Short-term efficacy of dapagliflozin in children with hereditary proteinuric kidney disease / 中华儿科杂志

Objective: To explore the short-term efficacy and safety of dapagliflozin in children with hereditary proteinuric kidney disease. Methods: This was a prospective cohort study. From August 2020 to December 2021, 23 children with hereditary kidney disease from Children's Hospital of Fudan University were enrolled. Patients received dapagliflozin 5 mg/d (weight≤30 kg) or initial dose 5 mg/d for 1 week, then 10 mg/d (weight>30 kg) and the dose of angiotensin converting enzyme inhibitors was stable during treatment. Clinical data including demographic parameters, primary diagnosis, estimated glomerular filtration rate (eGFR), 24 h proteinuria and characteristics in the follow-up were collected. The primary outcome was the change in 24 h proteinuria at 12 (±2) weeks, secondary outcomes included changes of 24 h proteinuria at 24 (±2) weeks, eGFR at both 12 (±2) and 24 (±2) weeks. The data were analysed by using mixed linear model. Results: Totally 23 patients were enrolled, including 16 males and 7 females. The age was (10.8±2.9) years. The primary diseases were Alport syndrome (12 cases), Dent disease (5 cases), proteinuria (4 cases), and focal segmental glomerulosclerosis (2 cases) respectively. Primary outcome showed that 24 h proteinuria decreased from baseline at 12 (±2) weeks during treatment (1.75 (1.46, 2.20) vs. 1.84 (1.14, 2.54) g/m2, P<0.05). Secondary outcomes showed that there was no significant difference in 24 h urine protein at 24 (±2) weeks (P>0.05). eGFR decreased slightly at 12 (±2) weeks ((107±21) vs. (112±28) ml/(min·1.73m2), P<0.05), and there was no significant difference at 24 (±2) weeks (P>0.05). Serum albumin increased at 12 (±2) and 24 (±2) weeks following the treatment ((39±8) vs. (37±8) g/L, (38±7) vs. (37±8) g/L, both P<0.05). No hypoglycemia event was reported during the treatment. Conclusion: The dapagliflozin had therapeutic effects on decreasing proteinuria and increasing serum albumin in short-term treatment in children with hereditary proteinuric kidney disease, no hypoglycemia or serious adverse events were observed.

Effect of polysaccharides from Polygonatum sibiricum on lipid-metabolism related mRNA and protein expression in hyperlipidemic mice / 中国中药杂志

To study the effect of polysaccharides from Polygonatum sibiricum on mRNA and protein expressions of blood lipid metabolism in hyperlipidemic mice. The mice were randomly divided into 6 groups, namely the blank control group, the hyperlipidemia model group, the simvastatin group, and low, middle and high-dose PSP groups (200, 400, 800 mg·kg⁻¹·d⁻¹). Each group of the mice was administrated intragastrically for 14 days, respectively. Subsequently, every group of mice, except for the blank control group, was intraperitoneally injected with 75% fresh egg yolk emulsion for establishing the hyperlipidemic mice model. Upon completion of the administration, the contents of TC, TG, LDL-C and HDL-C in serum of each group were investigated in details. In particular, the mRNA expression levels of PPAR-α, PPAR-, PPAR-, SREBP-1c, IL-6 and TNF-α of the liver tissues were detected by Real-time PCR, and the protein expression levels (including PPAR-α, PPAR-, PPAR-, SREBP-1c, IL-6, TNF-α) were examined by Western blot. Consequently, the obtained results showed that the contents of the serum TC, TG, LDL-C of low, middle and high-dose PSP groups significantly decreased compared with those of the hyperlipidemia model group. Simultaneously, there were significant differences between middle-dose and high-dose PSP groups (<0.01). In striking contrast, the contents of serum HDL-C of low, middle and high-dose PSP groups significantly increased, while obvious differences were also observed between middle-dose and high-dose PSP groups (<0.01). Moreover, middle-dose and high-dose PSR groups could up-regulate the protein and mRNA expressions of PPAR-α, PPAR- (<0.05) compared with those of the hyperlipidemia model group, and down-regulate the expressions of PPAR-,SREBP-1c, IL-6 and TNF-α(<0.05) compared with those of liver tissues of the hyperlipidemia model group. In conclusion, all of the above results suggested that PSP could inhibit the oxidation of the liver lipid, and regulate the expression levels of the corresponding genes and proteins relating to the lipid metabolism, so as to play a critical role for preventing hyperlipidemia.