Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD.

Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml/min per 1.73 m(2)) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemic-euglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg/min per µU/ml; P<0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P<0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P<0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, -0.7; 95% confidence interval, -1.4 to 0.0 mg/min per µU/ml) and insulin clearance (adjusted difference, -85; 95% confidence interval, -160 to -10 ml/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.

Dietary Acid Load is Associated With Serum Bicarbonate but not Insulin Sensitivity in Chronic Kidney Disease.

OBJECTIVE: In chronic kidney disease (CKD), dietary acid may promote metabolic acidosis and insulin resistance, which in turn may contribute to adverse clinical health outcomes. We examined associations between dietary acid load, serum bicarbonate, and insulin sensitivity in CKD. DESIGN: In a cross-sectional study, we collected 3-day prospective food diaries to quantify dietary acid load as net endogenous acid production (NEAP, the nonvolatile acid load produced by the diet's acid balance) and potential renal acid load (PRAL). We measured urine net acid excretion (NAE) in 24-hour urine samples. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp. SUBJECTS: Forty-two patients with CKD Stages 3 to 5 attending nephrology clinics in the Pacific Northwest and 21 control subjects (estimated glomerular filtration rate [eGFR] ≥ 60 mL/minute/1.73 m(2)). MAIN OUTCOME MEASURES: Serum bicarbonate and insulin sensitivity (SIclamp). RESULTS: Mean age was 60.8 ± 13.6 years, and 54% of participants were men. Mean eGFR and serum bicarbonate concentrations were 34.4 ± 13.1 mL/minute/1.73 m(2) and 24.1 ± 2.9 mEq/L for participants with CKD and 88.6 ± 14.5 mL/minute/1.73 m(2) and 26.3 ± 1.8 mEq/L for control subjects, respectively. Mean NEAP, PRAL, and NAE were 58.2 ± 24.3, 9.7 ± 18.4, and 32.1 ± 19.8 mEq/day, respectively. Considering all participants, dietary acid load was significantly, inversely associated with serum bicarbonate, adjusting for age, gender, race, eGFR, body mass index, and diuretic use: -1.2 mEq/L per standard deviation (SD) NEAP (95% confidence interval [CI] -1.8 to -0.6, P < .0001); -0.9 mEq/L bicarbonate per SD PRAL (95% CI -1.5 to -0.4, P = .0005); -0.7 mEq/L bicarbonate per SD NAE (95% CI -1.2 to -0.1, P = .01). These associations were similar in participants with and without CKD. However, neither NEAP and PRAL nor NAE was significantly associated with SIclamp. Serum bicarbonate was also not significantly associated with SIclamp. CONCLUSIONS: In CKD, dietary acid load is associated with serum bicarbonate, suggesting that acidosis may be improved by dietary changes, but not with insulin sensitivity.

Simultaneous Liquid Chromatographic Determination of 10 Ultra-Violet Filters in Sunscreens.

A rapid HPLC method was developed for the simultaneous determination of 10 UV filters found in sunscreen. The following UV filters were analyzed in this method; 2-phenylbenzimidazole-5-sulfonic acid, benzophenone-3, isoamyl p-methoxycinnamate, 4-methylbenzylidene camphor, octocrylene, ethylhexyl dimethyl 4-aminobenzoic acid, ethylhexyl methoxycinnamate, butyl methoxydibenzoylmethane, ethylhexyl salicylate and homosalate. The method was developed on two columns; a Thermo Hypersil C18 BDS, 3 µm column (4.6 × 100 mm) and a Chromolith RP-18e Monolithic column (4.6 × 100 mm). The same mobile phase of ethanol and 1% acetic acid (70:30, v/v) was employed for both columns. The separation of the 10 UV filters was carried out successfully on both columns; the optimal resolution was obtained on the Thermo Scientific Hypersil column in a time frame of 7 min. An isocratic elution utilizing ethanol and acetic acid (70:30, v/v) at a temperature of 35°C was employed. The method was applied to a number of commercial samples of sunscreen and lotions and was validated according to International Conference on Harmonisation guidelines for selectivity, linearity, accuracy, precision and robustness. A comparison of the performances of both columns was also carried out.

Rapid liquid chromatographic determination of itraconazole and its production impurities.

A simple, rapid ultra-performance liquid chromatography (UPLC) method was developed for the analysis of itraconazole and its associated production impurities. The optimum chromatographic conditions were achieved using an Agilent Zorbax Eclipse XDB C18 column, 1.8 µm (4.6 × 50 mm) installed in a column oven heater utilizing a gradient mobile phase of 0.08M tetrabutylammonium hydrogen sulfate buffer-acetonitrile (80:20, v/v), with ultraviolet detection at 235 nm. An Agilent 1200 RRLC Series was used for the UPLC analysis. UPLC is a technology that greatly reduces analysis time by utilizing columns packed with sub-2 µm particles. The method was validated according to International Conference on Harmonization guidelines with respect to precision, accuracy, linearity, robustness and limits of detection and quantification. All parameters were found to be well within the stated guidelines. The total analysis time was reduced by two-thirds, from over 30 min (the current European Pharmacopeia method) to under 10 min, and the method is applicable for assay and related substance determination. A method utilizing the sub-2 µm column on a conventional high-performance liquid chromatography system was also developed and validated, resulting in substantial time and solvent savings.