Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and major bleeding.

PURPOSE: We sought to explore whether adding kidney function biomarkers based on creatinine (eGFRCr), cystatin C (eGFRCys) or a combination of the two (eGFRCr-Cys) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. METHOD: We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFRCr, eGFRCys and eGFRCr-Cys (mL/min/1.73 m2) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. FINDINGS: Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8-12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFRCys was more strongly associated with ischaemic stroke than eGFRCr: an effect that was more pronounced in women (men - HR: 1.16, 95% CI: 1.12-1.19; female to male comparison - HR: 1.11, 95% CI: 1.05-1.16, per 10 mL/min/1.73 m2 decline in eGFRCys). This interaction effect was also demonstrated for eGFRCr-Cys, but not eGFRCr. eGFRCys and eGFRCr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFRCr in both men and women. Event numbers were small for haemorrhagic stroke. DISCUSSION: To a greater degree than is seen in men, eGFRCr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFRCys. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. CONCLUSION: Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women.

International Variability of Renal and Cardiovascular Outcomes and Mortality in Patients with Type 2 Diabetes Mellitus in Europe.

INTRODUCTION: Type 2 diabetes and its complications represent a huge burden to public health. With this prospective, observational cohort study, we aimed to estimate and to compare the incidence rate (IR) of renal and cardiovascular outcomes and all-cause mortality in patients with type 2 diabetes in different European countries. METHODS: The renal endpoint was a composite of a sustained decline in estimated GFR of at least 40%, a sustained increase in albuminuria of at least 30% including a transition in albuminuria class, progression to kidney failure with replacement therapy, or death from renal causes. The cardiovascular endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: 3,131 participants from four European countries (Austria, Hungary, The Netherlands, and Scotland) with a median follow-up time of 4.4 years were included. IRs were adjusted for several risk factors including sex, age, estimated GFR, albuminuria, HbA1c, blood pressure, and duration of type 2 diabetes. Across countries, the adjusted IR for the renal endpoint was significantly higher in Hungary and Austria, and the adjusted IR for the cardiovascular endpoint was significantly higher in Scotland and Austria. All-cause mortality was significantly higher in Scotland compared to all other countries. CONCLUSION: Our findings show how the longitudinal outcome of patients with type 2 diabetes varies significantly across European countries even after accounting for the distribution of underlying risk factors.

Gadolinium-enhanced MR imaging and nephrogenic systemic fibrosis: retrospective study of a renal replacement therapy cohort.

PURPOSE: To retrospectively compare the frequency of administration and cumulative dose of gadolinium-based contrast agent in dialysis-dependent patients who did and those who did not develop nephrogenic systemic fibrosis. MATERIALS AND METHODS: The ethics committees granted exempt status for this study and also waived the need for informed consent. A retrospective analysis was performed of all adult patients undergoing dialysis in the west of Scotland between January 1, 2000, and July 1, 2006. Diagnoses of nephrogenic systemic fibrosis, episodes of gadolinium-enhanced magnetic resonance (MR) imaging, and cumulative doses of gadolinium-based contrast agent were recorded. Outcomes were analyzed by means of parametric and nonparametric testing. RESULTS: Fourteen of 1826 patients had a diagnosis of nephrogenic systemic fibrosis. Mortality was similar for affected and nonaffected patients. Thirteen (93%) of 14 patients with nephrogenic systemic fibrosis had undergone gadolinium-enhanced MR imaging compared with 408 (22.5%) of 1812 nonaffected patients (P<.001). Patients with nephrogenic systemic fibrosis received a higher median cumulative dose of gadodiamide (0.39 vs 0.23 mmol per kilogram of body weight, P=.008) and underwent more gadolinium-enhanced MR imaging than their nonaffected gadolinium-exposed counterparts. CONCLUSION: The data support a positive association between gadolinium-based contrast agent administration and development of nephrogenic systemic fibrosis in the established renal failure population; in addition, there is a positive association between cumulative dose of gadodiamide used and dosing events.