The Association of Echocardiographic Peak Systolic Strain Rate with Cardiovascular Outcomes in Haemodialysis Patients.

BACKGROUND/AIMS: Echocardiographic abnormalities of systolic function can be detected earlier with advancing echocardiographic technologies. Given the high prevalence of left ventricular hypertrophy in dialysis patients, we hypothesised that one such marker of strain, peak systolic strain rate (SR) would demonstrate association with cardiovascular outcome in a haemodialysis cohort. METHODS: Recruited prevalent haemodialysis patients underwent standard transthoracic echocardiography as part of a detailed cardiovascular assessment on a non-dialysis day during a short inter-dialytic midweek break. Patients were followed up to mortality and cardiovascular end points. Multivariate Cox proportional hazard models were built to determine the association of above versus below median SR in a model adjusted for confounding factors. RESULTS: 183 patients were enrolled and followed up for a median 925 days. Median age was 64.9 years, prevalence of LVH 55%, and median SR -0.86 (-1.00 to -0.72). An SR greater than -0.86 S-1 (less negative) had a hazard ratio (HR) of 2.32 (1.36 to 3.95) in association with all-cause mortality after adjustment for EF, age, smoking history, MI, previous transplant, albumin and systolic blood pressure. For cardiovascular mortality, the HR was 2.343 (0.99 to 5.553) p =0.046. The only echocardiographic parameter independently associated with MACE was above median E/e (HR 2.09 [1.03 to 4.24], p=0.04). No echocardiographic parameter was associated with heart failure episodes. CONCLUSION: SR demonstrates association with outcome in this population and highlights the consideration that such sub-clinical cardiac changes should be routinely sought when referring haemodialysis patients for cardiac assessments.

Prevalence and outcomes of proton pump inhibitor associated hypomagnesemia in chronic kidney disease.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most widely prescribed medications across the world. PPIs have been associated with significant electrolyte abnormalities including hypomagnesaemia. We explored the prevalence of PPI associated hypomagnesaemia (PPIH) in different Chronic Kidney Disease (CKD) stages, in different PPI agents, and the impact of PPIH on survival in CKD. METHODS: This was a subgroup analysis of the Salford Kidney Study, a prospective, observational, longitudinal study of non-dialysis CKD patients. Patients with outpatient magnesium samples obtained between 2002 and 2013 were included in the analysis. The prevalence hypomagnesaemia based on mean values over 12 months as well as 'ever' hypomagnesaemia were investigated. RESULTS: 1,230 patients were included in this analysis, mean age 64.3± 32.3 years and mean eGFR 29.2±15.8 ml/min/1.73m2. Mean serum magnesium in those on PPI was significantly lower than those not on PPI overall (0.85±0.10 mmolL-1 versus 0.79±0.12 mmolL-1 respectively, p<0.001). This finding was maintained at all CKD stages. The adjusted odds ratio (OR) for mean hypomagnesaemia in PPI use was 1.12 (95% CI 1.06-1.18) p = <0. 'Ever hypomagnesaemia' had an OR of 1.12 (95% CI 1.07-1.16) p = <0.001. The expected rise in serum magnesium with declining eGFR was not observed in those on a PPI but was seen in those not on PPI. There was no difference in serum magnesium between PPI drugs. Thiazide diuretics were also associated with hypomagnesaemia independent of PPI use. Cox regression analysis demonstrated no reduction in survival in patients with PPI associated hypomagnesaemia. CONCLUSION: No specific PPI drugs show a favourable profile in regards of risk for hypomagnesaemia in CKD. Avoiding concurrent use of PPI and thiazide may be of value in patients with hypomagnesaemia.

Non-recruitment to and selection bias in studies using echocardiography in haemodialysis patients.

BACKGROUND: It is unknown whether patients recruited to renal cardiac imaging studies are fully representative of the investigated population and whether there are differences in characteristics and survival between participants and non-participants (excluded or declined consent). Subjects and Methods Four hundred thirty-five maintenance haemodialysis patients were screened in an observational, prospective study. Baseline demographics, laboratory results, social deprivation scores and survival data were collected from patient records. All patients were followed-up until death, renal transplantation or 16 November 2015. RESULTS: Forty-four patients were excluded (16 language barrier, 10 mental incapacity, 9 severe co-morbid illness and 9 because of immobility), 172 patients declined consent (84% due to reluctance to attend for an extra visit) and 219 patients were recruited. Excluded patients had a lower mean haemoglobin (10.2 g/dL vs 10.7 g/dL), phosphate (4.15 mg/dL vs 4.74 mg/dL), albumin (3.6 g/dL vs 3.8 g/dL) and higher C-reactive protein (3.2 mg/dL vs 1.6 mg/dL) compared with recruited patients. No difference was identified between groups for Charleston comorbidity index (P = 0.115) or social deprivation scores. After a median follow-up of 29.7 (25th-75th percentile, 21.1-34.3) months, there were 141 deaths. In a multivariable Cox regression model adjusting for BMI, age, Charleston comorbidity index, haemoglobin, albumin, smoking status and diabetes mellitus, patients who declined consent had an adjusted HR of 1.70, 95% CI 1.10-2.52, and excluded patients had an adjusted HR of 1.30, 95% CI 0.75-2.25, for all-cause mortality compared with recruited patients. CONCLUSIONS: Patients recruited to the study had longer survival compared with non-participants. Research studies should document phenotypes of non-participants to aid interpretation and generalizability of results.

Speckle tracking determination of mitral tissue annular displacement: comparison with strain and ejection fraction, and association with outcomes in haemodialysis patients.

Abnormal Global longitudinal strain (GLS) and reduced left ventricular ejection fraction (LVEF) are established poor prognostic risk factors in haemodialysis patients. Tissue motion annular displacement of mitral valve annulus (TMAD), determined by speckle tracking echocardiography (STE), can be performed rapidly and is an indicator of systolic dysfunction, but has been less well explored. This study aims to compare TMAD with GLS and LVEF and its association with outcomes in haemodialysis patients. 198 haemodialysis patients (median age 64.2 years, 69 % men) had 2D echocardiography, with STE determined GLS and TMAD. Bland-Altman analysis and linear regression assessed relationship between GLS, LVEF and TMAD. Cox regression analysis investigated association of TMAD with mortality and cardiac events. TMAD had low inter- and intra-observer variability with small biases and narrow limits of agreement (LOA) (bias of -0.01 ± 1.32 (95 % LOA was -2.60 to 2.58) and -0.07 ± 1.27 (95 % LOA -2.55 to 2.41) respectively). There was a moderate negative correlation between GLS and LVEF (r = -0.383, p < 0.001) and a weak positive correlation between TMAD and LVEF (r = 0.248, p < 0.001). There was strong negative correlation of TMAD with GLS (r = -0.614, p < 0.001). In a multivariable Cox regression analysis, TMAD was not associated with mortality (HR 1.04, 95 % CI 0.91-1.19), cardiac death (HR 1.03, 95 % CI 0.80-1.32) or cardiac events (HR 0.91, 95 % CI 0.80-1.02). TMAD is a quick and reproducible alternative to GLS which may be very useful in cardiovascular risk assessment, but does not have the same prognostic value in HD patients as GLS.

Novel Approach to Cardiovascular Outcome Prediction in Haemodialysis Patients.

BACKGROUND: Cardiovascular mortality is high in haemodialysis (HD) patients. Arterial stiffness and global longitudinal strain (GLS) are important non-atheromatous cardiovascular risk predictors. No study has encompassed both parameters in a combined model for prediction of outcomes in HD patients. This is important because left ventricular (LV) dysfunction can result from fibrotic remodelling secondary to increased arterial stiffness. METHODS: Two hundred and nineteen HD patients had pulse wave velocity (PWV) and echocardiography (including GLS) assessments. Patients were followed-up until death, transplantation or November 16, 2015, whichever happened first. Pearson's correlation coefficient was used to determine factors associated with PWV and GLS. A multivariable Cox regression model investigated factors associated with all-cause, cardiac death and events. RESULTS: One hundred and ninety eight HD patients had full datasets (median age 64.2, 68.7% males) with a mean LV ejection fraction (LVEF) of 61.7 ± 10.1% and GLS -13.5 ± 3.3%; 51% had LV hypertrophy. Forty eight deaths (15 cardiac) and 44 major cardiac events occurred during a median follow-up of 27.6 (25th-75th percentile, 17.3-32.7) months. In separate survival models, PWV and GLS were independently associated with all-cause mortality; however, in a combined model, LV mass indexed to height2.7 (LVMI/HT2.7; adjusted hazard ratio (HR) 1.02, 95% CI 1.00-1.04) and PWV (adjusted HR 1.23, 95% CI 1.03-1.47) were significant. PWV was neither associated with cardiac death nor associated with related cardiac events. However, GLS was associated with cardiac death (adjusted HR 1.24, 95% CI 1.00-1.54) and cardiac events (adjusted HR 1.13, 95% CI 1.03-1.25). CONCLUSIONS: PWV and LVMI/HT2.7 were superior to GLS in prediction of all-cause mortality. However, GLS was associated with cardiac death and events even when accounting for LVEF and LVMI/HT2.7.

Association of serum sodium levels with all-cause and cardiovascular mortality in chronic kidney disease: Results from a prospective observational study.

AIMS: The prevalence of hyponatraemia in the outpatient setting has not been thoroughly explored, and little is known about the prognostic implication of dysnatraemia in chronic kidney disease (CKD) patients, in particular accommodating the effect of concurrent medications. METHODS: This is a prospective observational study of non-dialysis-dependent CKD patients managed in a nephrology clinic. Patients enrolled between 2002 and 2012 in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed using baseline sodium and 12-month time-averaged sodium, with adjustment for co-morbid diseases, laboratory findings and concurrent medications. RESULTS: At baseline (n = 2093), mean estimated glomerular filtration rate was 32.8 ± 15.9 ml/min per 1.73 m(2) , median age was 67 (interquartile range 56-75) years and median serum sodium concentration was 140 (138-142) mmol/l. After a follow up of 41 (18-67) months, there were 684 deaths, 174 from cardiovascular causes; 1925 time-averaged sodium values were analysed. In the Cox multivariate adjusted regression, baseline hyponatraemia, but not hypernatraemia, was independently associated with all-cause mortality (hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.02-1.78, P = 0.04, and HR 1.15, 95% CI 0.84-1.57, P = 0.39, respectively). This was similarly the case for time-averaged hyponatraemia and hypernatraemia (HR 2.15, 95% CI 1.59-2.91, P < 0.01, and HR 1.47, 95% CI 0.93-2.38, P = 0.10, respectively). However, the association of baseline and time-averaged hyponatraemia with cardiovascular mortality was not significant. CONCLUSION: Hyponatraemia in the ambulatory setting is associated with all-cause but not cardiovascular mortality in CKD, independent of concomitant medications and co-morbidities.

Three-Dimensional Imaging of a Central Venous Dialysis Catheter Related Infected Thrombus.

Three-dimensional (3D) echocardiography is becoming widely available and with novel applications. We report an interesting case of a 68-year-old lady with a central venous thrombosis coincident with both a dialysis catheter infection and a recent pacemaker insertion. Two-dimensional transesophageal echocardiography was unable to delineate whether the thrombosis was involved with the pacemaker wire or due to the tunneled catheter infection. The use of 3D echocardiography was able to produce distinct images aiding diagnosis. This circumvented the need for invasive investigations and inappropriate, high-risk removal of the pacing wire. This case highlights the emerging application of 3D echocardiography in routine nephrology practice.

Risks for mortality and renal replacement therapy in atherosclerotic renovascular disease compared with other causes of chronic kidney disease.

AIM: Patients with atherosclerotic renovascular disease (ARVD) have an increased risk for death and likelihood of initiating renal replacement therapy (RRT) compared with the general population. No data exist to describe prognosis in ARVD compared with other causes of chronic kidney disease (CKD). We compare patient outcomes between ARVD and other causes of CKD. METHODS: Patients were selected from two prospective observational cohort studies of outcome in ARVD and CKD. Multivariate Cox regression was used to compare risk for RRT and death (both prior to and following initiation of RRT) between patients with ARVD and other causes of CKD. RESULTS: Of 1472 patients (563 (38%) ARVD, 909 (62%) non-ARVD), 242 (16%) progressed to RRT and 640 (44%) died over a median follow-up period of 4.1 (2.4-5.6) years. Patients with ARVD had an increased risk for death (HR 1.5 (1.2-1.8), P < 0.001) but not for RRT (HR 1.0 (0.7-1.4), P = 0.9). The largest increase in risk for death was observed relative to renal limited diseases, e.g. pyelonephritis (HR 2.4 (1.3-4.5), P = 0.004) and interstitial/infiltrative disease (HR 2.2 (1.3-4.5), P = 0.02). Following initiation of RRT, patients with ARVD had a significantly increased risk for death compared with patients without ARVD (HR 3.3 (2.2-5.0), P < 0.001). CONCLUSIONS: Patients with ARVD as a cause of CKD have an increased risk for death both prior to and following initiation of RRT. Further work should seek to identify modifiable risk factors relevant to prognosis.

Cardiac imaging in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) carry a high cardiovascular risk. In this patient group, cardiac structure and function are frequently abnormal and 74% of patients with CKD stage 5 have left ventricular hypertrophy (LVH) at the initiation of renal replacement therapy. Cardiac changes, such as LVH and impaired left ventricular systolic function, have been associated with an unfavourable prognosis. Despite the prevalence of underlying cardiac abnormalities, symptoms may not manifest in many patients. Fortunately, a range of available and emerging cardiac imaging tools may assist with diagnosing and stratifying the risk and severity of heart disease in patients with CKD. Moreover, many of these techniques provide a better understanding of the pathophysiology of cardiac abnormalities in patients with renal disease. Knowledge of the currently available cardiac imaging modalities might help nephrologists to choose the most appropriate investigative tool based on individual patient circumstances. This Review describes established and emerging cardiac imaging modalities in this context, and compares their use in CKD patients with their use in the general population.

Functional status and mortality in chronic kidney disease: results from a prospective observational study.

BACKGROUND/AIMS: Measures of functional status are used in the general population to aid prognostication but their use has not been explored in pre-dialysis chronic kidney disease (CKD). This analysis considers the association between the Karnofsky performance score (KPS) and all-cause mortality in a CKD stage 3-5 cohort. METHODS: Patients were selected from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS), a prospective observational study of outcome in CKD. Risk for death was assessed using multivariate Cox regression, and differences in progression of biochemical parameters were considered in a mixed-effects model. RESULTS: A total of 1,515 patients with a median follow-up time of 2.9 (1.5-4.8) years were considered. Baseline age was 60 ± 11 years and eGFR was 30 ± 12 ml/min/1.73 m(2). Patients with a reduced KPS had an increased risk for death. The hazard ratio (HR) for death was: KPS 90 group, HR 1.2 (95% CI 0.9-1.5), p = 0.1; KPS ≤ 80 group, HR 1.8 (95% CI 1.4-2.4), p < 0.001. In the mixed-effects model, the average annual loss of eGFR was greater in patients with a KPS ≤ 80 versus patients with a KPS >80 (5 vs. 3%, p = 0.008). CONCLUSION: A reduced KPS is independently associated with risk for mortality in patients with CKD stages 3-5. This may relate to a more rapid loss of eGFR.

Sudden cardiac death in haemodialysis patients: preventative options.

Sudden cardiac death (SCD) is the most common cause of death in haemodialysis patients, accounting for 25% of all-cause mortality. There are many potential pathological precipitants as most patients with end-stage renal disease have structurally or functionally abnormal hearts. For example, at initiation of dialysis, 74% of patients have left ventricular hypertrophy. The pathophysiological and metabolic milieu of patients with end-stage renal disease, allied to the regular stresses of dialysis, may provide the trigger to a fatal cardiac event. Prevention of SCD can be seen as a legitimate target to improve survival in this patient group. In the general population, this is most effective by reducing the burden of ischaemic heart disease. However, the aetiology of SCD in haemodialysis patients appears to be different, with myocardial fibrosis, vascular calcification and autonomic dysfunction implicated as possible causes. Thus, the range of therapies is different to the general population. There are potential preventative measures emerging as our understanding of the underlying mechanisms progresses. This article aims to review the evidence for therapies to prevent SCD effective in the general population when applied to dialysis patients, as well as promising new treatments specific to this population group.

Echocardiography in hemodialysis patients: uses and challenges.

Patients with end-stage renal disease undergoing hemodialysis have high rates of morbidity and mortality. Cardiovascular disease accounts for almost half of this mortality, with the single most common cause being sudden cardiac death. Early detection of abnormalities in cardiac structure and function may be important to allow timely and appropriate cardiac interventions. Echocardiography is noninvasive cardiac imaging that is widely available and provides invaluable information on cardiac morphology and function. However, it has limitations. Echocardiography is operator dependent, and image quality can vary depending on the operator's experience and the patient's acoustic window. Hemodialysis patients undergo regular hemodynamic changes that also may affect echocardiographic findings. An understanding of the prognostic significance and interpretation of echocardiographic results in this setting is important for patient care. There are some emerging techniques in echocardiographic imaging that can provide more detailed and accurate information compared with conventional 2-dimensional echocardiography. Use of these novel tools may further our understanding of the pathophysiology of cardiac disease in patients with end-stage renal disease undergoing hemodialysis.

Extreme Elevations in Blood Pressure and All-Cause Mortality in a Referred CKD Population: Results from the CRISIS Study.

Hypertension frequently complicates chronic kidney disease (CKD), with studies showing clinical benefit from blood pressure lowering. Subgroups of patients with severe hypertension exist. We aimed to identify patients with the greatest mortality risk from uncontrolled hypertension to define the prevalence and phenotype of patients who might benefit from adjunctive therapies. 1691 all-cause CKD patients from the CRISIS study were grouped by baseline blood pressure-target (<140/80 mmHg); elevated (140-190/80-100 mmHg); extreme (>190 and/or 100 mmHg). Groups were well matched for age, eGFR, and comorbidities. 77 patients had extreme hypertension at recruitment but no increased mortality risk (HR 0.9, P = 0.9) over a median follow-up period of 4.5 years. The 1.2% of patients with extreme hypertension at recruitment and at 12-months had a significantly increased mortality risk (HR 4.3, P = 0.01). This association was not seen in patients with baseline extreme hypertension and improved 12-month blood pressures (HR 0.86, P = 0.5). Most CKD patients with extreme hypertension respond to pharmacological blood pressure control, reducing their risk for death. Patients with extreme hypertension in whom blood pressure control cannot be achieved have an approximate prevalence of 1%. These patients have an increased mortality risk and may be an appropriate group to consider for further therapies, including renal nerve ablation.

Seroprevalence of hepatitis E virus in Hong Kong, 2008-2009.

The public health impact of hepatitis E virus (HEV) infection varies across the world. An HEV vaccine has been recently approved for clinical use in China. Population-specific seroprevalence data are essential for cost-effective assessment of vaccination programs. Here, a cross-sectional study was performed to provide an update on the local seroprevalence of HEV. An archive of serum samples submitted for virological investigation between 2008 and 2009 to a general hospital was used. A total of 450 samples with equal numbers from each gender covering the age groups from 1-10 to >80 years (25 samples per group) were tested for HEV immunoglobulin G (IgG) by enzyme-linked immunoassay. Age- and gender-specific seroprevalence were determined. The HEV IgG positive rate increased from 8% among 1-10 years to 56% among >80 years. The increase in prevalence was constant throughout all age groups without a steeper slope or plateau observed from any age group. The overall positive rate among males was significantly higher than among females (32.9% vs. 24.4%, P = 0.048). The best-fitted seroprevalence curves also suggested a higher positive rate for males across all age groups. Increased HEV IgG positivity was noted in comparison with historical local studies. Collectively, the prevalence of HEV in Hong Kong has increased over the past decade. A large proportion of the population is still susceptible to infection, and all age groups are at risk. Territory-wide vaccination program should be considered.

Predictive value of myocardial and coronary imaging in the long-term outcome of potential renal transplant recipients.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality in renal transplant recipients, but there is no agreed screening protocol. The value of myocardial perfusion imaging (MPI) and coronary angiography (CA) in predicting future cardiovascular events and mortality in unselected dialysis patients was studied. METHODS: Forty seven patients (mean age 51±14 years, 37 males), underwent both CA and MPI as part of pre-renal transplant assessment between 1995 and 1999. Follow-up period was 75±132 (range 3 to 143) months. RESULTS: Twenty-two (46.8%) patients had >50% stenosis of at least one major coronary artery (CAD), only 10 patients had abnormal MPI. Positive CA was found in all patients with angina and in 80% of diabetics. During follow-up 18 (38.3%) patients received a transplant and 28 (59.6%) patients died, of which 16 were proven or suspected cardiac deaths. Survival was significantly longer in patients with negative MPI or CA (92 and 96 versus 29 and 54 months for positive studies, respectively). CA had PPV of 95.7% and NPV of 54.2% for predicting the combined outcome of death and cardiovascular events whereas for MPI and MUGA, PPVs were 90.9% and 73.3% and NPVs 37.8% and 30%, respectively. CONCLUSIONS: Although MPI had a high specificity for CAD detection, its sensitivity appears limited in dialysis patients. The study suggests that those with angina and/or diabetes should undergo CA because of the high incidence of CAD in these groups, but MPI was at least as important as CA in overall mortality prediction over a long follow-up.

Comparison of intravenous iron sucrose versus low-molecular-weight iron dextran in chronic kidney disease.

BACKGROUND: Low-molecular-weight iron dextran (CosmoFer) is the only form of parenteral iron that can be administered as a total dose infusion (TDI) in the United Kingdom (UK). This study aimed to evaluate the safety and efficacy of TDI CosmoFer in comparison to intravenous iron sucrose infusion (Venofer) in patients with chronic kidney disease (CKD). METHODS AND RESULTS: A retrospective study of outpatients with CKD undergoing intravenous TDI CosmoFer or Venofer infusion was conducted at Salford Royal Hospital and Sunderland Royal Hospital. A total of 979 doses of CosmoFer and 504 doses of Venofer were administered. There were three minor adverse events in patients receiving CosmoFer compared with one minor event in a Venofer treated patient. There were no anaphylactoid-type reactions in either group. Serum haemoglobin, ferritin and transferrin saturation (TSAT) improved significantly 4-6 months postinfusion in both treatment groups. CONCLUSION: TDI CosmoFer is an efficacious method of replenishing iron stores in CKD patients in an outpatient setting. Furthermore, TDI CosmoFer is safe and not associated with an increase in adverse events compared to Venofer.