Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients.

BACKGROUND: In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges. METHODS: We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment. RESULTS: The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1; P=0.006). This effect was pronounced in older (aged 65-74 years) versus younger (aged 20-64 years) participants (P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores. CONCLUSIONS: Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048.

Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide.

BACKGROUND: Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide' s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6-8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations - such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies. METHODS: A single-center, PK interaction study was performed in a total of 14 healthy volunteers, to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine for the elimination of teriflunomide. Participants received teriflunomide for 14 days, followed by an AEP with colestipol HCl for 15 days. RESULTS AND CONCLUSIONS: The administration of colestipol HCl for 15 days was sufficient to reduce plasma teriflunomide concentrations by greater than 96%. Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options.

Bile acid sequestrants for glycemic control in patients with type 2 diabetes: A systematic review with meta-analysis of randomized controlled trials.

AIM: To evaluate the effects of bile acid sequestrants (BASs) versus placebo, no intervention or active comparators on glycemic control in type 2 diabetes. METHODS: Data were retrieved and a systematic review with meta-analyses was performed. We evaluated bias control and subgroup and sensitivity analyses were performed to evaluate heterogeneity and bias. RESULTS: We included 17 trials with a total of 2950 patients randomized to BASs (colesevelam or colestimide) versus placebo, no intervention, statins or sitagliptin. Random-effects meta-analysis showed that patients randomized to BASs had a lower hemoglobin A1c at the end of treatment compared with the control group (mean difference-0.55%; 95% confidence interval-0.64 to -0.46). Analysis of trials with low risk of bias in all domains confirmed the findings. Data on adverse events were limited. There were no differences between trials stratified by the control group and no evidence of publication bias or small study effects. CONCLUSIONS: Our analyses found that BAS treatment improves glycemic control. The size of the effect was clinically relevant and despite limited safety data, our findings support the inclusion of BASs in current diabetes management algorithms for type 2 diabetes.

Challenges in Diagnosing Medication Resins in Surgical Pathology Specimens: A Crystal-Clear Review Guide.

CONTEXT: - Medication resins, including Kayexalate, sevelamer, and bile acid sequestrants, can be encountered in gastrointestinal tract specimens. Their classic histologic appearances have been well documented, but pathologist recognition of the resins is 75%, patient history is not always available, and atypical morphologic findings are sometimes present. OBJECTIVE: - To offer a succinct overview of resins in the gastrointestinal tract, including typical and atypical appearances, in order to serve as a quick reference guide. DATA SOURCES: - The study comprises published literature, survey data, and our personal experiences. CONCLUSIONS: - Classic morphology is the benchmark for identifying these resins, but color, location, and fish scale pattern can deviate from the norm, making proper identification a challenge. Patient history should be sought whenever possible, and ancillary staining is an option when necessary. Additionally, the presence of resins should prompt the pathologist to search for potentially related diagnoses (namely, causes of diarrhea in patients on bile acid sequestrants and diagnoses associated with renal failure in patients on Kayexalate or sevelamer).