Clinical Outcomes of Rural Patients with Diabetes Treated by ECHO-Trained Providers Versus an Academic Medical Center.

BACKGROUND: Despite clinical practice guidelines prioritizing cardiorenal risk reduction, national trends in diabetes outcomes, particularly in rural communities, do not mirror the benefits seen in clinical trials with emerging therapeutics and technologies. OBJECTIVE: Project ECHO supports implementation of guidelines in under-resourced areas through virtual communities of practice, sharing of best practices, and case-based learning. We hypothesized that diabetes outcomes of patients treated by ECHO-trained primary care providers (PCPs) would be similar to those of patients treated by specialists at an academic medical center. DESIGN: Specialists from the University of New Mexico (UNM) launched a weekly diabetes ECHO program to mentor dyads consisting of a PCP and community health worker at ten rural clinics. PARTICIPANTS: We compared cardiorenal risk factor changes in patients with diabetes treated by ECHO-trained dyads to patients treated by specialists at the UNM Diabetes Comprehensive Care Center (DCCC). Eligible participants included adults with type 1 diabetes, type 2 diabetes on insulin, or diabetes of either type with A1c > 9%. MAIN MEASURES: The primary outcome was change from baseline in A1c in the ECHO and DCCC cohorts. Secondary outcomes included changes in body mass index (BMI), blood pressure, cholesterol, and urine albumin to creatinine ratio (UACR). KEY RESULTS: Compared to the DCCC cohort (n = 151), patients in the ECHO cohort (n = 856) experienced greater A1c reduction (-1.2% vs -0.6%; p = 0.02 for difference in difference). BMI decreased in the Endo ECHO cohort and increased in the DCCC cohort (-0.2 vs. +1.3 kg/m2; p = 0.003 for difference in difference). Diastolic blood pressure declined in the Endo ECHO cohort only. Improvements of similar magnitude were observed in low-density lipoprotein cholesterol in both groups. UACR remained stable in both groups. CONCLUSIONS: ECHO may be a suitable intervention for improving diabetes outcomes in rural, under-resourced communities with limited access to a specialist.

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.

Do pre-transplant cultural factors predict health-related quality of life after kidney transplantation?

BACKGROUND: Post-transplant health-related quality of life (HRQOL) is associated with health outcomes for kidney transplant (KT) recipients. However, pretransplant predictors of improvements in post-transplant HRQOL remain incompletely understood. Namely, important pretransplant cultural factors, such as experience of discrimination, perceived racism in healthcare, or mistrust of the healthcare system, have not been examined as potential HRQOL predictors. Also, few have examined predictors of decline in HRQOL post-transplant. METHODS: Using data from a prospective cohort study, we examined HRQOL change pre- to post-transplant, and novel cultural predictors of the change. We measured physical, mental, and kidney-specific HRQOL as outcomes, and used cultural factors as predictors, controlling for demographic, clinical, psychosocial, and transplant knowledge covariates. RESULTS: Among 166 KT recipients (57% male; mean age 50.6 years; 61.4% > high school graduates; 80% non-Hispanic White), we found mental and physical, but not kidney-specific, HRQOL significantly improved post-transplant. No culturally related factors outside of medical mistrust significantly predicted change in any HRQOL outcome. Instead, demographic, knowledge, and clinical factors significantly predicted decline in each HRQOL domain: physical HRQOL-older age, more post-KT complications, higher pre-KT physical HRQOL; mental HRQOL-having less information pre-KT, greater pre-KT mental HRQOL; and, kidney-specific HRQOL-poorer kidney functioning post-KT, lower expectations for physical condition to improve, and higher pre-KT kidney-specific HRQOL. CONCLUSIONS: Instead of cultural factors, predictors of HRQOL decline included demographic, knowledge, and clinical factors. These findings are useful for identifying patient groups that may be at greater risk of poorer post-transplant outcomes, in order to target individualized support to patients.

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).

Predicting Kidney Transplant Evaluation Non-attendance.

Non-attendance to kidney transplant evaluation (KTE) appointments is a barrier to optimal care for those with kidney failure. We examined the medical and socio-cultural factors that predict KTE non-attendance to identify opportunities for integrated medical teams to intervene. Patients scheduled for KTE between May, 2015 and June, 2018 completed an interview before their initial KTE appointment. The interview assessed various social determinants of health, including demographic (e.g., income), medical (e.g. co-morbidities), transplant knowledge, cultural (e.g., medical mistrust), and psychosocial (e.g., social support) factors. We used multiple logistic regression analysis to determine the strongest predictor of KTE non-attendance. Our sample (N = 1119) was 37% female, 76% non-Hispanic White, median age 59.4 years (IQR 49.2-67.5). Of note, 142 (13%) never attended an initial KTE clinic appointment. Being on dialysis predicted higher odds of KTE non-attendance (OR 1.76; p = .02; 64% of KTE attendees on dialysis vs. 77% of non-attendees on dialysis). Transplant and nephrology teams should consider working collaboratively with dialysis units to better coordinate care, (e.g., resources to attend appointment or outreach to emphasize the importance of transplant) adjusting the KTE referral and evaluation process to address access issues (e.g., using tele-health) and encouraging partnership with clinical psychologists to promote quality of life for those on dialysis.

The design and baseline characteristics for the HOPE Consortium Trial to reduce pain and opioid use in hemodialysis.

The HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis (HOPE Trial) is a multicenter randomized trial addressing chronic pain among patients receiving maintenance hemodialysis for end-stage kidney disease. The trial uses a sequential, multiple assignment design with a randomized component for all participants (Phase 1) and a non-randomized component for a subset of participants (Phase 2). During Phase 1, participants are randomized to Pain Coping Skills Training (PCST), an intervention designed to increase self-efficacy for managing pain, or Usual Care. PCST consists of weekly, live, coach-led cognitive behavioral therapy sessions delivered by video- or tele-conferencing for 12 weeks followed by daily interactive voice response sessions delivered by telephone for an additional 12 weeks. At 24 weeks (Phase 2), participants in both the PCST and Usual Care groups taking prescription opioid medications at an average dose of ≥20 morphine milligram equivalents per day are offered buprenorphine, a partial opioid agonist with a more favorable safety profile than full-agonist opioids. All participants are followed for 36 weeks. The primary outcome is pain interference ascertained, for the primary analysis, at 12 weeks. Secondary outcomes include additional patient-reported measures and clinical outcomes including falls, hospitalizations, and death. Exploratory outcomes include acceptability, tolerability, and efficacy of buprenorphine. The enrollment target of 640 participants was met 27 months after trial initiation. The findings of the trial will inform the management of chronic pain, a common and challenging issue for patients treated with maintenance hemodialysis. NCT04571619.

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.

Interventions for fatigue in people with kidney failure requiring dialysis.

BACKGROUND: Fatigue is a common and debilitating symptom in people receiving dialysis that is associated with an increased risk of death, cardiovascular disease and depression. Fatigue can also impair quality of life (QoL) and the ability to participate in daily activities. Fatigue has been established by patients, caregivers and health professionals as a core outcome for haemodialysis (HD). OBJECTIVES: We aimed to evaluate the effects of pharmacological and non-pharmacological interventions on fatigue in people with kidney failure receiving dialysis, including HD and peritoneal dialysis (PD), including any setting and frequency of the dialysis treatment. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 18 October 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Studies evaluating pharmacological and non-pharmacological interventions affecting levels of fatigue or fatigue-related outcomes in people receiving dialysis were included. Studies were eligible if fatigue or fatigue-related outcomes were reported as a primary or secondary outcome. Any mode, frequency, prescription, and duration of therapy were considered. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI) or standardised MD (SMD) if different scales were used. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Ninety-four studies involving 8191 randomised participants were eligible. Pharmacological and non-pharmacological interventions were compared either to placebo or control, or to another pharmacological or non-pharmacological intervention. In the majority of domains, risks of bias in the included studies were unclear or high. In low certainty evidence, when compared to control, exercise may improve fatigue (4 studies, 217 participants (Iowa Fatigue Scale, Modified Fatigue Impact Scale, Piper Fatigue Scale (PFS), or Haemodialysis-Related Fatigue scale score): SMD -1.18, 95% CI -2.04 to -0.31; I2 = 87%) in HD. In low certainty evidence, when compared to placebo or standard care, aromatherapy may improve fatigue (7 studies, 542 participants (Fatigue Severity Scale (FSS), Rhoten Fatigue Scale (RFS), PFS or Brief Fatigue Inventory score): SMD -1.23, 95% CI -1.96 to -0.50; I2 = 93%) in HD. In low certainty evidence, when compared to no intervention, massage may improve fatigue (7 studies, 657 participants (FSS, RFS, PFS or Visual Analogue Scale (VAS) score): SMD -1.06, 95% CI -1.47, -0.65; I2 = 81%) and increase energy (2 studies, 152 participants (VAS score): MD 4.87, 95% CI 1.69 to 8.06, I2 = 59%) in HD. In low certainty evidence, when compared to placebo or control, acupressure may reduce fatigue (6 studies, 459 participants (PFS score, revised PFS, or Fatigue Index): SMD -0.64, 95% CI -1.03 to -0.25; I2 = 75%) in HD. A wide range of heterogenous interventions and fatigue-related outcomes were reported for exercise, aromatherapy, massage and acupressure, preventing our capability to pool and analyse the data. Due to the paucity of studies, the effects of pharmacological and other non-pharmacological interventions on fatigue or fatigue-related outcomes, including non-physiological neutral amino acid, relaxation with or without music therapy, meditation, exercise with nandrolone, nutritional supplementation, cognitive-behavioural therapy, ESAs, frequent HD sections, home blood pressure monitoring, blood flow rate reduction, serotonin reuptake inhibitor, beta-blockers, anabolic steroids, glucose-enriched dialysate, or light therapy, were very uncertain. The effects of pharmacological and non-pharmacological treatments on death, cardiovascular diseases, vascular access, QoL, depression, anxiety, hypertension or diabetes were sparse. No studies assessed tiredness, exhaustion or asthenia. Adverse events were rarely and inconsistently reported. AUTHORS' CONCLUSIONS: Exercise, aromatherapy, massage and acupressure may improve fatigue compared to placebo, standard care or no intervention. Pharmacological and other non-pharmacological interventions had uncertain effects on fatigue or fatigue-related outcomes in people receiving dialysis. Future adequately powered, high-quality studies are likely to change the estimated effects of interventions for fatigue and fatigue-related outcomes in people receiving dialysis.

Managing the symptom burden associated with maintenance dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference-Symptom-Based Complications in Dialysis-to identify the optimal means for diagnosing and managing symptom-based complications in patients undergoing maintenance dialysis. Participants included patients, physicians, behavioral therapists, nurses, pharmacists, and clinical researchers. They outlined foundational principles and consensus points related to identifying and addressing symptoms experienced by patients undergoing dialysis and described gaps in the knowledge base and priorities for research. Healthcare delivery and education systems have a responsibility to provide individualized symptom assessment and management. Nephrology teams should take the lead in symptom management, although this does not necessarily mean taking ownership of all aspects of care. Even when options for clinical response are limited, clinicians should focus on acknowledging, prioritizing, and managing symptoms that are most important to individual patients. A recognized factor in the initiation and implementation of improvements in symptom assessment and management is that they will be based on locally existing needs and resources.

Ultraprocessed Foods and Kidney Disease Progression, Mortality, and Cardiovascular Disease Risk in the CRIC Study.

RATIONALE & OBJECTIVE: Ultraprocessed foods are widely consumed in the United States and are associated with cardiovascular disease (CVD), mortality, and kidney function decline in the general population. We investigated associations between ultraprocessed food intake and chronic kidney disease (CKD) progression, all-cause mortality, and incident CVD in adults with chronic kidney disease (CKD). STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort Study participants who completed baseline dietary questionnaires. EXPOSURE: Ultraprocessed food intake (in servings per day) classified according to the NOVA system. OUTCOMES: CKD progression (≥50% decrease in estimated glomerular filtration rate [eGFR] or initiation of kidney replacement therapy), all-cause mortality, and incident CVD (myocardial infarction, congestive heart failure, or stroke). ANALYTICAL APPROACH: Cox proportional hazards models adjusted for demographic, lifestyle, and health covariates. RESULTS: There were 1,047 CKD progression events observed during a median follow-up of 7 years. Greater ultraprocessed food intake was associated with higher risk of CKD progression (tertile 3 vs tertile 1, HR, 1.22; 95% CI, 1.04-1.42; P=0.01 for trend). The association differed by baseline kidney function, such that greater intake was associated with higher risk among people with CKD stages 1/2 (eGFR≥60mL/min/1.73m2; tertile 3 vs tertile 1, HR, 2.61; 95% CI, 1.32-5.18) but not stages 3a-5 (eGFR<60mL/min/1.73m2; P=0.003 for interaction). There were 1,104 deaths observed during a median follow-up of 14 years. Greater ultraprocessed food intake was associated with higher risk of mortality (tertile 3 vs tertile 1, HR, 1.21; 95% CI, 1.04-1.40; P=0.004 for trend). LIMITATIONS: Self-reported diet. CONCLUSIONS: Greater ultraprocessed food intake may be associated with CKD progression in earlier stages of CKD and is associated with higher risk of all-cause mortality in adults with CKD. PLAIN LANGUAGE SUMMARY: Ultraprocessed foods are industrial formulations produced using ingredients and processes that are not commonly used in culinary preparations and contain few, if any, intact unprocessed foods. Ultraprocessed foods are widely consumed in the United States, and high intakes of such foods have been linked to cardiovascular disease, kidney disease, and mortality in the general population. In this study, we found that greater intake of ultraprocessed foods was associated with higher risk of kidney disease progression and mortality in adults with chronic kidney disease. Our findings suggest that patients with kidney disease may benefit from greater consumption of fresh, whole, and homemade or hand-prepared foods and fewer highly processed foods.

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.

Implementing Advance Care Planning for dialysis patients: HIGHway project.

BACKGROUND: Patients undergoing hemodialysis have a high mortality rate and yet underutilize palliative care and hospice resources. The Shared Decision Making-Renal Supportive Care (SDM-RSC) intervention focused on goals of care conversations between patients and family members with the nephrologist and social worker. The intervention targeted deficiencies in communication, estimating prognosis, and transition planning for seriously ill dialysis patients. The intervention showed capacity to increase substantially completion of advance care directives. The HIGHway Project, adapted from the previous SDM-RSC, scale up training social workers or nurses in dialysis center in advance care planning (ACP), and then support them for a subsequent 9-month action period, to engage in ACP conversations with patients at their dialysis center regarding their preferences for end-of-life care. METHODS: We will train between 50-60 dialysis teams, led by social workers or nurses, to engage in ACP conversations with patients at their dialysis center regarding their preferences for end-of-life care. This implementation project uses the Knowledge to Action (KTA) Framework within the Consolidated Framework for Implementation Research (CFIR) to increase adoption and sustainability in the participating dialysis centers. This includes a curriculum about how to hold ACP conversation and coaching with monthly teleconferences through case discussion and mentoring. An application software will guide on the process and provide resources for holding ACP conversations. Our project will focus on implementation outcomes. Success will be determined by adoption and effective use of the ACP approach. Patient and provider outcomes will be measured by the number of ACP conversations held and documented; the quality and fidelity of ACP conversations to the HIGHway process as taught during education sessions; impact on knowledge and skills; content, relevance, and significance of ACP intervention for patients, and Supportive Kidney Care (SKC) App usage. Currently HIGHway is in the recruitment stage. DISCUSSION: Effective changes to advance care planning processes in dialysis centers can lead to institutional policy and protocol changes, providing a model for patients receiving dialysis treatment in the US. The result will be a widespread improvement in advance care planning, thereby remedying one of the current barriers to patient-centered, goal-concordant care for dialysis patients. TRIAL REGISTRATION: The George Washington University Protocol Record NCR213481, Honoring Individual Goals and Hopes: Implementing Advance Care Planning for Persons with Kidney Disease on Dialysis, is registered in ClinicalTrials.gov Identifier: NCT05324878 on April 11th, 2022.

Video Images about Decisions for Ethical Outcomes in Kidney Disease (VIDEO-KD): the study protocol for a multi-centre randomised controlled trial.

INTRODUCTION: Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes. METHODS AND ANALYSIS: The Video Images about Decisions for Ethical Outcomes in Kidney Disease trial is a multi-centre randomised controlled trial that will test the effectiveness of an intervention that includes a CKD-related video decision aid followed by recording personal video declarations about goals of care and treatment preferences in older adults with advancing CKD. We aim to enrol 600 patients over 5 years at 10 sites. ETHICS AND DISSEMINATION: Regulatory and ethical aspects of this trial include a single Institutional Review Board mechanism for approval, data use agreements among sites, and a Data Safety and Monitoring Board. We intend to disseminate findings at national meetings and publish our results. TRIAL REGISTRATION NUMBER: NCT04347629.

Medication, Healthcare Follow-up, and Lifestyle Nonadherence: Do They Share the Same Risk Factors?

Barriers to medication adherence may differ from barriers in other domains of adherence. In this study, we assessed the association between pre-kidney transplantation (KT) factors with nonadherent behaviors in 3 different domains post-KT. METHODS: We conducted a prospective cohort study with patient interviews at initial KT evaluation (baseline-nonadherence predictors in sociodemographic, condition-related, health system, and patient-related psychosocial factors) and at ≈6 mo post-KT (adherence outcomes: medications, healthcare follow-up, and lifestyle behavior). All patients who underwent KT at our institution and had ≈6-mo follow-up interview were included in the study. We assessed nonadherence in 3 different domains using continuous composite measures derived from the Health Habit Survey. We built multiple linear and logistic regression models, adjusting for baseline characteristics, to predict adherence outcomes. RESULTS: We included 173 participants. Black race (mean difference in adherence score: -0.72; 95% confidence interval [CI], -1.12 to -0.32) and higher income (mean difference: -0.34; 95% CI, -0.67 to -0.02) predicted lower medication adherence. Experience of racial discrimination predicted lower adherence (odds ratio, 0.31; 95% CI, 0.12-0.76) and having internal locus of control predicted better adherence (odds ratio, 1.46; 95% CI, 1.06-2.03) to healthcare follow-up. In the lifestyle domain, higher education (mean difference: 0.75; 95% CI, 0.21-1.29) and lower body mass index (mean difference: -0.08; 95% CI, -0.13 to -0.03) predicted better adherence to dietary recommendations, but no risk factors predicted exercise adherence. CONCLUSIONS: Different nonadherence behaviors may stem from different motivation and risk factors (eg, clinic nonattendance due to experiencing racial discrimination). Thus adherence intervention should be individualized to target at-risk population (eg, bias reduction training for medical staff to improve patient adherence to clinic visit).

Dysnatremias in Chronic Kidney Disease: Pathophysiology, Manifestations, and Treatment.

The decreased ability of the kidney to regulate water and monovalent cation excretion predisposes patients with chronic kidney disease (CKD) to dysnatremias. In this report, we describe the clinical associations and methods of management of dysnatremias in this patient population by reviewing publications on hyponatremia and hypernatremia in patients with CKD not on dialysis, and those on maintenance hemodialysis or peritoneal dialysis. The prevalence of both hyponatremia and hypernatremia has been reported to be higher in patients with CKD than in the general population. Certain features of the studies analyzed, such as variation in the cut-off values of serum sodium concentration ([Na]) that define hyponatremia or hypernatremia, create comparison difficulties. Dysnatremias in patients with CKD are associated with adverse clinical conditions and mortality. Currently, investigation and treatment of dysnatremias in patients with CKD should follow clinical judgment and the guidelines for the general population. Whether azotemia allows different rates of correction of [Na] in patients with hyponatremic CKD and the methodology and outcomes of treatment of dysnatremias by renal replacement methods require further investigation. In conclusion, dysnatremias occur frequently and are associated with various comorbidities and mortality in patients with CKD. Knowledge gaps in their treatment and prevention call for further studies.

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.