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- Rehnberg, Johanna, 1982-, et al.
(author)
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Cancer risk in patients with IgA nephropathy : a Swedish population-based cohort study
- 2022
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 37:4, s. 749-759
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Journal article (peer-reviewed)abstract
- 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.
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| 2. |
- Rehnberg, Johanna, 1982-, et al.
(author)
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Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD : A Swedish Population-Based Cohort Study
- 2021
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In: Journal of the American Society of Nephrology. - : American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 32:2, s. 411-423
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- Rehnberg, Johanna, 1982-, et al.
(author)
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Risk of primary infections in patients with IgA nephropathy : a Swedish population-based cohort study
- 2024
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 39:Suppl. 1, s. I2114-I2114
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Journal article (other academic/artistic)abstract
- Background and Aims: IgA nephropathy (IgAN) is the most common global kidney disease with a highly variable clinical presentation. Diagnosis IgAN requires a biopsy, and the immunohistologic examination is dominated by depositions of aberrant IgA1 antibodies. Since IgA antibodies are mainly produced by the mucosal associated lymphoid tissue the relationship between the mucosal immune system and IgAN has long been considered. The current theories on the origin of the disease involve genetic and environmental factors, with mucosal infections potentially playing a role. In some IgAN patients gastrointestinal and/or upper respiratory infections can aggravate the disease with episodic macrohematuria and/or increased proteinuria. Coincidently, these infections are also more common among patients with selective IgA deficiency. The aim of this study was to investigate whether the presence of IgAN confers an increased risk of infections in general to the IgAN patient.Method: IgAN was defined by a computerized biopsy record from 1997 to 2011 in Sweden. Each IgAN patient was matched with up to five reference individuals based on age, sex, calendar year, and county of residence. Exclusions included those with organ transplants, HIV, immunodeficiency, or end-stage kidney disease before study entry, and follow-up data were censored for subsequent occurrences. Linear and Cox regressions, adjusted for age, sex, and education, were performed to analyze total infections and antimicrobial treatments in both patient and reference groups. Sibling analyses were also performed, adjusted for baseline age, sex and educational attainment.Results: The linear regression analysis revealed a significant association between IgA nephropathy (IgAN) and the overall frequency of infections compared to the general population (β = 0.45; 95% CI: 0.37–0.54), women (β = 0.35; 95% CI: 0.19–0.50), men (β = 0.50; 95% CI: 0.40–0.60), and siblings (β = 0.37; 95% CI: 0.25–0.49) for women (β = 0.24; 95% CI: 0.06–0.41) and men (β = 0.43; 95% CI: 0.27–0.60). Similarly, a significant association was found for the frequency of prescribed antimicrobial agents compared to the general population (β = 0.66; 95% CI: 0.51–0.82), women (β = 0.92; 95% CI: 0.56–1.27), men (β = 0.55; 95% CI: 0.39–0.71), with similar estimates in the sibling analyses. The subtypes with the strongest association were urinary tract infections (β = 0.09; 95% CI: 0.07–0.11), ENT (ear, nose, and throat) infections (β = 0.08; 95% CI: 0.04–0.12), muscular infections (β = 0.08; 95% CI: 0.05–0.12), and infections in the GI (gastrointestinal) tract (β = 0.06; 95% CI: 0.04–0.09). Infections in the lower respiratory tract, skin and mycoses also had a significant positive association, however, no associations to infections in the central nervous system or infections caused by helminths and protozoans were identified. Cox regression showed an elevated risk of any infection with an adjusted hazard ratio (HR) of 2.05 (95% CI: 1.88–2.23), especially for sepsis (aHR = 3.13; 95% CI: 2.14–4.59), and time to the first prescription of antimicrobials with an aHR of 1.37 (95% CI: 1.30–1.45). Linear regression of prescribed antimicrobial treatments showed an overall β = 0.67; 95% CI: 0.51–0.82, and specifically for antibiotics (β = 0.64; 95% CI: 0.49–0.78).Conclusion: Our study demonstrates an increased prevalence of infections and antibiotic prescriptions in IgAN patients compared to the general population and their siblings. Further studies on the potential impact of IgAN and its immunological aberrations on overall infection susceptibility is warranted.
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| 4. |
- Rehnberg, Johanna, 1982-, et al.
(author)
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Validation of IgA nephropathy diagnosis in the Swedish Renal Registry
- 2024
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In: BMC Nephrology. - : BioMed Central (BMC). - 1471-2369. ; 25:1
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Journal article (peer-reviewed)abstract
- 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.
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