Predicting the risks of kidney failure and death in adults with moderate to severe chronic kidney disease: multinational, longitudinal, population based, cohort study.

OBJECTIVE: To train and test a super learner strategy for risk prediction of kidney failure and mortality in people with incident moderate to severe chronic kidney disease (stage G3b to G4). DESIGN: Multinational, longitudinal, population based, cohort study. SETTINGS: Linked population health data from Canada (training and temporal testing), and Denmark and Scotland (geographical testing). PARTICIPANTS: People with newly recorded chronic kidney disease at stage G3b-G4, estimated glomerular filtration rate (eGFR) 15-44 mL/min/1.73 m2. MODELLING: The super learner algorithm selected the best performing regression models or machine learning algorithms (learners) based on their ability to predict kidney failure and mortality with minimised cross-validated prediction error (Brier score, the lower the better). Prespecified learners included age, sex, eGFR, albuminuria, with or without diabetes, and cardiovascular disease. The index of prediction accuracy, a measure of calibration and discrimination calculated from the Brier score (the higher the better) was used to compare KDpredict with the benchmark, kidney failure risk equation, which does not account for the competing risk of death, and to evaluate the performance of KDpredict mortality models. RESULTS: 67 942 Canadians, 17 528 Danish, and 7740 Scottish residents with chronic kidney disease at stage G3b to G4 were included (median age 77-80 years; median eGFR 39 mL/min/1.73 m2). Median follow-up times were five to six years in all cohorts. Rates were 0.8-1.1 per 100 person years for kidney failure and 10-12 per 100 person years for death. KDpredict was more accurate than kidney failure risk equation in prediction of kidney failure risk: five year index of prediction accuracy 27.8% (95% confidence interval 25.2% to 30.6%) versus 18.1% (15.7% to 20.4%) in Denmark and 30.5% (27.8% to 33.5%) versus 14.2% (12.0% to 16.5%) in Scotland. Predictions from kidney failure risk equation and KDpredict differed substantially, potentially leading to diverging treatment decisions. An 80-year-old man with an eGFR of 30 mL/min/1.73 m2 and an albumin-to-creatinine ratio of 100 mg/g (11 mg/mmol) would receive a five year kidney failure risk prediction of 10% from kidney failure risk equation (above the current nephrology referral threshold of 5%). The same man would receive five year risk predictions of 2% for kidney failure and 57% for mortality from KDpredict. Individual risk predictions from KDpredict with four or six variables were accurate for both outcomes. The KDpredict models retrained using older data provided accurate predictions when tested in temporally distinct, more recent data. CONCLUSIONS: KDpredict could be incorporated into electronic medical records or accessed online to accurately predict the risks of kidney failure and death in people with moderate to severe CKD. The KDpredict learning strategy is designed to be adapted to local needs and regularly revised over time to account for changes in the underlying health system and care processes.

Hypoparathyroidism and mortality after total thyroidectomy: A nationwide matched cohort study.

OBJECTIVE: Total thyroidectomy (TT) carries a risk of hypoparathyroidism (hypoPT). Recently, hypoPT has been associated with higher overall mortality rates. We aimed to evaluate the frequency of hypoPT and mortality in patients undergoing TT in Denmark covering 20 years. DESIGN: Retrospective Cohort study. PATIENTS AND MEASUREMENTS: Using population-based registries, we identified all Danish individuals who had undergone TT between January 1998 and December 2017. We included a comparison cohort by randomly selecting 10 citizens for each patient, matched on sex and birth year. HypoPT was defined as treatment with active vitamin D after 12 months postoperatively. We used cumulative incidence to calculate risks and Cox regression to compare the rate of mortality between patients and the comparison cohort. We evaluated patients in different comorbidity groups using the Charlson Comorbidity Index and by different indications for surgery. RESULTS: 7912 patients underwent TT in the period. The prevalence of hypoPT in the study period was 16.6%, 12 months postoperatively. After adjusting for potential confounders the risk of death due to any causes (hazard ratio; 95% confidence intervals) following TT was significantly increased (1.34; 1.15-1.56) for patients who developed hypoPT. However, subgroup analysis revealed mortality was only increased in malignancy cases (2.48; 1.99-3.10) whereas mortality was not increased when surgery was due to benign indications such as goitre (0.88; 0.68-1.15) or thyrotoxicosis (0.86; 0.57-1.28). CONCLUSIONS: The use of active vitamin D for hypoPT was prevalent one year after TT. Patients with hypoPT did not have an increased risk of mortality following TT unless the indication was due to malignancy.

Oral anticoagulant treatment and risk of kidney disease-a nationwide, population-based cohort study.

Background: Direct oral anticoagulants (DOACs) are recommended as first-line treatment of atrial fibrillation. Whether DOAC use is associated with lower risks of kidney complications compared with vitamin K antagonists (VKAs) remains unclear. We examined this association in a nationwide, population-based cohort study. Methods: We conducted a cohort study including patients initiating oral anticoagulant treatment within 3 months after an atrial fibrillation diagnosis in Denmark during 2012-18. Using routinely collected creatinine measurements from laboratory databases, we followed patients in an intention-to-treat approach for acute kidney injury (AKI) and chronic kidney disease (CKD) progression. We used propensity-score weighting to balance baseline confounders, computed weighted risks and weighted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing DOACs with VKAs. We performed several subgroup analyses and a per-protocol analysis. Results: We included 32 781 persons with atrial fibrillation initiating oral anticoagulation (77% initiating DOACs). The median age was 75 years, 25% had a baseline estimated glomerular filtration rate <60 mL/min/1.73 m2, and median follow-up was 2.3 (interquartile range 1.1-3.9) years. The weighted 1-year risks of AKI were 13.6% in DOAC users and 15.0% in VKA users (HR 0.86, 95% CI 0.82; 0.91). The weighted 5-year risks of CKD progression were 13.9% in DOAC users and 15.4% in VKA users (HR 0.85, 95% CI 0.79; 0.92). Results were similar across subgroups and in the per-protocol analysis. Conclusions: Initiation of DOACs was associated with a decreased risk of AKI and CKD progression compared with VKAs. Despite the potential limitations of observational studies, our findings support the need for increased clinical awareness to prevent kidney complications among patients who initiate oral anticoagulants.

Proton pump inhibitors and the risk of acute kidney injury in cancer patients receiving immune checkpoint inhibitors: A Danish population-based cohort study.

Previous studies have suggested that the use of proton pump inhibitors (PPIs) more than doubles the risk of acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs). However, this association may be confounded. Therefore, we conducted a register-based cohort study to examine the risk of AKI in users and nonusers of PPIs among cancer patients treated with ICIs in Denmark from 2011 through 2021 while accounting for a comprehensive range of potential confounders. PPI use was determined based on redeemed prescriptions of PPIs before ICI initiation. We identified laboratory-recorded AKI events within the first year after ICI initiation. We estimated the risks and hazard ratios (HRs) of AKI while accounting for a comprehensive range of confounders (including comorbidities and comedication) by propensity score weighting. Furthermore, we performed an additional per-protocol analysis while accounting for informative censoring by weighting. We identified 10 200 cancer patients including 2749 (27%) users, 6214 (61%) nonusers, and 1237 (12%) former users of PPIs. PPI users had an increased risk of AKI compared to nonusers (1-year risk, 24.7% vs 19.9%; HR, 1.42 [95% confidence interval (CI), 1.29-1.56]); however, this association attenuated when accounting for confounders (weighted 1-year risk, 24.2% vs 23.8%; weighted HR, 1.06 [95% CI, 0.93-1.21]). In the per-protocol analysis, the crude HR was 1.86 (95% CI, 1.63-2.12), while the weighted HR was 1.24 (95% CI, 1.03-1.49). Thus, the association between PPI use and AKI could largely be explained by confounding, suggesting that previous studies may have overestimated the association.

Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

Fifteen-year temporal changes in rates of acute kidney injury among children in Denmark.

BACKGROUND: We aimed to examine temporal changes in the annual rate of acute kidney injury (AKI) in Danish children and associated changes in patient characteristics including potential underlying risk factors. METHODS: In this population-based cohort study, we used plasma creatinine measurements from Danish laboratory databases to identify AKI episodes in children aged 0-17 years from 2007 to 2021. For each child, the first AKI episode per calendar year was included. We estimated the annual crude and sex- and age-standardized AKI rate as the number of children with an AKI episode divided by the total number of children as reported by census numbers. Using Danish medical databases, we assessed patient characteristics including potential risk factors for AKI, such as use of nephrotoxic medication, surgery, sepsis, and perinatal factors. RESULTS: In total, 14,200 children contributed with 16,345 AKI episodes over 15 years. The mean annual AKI rate was 148 (95% CI: 141-155) per 100,000 children. From 2007 to 2021, the annual AKI rate demonstrated minor year-to-year variability without any discernible overall trend. The highest AKI rate was recorded in 2007 at 174 (95% CI: 161-187) per 100,000 children, while the lowest rate occurred in 2012 at 129 (95% CI: 118-140) per 100,000 children. In 2021, the AKI rate was 148 (95% CI: 141-155) per 100,000 children. Characteristics of children with AKI were similar throughout the study period. CONCLUSION: The rate of AKI among Danish children was stable from 2007 to 2021 with little variation in patient characteristics over time.

Performance of the race-free CKD-EPI creatinine-based eGFR equation in a Danish cohort with measured GFR.

Background: In 2021, an updated Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimated glomerular filtration rate (eGFR) without a coefficient for race (CKD-EPI21) was developed. The performance of this new equation has yet to be examined among specific patient groups. Methods: We compared the performances of the new CKD-EPI21 equation and the 2009 equation assuming non-Black race (CKD-EPI09-NB) in patients with GFR measured by chromium-51-EDTA plasma clearance at Aarhus University Hospital in Denmark during 2010-18. We examined bias, accuracy, precision and correct classification of chronic kidney disease (CKD) stage using chromium-51-EDTA clearance as the reference standard. We assessed the performance in the total cohort, cancer patients and potential living kidney donors. We also assessed the performance stratified by CKD stage in the total cohort. Results: In this predominantly white population, the CKD-EPI21 equation performed slightly better than the CKD-EPI09-NB equation in both the total cohort (N = 4668), and in cancer patients (N = 3313) and potential living kidney donors (N = 239). In the total cohort, the CKD-EPI21 equation demonstrated a slightly lower median absolute bias (-0.2 versus -4.4 mL/min/1.73 m2), and a similar accuracy, precision and correct classification of CKD stage compared with the CKD-EPI09-NB equation. When stratified by CKD stage, the CKD-EPI09-NB equation performed slightly better than the CKD-EPI21 equation among patients with a measured GFR (mGFR) <60 mL/min/1.73 m2. Conclusions: In a selected cohort of Danish patients with mGFR, the CKD-EPI21 equation performed slightly better than the CKD-EPI09-NB equation except for patients with a mGFR <60 mL/min/1.73 m2, where CKD-EPI09-NB performed slightly better although the differences were considered clinically insignificant.

Cohort Profile: Better Health in Late Life.

Purpose: Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population. Methods: A randomly-selected sample of Danish residents who were 50-65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization. Results: Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50-65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).

Regional variation in incidence and prognosis of acute kidney injury.

BACKGROUND: Examining regional variation in acute kidney injury (AKI) and associated outcomes may reveal inequalities and possibilities for optimization of the quality of care. Using the Danish medical databases, we examined regional variation in the incidence, follow-up, and prognosis of AKI in Denmark. METHODS: Patients with one or more AKI episodes in 2017 were identified using population-based creatinine measurements covering all Danish residents. Crude and sex-and-age-standardized incidence rates of AKI were estimated using census statistics for each municipality. Adjusted hazard ratios (aHR) of chronic kidney disease (CKD), all-cause death, biochemical follow-up, and outpatient contact with a nephrology department after AKI were estimated across geographical regions and categories of municipalities, accounting for differences in demographics, comorbidities, medication use, lifestyle and social factors, and baseline kidney function. RESULTS: We identified 63 382 AKI episodes in 58 356 adults in 2017. The regional standardized AKI incidence rates ranged from 12.9 to 14.9 per 1 000 person-years. Compared with the Capital Region of Denmark, the aHRs across regions ranged from 1.04 to 1.25 for CKD, from 0.97 to 1.04 for all-cause death, from 1.09 to 1.15 for biochemical follow-up, and from 1.08 to 1.49 for outpatient contact with a nephrology department after AKI. Similar variations were found across municipality categories. CONCLUSIONS: Within the uniform Danish healthcare system, we found modest regional variation in AKI incidence. The mortality after AKI was similar; however, CKD, biochemical follow-up, and nephrology follow-up after AKI varied across regions and municipality categories.

Temporal changes in incidence of hospital-diagnosed acute pyelonephritis: A 19-year population-based Danish cohort study.

Objectives: To examine temporal changes in the incidence of hospital-diagnosed acute pyelonephritis (APN) and characterize associated demographics. Methods: Cohort study including Danish patients with hospital-diagnosed APN during 2000-2018, identified by International Classification of Diseases, 10th Revision codes. Annual sex- and age-standardized incidence rates per 10,000 person years with 95% confidence intervals (CIs) were stratified by sex, age group, diagnosis code, and region of residence. Incidence rates for selected urinary tract infections and sepsis diagnoses were also computed. Results: We included 66,937 hospital-diagnosed APN episodes in 57,162 patients. From 2000 to 2018, the incidence increased from 6.8 (95% CI: 6.8-6.8) to 15.4 (95% CI: 15.4-15.4) in women and from 2.7 (95% CI: 2.7-2.7) to 4.5 (95% CI: 4.5-4.5) in men. Among infants, the rate rose from 7.4 (95% CI: 7.4-7.4) to 64.8 (95% CI: 64.7-64.9) in girls and from 17.1 (95% CI: 17.1-17.2) to 52.5 (95% CI: 52.4-52.6) in boys. Concomitant declines were observed in incidences of hospital-diagnosed unspecified urinary tract infections and sepsis. Conclusion: The APN incidence roughly doubled during 2000-2018. The increase was largely driven by a prominently increasing incidence among young children which was not explained by the enlarging prevalence of congenital anomalies of the kidney and urinary tract.

Comorbidity, Criminality, and Costs of Patients Treated for Gambling Disorder in Denmark.

Gambling disorder is associated with increased mental comorbidity, unhealthy lifestyle, criminality, and costs-of-illness, but the available evidence is mainly based on self-reported survey data. We examined the registry-recorded mental and somatic comorbidities, medication use, criminality, and costs-of-illness associated with gambling disorder. We identified individuals diagnosed with or treated for gambling disorder in hospitals or specialized treatment centers during 2013-2017 and matched them by age and sex to general population comparisons. Using individual-level healthcare and socioeconomic registries, we characterized their history of mental and somatic comorbidities, medication use, and criminality. We estimated their cost-of-illness of welfare services (direct) and lowered productivity (indirect) using the human capital approach. We identified 1381 individuals with gambling disorder, primarily young (median age: 34 years) men (87%). Individuals with gambling disorder more frequently than their comparisons had previous hospital-recorded comorbidity [e.g., myocardial infarction (0.8% vs. 0.5%)], medication use [e.g., respiratory system drugs (35.6% vs. 28.6%)], and hospital-recorded or pharmacologically treated mental comorbidity [e.g., depression (39.8% vs. 14.9%)]. Also, sentenced criminality was much more common in individuals with gambling disorder (7.0%) than in comparisons (1.1%). The estimated attributable direct costs were €4.0 M corresponding to €2.9 K per person with gambling disorder, and attributable indirect costs were €17.6 M, corresponding to €13.2 K per person with gambling disorder in 2018. In conclusion, individuals diagnosed with or treated for gambling disorder have a high burden of mental and somatic comorbidities as well as criminality compared with the general population. This needs attention to minimize the societal and personal costs of gambling disorder.

Labor market affiliation of patients with myeloproliferative neoplasms: a population-based matched cohort study.

BACKGROUND: Patients with myeloproliferative neoplasms (MPNs) suffer from substantial symptoms and risk of debilitating complications, yet observational data on their labor market affiliation are scarce. MATERIAL AND METHODS: We conducted a descriptive cohort study using data from Danish nationwide registries, including patients diagnosed with MPN in 2010-2016. Each patient was matched with up to ten comparators without MPN on age, sex, level of education, and region of residence. We assessed pre- and post-diagnosis labor market affiliation, defined as working, unemployed, or receiving sickness benefit, disability pension, retirement pension, or other health-related benefits. Labor market affiliation was assessed weekly from two years pre-diagnosis until death, emigration, or 31 December 2018. For patients and comparators, we reported percentage point (pp) changes in labor market affiliation cross-sectionally from week -104 pre-diagnosis to week 104 post-diagnosis. RESULTS: The study included 3,342 patients with MPN and 32,737 comparators. From two years pre-diagnosis until two years post-diagnosis, a larger reduction in the proportion working was observed among patients than comparators (essential thrombocythemia: 10.2 [95% CI: 6.3-14.1] vs. 6.8 [95% CI: 5.5-8.0] pp; polycythemia vera: 9.6 [95% CI: 5.9-13.2] vs. 7.4 [95% CI: 6.2-8.7] pp; myelofibrosis: 8.1 [95% CI: 3.0-13.2] vs. 5.8 [95% CI: 4.2-7.5] pp; and unclassifiable MPN: 8.0 [95% CI: 3.0-13.0] vs. 7.4 [95% CI: 5.7-9.1] pp). Correspondingly, an increase in the proportion of patients receiving sickness benefits including other health-related benefits was evident around the time of diagnosis. CONCLUSION: Overall, we found that Danish patients with essential thrombocythemia, polycythemia vera, myelofibrosis, and unclassifiable MPN had slightly impaired labor market affiliation compared with a population of the same age and sex. From two years pre-diagnosis to two years post-diagnosis, we observed a larger reduction in the proportion of patients with MPN working and a greater proportion receiving sickness benefits compared with matched individuals.

Healthcare Costs at the End of Life for Patients with Non-cancer Diseases and Cancer in Denmark.

OBJECTIVES: To examine costs of care from a healthcare sector perspective within 1 year before death in patients with non-cancer diseases and patients with cancer. METHODS: This nationwide registry-based study identified all Danish citizens dying from major non-cancer diseases or cancer in 2010-2016. Applying the cost-of-illness method, we included costs of somatic hospitals, including hospital-based specialist palliative care, primary care, prescription medicine and hospice expressed in 2022 euros. Costs of patients with non-cancer diseases and cancer were compared using regression analyses adjusting for sex, age, comorbidity, residential region, marital/cohabitation status and income level. RESULTS: Within 1 year before death, mean total healthcare costs were €27,185 [95% confidence interval (CI) €26,970-27,401] per patient with non-cancer disease (n = 109,723) and €51,348 (95% CI €51,098-51,597) per patient with cancer (n = 108,889). The adjusted relative total healthcare costs, i.e. the ratio of the mean costs, of patients with non-cancer diseases was 0.64 (95% CI 0.63-0.66) at 12 months before death and 0.91 (95% CI 0.90-0.92) within 30 days before death compared with patients with cancer. Mean costs of hospital-based specialist palliative care and hospice in the year leading up to death were €17 (95% CI €13-20) and €90 (95% CI €77-102) per patient with non-cancer disease but €1552 (95% CI €1506-1598) and €3411 (95% CI €3342-3480) per patient with cancer. CONCLUSIONS: Within 1 year before death, total healthcare costs, mainly driven by hospital costs, were substantially lower for patients with non-cancer diseases compared with patients with cancer. Moreover, the costs of hospital-based specialist palliative care and hospice were minimal for patients with non-cancer diseases.

Utilisation of hospital-based specialist palliative care in patients with gynaecological cancer: Temporal trends, predictors and association with high-intensity end-of-life care.

OBJECTIVE: To examine hospital-based specialist palliative care (SPC) utilisation among patients with gynaecological cancer, including temporal trends, predictors and associations with high-intensity end-of-life care. METHODS: We conducted a nationwide registry-based study for all patients dying from gynaecological cancer in Denmark during 2010-2016. We estimated the proportions of patients receiving SPC by year of death and used regression analyses to examine predictors of SPC utilisation. Use of high-intensity end-of-life care according to SPC utilisation was compared by regression analyses adjusting for type of gynaecological cancer, year of death, age, comorbidities, residential region, marital/cohabitation status, income level and migrant status. RESULTS: Among 4502 patients dying from gynaecological cancer, the proportion of patients receiving SPC increased from 24.2% in 2010 to 50.7% in 2016. Young age, three or more comorbidities, residence outside the Capital Region and being immigrant/descendant were associated with increased SPC utilisation, whereas income, cancer type and stage were not. SPC was associated with lower high-intensity end-of-life care utilisation. Particularly, when compared with patients not receiving SPC, patients who accessed SPC >30 days before death had 88% lower risk of intensive care unit admissions within 30 days before death (adjusted relative risk: 0.12 (95% CI: 0.06; 0.24)) and 96% lower risk of surgery within 14 days before death (adjusted relative risk: 0.04 (95% CI: 0.01; 0.31)). CONCLUSIONS: Among patients dying from gynaecological cancer, SPC utilisation increased over time and age, comorbidities, residential region and migrant status were associated with access to SPC. Furthermore, SPC was associated with lower use of high-intensity end-of-life care.

Kidney function before and after acute kidney injury: a nationwide population-based cohort study.

Background: Acute kidney injury (AKI) is a common and serious condition defined by a rapid decline in kidney function. Data on changes in long-term kidney function following AKI are sparse and conflicting. Therefore, we examined the changes in estimated glomerular filtration rate (eGFR) from before to after AKI in a nationwide population-based setting. Methods: Using Danish laboratory databases, we identified individuals with first-time AKI defined by an acute increase in plasma creatinine (pCr) during 2010 to 2017. Individuals with three or more outpatient pCr measurements before and after AKI were included and cohorts were stratified by baseline eGFR (≥/<60 mL/min/1.73 m2). Linear regression models were used to estimate and compare individual eGFR slopes and eGFR levels before and after AKI. Results: Among individuals with a baseline eGFR ≥60 mL/min/1.73 m2 (n = 64 805), first-time AKI was associated with a median difference in eGFR level of -5.6 mL/min/1.73 m2 [interquartile range (IQR) -16.1 to 1.8] and a median difference in eGFR slope of -0.4 mL/min/1.73 m2/year (IQR -5.5 to 4.4). Correspondingly, among individuals with a baseline eGFR <60 mL/min/1.73 m2 (n = 33 267), first-time AKI was associated with a median difference in eGFR level of -2.2 mL/min/1.73 m2 (IQR -9.2 to 4.3) and a median difference in eGFR slope of 1.5 mL/min/1.73 m2/year (IQR -2.9 to 6.5). Conclusion: Among individuals with first-time AKI surviving to have repeated outpatient pCr measurements, AKI was associated with changes in eGFR level and eGFR slope for which the magnitude and direction depended on baseline eGFR.

Preadmission Opioid Use and 1-Year Mortality Following Incident Myocardial Infarction: A Danish Population-Based Cohort Study (1997-2016).

Background Opioid use has been linked to an increased risk of myocardial infarction and cardiovascular mortality, but the prognostic impact of opioid use before an incident myocardial infarction is largely unknown. Methods and Results We conducted a nationwide population-based cohort study including all patients hospitalized for an incident myocardial infarction in Denmark (1997-2016). Based on their last redeemed opioid prescription before admission, patients were categorized as current users (0-30 days), recent users (31-365 days), former users (>365 days), and nonusers. One-year all-cause mortality was calculated using the Kaplan-Meier method. Hazard ratios (HRs) were computed using Cox proportional hazards regression analyses, adjusting for age, sex, comorbidity, any preceding surgery within 6 months before the myocardial infarction admission, and medication use before the myocardial infarction admission. We identified 162 861 patients with an incident myocardial infarction. Of these, 8% were current opioid users, 10% were recent opioid users, 24% were former opioid users, and 58% were nonusers of opioids. One-year mortality was highest among current users (42.5% [95% CI, 41.7%-43.3%]) and lowest among nonusers (20.5% [95% CI, 20.2%-20.7%]). Compared with nonusers, current users had an elevated 1-year all-cause mortality risk (adjusted HR, 1.26 [95% CI, 1.22-1.30]). Following adjustment, neither recent users nor former users of opioids were at elevated risk. Conclusions Preadmission opioid use was associated with an increased 1-year all-cause mortality risk following an incident myocardial infarction. Opioid users thus represent a high-risk subgroup of patients with myocardial infarction.

Twenty-Three-Year Trends in the Use of Potentially Nephrotoxic Drugs in Denmark.

Background: The occurrence of acute and chronic kidney diseases has been rising in the last decades. Although drug use is a common risk factor for impaired kidney function, changes in utilization of potential nephrotoxic drugs have received little attention. Purpose: To describe temporal trends in the utilization of potentially nephrotoxic drugs in Denmark between 1999 and 2021. Methods: Specific drugs known or suspected to be nephrotoxic were identified in the literature. Data on the sold defined daily doses (DDDs) of potentially nephrotoxic drugs between 1999 and 2021 were retrieved using the Danish Register of Medical Product Statistics. Trends in sales of DDDs per 1000 inhabitants per day were tabulated and illustrated graphically. Results: From 1999 to 2021, the total sale of all selected drugs increased from 286 to 457 DDDs per 1000 inhabitants per day. The overall sale reached a preliminary peak in 2012 with 449 DDDs per 1000 inhabitants per day and remained relatively stable thereafter until reaching an all-time high in 2021 with 457 DDDs per 1000 inhabitants per day. Contributing with the majority in volume, sales of drugs inhibiting the renin-angiotensin-aldosterone system (RAAS) increased dramatically throughout the period. The same was observed for acetaminophen, methotrexate, tacrolimus, and iodinated contrast dye. In contrast, the sales of diuretics, acetylsalicylic acid, and ciclosporin decreased during the last decade of the study period. Conclusion: From 1999-2021 considerable changes in sales of potentially nephrotoxic drugs were observed. In general, the sales increased, in volume predominated by RAAS inhibiting drugs. This increase in sales of potential nephrotoxins could contribute to an increasing occurrence of kidney diseases.

Twenty-four-Year Trends in Incidence and Mortality of Nephrotic Syndrome: A Population-Based Cohort Study.

BACKGROUND: With the increasing prevalence of risk factors for nephrotic syndrome, updated epidemiologic data on the syndrome are needed. We examined its age- and sex-specific incidence, histopathology, and mortality over 24 years. METHODS: This nationwide cohort study included all adults with first-time-recorded nephrotic syndrome in Denmark during 1995-2018 using the Danish National Patient Registry. We obtained data on age, sex, hospital-diagnosed comorbidities, and histopathologic findings. We computed overall, and age- and sex-specific, incidence rates of nephrotic syndrome, 1- and 5-year mortality by calendar period, and 1-year hazard ratios (HRs) of death using Cox models. RESULTS: We identified 3,970 adults with first-time nephrotic syndrome diagnosis. Incidence was highest in men and increased with age to 11.77 per 100,000 person-years (95% confidence interval [CI]: 10.21-13.32) in men aged 80+ years, and 6.56 per 100,000 person-years (95% CI: 5.71-7.41) in women aged 80+ years. Incidence of nephrotic syndrome increased from 3.35 per 100,000 person-years (95% CI: 3.12-3.58) in 1995-2000 to 4.30 per 100,000 person-years (95% CI: 4.05-4.54) in 2013-2018. Over time, 1-year mortality of nephrotic syndrome was stable at 13%-16%, but HR of death was 0.54 (95% CI: 0.42-0.69), adjusted for age, sex, and comorbidities, in 2013-2018 compared with 1995-2000. Subdistribution of glomerulopathies was stable over time with membranous nephropathy and minimal change disease being the most common. CONCLUSION: During 1995-2018, the incidence of recorded adult nephrotic syndrome increased slightly, and the adjusted mortality of nephrotic syndrome decreased markedly. Whether these findings reflect changes in epidemiology or awareness and coding of nephrotic syndrome, remains to be clarified.

Increased Cancer Risk in Patients with Kidney Disease and Venous Thromboembolism: A Population-Based Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) may be a harbinger of cancer in the general population. Patients with kidney disease have an a priori increased VTE risk. However, it remains unknown how a VTE affects subsequent cancer risk in these patients. OBJECTIVES: To examine the cancer risk in patients with kidney disease following a VTE. METHODS: We conducted a nationwide population-based cohort study in Denmark (1996-2017), including all VTE patients with a diagnosis of kidney disease. We calculated absolute risks of cancer (accounting for competing risk of death) and age-, sex-, and calendar-period standardized incidence ratios (SIRs) comparing the observed cancer incidence with national cancer incidence rates and cancer incidence rates of VTE patients without kidney disease. RESULTS: We followed 3,362 VTE patients with kidney disease (45.9% females) for a median follow-up time of 2.4 years (interquartile range: 0.6-5.4). During follow-up, 464 patients were diagnosed with cancer, of whom 169 (36.4%) were diagnosed within the first year. The 1-year absolute risk of any cancer was 5.0% (95% confidence interval [CI]: 4.3-5.8), with a SIR of 2.9 (95% CI: 2.5-3.4) when compared with the general population, and 2.0 (95% CI: 1.8-2.4) when compared with VTE patients without kidney disease. During subsequent years of follow-up, the SIRs declined to 1.5 (95% CI: 1.3-1.6) when compared with the general population, and 1.1 (95% CI: 0.9-1.2) compared with VTE patients without kidney disease. CONCLUSION: Patients with hospital-diagnosed kidney disease have increased cancer risk after VTE, especially within the first year following the VTE diagnosis.

Routine Clinical Care Creatinine Data in Denmark - An Epidemiological Resource for Nationwide Population-Based Studies of Kidney Disease.

Purpose: Creatinine data are key in identifying acute and chronic kidney disease. In Denmark, routine clinical care creatinine data have been collected regionally in the Clinical Laboratory Information System Research Database (LABKA) since the 1990s and nationwide in the Register of Laboratory Results for Research (RLRR) since 2013. Here we describe the geographical coverage of the databases and characteristics of Danish individuals with creatinine tests. This information is pivotal for the design and interpretation of studies using these data to examine kidney disease epidemiology. Patients and Methods: We included all creatinine tests in LABKA and RLRR from 1990 through 2018. The daily number of creatinine tests by municipality and region of residence were plotted and geographical coverage was ascertained. In addition, we characterized a contemporary cohort of creatinine-tested individuals in 2016-2018. Results: During 1990-2018, 61,011,941 creatinine tests were available for 4,647,966 unique Danish residents. The North Denmark Region was the first region to achieve complete reporting in November 2004, and nationwide reporting was complete starting in October 2015. In each year from 2016 to 2018, more than a third of Danish residents had a recorded creatinine measurement, with the highest proportion of tested individuals aged 77-87 years and the lowest proportion aged 3-5 years. During 2016-2018, the creatinine-tested cohort had a median age of 53 years (IQR, 35-67 years) and included 54.3% women. The most common comorbidity was a hospital-based diagnosis of hypertension (12.0%), and the most common prescription drug was angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (15.8%). Conclusion: In combination, the population-based LABKA and RLRR databases provide regional creatinine data with long follow-up and nationwide data for the Danish population. There was considerable variation in the time of complete geographical coverage by region, which needs to be considered when using these data for studies on kidney disease epidemiology.