Association of Symptoms and Collaborative Care Intervention (TACcare) with Systemic Inflammation Biomarkers in End-Stage Kidney Disease.

BACKGROUND: Patient-reported symptoms are associated with inflammation biomarkers in many chronic diseases. We examined associations of inflammation biomarkers with pain, fatigue, and depression in patients with end-stage kidney disease (ESKD) and the effects of a Technology Assisted stepped Collaborative Care (TACcare) intervention on these biomarkers. METHODS: In the TACcare multi-site randomized control trial, data on patient-reported symptoms were collected at baseline, 3, and 6 months. Anti-inflammatory [interleukin 1 receptor agonist (IL-1RA), IL-10], pro-inflammatory [tumor necrosis factor alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), IL-6] and regulatory [IL-2] biomarkers were assayed. Linear mixed-effects modeling was used to examine within- and between-group differences after adjusting for age, sex, race, and comorbidities. RESULTS: Among the 160 patients (mean age 58±14 years, 55% men, 52% white), there were no significant associations between inflammation biomarkers and pain, fatigue or depression at baseline. Both intervention and control group demonstrated reductions in IL-10 and IL-1RA over 6 months (ß range=-1.22 to -0.40, p range=<0.001 to 0.02) At 3 months, the treatment group exhibited decreases in TNF-α (ß=-0.22, p<0.001) and IL-2 (ß=-0.71, p<0.001), whereas the control group showed increases in IL-6/IL-10 ratio (ß=0.33, p=0.03). At 6 months, both groups exhibited decreases in IL-2 (ß range=-0.66 to -0.57,p<0.001); the control group showed significant increases in the ratio of IL-6/IL-10 (ß=0.75,p<0.001) and decrease in TNF-α (ß=-0.16, p=0.02). Compared to controls, the treatment group demonstrated significantly decreased IL-2 at 3 months (ß=-0.53, p<0.001). Significant interaction effects of treatment were observed on the association between changes in pro-inflammatory biomarkers (TNF-α and hs-CRP) levels and changes in symptom scores from baseline to 6 months. CONCLUSIONS: The TACcare intervention had a short-term impact on reducing inflammatory burden in patients with ESKD. More studies are needed to confirm our findings and to determine if these biomarkers mediate the link between symptoms and disease progression.

Diurnal and Daily Symptom Variation in Patients with End-Stage Kidney Disease: An Ecological Momentary Assessment Study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) on hemodialysis (HD) experience a high symptom burden which is compounded by unpredictable fluctuations in symptom severity. Few studies have used ecological momentary assessment (EMA) to determine how symptoms vary over time. This study aimed to characterize the diurnal and day-to-day variability in symptoms among HD patients. METHODS: Patients enrolled in the Technology Assisted Collaborative Care (TACcare) trial rated the intensity of physical, cognitive, and mood symptoms using an automated telephone-administered version of the Daytime Insomnia Symptom Scale (DISS) at four time-points (morning, early afternoon, late afternoon, evening) for seven consecutive days at baseline. Confirmatory factor analysis (CFA) was used to verify the original four-factor solution for the DISS: sleepiness/fatigue (SF), alert cognition (AC), positive mood (PM), and negative mood (NM). Symptom domain scores were calculated for each time point and mixed modeling with random patient effects was used to examine differences in daily symptoms daily time points between HD and non-HD days after controlling for age, gender, race, and comorbidity burden. RESULTS: One hundred and sixty patients were enrolled (mean±SD age 58±14 years, 45% women, 52% White). Diurnal symptom variation existed; trends were non-linear and differed by HD vs. non-HD days. Day-to-day symptom variation also existed; patients endorsed better physical, cognitive, and mood states (i.e., higher AC and PM) as well as lower symptom burden (i.e., lower SF and NM) on non-HD days compared to HD days at all time-points. The greatest day-to-day mean differences (MDs) were observed in the early afternoon for all symptom domains: AC (MD=0.17 p<0.001), PM (MD=0.28, p<0.001), SF (MD=-0.66, p<0.001), and NM (MD=-0.26, p<0.001). CONCLUSIONS: Patients with ESKD demonstrate diurnal variation in symptoms and greater symptom burden on HD days compared to non-HD days, with the most extreme differences in symptom severity occurring in the early afternoon.

Comparison of Glomerular Filtration Rate Equations in a Rural New Mexico Cohort: Results from the COMPASS Study.

Rationale and Objective: The NKF-ASN Task Force recommends accurate kidney function estimation avoiding biases through racial adjustments. We explored the use of multiple kidney function biomarkers and hence estimated glomerular filtration rate (eGFR) equations to improve kidney function calculations in an ethnically diverse patient population. Study design: Prospective community cohort study. Setting and Participants: rural New Mexico clinic with patients > 18 yo. Methods: Markers of kidney function, IDMS-Creatinine (SCr), chemiluminescence Beta-2 Microglobulin (B2M), Nephelometry-calibrated ELISA Cystatin C (CysC), inflammation, glucose tolerance, demographics, BUN/UACR from the baseline visit of the COMPASS cohort, were analyzed by Kernel-based Virtual Machine learning methods. Results: Among 205 participants, the mean age was 50.1, 62% were female, 54.1% Hispanic American and 30.2% Native American. Average kidney function biomarkers were: SCr 0.9 mg/dl, B2M 1.8 mg/L, and CysC 0.7 mg/dl. The highest agreement was observed between SCr and B2M-based eGFR equations [mean difference in eGFRs: (4.48 ml/min/1.73m2], and the lowest agreement between B2M and CysC-based eGFR equations (-24.75 ml/min/1.73m2). There was no pattern of association between the differences in eGFR measures and gender. In the continuous analyses, the absolute eGFR value (p<2 x 10-16) and serum albumin (p =6.4 x 10-5) predicted the difference between B2M- and SCr-based e-GFR. The absolute eGFR value (p<2 x 10-16) and age (p =7.6 x 10-5) predicted the difference between CysC- and SCr-based e-GFR. Limitations: Relatively small sample size, elevated inflammatory state in majority of study participants and no inulin excretion rate measurements. Conclusion: B2M should be strongly considered as a kidney function biomarker fulfilling the criteria for the NKF-ASN. B2M's eGFR equation does not need adjustment for gender or race and showed the highest agreement with SCr-based eGFR equations.

Hypernatremia in Hyperglycemia: Clinical Features and Relationship to Fractional Changes in Body Water and Monovalent Cations during Its Development.

In hyperglycemia, the serum sodium concentration ([Na]S) receives influences from (a) the fluid exit from the intracellular compartment and thirst, which cause [Na]S decreases; (b) osmotic diuresis with sums of the urinary sodium plus potassium concentration lower than the baseline euglycemic [Na]S, which results in a [Na]S increase; and (c), in some cases, gains or losses of fluid, sodium, and potassium through the gastrointestinal tract, the respiratory tract, and the skin. Hyperglycemic patients with hypernatremia have large deficits of body water and usually hypovolemia and develop severe clinical manifestations and significant mortality. To assist with the correction of both the severe dehydration and the hypovolemia, we developed formulas computing the fractional losses of the body water and monovalent cations in hyperglycemia. The formulas estimate varying losses between patients with the same serum glucose concentration ([Glu]S) and [Na]S but with different sums of monovalent cation concentrations in the lost fluids. Among subjects with the same [Glu]S and [Na]S, those with higher monovalent cation concentrations in the fluids lost have higher fractional losses of body water. The sum of the monovalent cation concentrations in the lost fluids should be considered when computing the volume and composition of the fluid replacement for hyperglycemic syndromes.

Peritoneal Dialysis Technique Survival: A Cohort Study.

RATIONALE & OBJECTIVE: Reasons for transfer from peritoneal dialysis (PD) to hemodialysis (HD) remain incompletely understood. Among incident and prevalent patients receiving PD, we evaluated the association of clinical factors, including prior treatment with HD, with PD technique survival. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults who initiated PD at a Dialysis Clinic, Inc (DCI) outpatient facility between January 1, 2010, and September 30, 2019. EXPOSURE: The primary exposure of interest was timing of PD start, categorized as PD-first, PD-early, or PD-late. Other covariates included demographics, clinical characteristics, and routine laboratory results. OUTCOME: Modality switch from PD to HD sustained for more than 90 days. ANALYTICAL APPROACH: Multivariable Fine-Gray models with competing risks and time-varying covariates, stratified at 9 months to account for lack of proportionality. RESULTS: Among 5,224 patients who initiated PD at a DCI facility, 3,174 initiated dialysis with PD ("PD-first"), 942 transitioned from HD to PD within 90 days ("PD-early"), and 1,108 transitioned beyond 90 days ("PD-late"); 1,472 (28%) subsequently transferred from PD to HD. The PD-early and PD-late patients had a higher risk of transfer to HD as compared with PD-first patients (in the first 9 months: adjusted hazard ratio [AHR], 1.51 [95% CI, 1.17-1.96] and 2.41 [95% CI, 1.94-3.00], respectively; and after 9 months: AHR, 1.16 [95% CI, 0.99-1.35] and AHR, 1.43 [95% CI, 1.24-1.65], respectively). More peritonitis episodes, fewer home visits, lower serum albumin levels, lower residual kidney function, and lower peritoneal clearance calculated with weekly Kt/V were additional risk factors for PD-to-HD transfer. LIMITATIONS: Missing data on dialysis adequacy and residual kidney function, confounded by short PD technique survival. CONCLUSIONS: Initiating dialysis with PD is associated with greater PD technique survival, though many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower Kt/V are risk factors for PD-to-HD transfer that may be amenable to intervention. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is an important kidney replacement modality with several potential advantages compared with in-center hemodialysis (HD). However, a substantial number of patients transfer to in-center HD early on, without having experienced the quality-of-life and other benefits that come with sustained maintenance of PD. Using retrospective data from a midsize national dialysis provider, we found that initiating dialysis with PD is associated with longer maintenance of PD, compared with initiating dialysis with HD and a later switch to PD. However, many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower small protein removal are other risk factors for PD-to-HD transfer that may be amenable to intervention.

Chronic Kidney Disease in the Older Adult Patient with Diabetes.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and older adult individuals. DM may accelerate the aging process, and the age-related declines in the estimated glomerular filtration rate (eGFR) can pose a challenge to diagnosing diabetic kidney disease (DKD) using standard diagnostic criteria especially with the absence of severe albuminuria among older adults. In the presence of CKD and DM, older adult patients may need multidisciplinary care due to susceptibility to various health issues, e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to older adults. We review the evidence that the benefits from these newer therapies apply equally to older and younger patients with CKD and diabetes type 2 and propose a comprehensive management. This framework will address nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), sodium glucose co-transporter 2 inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and glucagon like peptide 1 receptor agonists (GLP1-RAs).

Effectiveness of Existing Insomnia Therapies for Patients Undergoing Hemodialysis : A Randomized Clinical Trial.

BACKGROUND: Chronic insomnia is common in patients undergoing in-center hemodialysis, yet there is limited evidence on effective treatments for this population. OBJECTIVE: To compare the effectiveness of cognitive behavioral therapy for insomnia (CBT-I), trazodone, and placebo for insomnia in patients undergoing long-term hemodialysis. DESIGN: Randomized, multicenter, double-blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT03534284). SETTING: 26 dialysis units in Albuquerque, New Mexico, and Seattle, Washington. PARTICIPANTS: Patients with Insomnia Severity Index (ISI) score of 10 or greater, with sleep disturbances on 3 or more nights per week for 3 or more months. INTERVENTION: Participants were randomly assigned to 6 weeks of CBT-I, trazodone, or placebo. MEASUREMENTS: The primary outcome was the ISI score at 7 and 25 weeks from randomization. RESULTS: A total of 923 patients were prescreened, and of the 411 patients with chronic insomnia, 126 were randomly assigned to CBT-I (n = 43), trazodone (n = 42), or placebo (n = 41). The change in ISI scores from baseline to 7 weeks with CBT-I or trazodone was no different from placebo: CBT-I, -3.7 (95% CI, -5.5 to -1.9); trazodone, -4.2 (CI, -5.9 to -2.4); and placebo, -3.1 (CI, -4.9 to -1.3). There was no meaningful change in ISI scores from baseline to 25 weeks: CBT-I, -4.8 (CI, -7.0 to -2.7); trazodone, -4.0 (CI, -6.0 to -1.9); and placebo, -4.3 (CI, -6.4 to -2.2). Serious adverse events (SAEs), particularly serious cardiovascular events, were more frequent with trazodone (annualized cardiovascular SAE incidence rates: CBT-I, 0.05 [CI, 0.00 to 0.29]; trazodone, 0.64 [CI, 0.34 to 1.10]; and placebo, 0.21 [CI, 0.06 to 0.53]). LIMITATION: Modest sample size and most participants had mild or moderate insomnia. CONCLUSION: In patients undergoing hemodialysis with mild or moderate chronic insomnia, there was no difference in the effectiveness of 6 weeks of CBT-I or trazodone compared with placebo. The incidence of SAEs was higher with trazodone. PRIMARY FUNDING SOURCE: National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases.

Outcomes of Hospital-Acquired Hypernatremia.

BACKGROUND: Hospital-acquired hypernatremia is highly prevalent, overlooked, and associated with unfavorable consequences. There are limited studies examining the outcomes and discharge dispositions of various levels of hospital-acquired hypernatremia in patients with or without CKD. METHODS: We conducted an observational retrospective cohort study, and we analyzed the data of 1,728,141 patients extracted from the Cerner Health Facts database (January 1, 2000, to June 30, 2018). In this report, we investigated the association between hospital-acquired hypernatremia (serum sodium [Na] levels >145 mEq/L) and in-hospital mortality or discharge dispositions with kidney function status at admission using adjusted multinomial regression models. RESULTS: Of all hospitalized patients, 6% developed hypernatremia after hospital admission. The incidence of in-hospital mortality was 12% and 1% in patients with hypernatremia and normonatremia, respectively. The risk of all outcomes was significantly greater for serum Na >145 mEq/L compared with the reference interval (serum Na, 135-145 mEq/L). In patients with hypernatremia, odds ratios (95% confidence interval) for in-hospital mortality, discharge to hospice, and discharge to nursing facilities were 14.04 (13.71 to 14.38), 4.35 (4.14 to 4.57), and 3.88 (3.82 to 3.94), respectively ( P < 0.001, for all). Patients with eGFR (Chronic Kidney Disease Epidemiology Collaboration) 60-89 ml/min per 1.73 m 2 and normonatremia had the lowest odds ratio for in-hospital mortality (1.60 [1.52 to 1.70]). CONCLUSIONS: Hospital-acquired hypernatremia is associated with in-hospital mortality and discharge to hospice or to nursing facilities in all stages of CKD.

Effects of Technology Assisted Stepped Collaborative Care Intervention to Improve Symptoms in Patients Undergoing Hemodialysis: The TACcare Randomized Clinical Trial.

Importance: Patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis often experience a high burden of debilitating symptoms for which effective treatment options are limited. Objective: To compare the effectiveness of a stepped collaborative care intervention vs attention control for reducing fatigue, pain, and depression among patients with ESKD undergoing long-term hemodialysis. Design, Setting, and Participants: Technology Assisted Stepped Collaborative Care (TACcare) was a parallel-group, single-blinded, randomized clinical trial of adult (≥18 years) patients undergoing long-term hemodialysis and experiencing clinically significant levels of fatigue, pain, and/or depression for which they were considering treatment. The trial took place in 2 US states (New Mexico and Pennsylvania) from March 1, 2018, to June 31, 2022. Data analyses were performed from July 1, 2022, to April 10, 2023. Interventions: The intervention group received 12 weekly sessions of cognitive behavioral therapy delivered via telehealth in the hemodialysis unit or patient home, and/or pharmacotherapy using a stepped approach in collaboration with dialysis and primary care teams. The attention control group received 6 telehealth sessions of health education. Main Outcomes and Measures: The coprimary outcomes were changes in fatigue (measured using the Functional Assessment of Chronic Illness Therapy Fatigue), average pain severity (Brief Pain Inventory), and/or depression (Beck Depression Inventory-II) scores at 3 months. Patients were followed up for 12 months to assess maintenance of intervention effects. Results: There were 160 participants (mean [SD] age, 58 [14] years; 72 [45%] women and 88 [55%] men; 21 [13%] American Indian, 45 [28%] Black, 28 [18%] Hispanic, and 83 [52%] White individuals) randomized, 83 to the intervention and 77 to the control group. In the intention-to-treat analyses, when compared with controls, patients in the intervention group experienced statistically and clinically significant reductions in fatigue (mean difference [md], 2.81; 95% CI, 0.86 to 4.75; P = .01) and pain severity (md, -0.96; 95% CI, -1.70 to -0.23; P = .02) at 3 months. These effects were sustained at 6 months (md, 3.73; 95% CI, 0.87 to 6.60; P = .03; and BPI, -1.49; 95% CI, -2.58 to -0.40; P = .02). Improvement in depression at 3 months was statistically significant but small (md -1.73; 95% CI, -3.18 to -0.28; P = .02). Adverse events were similar in both groups. Conclusions and Relevance: This randomized clinical trial found that a technology assisted stepped collaborative care intervention delivered during hemodialysis led to modest but clinically meaningful improvements in fatigue and pain at 3 months vs the control group, with effects sustained until 6 months. Trial Registration: ClinicalTrials.gov Identifier: NCT03440853.

Pseudohyponatremia: Mechanism, Diagnosis, Clinical Associations and Management.

Pseudohyponatremia remains a problem for clinical laboratories. In this study, we analyzed the mechanisms, diagnosis, clinical consequences, and conditions associated with pseudohyponatremia, and future developments for its elimination. The two methods involved assess the serum sodium concentration ([Na]S) using sodium ion-specific electrodes: (a) a direct ion-specific electrode (ISE), and (b) an indirect ISE. A direct ISE does not require dilution of a sample prior to its measurement, whereas an indirect ISE needs pre-measurement sample dilution. [Na]S measurements using an indirect ISE are influenced by abnormal concentrations of serum proteins or lipids. Pseudohyponatremia occurs when the [Na]S is measured with an indirect ISE and the serum solid content concentrations are elevated, resulting in reciprocal depressions in serum water and [Na]S values. Pseudonormonatremia or pseudohypernatremia are encountered in hypoproteinemic patients who have a decreased plasma solids content. Three mechanisms are responsible for pseudohyponatremia: (a) a reduction in the [Na]S due to lower serum water and sodium concentrations, the electrolyte exclusion effect; (b) an increase in the measured sample's water concentration post-dilution to a greater extent when compared to normal serum, lowering the [Na] in this sample; (c) when serum hyperviscosity reduces serum delivery to the device that apportions serum and diluent. Patients with pseudohyponatremia and a normal [Na]S do not develop water movement across cell membranes and clinical manifestations of hypotonic hyponatremia. Pseudohyponatremia does not require treatment to address the [Na]S, making any inadvertent correction treatment potentially detrimental.

Hypernatremia in Hospitalized Patients: A Large Population-Based Study.

Background: Hypernatremia is a frequently encountered electrolyte disorder in hospitalized patients. Controversies still exist over the relationship between hypernatremia and its outcomes in hospitalized patients. This study examines the relationship of hypernatremia to outcomes among hospitalized patients and the extent to which this relationship varies by kidney function and age. Methods: We conducted an observational study to investigate the association between hypernatremia, eGFR, and age at hospital admission and in-hospital mortality, and discharge dispositions. We analyzed the data of 1.9 million patients extracted from the Cerner Health Facts databases (2000-2018). Adjusted multinomial regression models were used to estimate the relationship of hypernatremia to outcomes of hospitalized patients. Results: Of all hospitalized patients, 3% had serum sodium (Na) >145 mEq/L at hospital admission. Incidence of in-hospital mortality was 12% and 2% in hyper- and normonatremic patients, respectively. The risk of all outcomes increased significantly for Na >155 mEq/L compared with the reference interval of Na=135-145 mEq/L. Odds ratios (95% confidence intervals) for in-hospital mortality and discharge to a hospice or nursing facility were 34.41 (30.59-38.71), 21.14 (17.53-25.5), and 12.21 (10.95-13.61), respectively (all P<0.001). In adjusted models, we found that the association between Na and disposition was modified by eGFR (P<0.001) and by age (P<0.001). Sensitivity analyses were performed using the eGFR equation without race as a covariate, and the inferences did not substantially change. In all hypernatremic groups, patients aged 76-89 and ≥90 had higher odds of in-hospital mortality compared with younger patients (all P<0.001). Conclusions: Hypernatremia was significantly associated with in-hospital mortality and discharge to a hospice or nursing facility. The risk of in-hospital mortality and other outcomes was highest among those with Na >155 mEq/L. This work demonstrates that hypernatremia is an important factor related to discharge disposition and supports the need to study whether protocolized treatment of hypernatremia improves outcomes.

High performance implementation of the hierarchical likelihood for generalized linear mixed models: an application to estimate the potassium reference range in massive electronic health records datasets.

BACKGROUND: Converting electronic health record (EHR) entries to useful clinical inferences requires one to address the poor scalability of existing implementations of Generalized Linear Mixed Models (GLMM) for repeated measures. The major computational bottleneck concerns the numerical evaluation of multivariable integrals, which even for the simplest EHR analyses may involve millions of dimensions (one for each patient). The hierarchical likelihood (h-lik) approach to GLMMs is a methodologically rigorous framework for the estimation of GLMMs that is based on the Laplace Approximation (LA), which replaces integration with numerical optimization, and thus scales very well with dimensionality. METHODS: We present a high-performance, direct implementation of the h-lik for GLMMs in the R package TMB. Using this approach, we examined the relation of repeated serum potassium measurements and survival in the Cerner Real World Data (CRWD) EHR database. Analyzing this data requires the evaluation of an integral in over 3 million dimensions, putting this problem beyond the reach of conventional approaches. We also assessed the scalability and accuracy of LA in smaller samples of 1 and 10% size of the full dataset that were analyzed via the a) original, interconnected Generalized Linear Models (iGLM), approach to h-lik, b) Adaptive Gaussian Hermite (AGH) and c) the gold standard for multivariate integration Markov Chain Monte Carlo (MCMC). RESULTS: Random effects estimates generated by the LA were within 10% of the values obtained by the iGLMs, AGH and MCMC techniques. The H-lik approach was 4-30 times faster than AGH and nearly 800 times faster than MCMC. The major clinical inferences in this problem are the establishment of the non-linear relationship between the potassium level and the risk of mortality, as well as estimates of the individual and health care facility sources of variations for mortality risk in CRWD. CONCLUSIONS: We found that the direct implementation of the h-lik offers a computationally efficient, numerically accurate approach for the analysis of extremely large, real world repeated measures data via the h-lik approach to GLMMs. The clinical inference from our analysis may guide choices of treatment thresholds for treating potassium disorders in the clinic.

Sleep-HD trial: short and long-term effectiveness of existing insomnia therapies for patients undergoing hemodialysis.

BACKGROUND: Patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) experience many distressing symptoms. One frequently reported symptom is insomnia. There are unique issues about HD treatments and schedules that disrupt regular sleep/wake routines and possibly contribute to the high severity of insomnia. Despite evidence for broad-ranging health effects of insomnia, very few clinical trials have tested the efficacy of treatments for HD patients. Cognitive-behavioral therapy for insomnia (CBT-I) is a recommended first-line therapy but largely inaccessible to HD patients in the United States, partly because they commit considerable amounts of time to thrice-weekly dialysis treatments. Another important reason could be the logistical and reimbursement challenges associated with providing behavioral health care at the dialysis center. CBT-I delivered by telehealth can overcome barriers to access, but its efficacy has never been rigorously tested for these patients. Pharmacotherapy is the most widely used treatment for insomnia; however, some drugs presently used are unsafe as they are associated with a higher risk for death for HD patients (benzodiazepines and zolpidem-like drugs). The efficacy and safety of other medications (trazodone) for the treatment of insomnia has never been tested for patients treated with HD. METHODS: This trial tests the short- and long-term comparative effectiveness of 6-week treatment with telehealth CBT-I, trazodone, or medication placebo. This will be accomplished with a randomized controlled trial (RCT) in which 126 participants treated with HD in community-based dialysis facilities with chronic insomnia will be assigned 1:1:1 to telehealth CBT-I, trazodone, or medication placebo, respectively; short-term effectiveness of each treatment arm will be determined at the end of 6-weeks of treatment and long-term effectiveness at 25-weeks. The primary and secondary patient-reported outcomes will be assessed with computer-based telephone interviewing by research scientists blinded to treatment assignment; additional secondary outcomes will be assessed by participant interview and actigraphy. DISCUSSION: This clinical RCT will provide the first evidence for the comparative effectiveness of two distinct approaches for treating chronic insomnia and other patient-reported outcomes for patients receiving maintenance HD. TRIAL REGISTRATION: NCT03534284 May 23, 2018. SLEEP-HD Protocol Version: 1.3.4 (7/22/2020).

Management of extracellular volume in patients with end-stage kidney disease and severe hyperglycemia.

This commentary addresses volume replacement in hyperglycemic crises in patients with end-stage kidney disease (ESKD). The management of volume issues in this group of patients should not be based on guidelines for management of hyperglycemic crises, but should be individualized and based on directed patient medical history, physical examination, and imaging of the heart and lungs. A scheme for combining information from these three sources is provided.

Association of Sleep Apnea with Mortality in Patients with Advanced Kidney Disease.

BACKGROUND AND OBJECTIVES: In the general population, sleep disorders are associated with mortality. However, such evidence in patients with CKD and ESKD is limited and shows conflicting results. Our aim was to examine the association of sleep apnea with mortality among patients with CKD and ESKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective cohort study, 180 patients (88 with CKD stage 4 or 5, 92 with ESKD) underwent in-home polysomnography, and sleep apnea measures such as apnea hypopnea index (AHI) and nocturnal hypoxemia were obtained. Mortality data were obtained from the National Death Index. Cox proportional hazard models were used for survival analysis. RESULTS: Among the 180 patients (mean age 54 years, 37% women, 39% with diabetes, 49% CKD with mean eGFR 18±7 ml/min per 1.73 m2), 71% had sleep apnea (AHI>5) and 23% had severe sleep apnea (AHI>30). Median AHI was 13 (range, 4-29) and was not significantly different in patients with advanced CKD or ESKD. Over a median follow-up of 9 years, there were 84 (47%) deaths. AHI was not significantly associated with mortality after adjusting for age, sex, race, diabetes, body mass index, CKD/ESKD status, and kidney transplant status (AHI>30: hazard ratio [HR], 1.5; 95% confidence interval [95% CI], 0.6 to 4.0; AHI >15 to 30: HR, 2.3; 95% CI, 0.9 to 5.9; AHI >5 to 15: HR, 2.1; 95% CI, 0.8 to 5.4, compared with AHI≤5). Higher proportion of sleep time with oxygen saturation <90% and lower mean oxygen saturation were significantly associated with higher mortality in adjusted analysis (HR, 1.4; 95% CI, 1.1 to 1.7; P=0.007 for every 15% higher proportion, and HR, 1.6; 95% CI, 1.2 to 2.1; P=0.003 for every 2% lower saturation, respectively). Sleep duration, sleep efficiency, or periodic limb movement index were not associated with mortality. CONCLUSIONS: Hypoxemia-based measures of sleep apnea are significantly associated with increased risk of death among advanced CKD and ESKD.

Dialysis-associated hyperglycemia: manifestations and treatment.

PURPOSE: Dialysis-associated hyperglycemia (DAH), is associated with a distinct fluid and electrolyte pathophysiology. The purpose of this report was to review the pathophysiology and provide treatment guidelines for DAH. METHODS: Review of published reports on DAH. Synthesis of guidelines based on these reports. RESULTS: The following fluid and solute abnormalities have been identified in DAH: (a) hypoglycemia: this is a frequent complication of insulin treatment and its prevention requires special attention. (b) Elevated serum tonicity. The degree of hypertonicity in DAH is lower than in similar levels of hyperglycemia in patients with preserved renal function. Typically, correction of hyperglycemia with insulin corrects the hypertonicity of DAH. (c) Extracellular volume abnormalities ranging from pulmonary edema associated with osmotic fluid shift from the intracellular into the extracellular compartment as a consequence of gain in extracellular solute (glucose) to hypovolemia from osmotic diuresis in patients with residual renal function or from fluid losses through extrarenal routes. Correction of DAH by insulin infusion reverses the osmotic fluid transfer between the intracellular and extracellular compartments and corrects the pulmonary edema, but can worsen the manifestations of hypovolemia, which require saline infusion. (d) A variety of acid-base disorders including ketoacidosis correctable with insulin infusion and no other interventions. (e) Hyperkalemia, which is frequent in DAH and is more severe when ketoacidosis is also present. Insulin infusion corrects the hyperkalemia. Extreme hyperkalemia at presentation or hypokalemia developing during insulin infusion require additional measures. CONCLUSIONS: In DAH, insulin infusion is the primary management strategy and corrects the fluid and electrolyte abnormalities. Patients treated for DAH should be monitored for the development of hypoglycemia or fluid and electrolyte abnormalities that may require additional treatments.

Psychosocial Impact of COVID-19 Pandemic on Patients with End-Stage Kidney Disease on Hemodialysis.

Background: The coronavirus disease 2019 (COVID-19) may have a negative effect on the mental and social health of patients with ESKD on chronic in-center hemodialysis (HD), who have a high burden of psychologic symptoms at baseline and unavoidable treatment-related COVID exposures. The goal of our study was to assess the effect of the COVID-19 pandemic on the psychosocial health of patients on chronic in-center HD. Methods: Participants enrolled in the ongoing Technology Assisted Collaborative Care (TACcare) trial in Western Pennsylvania and New Mexico were approached for participation in a phone survey in May 2020. Data on the pandemic's effects on participants' physical and mental health, symptoms (such as anxiety, mood, loneliness, sleep, and stress), and food and housing security were collected. Results: Surveys were completed by 49 participants (mean age 56 years; 53% men, 18% Black, 20% American Indian, and 22% Hispanic). Almost 80% of participants reported being moderately to extremely worried about the pandemic's effects on their mental/emotional health and interpersonal relationships. More than 85% of the participants were worried about obtaining their dialysis treatments due to infection risk from close contact in the dialysis facility or during transportation. Despite this, 82% of participants reported being not at all/slightly interested in trying home dialysis as an alternative option. Overall, 27% of the participants had clinical levels of depressive symptoms but only 12% had anxiety meeting clinical criteria. About 33% of participants reported poor sleep quality over the last month. Perceived stress was high in about 30% of participants and 85% felt overwhelmed by difficulties with COVID-19, although 41% felt that things were fairly/very often going their way. Conclusions: Our study provides preliminary insights into the psychosocial distress caused by the COVID-19 pandemic among a diverse cohort of patients receiving chronic HD who are participating in an ongoing clinical trial.