High-sensitivity cardiac troponin and the diagnosis of myocardial infarction in patients with kidney impairment.

The benefit and utility of high-sensitivity cardiac troponin (hs-cTn) in the diagnosis of myocardial infarction in patients with kidney impairment is unclear. Here, we describe implementation of hs-cTnI testing on the diagnosis, management, and outcomes of myocardial infarction in patients with and without kidney impairment. Consecutive patients with suspected acute coronary syndrome enrolled in a stepped-wedge, cluster-randomized controlled trial were included in this pre-specified secondary analysis. Kidney impairment was defined as an eGFR under 60mL/min/1.73m2. The index diagnosis and primary outcome of type 1 and type 4b myocardial infarction or cardiovascular death at one year were compared in patients with and without kidney impairment following implementation of hs-cTnI assay with 99th centile sex-specific diagnostic thresholds. Serum creatinine concentrations were available in 46,927 patients (mean age 61 years; 47% women), of whom 9,080 (19%) had kidney impairment. hs-cTnIs were over 99th centile in 46% and 16% of patients with and without kidney impairment. Implementation increased the diagnosis of type 1 infarction from 12.4% to 17.8%, and from 7.5% to 9.4% in patients with and without kidney impairment (both significant). Patients with kidney impairment and type 1 myocardial infarction were less likely to undergo coronary revascularization (26% versus 53%) or receive dual anti-platelets (40% versus 68%) than those without kidney impairment, and this did not change post-implementation. In patients with hs-cTnI above the 99th centile, the primary outcome occurred twice as often in those with kidney impairment compared to those without (24% versus 12%, hazard ratio 1.53, 95% confidence interval 1.31 to 1.78). Thus, hs-cTnI testing increased the identification of myocardial injury and infarction but failed to address disparities in management and outcomes between those with and without kidney impairment.

Long-term all-cause mortality and cardiovascular outcomes in Scottish children after initiation of renal replacement therapy: a national cohort study.

BACKGROUND: Data on long-term outcomes in children who have received renal replacement therapy (RRT) for end-stage renal disease are limited. METHODS: We studied long-term survival and incidence of fatal and nonfatal cardiovascular disease (CVD) events and determinants of these outcomes in children who initiated RRT between 1961 and 2013 using data from the Scottish Renal Registry (SRR). Linkage to morbidity records was available from 1981. RESULTS: A total of 477 children of whom 55% were boys, almost 50% had congenital urinary tract disease (CAKUT), 10% received a transplant as the first mode of RRT and almost 60% were over 11 years of age at start of RRT were followed for a median of 17.8 years (interquartile range (IQR) 8.7-26.6 years). Survival was 87.3% (95% confidence interval (CI) 84.0-90.1) at 10 years and 77.6% (95% CI 73.3-81.7) at 20 years. During a median follow-up of 14.96 years (IQR 7.1-22.9), 20.9% of the 381 patients with morbidity data available had an incident of CVD event. Age < 2 years at start of RRT, receiving dialysis rather than a kidney transplant and primary renal disease (PRD) other than CAKUT or glomerulonephritis (GN), were associated with a higher risk of all-cause mortality. Male sex, receiving dialysis rather than a kidney transplant and PRD other than CAKUT or GN, was associated with a higher risk of CVD incidence. CONCLUSIONS: Mortality and CVD incidence among children receiving RRT are high. PRD and RRT modality were associated with increased risk of both all-cause mortality and CVD incidence.

High-Sensitivity Cardiac Troponin and the Risk Stratification of Patients With Renal Impairment Presenting With Suspected Acute Coronary Syndrome.

BACKGROUND: High-sensitivity cardiac troponin testing may improve the risk stratification and diagnosis of myocardial infarction, but concentrations can be challenging to interpret in patients with renal impairment, and the effectiveness of testing in this group is uncertain. METHODS: In a prospective multicenter study of consecutive patients with suspected acute coronary syndrome, we evaluated the performance of high-sensitivity cardiac troponin I in those with and without renal impairment (estimated glomerular filtration rate <60mL/min/1.73m2). The negative predictive value and sensitivity of troponin concentrations below the risk stratification threshold (5 ng/L) at presentation were reported for a primary outcome of index type 1 myocardial infarction, or type 1 myocardial infarction or cardiac death at 30 days. The positive predictive value and specificity at the 99th centile diagnostic threshold (16 ng/L in women, 34 ng/L in men) was determined for index type 1 myocardial infarction. Subsequent type 1 myocardial infarction and cardiac death were reported at 1 year. RESULTS: Of 4726 patients identified, 904 (19%) had renal impairment. Troponin concentrations <5 ng/L at presentation identified 17% of patients with renal impairment as low risk for the primary outcome (negative predictive value, 98.4%; 95% confidence interval [CI], 96.0%-99.7%; sensitivity 98.9%; 95%CI, 97.5%-99.9%), in comparison with 56% without renal impairment (P<0.001) with similar performance (negative predictive value, 99.7%; 95% CI, 99.4%-99.9%; sensitivity 98.4%; 95% CI, 97.2%-99.4%). The positive predictive value and specificity at the 99th centile were lower in patients with renal impairment at 50.0% (95% CI, 45.2%-54.8%) and 70.9% (95% CI, 67.5%-74.2%), respectively, in comparison with 62.4% (95% CI, 58.8%-65.9%) and 92.1% (95% CI, 91.2%-93.0%) in those without. At 1 year, patients with troponin concentrations >99th centile and renal impairment were at greater risk of subsequent myocardial infarction or cardiac death than those with normal renal function (24% versus 10%; adjusted hazard ratio, 2.19; 95% CI, 1.54-3.11). CONCLUSIONS: In suspected acute coronary syndrome, high-sensitivity cardiac troponin identified fewer patients with renal impairment as low risk and more as high risk, but with lower specificity for type 1 myocardial infarction. Irrespective of diagnosis, patients with renal impairment and elevated cardiac troponin concentrations had a 2-fold greater risk of a major cardiac event than those with normal renal function, and should be considered for further investigation and treatment. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Measuring the Association Between Body Mass Index and All-Cause Mortality in the Presence of Missing Data: Analyses From the Scottish National Diabetes Register.

Incorrectly handling missing data can lead to imprecise and biased estimates. We describe the effect of applying different approaches to handling missing data in an analysis of the association between body mass index and all-cause mortality among people with type 2 diabetes. We used data from the Scottish diabetes register that were linked to hospital admissions data and death registrations. The analysis was based on people diagnosed with type 2 diabetes between 2004 and 2011, with follow-up until May 31, 2014. The association between body mass index and mortality was investigated using Cox proportional hazards models. Findings were compared using 4 different missing-data methods: complete-case analysis, 2 multiple-imputation models, and nearest-neighbor imputation. There were 124,451 cases of type 2 diabetes, among which there were 17,085 deaths during 787,275 person-years of follow-up. Patients with missing data (24.8%) had higher mortality than those without missing data (adjusted hazard ratio = 1.36, 95% confidence interval: 1.31, 1.41). A U-shaped relationship between body mass index and mortality was observed, with the lowest hazard ratios occurring among moderately obese people, regardless of the chosen approach for handling missing data. Missing data may affect absolute and relative risk estimates differently and should be considered in analyses of routinely collected data.

Illness Perceptions in Patients on Predialysis Care: Associations With Time Until Start of Dialysis and Decline of Kidney Function.

OBJECTIVES: Illness perceptions in patients with end-stage renal disease are associated with nonadherence and increased mortality. However, no data are available regarding the relationship between illness perceptions and accelerated disease progression in predialysis patients. METHODS: A total of 416 incident predialysis patients participating in a prospective cohort (PREPARE-2, Predialysis Patient Record-2) completed the Revised Illness Perception Questionnaire at the start of specialized predialysis care. The association between illness perceptions and time until start of dialysis was investigated using Cox regression models. Linear mixed modeling was used to test associations between illness perceptions and change of kidney function during predialysis care. Adjustments were made for sociodemographic, clinical, and biochemical factors. RESULTS: Five illness perceptions were associated with disease progression. Dialysis started earlier and kidney function declined faster (ml/min per 1.73 m/y) in patients who perceived their kidney disease as being cyclical in nature (adjusted hazard ratio [HRadj] = 1.32 [95% confidence interval {CI} = 1.11-1.56]; adjusted additional change = -0.64 [95% CI = -1.16 to -0.13]), having many negative consequences (HRadj = 1.47 [95% CI = 1.18-1.85]; adjusted additional change = -0.67 [-1.30 to -0.04]) and causing negative feelings (HRadj = 1.21 [95% CI = 1.03-1.42]; adjusted additional change = -0.65 [95% CI = -1.13 to -0.16]). In addition, kidney function declined faster in patients who perceived that their kidney disease cannot be personally controlled (adjusted additional change = -0.69 [95% CI = -1.31 to -0.09]) and who perceived that they did not fully understand their kidney disease (adjusted additional change = -0.53 [-1.05 to -0.01]). CONCLUSIONS: Stronger negative perceptions of illness at the start of predialysis care are a marker for accelerated disease progression. Detecting illness perceptions in predialysis patients may provide opportunities to intervene and slow down disease progression.

The nutritional status of patients starting specialized predialysis care.

OBJECTIVE: To examine the prevalence of and risk factors for malnutrition at the start of specialized predialysis care. DESIGN: The present analysis was performed on cross-sectional data collected at inclusion in the study. The study included 25 outpatient clinics delivering specialized predialysis care in the Netherlands. SUBJECTS: Three hundred seventy-six incident patients with advanced chronic kidney disease attending one of the participating outpatient clinics. MAIN OUTCOME MEASURE: Subjective global assessment (SGA) of nutritional status. RESULTS: At the start of specialized predialysis care, 11% of patients suffer from moderate protein-energy wasting as measured by SGA. Independent risk factors are age >75 years (Odds ratio [OR], 3.88 [1.74-8.66]), female gender (OR, 2.95 [1.37-6.32]), and having a body mass index <25 kg/m(2) (OR, 2.56 [1.19-5.49]). Estimated glomerular filtration rate was not significantly associated with SGA (OR, 1.63 [0.76-3.48]). CONCLUSIONS: Eleven percent of patients started on specialized predialysis care suffer from moderate protein-energy wasting; risk factors are age >75 years, female gender, and BMI <25 kg/m(2).

Haemoglobin levels and health-related quality of life in young and elderly patients on specialized predialysis care.

BACKGROUND: In predialysis patients, the optimal treatment choices for controlling haemoglobin (Hb) are unknown, because targeting high Hb levels has negative effects--poorer survival--but possible positive effects as well--better health-related quality of life (HRQOL). Moreover, these effects may be different in specific subgroups (e.g. young versus elderly). METHODS: In the PREPARE-2 follow-up study, incident predialysis patients were included (2004-2011) when referred to 1 of the 25 participating Dutch outpatient clinics. HRQOL was assessed at 6-month intervals with the short form-36 (SF-36) questionnaire [physical/mental summary measure and eight subscales (range 0-100)]. A linear mixed model was used to associate Hb [<11, ≥ 11 to <12 (reference), ≥ 12 to <13 and ≥ 13 g/dL] with HRQOL, stratified by prescription of anaemia medication (erythropoietin-stimulating agent (ESA)/iron) and age (young: <65 years and elderly: ≥ 65 years). RESULTS: Only elderly patients (n = 214) not prescribed ESA/iron and with a high Hb (≥ 13 versus ≥ 11 to <12 g/dL) had a statistically significant (P < 0.05) and/or clinically relevant (>3-5 points) higher physical [11.9, 95% confidence interval (CI) 1.7, 22.2] and mental (6.4, 95% CI -1.7, 14.6) summary score. High Hb was not associated with a higher HRQOL in elderly patients who were prescribed ESA/iron. However, only young patients (n = 157) prescribed ESA/iron and with a high Hb (≥ 13 versus ≥ 11 to <12 g/dL) had a higher physical (8.9, 95% CI 2.1, 15.8) and mental (6.2, 95% CI -0.4, 12.8) summary score. CONCLUSIONS: The association of Hb levels with HRQOL differs by age and use of ESA/iron medication on predialysis care. Therefore, medical care should aim for shared decision-making regarding the appropriate Hb target leading to more individualized care.

Severe depression and all-cause and cause-specific mortality in Scotland: 20 year national cohort study.

BACKGROUND: Understanding cause of death in people with depression could inform approaches to reducing premature mortality. AIM: To describe all-cause and cause-specific mortality for people with severe depression in Scotland, by sex, relative to the general population. METHOD: We performed a retrospective cohort study, using psychiatric hospital admission data linked to death data, to identify adults (≥18 years old) with severe depression and ascertain cause-specific deaths, during 2000-2019. We estimated relative all-cause and cause-specific mortality for people with severe depression using standardised mortality ratios (SMRs), stratified by sex using the whole Scottish population as the standard. RESULTS: Of 28 808 people with severe depression, 7903 (27.4%) died during a median follow-up of 8.7 years. All-cause relative mortality was over three times higher than expected (SMR, both sexes combined: 3.26, 95% CI 3.19-3.34). Circulatory disease was the leading cause of death, and, among natural causes of death, excess relative mortality was highest for circulatory diseases (SMR 2.51, 2.40-2.66), respiratory diseases (SMR 3.79, 3.56-4.01) and 'other' causes (SMR 4.10, 3.89-4.30). Among circulatory disease subtypes, excess death was highest for cerebrovascular disease. Both males and females with severe depression had higher all-cause and cause-specific mortality than the general population. Suicide had the highest SMR among both males (SMR 12.44, 95% CI 11.33-13.54) and females (22.86, 95% CI 20.35-25.36). CONCLUSION: People with severe depression have markedly higher all-cause mortality than the general population in Scotland, with relative mortality varying by cause of death. Effective interventions are needed to reduce premature mortality for people with severe depression.

Is the decline of renal function different before and after the start of dialysis?

BACKGROUND: The presence of glomerular filtration in dialysis patients is associated with improved survival and quality of life. This study explores the time course of the glomerular filtration rate (GFR) between 1 year before and 1 year after the start of haemodialysis (HD) and peritoneal dialysis (PD). METHODS: This study included 1861 incident dialysis patients (NECOSAD cohort; 62% male, 60 ± 15 years, 61% HD, GFR 5.2 ± 3.6 mL/min/1.73 m(2)). A decline of the GFR was estimated using linear mixed-effects models adjusted for age, sex, primary kidney disease, cardiovascular disease and diabetes. The rate of decline was allowed to change at a certain point in time. RESULTS: The decline of the GFR attenuated from -0.53 mL/min/1.73 m(2)/month (95% CI: -0.58, -0.48) in the period before the start of dialysis to -0.12 (95% CI: -0.20, -0.04) at 2-4 months of dialysis in all patients. In HD, decline attenuated from -0.51 (95% CI: -0.57, -0.44) to -0.14 (95% CI: -0.26, -0.02); in PD from -0.55 (95% CI: -0.62, -0.48) to -0.11 (95% CI: -0.23, 0.01). In patients who started dialysis with a GFR equal/above median GFR at dialysis start, the decline attenuated (at 3 months) from -0.70 (95% CI: -0.78; -0.62) to -0.21 (95% CI: -0.36; -0.05). In patients who started dialysis with a GFR below median GFR at dialysis start, the decline attenuated (at 1 month) from -0.73 (95% CI: -0.88; -0.58) to -0.04 (95% CI: -0.27 , 0.19). CONCLUSIONS: The apparent decline of the GFR slows down after 2-4 months of dialysis. This decline was similar in HD and PD patients, although at a different level of GFR. Further studies are needed to examine explanations for this phenomenon.

Association between sex and survival after out-of-hospital cardiac arrest: A systematic review and meta-analysis.

The current literature on sex differences in 30-day survival following out-of-hospital cardiac arrest (OHCA) is conflicting, with 3 recent systematic reviews reporting opposing results. To address these contradictions, this systematic literature review and meta-analysis aimed to synthesize the literature on sex differences in survival after OHCA by including only population-based studies and through separate meta-analyses of crude and adjusted effect estimates. MEDLINE and Embase databases were systematically searched from inception to March 23, 2022 to identify observational studies reporting sex-specific 30-day survival or survival until hospital discharge after OHCA. Two meta-analyses were conducted. The first included unadjusted effect estimates of the association between sex and survival (comparing males vs females), whereas the second included effect estimates adjusted for possible mediating and/or confounding variables. The PROSPERO registration number was CRD42021237887, and the search identified 6712 articles. After the screening, 164 potentially relevant articles were identified, of which 26 were included. The pooled estimate for crude effect estimates (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.22-1.66) indicated that males have a higher chance of survival after OHCA than females. However, the pooled estimate for adjusted effect estimates shows no difference in survival after OHCA between males and females (OR, 0.93; 95% CI, 0.84-1.03). Both meta-analyses involved high statistical heterogeneity between studies: crude pooled estimate I2 = 95.7%, adjusted pooled estimate I2 = 91.3%. There does not appear to be a difference in survival between males and females when effect estimates are adjusted for possible confounding and/or mediating variables in non-selected populations.

Non-pharmacological interventions for the treatment of post-stroke fatigue: A systematic review.

BACKGROUND: Post-stroke fatigue (PSF) affects 50% of stroke survivors. Current guidance on management of this condition is limited. AIMS: This systematic review and meta-analysis aimed to identify and analyze all randomized clinical trials (RCTs) of non-pharmacological interventions for the treatment of PSF. SUMMARY OF REVIEW: Six electronic databases were searched from inception to January 2023 for English-language RCTs investigating the efficacy of non-pharmacological interventions versus passive controls in patients with PSF. The primary outcome was fatigue severity at the end of the intervention. The Cochrane risk-of-bias (ROB)2 tool was used to assess evidence quality. A total of 7990 records were retrieved, 333 studies were scrutinized, and 13 completed RCTs (484 participants) were included. Interventions included psychological therapies, physical therapies, and brain stimulation. Nine studies provided sufficient data for meta-analysis, of which seven also had follow-up data. Fatigue severity was lower in the intervention groups at the end of the intervention compared with control (participants = 310, standardized mean difference (SMD) = -0.57, 95% confidence intervals (CIs) (-0.87 to -0.28)) and at follow-up (participants = 112, SMD = -0.36, 95% CIs (-0.83 to 0.10)). Certainty in the effect estimate was downgraded to low for a serious ROB and imprecision. Subgroup analysis revealed significant benefits with physical therapy and brain stimulation but not psychological therapies, though sample sizes were low. CONCLUSION: Non-pharmacological interventions improved fatigue but the quality of evidence was low. Further RCTs are needed for PSF management.

Association of socioeconomic status with 30-day survival following out-of-hospital cardiac arrest in Scotland, 2011-2020.

BACKGROUND AND AIMS: The aim of this study was to investigate the crude and adjusted association of socioeconomic status with 30-day survival after out-of-hospital cardiac arrest (OHCA) in Scotland and to assess whether the effect of this association differs by sex or age. METHODS: This is a population-based, retrospective cohort study, including non-traumatic, non-Emergency Medical Services witnessed patients with OHCA where resuscitation was attempted by the Scottish Ambulance Service, between April 1, 2011 and March 1, 2020. Socioeconomic status was defined using the Scottish Index of Multiple Deprivation (SIMD). The primary outcome was 30-day survival after OHCA. Crude and adjusted associations of SIMD quintile with 30-day survival after OHCA were estimated using logistic regression. Effect modification by age and sex was assessed by stratification. RESULTS: Crude analysis showed lower odds of 30-day survival in the most deprived quintile relative to least deprived (OR 0.74, 95%CI 0.63-0.88). Adjustment for age, sex and urban/rural residency decreased the relative odds of survival further (OR 0.56, 95%CI 0.47-0.67). The strongest association was observed in males < 45 years old. Across quintiles of increasing deprivation, evidence of decreasing trends in the proportion of those presenting with shockable initial cardiac rhythm, those receiving bystander cardiopulmonary resuscitation and 30-day survival after OHCA were found. CONCLUSIONS: Socioeconomic status is associated with 30-day survival after OHCA in Scotland, favouring people living in the least deprived areas. This was not explained by confounding due to age, sex or urban/rural residency. The strongest association was observed in males < 45 years old.

Proteinuria as a risk marker for the progression of chronic kidney disease in patients on predialysis care and the role of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment.

BACKGROUND/AIMS: Proteinuria is a risk marker for progression of chronic kidney disease (CKD) and treatment with an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) is beneficial in these patients. However, little is known about proteinuria and ACEi/ARB treatment in patients on specialized predialysis care. Therefore, we investigated the association of urinary protein excretion (UPE) and ACEi/ARB treatment with renal function decline (RFD) and/or the start of renal replacement therapy (RRT) in patients on predialysis care. METHODS: In the PREPARE-1 cohort, 547 incident predialysis patients (CKD stages IV-V), referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included (1999-2001) and followed until the start of RRT, mortality, or January 1, 2008. The main outcomes were rate of RFD, estimated as the slope of available eGFR measurements, and the start of RRT. RESULTS: Patients with mild proteinuria (>0.3 to ≤1.0 g/24 h) had an adjusted additional RFD of 0.35 ml/min/1.73 m(2)/month (95% CI: 0.01; 0.68) and a higher rate of starting RRT [adjusted HR: 1.70 (1.05; 2.77)] compared with patients without proteinuria (≤0.3 g/24 h). With every consecutive UPE category (>1.0 to ≤3.0, >3.0 to ≤6.0, and >6.0 g/24 h), RFD accelerated and the start of RRT was earlier. Furthermore, patients starting (n = 16) or continuing (n = 133) treatment with ACEi/ARBs during predialysis care had a lower rate of starting RRT compared with patients not using treatment [n = 152, adjusted HR: 0.56 (0.29; 1.08) and 0.90 (0.68; 1.20), respectively]. CONCLUSION: In patients on predialysis care, we confirmed that proteinuria is a risk marker for the progression of CKD. Furthermore, no evidence was present that the use of ACEi/ARBs is deleterious.

Incidence, characteristics and outcomes of out-of-hospital cardiac arrests in patients with psychiatric illness: A systematic review.

AIM: To conduct a systematic literature review of the existing evidence on incidence, characteristics and outcomes after out-of-hospital cardiac arrest (OHCA) in patients with psychiatric illness. METHODS: We searched Embase, Medline, PsycINFO and Web of Science using a comprehensive electronic search strategy to identify observational studies reporting on OHCA incidence, characteristics or outcomes by psychiatric illness status. One reviewer screened all titles and abstracts, and a second reviewer screened a random 10%. Two reviewers independently performed data extraction and quality assessment. RESULTS: Our search retrieved 11,380 studies, 10 of which met our inclusion criteria (8 retrospective cohort studies and two nested case-control studies). Three studies focused on depression, whilst seven included various psychiatric conditions. Among patients with an OHCA, those with psychiatric illness (compared to those without) were more likely to have: an arrest in a private location; an unwitnessed arrest; more comorbidities; less bystander cardiopulmonary resuscitation; and an initial non-shockable rhythm. Two studies reported on OHCA incidence proportion and two reported on survival, showing higher risk, but lower survival, in patients with psychiatric illness. CONCLUSION: Psychiatric illness in relation to OHCA incidence and outcomes has rarely been studied and only a handful of studies have reported on OHCA characteristics, highlighting the need for further research in this area. The scant existing literature suggests that psychiatric illness may be associated with higher risks of OHCA, unfavourable characteristics and poorer survival. Future studies should further investigate these links and the role of potential contributory factors such as socioeconomic status and comorbidities.

Long-term mortality and recurrent vascular events in lacunar versus non-lacunar ischaemic stroke: A cohort study.

Introduction: Studies of differences in very long-term outcomes between people with lacunar/small vessel disease (SVD) versus other types of ischaemic stroke report mixed findings, with limited data on myocardial infarction (MI). We investigated whether long-term mortality, recurrent stroke and MI risks differ in people with versus without lacunar/SVD ischaemic stroke. Patients and methods: We included first-ever strokes from a hospital-based stroke cohort study recruited in 2002-2005. We compared risks of death, recurrent stroke and MI during follow-up among lacunar/SVD versus other ischaemic stroke subtypes using Cox regression, adjusting for confounding factors. Results: We included 812 participants, 283 with lacunar/SVD ischaemic stroke and 529 with other stroke. During a median of 9.2 years (interquartile range 3.1-11.8), there were 519 deaths, 181 recurrent strokes and 79 MIs. Lacunar/SVD stroke was associated with lower mortality (adjusted HR 0.79, 95% CI 0.65 to 0.95), largely due to markedly lower all-cause mortality in the first year. From one year onwards this difference attenuated, with all-cause mortality only slightly and not statistically significantly lower in the lacunar/SVD group (0.86, 95% CI 0.70 to 1.05). There was no clear difference in risk of recurrent stroke (HR 0.84, 95% CI 0.61-1.15) or MI (HR 0.83, 95% CI 0.52-1.34). Conclusion: Long-term risks of all-cause mortality, recurrent stroke and MI are similar, or only slightly lower, in patients with lacunar/SVD as compared to other ischaemic stroke. Patients and physicians should be as vigilant in optimising short- and long-term secondary prevention of vascular events in lacunar/SVD as for other stroke types.

Development and Validation of a Lifetime Risk Model for Kidney Failure and Treatment Benefit in Type 2 Diabetes: 10-Year and Lifetime Risk Prediction Models.

BACKGROUND AND OBJECTIVES: Individuals with type 2 diabetes are at a higher risk of developing kidney failure. The objective of this study was to develop and validate a decision support tool for estimating 10-year and lifetime risks of kidney failure in individuals with type 2 diabetes as well as estimating individual treatment effects of preventive medication. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The prediction algorithm was developed in 707,077 individuals with prevalent and incident type 2 diabetes from the Swedish National Diabetes Register for 2002-2019. Two Cox proportional regression functions for kidney failure (first occurrence of kidney transplantation, long-term dialysis, or persistent eGFR <15 ml/min per 1.73 m2) and all-cause mortality as respective end points were developed using routinely available predictors. These functions were combined into life tables to calculate the predicted survival without kidney failure while using all-cause mortality as the competing outcome. The model was externally validated in 256,265 individuals with incident type 2 diabetes from the Scottish Care Information Diabetes database between 2004 and 2019. RESULTS: During a median follow-up of 6.8 years (interquartile range, 3.2-10.6), 8004 (1%) individuals with type 2 diabetes in the Swedish National Diabetes Register cohort developed kidney failure, and 202,078 (29%) died. The model performed well, with c statistics for kidney failure of 0.89 (95% confidence interval, 0.88 to 0.90) for internal validation and 0.74 (95% confidence interval, 0.73 to 0.76) for external validation. Calibration plots showed good agreement in observed versus predicted 10-year risk of kidney failure for both internal and external validation. CONCLUSIONS: This study derived and externally validated a prediction tool for estimating 10-year and lifetime risks of kidney failure as well as life years free of kidney failure gained with preventive treatment in individuals with type 2 diabetes using easily available clinical predictors. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2022_11_04_CJN05020422.mp3.

Trimestral variations of C-reactive protein, interleukin-6 and tumour necrosis factor-α are similarly associated with survival in haemodialysis patients.

BACKGROUND: The impact of intra-individual changes of inflammatory markers [other than C-reactive protein (CRP)] on mortality in haemodialysis (HD) patients is unknown. We therefore studied survival in relation to trimestral variations of CRP, interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). METHODS: In 201 prevalent HD patients from the Mapping of Inflammatory Markers in Chronic Kidney Disease cohort, serum CRP, IL-6 and TNF-α were measured 3 months apart and survival was assessed during follow-up. Based on fluctuations along tertiles of distribution, four patterns were defined for each inflammatory marker: stable low, decrease, increase and stable high. Hazard ratios were calculated by the Cox proportional hazard model, and Pearson's test was used to correlate changes. CRP analyses were replicated in 472 incident HD patients from the Netherlands Cooperative Study on the Adequacy of Dialysis. RESULTS: Patients with persistently elevated CRP values had the worst mortality in crude [HR 2.98 (95% CI 1.71-5.20)] and adjusted [2.79 (1.58-4.94)] Cox models, together with those who increased in their CRP levels [crude 3.27 (1.91-5.60); adjusted 3.13 (1.79-5.45)]. Similar survival patterns were observed for IL-6 and TNF-α variation categories. Correlations among these changes were, however, not strong. In the replication cohort, individuals with persistently elevated CRP values also showed the highest mortality risk [crude 3.38 (2.31-4.94); adjusted 2.33 (1.58-3.45)]. CONCLUSIONS: Trimestral variations of TNF-α, IL-6, and CRP are similarly associated with survival in HD patients. The agreement between changes of these biomarkers was low, suggesting that different pathways may trigger each of these markers.

Haemodialysis catheters increase mortality as compared to arteriovenous accesses especially in elderly patients.

BACKGROUND: Catheter use has been associated with an increased mortality risk in haemodialysis patients. However, differences in the all-cause and cause-specific mortality risk between catheter use and arteriovenous access use in young and elderly haemodialysis patients have not yet been investigated. METHODS: In this prospective cohort study of 1109 incident haemodialysis patients from 38 centres in the Netherlands, hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated for 2-year all-cause, infection-related and cardiovascular mortality in patients with a catheter as compared to patients with an arteriovenous access stratified for age (< 65 years and ≥ 65 years). RESULTS: Of the 1109 patients, 919 had an arteriovenous access and 190 had a catheter. The mortality rate was 76 per 1000 person-years in young patients with an arteriovenous access, 129 per 1000 person-years in young patients with a catheter, 222 per 1000 person-years in elderly patients with an arteriovenous access and 427 per 1000 person-years in elderly patients with a catheter. The adjusted HR was 3.15 (95% CI: 2.09-4.75) for elderly patients with a catheter as compared to young patients with an arteriovenous access. The adjusted HRs in elderly patients with a catheter as compared to elderly patients with an arteriovenous access were 1.54 (95% CI: 1.13-2.12) for all-cause mortality, 1.60 (95%: CI 0.62-4.19) for infection-related mortality and 1.67 (95% CI: 1.04-2.68) for cardiovascular mortality. CONCLUSIONS: Especially, elderly haemodialysis patients with a catheter have an increased all-cause, infection-related and cardiovascular mortality risk as compared to patients with an arteriovenous access.

Association of blood pressure with decline in renal function and time until the start of renal replacement therapy in pre-dialysis patients: a cohort study.

BACKGROUND: To investigate whether high blood pressure accelerates renal function decline in patients with advanced chronic kidney disease (CKD), we studied the association of systolic (SBP) and diastolic blood pressure (DBP) with decline in renal function and time until the start of renal replacement therapy (RRT) in patients with CKD stages IV-V on pre-dialysis care. METHODS: In the PREPARE-1 cohort 547 incident pre-dialysis patients, referred as part of the usual care to outpatient clinics of eight Dutch hospitals, were included between 1999 and 2001 and followed until the start of RRT, mortality, or end of follow-up (January 1st 2008). Main outcomes were rate of decline in renal function, estimated as the slope of available eGFR measurements, and time until the start of RRT. RESULTS: A total of 508 patients, 57% men and median (IQR) age of 63 (50-73) years, were available for analyses. Mean (SD) decline in renal function was 0.35 (0.75) ml/min/1.73 m2/month. Every 10 mmHg increase in SBP or DBP resulted in an accelerated decline in renal function (adjusted additional decline 0.04 (0.02;0.07) and 0.05 (0.00;0.11) ml/min/1.73 m2/month respectively) and an earlier start of RRT (adjusted HR 1.09 (1.04;1.14) and 1.16 (1.05;1.28) respectively). Furthermore, patients with SBP and DBP above the BP target goal of < 130/80 mmHg experienced a faster decline in renal function (adjusted additional decline 0.31 (0.08;0.53) ml/min/1.73 m2/month) and an earlier start of RRT (adjusted HR 2.08 (1.25;3.44)), compared to patients who achieved the target goal (11%). Comparing the decline in renal function and risk of starting RRT between patients with only SBP above the target (≥ 130 mmHg) and patients with both SBP and DBP below the target (< 130/80 mmHg), showed that the results were almost similar as compared to patients with both SBP and DBP above the target (adjusted additional decline 0.31 (0.04;0.58) ml/min/1.73 m2/month and adjusted HR 2.24 (1.26;3.97)). Therefore, it seems that especially having SBP above the target is harmful. CONCLUSIONS: In pre-dialysis patients with CKD stages IV-V, having blood pressure (especially SBP) above the target goal for CKD patients (< 130/80 mmHg) was associated with a faster decline in renal function and a later start of RRT.

Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort.

Urinary albumin excretion is a powerful predictor of progressive cardiovascular and renal disease. In rats and humans, administration of a synthetic vasopressin analogue, 1-desamino-8-D-arginine-vasopressin, increases urinary albumin excretion; however, it is unknown if endogenous vasopressin levels influence albumin excretion. To determine this we measured copeptin, a marker of endogenous vasopressin levels, and its association with urinary albumin excretion in 7593 patients in the PREVEND study, a prospective population based, observational cohort. Urinary albumin excretion was measured in two consecutive 24-h urine samples by nephelometry while copeptin was measured by an immunoassay. Median copeptin concentrations were significantly higher in males than females and high levels were associated with significantly lower 24-h urine volumes of high osmolarity. With increasing quintiles of copeptin levels, the percentage of microalbuminuric subjects increased from 13 to 25 for males and from 8 to15 for females. This association was independent of age and other potential confounders; however, we found an interaction between age and copeptin in their association with urinary albumin excretion. Our study shows that plasma copeptin levels are associated with microalbuminuria, consistent with the hypothesis that vasopressin is involved in urinary albumin excretion. If future studies show that this association is causal, then drinking more water or pharmacological intervention to decrease plasma vasopressin may have beneficial effects on the kidney, especially in the elderly.