To Örebro University

BACKGROUND: Case reports suggest an association between inflammatory bowel disease, a chronic autoimmune condition linked to increased circulating IgA levels, and IgA nephropathy, the most common form of primary GN and a leading cause of ESKD.

METHODS: In a Swedish population-based cohort study, we compared 3963 biopsy-verified IgA nephropathy patients with 19,978 matched controls between 1974 and 2011, following up participants until 2015. Inflammatory bowel disease data and ESKD status were obtained through national medical registers. We applied Cox regression to estimate hazard ratios (HRs) for future inflammatory bowel disease in IgA nephropathy and conditional logistic regression to assess risk of earlier inflammatory bowel disease in IgA nephropathy. We also explored whether inflammatory bowel disease affects development of ESKD in IgA nephropathy.

RESULTS: During a median follow-up of 12.6 years, 196 (4.95%) patients with IgA nephropathy and 330 (1.65%) matched controls developed inflammatory bowel disease (adjusted HR, 3.29; 95% confidence interval [95% CI], 2.73 to 3.96). Inflammatory bowel disease also was more common before a confirmed IgA nephropathy diagnosis. Some 103 (2.53%) IgA nephropathy patients had an earlier inflammatory bowel disease diagnosis compared with 220 (1.09%) controls (odds ratio [OR], 2.37; 95% CI, 1.87 to 3.01). Both logistic regression (OR, 2.60; 95% CI, 2.02 to 3.35) and time-varying Cox regression (HR, 1.84; 95% CI, 1.33 to 2.55) demonstrated that inflammatory bowel disease was associated with increased ESKD risk in patients with IgA nephropathy.

CONCLUSIONS: Patients with IgA nephropathy have an increased risk of inflammatory bowel disease both before and after their nephropathy diagnosis. In addition, among patients with IgA nephropathy, comorbid inflammatory bowel disease elevates the risk of progression to ESKD.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis affecting all ages and both sexes, but there is a lack of studies on its association with cancer and whether it is a paramalignant condition.

METHODS: In a Swedish population-based cohort study we compared the risk of cancer among 3,882 biopsy-verified IgAN patients diagnosed during 1974-2011 with 19,341 reference individuals and followed them until 2015. Cox regression was used to estimate hazard ratios (HRs) for cancer in IgAN patients versus controls, and conditional logistic regression assessed the risk of cancer before the IgAN was confirmed.

RESULTS: During a median follow-up of 12.6 years, 488 (12.6%) patients with IgAN and 1,783 (9.2%) matched reference individuals were diagnosed with cancer (HR 1.70; 95% confidence interval, 95%CI, 1.52-1.89). The increased risk was only seen in IgAN patients developing end stage renal disease (ESRD), with an HR of 4.01 (95%CI 3.33-4.82) for any cancer and HR of 2.22 (95%CI 1.79-2.75) when excluding non-melanoma skin cancer (NMSC). Non-ESRD IgAN patients did not have an increased overall cancer risk (HR 1.13; 95%CI 0.99-1.30). There was no increased risk of cancer preceding IgAN diagnosis (odds ratio 1.10; 95%CI 0.92-1.32).

CONCLUSION: We found no support for IgAN being a paramalignant condition. There was an increased risk of cancer in IgAN patients, but only for those with ESRD. Our results indicate approximately 6 extra cancer case per 100 IgAN patients with ESRD per 10 years, or >17 extra cases if including NMSC as well.

AIM: The Swedish Renal Registry (SRR) is a unique national quality registry that monitors the clinical trajectory of patients with chronic kidney disease (CKD). We have validated the biopsy data registered in the SRR for IgA Nephropathy (IgAN) diagnosis.

METHODS: In total 25% of all patients (n = 142), registered with IgAN in the SRR after having performed a kidney biopsy during 2015-2019, were randomly selected. We obtained original biopsy and medical records for 139 (98%) patients. We evaluated the IgAN diagnosis using a standardized template, calculated its positive predictive value (PPV) with 95% confidence interval (CI) and reported clinical features at the time of diagnosis.

RESULTS: A histological and clinical diagnosis of IgAN was confirmed in 132 of the 139 patients, yielding a PPV of 95% (95% CI 90-98%). Median age was 46 years (range: 18-85) and the male:female ratio was 2.1:1. The median creatinine level was 123 µmol/L, with a corresponding estimated glomerular filtration rate (eGFR) level of 51 mL/min/1.73m2. Histological features of IgA deposits were seen in all patients, hypercellularity in 102/132 (77.2%), C3 deposits in 98/132 (72.4%) and C1q deposits in 27/132 (20.5%) of the cases.

CONCLUSION: Validating data is not research per se, but continuous validation of medical registries is an important feature necessary to ensure reliable data and the foundation of good epidemiological data for future research. Our validation showed a high PPV (95%) for IgAN diagnosis registered in the SRR. Clinical characteristics were consistent with previous reports. The biopsy data in the SRR will be a valuable resource in future IgAN research.

INTRODUCTION: IgA nephropathy is the most common primary kidney disease in the world and has a highly variable clinical presentation. While studies have indicated a link between glomerular disease and infections, large-scale studies on IgA nephropathy are missing.

METHODS: In our study, IgA nephropathy was defined as having a kidney biopsy record 1997-2011 in Sweden. Each IgA nephropathy patient was matched with five reference individuals based on age, sex, calendar year, and county of residence. We excluded individuals with earlier organ transplants, HIV, immunodeficiency, or end-stage kidney disease. Linear and Cox regressions, adjusted for age, sex, education, and diabetes, were performed to analyze total infections and antimicrobial treatments in both patients and reference individuals. Sibling analyses were also performed.

RESULTS: The linear regression analysis revealed a significant association between IgA nephropathy and the overall frequency of infections compared to the general population (β = 0.44; 95% CI: 0.35-0.53) and siblings (β = 0.36; 95% CI: 0.23-0.49). Similarly, antimicrobial prescriptions, especially antibiotics, were more common in IgA nephropathy compared to the general population and to siblings. Cox regression showed an elevated risk of any infection (adjusted hazard ratio [aHR] = 2.00; 95% CI: 1.84-2.18) and sepsis (aHR = 3.18; 95% CI: 2.17-4.65) corresponding to one extra case of sepsis per 63 patients followed for 10 years. The strongest associations were seen for urinary tract infections; ear, nose, and throat infections; and musculoskeletal and gastrointestinal infections.

CONCLUSION: Conclusively, our study demonstrates an increased prevalence of infections and antibiotic prescriptions in IgA nephropathy patients. The increased risk of sepsis warrants clinical awareness and prevention.