Resistant Hypertension in Dialysis: Epidemiology, Diagnosis, and Management.

Apparent treatment-resistant hypertension is defined as an elevated BP despite the use of ≥3 antihypertensive medications from different classes or the use of ≥4 antihypertensives regardless of BP levels. Among patients receiving maintenance hemodialysis or peritoneal dialysis, using this definition, the prevalence of apparent treatment-resistant hypertension is estimated to be between 18% and 42%. Owing to the lack of a rigorous assessment of some common causes of pseudoresistance, the burden of true resistant hypertension in the dialysis population remains unknown. What distinguishes apparent treatment-resistance from true resistance is white-coat hypertension and adherence to medications. Accordingly, the diagnostic workup of a dialysis patient with apparent treatment-resistant hypertension on dialysis includes the accurate determination of BP control status with the use of home or ambulatory BP monitoring and exclusion of nonadherence to the prescribed antihypertensive regimen. In a patient on dialysis with inadequately controlled BP, despite adherence to therapy with maximally tolerated doses of a ß -blocker, a long-acting dihydropyridine calcium channel blocker, and a renin-angiotensin system inhibitor, volume-mediated hypertension is the most important treatable cause of resistance. In daily clinical practice, such patients are often managed with intensification of antihypertensive therapy. However, this therapeutic strategy is likely to fail if volume overload is not adequately recognized or treated. Instead of increasing the number of prescribed BP-lowering medications, we recommend diet and dialysate restricted in sodium to facilitate achievement of dry weight. The achievement of dry weight is facilitated by an adequate time on dialysis of at least 4 hours for delivering an adequate dialysis dose. In this article, we review the epidemiology, diagnosis, and management of resistant hypertension among patients on dialysis.

NIH Funding, Research Productivity, and Scientific Impact: a 20-Year Study.

BACKGROUND: The Research Project Grant (R01) is the oldest grant mechanism used by the National Institutes of Health (NIH). Receiving an R01 award is often taken as a sign of scientific success. We presented normative data on multiple productivity and impact metrics for a more objective assessment of funded grants' scientific success. METHODS: All initial R01 grants awarded by NIH in the year 2000 were prospectively followed and evaluated using the numbers of publications and citations, as well as the h-indices at the grant level. We examined the variability, time trends, and relations among these metrics to better understand the funded projects' cumulative output and impact. RESULTS: In the 20 years since initial funding, 4451 R01 grants generated a total of 55,053 publications. These publications were cumulatively cited 3,705,553 times over 736,811 citation years. The median number of publications was 8 (25th, 75th percentiles 4, 17) per grant for the entire 20-year duration. The median number of citations and the median h-index were 441 (25th, 75th percentiles 156, 1061) and 7 (25th, 75th percentiles 4, 13) per grant, respectively. The time courses of publication, citation, and accumulation of h-index were highly variable among the awarded grants. Although the metrics were correlated within an award, they reflected the grant's success in different domains. CONCLUSION: Numbers of publications, citations, and h-indices vary greatly among funded R01 grants. When used together, these metrics provide a more complete picture of the productivity and long-term impact of a funded grant.

Needs and Perspectives of Cancer Center Stakeholders for Access to Patient Values in the Electronic Health Record.

PURPOSE: High-quality cancer care must incorporate patients' personal values in decision making throughout illness. Unfortunately, patient values are neither consistently elicited nor easily accessible in the electronic health record (EHR). Memorial Sloan Kettering Cancer Center is deploying a major EHR innovation, called the Patient Values Tab, which provides ready access to patients' values and personhood. To inform the Tab's design, we interviewed a large, diverse group of institutional stakeholders to understand their user needs for this Tab. METHODS: Qualitative data were collected through semistructured, audio-recorded, in-person, individual interviews. An interdisciplinary team of four coders conducted a process of thematic content analysis. Thematic saturation was achieved, and member checking was performed. RESULTS: A total of 110 stakeholders were approached and interviewed. Participants comprised a wide range of disciplines or professions and others involved in hospital and/or clinic administration. Analysis revealed the following themes related to important Tab content: personhood, support system or resources, social history, communication preferences, future planning, end of life, and illness and treatment understanding. Participants also discussed implementation considerations, the Tab's potential to improve communication, and privacy implications. CONCLUSION: This study focused on a major EHR innovation to centralize information about values and personhood of patients with cancer. We elicited views of over 100 institutional stakeholders through in-depth interviews that were rigorously analyzed, yielding themes related to content and format that helped guide the Tab's design. The interviews generated a sense of ownership and enthusiasm for the Tab among future users. The Tab's introduction advances the use of the EHR as a driver of the delivery of patient-centered care.

Assessment and Management of Hypertension among Patients on Peritoneal Dialysis.

Approximately 7%-10% of patients with ESKD worldwide undergo peritoneal dialysis (PD) as kidney replacement therapy. The continuous nature of this dialytic modality and the absence of acute shifts in pressure and volume parameters is an important differentiation between PD and in-center hemodialysis. However, the burden of hypertension and prognostic association of BP with mortality follow comparable patterns in both modalities. Although management of hypertension uses similar therapeutic principles, long-term preservation of residual diuresis and longevity of peritoneal membrane function require particular attention in the prescription of the appropriate dialysis regimen among those on PD. Dietary sodium restriction, appropriate use of icodextrin, and limited exposure of peritoneal membrane to bioincompatible solutions, as well as adaptation of the PD regimen to the peritoneal transport characteristics, are first-line therapeutic strategies to achieve adequate volume control with a potential long-term benefit on technique survival. Antihypertensive drug therapy is a second-line therapeutic approach, used when BP remains unresponsive to the above volume management strategies. In this article, we review the available evidence on epidemiology, diagnosis, and treatment of hypertension among patients on PD and discuss similarities and differences between PD and in-center hemodialysis. We conclude with a call for randomized trials aiming to elucidate several areas of uncertainty in management of hypertension in the PD population.

Epidemiology, diagnosis and management of hypertension among patients on chronic dialysis.

The diagnosis and management of hypertension among patients on chronic dialysis is challenging. Routine peridialytic blood pressure recordings are unable to accurately diagnose hypertension and stratify cardiovascular risk. By contrast, blood pressure recordings taken outside the dialysis setting exhibit clear prognostic associations with survival and might facilitate the diagnosis and long-term management of hypertension. Once accurately diagnosed, management of hypertension in individuals on chronic dialysis should initially involve non-pharmacological strategies to control volume overload. Accordingly, first-line strategies should focus on achieving dry weight, individualizing dialysate sodium concentrations and ensuring dialysis sessions are at least 4 h in duration. If blood pressure remains unresponsive to volume management strategies, pharmacological treatment is required. The choice of appropriate antihypertensive regimen should be individualized taking into account the efficacy, safety, and pharmacokinetic properties of the antihypertensive medications as well as any comorbid conditions and the overall risk profile of the patient. In contrast to their effects in the general hypertensive population, emerging evidence suggests that ß-blockers might offer the greatest cardioprotection in hypertensive patients on dialysis. In this Review, we discuss estimates of the epidemiology of hypertension in the dialysis population as well as the challenges in diagnosing and managing hypertension among these patients.

Assessment of voice related quality of life and its correlation with socioeconomic status after total laryngectomy.

BACKGROUND: After total laryngectomy for laryngeal cancer, the major determinants of QOL is the patient's voice related quality of life (V-RQOL). The primary aim of this study was to assess the V-RQOL and impact of socioeconomic status over it in Indian population by using two validated scales [voice handicap index (VHI) and V-RQOL questionnaires]. METHODS: Total 104 patients underwent total laryngectomy but 71 were eligible for study. Patients filled the VHI and V-RQOL questionnaires after completion of 1 year of usage of the TEP voice. The socioeconomic status of the patients was calculated according to various domains related to their life and were divided into lower and higher status. RESULTS: A total of 76.1% patients had VHI score between 0 to 30 (minimal voice handicap), 19.7% had score between 31 to 60 (moderate voice handicap) and only 4.2% patients had VHI score more than 61 (serious voice handicap). On V-RQOL scores, 16.9% patients had score between 10 to 15 (excellent), 40.8% patients, between 16 to 20 (very good), 22.5% patients, between 21 and 25 (good voice), 15.5% patients, between 26 and 30 (fair) and only 4.2% patients scored more than 30 with poor quality of voice. Patients with lower socioeconomic group had better V-RQOL than with high socioeconomic group. CONCLUSIONS: VHI and V-RQOL scores in our series were superior to other studies due to major population with lower socioeconomic status and better social support which exists in our society.

Assessment of achieved clinic and ambulatory blood pressure recordings and outcomes during treatment in hypertensive patients with CKD: a multicenter prospective cohort study.

BACKGROUND: We investigated the effect of having clinic and/or ambulatory blood pressures (BPs) not at goal on cardiorenal risk in patients with non-dialysis-dependent chronic kidney disease (CKD). STUDY DESIGN: Multicenter prospective study. SETTING & PARTICIPANTS: 489 consecutive hypertensive patients with CKD (stages 1-5) with concomitant assessment of ambulatory and clinic BPs followed up in tertiary nephrology clinics. PREDICTORS: Achievement of goal for ambulatory (day- and night-time BPs <135/85 and <120/70mmHg, respectively) and clinic (<140/90mmHg) BPs was used to create 4 BP groups: clinic and ambulatory BPs at goal (group 1), clinic BP above goal and ambulatory BP at goal (group 2), clinic BP at goal and ambulatory BP above goal (group 3), and clinic and ambulatory BPs above goal (group 4). OUTCOMES: Composite cardiovascular event outcome (fatal and nonfatal myocardial infarction, congestive heart failure, stroke, revascularization, peripheral vascular disease, and nontraumatic amputation) and a composite renal outcome (maintenance dialysis therapy or death). MEASUREMENTS: Clinic and 24-hour ambulatory BPs. RESULTS: Mean age was 64.4±14.2 (SD) years; 41% were women, and diabetes and previous cardiovascular disease were present in 36% and 30%, respectively. Groups 1-4 contained 16.8%, 22.1%, 14.5%, and 46.6%, respectively, of the overall number of participants. Median follow-up was 5.2 years. Compared to group 1, the adjusted risk of the composite cardiovascular outcome was higher in groups 3 (HR, 3.17; 95%CI, 1.50-6.69) and 4 (HR, 2.83; 95%CI, 1.50-5.34), but not in group 2 (HR, 1.55; 95%CI, 0.75-3.19). Similarly, the risk of the composite renal outcome was higher in groups 3 (HR, 3.59; 95%CI, 2.05-6.27) and 4 (HR, 2.96; 95%CI, 1.83-4.78), but not group 2 (HR, 1.24; 95%CI, 0.67-2.27). Sensitivity analyses confirmed that these results were independent from the thresholds used for defining groups. LIMITATIONS: Only white patients were enrolled. Observational design does not allow for causality to be established. CONCLUSIONS: In patients with treated CKD, clinic BP above goal and ambulatory BP at goal identify a low-risk condition, whereas clinic BP at goal and ambulatory BP above goal are associated with higher cardiorenal risk, similar to that observed in patients with both clinic and ambulatory BPs above goal.

Assessment and management of hypertension in patients on dialysis.

Hypertension is common, difficult to diagnose, and poorly controlled among patients with ESRD. However, controversy surrounds the diagnosis and treatment of hypertension. Here, we describe the diagnosis, epidemiology, and management of hypertension in dialysis patients, and examine the data sparking debate over appropriate methods for diagnosing and treating hypertension. Furthermore, we consider the issues uniquely related to hypertension in pediatric dialysis patients. Future clinical trials designed to clarify the controversial results discussed here should lead to the implementation of diagnostic and therapeutic techniques that improve long-term cardiovascular outcomes in patients with ESRD.

Review of blood pressure control rates and outcomes.

Despite the high prevalence of hypertension and documented benefits of blood pressure (BP) control, >40% of patients with hypertension are not controlled. A majority of uncontrolled hypertensive patients receive two or more antihypertensive drugs. The current review examined the relationship between antihypertensive combination drug therapy, achievement of goal BP, and cardiovascular (CV) outcomes. Articles were selected from a PubMed search using a prespecified search strategy. Randomized, controlled clinical trials of adult human subjects published in English between January 1991 and January 2013 were included. From 2319 identified articles, 28 met inclusion criteria and contained a total of 226,877 subjects. There were seven placebo-controlled studies and 21 treatment comparator and combination therapy studies. The studies included in this review reported a positive association between the degree of BP lowering, number of medications, and CV outcomes. As combination therapy became available, it was increasingly utilized in clinical trials and enabled an increased proportion of patients to achieve a prespecified BP target. Adverse events with monotherapy and combination therapy were as anticipated for the specific classes of antihypertensive therapy. Although many patients reach BP goal, combination antihypertensive therapy is often needed to reach BP goal. Effective BP lowering has been shown to result in improvements in CV outcomes.

Thiazide diuretics in advanced chronic kidney disease.

Chronic kidney disease (CKD) is prevalent in 3%-4% of the adult population in the United States, and the vast majority of these people are hypertensive. Compared with those with essential hypertension, hypertension in CKD remains poorly controlled despite the use of multiple antihypertensive drugs. Hypervolemia is thought to be a major cause of hypertension, and diuretics are useful to improve blood pressure control in CKD. Non-osmotic storage of sodium in the skin and muscle may be a novel mechanism by which sodium may modulate hypertension; further work is need to study this novel phenomenon with diuretics. Among people with stage 4 CKD, loop diuretics are recommended over thiazides. Thiazide diuretics are deemed ineffective in people with stage 4 CKD. Review of the literature suggests that thiazides may be useful even among people with advanced CKD. They cause a negative sodium balance, increasing sodium excretion by 10%-15% and weight loss by 1-2 kg in observational studies. Observational data show improvement in seated clinic blood pressure of about 10-15 mm Hg systolic and 5-10 mm Hg diastolic, whereas randomized trials show about 15 mm Hg improvement in mean arterial pressure. Volume depletion, hyponatremia, hypokalemia, hypercalcemia, and acute kidney injury are adverse effects that should be closely monitored. Our review suggests that adequately powered randomized trials are needed before the use of thiazide diuretics can be firmly recommended in those with advanced CKD.

Diagnosis and Treatment of Sleep Apnea in patients' homes: the rationale and methods of the "GoToSleep" randomized-controlled trial.

BACKGROUND: The "Diagnosis and Treatment of Sleep Apnea in Cerebrovascular Disease" (GoToSleep) study is evaluating a strategy to improve the diagnosis and treatment of sleep apnea among veterans with stroke or transient ischemic attack (TIA) who also have hypertension. Specifically, the GoToSleep study was designed to overcome some of the barriers that exist within the Veterans Health Administration (VHA) to the timely diagnosis and treatment of sleep apnea by using ambulatory home-based polysomnography and auto-titrating continuous positive airway pressure (CPAP) to reduce the reliance on laboratory-based sleep studies. METHODS: The GoToSleep study is a prospective, multi-site, randomized, controlled strategy trial among an expected 318 veterans with cerebrovascular disease and hypertension who are assigned to an intervention group or a control group. Patients in the intervention group receive unattended polysomnography at baseline, and those with sleep apnea receive auto-titrating CPAP therapy for up to one year. Patients in the control group receive usual care and unattended polysomnography at the end of the study to identify the rate of undiagnosed sleep apnea. The primary objectives of the GoToSleep study are to determine whether a diagnostic and therapeutic intervention strategy among veterans with cerebrovascular disease and hypertension improves: (1) detection of sleep apnea; (2) appropriate treatment for sleep apnea; and (3) control of hypertension. Twenty-four-hour blood pressure assessments are made at baseline and at the end of the one-year study period for both groups. Antihypertensive medications and their doses are recorded at the time of the 24-hour blood pressure measurements. DISCUSSION: This manuscript provides the rationale for 4 key components of the design of the GoToSleep trial: the inclusion of patients with cerebrovascular disease and hypertension without the use of a measure of daytime sleepiness as an eligibility criterion; the use of portable polysomnography and auto-titrating CPAP in patients' homes rather than using sleep laboratory polysomnography with fixed pressure CPAP; the analytic approach to evaluating change in blood pressure in the context of change in antihypertensive medications; and the use of a usual care control group.

Developing a self-administered CKD symptom assessment instrument.

BACKGROUND: Current disease-centred therapies for CKD focus on preserving the GFR but often ignore patient-reported symptoms. This purpose of this report is to describe the development of an instrument to measure the presence and severity of a wide range of symptoms commonly attributable to CKD. METHODS: A 37-item questionnaire was administered along with the Kidney Disease Quality of Life instrument to 92 patients with CKD not on dialysis (24% black, 5% women, mean age 68 years, 68% with diabetes mellitus). To discover groups of symptoms, agglomerative cluster analysis followed by exploratory common factor analysis was performed. Construct validity, internal reliability, convergent and discriminant validity, test-retest reliability and finally the association of various symptom domains with objective measurements such as estimated GFR and haemoglobin were tested. RESULTS: The top five symptoms of at least moderate severity in decreasing order of prevalence were 'tire easily', limited physical activity, nocturia, joint pain and 'stop and rest often'. Four common factors emerged that could be broadly classified into neuropsychiatric, cardiovascular, uraemia and anaemia symptoms accounting for 73% of the total variance in the sample. The coefficient alpha for each of these factors approached 0.9. The test-retest reliability in 41 patients over 8 weeks was likewise high. There was good convergent and divergent validity. However, there was little relationship between estimated GFR and symptom scores. CONCLUSIONS: The assessment of symptom burden among patients with CKD may be facilitated by incorporating this instrument in routine practice and clinical trials.

Relative plasma volume monitoring during hemodialysis AIDS the assessment of dry weight.

Among hemodialysis patients, the assessment of dry weight remains a matter of clinical judgment because tests to assess dry weight have not been validated. The objective of this study was to evaluate and validate relative plasma volume (RPV) monitoring as a marker of dry weight. We performed RPV monitoring using the Crit-Line monitor at baseline and at 8 weeks in 150 patients participating in the Dry-Weight Reduction in Hypertensive Hemodialysis Patients Trial. The intervention group of 100 patients had dry weight probed, whereas 50 patients served as time controls. RPV slopes were defined as flat when they were less than the median (1.33% per hour) at the baseline visit. Among predominantly (87%) black hemodialysis patients, we found that flat RPV slopes suggest a volume-overloaded state for the following reasons: (1) probing dry weight in these patients led to steeper slopes; (2) those with flatter slopes at baseline had greater weight loss; (3) both baseline RPV slopes and the intensity of weight loss were found to be important for subsequent change in RPV slopes; and, most importantly, (4) RPV slopes predicted the subsequent reduction in interdialytic ambulatory systolic blood pressure. Those with the flattest slopes had the greatest decline in blood pressure on probing dry weight. Both baseline RPV slopes and the change in RPV slopes were important for subsequent changes in ambulatory systolic blood pressure. We conclude that RPV slope monitoring is a valid method to assess dry weight among hypertensive hemodialysis patients.

Assessment of iothalamate plasma clearance: duration of study affects quality of GFR.

BACKGROUND AND OBJECTIVES: Measurement of GFR is important for the management of chronic kidney disease (CKD). Although bolus administration of radiocontrast agents is commonly used to measure GFR, the optimal duration of sampling to assess their plasma clearance is unknown. The purpose of this study was to evaluate whether the duration of plasma sampling influences precision and estimation of GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: GFR was measured by sampling plasma 12 times over 5 h in 56 patients with CKD (mean age 64 yr, 98% men, 79% Caucasian, 34% diabetics, estimated GFR 31.8 +/- 14.2 ml/min/1.73 m(2)). In a subset of 12 patients we measured GFR by sampling plasma 17 times over 10 h. RESULTS: Short sampling intervals considerably overestimated GFR measured using total plasma iothalamate clearance, especially in larger patients. In the higher estimated GFR group (>30 ml/min/1.73 m(2)), the 5-h GFR was 17% higher and 2-h GFR 54% higher compared with the 10-h GFR, which averaged 40.3 ml/min/1.73 m(2). In the lower estimated GFR group (<30 ml/min/1.73 m(2)), the 5-h GFR was 36% higher and 2-h GFR 126% higher compared with the 10-h GFR, which averaged 22.2 ml/min/1.73 m(2). Short sampling duration also reduced the precision of the estimated GFR from 1.67% for 10-h GFR, to 3.48% for 5-h GFR, and to 7.07% for 2-h GFR. CONCLUSIONS: GFR measured over a longer duration with multiple plasma samples spanning the distribution and elimination phases may improve precision and provide a better measure of renal function.

Proteinuria is a determinant of quality of life in diabetic nephropathy: modeling lagged effects with path analysis.

BACKGROUND: Diabetic nephropathy with overt proteinuria often progresses relentlessly to end-stage renal disease (ESRD). MATERIAL AND METHODS: To answer the question whether it is impaired glomerular filtration rate (GFR) or its precursor proteinuria which is more related with multiple domains of health-related quality of life (HRQOL), we measured GFR and proteinuria in 44 patients with type 2 diabetes and overt nephropathy and repeated the measurements after 4 months. 38 patients with ESRD due to diabetic nephropathy served as a control group. We used path analysis to examine the association of baseline proteinuria and GFR with baseline and subsequent HRQOL scales. RESULTS: Compared to patients with ESRD, patients with non-dialysis CKD had Kidney Disease Burden (KDB) that was, on a scale from 0 to 100, 19.8 better (95% CI 6.9-32.8) (p = 0.003). Mental component score (MCS) did not differ and physical component score (PCS) was worse in non-dialysis CKD patients by 8.5 (p < 0.001). Proteinuria at baseline was a predictor of PCS, MCS and KDB score at 4 months, suggesting a lagged effect of proteinuria on HRQOL after controlling for the autoregressive effects. GFR was not shown to have a significant impact on HRQOL. One log unit increase in proteinuria was associated with 3.8 (p = 0.011) fall in PCS, 3.3 (p = 0.043) fall in MCS and 10.6 (p = 0.006) fall in KDB. CONCLUSION: In patients with advanced diabetic nephropathy, we found that proteinuria has a lagged and profound effect on multiple domains of HRQOL.