Manisha Jhamb

Fatigue in Patients Receiving Maintenance Dialysis: A Review of Definitions, Measures, and Contributing Factors

Fatigue is a debilitating symptom or side effect experienced by many patients on long-term dialysis therapy. Fatigue has a considerable effect on patient health-related quality of life and is viewed as being more important than survival by some patients. Renal providers face many challenges when attempting to reduce fatigue in dialysis patients. The lack of a reliable, valid, and sensitive fatigue scale complicates the accurate identification of this symptom. Symptoms of daytime sleepiness and depression overlap with fatigue, making it difficult to target specific therapies. Moreover, many chronic health conditions common in the long-term dialysis population may lead to the development of fatigue and contribute to the day-to-day and diurnal variation in fatigue in patients. Key to improving the assessment and treatment of fatigue is improving our understanding of potential mediators, as well as potential therapies. Cytokines have emerged as an important mediator of fatigue and have been studied extensively in patients with cancer-related fatigue. In addition, although erythropoietin-stimulating agents have been shown to mitigate fatigue, the recent controversy regarding erythropoietin-stimulating agent dosing in patients with chronic kidney disease suggests that erythropoietin-stimulating agent therapy may not serve as the sole therapy to improve fatigue in this population. In conclusion, fatigue is an important and often underrecognized symptom in the dialysis population. Possible interventions for minimizing fatigue in patients on long-term dialysis therapy should aim at improving health care provider awareness, developing improved methods of measurement, understanding the pathogenesis better, and managing known contributing factors.

Correlates and Outcomes of Fatigue among Incident Dialysis Patients

BACKGROUND & OBJECTIVES Fatigue is a debilitating symptom experienced by patients undergoing dialysis, but there is only limited information on its prevalence and its association with patient outcomes. This study examines the correlates of self-reported fatigue at initiation of dialysis and after 1 yr and assesses the extent to which fatigue was associated with health-related quality of life and survival. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A longitudinal cohort of 917 incident hemodialysis and peritoneal dialysis patients who completed the CHOICE Health Experience Questionnaire (CHEQ) participated in the study. Fatigue was assessed using the SF-36 vitality scale. Known predictors of fatigue including sociodemographic and psychosocial factors, dialysis-related factors, biochemical variables including inflammatory markers, comorbidities, and medications were used as covariates. RESULTS A low vitality score was independently associated with white race, higher Index of Coexistent Disease score, higher body mass index, lack of physical exercise, antidepressant use, and higher C-reactive protein levels (CRP). A lower vitality score was strongly associated with lower SF-36 physical functioning, mental health, bodily pain scores, and decreased sleep quality (all P < 0.001) at baseline. Among surviving participants, higher serum creatinine at baseline was associated with preserved vitality at 1 yr. Patients with the highest baseline vitality scores were associated with longer survival (hazard ratio 0.75; 95% CI 0.58 to 0.96, P = 0.03). CONCLUSIONS The findings of this study demonstrate that ESRD patients experience profound levels of fatigue and elucidate its correlates. Also, the association of fatigue with survival may have significant implications for this population.

Impact of Fatigue on Outcomes in the Hemodialysis (HEMO) Study

Background: Fatigue is a common debilitating symptom in chronic kidney disease patients on maintenance hemodialysis. However, little is known about its pathogenesis and association with survival. Methods: This study examines the correlates and outcomes of fatigue among 1,798 hemodialysis patients enrolled in the HEMO study. Fatigue was assessed using the SF-36 vitality scale. Multivariable analysis was used to assess independent associations of demographic and clinical characteristics with baseline fatigue and longitudinal changes in fatigue. The association of fatigue with all-cause and cause-specific mortality and cardiac hospitalizations was also assessed. Results: Higher index of coexistent diseases (ICED) score, diabetes, non-African-American race, lower serum albumin, use of medications for sleep and poor sleep quality were found to be significantly associated with more fatigue at baseline. In longitudinal analyses, patients who were older, had been on dialysis longer, had higher ICED score, and reported using medications for sleep were more likely to experience worsening fatigue, whereas higher serum albumin was strongly associated with an improvement in level of fatigue. A 10-point increase in vitality score was associated with 10% increase in mean survival (p < 0.0001). Conclusions: Demographic and clinical factors have significant associations with fatigue, which itself predicts mortality. Improving fatigue in the end-stage renal disease population may positively impact patient well-being and survival.

Resistant Hypertension and Obstructive Sleep Apnea in the Setting of Kidney Disease

Objectives: To explore the relationship between obstructive sleep apnea (OSA) and resistant hypertension in chronic kidney disease (CKD) and end-stage renal disease (ESRD). Methods: We examined sleep parameters and blood pressure (BP) in 224 community-based, non-CKD participants from the Sleep-SCORE study: 88 nondialysis-dependent CKD and 95 ESRD participants. Unattended home polysomnography with standardized scoring protocols and automated BP monitors were used. Resistant hypertension was defined as a BP of at least 140/90 mmHg despite at least three antihypertensive drugs. Results: Mean SBP of the CKD and ESRD groups were significantly higher than that of the non-CKD group [148.2 (23.8), 144.5 (26.7) vs. 132.2 mmHg (26.7), respectively; P < 0.0001] despite the use of more antihypertensive medications. The CKD and ESRD groups had higher rates of resistant hypertension than the non-CKD group (41.4, 22.6 vs. 6.7%, respectively; P < 0.0001). The severity of sleep apnea was associated with a higher risk of resistant hypertension. Although resistant hypertension was associated with severe sleep apnea in participants with ESRD [odds ratio (OR) 7.1, 95% confidence interval (CI) 2.2–23.2), there was no significant association in the non-CKD (OR 3.5, 95% CI 0.8–15.4) or CKD groups (OR 1.2, 95% CI 0.4–3.7) after accounting for case-mix. Conclusion: The association between resistant hypertension and sleep apnea appeared robust in ESRD. OSA may contribute to resistant hypertension or both may be linked to a common underlying process such as volume excess. Future studies in patients with kidney disease should further characterize the resistant hypertension–OSA relationship and determine whether treatment of underlying mechanisms may improve outcomes.

Prevalence and correlates of fatigue in chronic kidney disease and end-stage renal disease: are sleep disorders a key to understanding fatigue?

Background: Fatigue is an important symptom to patients with advanced chronic kidney disease (CKD). The aim of this study is to examine the prevalence and severity of fatigue among non-dialysis-dependent CKD and end-stage renal disease (ESRD) patients, to examine the association of fatigue with subjective and objective sleep quality, and to identify other modifiable factors associated with fatigue. Methods: A cross-sectional survey of 87 non-dialysis-dependent CKD (eGFR ≤45 ml/min/1.73 m2) and 86 ESRD patients was done using the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) and 36-Item Short-Form (SF-36) vitality scale. Higher FACIT-F score denoted less fatigue. Objective sleep was assessed using in-home polysomnography. Predictors of fatigue were determined using a linear regression model. Results: The mean FACIT-F score among all participants was 34.5 ± 11.0. Mean scores were similar among CKD and ESRD groups (34.25 ± 11.28 vs. 34.73 ± 10.86; p = 0.73). On univariate analyses, patients with higher levels of fatigue were more likely to have cardiovascular disease, benzodiazepine use, depressive symptoms, and slightly lower hemoglobin and serum albumin levels. There was no significant association between severity of sleep apnea and level of fatigue (Apnea Hypopnea Index 20.1 ± 27.6 vs. 20.3 ± 22.0; p = 0.69). Presence of cardiovascular disease, low serum albumin, depressive symptoms, poor subjective sleep quality, excessive daytime sleepiness and restless legs syndrome were independently associated with greater fatigue in multivariable regression models. The FACIT-F score correlated closely with the SF-36 vitality score (r = 0.81, p < 0.0001). Conclusions: Patients with advanced CKD and ESRD experience profound fatigue. Depressive symptoms, restless legs syndrome, excessive daytime sleepiness, and low albumin levels may provide targets for interventions to improve fatigue in patients with advanced CKD.

Disparities in Electronic Health Record Patient Portal Use in Nephrology Clinics

BACKGROUND AND OBJECTIVES Electronic health record (EHR) patient portals allow individuals to access their medical information with the intent of patient empowerment. However, little is known about portal use in nephrology patients. We addressed this gap by characterizing adoption of an EHR portal, assessing secular trends, and examining the association of portal adoption and BP control (<140/90 mmHg). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients seen between January 1, 2010, and December 31, 2012, at any of four university-affiliated nephrology offices who had at least one additional nephrology follow-up visit before June 30, 2013, were included. Sociodemographic characteristics, comorbidities, clinical measurements, and office visits were abstracted from the EHR. Neighborhood median household income was obtained from the American Community Survey 2012. RESULTS Of 2803 patients, 1098 (39%) accessed the portal. Over 87% of users reviewed laboratory results, 85% reviewed their medical information (e.g., medical history), 85% reviewed or altered appointments, 77% reviewed medications, 65% requested medication refills, and 31% requested medical advice from their renal provider. In adjusted models, older age, African-American race (odds ratio [OR], 0.50; 95% confidence interval [95% CI], 0.39 to 0.64), Medicaid status (OR, 0.53; 95% CI, 0.36 to 0.77), and lower neighborhood median household income were associated with not accessing the portal. Portal adoption increased over time (2011 versus 2010: OR, 1.38 [95% CI, 1.09 to 1.75]; 2012 versus 2010: OR, 1.95 [95% CI, 1.44 to 2.64]). Portal adoption was correlated with BP control in patients with a diagnosis of hypertension; however, in the fully adjusted model this was somewhat attenuated and no longer statistically significant (OR, 1.11; 95% CI, 0.99 to 1.24). CONCLUSION While portal adoption appears to be increasing, greater attention is needed to understand why vulnerable populations do not access it. Future research should examine barriers to the use of e-health technologies in underserved patients with CKD, interventions to address them, and their potential to improve outcomes.

E-cadherin promoter polymorphism (C-160A) and risk of recurrence in patients with superficial bladder cancer

Tumor recurrence is a hallmark of superficial bladder cancer. Currently, a molecular marker for bladder cancer recurrence is lacking. E‐cadherin plays an important role in epithelial development and in the establishment and maintenance of cell–cell adhesion and tissue architecture. The purpose of this study is to investigate the association of an E‐cadherin promoter polymorphism (CDH1c‐160a) with the risk of bladder cancer recurrence. This study included 302 patients with superficial bladder cancer. Genomic DNA was extracted from peripheral blood lymphocytes and genotyping was performed using Taqman assay. Clinical data were collected by medical chart review. Cox proportional hazard model was used to estimate the hazard ratios (HRs) associated with genotypes while adjusting for age, gender, smoking status, tumor stage and grade where appropriate. During a median follow‐up of 27.65 months, 151 patients experienced disease recurrence. Subsequent analyses were restricted to Caucasians only due to the small sample size of other ethnic groups (13 in recurrence group and 15 in non‐recurrence group). Among the 274 Caucasian patients, 138 developed recurrence during the same length of follow‐up time. In Caucasian patients, having at least one variant A allele conferred a 32% reduction in recurrence risk (adjusted HR: 0.68; 95% CI: 0.48–0.96). The median recurrence‐free survival for patients carrying at least one variant A allele was significantly longer than that for patients with a homozygous CC genotype (40.4 vs 12.5 months, p = 0.04). Our findings suggest that the E‐cadherin promoter polymorphism may be a valuable molecular marker for bladder cancer recurrence.

Design and Rationale of Health-Related Quality of Life and Patient-Reported Outcomes Assessment in the Frequent Hemodialysis Network Trials

Background: End-stage renal disease patients experience significant impairments in health-related quality of life (HRQOL). Testing various strategies to improve patient HRQOL in multicenter clinical trials, such as the Frequent Hemodialysis Network (FHN) trials is vitally important. Aims: Theaim of this paper is to describe the design and conduct of HRQOL and patient-reported outcomes (PRO) assessment in the FHN trials. Methods: In the FHN trials, HRQOL was examined as a multidimensional concept, and the SF-36 RAND Physical Health Composite score was one of the co-primary outcomes. The instruments completed to assess HRQOL included the Medical Outcomes Study Short Form SF-36, Health Utilities Index 3, Sleep Problems Index, Beck Depression Inventory and feeling thermometer. These instruments have been shown to have high reliability, validity and responsiveness to change in the end-stage renal disease population. Additional items evaluating PRO including sexual function, time to recovery after dialysis and patients’ self-perceived burden to caregiver were also assessed. All questionnaires were administered by trained interviewers using computer-assisted telephone interviewing to ensure blinding and minimizing selection bias. Interim analysis reveals that these instruments can be used to collect a comprehensive set of HRQOL measures with minimal patient burden. Conclusions: Accurate measurement of HRQOL and PRO can help us test whether hemodialysis interventions improve the health and well-being of this compromised patient population. We have shown that a comprehensive set of HRQOL measures can be centrally collected through telephone interviews in a blinded fashion, in a way that is well tolerated with minimum respondent burden.

Bidirectional relationship of hypertension with obstructive sleep apnea.

Purpose of review Hypertension (HTN) and obstructive sleep apnea (OSA) are coexistent in millions of people, and both have been associated with heart disease, stroke, and premature death. OSA is an important risk factor for HTN. However, the relationship between OSA and HTN may be bidirectional, with high blood pressure (BP) contributing to an increased risk and severity of OSA. The aim of this review is to summarize the current literature supporting a bidirectional relationship of sleep apnea and HTN. Recent findings The treatment of HTN to a lower BP target may improve sleep apnea by improving upper airway tone, by targeting hormone pathways (aldosterone, renin–angiotensin system) that may exacerbate OSA, and by reducing the nocturnal rostral fluid shifts through the use of a low-sodium diet, diuretics, and dialysis. Summary Intensive BP and volume overload control may be a promising approach to treat OSA. Future studies examining the hormonal mechanisms and comparing the effect of different antihypertensive medications on OSA are needed.

BP in Dialysis: Results of a Pilot Study

The optimal BP target for patients receiving hemodialysis is unknown. We randomized 126 hypertensive patients on hemodialysis to a standardized predialysis systolic BP of 110-140 mmHg (intensive arm) or 155-165 mmHg (standard arm). The primary objectives were to assess feasibility and safety and inform the design of a full-scale trial. A secondary objective was to assess changes in left ventricular mass. Median follow-up was 365 days. In the standard arm, the 2-week moving average systolic BP did not change significantly during the intervention period, but in the intensive arm, systolic BP decreased from 160 mmHg at baseline to 143 mmHg at 4.5 months. From months 4-12, the mean separation in systolic BP between arms was 12.9 mmHg. Four deaths occurred in the intensive arm and one death occurred in the standard arm. The incidence rate ratios for the intensive compared with the standard arm (95% confidence intervals) were 1.18 (0.40 to 3.33), 1.61 (0.87 to 2.97), and 3.09 (0.96 to 8.78) for major adverse cardiovascular events, hospitalizations, and vascular access thrombosis, respectively. The intensive and standard arms had similar median changes (95% confidence intervals) in left ventricular mass of -0.84 (-17.1 to 10.0) g and 1.4 (-11.6 to 10.4) g, respectively. Although we identified a possible safety signal, the small size and short duration of the trial prevent definitive conclusions. Considering the high risk for major adverse cardiovascular events in patients receiving hemodialysis, a full-scale trial is needed to assess potential benefits of intensive hypertension control in this population.