Rationale & objective: Cystatin C is recommended for measuring estimated glomerular filtration rate (eGFR) when estimates based on creatinine (eGFR(cr)) are not thought to be accurate enough... Show moreRationale & objective: Cystatin C is recommended for measuring estimated glomerular filtration rate (eGFR) when estimates based on creatinine (eGFR(cr)) are not thought to be accurate enough for clinical decision making. While global adoption is slow, routine cystatin C testing in Sweden has been available for over a decade, providing real-world evidence about the magnitude of differences between eGFR(cys) and eGFR(cr) and their association with clinical outcomes.Study design: Observational study.Setting & participants: 158,601 adults (48% women; mean age 62 years, eGFR(cr) 80, and eGFR(cys) 73mL/min/1.73/m(2)) undergoing testing for creatinine and cystatin C on the same day in connection with a health care encounter during 2010-2018 in Stockholm, Sweden.Exposure: Percentage difference of eGFR(cys) minus eGFR(cr) (eGFR(diff)).Outcome: Kidney failure with replacement therapy (KFRT), acute kidney injury (AKI), atherosclerotic cardiovascular disease (ASCVD), heart failure, and death.Analytical approach: Multivariable Cox proportional hazards regression.Results: Discordances between eGFR(cr) and eGFR(cys) were common, with eGFR(cys) being lower than eGFR(cr) (negative eGFR(diff)) in most cases (65%). Patients with larger negative eGFR(diff) were older, more often female, with higher eGFR(cr) and albuminuria, and more comorbid conditions. Compared with patients with similar eGFR(cys) and eGFR(cr), the lowest quartile (eGFR(cys) > 27% lower than eGFR(cr)) had the higher HR of all study outcomes: AKI, 2.6 (95% CI, 2.4-2.9); KFRT, 1.4 (95% CI, 1.2-1.6); ASCVD, 1.4 (95% CI, 1.3-1.5); heart failure, 2.0 (95% CI, 1.9-2.2); and all-cause death, 2.6 (95% CI, 2.5-2.7). Conversely, patients in the highest quartile (positive eGFR(diff)) were at lower risk.Limitations: Observational study, lack of information on indications for cystatin C testing.Conclusions: Cystatin C testing in routine care shows that many patients have a lower eGFR(cys) than eGFR(cr), and these patients have a higher risk of multiple adverse outcomes. Show less
Background Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin ... Show moreBackground Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin (eGFR(cr-cys)) is the most accurate estimate in research studies, it is uncertain whether this is true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFR(cr)) and that based on cystatin C (eGFR(cys))Methods We included 6185 adults referred for measured GFR (mGFR) using plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance. The performance of eGFR(cr), eGFR(cys), and eGFR(cr-cys) was assessed against mGFR with median bias, P-30, and correct classification of GFR categories. We stratified analyses within three categories: eGFR(cys) at least 20% lower than eGFR(cr) (eGFR(cys)eGFR(cr)).Results eGFR(cr) and eGFR(cys) were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR(cr-cys) was much more accurate in cases of discordance. For example, when eGFR(cys)eGFR(cr) (8% of samples), the median biases were -4.5, 8.4, and 1.4 ml/min per 1.73m(2). The findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer.Conclusions When eGFR(cr) and eGFR(cys) are highly discordant in clinical practice, eGFR(cr-cys) is more accurate than either eGFR(cr) or eGFR(cys). Show less
Introduction Little is known about the comparative effects of sodium glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), or dipeptidyl peptidase-4... Show moreIntroduction Little is known about the comparative effects of sodium glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), or dipeptidyl peptidase-4 inhibitors (DPP-4i) on the risk of acute kidney injury (AKI) in routine care, which may differ from the controlled setting of trials.Methods Observational study comparing risks of AKI among new users of SGLT2i, GLP1-RA or DPP-4i in the region of Stockholm, Sweden, during 2008-2018. AKI was defined by ICD-10 codes and creatinine-based KDIGO criteria. We used inverse probability of treatment weighting (IPTW) to adjust for 60 potential confounders, weighted Kaplan-Meier curves and Cox regression to estimate hazard ratios and absolute risks.Results We included 17,407 participants who newly initiated DPP-4i (N = 10,605), GLP1-RA (N = 4448) or SGLT2i (N = 2354). Mean age was 63 years (39% women) and median (IQR) eGFR was 89 (73-100) ml/min/1.73 m(2). During a median follow-up of 2.5 years, 1411 participants experienced AKI. SGLT2i users had the lowest incidence rate of AKI, 18.3 [CI 95% 14.1-23.4] per 1000 person years, followed by GLP1-RA (22.5; 19.9-25.3) and DPP-4i (26.6; 25-28.2). The weighted 3-year absolute risk for AKI was 5.79% [3.63-8.52] in the SGLT2i group, compared with 7.03% [5.69-8.69] and 7.00% [6.43-7.58] in the GLP1-RA and DPP-4i groups, respectively. The adjusted hazard ratio was 0.73 [CI 95% 0.45-1.16] for SGLT2i vs. DPP-4i, and 0.98 [CI 95% 0.82-1.18] for GLP1-RA vs. DPP-4i.Conclusion This study of routine care patients initiating novel glucose-lowering drugs showed similar occurrence of AKI between therapies, and suggests lower risk for SGLT2i. Show less
BACKGROUND Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously... Show moreBACKGROUND Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously been assessed. OBJECTIVES This study determined whether various parameterizations of longitudinal cTnT measurements were associated with patient survival in the older population with advanced CKD. METHODS The EQUAL (European QUALity) study is an observational prospective cohort study that includes subjects with stage 4-5 CKD aged $65 years and not on dialysis. The study includes 176 participants in Sweden, where longitudinal information of cTnT was collected. The study uses joint models for longitudinal and time-to-event data to assess the longitudinal association between cTnT and survival. RESULTS There were 927 cTnT measurements (median 6 per patient) collected over a median follow-up of 2.4 years. The overall 5-year survival was 57% (95% CI: 46%-69%). Longitudinally measured cTnT was associated with mortality risk, with every SD increase in cTnT, at any time point, associated with a 3.3-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). The slope of the cTnT trajectory was also associated with increased mortality risk (HR: 3.2; 95% CI: 2.06.0), as was the area under the cTnT trajectory (HR: 4.2; 95% CI: 2.6-7.2), which reflected the cumulative cTnT exposure. CONCLUSIONS Longitudinally measured cTnT is independently associated with mortality risk in older patients with stage 4 and 5 CKD, which suggests that monitoring patients with cTnT could be a valuable tool for the identification of subjects with a high mortality risk. (J Am Coll Cardiol 2022;79:327-336) (c) 2022 by the American College of Cardiology Foundation. Show less
Background-People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic... Show moreBackground-People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis.Methods and Results-The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged >= 65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m(2)). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (<= 14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19; P<0.0001). Each 15 mL/min/1.73 m(2) lower mean estimated GFR was associated with a 23% (95% CI, 14-31; P<0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%; P<0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%).Conclusions-In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m2 lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors. Show less
Janmaat, C.J.; Diepen, M. van; Gasparini, A.; Evans, M.; Qureshi, A.R.; Arnlov, J.; ... ; Carrero, J.J. 2018
Background. An increase in C-reactive protein (CRP) levels during a single haemodialysis (HD) session has been associated with mortality. These associations, however, are difficult to understand... Show moreBackground. An increase in C-reactive protein (CRP) levels during a single haemodialysis (HD) session has been associated with mortality. These associations, however, are difficult to understand from the current understanding of CRP metabolism. Methods. In 190 Swedish haemodialysis (HD) patients from the Mapping of Inflammatory Markers in Chronic Kidney Disease (MIMICK) cohort, CRP was measured before and after a HD session. During follow-up, events of death and censoring were recorded, and hazard ratios were calculated and analysed as a function of CRP variation. Results were replicated in 94 Dutch HD patients from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD). In this cohort, also correlation and kappa statistics were calculated to assess concordance in CRP changes amid multiple dialysis sessions from the same individuals. Results. In both cohorts, mean CRP values did not increase during a single HD session. In the MIMICK, median (interquartile range) dialysis vintage was 29.0 (14.8-57.0) months. In both crude [hazard ratio (95% confidence interval): 1.008 (0.971-1.047)] and multivariate Cox models [0.996 (0.949-1.046)], no association was observed with mortality. In the NECOSAD, individuals endured 6.0 (6.012.0) months on dialysis. No association was found with mortality neither in a crude [0.961 (0.908-1.018)] nor in an adjusted analysis [0.978 (0.923-1.037)]. Finally, the concordance between changes in different sessions was poor. Conclusions. CRP changes during a single HD session do not associate with mortality, thereby adding to the biological uncertainty concerning the ability of CRP to rise in such a short period. Show less
