Defining renal phenotype in Alström syndrome.

BACKGROUND: Alström syndrome (AS) is a rare autosomal recessive ciliopathy with a wide spectrum of clinical features, including cone-rod retinal dystrophy, neuronal deafness, severe insulin resistance and major organ failure. The characteristics of renal disease in the syndrome have not been systematically described. The aim of this study is to define the onset and progression of renal disease in AS. METHOD: Prospective observational cohort study. SETTING AND PARTICIPANTS: Thirty-two adult subjects from a national specialist clinic in UK and 86 subjects from an international AS registry were studied. OUTCOMES: First, an international registry cross-sectional study across all age groups to determine change in kidney function was performed. Secondly, a detailed assessment was carried out of adult AS patients with serial follow-up to determine incidence, aetiology and progression of renal disease. ANALYTICAL APPROACH: Generalized estimating equations were used to evaluate the relationship between age and estimated glomerular filtration rate (eGFR). Associations between patient factors and eGFR levels were then assessed in the adult AS cohort. RESULTS: The international registry study of the renal function of 118 subjects with AS (median age 21 years) showed a rapid decline with age, at an average of -16.7 and -10.9 mL/min/1.73 m2 per decade in males and females, respectively. In a UK national cohort of 32 patients with AS (median age 22 years), 20/32 (63%) had chronic kidney disease (CKD) Stage 3 or above based on eGFR <60 mL/min/1.73 m2 or evidence of albuminuria. Hyperuricaemia was noted in 25/32 (79%). Structural abnormalities such as nephrocalcinosis without hypercalcaemia and cysts were observed in 20/32 (63%) subjects. Lower urinary tract symptoms were frequent in 17/19 (70%) of AS patients. Histological evidence showed mixed tubulo-interstitial and glomerular disease. CONCLUSIONS: This is the first study to demonstrate that renal disease is the hallmark of AS, which starts early and progresses with age, leading to a high prevalence of advanced CKD at young age. AS should be considered in the differential diagnosis of rare genetic renal diseases.

Myocardial characterization in pre-dialysis chronic kidney disease: a study of prevalence, patterns and outcomes.

BACKGROUND: Late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) characterizes myocardial disease and predicts an adverse cardiovascular (CV) prognosis. Myocardial abnormalities, are present in early chronic kidney disease (CKD). To date there are no data defining prevalence, pattern and clinical implications of LGE-CMR in CKD. METHODS: Patients with pre-dialysis CKD (stage 2-5) attending specialist renal clinics at University Hospital Birmingham (UK) who underwent gadolinium enhanced CMR (1.5 T) between 2005 and 2017 were included. The patterns and presence (LGEpos) / absence (LGEneg) of LGE were assessed by two blinded observers. Association between LGE and CV outcomes were assessed. RESULTS: In total, 159 patients received gadolinium (male 61%, mean age 55 years, mean left ventricular ejection fraction 69%, left ventricular hypertrophy 5%) with a median follow up period of 3.8 years [1.04-11.59]. LGEpos was present in 55 (34%) subjects; the patterns were: right ventricular insertion point n = 28 (51%), mid wall n = 18 (33%), sub-endocardial n = 5 (9%) and sub-epicardial n = 4 (7%). There were no differences in left ventricular structural or functional parameters with LGEpos. There were 12 adverse CV outcomes over follow up; 7 of 55 with LGEpos and 5 of 104 LGEneg. LGEpos was not predicted by age, gender, glomerular filtration rate or electrocardiographic abnormalities. CONCLUSIONS: In a selected cohort of subjects with moderate CKD but low CV risk, LGE was present in approximately a third of patients. LGE was not associated with adverse CV outcomes. Further studies in high risk CKD cohorts are required to assess the role of LGE with multiplicative risk factors.

A randomized, multicenter, open-label, blinded end point trial comparing the effects of spironolactone to chlorthalidone on left ventricular mass in patients with early-stage chronic kidney disease: Rationale and design of the SPIRO-CKD trial.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased left ventricular (LV) mass and arterial stiffness. In a previous trial, spironolactone improved these end points compared with placebo in subjects with early-stage CKD, but it is not known whether these effects were specific to the drug or secondary to blood pressure lowering. AIM: The aim was to investigate the hypothesis that spironolactone is superior to chlorthalidone in the reduction of LV mass while exerting similar effects on blood pressure. DESIGN: This is a multicenter, prospective, randomized, open-label, blinded end point clinical trial initially designed to compare the effects of 40weeks of treatment with spironolactone 25mg once daily to chlorthalidone 25mg once daily on the co-primary end points of change in pulse wave velocity and change in LV mass in 350 patients with stages 2 and 3 CKD on established treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Because of slow recruitment rates, it became apparent that it would not be possible to recruit this sample size within the funded time period. The study design was therefore changed to one with a single primary end point of LV mass requiring 150 patients. Recruitment was completed on 31 December 2016, at which time 154 patients had been recruited. Investigations included cardiac magnetic resonance imaging, applanation tonometry, 24-hour ambulatory blood pressure monitoring, and laboratory tests. Subjects are assessed before and after 40weeks of randomly allocated drug therapy and at 46weeks after discontinuation of the study drug.

Infection-related mortality is higher for kidney allograft recipients with pretransplant diabetes mellitus.

AIMS/HYPOTHESIS: The risk of infection-related mortality in kidney allograft recipients with pre-existing diabetes mellitus is unknown. We determined the risk of infection-related mortality after kidney transplantation in a population-based cohort stratified by diagnosis of pre-existing diabetes mellitus. METHODS: We linked data between two national registries (Hospital Episode Statistics and the Office for National Statistics) to select all mortality events after kidney transplantation in England between April 2001 and March 2012. The primary outcome measure was infection-related mortality after transplantation comparing diabetic with non-diabetic recipients. RESULTS: A total of 19,103 kidney allograft recipients were analysed; 2,968 (15.5%) were known to have diabetes before kidney transplantation. After transplantation, 2,085 deaths (10.9%) occurred (median follow-up 4.4 years [interquartile range 2.2-7.3]), with 434 classified as secondary to infection (20.8% of all deaths). Risk of overall (16.0% vs 10.0%, p < 0.001) and infection-related (3.3% vs 2.1%, p < 0.001) mortality after kidney transplantation was higher for diabetic than non-diabetic recipients, respectively. No cytomegalovirus-related deaths occurred in diabetic recipients compared with 5.7% in non-diabetic recipients (p < 0.007), with a trend towards more unspecified sepsis in diabetic recipients (30.6% vs 22.6%, respectively, p = 0.070). Diabetes at the time of transplantation was an independent risk factor predicting infection-related mortality in kidney allograft recipients after transplantation (HR 1.71 [95% CI 1.36, 2.15], p < 0.001). CONCLUSIONS/INTERPRETATION: Infection-related mortality is more common in kidney allograft recipients with pre-existing diabetes mellitus. Further work is required to determine whether attenuated immunosuppression is beneficial for diabetic kidney allograft recipients.

Reverse Myocardial Remodeling Following Valve Repair in Patients With Chronic Severe Primary Degenerative Mitral Regurgitation.

OBJECTIVES: The aims of this study were to quantify preoperative myocardial fibrosis using late gadolinium enhancement (LGE), extracellular volume fraction (ECV%), and indexed extracellular volume (iECV) on cardiac magnetic resonance; determine whether this varies following surgery; and examine the impact on postoperative outcomes. BACKGROUND: Myocardial fibrosis complicates chronic severe primary mitral regurgitation and is associated with left ventricular dilatation and dysfunction. It is not known if this nonischemic fibrosis is reversible following surgery or if it affects ventricular remodeling and patient outcomes. METHODS: A multicenter prospective study was conducted among 104 subjects with primary mitral regurgitation undergoing mitral valve repair. Cardiac magnetic resonance and cardiopulmonary exercise stress testing were performed preoperatively and ≥6 months after surgery. Symptoms were assessed using the Minnesota Living With Heart Failure Questionnaire. RESULTS: Mitral valve repair was performed for Class 2a indications in 65 patients and Class 1 indications in 39 patients. Ninety-three patients were followed up at 8.8 months (IQR: 7.4 months-10.6 months). Following surgery, there were significant reductions in both ECV% (from 27.4% to 26.6%; P = 0.027) and iECV (from 17.9 to 15.4 mL/m2; P < 0.001), but the incidence of LGE was unchanged. Neither preoperative ECV% nor LGE affected postoperative function, but iECV predicted left ventricular end-systolic volume index (ß = 1.04; 95% CI: 0.49 to 1.58; P < 0.001) and left ventricular ejection fraction (ß = -0.61; 95% CI: -1.05 to -0.18; P = 0.006). Patients with above-median iECV of ≥17.6 mL/m2 had significantly larger postoperative values of left ventricular end-systolic volume index (30.5 ± 12.7 mL/m2 vs 23.9 ± 8.0 mL/m2; P = 0.003), an association that remained significant in subcohort analyses of patients in New York Heart Association functional class I. CONCLUSIONS: Mitral valve surgery results in reductions in ECV% and iECV, which are surrogates of diffuse myocardial fibrosis, and preoperative iECV predicts the degree of postoperative remodeling irrespective of symptoms. (The Role of Myocardial Fibrosis in Degenerative Mitral Regurgitation; NCT02355418).

Cardiovascular Effects of Unilateral Nephrectomy in Living Kidney Donors at 5 Years.

[Figure: see text].

Perceptions of sexual coercion among young women in Uganda.

PURPOSE: This paper sets out to explore Ugandan young women's definitions and perceptions of sexual coercion. DESIGN/METHODOLOGY/APPROACH: A qualitative study was conducted with seven young women in rural Uganda. Participants filmed videos, wrote stories, made drawings and participated in transect walks before analysing their data through formal and informal discussions. FINDINGS: Forced sex is defined narrowly to mean only rape. Verbal forms of sexual coercion were recognised, but only after some discussion. Verbal coercion is referred to as "abusing" or "convincing". Young women are commonly pressured into consenting to have sex, despite what they really want, owing to the socio-cultural circumstances. Young women in Uganda are significantly tolerant of sexual coercion. This tolerance appears to arise from power differentials between genders, and the socio-cultural environment shaping their lives. ORIGINALITY/VALUE: The paper improves understanding of young women's definitions and perceptions of sexual coercion, which is essential to provide effective violence prevention programmes. It also suggests that further research is warranted in this field.

Defining Myocardial Abnormalities Across the Stages of Chronic Kidney Disease: A Cardiac Magnetic Resonance Imaging Study.

OBJECTIVES: A proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance. BACKGROUND: CKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown. METHODS: A total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T1 mapping (biomarker of diffuse fibrosis), T2 mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro-B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography. RESULTS: Native myocardial T1 times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p < 0.001), independent of hypertension and aortic distensibility. Left atrial volume, E/e', N-terminal pro-B-type natriuretic peptide, P1NP, and P3NP increased with CKD stage (p < 0.05), while effort tolerance (% predicted VO2Peak, %VO2VT) decreased (p < 0.001). In multivariable linear regression models, estimated glomerular filtration rate was the strongest predictor of native myocardial T1 time (p < 0.001). Native myocardial T1 time, left atrial dilatation, and high-sensitivity troponin T were independent predictors of % predicted VO2Peak (p < 0.001). CONCLUSIONS: Imaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862).

Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation.

BACKGROUND AND OBJECTIVES: The Effect of a Reduction in GFR after Nephrectomy on Arterial Stiffness and Central Hemodynamics (EARNEST) study was a multicenter, prospective, controlled study designed to investigate the associations of an isolated reduction in kidney function on BP and arterial hemodynamics. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective living kidney donors and healthy controls who fulfilled criteria for donation were recruited from centers with expertise in vascular research. Participants underwent office and ambulatory BP measurement, assessment of arterial stiffness, and biochemical tests at baseline and 12 months. RESULTS: A total of 469 participants were recruited, and 306 (168 donors and 138 controls) were followed up at 12 months. In the donor group, mean eGFR was 27 ml/min per 1.73 m2 lower than baseline at 12 months. Compared with baseline, at 12 months the mean within-group difference in ambulatory day systolic BP in donors was 0.1 mm Hg (95% confidence interval, -1.7 to 1.9) and 0.6 mm Hg (95% confidence interval, -0.7 to 2.0) in controls. The between-group difference was -0.5 mm Hg (95% confidence interval, -2.8 to 1.7; P=0.62). The mean within-group difference in pulse wave velocity in donors was 0.3 m/s (95% confidence interval, 0.1 to 0.4) and 0.2 m/s (95% confidence interval, -0.0 to 0.4) in controls. The between-group difference was 0.1 m/s (95% confidence interval, -0.2 to 0.3; P=0.49). CONCLUSIONS: Changes in ambulatory peripheral BP and pulse wave velocity in kidney donors at 12 months after nephrectomy were small and not different from controls. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: NCT01769924 (https://clinicaltrials.gov/ct2/show/NCT01769924).

Early effects of kidney transplantation on the heart - A cardiac magnetic resonance multi-parametric study.

Increased native myocardial T1 times in chronic kidney disease (CKD) may be due to diffuse interstitial myocardial fibrosis (DIF) or due to interstitial edema/inflammation. Concerns relating to nephrogenic systemic fibrosis with gadolinium-based contrast agents (GBCA) limit their use in end-stage kidney disease (ESKD) to measure extracellular volume (ECV) and characterise myocardial fibrosis. This study aimed to examine stability of myocardial T1 and T2 times before, and within 2 months after kidney transplantation; a time frame when volume status normalises but myocardial remodelling is unlikely to have occurred, and to compare these with ECV using GBCA after transplantation. Twenty-four patients with ESKD underwent serial cardiovascular magnetic resonance imaging, including T1 and T2 mapping. GBCA was administered on follow-up provided eGFR was >30 ml/min/1.73 m2. Eighteen age- and sex-matched controls were studied at one timepoint. ECV (ECV 28 ±â€¯2% vs. 24 ±â€¯2%, p = 0.001) and T2 times were higher in ESKD compared to controls. After transplantation, septal T1 times increased (MOLLI 985 ms ±â€¯25 vs. 1002 ms ±â€¯30, p = 0.014; ShMOLLI 974 ms ±â€¯39 vs. 992 ms ±â€¯33, p = 0.113), LV volumes reduced (LVEDvol indexed 79 ±â€¯24 vs. 63 ±â€¯20 ml/m2, p = 0.005) but LV mass was unchanged (LV mass index 89 g/m2 ±â€¯38 to 83 g/m2 ±â€¯23, p = 0.141). T2 times did not change after transplantation. Both ECV and myocardial T1 times are elevated in ESKD, supporting the theory that elevated T1 times are due to DIF, although a contribution from myocardial edema cannot be fully excluded. The lack of any fall in T1 or T2 times after transplantation suggests that myocardial T1 times are a stable measure of DIF in CKD.

Diffuse Myocardial Interstitial Fibrosis and Dysfunction in Early Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) have a disproportionately high risk of cardiovascular (CV) morbidity and mortality from the very early stages of CKD. This excess risk is believed to be the result of myocardial disease commonly termed uremic cardiomyopathy (UC). It has been suggested that interstitial myocardial fibrosis progresses with advancing kidney disease and may be the key mediator of UC. This longitudinal study reports data on the myocardial structure and function of 30 patients with CKD with no known cardiovascular disease and healthy controls. All patients underwent cardiac magnetic resonance imaging including T1 mapping and late gadolinium enhancement (if estimated glomerular filtration rate > 30 ml/min/1.73 m2). Over a mean follow-up period of 2.7 ± 0.8 years, there was no change in left ventricular mass, volumes, ejection fraction, native myocardial T1 times, or extracellular volume with CKD or in healthy controls. Global longitudinal strain (20.6 ± 2.9 s-1 vs 19.8 ± 2.9 s-1, p = 0.03) and mitral annular planar systolic excursion (13 ± 2 mm vs 12 ± 2 mm, p = 0.009) decreased in CKD but were clinically insignificant. Midwall late gadolinium enhancement was present in 4 patients at baseline and was unchanged at follow-up. Renal function was stable in this cohort over follow-up (change in estimated glomerular filtration rate was -3 ml/min/1.73 m2) with no adverse clinical CV events. In conclusion, this study demonstrates that in a cohort of patients with stable CKD, left ventricular mass, native T1 times, and extracellular volume do not increase over a period of 2.7 years.

Reference ranges for three-dimensional feature tracking cardiac magnetic resonance: comparison with two-dimensional methodology and relevance of age and gender.

Myocardial deformation is a sensitive marker of sub-clinical myocardial dysfunction that carries independent prognostic significance across a broad range of cardiovascular diseases. It is now possible to perform 3D feature tracking of SSFP cines on cardiac magnetic resonance imaging (FT-CMR). This study provides reference ranges for 3D FT-CMR and assesses its reproducibility compared to 2D FT-CMR. One hundred healthy individuals with 10 men and women in each of 5 age deciles from 20 to 70 years, underwent 2D and 3D FT-CMR of left ventricular myocardial strain and strain rate using SSFP cines. Good health was defined by the absence of hypertension, diabetes, obesity, dyslipidaemia, or any cardiovascular, renal, hepatic, haematological and systemic inflammatory disease. Normal values for myocardial strain assessed by 3D FT-CMR were consistently lower compared with 2D FT-CMR measures [global circumferential strain (GCS) 3D - 17.6 ± 2.6% vs. 2D - 20.9 ± 3.7%, P < 0.005]. Validity of 3D FT-CMR was confirmed against other markers of systolic function. The 3D algorithm improved reproducibility compared to 2D, with GCS having the best inter-observer agreement [intra-class correlation (ICC) 0.88], followed by global radial strain (GRS; ICC 0.79) and global longitudinal strain (GLS, ICC 0.74). On linear regression analyses, increasing age was weakly associated with increased GCS (R2 = 0.15, R = 0.38), peak systolic strain rate, peak late diastolic strain rate, and lower peak early systolic strain rate. 3D FT-CMR offers superior reproducibility compared to 2D FT-CMR, with circumferential strain and strain rates offering excellent intra- and inter-observer variability. Normal range values for myocardial strain measurements using 3D FT-CMR are provided.

Chronic kidney disease as a cardiovascular risk factor: lessons from kidney donors.

Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease but is often associated with other risks such as diabetes and hypertension and can be both a cause and an effect of cardiovascular disease. Although epidemiologic data of an independent association of reduced glomerular filtration rate with cardiovascular risk are strong, causative mechanisms are unclear. Living kidney donors provide a useful model for assessing the "pure" effects of reduced kidney function on the cardiovascular system. After nephrectomy, the glomerular filtration rate ultimately falls by about one-third so many can be classified as having chronic kidney disease stages 2 or 3. This prompts concern based on the data showing an elevated cardiovascular risk with these stages of chronic kidney disease. However, initial data suggested no increase in adverse cardiovascular effects compared with control populations. Recent reports have shown a possible late increase in cardiovascular event rates and an early increase in left ventricular mass and markers of risk such as urate and albuminuria. The long-term significance of these small changes is unknown. More detailed and long-term research is needed to determine the natural history of these changes and their clinical significance.

Gender Disparity in Living-Donor Kidney Transplant Among Minority Ethnic Groups.

OBJECTIVES: We have limited data on gender disparities between living kidney transplant donors and recipients across ethnic groups. MATERIALS AND METHODS: This was a retrospective cohort study of all living-donor kidney transplants performed at a single center in an ethnically diverse region of England. Data were extracted from the United Kingdom National Transplant Database and University Hospitals Birmingham electronic medical records. RESULTS: We analyzed 713 living-donor kidney transplant procedures that were performed from 1987 to 2014. Gender disparities were observed, with women more likely to be living donors (54.7%) and less likely to be recipients (39.4%). Most male recipients received kidneys from female donors versus male donors (70.2% vs 29.8%), whereas the proportion of men receiving kidneys from women (50.9%) and from men (49.1%) were similar (P < .001). Black, Asian, and donors from other minority groups comprised 18.7% of the donor cohort. South Asian partner-to-partner transplants (n = 22) were predominantly men receiving transplants from women (90.9%) versus women receiving transplants from men (9.1%; P = .003). Male patients more commonly donated their kidney to children than to women (10.2% vs 6.4%; P = .046). South Asian donations to children were similar between males and females; however, boys exclusively received kidneys from male donors (8/8) versus from female donors (8/12). CONCLUSIONS: Gender disparity exists in living-donor kidney transplant, with disparities more pronounced in some ethnic groups and among particular relationships. This finding requires targeted counseling and research to understand whether the cause is medical or sociocultural obstacles.

Do Obese Individuals With Hypertension Have More Difficult-to-Control Blood Pressure and End Organ Damage Than Their Nonobese Counterparts?

The authors assessed whether individuals with elevated body mass index (BMI) and hypertension had more difficult-to-control blood pressure (BP) and more evidence of end organ damage using data collected prospectively over 11 years from a secondary care hypertension clinic. A total of 1114 individuals were divided by BMI criteria into normal (n=207), overweight (n=440), and obese (n=467). Mean daytime, nighttime, and 24-hour systolic BP and diastolic BP were similar in all groups. There was less nocturnal dip in obese compared with overweight groups (P=.025). Individuals with a normal BMI were taking fewer antihypertensive medications than those in the obese group (P=.01). Individuals classified as obese had a higher left ventricular mass index than those with a normal BMI (female, P=.028; male, P<.001); this relationship remained after multivariate linear regression. Obese individuals with hypertension required more medication to achieve similar mean ambulatory BP values, had less nocturnal dip in BP, and had a higher prevalence of left ventricular hypertrophy. As such, obese patients are at potentially increased risk of cardiovascular events.

Diffuse interstitial fibrosis and myocardial dysfunction in early chronic kidney disease.

Early-stage chronic kidney disease (CKD) is an under-recognized highly prevalent cardiovascular (CV) risk factor. Despite a clustering of conventional atherosclerotic risk factors, it is hypothesized that nonatherosclerotic processes, including left ventricular (LV) hypertrophy and fibrosis, account for a significant excess of CV risk. This cross-sectional observational study of 129 age- (mean age 57±10 years) and gender-matched subjects examined: nondiabetic CKD stages 2 to 4 (mean glomerular filtration rate 50±22 ml/min/1.73 m2) with no history of CV disease, subjects who are hypertensive with normal renal function, and healthy controls. Cardiac magnetic resonance imaging was performed for assessment of LV volumes and systolic function (myocardial deformation). Diffuse myocardial fibrosis was assessed using T1 mapping for native myocardial T1 times before contrast and myocardial extracellular volume (ECV) after gadolinium administration in combination with standard late gadolinium enhancement techniques for detection of coarse fibrosis. Patients with CKD had increased native T1 times (986±37 ms) and ECV (0.28±0.04) compared with controls (955±30 ms, 0.25±0.03) and subjects who are hypertensive (956±31 ms, 0.25±0.02, p<0.05). Both T1 times and ECV were correlated with impaired systolic function as assessed by global longitudinal systolic strain (r=-0.22, p<0.05, and r=-0.43, p<0.01, respectively). There were no differences in LV volumes, ejection fraction, or LV mass. T1 times and ECV did not correlate with conventional CV risk factors. In conclusion, diffuse myocardial fibrosis is increased in early CKD and is associated with abnormal global longitudinal strain, an early feature of uremic cardiomyopathy and a key indicator of adverse CV prognosis.

Acute Care QUAliTy in chronic Kidney disease (ACQUATIK): a prospective cohort study exploring outcomes of patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is common and carries a high risk of morbidity, including hospital admissions and readmissions and mortality. This is largely attributed to an increased risk of cardiovascular disease. Patients with CKD are less likely to receive evidence-based treatments for cardiovascular disease. However, these treatments are based on trials which generally exclude patients with CKD. It is therefore unclear whether this patient group derives the same benefits without an increased risk of adverse effects. METHODS AND ANALYSIS: The Acute Care QUAliTy in chronic Kidney disease (ACQUATIK) study is a prospective, observational, multicentre cohort study. Over 4000 patients will be recruited with an enrolment period of 2 years and a follow-up period of 2-4 years. Patients under follow-up by a renal team will be excluded. Data will be obtained from patient and hospital records during the index admission. Preadmission data will be extracted from general practice records based on the Quality and Outcomes Framework. Diagnosis, comorbidities and procedure data pertaining to the index and subsequent admissions will be extracted from the Hospital Episode Statistics database and long-term mortality data will be tracked using the Office of National Statistics. This information will allow us to examine a complete patient journey through primary and secondary care, providing unequalled levels of information on treatment and outcomes of patients with CKD. The combined data set will be used to compare outcomes and treatments among patients with CKD versus patients without CKD. The primary end point is hospital readmission rates. The relationship between age, sex, ethnicity, socioeconomic status and concurrent comorbidities will be analysed to determine their influence on outcomes and treatments. ETHICS AND DISSEMINATION: The ACQUATIK study has been approved by the NRES Committee West Midlands-South Birmingham-Reference 13/WM/0317. The results from ACQUATIK will be submitted for publication in peer-reviewed journals and presented at primary and secondary care conferences. TRIAL REGISTRATION NUMBER: ISRCTN37237454.

Increased incidence of cardiovascular events in patients with antineutrophil cytoplasmic antibody-associated vasculitides: a matched-pair cohort study.

OBJECTIVE: To explore the risk of cardiovascular disease in patients with antineutrophil cytoplasmic antibody-associated vasculitides (AAVs) and to assess contributing risk factors. METHODS: In a retrospective matched-pair cohort study, 113 of 131 patients with AAVs from a vasculitis clinic registry were matched 1:1 for renal function, age at diagnosis, sex, smoking status, and previous history of a cardiovascular disease to patients with noninflammatory chronic kidney disease (CKD). Cardiovascular events were defined as acute coronary syndrome, new-onset angina, symptomatic peripheral vascular disease, stroke, and transient ischemic attack. RESULTS: Median followup times were 3.4 years for the AAV patients and 4.2 years for the CKD patients. More cardiovascular events occurred in the AAV group (23 of 113) than in the CKD group (16 of 113). Cox regression survival analysis showed a significantly increased risk of a cardiovascular event for AAV patients, with a hazard ratio (HR) of 2.23 (95% confidence interval [95% CI] 1.1-4.4) (P = 0.017). Within the cohort of AAV patients, the most strongly predictive factors were previous history of cardiovascular disease (HR 4 [95% CI 1.7-9.8]), history of dialysis dependency (HR 4.3 [95% CI 1.5-12.1]), ever having smoked (HR 3.9 [95% CI 1.5-10]), age at diagnosis (HR 1.038 [95% CI 1.006-1.072]), estimated glomerular filtration rate at remission (HR 0.977 [95% CI 0.957-0.998]), and serum cholesterol concentration at presentation (HR 0.637 [95% CI 0.441-0.92]). CONCLUSION: In this retrospective study, patients with AAVs appear at greater risk of cardiovascular disease, with increased risk in those with a previous history of cardiovascular disease, dialysis dependency, poor renal function at remission, or a history of smoking. Measures to reduce the risk of cardiovascular disease should be integral to the management of systemic vasculitis.