgery. Compared with inpatients as reference individuals, CD individuals remained at increased risk of subsequent VTE (adjusted HR = 1.27; 95% CI = 1.06-1.52). In conclusion, this study found a statistically significantly positive association between CD and VTE. This modest association might be explained by a combination of surveillance bias and chronic inflammation.