Mechanism of Modified Liuwei Dihuangtang in Bone Protection of CKD-MBD Model Rats： An Exploration Based on Klotho-FGF23 Axis / 中国实验方剂学杂志

Objective:To observe the effects of modified Liuwei Dihuangtang on serum fibroblast growth factor 23 （FGF23）， full-length intact parathyroid hormone （iPTH）， and 1，25-dihydroxyvitamin D₃［1，25（OH）₂D₃］ levels and Klotho and FGF23 protein expression in renal and bone tissues of rats exposed to high phosphorus combined with adenine， so as to explore the mechanism of modified Liuwei Dihuangtang against renal osteopathy. Method:One hundred and thirty healthy adult SD rats were randomly divided into five groups， namely normal group（<italic>n</italic>=10），high phosphorus group（<italic>n</italic>=30），model group（<italic>n</italic>=30），modified Liuwei Dihuangtang group（<italic>n</italic>=30） ， and calcitriol group（<italic>n</italic>=30），and rats in each group were further classified based on three time points， namely 8，10， and 12 weeks. Rats in the normal group were fed with normal diet， the ones in the high phosphorus group with high phosphorus diet， and those in the other groups with adenine and high phosphorus diet for inducing renal osteopathy. Rats in the normal group，high phosphorus group， and model group were intragastrically administered with distilled water （10 mL·kg^-1·d^-1），the ones in the modified Liuwei Dihuangtang group with modified Liuwei Dihuangtang （2.556 g·kg^-1·d^-1） ， and those in the calcitriol group with calcitriol （0.09 μg·kg^-1·d^-1）. Result:Compared with the normal group and high phosphorus group at the weeks of 8，10 and 12，the model group displayed significantly elevated blood urea nitrogen（BUN），serum creatinine（SCr），serum phosphorus，iPTH，FGF23，renal interstitial fibrosis score， and FGF23 expression in renal and bone tissues， but lowered serum calcium and 1，25（OH）₂D₃ and Klotho protein expression in renal and bone tissues（<italic>P</italic><0.05 ，<italic>P</italic><0.01）. Compared with the model group at the weeks of 8，10 and 12， the modified Liuwei Dihuangtang and calcitriol both significantly decreased the serum BUN，SCr，serum phosphorus，iPTH， FGF23， tubulointerstitial semi-quantitative score， and FGF23 expression in renal and bone tissues， while increased the serum calcium，1，25（OH）₂D₃， and Klotho protein expression in renal and bone tissues （<italic>P</italic><0.05，<italic>P</italic><0.01）. There was no significant difference in the above-mentioned indexes between the modified Liuwei Dihuangtang group and the calcitriol group at the same time point. Conclusion:Klotho-FGF23 axis is probably involved in renal osteopathy. The modified Liuwei Dihuangtang effectively improves renal function，alleviates pathological changes in renal and bone tissues，and regulates calcium and phosphorus metabolism to protect the bone， which is related to its regulation of Klotho-FGF23 axis.

Research on relationship of FGF-23 and sKL with cardiac valve calcification in CAPD patients / 上海交通大学学报（医学版）

Objective: To explore the relationship of fibroblast growth factor-23 (FGF-23) and soluble klotho (sKL) with cardiac valve calcification in patients with continuous ambulatory peritoneal dialysis (CAPD). Methods: 147 CAPD patients from the dialysis center of the First Affiliated Hospital of Soochow University were enrolled. The concentrations of FGF-23 and sKL were measured by enzyme-linked immunosorbent assays (ELISA). Echocardiography was applied to evaluate cardiac valve calcification. The patients were divided into normal cardiac valve group (group A) and cardiac valve calcification group (group B). SPSS 23.0 software was used for data analysis. Results: The incidence of cardiac valve calcification in CAPD patients was 54.42%. The risk of cardiac valve calcification showed positive correlation with age, dialysis age, serum creatinine, corrected calcium, serum phosphorus, serum alkaline phosphatase, parathyroid hormone, and the level of FGF-23 (P=0.045, P=0.022, P=0.006, P=0.024, P=0.000, P=0.017, P=0.022, P=0.000), and negative correlation with urea clearance index, the level of sKL and residual renal function (P=0.045, P=0.000, P=0.011). Multivariate Logistic regression analysis showed that the increase of FGF-23 (OR=5.007, 95% CI 1.446-17.339, P=0.011) and serum phosphorus (OR=7.433, 95% CI 1.558-35.470, P=0.012) were two independent risk factors for cardiac valve calcification in CAPD patients, and the decrease of sKL (OR=0.310, 95% CI 0.108-0.891, P=0.030) was another independent risk factor as well. Receiver operator characteristic curves (ROC) indicated that to predict cardiac valve calcification in patients with CAPD, the optimal cut off points of FGF-23 and sKL were 2 172.64 pg/mL (sensitivity was 91.3%, specificity was 91%) and 231.88 pg/mL (sensitivity was 88.8%, specificity was 92.5%), respectively. Conclusion: The high level of FGF-23 and low level of sKL are two independent risk factors for cardiac valve calcification in CAPD patients. FGF-23 and sKL can be used to diagnose cardiac valve calcification in CAPD patients.

Research on relationship of FGF-23 and sKL with cardiac valve calcification in CAPD patients / 上海交通大学学报（医学版）

Objective· To explore the relationship of fibroblast growth factor-23 (FGF-23) and soluble klotho (sKL) with cardiac valve calcification in patients with continuous ambulatory peritoneal dialysis (CAPD).Methods· 147 CAPD patients from the dialysis center of the First Affiliated Hospital of Soochow University were enrolled.The concentrations of FGF-23 and sKL were measured by enzyme-linked immunosorbent assays (ELISA).Echocardiography was applied to evaluate cardiac valve calcification.The patients were divided into normal cardiac valve group (group A) and cardiac valve calcification group (group B).SPSS 23.0 software was used for data analysis.Results· The incidence of cardiac valve calcification in CAPD patients was 54.42％.The risk of cardiac valve calcification showed positive correlation with age,dialysis age,serum creatinine,corrected calcium,serum phosphorus,serum alkaline phosphatase,parathyroid hormone,and the level of FGF-23 (P=0.045,P=0.022,P=0.006,P=0.024,P=0.000,P=0.017,P=0.022,P=0.000),and negative correlation with urea clearance index,the level of sKL and residual renal function (P=0.045,P=0.000,P=0.011).Multivariate Logistic regression analysis showed that the increase of FGF-23 (OR=5.007,95％ CI 1.446-17.339,P=0.011) and serum phosphorus (OR=7.433,95％ CI 1.558-35.470,P=0.012) were two independent risk factors for cardiac valve calcification in CAPD patients,and the decrease of sKL (OR=0.310,95％ CI 0.108-0.891,P=0.030) was another independent risk factor as well.Receiver operator characteristic curves (ROC) indicated that to predict cardiac valve calcification in patients with CAPD,the optimal cut off points of FGF-23 and sKL were 2 172.64 pg/mL (sensitivity was 91.3％,specificity was 91％) and 231.88 pg/mL (sensitivity was 88.8％,specificity was 92.5％),respectively.Conclusion· The high level of FGF-23 and low level of sKL are two independent risk factors for cardiac valve calcification in CAPD patients.FGF-23 and sKL can be used to diagnose cardiac valve calcification in CAPD patients.