Methods: A total of 63 unilateral nephrectomised male and female Wistar rats were divided into five groups. Group 1 (ShOPR): Rats as sham-operated group were subjected to surgical procedure without RIR. Group 2 (Isch): Rats underwent RIR (left kidney ischemia for 30 min followed by 48 h reperfusion). Group 3 (Zn+Isch): Rats were treated as group 2 but they received Zn sulphate (30 mg/kg) 1 h before induction of RIR. Group 4 (IPC+Isch): Rats were treated as group 2 but they underwent 1 min of ischemia followed by 3 min reperfusion as IPC, which was repeated for three times before induction of RIR. Group 5 (Zn+IPC+Isch): Rats were subjected to receive both Zn sulphate and IPC before induction of RIR. Urine samples were collected in the last 6 h of reperfusion, and finally biochemical and histological measurements were performed.
Results: The serum level of creatinine (Cr), normalised kidney weight (KW) and kidney tissue damage score (KTDS) increased by RIR alone significantly (P < 0.05). These parameters were attenuated statistically by Zn supplementation (P < 0.05). However, IPC alone or co-treatment of Zn and IPC did not improve the biochemical and histological markers altered by RIR injury.
Conclusion: Zn supplementation had a protective role against RIR while such protective effect was not observed by IPC alone or by co-treatment of Zn and IPC.
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.
Aim: To evaluate the nephroprotective activity of CAE and its fractions in cisplatin-induced nephrotoxicity and to assess whether they compromise the anticancer efficacy of cisplatin.
Materials and methods: Cisplatin-induced renal damage was induced in Ehrlich Ascites Carcinoma (EAC) bearing mice during mild phase of tumor growth. CAE and its butanol (BF) and aqueous (AF) fractions were administered orally from the 5th day for five days. Nephroprotective potential (serum urea, creatinine, renal histology) and effect of VC on cisplatin anticancer efficacy (tumor volume, viable tumor cells, percentage increase in life span (% ILS)) were calculated.
Result: CAE and its fractions significantly reversed the cisplatin-induced renal damage. CAE and BF treated animals showed regeneration of 50%-75% of proximal tubular cells. Compared to EAC control mice, the % ILS of the cisplatin-treated group was 244% and it was further extended to 379% after CAE administration. The % ILS in the CAE treated group was 1.6 times higher than the cisplatin alone treated group. GC-MS study showed the presence of astaxanthin and betulin.
Conclusion: CAE of VC reverses cisplatin-induced kidney damage as well as regenerates proximal tubular epithelial cells, without compromising the anticancer effect of cisplatin. When CAE was further fractionated, the nephroprotective activity was retained, but the beneficial anticancer effect of cisplatin was compromised.
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.
METHOD: The meta-analysis included all studies that examined the effect of prebiotic, probiotic, and synbiotic supplements on one or more renal function parameters and had a control group. We searched July 1967 through to March 2016 MEDLINE, Scopus, and Google Scholar databases.
RESULTS: Of 437 studies, 13 were eligible for inclusion in the meta-analysis. GFR levels tended to be reduced; whereas creatinine levels increased in the intervention group compared with the placebo group, both in a non-significant manner. The pooled effect on BUN demonstrated a significant decline compared with the placebo group (MD, -1.72 mmol/L; 95% confidence interval [CI], -2.93 to -0.51; P = 0.005). Urea significantly decreased after intervention (-0.46 mmol/L; 95% CI, -0.60 to -0.32; P <0.0001). The UA levels significantly increased in the intervention group compared with the placebo group (12.28 µmol/L; 95% CI, 0.85-23.71; P = 0.035).
CONCLUSION: This study showed a significant increase in UA and a decrease in urea and BUN. The use of prebiotic, probiotic, and synbiotic supplements among those with compromised renal function or those at risk for renal failure should be limited until large-scale, well-designed randomized controlled trials prove the safety and efficacy of these supplements in improving renal function.