Although the cardiac biomarker B-type natriuretic peptide (BNP) is strongly related to mortality in end-stage renal disease (ESRD), whether it is a predictor of weight change or blood pressure (BP) response upon probing dry weight among hypertensive hemodialysis patients remains unknown. The purpose of this study was to examine among people with hypertension on hemodialysis whether BNP is a biomarker of excess volume.
Hypertensive hemodialysis patients (n = 150) were randomized to a control group (n = 50) or an ultrafiltration group (n = 100) and followed up for 30 dialysis treatments. After a baseline run-in of six treatments, those assigned to the ultrafiltration group had dry weight probed over 8 weeks. Forty-four-hour interdialytic ambulatory BP and predialysis BNP were measured at the end of run-in period, at 4 weeks and at 8 weeks.
The median BNP concentration was 93 pg/mL (interquartile range 31–257 pg/mL). The magnitude of decline in the BNP depended on the baseline concentration of BNP, but did not require probing dry weight or weight loss. No relationship existed between decline in postdialysis weight upon probing dry weight and baseline BNP. Furthermore, reduction in the BNP was not required for decline in postdialysis weight. Predialysis log BNP modestly predicted ambulatory systolic and pulse pressure independently of other risk factors. No relationship was found between decline in BP upon probing dry weight and baseline BNP. Upon probing dry weight, reduction in BNP was not required for decline in systolic ambulatory BP.
Taken together, these data suggest that among hypertensive patients on hemodialysis BNP is not a volume marker.
BNP; dry weight; ESRD; hemodialysis; hypertension
Endothelial dysfunction resulting in disintegration of vascular structure and function is a key element in the progression of chronic kidney disease (CKD). Many risk factors—traditional and non-traditional—are thought to have a role in the progression and development of cardiovascular disease (CVD) in patients with CKD. However, many risk factors await definitive confirmation of their clinical relevance obtained from intervention trials. Moreover, the investigation of the relative contribution of these factors to the twin-risk problem of CVD and progression in patients with CKD is one of the most important future challenges for nephrologists.
biomarkers; cardiovascular disease; chronic kidney disease; endothelium
Bidirectional mechanisms exist that link diseases affecting the heart and kidney. This link is complex and remains poorly understood; therefore, charting the shared territory of cardiovascular (CV) and renal medicine poses major problems. Until now, no convincing rationale for delineating new syndromes existed. The multiple connections of the arterial system and the heart and kidney with other systems, from energy and protein balance to the musculoskeletal, clearly require special focus and rigorous framing. Nephrologists have yet to fully understand why the application of dialysis has had only limited success in halting the parallel burdens of CV and non-CV death in patients with end-stage renal disease. Cardiologists, intensivists, and nephrologists alike should settle whether and when extracorporeal ultrafiltration benefits patients with decompensated heart failure. These sparse but interconnected themes spanning from the basic science–clinical transition phase to clinical science, epidemiology, and medical technology already form the basis for the young discipline of ‘CV and renal medicine'.
cardio-renal; cardiovascular risk; CKD; death; ESRD; progression of CKD
Despite many advances in the management of hypertensive chronic kidney disease (CKD) patients, both on and off dialysis, there exist several gaps in our knowledge. Although the modern techniques to measure blood pressure (BP) indirectly have been available for a long time, among those with CKD, how to best assess hypertension and the level to which it should be lowered are mired in controversy. Other controversial areas relate to a lack of a consensus definition of hypertension among hemodialysis patients, uncertainty in the definition and assessment of volume excess, and the lack of adequately powered randomized trials to evaluate the level to which BP can be lowered in those on dialysis. This review discusses the limitations of the available evidence base and suggests areas for future research. Suggestions include evaluation of techniques to assess volume, randomized trials to target different levels of BP among hypertensive hemodialysis patients, evaluation of ambulatory BP monitoring, and non-pharmacological means to lower BP in CKD. It is hoped that among patients with CKD these data will improve the dismal cardiovascular outcomes.
ambulatory blood pressure; cardiovascular disease; CKD; hypervolemia; outcome studies; risk factors
Cardiovascular disease is an important cause of morbidity and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). All epidemiological studies have clearly shown that accelerated arterial and cardiac aging is characteristic of these populations. Arterial premature aging is heterogeneous. It principally involves the aorta and central capacitive arteries, and is characterized by preferential aortic stiffening and disappearance of stiffness/impedance gradients between the central and peripheral arteries. These changes have a double impact: on the heart, upstream, with left ventricular hypertrophy and decreased coronary perfusion; and, downstream, on renal and brain microcirculation (decrease in glomerular filtration and cognitive functions). Multifactorial at origin, the pathophysiology of aortic ‘progeria' and microvascular disorders in CKD/ESRD is not well understood and should be the focus of interest in future studies.
aging; arteriosclerosis; arterial stiffness; end-stage renal disease; pressure waves
Over the past decade, the research agenda in dialysis has been dominated by studies on risk factors associated with cardiovascular mortality. It has now become increasingly clear that in dialysis patients, non-cardiovascular causes of death are increased to the same extent as cardiovascular mortality, and therefore research efforts in this area deserve an equally prominent place on the nephrology research agenda. As previous research has suggested an association between cardiovascular disease and infections, more research on potential links between the causal pathways of cardiovascular events and infections is also warranted.
cardiovascular disease; cardiovascular mortality; dialysis; mortality; non-cardiovascular mortality; renal replacement therapy
Chronic kidney disease is often characterized by enhanced activity of the renin–angiotensin system (RAS) and the sympathetic nervous system. Independent of their effect on blood pressure, these systems also contribute to the pathogenesis of both structural and functional cardiovascular abnormalities and contribute importantly to clinical outcome. There is much evidence that the diseased kidneys are of central importance in the pathogenesis of both abnormalities. Inhibitors of the RAS also reduce sympathetic overactivity. Future research should be aimed at addressing the pathophysiological mechanisms causing the enhanced activities. Given the fact that even a small kidney lesion can cause enhanced activity of the RAS and the sympathetic nervous system, it is likely that these pathophysiological mechanisms are operational in more disease conditions, including essential hypertension, heart failure, and obesity/metabolic syndrome.
chronic kidney disease; hypertension; renin angiotensin; sympathetic activity
Shorter delivered dialysis times are associated with increased all-cause mortality. Whether shorter delivered dialysis times also associate with an increase in blood pressure (BP) and reduce the ability of probing dry weight to lower BP is unclear.
Among patients participating in the Dry-Weight Reduction in Hypertensive Hemodialysis Patients (DRIP) trial, interdialytic ambulatory BP was recorded at baseline, 4 weeks and 8 weeks. Median intradialytic BP was also calculated at each dialysis treatment and associated with the delivered daily dialysis time.
The median time on dialysis at baseline was 3.6 h per treatment (range 2.5–4.5 h). At baseline, modeled median intradialytic systolic BPs were higher among those who received fewer hours of dialysis. Among subjects who did not have their dry weight probed (control group), the median intradialytic systolic BP continued to be elevated. Probing dry weight (ultrafiltration group) provoked a drop in median intradialytic systolic BP regardless of the delivered dialysis time. However, the reduction in BP was achieved after fewer sessions of dialysis when delivered dialysis was longer in duration. The pattern of change was confirmed using interdialytic ambulatory BP monitoring.
Fewer hours of delivered dialysis are associated with a higher systolic BP. Upon probing dry weight, compared with shorter dialysis treatment times, 4 h of delivered dialysis per session provokes reductions in systolic BP over fewer dialysis treatment sessions. Reduction of BP may lag dry-weight reduction when shorter dialysis is delivered.
In response to the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guideline for blood pressure management in patients with chronic kidney disease not on dialysis, the National Kidney Foundation organized a group of US experts in hypertension and transplant nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The overriding message was the dearth of clinical trial evidence to provide strong evidence-based recommendations. For patients with CKD with normal to mildly increased albuminuria, goal blood pressure has been relaxed to ≤140/90 mm Hg for both diabetic and nondiabetic patients. In contrast, KDIGO continues to recommend goal blood pressure ≤130/80 mm Hg for patients with chronic kidney disease with moderately or severely increased albuminuria and for all renal transplant recipients regardless of the presence of proteinuria, without supporting data. The expert panel thought the KDIGO recommendations were generally reasonable but lacking in sufficient evidence support and that additional studies are greatly needed.
Kidney Disease: Improving Global Outcomes (KDIGO); guideline; blood pressure
The overall control of the quality of botanical drugs starts from the botanical raw material, continues through preparation of the botanical drug substance and culminates with the botanical drug product. Chromatographic and spectroscopic fingerprinting has been widely used as a tool for the quality control of herbal/botanical medicines. However, discussions are still on-going on whether a single technique provides adequate information to control the quality of botanical drugs. In this study, high performance liquid chromatography (HPLC), ultra performance liquid chromatography (UPLC), capillary electrophoresis (CE) and near infrared spectroscopy (NIR) were used to generate fingerprints of different plant parts of Panax notoginseng. The power of these chromatographic and spectroscopic techniques to evaluate the identity of botanical raw materials were further compared and investigated in light of the capability to distinguishing different parts of Panax notoginseng. Principal component analysis (PCA) and clustering results showed that samples were classified better when UPLC- and HPLC-based fingerprints were employed, which suggested that UPLC- and HPLC-based fingerprinting are superior to CE- and NIR-based fingerprinting. The UPLC- and HPLC- based fingerprinting with PCA were able to correctly distinguish between samples sourced from rhizomes and main root. Using chemometrics and its ability to distinguish between different plant parts could be a powerful tool to help assure the identity and quality of the botanical raw materials and to support the safety and efficacy of the botanical drug products.
The staggering cardiovascular risk of kidney failure and the disappointing results of very recent and older trials are a sounding board that nephrologists should multiply efforts at identifying modifiable risk factors, to improve the dim health perspectives of dialysis patients. Moving PH from the limbo category (WHO V) where it stands now, to categories of known aetiology, may perhaps be a significant step towards this tantalizing goal.
The prevalence, determinants and prognosis of pulmonary hypertension among long-term hemodialysis patients in the USA are poorly understood.
A cross-sectional survey of prevalence and determinants of pulmonary hypertension was performed, followed by longitudinal follow-up for all-cause mortality. Pulmonary hypertension was defined as an estimated systolic pulmonary artery pressure of >35 mmHg using echocardiograms performed within an hour after the end of dialysis.
Prevalent in 110/288 patients (38%), the independent determinants of pulmonary hypertension were the following: left atrial diameter (odds ratio 10.1 per cm/m2, P < 0.0001), urea reduction ratio (odds ratio 0.94 per %, P < 0.01) and vitamin D receptor activator use (odds ratio 0.41 for users, P < 0.01). Over a median follow-up of 2.15 years, 97 (34%) patients died yielding a crude mortality rate (CMR) of 114.2 per 1000 patient-years. Of these, 58 deaths occurred among 110 patients with pulmonary hypertension (53%, CMR 168.9/1000 patient-years) and 39 among 178 without pulmonary hypertension (22%, CMR 52.5/1000 patient-years) [unadjusted hazard ratio (HR) for death 2.12 (95% confidence interval 1.41–3.19), P < 0.001]. After multivariate adjustment, pulmonary hypertension remained an independent predictor for all-cause mortality [HR 2.17 (95% confidence interval 1.31–3.61), P < 0.01].
Among hemodialysis patients, pulmonary hypertension is common and is strongly associated with an enlarged left atrium and poor long-term survival. Reducing left atrial size such as through volume control may be an attractive target to improve pulmonary hypertension. Improving pulmonary hypertension in this group of patients may improve the dismal outcomes.
epidemiology; hemodialysis; pulmonary hypertension; risk factors; survival
This review discusses ten current controversies regarding the dialysis patient with hypertension. The clinician is faced with a dilemma at the bedside on how to evaluate blood pressure and treat this condition in a patient on long-term hemodialysis. The evidence base to give firm recommendations is thin, but the epidemiological evidence tells us to do nothing. This appears to be the incorrect strategy, at least based on what we know today. Evaluating home BP in every dialysis patient, evaluating volume status on a regular basis, and treating hypertension predominantly with non-pharmacological strategies are worthwhile.
Distraction osteogenesis has revolutionised the management of craniofacial abnormalities. The technique however requires precise planning, patient selection, execution and follow-up to achieve consistent and positive results and to avoid unfavourable results. The unfavourable results with craniofacial distraction stem from many factors ranging from improper patient selection, planning and use of inappropriate distraction device and vector. The present study analyses the current standards and techniques of distraction and details in depth the various errors and complications that may occur due to this technique. The commonly observed complications of distraction have been detailed along with measures and suggestions to avoid them in clinical practice.
Complications; distraction osteogenesis; unfavourable results
It is unknown whether systemic endothelial dysfunction underlies the association between nephropathy and cardiovascular disease (CVD) in persons infected with human immunodeficiency virus (HIV). Spot urine protein to creatinine ratio, spot urine albumin to creatinine ratio, creatinine clearance, estimated glomerular filtration rate, and flow-mediated dilation (FMD) of the brachial artery were evaluated in 123 study participants infected with HIV (58 receiving antiretroviral therapy [ART] and 65 not receiving ART) with no history of diabetes or hypertension. None of the renal markers, modeled as either continuous or categorical variables, correlated with FMD. Contrary to expectations, endothelial dysfunction may not be the link between nephropathy and CVD in HIV.
Unlike the general population, among hemodialysis patients body-mass index(BMI)is inversely related to blood pressure (BP) and mortality. To explore the reasons for this risk-factor paradox the cross-sectional association of obesity with the following factors was examined: the prevalence of hypertension, its control and echocardiographic left ventricular mass index (LVMI). Longitudinal follow-up explored the relationship of BMI with all-cause mortality. Further it explored whether poorer survival in leaner individuals was related to either high BP or greater LVMI. Among 368 hemodialysis patients both the prevalence of hypertension and its poor control were inversely related to BMI. BMI was also inversely associated with evidence of excess extracellular fluid volume but adjustment for this variable did not completely remove the inverse relationship between BP and BMI. Over 1122 patient-years of cumulative follow up (median 2.7 years) 119 (32%) patients died. In the first two years of follow up, the mortality hazard for the lowest BMI group was increased; thereafter, the survival curves were similar. Adjusting for several risk factors including BP and LVMI did not remove the inverse relationship of BMI with mortality. In conclusion, leaner patients on dialysis have a higher prevalence of hypertension, poorer control of hypertension, more LVMI, and greater evidence of extracellular fluid volume excess. However, volume only partially explains the greater prevalence or poorer control of hypertension. Leaner patients have an accelerated mortality rate in the first two years; this is not completely explained by BP, LVMI or other cardiovascular or dialysis-specific risk factors.
Body mass index; epidemiology; hemodialysis; ambulatory blood pressure; left ventricular hypertrophy; survival
The epidemiology of hypertension among hemodialysis (HD) patients is difficult to describe accurately because of difficulties in the assessment of blood pressure (BP).
Using 44-hour interdialytic ambulatory BP measurements, we describe the epidemiology of hypertension in a cohort of 369 patients. To seek correlates of hypertension control, antihypertensive agents were withdrawn among patients with controlled hypertension and ambulatory BP monitoring was repeated.
Hypertension (defined as an average ambulatory systolic BP ≥135 mm Hg or diastolic BP ≥85 mm Hg, or the use of antihypertensive medications) was prevalent in 82% of the patients and independently associated with epoetin use, lower body mass index and fewer years on dialysis. Although 89% of the patients were being treated, hypertension was controlled adequately in only 38%. Poor control was independently associated with greater antihypertensive drug use. Inferior vena cava (IVC) diameter in expiration was associated with increased risk of poorly controlled hypertension both in cross-sectional analysis and after withdrawal of antihypertensive drugs.
Interdialytic hypertension is highly prevalent and difficult to control among HD patients. End-expiration IVC diameter is associated with poor control of hypertension in cross-sectional analyses as well as after washout of antihypertensive drugs. Among HD patients, an attractive target for improving hypertension control appears to be the reduction of extracellular fluid volume.
Ambulatory blood pressure monitoring; Epidemiology; Epoetin; Hemodialysis; Hypertension; Vitamin D receptor activators
Most management decisions for the diagnosis and treatment of hypertension are made using blood pressure (BP) measurements made in the clinic. However, home BP recordings may be of superior prognostic value. In this review, we show that home BP recordings are generally superior to clinic BP measurements in predicting long-term prognosis. Home BP has been shown to significantly predict important end points including all-cause mortality, progression of chronic kidney disease, and functional decline in the elderly. In addition, home BP recordings significantly and strongly predict cardiovascular events. These findings are robust, as they concur despite having been studied in disparate populations, using heterogeneous methods of clinic and home BP measurement, and with varied methods of statistical analysis. The advantages of home BP recordings are not due solely to a larger number of measurements, and they extend to the elderly, patients with chronic kidney disease, and those on hemodialysis. Because home BP recordings combine improved accuracy with the advantages of low cost and easy implementation, most patients with known or suspected hypertension should have their BP assessed and managed by means of home BP recordings.
BP measurement; Home BP; Clinic BP; Comparative study; Prognosis; Chronic kidney disease; Hemodialysis
Although probing dry-weight improves blood pressure control, its effect on echocardiographic left ventricular mass index (LVMI) is unknown.
Shortly following dialysis, 292 echocardiograms in 150 patients participating in the DRIP trial were obtained at baseline and longitudinally every 4 weeks on 2 occasions.
At baseline, LVMI was 136.3 g/m2 in the control group and 138.7 g/m2 in the ultrafiltration group (p > 0.2 for difference). The change from baseline in LVMI in the control group was +3.5 g/m2 at 4 weeks and +0.3 g/m2 at 8 weeks (p > 0.2 for both changes). The change from baseline in LVMI in the ultrafiltration group was −7.4 g/m2 at 4 weeks (p = 0.005) and −6.3 g/m2 at 8 weeks (p = 0.045). With ultrafiltration, the change in LVMI diameter was −10.9 g/m2 more compared to the control group at 4 weeks (p = 0.012) and −6.6 g/m2 more compared to the control group at 8 weeks (p = 0.21). The reduction in interdialytic ambulatory blood pressure was also greater in response to probing dry-weight in those in the top half of LVMI at baseline (p = 0.02 for interaction effect at week 8).
LVMI, an important determinant of prognosis among long-term dialysis patients, is responsive to probing dry-weight.
Hemodialysis; Hypertension; Ultrafiltration; Ambulatory blood pressure; Volume overload; Echocardiogram; Left ventricular hypertrophy; Left ventricular systolic function
The reference standard for making a diagnosis of hypertension among hemodialysis patients is 44-hour interdialytic ambulatory BP monitoring. However, a more practical way to diagnose and manage hypertension is to perform home BP monitoring that spans the interdialytic interval. In contrast to pre- and postdialysis BP recordings, measurements of BP made outside the dialysis unit correlate with the presence of left ventricular hypertrophy and directly and strongly with all-cause mortality. Hypervolemia that is not clinically obvious is the most common treatable cause of difficult to control hypertension; volume control should be the initial therapy to treat hypertension in most hemodialysis patients. To diagnose hypervolemia, continuous blood volume monitoring is emerging as an effective and simple technique. Reducing dietary and dialysate sodium is an often overlooked strategy to improve BP control. Although definitive randomized trials that demonstrate cardiovascular benefits of BP lowering among hypertensive hemodialysis have not been performed, emerging evidence suggests that lowering BP may reduce cardiovascular events. Since predialysis and post-dialysis BP are quite variable and agree poorly with measurements obtained outside the dialysis unit, treatment should be guided by BP obtained outside the dialysis unit. While the appropriate level to which BP should be lowered remains elusive, current data suggests that interdialytic ambulatory systolic BP should be lowered to <130 mmHg and averaged home systolic BP to <140 mmHg. Antihypertensive drugs will be required by most patients receiving 4 hour thrice weekly dialysis. Beta blockers, dihydropyridine calcium blockers and agents that block the renin-angiotensin system appear to be effective in lowering BP in these patients.
Hypertension; diagnosis; hemodialysis; home BP monitoring; ambulatory BP monitoring; treatment; pathophysiology