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Background: Clinical guidelines recommend monitoring of creatinine and lithium throughout treatment with lithium. We here assessed the extent to which this occurs in healthcare in Sweden. Methods: This is an observational study of all adults with bipolar disorder starting lithium therapy in Stockholm, Sweden, during 2007–2018. The main outcome was monitoring of blood lithium and creatinine at therapy initiation and/or once annually. The secondary outcome was monitoring of calcium and thyroid-stimulating hormone (TSH). Patients were followed up until therapy cessation, death, out-migration, or to the end of 2018. Results: We identified 4428 adults with bipolar disorder who started lithium therapy and were followed up for up to 11 years. Their median age was 39 years, and 63% were women. The median duration on lithium therapy was 4.3 (IQR: 1.9–7.45) years, and the majority who discontinued therapy started another mood stabilizer soon after. Overall, 21% started lithium therapy without assessing the serum/plasma concentration of creatinine. The proportion of people who did not have both lithium and creatinine measured increased from 21% in the first year to 33% in the eleventh year. The proportion with annual testing for TSH or calcium was slightly lower. As few as 16% of patients had both lithium and creatinine tested once annually during their complete time on lithium. Conclusions: In a Swedish community sample, lithium and creatinine monitoring was inconsistent with guideline recommendations that call for measurement of annual biomarker levels.

Fractures are common in dialysis patients, but little is known about the trajectory of incidence rates of different types of fractures before and after dialysis initiation. To address this, we investigated the incidence of major fractures before and after dialysis initiation. We performed a retrospective statistical analysis using the Swedish Renal Registry of 9041 incident dialysis patients (median age 67 years, 67% men) starting dialysis 2005 through 2015 to identify major fractures (hip, spine, humerus, and forearm) occurring during the dialysis transition period from 1 year before until 1 year after dialysis initiation. Using flexible parametric hazard models and the Fine‐Gray model, we estimated adjusted fracture incidence rates and predictors of major fractures. We identified 361 cases with primary diagnosis of major fracture, of which 196 (54%) were hip fractures. The crude incidence rate of major fractures before dialysis initiation was 17 per 1000 patient‐years (n = 157) and after dialysis initiation it was 24 per 1000 patient‐years (n = 204). The adjusted incidence rate of major fractures began to increase 6 months before dialysis initiation, and then stabilized at a higher rate after 1 year. The adjusted incidence rate of hip fractures started to increase sharply 3 months before dialysis initiation, peaked at initiation, and declined thereafter. In contrast, the adjusted incidence rate of non‐hip fractures was stable during the transition period and gradually increased over time. Higher age, female sex, and history of previous major fractures were associated with increased fracture incidence both before and after dialysis initiation. We conclude that the incidence of major fractures, especially hip fractures, start to rise 6 months before initiation of dialysis therapy, indicating that heightened surveillance with implementation of preventive measures to avoid fractures is warranted during the transition period to dialysis. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

BACKGROUND AND AIMS Lithium is an established treatment for bipolar disorder and treatment-resistant depression. Despite awareness of potential kidney damage, there is a lack of research evidence to inform on the existence and magnitude of the risk. Observational studies to date show conflicting findings, possibly explained by inadequate control populations, prevalent user bias and a lack of information on kidney function or serum lithium levels. METHOD We conducted a cohort study to compare kidney outcomes in adults who started lithium or valproate therapy in Stockholm, Sweden, during 2007–18. Within lithium users, we also compared outcomes by average serum lithium concentrations during the first year of therapy. Kidney outcomes were CKD progression (composite of >30% eGFR decline and kidney failure) and AKI (by diagnosis or KDIGO transient creatinine elevations). Propensity score weighted Cox regression was used to estimate hazard ratios with [95% confidence intervals (95% CI)] and balance 46 identified confounders. Complete collection of repeated dispensations at Swedish pharmacies allowed modelling of the time-dependent risk associated with cumulative lithium exposure. Sensitivity analyses included restricting to patients with a diagnosis of bipolar disorder, apply a 1-year lag, use of alternative weighting methods and evaluation of eGFR monitoring rates to ascertain surveillance bias between groups. RESULTS We included 16 645 individuals, of whom 5308 initiated lithium and 5638 valproate therapy. Their median age was 45 years (57% women) and median eGFR was 99 mL/min/1.73 m2. A total of 179 CKD progression events and 234 AKI were identified during a median of follow-up of 4.3 and 4.2 years, respectively. After propensity score weighting, the adjusted hazard ratio for the risk of CKD progression was 1.12 (95% CI 0.86–1.47) and for AKI 0.88 (95% CI 0.7–1.09). There was a weak, non-statistically significant association between cumulative exposure to lithium and the risk of CKD progression that was not observed for cumulative use of valproate. Results were consistent among patients with a bipolar disorder diagnosis and robust to 1-year lag or alternative weighing methods. A total of 3913 lithium users were on therapy for at least one year and underwent routine serum lithium monitoring. Compared with patients with average serum lithium levels CONCLUSION In this analysis of patients from routine clinical practice, the risk of kidney outcomes associated with lithium therapy did not differ from that of valproate. Modest risk magnitudes need to be offset with the effectiveness and anti-suicidal benefits of lithium. However, elevated serum lithium levels strongly predicting kidney risk, emphasizing the need for close monitoring and lithium dose-adjustment.

Introduction People undergoing maintenance dialysis are at high risk for fractures, but less is known about fracture incidence and associated outcomes in earlier stages of chronic kidney disease (CKD). Methods We conducted an observational analysis from the Stockholm Creatinine Measurement project, a Swedish health care utilization cohort during 2006–11. We identified all adults with confirmed CKD Stages 3–5 and no documented history of fractures and extracted information on comorbid history, ongoing medication, cardiovascular events and death. We studied incidence rates of fractures (overall and by location), with the estimated glomerular filtration rate (eGFR) as time-dependent exposure. We then studied hazard ratios [HRs and 95% confidence intervals (CIs)] for the events of death and major adverse cardiac events (MACE) using Cox regression with fracture as time-varying exposure. Results We identified 68 764 individuals with confirmed CKD (mean age 79 years, 56% women). During a median follow-up of 2.7 years, 9219 fractures occurred, of which 3105 were hip fractures. A more severe CKD stage was associated with a higher risk of fractures, particularly hip fractures: compared with CKD Stage 3a, the adjusted HR was 1.10 (95% CI 1.02–1.19), 1.32 (1.17–1.49) and 2.47 (1.94–3.15) for CKD Stage 3b, 4 and 5, respectively. Spline curves suggested a linear association with fracture risk with an eGFR Conclusion Our findings highlight the commonness of fractures and the increased risk for subsequent adverse outcomes in CKD patients. These results may inform clinical decisions regarding post-fracture clinical surveillance and fracture prevention strategies.

Background and Aims Major osteoporotic fractures (MOF) are common in dialysis patients. We investigated incidence, predictors and clinical outcomes associated with first MOF occurring after initiation of dialysis (MOFfirst). Method In Swedish Renal Registry of 9714 incident (2005 -2016) dialysis patients (median age 68 years, 67% men), we identified all MOFfirst in hip, spine, humerus and forearm. Using flexible parametric hazard models and Fine-Gray analysis, we estimated incidence, mortality rates and predictors of MOFfirst, and, in time-dependent analysis, risk of all-cause and cardiovascular disease (CVD) mortality following MOFfirst. Results During median follow-up of 2.2 years, the crude incidence rate of MOFfirst (n=835) was 24/1000 patient-years (pt-yrs) and that of hip fractures (n=470) 13/1000 pt-yrs. The multivariate-adjusted fracture incidence rates increased gradually after dialysis initiation and were 47% higher among women. Female sex, higher age, presence of comorbidities, and previous history of MOF (MOFprevious) were associated with increased risk for MOFfirst, whereas peritoneal dialysis as compared to hemodialysis was associated with decreased fracture risk. The adjusted fracture incidence rate of MOFfirst during the first 90 days following dialysis initiation was higher in patients with MOFprevious than in those without MOFprevious. MOFfirst independently predicted increased all-cause mortality (sub-distribution hazard ratio, sHR, 1.67(95%CI 1.47-1.91) and CVD-related mortality (sHR 1.49 (95%CI 1.22-1.84). Adjusted mortality rate following hip fractures was higher than for other types of MOF. Spline curves showed that mortality following MOFfirst was highest during the first 6 months of follow-up. Conclusion Major osteoporotic fractures are common and associated with increased mortality in incident dialysis patients.

Background and Aims Major osteoporotic fractures (MOF) are associated with increased morbidity and mortality in ESRD patients. We investigated incidence, predictors and clinical outcomes associated with first MOF (MOFfirst) following kidney transplantation (KT). Method In Swedish Renal Registry of 3992 first KT recipients (2005 -2016) (age 53 years, 65% men), we identified all MOFfirst in hip, spine, humerus and forearm following KT. We estimated incidence rates and predictors of MOFfirst using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death, and risk of all-cause mortality following MOFfirst using Cox proportional hazards models with fracture as time-varying exposure. Results During median follow-up of 4.8 years (IQR 2.2-7.9 years), there were 279 fractures of which 139 were forearm fractures. The crude incidence rate of MOFfirst (n=279) was 14/1000 patient-years and that of hip fractures (n=69) 3/1000 patient-years. The multivariate-adjusted fracture incidence rates were highest during the first 6 months following KT, and two-fold increased among women. High age, female sex, previous history of MOF, diabetes nephropathy, pretransplant dialysis therapy and acute rejection were associated with increased risk for MOFfirst, whereas pre-emptive KT was associated with lower risk of MOFfirst. Spline curves showed that impact of age in women on MOFfirst was markedly higher than in men. MOFfirst (including all cases) independently predicted increased all-cause mortality (hazard ratio, HR, 1.78(95%CI 1.35-2.36)). Among MOFfirst, hip fracture (HR, 4.68(95%CI 1.56-14.06)) and spine fracture (HR, 4.02(95%CI 1.19-13.54)) were significantly associated with increased all-cause mortality. Conclusion The initial six months following kidney transplantation is a high-risk period for major osteoporotic fractures, especially forearm fractures. MOFs, especially hip and spine fracture, are associated with increased mortality.

Background and Aims The incidence of fractures is markedly higher in dialysis patients than in pre-dialysis patients, but it is not clear to what extent the initiation of dialysis as such is associated with accelerated fracture incidence or if fracture rates are already increasing prior to dialysis start among incident dialysis patients. Here we investigated the temporal pattern of occurrence of a first major osteoporotic fracture (MOF) among incident dialysis patients in the pre-dialysis period and in the period following dialysis initiation. Method We analyzed data from Swedish Renal Registry (SRR) and identified 9041 incident dialysis patients (2005 -2015; age 67 years, 67% men). We identified all first MOF (MOFfirst) in hip, spine, humerus and forearm during 12 months before and after dialysis initiation. Using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death and renal transplantation, we estimated adjusted fracture incidence rates and predictors of MOFfirst. Results During the whole follow-up period, there were 361 fractures including 196 hip fractures. The crude incidence rate of MOFfirst (n=157) before dialysis initiation was 17/1000 patient-years and after initiation of dialysis the incidence rate of MOFfirst increased to 24/1000 patient-years. Overall the adjusted MOFfirst incidence rates increased from 6 months before initiation of dialysis, fluctuated, and stabilized at a higher rate than that of the baseline rate after 12 months. The adjusted hip fracture rate rose steeply 3 months before dialysis initiation, declined 3 months after dialysis initiation, fluctuated, and then became stabilized. On the contrary, the adjusted incidence rates of other fractures, i.e., non-hip fractures, appeared to be stable all the time, before as well as after initiation of dialysis. Female gender, higher age and previous history of MOF had a negative impact on fracture incidence rates before and after dialysis initiation. Conclusion We conclude that the incidence of MOFfirst is increasing already from 6 months prior to dialysis initiation among incident dialysis patients, and that there is a further increase following dialysis initiation. For hip fracture, which was the most common MOF, the temporal pattern of incidence rates was compressed to a high risk period lasting from 3 months before to 3 months after dialysis initiation, underlining the need of increased attention to prevent hip fractures in incident dialysis patients during this critical period.

Background Major fractures (MF) are associated with increased mortality in the general population and represent an even higher risk in patients with chronic kidney disease. We investigated incidence, predictors and clinical outcomes associated with first MF (MFfirst) following kidney transplantation (KT). Methods We used the Swedish National Renal Registry of 3992 first KT recipients (2005–2016) (median age 53 years, 65% men) and identified all MFfirst in hip, spine, humerus and forearm following KT. We estimated incidence rates and predictors of MFfirst using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death, and risk of all-cause mortality following MFfirst using Cox proportional hazards models with fracture as time-varying exposure. Results During median follow-up of 4.8 years (IQR 2.2–7.9 years), there were 279 fractures of which 139 were forearm fractures. The crude incidence rate of MFfirst (n = 279) was 13.5/1000 patient-years and that of hip fractures (n = 69) 3.4/1000 patient-years. The multivariate-adjusted fracture incidence rates were highest during the first 6 months following KT, and 86% higher in women than in men. High age, female sex, previous history of MF, diabetes nephropathy, pretransplant dialysis therapy and acute rejection were associated with increased risk for MFfirst, whereas pre-emptive KT was associated with lower risk of MFfirst. Spline curves showed markedly higher impact of higher age on risk of MFfirst in women than in men. MFfirst (n = 279) independently predicted increased all-cause mortality risk (hazard ratio, HR, 1.78(95%CI 1.35–2.36)). Among MFfirst, with humerus fracture as reference, hip fracture (HR, 4.68(95%CI 1.56–14.06)) and spine fracture (HR, 4.02(95%CI 1.19–13.54)), but not forearm fracture (HR, 1.17 (95%CI 0.38–3.53)), were associated with increased all-cause mortality risk. Conclusions The initial 6 months following kidney transplantation is a high-risk period for MF. Among MF, hip fracture and spine fracture associate with substantially increased all-cause mortality risk.

AIM To evaluate possible associations between estimated glomerular filtration rate (eGFR) and hypoglycaemia in adults with diabetes. METHODS We conducted an observational study in adults with diabetes from the Stockholm Creatinine Measurement (SCREAM) project, a Swedish healthcare utilization cohort during 2007 to 2011. We evaluated diagnoses and outpatient glucose tests for incidence rate ratios (IRRs) of hypoglycaemia (overall and by severity) in outpatient care by eGFR strata using zero-inflated negative binomial regression. We identified clinical predictors through ordinal logistic regression and assessed 7-day and 30-day mortality from hypoglycaemia in relation to eGFR with Cox proportional hazard models. RESULTS We identified 29 434 people with diabetes (13% with type 1 diabetes). Their mean age was 66 years, 43% were women and the median eGFR was 80 mL/min/1.73 m2 . During 2 years of follow-up, 1812 patients (6.2%) had hypoglycaemia registered at least once. The risk of hypoglycaemia increased linearly with lower eGFR, with an IRR of 1.2 (95% confidence interval [CI] 1.0-1.4) for eGFR 60-89 mL/min/1.73 m2 and 5.8 (95% CI 3.8-9.0) for eGFR

Background Declining trends of hip fracture incidence in dialysis patients were reported from USA and Japan while studies from Europe are lacking. We investigated trends in hip fracture incidence and subsequent mortality in Swedish dialysis patients, comparing with the Swedish general population. Methods We used the population-based Swedish national database of fractures and the Swedish National Renal Registry to retrieve data on hip fractures incidence and subsequent mortality for years 2007–2016. Trends for age-standardized hip fracture incidence rate (ASRhip fracture) and age-standardized 30-day (ASMR30day) and 180-day (ASMR180day) post-hip fracture mortality rate in Swedish general population were evaluated by joinpoint regression analysis. Standardized incidence ratios of hip fracture (SIR) and standardized mortality ratios (SMR) were calculated for Swedish dialysis patients. Results In the general population, ASRhip fracture declined significantly: in women from 2007 and in men from 2009. In dialysis patients, SIR was 3–5 times higher compared to the general population and declined over time in women but not in men. In general population, mortality (ASMR30day and ASMR180day) declined significantly in women and men. In dialysis patients, post-fracture mortality (SMR, mainly for 180-day mortality) remained two-fold higher than in general population with no consistent trend towards improvement. Conclusions Hip fracture incidence and subsequent mortality fell among women and men in the Swedish general population. In dialysis patients, hip fracture incidence declined in women but not in men while post-fracture mortality did not improve, and the incidence and subsequent mortality remained 3 to 5-fold and 2-fold higher than in the general population.

Item does not contain fulltext BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0.83 (95% CI 0.74-0.94), decreasing to 0.78 (0.66-0.92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction

IntroductionReduced kidney function increases the risk of death, but there is limited information on causes of death across stages of chronic kidney disease (CKD). We aimed to identify leading causes of death in community-dwelling individuals with differing kidney function.MethodsObservational analysis from SCREAM, a healthcare utilization cohort of Stockholm, Sweden. We included all individuals who died during 2006-2012 and had one serum creatinine measured in the year prior to death. Using the CKD-EPI formula, we calculated eGFR and stratified individuals according to CKD stages. Causes of death were classified as cardiovascular (CVD), cancer, infection and other, using ICD-10 codes. We compared age- and sex-adjusted differences in the proportions of deaths from each cause.ResultsOut of 89,117 registered deaths, 70,547 (79%) had a recent eGFR estimation and were included in this study. Individuals had a median age of 82 (IRE 62-93) years and 52% were women. The proportions of deaths from CVD increased with lower eGFR, along with the proportion of deaths from infections. Deaths due to diabetes and genito-urinary diseases increased. Deaths due to cancer decreased, but other death causes did not vary. Within CVD causes of death, the proportion of arrhythmias and heart failure increased, but ischemic heart disease and cerebrovascular disease remained stable.ConclusionIn a region-representative Swedish healthcare extraction, we observe differences regarding specific causes of death across different CKD stages. Increasing patient and provider awareness of this differential pattern of risk may have benefits for patient management, prevention strategies, and health service planning.

Background We here describe the construction of the Stockholm CREAtinine Measurement (SCREAM) cohort and assess its coverage/representativeness of the Stockholm county in Sweden. SCREAM has the principal aims to estimate the burden and consequences of chronic kidney disease (CKD) and to identify inappropriate drug use (prescription of nephrotoxic, contraindicated or ill-dosed drugs). Methods SCREAM is a repository of laboratory data of individuals, residing or accessing healthcare in the region of Stockholm, who underwent creatinine assessments between 2006-11. Laboratory tests were linked to administrative databases with complete information on socioeconomic status, demographic data, healthcare utilization, diagnoses, vital status and dispensed prescription medicines. Results SCREAM identified 1 118 507 adult Stockholm citizens with available creatinine tests between 2006-11. This corresponded to 66% of the complete population in the region. Geographical coverage was uniform, ranging between 62 and 72% throughout its 26 municipalities. Population coverage was higher across older age strata (50% coverage for age range 18-44 years, >75% for 45-64 years and >90% coverage for ≥65 years). Of note, 97 and 98% of all individuals with a diagnosis of diabetes mellitus or cardiovascular disease, respectively, were captured by SCREAM. Further, 89% of all deaths registered in the period occurred in individuals with a creatinine test undertaken. Conclusion SCREAM represents the largest cohort to estimate the burden and healthcare implications of CKD in Sweden. The coverage and representativeness of the region of Stockholm was high and in accordance to both the commonness of creatinine assessment, and the medical indications for creatinine testing. The inclusion of individuals who sought medical care and had a creatinine test undertaken resulted in a slight over-representation of elderly and comorbid patients.