Objective: To observe the effect of Ronghuang granule on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptor (FGFRs) and Klotho protein levels in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and kidney deficiency and damp heat syndrome.
Methods: Seventy non-dialysis CKD-MBD patients with kidney deficiency and dampness-heat syndrome were randomized into control group (n=35) and treatment group (n=35). All the patients were given routine treatment combined with traditional Chinese medicine retention enema, and the patients in the treatment group received additional Ronghuang granule treatment (3 times a day). After the 12-week treatments, the patients were examined for changes of TCM syndromes. Serum levels of Ca, P, parathyroid hormone (iPTH), FGF23, FGFRs and Klotho proteins were detected before and after treatment. These parameters were also examined in 20 healthy volunteers.
Results: Sixty-five patients completed the study, including 33 in the control group and 32 in the treatment group. The patients in the treatment group showed significantly better treatment responses than those in the control group (P < 0.05 or 0.01). At 4, 8, and 12 weeks of treatment, the patients in the treatment group had significantly lowered scores of TCM syndromes compared with the score before treatment (P < 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks (P < 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group (P < 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group (P < 0.05) but only at 12 weeks in the control group (P < 0.05). The patients in the control and treatment groups all showed elevated serum levels of FGF23, FGFRs and Klotho protein compared with the normal subjects (P < 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group (P < 0.05) but remained unchanged in the control group (P>0.05), showing significant differences between the two groups.
Conclusions: Ronghuang granule improves the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and dampness heat syndrome by reducing serum levels of FGF23, FGFRs and Klotho, improving calcium and phosphorus metabolism disorder, and inhibiting secondary hyperparathyroidism.
目的: 观察非透析慢性肾脏病矿物质和骨代谢异常（CKD-MBD）肾虚湿热证患者血清成纤维细胞生长因子23（FGF23）、成纤维细胞生长因子受体（FGFRs）、Klotho蛋白水平的变化及蓉黄颗粒的干预作用。
方法: 将符合纳入标准的70例非透析CKD-MBD肾虚湿热证患者，随机分为治疗组和对照组各35例，最终实际完成65例，对照组33例，治疗组32例，并设正常组20例。两组患者均给予常规治疗并结合中药保留灌肠，治疗组在此基础上加用蓉黄颗粒，温水冲服，3次/d，1袋/次。疗程均为12周。观察并记录两组患者中医证候变化，并检测两组患者治疗前后血清钙（Ca）、磷（P）、甲状旁腺激素（iPTH）、FGF23、FGFRs及Klotho蛋白，同时检测正常组血清FGF23、FGFRs、Klotho蛋白水平。
结果: 治疗组治疗后CKD-MBD疗效显著优于对照组（P < 0.05）。治疗组各时间节点中医证候积分值分别与治疗前比较均显著降低（P < 0.05或P < 0.01）；对照组仅治疗12周末的中医证候积分值较治疗前降低（P < 0.05）；治疗组均显著优于对照组（P < 0.01）。治疗组治疗后各时间节点血清Ca、P、iPTH均较治疗前改善（P < 0.05或P < 0.01）。对照组仅在治疗12周末，血清Ca升高，血清P、iPTH降低（P < 0.05）。治疗前，对照组、治疗组血清FGF23、FGFRs、Klotho蛋白水平与正常组比较，差异均有统计学意义（P < 0.01）。治疗后，治疗组血清FGF23、FGFRs、Klotho蛋白水平均较治疗前明显改善（P < 0.05）；对照组血清FGF23、FGFRs、Klotho蛋白水平与治疗前比较均无明显差异（P>0.05）；治疗组均优于对照组（P < 0.05）。
结论: 蓉黄颗粒可显著改善非透析CKD-MBD肾虚湿热证患者的临床症状，纠正非透析CKD-MBD肾虚湿热证患者钙磷代谢紊乱，抑制继发性甲状旁腺功能亢进，从而有效防治CKD-MBD，其主要作用机制可能与其显著改善患者血清FGF23、FGFRs、Klotho蛋白水平密切相关。
Keywords: Klotho protein; Ronghuang granule; chronic kidney disease-mineral and bone disorder; fibroblast growth factor 23; fibroblast growth factor receptor; syndrome of kidney deficiency and dampness heat.