Christian Fynbo Christiansen

Background: Within the current criteria for acute kidney injury (AKI), it remains debated whether small absolute creatinine increases are associated with higher mortality in patients with low baseline estimated glomerular filtration rates (eGFRs), and whether these changes carry prognostic value comparable to relative increases. We therefore examined the prognostic impact of rapid creatinine increases across baseline eGFRs in patients undergoing major elective surgery. Methods: We pooled data on patients undergoing major elective surgery from Canada, Denmark, Scotland, and Wales. This clinical setting was chosen because creatinine levels in this group are routinely monitored both before and after an acute stress event, regardless of clinical status. We ascertained the highest relative creatinine increase within 7 days and the highest absolute creatinine increase within 2 days during the first 7 days after surgery. We used logistic regressions with splines and interaction terms to construct heatmaps depicting age-, sex-, year-, and surgery type-standardized 90-day mortality according to creatinine increases across baseline eGFRs. Results: There were 311 975 surgical procedures performed in 279 554 patients, with 11 568 deaths. Compared to no change in creatinine, a 0.3 mg/dl (26.5 µmol/l) absolute increase was associated with a consistent 2.2–3.3 percentage point increase in mortality for eGFR between 15 and 90 ml/min/1.73 m2. However, while the excess mortality associated with a 0.3 mg/dl and a 50% creatinine increase was similar at baseline eGFR of 90 ml/min/1.73 m2, the excess mortality of a 50% creatinine increase was substantially greater among those with baseline eGFRs <30 ml/min/1.73 m2. Conclusions: A small absolute creatinine increase of 0.3 mg/dl is associated with a consistent increase in mortality across baseline eGFRs, indicating its relevance as a component of the AKI criteria. However, the higher excess mortality associated with a 50% increase at low eGFRs should be emphasized in future guidelines to improve clinical discussions.

Background: Postoperative acute kidney injury (PO-AKI) occurs in 8–20% of patients undergoing colorectal cancer surgery and is associated with increased mortality and morbidity. A prediction model can help in the identification of high-risk patients and guide clinicians in implementing preventive measures. The present study aimed to develop and validate internally a clinical prediction model for the risk of PO-AKI within 7 days after an elective resection of colorectal cancer, using predictors known before surgery. Methods: Using a nationwide clinical quality database, all patients with stage I–IV colorectal cancer undergoing an elective colorectal resection from 2015 to 2021 in Denmark were identified. Patient characteristics, comorbidities, medications, and laboratory values were obtained through linkage across national health registries. The outcome was PO-AKI within 7 days after surgery, defined according to the Kidney Disease Improving Global Outcomes criteria. A logistic regression model was fitted using preoperative predictors, backward selection was applied to derive the final model, and internal validation was performed through two-fold bootstrapping. The performance was assessed using discrimination and calibration measures. Results: Among 26 104 identified patients, 20 277 patients were included, and 1747 (8.6%) developed AKI within 7 days. Fifty-four per cent were men, and the median age was 71 years (interquartile range, 64–78 years). The final model included 14 preoperative predictors. The model showed moderate discriminative performance with an optimism-corrected c-statistic of 0.70 (95% confidence interval 0.68 to 0.71) and was well calibrated at PO-AKI risks between 0% and 20% but somewhat overestimated higher risks (overall slope 0.95; intercept −0.001). The prediction model is available as a calculator at https://po-aki.streamlit.app. Conclusion: The model predicted PO-AKI with moderate accuracy and may support the implementation of preventive measures. However, external validation is required to confirm its applicability.

Background and ObjectivesPerioperative stroke (POS), defined as stroke occurring within 30 days after surgery, is a serious complication associated with substantial short-term mortality. However, f...

Denmark has a well-established tradition of utilizing national registries for epidemiological research. Healthcare services in Denmark are managed by five administrative regions and documented in electronic health records (EHRs). While certain EHR data are mandatorily transferred to national registries, the national registries capture only a fraction of the information available within regional EHR systems. In this review, we describe and discuss the context, content, and research potential of regional EHR data in Denmark for observational studies and pragmatic clinical trials. Throughout, examples and descriptions of data infrastructure primarily stem from one region (the Central Denmark Region). As each region governs its own healthcare delivery and IT systems, there are regional variations in EHR data sources and availability for research purposes. Overall, EHRs integrate clinical information, including structured entries (diagnoses, procedures, and treatments); semi-structured input of clinical information; free-text clinical notes; results from biochemical, microbiological, and pathological analyses; radiological images and descriptions; administered medicines; and administrative data such as appointment and procedure bookings. Regional EHRs include several data types unavailable or incompletely captured in national registries, including semi-structured and free-text clinical information, certain laboratory results, radiology descriptions, and hospital-administered or prescribed medicines before 2018. These data hold specific potential for research. Overall, the utilization of EHR data holds significant promise for improving both clinical trials and observational studies. In pragmatic trials, EHRs can facilitate patient recruitment and data collection on patient characteristics, outcomes, and adverse events within routine care, enabling larger, more generalizable study designs at lower costs. In observational research, EHR data can provide highly detailed clinical information and data types not captured in population-based registries. However, the use of regional EHR data also presents important challenges, including inter-regional heterogeneity in data systems and governance, variable data completeness, and methodological difficulties related to the extraction and analysis of unstructured clinical information. Despite these limitations, EHR data in Denmark provide large-scale, unique clinical information that complements population-based registries and represents an increasingly important resource for research. As data systems mature and the methods to utilize unstructured clinical information develop, the potential of these data to facilitate observational studies and pragmatic trials will continue to expand.

Background: The understanding of acute kidney injury (AKI) has evolved, but it remains uncertain whether outcomes have improved over time. This study aimed to describe temporal changes in outcomes among intensive care unit (ICU) patients with AKI in Denmark from 2010 to 2024. Methods: This cohort study included adult patients with a first-time ICU admission, and AKI identified using creatinine changes in the seven days following ICU admission. The risks of chronic kidney disease (CKD), kidney failure (KF), and death were assessed one year after ICU admission across three periods: 2010–2014, 2015–2019, and 2020–2024. CKD was defined as an outpatient estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m2 for more than 90 days. Similarly, KF was defined as an eGFR below 15 ml/min/1.73 m2, a hospital diagnosis, kidney transplantation, or initiation of chronic kidney replacement therapy. Follow-up was divided into seven to 89 days and from 90 to 365 days, and death was considered a competing risk for CKD and KF. Results: A total of 48,529 patients with AKI were identified. The seven to 89-day mortality was 23.4% (95% confidence interval (CI): 22.5%—24.3%) in 2010–2014, compared to 22.3% (95% CI: 21.7%—22.9%) in 2015–2019, and 20.7% (95% CI: 20.2%—21.2%) in 2020–2024. The 90- to 365-day mortality was 10.3% (95% CI: 9.5%—11.0%) in 2010–2014, 10.2% (95% CI: 9.7%—10.7%) in 2015–2019, and 9.5% (95% CI: 9.1%—10.0%) in 2020–2024. The 90- to 365-day risk of CKD was 21.0% (95% CI: 19.9%—22.1%) in 2010–2014, compared to 19.8% (95% CI: 19.1%—20.6%) in 2015–2019 and 17.3% (95% CI: 16.7%—17.9%) in 2020–2024. The 90- to 365-day risk of KF was 2.2% (95% CI: 1.9%—2.6%) in 2010–2014, 2.1% (95% CI: 1.9%—2.3%) in 2015–2019, and 2.0% (95% CI: 1.8%-2.3%) in 2020–2024. Conclusions: In this cohort of ICU patients with AKI, mortality and risk of CKD decreased over time, while the risk of KF remained stable. These improvements are encouraging and may reflect changes in ICU management or post-AKI care, although the observational design precludes inference about underlying mechanisms .

Objective: To examine the association between urinary protein excretion (UPE) level in preeclampsia and long‐term risk of maternal hypertension, chronic kidney disease (CKD), and cardiovascular disease (CVD). Design: Nationwide, population‐based cohort study utilising routinely collected individual‐level data from medical databases. Setting: Denmark, 1998–2018, with follow‐up through 2021. Population: All pregnancies ≥ 20 weeks among women aged ≥ 15 years. Methods: We calculated cumulative incidences (risks) of hypertension, CKD, and CVD by preeclampsia status, including UPE level (no/mild versus moderate/severe, based on established urine protein/albumin cutoffs). Adjusted risk differences and risk ratios were computed for women with preeclampsia compared with those without, adjusting for age, smoking, obesity, residential region, and year. Main Outcome Measures: 10‐year risk, adjusted risk difference, and risk ratio of hypertension, CKD and CVD by preeclampsia status and UPE level. Results: Among 286 078 pregnant women, 9538 (3.3%) developed preeclampsia, which was associated with higher risks of later hypertension, CKD or CVD. Among women with preeclampsia with no/mild UPE, 10‐year risks were 11.9% (95% CI: 10.9–13.0) for hypertension, 1.2% (95% CI: 0.9–1.6) for CKD and 1.1% (95% CI: 0.8–1.5) for CVD. With moderate/severe UPE, 10‐year risks were 16.0% (95% CI: 14.6–17.5) for hypertension, 5.1% (95% CI: 4.3–5.9) for CKD and 1.2% (95% CI: 0.8–1.7) for CVD. For hypertension and CVD, adjusted risk differences and risk ratios were similar across UPE levels, whereas CKD risk increased with higher UPE. Conclusion: Preeclampsia is associated with increased long‐term maternal risk of hypertension, CKD, and CVD. Higher UPE levels correlate with higher risk of later hypertension and CKD.

Introduction: Brain disorders, including neurological conditions and mental disorders, pose a considerable economic burden in Denmark. However, the costs of illness are not limited to the patients themselves, as the consequences of living with a brain disorder may also impact close relatives. We aimed to describe any societal costs related to healthcare utilisation and income loss for the closest family relatives of patients with brain disorders. Methods: This population-based cohort study included the closest family relatives (proxies for caregivers) of patients with prevalent (by 1 January 2021) or incident (during 2016–2021) brain disorders, using registry data. They were compared with corresponding relatives of matched population comparisons. Patients were categorised into three age strata: children and young people (0–24 years), adults (25–64 years) and older adults (65+years). We specified criteria for identifying the closest family relative for each age stratum. Using data from national registries, we estimated attributable healthcare costs and, for working-age relatives (18–65 years), income loss. Results: In 2021, close relatives of patients with brain disorders included 125 495 fathers and 96 154 mothers of children and young people, 880 661 relatives of adults and 378 826 relatives of older adults. The pooled attributable costs of brain disorders incurred by closest family relatives were €2407 million for prevalent disease in 2021 and €794 million for incident disease the first year following incidence. The dominating cost component was income loss for working-age relatives. Conclusions: The higher healthcare costs and especially the lower income for relatives of patients with brain disorders could be associated with the societal economic burden of brain disorders in Denmark. Informal care provided by relatives should be considered in discussions of healthcare prioritisation.

Background: Kidney transplant recipients face a high risk of adverse events, including fractures. Reported fracture rates post-transplant vary widely and may have changed over time. The consequences of a fracture, especially subsequent fractures, remain under-investigated. This study examined the risk and prognosis of fractures after kidney transplantation in the current era. Methods: This retrospective cohort study included all adults who received a first single-organ kidney transplant between 2000 and 2022 in Denmark. Nationwide healthcare registries were utilized to identify the study population and provide demographic data, diagnostic and procedural codes, and prescription data. Cumulative incidence (risk) of both first fracture and subsequent fracture was computed, treating death as a competing risk. Crude, and sex- and age-standardized incidence rates were estimated for different time periods. Results: The study included 3977 first kidney transplant recipients, of whom 788 sustained any post-transplant fracture. The 10-year risk of fracture was 21% (95% confidence interval 20–23). Crude incidence rates of any fracture remained unchanged over time, while standardized estimates showed a slight decline. Fractures were primarily located at the peripheral skeleton. Twenty-eight percent of patients with a fracture sustained a subsequent fracture, with the highest incidence at 6–12 months following the first event. Conclusions: Kidney transplant recipients remain at high fracture risk, with unchanged fracture rates over the past 20 years. The imminent fracture risk following a first fracture is high and largely unaddressed. Although formal guidelines have yet to be established, this knowledge should urge clinicians to perform risk assessment and consider intervention following a post-transplant fracture.

IgA nephropathy (IgAN) is the leading cause of primary glomerulonephritis; however, reported incidences and prevalences vary substantially across countries. This study assessed the epidemiology of IgAN including changes in incidence, prevalence, treatment, and prognosis in Denmark during 2002–2023. This population-based cohort study included all adult patients with a biopsy-verified diagnosis of IgAN in Denmark during 22 years. Danish health registries with data on hospital diagnoses, pharmacological therapy, and laboratory results were used. The study period was divided into three calendar periods. Crude and age- and sex-standardized incidence rates and prevalences of IgAN in the Danish population were computed. The period specific five-year and the overall 15-year cumulative incidence (risk) of kidney failure with replacement therapy (KFRT) and of all-cause death (mortality) were estimated. The study population included 1 298 incident adult patients with IgAN. The overall incidence of IgAN was 13.1 per 1 000 000 person-years (95% CI 9.8–16.5). The annual incidence increased threefold during the study period. The prevalence reached 261 per 1 000 000 people in year 2023 (95% CI 246–275). Median eGFR was 60 ml/min/1.73 m² (IQR 40–85) and median uACR was 1.2 g/g (IQR 0.6–2.2) at time of diagnosis. Following diagnosis, renin-angiotensin system inhibitors constituted a mainstay of treatment while corticosteroid use declined throughout the period. The 15-year risk of KFRT was 42.7% (95% CI 38.4–46.9). The 15-year all-cause mortality was 22.8% (95% CI 19.4–26.4). There were no substantial changes in the 5-year risk of KFRT or mortality during the study period. The annual incidence of IgAN in Denmark increased during the study period. At the time of biopsy, many patients had preserved kidney function and substantial albuminuria. The risk of KFRT and mortality was substantial, and overall, the prognosis for Danish IgAN patients did not improve over the past two decades.