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

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 & 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 (<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 <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.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, & 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

Chronic kidney disease and peripheral nerve function in the Health, Aging and Body Composition Study

BACKGROUND: Chronic kidney disease (CKD) is associated with poor mobility. Peripheral nerve function alterations play a significant role in low mobility. We tested the hypothesis that early CKD is associated with altered sensory, motor and autonomic nerve function. METHODS: Participants in the Health, Aging and Body Composition cohort who had kidney function measures in Year 3 (1999-2000) and nerve function measurements at Year 4 (2000-01) were analyzed (n = 2290). Sensory (vibration threshold, monofilament insensitivity to light and standard touch), motor [compound motor action potentials (CMAPs), nerve conduction velocities (NCVs)] and autonomic (heart rate response and recovery after a 400-m walk test) nerve function as well as participant characteristics were compared across cystatin C- and creatinine-based estimated glomerular filtration rate categorized as ≤60 (CKD) or >60 mL/min/1.73 m2 (non-CKD). The association between CKD and nerve function was examined with logistic regression adjusted for covariates. RESULTS: Participants with CKD (n = 476) were older (77 ± 3 versus 75 ± 3 years; P < 0.05) and had a higher prevalence of diabetes (20.6% versus 13.1%; P < 0.001). CKD was associated with higher odds for vibration detection threshold {odds ratio [OR] 1.7 [95% confidence interval (CI) 1.1-2.7]} and light touch insensitivity [OR 1.4 (95% CI 1.1-1.7)]. CMAPs and NCVs were not significantly different between CKD and non-CKD patients. In adjusted analyses, participants with CKD had higher odds of an abnormal heart rate response [OR 1.6 (95% CI 1.1-2.2)] and poor heart rate recovery [OR 1.5 (95% CI 1.1-2.0)]. CONCLUSIONS: CKD is associated with changes in sensory and autonomic nerve function, even after adjustment for demographics and comorbidities, including diabetes. Longitudinal studies in CKD are needed to determine the contribution of nerve impairments to clinically important outcomes