CHRONIC KIDNEY DISEASE, MUSCLE WEAKNESS, AND MOBILITY LIMITATION

Objectives: Chronic kidney disease (CKD) is associated with increased mobility limitation. Prior research has documented that peripheral nerve abnormalities occur early in CKD and progressively worsen. Loss of balance, impaired muscle strength, and slow gait predispose older adults to falls and frailty. However, the current literature is limited by a lack of nationally representative data that includes objective measures of kidney disease and physical functioning. Thus, this research examines whether CKD is associated with muscle strength, balance, gait, and self-reported mobility limitations. Methods: Data come from the 2016 Health and Retirement Study (HRS). Estimated GFR, a measure of kidney functioning derived from creatinine levels in the blood, was used to classify CKD (i.e, eGFR<45 or Stage 3b CKD). Logistic and linear regression models were generated to examine the association of CKD with physical functioning, net of demographic characteristics (i.e., age, sex, race, and education) and comorbidities (i.e., obesity, pain, and number of diagnosed medical conditions). Results: In unadjusted models, CKD was significantly associated (p<0.05) with more mobility limitations, slower walking speeds, stronger grip strengths, and non-participation in balance tests. After adjusting for covariates, CKD (β=-1.43, p=0.01) was negatively associated with grip strength. In sex-stratified models, CKD was associated with slower walking speeds among men, whereas CKD was associated with more mobility limitations among women. Discussion: In a nationally representative sample of older adults, CKD was associated with poorer physical functioning on multiple measures. After adjusting for demographic characteristics and comorbidities, CKD was associated with increased muscle weakness

EOS789, a broad-spectrum inhibitor of phosphate transport, is safe with an indication of efficacy in a phase 1b randomized crossover trial in hemodialysis patients

The treatment of hyperphosphatemia remains challenging in patients receiving hemodialysis. This phase 1b study assessed safety and efficacy of EOS789, a novel pan-inhibitor of phosphate transport (NaPi-2b, PiT-1, PiT-2) on intestinal phosphate absorption in patients receiving intermittent hemodialysis therapy. Two cross-over, randomized order studies of identical design (ten patients each) compared daily EOS789 50 mg to placebo with meals and daily EOS789 100 mg vs EOS789 100 mg plus 1600 mg sevelamer with meals. Patients ate a controlled diet of 900 mg phosphate daily for two weeks and began EOS789 on day four. On day ten, a phosphate absorption testing protocol was performed during the intradialytic period. Intestinal fractional phosphate absorption was determined by kinetic modeling of serum data following oral and intravenous doses of 33Phosphate ( 33P). The results demonstrated no study drug related serious adverse events. Fractional phosphate absorption was 0.53 (95% confidence interval: 0.39,0.67) for placebo vs. 0.49 (0.35,0.63) for 50 mg EOS789; and 0.40 (0.29,0.50) for 100 mg EOS789 vs. 0.36 (0.26,0.47) for 100 mg EOS789 plus 1600 mg sevelamer (all not significantly different). The fractional phosphate absorption trended lower in six patients who completed both studies with EOS789 100 mg compared with placebo. Thus, in this phase 1b study, EOS789 was safe and well tolerated. Importantly, the use of 33P as a sensitive and direct measure of intestinal phosphate absorption allows specific testing of drug efficacy. The effectiveness of EOS789 needs to be evaluated in future phase 2 and phase 3 studies

Potential role of statins as immunomodulators in pneumococcal pneumonia

Background: Mortality in pneumococcal pneumonia remains as high as 20%, and most deaths occur within the first two weeks of hospitalization despite eradication of the causative organisms by antimicrobials in the first 24 hours. An inflammatory response rather than active infection could be responsible for this early mortality. Statins have been shown to have potent immunomodulatory activity in vitro. We investigated whether there was decreased severity or improved outcome in patients who were receiving statins at the time they were admitted for pneumococcal pneumonia. ^ Methods: Patients seen at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas from January, 2000 to June, 2010 with a diagnosis of pneumococcal pneumonia were included in this retrospective cohort study. Electronic medical records were reviewed to record demographic characteristics, comorbidities, laboratory values and statin use at the time of admission. Severity of pneumonia was determined using the Pneumonia Outcomes Research Team (PORT) classification. Uni- and multivariate Cox regression was used to evaluate survival. We adjusted for all variables in the multivariate model if they were significant in the univariate model at p\u3c0.05. ^ Results: Of 347 patients admitted for pneumococcal pneumonia, 90 (25.9%) were taking statins at the time of presentation. Patients in the statin group were older (age: 68.0±9.7 vs. 62.5±12.3 years, p\u3c0.001) and had higher prevalence of diabetes, coronary artery disease and kidney disease (p\u3c0.05 for each comparison). Liver disease and alcohol consumption were less prevalent among statin users (p\u3c0.05). The PORT scores were normally distributed in both groups with statin users having higher mean scores at admission as compared to patients not on statins (108±32 vs. 96±32, p = 0.002). The Cox proportional hazard analyses, adjusted for age, comorbidities, length of stay and PORT scores, showed a significantly reduced risk of mortality among statin users at 14 days (HR: 0.39; 0.15-0.98, p=0.045), 20 days (0.35; 0.14- 0.88, p=0.03) and 30 days(0.41; 0.17-0.95, p=0.01) after presentation. ^ Conclusion: Statin use is associated with improved clinical outcomes in patients with pneumococcal pneumonia.

Strategies to Reduce Rehospitalization in Patients with CKD and Kidney Failure

Readmissions in patients with nondialysis-dependent CKD and kidney failure are common and are associated with significant morbidity, mortality, and economic consequences. In 2013, the Centers for Medicare and Medicaid Services implemented the Hospital Readmissions Reduction Program in an attempt to reduce high hospitalization-associated costs. Up to 50% of all readmissions are deemed avoidable and present an opportunity for intervention. We describe factors that are specific to the patient, the index hospitalization, and underlying conditions that help identify the “high-risk” patient. Early follow-up care, developing volume management strategies, optimizing nutrition, obtaining palliative care consultations for seriously ill patients during hospitalization and conducting goals-of-care discussions with them, instituting systematic advance care planning during outpatient visits to avoid unwanted hospitalizations and intensive treatment at the end of life, and developing protocols for patients with incident or prevalent cardiovascular conditions may help prevent avoidable readmissions in patients with kidney disease

Past, Present, and Future of Phosphate Management

Cardiovascular (CV) disease (CVD) accounts for >50% of deaths with known causes in patients on dialysis. Elevated serum phosphorus levels are an important nontraditional risk factor for bone mineral disease and CVD in patients with chronic kidney disease (CKD). Given that phosphorus concentrations drive other disorders associated with increased CV risk (e.g., endothelial dysfunction, vascular calcification, fibroblast growth factor-23, parathyroid hormone), phosphate is a logical target to improve CV health. Phosphate binders are the only pharmacologic treatment approved for hyperphosphatemia. Although their safety has improved since inception, the mechanism of action leads to characteristics that make ingestion difficult and unpleasant; large pill size, objectionable taste, and multiple pills required for each meal and snack make phosphate binders a burden. Side effects, especially those affecting the gastrointestinal (GI) system, are common with binders, often leading to treatment discontinuation. The presence of "hidden" phosphates in processed foods and certain medications makes phosphate management even more challenging. Owing to these significant issues, most patients on dialysis are not consistently achieving and maintaining target phosphorus concentrations of <5.5 mg/dl, let alone more normal levels of <4.5 mg/dl, indicating novel approaches to improve phosphate management and CV health are needed. Several new nonbinder therapies that target intestinal phosphate absorption pathways have been developed. These include EOS789, which acts on the transcellular pathway, and tenapanor, which targets the dominant paracellular pathway. As observational evidence has established a strong association between phosphorus concentration and clinical outcomes, such as mortality, phosphate is an important target for improving the health of patients with CKD and end-stage kidney disease (ESKD)

Diagnosis and Management of Type 2 Diabetic Kidney Disease

Type 2 diabetic kidney disease (DKD) is the most common cause of CKD and ESRD worldwide, and carries with it enormous human and societal costs. The goal of this review is to provide an update on the diagnosis and management of DKD based on a comprehensive review of the medical literature. Topics addressed include the evolving presentation of DKD, clinical differentiation of DKD from non-DKD, a state-of-the-art evaluation of current treatment strategies, and promising emerging treatments. It is expected that the review will help clinicians to diagnose and manage patients with DKD

Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes.

BackgroundHyponatremia is the most common electrolyte abnormality in clinical practice, yet little is known about its frequency in patients with cancer or its impact on their clinical outcomes.Study designRetrospective analysis of prospectively collected data.Setting &amp; participantsPatients with cancer admitted to the University of Texas M.D. Anderson Cancer Center in 2006 for 3 months.PredictorSerum sodium levels categorized as eunatremia (serum sodium, 135-147 mEq/L) and mild (134-130 mEq/L), moderate (129-120 mEq/L), and severe (&lt;120 mEq/L) hyponatremia.Outcomes(1) Length of hospital stay and (2) 90-day mortality.ResultsIn 4,702 admissions in 3,357 patients with cancer, hyponatremia (serum sodium &lt;135 mEq/L) was noted in 47% of admissions. It was mild in 36%, moderate in 10%, and severe in 1%. Hyponatremia was acquired during the hospital stay in 24%. Using the first admission data, mean length of stay was 5.6 ± 5.0 days for patients with eunatremia and 9.9 ± 9.2, 13.0 ± 14.1, and 11.5 ± 12.6 days for those with mild, moderate, and severe hyponatremia, respectively. The respective HRs in the multivariate Cox model for longer hospital stay, using patients with eunatremia as reference, were 1.92 (95% CI, 1.75-2.13; P &lt; 0.01), 2.94 (95% CI, 2.56-3.45; P &lt; 0.01), and 2.32 (95% CI, 1.32-4.00; P = 0.01). 283 (8.4%) deaths occurred during 90 days, and in the multivariate model, the respective HRs for 90-day mortality for mild, moderate, and severe hyponatremia were 2.04 (95% CI, 1.42-2.91; P &lt; 0.01); 4.74 (95% CI, 3.21-7.01; P &lt; 0.01), and 3.46 (95% CI, 1.05-11.44; P = 0.04). These findings were consistent when analyses were repeated with sodium levels in tertiles.LimitationsObservational study, retrospective, inability to adjust for all comorbid conditions.ConclusionHyponatremia in patients with cancer is associated with longer hospital stay and higher mortality. Whether long-term correction of hyponatremia would improve these outcomes remains to be determined

Incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a comprehensive cancer center.

Background and objectivesIncidence of AKI in hospitalized patients with cancer is increasing, but reports are scant. The objective of this study was to determine incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a cancer center.Design, setting, participants, &amp; measurementsCross-sectional analysis of prospectively collected data on 3558 patients admitted to the University of Texas M.D. Anderson Cancer Center over 3 months in 2006.ResultsUsing modified RIFLE (Risk, Injury, Failure, Loss, ESRD) criteria, 12% of patients admitted to the hospital had AKI, with severity in the Risk, Injury, and Failure categories of 68%, 21%, and 11%, respectively. AKI occurred in 45% of patients during the first 2 days and in 55% thereafter. Dialysis was required in 4% of patients and nephrology consultation in 10%. In the multivariate model, the odds ratio (OR) for developing AKI was significantly higher for diabetes (OR, 1.89; 95% confidence interval [CI], 1.51-2.36), chemotherapy (OR, 1.61; 95% CI, 1.26-2.05), intravenous contrast (OR, 4.55; 95% CI, 3.51-5.89), hyponatremia (OR, 1.97; 95% CI, 1.57-2.47), and antibiotics (OR, 1.52; 95% CI, 1.15-2.02). In patients with AKI, length of stay (100%), cost (106%), and odds for mortality (4.7-fold) were significantly greater.ConclusionThe rate of AKI in patients admitted to a comprehensive cancer center was higher than the rate in most noncancer settings; was correlated significantly with diabetes, hyponatremia, intravenous contrast, chemotherapy, and antibiotics; and was associated with poorer clinical outcomes. AKI developed in many patients after admission. Studies are warranted to determine whether proactive measures may limit AKI and improve outcomes

Incidence Rate, Clinical Correlates, and Outcomes of AKI in Patients Admitted to a Comprehensive Cancer Center

BACKGROUND AND OBJECTIVES: Incidence of AKI in hospitalized patients with cancer is increasing, but reports are scant. The objective of this study was to determine incidence rate, clinical correlates, and outcomes of AKI in patients admitted to a cancer center. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cross-sectional analysis of prospectively collected data on 3558 patients admitted to the University of Texas M.D. Anderson Cancer Center over 3 months in 2006. RESULTS: Using modified RIFLE (Risk, Injury, Failure, Loss, ESRD) criteria, 12% of patients admitted to the hospital had AKI, with severity in the Risk, Injury, and Failure categories of 68%, 21%, and 11%, respectively. AKI occurred in 45% of patients during the first 2 days and in 55% thereafter. Dialysis was required in 4% of patients and nephrology consultation in 10%. In the multivariate model, the odds ratio (OR) for developing AKI was significantly higher for diabetes (OR, 1.89; 95% confidence interval [CI], 1.51–2.36), chemotherapy (OR, 1.61; 95% CI, 1.26–2.05), intravenous contrast (OR, 4.55; 95% CI, 3.51–5.89), hyponatremia (OR, 1.97; 95% CI, 1.57–2.47), and antibiotics (OR, 1.52; 95% CI, 1.15–2.02). In patients with AKI, length of stay (100%), cost (106%), and odds for mortality (4.7-fold) were significantly greater. CONCLUSION: The rate of AKI in patients admitted to a comprehensive cancer center was higher than the rate in most noncancer settings; was correlated significantly with diabetes, hyponatremia, intravenous contrast, chemotherapy, and antibiotics; and was associated with poorer clinical outcomes. AKI developed in many patients after admission. Studies are warranted to determine whether proactive measures may limit AKI and improve outcomes