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.

The frequency, cost, and clinical outcomes of hypernatremia in patients hospitalized to a comprehensive cancer center.

PURPOSE: To study the frequency of hypernatremia in hospitalized cancer patients and its impact on clinical outcomes and healthcare cost. METHODS: Cross-sectional analysis of data obtained from patients admitted to the University of Texas M. D. Anderson Cancer Center over a 3-month period in 2006. The clinical outcomes and hospital costs were compared among hypernatremics, eunatremics, and hyponatremics (serum sodium values include >147, 135-147, and <135 mEq/L, respectively). RESULTS: Of 3,446 patients with at least one serum sodium value, 51.4 % were eunatremic, 46.0 % hyponatremic, and 2.6 % hypernatremic with most of the hypernatremia (90 %) acquired during hospital stay. The multivariate hazard ratio (HR) for mortality in hypernatremic was 5-fold higher than eunatremic (HR for 90 days-5.09 (95 % CI, 3.32-7.81); p < 0·01) and over 2-fold higher than hyponatremic (HR for 90 days-2.79 (95 % CI, 1.91-4.11), p < 0.01). The length of hospital stay in hypernatremic was 2-fold higher than in hyponatremic and 4-fold higher than in eunatremic (e.g., 27 ± 22 days in hypernatremic vs. 6 ± 5 days in eunatremic; mean ± SD, p < 0.01). The hospital bill was higher for hypernatremic compared with the rest of the groups (46 % over eunatremic and 37 % over hyponatremic, p < 0.01 for both). CONCLUSIONS: Although hypernatremia was far less frequent than hyponatremia in the hospitalized cancer patients, most hypernatremia were acquired in the hospital and had substantially higher mortality, hospital stay, and hospital bills than eunatremic or even hyponatremic patients. Studies are warranted to determine whether avoidance of hypernatremia or its prompt and sustained correction improves clinical outcomes.

The impact of statin and macrolide use on early survival in patients with pneumococcal pneumonia.

BACKGROUND: Mortality in pneumococcal pneumonia remains high despite early antibiotic eradication of bacteria. Most deaths occur within the first week, the time of peak inflammatory responses. Statins and macrolides have broad immunosuppressive activity; their impact, separately and together, on survival in patients with pneumococcal pneumonia was evaluated. METHODS: All patients with pneumococcal pneumonia seen at a single medical center from 2000 through 2010 were included in this retrospective cohort study. A multivariate-adjusted Cox proportional hazard model was used to evaluate survival. RESULTS: Of 347 patients with pneumococcal pneumonia, 90 (26%) were taking a statin at presentation and 126 (36%) were started on treatment with a macrolide. Thirty-two (9%) statin users were treated with a macrolide. Statin users were older than non-statin users, with a higher prevalence of diabetes, coronary artery disease and chronic kidney disease and a lower prevalence of alcohol consumption and liver disease. Statin users had higher mean Pneumonia Patient Outcomes Research Team scores. Patients treated with a macrolide were not different from those who received other antibiotics. The risk of mortality among statin users was reduced at 7, 14, 20 and 30 days after admission. Mortality was not reduced in patients treated with a macrolide or with a macrolide plus a statin compared with those who did not receive a macrolide. CONCLUSIONS: Patients who are receiving statins at the time of admission for pneumococcal pneumonia have better clinical outcomes than those who are not. Treatment with a macrolide does not appear to confer a survival benefit.

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.

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

BACKGROUND: Hyponatremia 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 DESIGN: Retrospective analysis of prospectively collected data. SETTING & PARTICIPANTS: Patients with cancer admitted to the University of Texas M.D. Anderson Cancer Center in 2006 for 3 months. PREDICTOR: Serum sodium levels categorized as eunatremia (serum sodium, 135-147 mEq/L) and mild (134-130 mEq/L), moderate (129-120 mEq/L), and severe (<120 mEq/L) hyponatremia. OUTCOMES: (1) Length of hospital stay and (2) 90-day mortality. RESULTS: In 4,702 admissions in 3,357 patients with cancer, hyponatremia (serum sodium <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 < 0.01), 2.94 (95% CI, 2.56-3.45; P < 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 < 0.01); 4.74 (95% CI, 3.21-7.01; P < 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. LIMITATIONS: Observational study, retrospective, inability to adjust for all comorbid conditions. CONCLUSION: Hyponatremia 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.