Mapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns ...that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping.
This is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2.
Twenty-six participants (16 male, 65 ± 9 years) were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L (IQR 1.8, 2.5), resulting in a median weight reduction at post-dialysis scan of 1.35 kg (IQR 1.0, 1.9), with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L (IQR 0.5, 1.4). Significant reductions were observed in LV end-diastolic volume (- 25 ml, p = 0.002), LV stroke volume (- 13 ml, p = 0.007), global T1 (21 ms, p = 0.02), global T2 (- 1.2 ms, p = 0.02) following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters.
Acute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.
Background South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine- rather than cystatin C-based estimated glomerular filtration rate (eGFRcys) may ...underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m
) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio HR, 2.38 95% CI, 1.55-3.65) and incident HF (sub-HR sHR, 1.87 95% CI, 1.09-3.22) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 95% CI, 2.56-9.31), incident HF (sHR, 4.96 95% CI, 2.21-11.16), and incident atherosclerotic cardiovascular disease (sHR, 2.29 95% CI, 1.14-4.61) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 95% CI, 1.45-3.51). Conclusions Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate-based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.
Abstract Background Patients with end-stage renal disease undergoing haemodialysis are at high risk of sudden cardiac death. Advanced renal disease is associated with cardiac hypertrophy, which ...increases risk of life-threatening arrhythmias. Using a new MRI technique, T1 mapping, and the blood biomarker brain natriuretic peptide (BNP), we aimed to measure changes in function and structure of the heart muscle during the first year of haemodialysis treatment in the Cardiac Uraemic Fibrosis Detection in Dialysis Patients study. Methods 28 adults with kidney disease on haemodialysis within Glasgow, UK, participated in this single-centre observational study. To be eligible for the study patients had to have been on haemodialysis for less than 1 year. Patients with MRI contraindications or who were expected to be on dialysis for less than 6 months were excluded. Primary outcome was volume of myocardial fibrosis (septal T1 time) on MRI at baseline and at 6 months' follow-up. Secondary outcome was change in serum BNP. Patients gave written consent, and ethics approval was given (13/WS/0301). This study is registered with the ISCTRN registry, number ISCTRN99591655. Findings 22 patients completed both baseline and follow-up visits. There was no significant change in septal T1 time after 6 months of haemodialysis (septal T1 time baseline 1276·727 ms, follow-up 1271·837 ms). Left ventricular mass index (LVMI) was reduced at follow-up (baseline mean LVMI 78·3 g/m2 SD 18·2, follow-up 67·9 19·0; p<0·0001). Differences in septal T1 times correlated with difference in LVMI ( r =0·545, p=0·009). Median BNP did not significantly change between baseline and follow-up (2908 pg/mL IQR 1639–5215 vs 2274·5 1550–7055). Change in LVMI was correlated with baseline BNP ( r =0·492, p=0·02). Correlation between change in BNP and difference in septal T1 time was not significant. Interpretation 6 months of haemodialysis therapy was associated with significant improvement in left ventricular hypertrophy but no significant change in T1 mapping markers of cardiac fibrosis or BNP. This small study suggests that starting haemodialysis might be associated with changes in myocardial structure. These changes could potentially be linked to control of uraemia, blood pressure, or both, which commonly occur on starting renal replacement therapy. Funding Kidney Research UK (Innovation Grant IN02/2013).
Stroke incidence is high in end‐stage renal disease, and risk factors differ between the dialysis and general populations. However, risk factors and outcomes following renal transplantation remain ...unclear. We analyzed all adult patients with a functioning renal transplant from 01/01/2007 to 12/31/2012. Data were extracted from the electronic patient record. Variables associated with stroke were identified by survival analyses; demographic, clinical, and imaging and laboratory variables were assessed and case fatality determined. Follow‐up was until 05/12/2013. A total of 956 patients were identified (median age 40.1 years, 59.9% male). Atrial fibrillation (AF) prevalence was 9.2%, and 38.2% received a transplant during follow‐up. A total of 26 (2.7%) experienced a stroke during 4409 patient‐years of follow‐up (84.6% ischemic). Stroke incidence was 5.96/1000 patient‐years. Factors associated with stroke on regression analysis were prior stroke, diabetes, age, systolic hypertension, and hemoglobin. Atrial fibrillation was associated with time to stroke (P<0.001). Warfarin did not associate with ischemic stroke risk in those with AF. Fatality was 19.2% at 7, 23.1% at 28, and 42.3% at 365 days after stroke. Patients with a functioning renal transplant have a high stroke incidence and case fatality. Unlike those on hemodialysis, risk factors are similar to the general population. We did not demonstrate benefit from warfarin use in those with AF.
Large differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to ...these differences is needed to guide the interpretation of discrepant eGFR values.
Cohort study.
468,969 participants in the UK Biobank.
Candidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors.
eGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than−15mL/min/1.73m2), concordant eGFRcys and eGFRcr (eGFRdiff, −15 to<15mL/min/1.73m2), and lower eGFRcr (eGFRdiff, ≥15mL/min/1.73m2).
Multinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants.
Mean±standard deviation of eGFRcys was 88±16mL/min/1.73m2, and eGFRcr was 95±13mL/min/1.73m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio>300mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model’s area under the curve was 0.75 in the validation set, with good calibration (1.00).
Limited generalizability.
This study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.
Estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine may differ substantially within an individual. Although most clinicians are aware that creatinine is influenced by muscle mass, there are additional numerous lifestyle and health characteristics that may affect serum concentrations of either biomarker. Our analyses of 468,969 individuals in the UK Biobank identified independent predictors of large differences between eGFR based on cystatin C and eGFR based on creatinine, which may inform the interpretation of discrepant eGFR values within an individual. We developed models that may be implemented at a population level to help health systems identify individuals who are likely to have large differences between eGFR based on cystatin C and eGFR based on creatinine and thus should be prioritized for cystatin C testing.
BackgroundRenal transplant recipients (RTRs) exhibit increased vascular stiffness and calcification; these parameters are associated with increased cardiovascular risk. Activity of endogenous ...calcification inhibitors such as matrix gla protein (MGP) is dependent on vitamin K. RTRs commonly have subclinical vitamin K deficiency. The Vitamin K in kidney Transplant Organ Recipients: Investigating vEssel Stiffness (ViKTORIES) study assesses whether vitamin K supplementation reduces vascular stiffness and calcification in a diverse population of RTR.Methods and analysisViKTORIES (ISRCTN22012044) is a single-centre, phase II, parallel-group, randomised, double-blind, placebo-controlled trial of the effect of vitamin K supplementation in 90 prevalent RTR. Participants are eligible if they have a functioning renal transplant for >1 year. Those on warfarin, with atrial fibrillation, estimated glomerular filtration rate <15 mL/min/1.73 m2 or contraindications to MRI are excluded. Treatment is with vitamin K (menadiol diphosphate) 5 mg three times per week for 1 year or matching placebo. All participants have primary and secondary endpoint measures at 0 and 12 months. The primary endpoint is ascending aortic distensibility on cardiac MR imaging. Secondary endpoints include vascular calcification (coronary artery calcium score by CT), cardiac structure and function on MR, carotid-femoral pulse wave velocity, serum uncarboxylated MGP, transplant function, proteinuria and quality of life. The study is powered to detect 1.0×10–3 mm Hg-1 improvement in ascending aortic distensibility in the vitamin K group relative to placebo at 12 months. Analyses will be conducted as between-group differences at 12 months by intention to treat.DiscussionThis trial may identify a novel, inexpensive and low-risk treatment to improve surrogate markers of cardiovascular risk in RTR.
Renal involvement is rare in primary Sjögren syndrome (PSS). In this study, we examined renal biopsy findings in patients with PSS and correlated them with their clinical and renal findings.
...Twenty-five patients with PSS who underwent renal biopsies from two renal units in Scotland between 1978 and 2013 were identified from renal biopsy database. We examined the renal morphologic, clinical and renal findings at the time of renal biopsy, renal and patient outcomes.
The diagnosis of PSS preceded renal biopsy in 18/25 patients. In this group, the median duration of the disease was 5.5 years. Significant proteinuria, combined microscopic haematuria and proteinuria and reduced renal excretory function were found in 76, 56 and 84% of patients, respectively. The 3-year actuarial patient survival was significantly lower in patients with glomerulonephritis as compared with tubulointerstitial nephritis (66 versus 100%, P = 0.02). There was no difference in 3-year actuarial renal survival between these two groups (92 versus 92%, P = 1.0).
Renal biopsy is rare in PSS and often reveals diverse pathological findings. Glomerulonephritis, as compared with tubulointerstitial nephritis, is associated with higher early mortality. Further studies are needed to evaluate the utility of renal biopsy and its impact on disease management.
Abstract
BACKGROUND AND AIMS
Age-adapted thresholds of estimated glomerular filtration rate (eGFR) have been proposed for the diagnosis of chronic kidney disease (CKD) 1 to acknowledge decline in ...kidney function with increasing age 2. Proponents of age-adapted thresholds suggest that subjects over the age of 65 with eGFR 45–59 mL/min/1.73 m2 and without albuminuria appear to be at low risk of adverse outcomes 1; however, the risks associated with CKD extend beyond kidney failure 3. We evaluated whether cystatin C testing (eGFRcys) could improve risk stratification in CKD without adopting age-adapted thresholds.
METHOD
Data were from participants in the UK Biobank cohort with eGFR based on serum creatinine (eGFRcr) ≥45 mL/min/1.73 m2 and without albuminuria. Participants with a history of cardiovascular disease or kidney failure at baseline were excluded. CKD status was initially categorized by eGFRcr, then concordance of eGFRcys < 60 mL/min/1.73 m2 was determined. Multivariable-adjusted Cox proportional hazards models evaluated associations of CKD status with death, myocardial infarction (MI), stroke and kidney failure. Analyses were stratified by age: older (65–73 years) and younger (<65 years) participants.
RESULTS
Among 76 629 older and 351 773 younger participants, followed over median 11.5 (IQR 10.8–12.2) years, there were 24 251 deaths, 6983 MI, 4081 strokes and 209 kidney failure events. Of 2016 older participants with eGFRcr 45–59 mL/min/1.73 m2 37% had eGFRcys > 60 mL/min/1.73 m2. Furthermore, eGFRcr alone did not detect 6278 (8%) of older participants with eGFRcys < 60 mL/min/1.73 m2. In cross-sectional analyses, the median baseline eGFR was lower at higher age for all equations: this was most pronounced for eGFRcys (Figure 1). CKD by eGFRcys only or with both markers experienced higher absolute incidence of MI, stroke and mortality compared to those without CKD by either marker (Figure 2). Compared to those without CKD, older participants with concordant eGFRcr and eGFRcys < 60mL/min/1.73 m2 had elevated adjusted risks of death (HR 1.8, 1.6–2.0), MI (HR 1.9, 1.5–2.4), stroke (HR 1.7, 1.2–2.3) and kidney failure (HR 4.2, 1.2–14.1). Findings were similar in younger participants with concordant eGFRcr and eGFRcys < 60 mL/min/1.73 m2 for death (HR 2.2, 1.9–2.6) and stroke (HR 2.1, 1.4–3.2), though not MI (HR 1.2, 0.8–1.8). When CKD was not confirmed by eGFRcys, eGFRcr 45–59 mL/min/1.73 m2 was not associated with increased hazards of death (HR 1.1, 0.9–1.4), MI (HR 1.1, 0.7–1.7) or stroke (HR 1.1, 0.7–1.9) in older participants, nor in younger participants for the same outcomes: death (HR 1.1, 0.8–1.3), MI (HR 1.2, 0.8–1.9) and stroke (HR 0.8, 0.4–1.6).
CONCLUSION
Among persons with CKD, cardiovascular disease and mortality are important risks that should be considered when determining CKD status. CKD categorization by eGFRcr alone includes a large proportion of individuals who have similar risks to persons without CKD. eGFRcys detects a substantial number of high-risk individuals not identified to have CKD by eGFRcr. In the absence of cystatin C testing, lower, age-adapted thresholds for diagnosis of CKD may inadequately detect the broader risks associated with kidney disease in older people.
Abstract
BACKGROUND AND AIMS
Age-adapted thresholds of estimated glomerular filtration rate (eGFR) have been proposed for the diagnosis of chronic kidney disease (CKD) 1 to acknowledge decline in ...kidney function with increasing age 2. Proponents of age-adapted thresholds suggest that subjects over the age of 65 with eGFR 45–59 mL/min/1.73 m2 and without albuminuria appear to be at low risk of adverse outcomes 1; however, the risks associated with CKD extend beyond kidney failure 3. We evaluated whether cystatin C testing (eGFRcys) could improve risk stratification in CKD without adopting age-adapted thresholds.
METHOD
Data were from participants in the UK Biobank cohort with eGFR based on serum creatinine (eGFRcr) ≥45 mL/min/1.73 m2 and without albuminuria. Participants with a history of cardiovascular disease or kidney failure at baseline were excluded. CKD status was initially categorized by eGFRcr, then concordance of eGFRcys < 60 mL/min/1.73 m2 was determined. Multivariable-adjusted Cox proportional hazards models evaluated associations of CKD status with death, myocardial infarction (MI), stroke and kidney failure. Analyses were stratified by age: older (65–73 years) and younger (<65 years) participants.
RESULTS
Among 76 629 older and 351 773 younger participants, followed over median 11.5 (IQR 10.8–12.2) years, there were 24 251 deaths, 6983 MI, 4081 strokes and 209 kidney failure events. Of 2016 older participants with eGFRcr 45–59 mL/min/1.73 m2 37% had eGFRcys > 60 mL/min/1.73 m2. Furthermore, eGFRcr alone did not detect 6278 (8%) of older participants with eGFRcys < 60 mL/min/1.73 m2. In cross-sectional analyses, the median baseline eGFR was lower at higher age for all equations: this was most pronounced for eGFRcys (Figure 1). CKD by eGFRcys only or with both markers experienced higher absolute incidence of MI, stroke and mortality compared to those without CKD by either marker (Figure 2). Compared to those without CKD, older participants with concordant eGFRcr and eGFRcys < 60mL/min/1.73 m2 had elevated adjusted risks of death (HR 1.8, 1.6–2.0), MI (HR 1.9, 1.5–2.4), stroke (HR 1.7, 1.2–2.3) and kidney failure (HR 4.2, 1.2–14.1). Findings were similar in younger participants with concordant eGFRcr and eGFRcys < 60 mL/min/1.73 m2 for death (HR 2.2, 1.9–2.6) and stroke (HR 2.1, 1.4–3.2), though not MI (HR 1.2, 0.8–1.8). When CKD was not confirmed by eGFRcys, eGFRcr 45–59 mL/min/1.73 m2 was not associated with increased hazards of death (HR 1.1, 0.9–1.4), MI (HR 1.1, 0.7–1.7) or stroke (HR 1.1, 0.7–1.9) in older participants, nor in younger participants for the same outcomes: death (HR 1.1, 0.8–1.3), MI (HR 1.2, 0.8–1.9) and stroke (HR 0.8, 0.4–1.6).
CONCLUSION
Among persons with CKD, cardiovascular disease and mortality are important risks that should be considered when determining CKD status. CKD categorization by eGFRcr alone includes a large proportion of individuals who have similar risks to persons without CKD. eGFRcys detects a substantial number of high-risk individuals not identified to have CKD by eGFRcr. In the absence of cystatin C testing, lower, age-adapted thresholds for diagnosis of CKD may inadequately detect the broader risks associated with kidney disease in older people.
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