Darren Green

Sudden Cardiac Death in Hemodialysis Patients: An In-Depth Review

Sudden cardiac death (SCD) is the leading cause of death in hemodialysis patients, accounting for death in up to one-quarter of this population. Unlike in the general population, coronary artery disease and heart failure often are not the underlying pathologic processes for SCD; accordingly, current risk stratification tools are inadequate when assessing these patients. Factors assuming greater importance in hemodialysis patients may include left ventricular hypertrophy, electrolyte shift, and vascular calcification. Knowledge regarding SCD in hemodialysis patients is insufficient, in part reflecting the lack of an agreed-on definition of SCD in this population, although epidemiologic studies suggest the most common times for SCD to occur are toward the end of the long 72-hour weekend interval between dialysis sessions and in the 12 hours immediately after hemodialysis. Accordingly, it is hypothesized that the dialysis procedure itself may have important implications for SCD. Supporting this is recognition that hemodialysis is associated with both ventricular arrhythmias and dynamic electrocardiographic changes. Importantly, echocardiography and electrocardiography may show changes that are modifiable by alterations to dialysis prescription. The most effective preventative strategy in the general population, implanted cardioverter-defibrillator devices, are less effective in the presence of chronic kidney disease and have not been studied adequately in dialysis patients. Last, many dialysis patients experience SCD despite not fulfilling current criteria for implantation, making appropriate allocation of defibrillators uncertain.

High-risk clinical presentations in atherosclerotic renovascular disease: prognosis and response to renal artery revascularization

BACKGROUND Current trial data may not be directly applicable to patients with the highest risk presentations of atherosclerotic renovascular disease, including flash pulmonary edema, rapidly declining kidney function, and refractory hypertension. We consider the prognostic implications of these presentations and response to percutaneous revascularization. STUDY DESIGN Single-center prospective cohort study; retrospectively analyzed. SETTING & PARTICIPANTS 467 patients with renal artery stenosis ≥50%, managed according to clinical presentation and physician/patient preference. PREDICTORS Presentation with flash pulmonary edema (n = 37 [7.8%]), refractory hypertension (n = 116 [24.3%]), or rapidly declining kidney function (n = 46 [9.7%]) compared to low-risk presentation with none of these phenotypes (n = 230 [49%]). Percutaneous revascularization (performed in 32% of flash pulmonary edema, 28% of rapidly declining kidney function, and 28% of refractory hypertension patients) compared to medical management. OUTCOMES Death, cardiovascular (CV) event, end-stage kidney disease. RESULTS During a median follow-up of 3.8 (IQR, 1.8-5.8) years, 55% died, 33% had a CV event, and 18% reached end-stage kidney disease. In medically treated patients, flash pulmonary edema was associated with increased risk of death (HR, 2.2; 95% CI, 1.4-3.5; P < 0.001) and CV event (HR, 3.1; 95% CI, 1.7-5.5; P < 0.001), but not end-stage kidney disease, compared to the low-risk phenotype. No increased risk for any end point was observed in patients presenting with rapidly declining kidney function or refractory hypertension. Compared to medical treatment, revascularization was associated with reduced risk for death (HR, 0.4; 95% CI, 0.2-0.9; P = 0.01), but not CV event or end-stage kidney disease, in patients presenting with flash pulmonary edema. Revascularization was not associated significantly with reduced risk for any end point in rapidly declining kidney function or refractory hypertension. When these presentations were present in combination (n = 31), revascularization was associated with reduced risk for death (HR, 0.15; 95% CI, 0.02-0.9; P = 0.04) and CV event (HR, 0.23; 95% CI, 0.1-0.6; P = 0.02). LIMITATIONS Observational study; retrospective analysis; potential treatment bias. CONCLUSIONS This analysis supports guidelines citing flash pulmonary edema as an indication for renal artery revascularization in atherosclerotic renovascular disease. Patients presenting with a combination of rapidly declining kidney function and refractory hypertension also may benefit from revascularization and may represent a subgroup worthy of further investigation in more robust trials.

High-risk clinical presentations in atherosclerotic renovascular disease

BACKGROUND Current trial data may not be directly applicable to patients with the highest risk presentations of atherosclerotic renovascular disease, including flash pulmonary edema, rapidly declining kidney function, and refractory hypertension. We consider the prognostic implications of these presentations and response to percutaneous revascularization. STUDY DESIGN Single-center prospective cohort study; retrospectively analyzed. SETTING & PARTICIPANTS 467 patients with renal artery stenosis ≥50%, managed according to clinical presentation and physician/patient preference. PREDICTORS Presentation with flash pulmonary edema (n = 37 [7.8%]), refractory hypertension (n = 116 [24.3%]), or rapidly declining kidney function (n = 46 [9.7%]) compared to low-risk presentation with none of these phenotypes (n = 230 [49%]). Percutaneous revascularization (performed in 32% of flash pulmonary edema, 28% of rapidly declining kidney function, and 28% of refractory hypertension patients) compared to medical management. OUTCOMES Death, cardiovascular (CV) event, end-stage kidney disease. RESULTS During a median follow-up of 3.8 (IQR, 1.8-5.8) years, 55% died, 33% had a CV event, and 18% reached end-stage kidney disease. In medically treated patients, flash pulmonary edema was associated with increased risk of death (HR, 2.2; 95% CI, 1.4-3.5; P < 0.001) and CV event (HR, 3.1; 95% CI, 1.7-5.5; P < 0.001), but not end-stage kidney disease, compared to the low-risk phenotype. No increased risk for any end point was observed in patients presenting with rapidly declining kidney function or refractory hypertension. Compared to medical treatment, revascularization was associated with reduced risk for death (HR, 0.4; 95% CI, 0.2-0.9; P = 0.01), but not CV event or end-stage kidney disease, in patients presenting with flash pulmonary edema. Revascularization was not associated significantly with reduced risk for any end point in rapidly declining kidney function or refractory hypertension. When these presentations were present in combination (n = 31), revascularization was associated with reduced risk for death (HR, 0.15; 95% CI, 0.02-0.9; P = 0.04) and CV event (HR, 0.23; 95% CI, 0.1-0.6; P = 0.02). LIMITATIONS Observational study; retrospective analysis; potential treatment bias. CONCLUSIONS This analysis supports guidelines citing flash pulmonary edema as an indication for renal artery revascularization in atherosclerotic renovascular disease. Patients presenting with a combination of rapidly declining kidney function and refractory hypertension also may benefit from revascularization and may represent a subgroup worthy of further investigation in more robust trials.

The benefit of renal artery stenting in patients with atheromatous renovascular disease and advanced chronic kidney disease

Background: Around 16% of all patients who present with atheromatous renovascular disease (ARVD) in the United States undergo revascularization. Historically, patients with advanced chronic kidney disease (CKD) have been considered least likely to show improvement in renal functional terms, or survival. We aimed to investigate whether differences in outcomes after revascularization compared to medical management might be observed in ARVD patients if stratified by their CKD classes. Methods: Two prospective cohorts, a UK center with a traditionally conservative approach, and a German center who undertook a proactive revascularization approach, were compared. An improvement in renal function was defined as > 20% renal improvement at one years follow‐up. To improve validity and comparability, revascularized patients in the UK center were also used within analyses, Results: 347 (UK conservative group), 89 (UK revascularized group), and 472 (German center) patients were included in the analysis. When subdivided by CKD stage, patient ages between the two centers were comparable. Improvements in renal function were observed in twice as many patients who underwent revascularization as compared to medical treatment, particularly in the latter CKD stages, 15.2 (German revascularization) vs. 0% in CKD 1–2, 12.2 (UK), and 32.8 (German) revascularization vs. 14.1% in CKD3, and 53.1 and 53.8 vs. 28.3 in patients with CKD 4–5. The improvements in eGFR were 10.2 (16) and 8.1 (12.5) ml/min/year in the German and UK revascularized groups, respectively, vs. −0.05 (6.8) ml/min/year in the medical cohort in CKD 4–5. Improvements in blood pressure control were noted at 1 year overall and within each CKD category. Multivariate analysis revealed that revascularization independently reduced the risk of death by 45% in all patients combined (RR 0.55, P = 0.013). Conclusions: Although this study has significant methodological limitations, it does shows that percutaneous renal revascularization can improve renal function in advanced CKD (stages 4–5), and that this can provide a survival advantage in prospective analysis.

Arrhythmias in chronic kidney disease

Chronic kidney disease (CKD) is defined as evidence of kidney damage or a glomerular filtration rate (GFR) ≤60 ml/min/1.73 m2 (table 1). The most common causes of CKD are hypertension and diabetes mellitus. The many causes of CKD are associated with different varying prognoses. Patients with adult polycystic kidney disease have a 50% lifetime risk of needing dialysis compared with 25% for type 1 diabetes and <5% for type 2 diabetes. Dialysis is usually considered when GFR falls below 10 ml/min/1.73 m2 but the exact timing will often be dictated by clinical circumstances. This may be refractory oedema, hyperkalaemia and acidosis, uraemia or unacceptable symptoms. Dialysis only partially replaces the excretory function of the kidneys and so the morbidity and mortality associated with CKD are not completely resolved with dialysis. In fact, mortality in the dialysis patient is very high. The life expectancy of a 25-year-old dialysis patient is 12 years, compared with 32 years for an age equivalent transplant recipient and 52 years for a 25-year-old in the general population.1 Even patients with CKD stage 5 will only have a 20–25% chance of surviving long enough to require dialysis. The greatest cause of death in CKD is premature cardiovascular disease. For example, fewer than one in five patients with heart failure will have a normal GFR and 38% of the prevalent dialysis population have coronary artery disease (CAD) (17% previous myocardial infarction, 23% symptoms of angina).2 Both cardiac and renal systems appear to be completely interdependent, further emphasising the concept of the ‘cardiorenal syndrome’. This is highlighted when considering arrhythmias in patients with impaired renal function. View this table: Table 1 Stages of chronic kidney disease The arrhythmia burden of the patient with CKD is high, with the single greatest contributor to mortality in end stage renal disease (ESRD) being sudden cardiac death (SCD). SCD accounts for …

ROTATION ABOUT THE C-N BOND IN FORMAMIDE : AN AB INITIO MOLECULAR ORBITAL STUDY OF STRUCTURE AND ENERGETICS IN THE GAS PHASE AND IN SOLUTION

The structural and energetic changes associated with C—N bond rotation in formamide both in the gas phase and in solution have been studied theoretically using ab initio molecular orbital methods. The barrier predicted in the gas phase and in acetone are in good agreement with experimental estimates. Details of the rotation in the gas phase and in water have been studied using a new reaction-path-following technique.

Body mass index has no effect on rate of progression of chronic kidney disease in non-diabetic subjects

BACKGROUND Chronic kidney disease (CKD) is increasingly prevalent worldwide. Furthermore, obesity is now a global problem with major health implications. There is a clear association between obesity and the development of CKD but it is not known whether obesity is a risk factor for the progression of pre-existing kidney disease. We examined the relationship between the body mass index (BMI) and the rate of progression of CKD in non-diabetic adults. METHODS The Chronic Renal Insufficiency Standards Implementation Study (CRISIS) is a prospective observational study in a predominantly white population in Greater Manchester. From the CRISIS database, we assessed rate of progression of CKD in 499 adults attending the hospital. Baseline measurements including BMI were obtained and estimated glomerular filtration rate (eGFR) was monitored. The rate of deterioration of eGFR was derived over time, defined as ΔeGFR (mL/min/1.73 m2/year) and assessed using univariate analysis of variance. RESULTS In the groups as a whole, no relationship between BMI and ΔeGFR was shown. Dividing the subjects into obese (BMI≥30) and non-obese (BMI<30) groups and further breakdown into CKD stages 3, 4 and 5, also showed no relationship between BMI and ΔeGFR. Univariate analysis of variance was used. CONCLUSIONS Neither BMI as a continuous variable nor obesity (BMI≥30) as a categorical variable was associated with an increased rate of progression of existing CKD in this predominantly white population.

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.

Assessment of quantum mechanical continuum models of solvation: the prediction of tautomer equilibria, partition coefficients and amine basicity

Quantum mechanical continuum models of solvation, the self-consistent reaction field (SCRF), and polarizable continuum method, are used at the ab initio SCF level, to study tautomer equilibria, partition coefficients and amine basicity. The predictions are compared both with experimental data and with results from free energy perturbation (FEP) studies. In the SCRF studies, the description of the solute charge distribution beyond the dipole level does not lead to a significant improvement in the accuracy of the predictions. For the range of properties studied, the quality of predictions by these continuum models rivals that obtained by traditional molecular dynamics calculations.

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 operators experience and the patients 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.