MATERIALS AND METHODS: Participants with an estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of >300-5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre-specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants.
RESULTS: Of 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end-stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35-0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non-EA participants.
CONCLUSIONS: In the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events.
MATERIALS AND METHODS: This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages.
RESULTS: The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events.
CONCLUSION: This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.
METHODS: A pooled population-pharmacokinetic model was built in NONMEM based on data from 14 different studies in different patient populations. Steady-state exposure was simulated and compared across patient subgroups for two US Food and Drug Administration/European Medicines Agency-approved drug labels and optimised doses were derived.
RESULTS: The final model uses postmenstrual age, weight and serum creatinine as covariates. A 35-year-old, 70-kg patient with a serum creatinine level of 0.83 mg dL-1 (73.4 µmol L-1) has a V1, V2, CL and Q2 of 42.9 L, 41.7 L, 4.10 L h-1 and 3.22 L h-1. Clearance matures with age, reaching 50% of the maximal value (5.31 L h-1 70 kg-1) at 46.4 weeks postmenstrual age then declines with age to 50% at 61.6 years. Current dosing guidelines failed to achieve satisfactory steady-state exposure across patient subgroups. After optimisation, increased doses for the Food and Drug Administration label achieve consistent target attainment with minimal (± 20%) risk of under- and over-dosing across patient subgroups.
CONCLUSIONS: A population model was developed that is useful for further development of age and kidney function-stratified dosing regimens of vancomycin and for individualisation of treatment through therapeutic drug monitoring and Bayesian forecasting.
METHODS: Predialysis CKD patients were included in this cross-sectional study. Patient demographics, medical/medication histories, and laboratory parameters (serum 25-hydroxyvitamin D (25(OH)D), creatinine, phosphate (P), calcium, albumin, and intact-PTH (i-PTH)) were collected and compared among patients with various CKD stages. The association between 25(OH)D and these parameters was determined by multiple linear regression.
RESULTS: A total of 196 patients with mean ± SD eGFR of 26.4 ± 11.2 mL/min/1.73 m2 was included. Vitamin D deficiency (25(OH)D concentration < 15 ng/mL) and insufficiency (25(OH)D concentration 16 - 30 ng/mL) was found in 29.1% and 57.7% of the patients, respectively. Mean ± SD serum 25(OH)D was 20.8 ± 9.3 ng/mL. Female patients had lower vitamin D concentrations than males (16.9 ng/mL vs. 23.9 ng/mL; p < 0.001). Vitamin D levels were also higher in Chinese (22.3 ng/mL) than Malay (17.3 ng/mL) and Indian (13.1 ng/mL) patients (p < 0.05). Nonadjusted analyses showed higher i-PTH concentration in vitamin D deficient patients (p < 0.05).
CONCLUSION: Despite being a sun-rich country all year round, the majority (86.8%) of predialysis CKD patients in Singapore have suboptimal vitamin D status. Lower vitamin D concentrations were found in females and in those with darker skin tone. Vitamin D deficient patients also tended to have higher i-PTH levels.