Elaine Rutherford

Defining myocardial tissue abnormalities in end-stage renal failure with cardiac magnetic resonance imaging using native T1 mapping

Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking–derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.

Kidney biopsy findings in primary Sjögren syndrome

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Risk factors and outcome of Stroke in renal transplant recipients

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.

Effect of left atrial and ventricular abnormalities on renal transplant recipient outcome—a single-center study

BackgroundPremature cardiovascular (CV) death is the commonest cause of death in renal transplant recipients. Abnormalities of left ventricular (LV) structure (collectively termed uremic cardiomyopathy) and left atrial (LA) dilation, a marker of fluid status and diastolic function, are risk factors for reduced survival in patients with end stage renal disease (ESRD). In the present analysis, we studied the impact of pre-transplant LA and LV abnormalities on survival after successful renal transplantation (RT).MethodsOne hundred nineteen renal transplant recipients (first transplant, deceased donors) underwent cardiovascular MRI (CMR) as part of CV screening prior to inclusion on the waiting list. Data regarding transplant function and patient survival after transplantation were collected.ResultsMedian post-transplant follow-up was 4.3 years (interquartile range (IQR) 1.9, 6.2). During the post-transplant period, 13 patients returned to dialysis after graft failure and 23 patients died with a functioning graft. Survival analyses, censoring for patients returning to dialysis, showed that pre-transplant LV hypertrophy and elevated LA volume were significantly associated with reduced survival after transplantation. Multivariate Cox regression analyses demonstrated that longer waiting time, poorer transplant function, presence of LV hypertrophy and higher LA volume on screening CMR and female sex were independent predictors of death in patients with a functioning transplant.ConclusionsPresence of LVH and higher LA volume are significant, independent predictors of death in patients who are wait-listed and proceed with renal transplantation.

An Open-Label Dose-Finding Study of Allopurinol to Target Defined Reduction in Urate Levels in Hemodialysis Patients

Allopurinol is a xanthine oxidase inhibitor mainly used to reduce circulating urate (also known as uric acid) levels. This helps to prevent recurrent urate crystal deposition in the form of gout.1 Gout is relatively common in patients with renal failure. Although routine dose reduction of allopurinol is recommended in the hemodialysis (HD) population this is not based on evidence from robust clinical trials.2 Guidelines generally recommend aiming to reduce urate levels by 50% to protect against future gout episodes.3 This study aimed to determine the optimal dose of allopurinol to achieve this in the HD population. Determining an optimal dose of allopurinol to use in the HD population will first help to guide clinicians in their treatment of their HD patients who develop gout. Second, patients with end-stage renal disease are at greatly increased risk of cardiovascular disease and death.4 Urate levels are known to be higher in the chronic kidney disease (CKD) population than in the general population.5 We know from large observational studies that increased urate levels are strongly associated with an increased cardiovascular risk, in both the general and CKD populations.6–9 In addition to its urate-lowering abilities, allopurinol itself has some specific properties that make it a potentially attractive drug to use in the HD population. Allopurinol has been shown to improve endothelial function in several population groups— including CKD patients—who are prone to endothelial dysfunction.10–12 In a large observational study the use of allopurinol was associated with reduced cardiovascular and all-cause mortality in patients undergoing HD who had no history of cardiovascular disease.13 In addition to this, allopurinol has also been demonstrated to regress left ventricular hypertrophy (LVH) in CKD, diabetic patients and in those with ischemic heart disease.10,11,14 Given that reduction in left ventricular mass is a common therapeutic target in the HD population,15–18 it is a natural question whether allopurinol might also regress LVH in this population. Until now this had not been investigated in a robust prospective clinical trial. We therefore designed a clinical trial to investigate this, the ALTERED (Does ALlopurinol regress lefT ventricular hypertrophy in End stage REnal Disease) study. This study looked to address this question through a multicenter randomized, placebo-controlled, double-blind trial of allopurinol. The primary outcome of the ALTERED study is change in left ventricular mass measured by cardiac magnetic resonance imaging at follow-up from baseline after 1 year of therapy. For the reasons described above, defining the optimal dose of allopurinol to use in this study was a priority. The first stage of the ALTERED study was therefore an open-label dose-escalation study to determine the

Myocardial changes in incident haemodialysis patients over 6-months: an observational cardiac magnetic resonance imaging study

Patients commencing on haemodialysis (HD) have an increased risk of cardiovascular events in the first year after starting HD compared to those patients established on HD longer. Left ventricular (LV) hypertrophy and abnormal myocardial strain predict mortality. There may be changes in the myocardium of incident HD patients over a 6-month period of HD which may explain changes in cardiovascular risk. We used CMR to consider changes in LV mass, myocardial strain and T1 mapping. We examined changes in pre-dialysis highly sensitive troponin T. 33 patients undergoing HD for <12 months were recruited. Participants underwent CMR at baseline and after 6-months of standard care. 6-months of HD was associated with reduction in LV mass index (Baseline: 78.8 g/m2 follow up: 69.9 g/m2, p = <0.001). LV global longitudinal strain also improved (Baseline: −17.9%, follow up: −21.6%, p = <0.001). Change in T1 time was not significant (Baseline septal T1 1277.4 ms, follow up 1271.5 p = 0.504). Highly sensitive troponin T was lower at follow up (Baseline 38.8 pg/L, follow up 30.8 pg/L p = 0.02). In incident HD patients, 6-months of HD was associated with improvements in LV mass, strain and troponin. These findings may reflect improvement in known cardiac tissue abnormalities found in patients over the first year of HD.