| Background:Recently,a growing population of chronic kidney disease(CKD),which has a poor prognosis and low awareness rate,has been reported worldwide,and thus makes CKD a global public health concern that seriously threats human health.Since the current treatment options for stage 3-4 CKD are limited,more and more researchers and clinicians have begun to seek alternative and complementary medical care for conventional Western medicine.Chinese herbal medicine(CHM)has been widely used to prevent and treat diseases globally.In China and other Asian countries,it has long been used to treat CKD,and has accumulated rich clinical experience in the treatment of stage 3-4 CKD.Under the guidance of syndrome differentiation as the fundamental principles of traditional Chinese medicine(TCM),CHM has been improving the clinical symptoms and glomerular filtration rate,preserving residual renal function in stage 3-4 CKD patients with considerable clinical efficacy and fewer side effects.However,large-scale,multi-center clinical trials of CHM interventions in preventing and slowing the progression of renal function in stage 3-4 CKD patients are still limited to provide reliable evidence-based proof.Additionally,many active constituents and toxicity in CHM formulations remains unknown.Therefore,the safety of CHM treatment of CKD is still widely questioned,especially for its potential nephrotoxicity.Therefore,some epidemiological studies around the world still questioned that further adverse reactions might exist after taking herbal medicines in stage 3-4 CKD patients.Objective:To retrospectively analyze the correlation between CHM intervention and the risk of CKD progression in stage 3-4 CKD patients and to provide a clinical evidence-based proof for Chinese medicine to delay the progression of CKD.Methods:We used a retrospective cohort study to retrieve patient records,as well as status of end stage renal disease and renal replacement therapy,of newly diagnosed stage 3-4 CKD patients from 2010 to 2017,based on the electronic medical record system(EMRS)from China-Japan Friendship Hospital and telephone follow-up.Patients were assigned to the Chinese medicine(CM)group only if they were prescribed Chinese medicine in China-Japan Friendship Hospital,regardless of the duration of treatment,whereas those with no such prescription but only conventional Western medicine treatment were assigned to the non-Chinese medicine(non-CM)group.Furthermore,we conducted propensity score matching(PSM)method to balance the confounding factors of patients in the CM group and non-CM groups,and the Cox regression model to further statistically analyze the correlation between CM interventions and the risk of RRT,CKD progression,overall mortality and ESRD,thus to investigate the relationship between the intervention of prescribed Chinese medicine and the risk of CKD progression in patients with stage 3-4 CKD.Results:A total of 5035 patients in the EMRS from 2010 to 2017 were eligible for this study,while 1921 patients had primary diagnosis of CKD,including 959 primary glomerular disease(49.9%),461 diabetic nephropathy(24.0%),160 IgA nephropathy(8.4%),178 hypertensive nephropathy(9.3%),59 renal artery stenosis(3.1%),71 ischemic nephropathy(3.7%),and 16 occult nephropathy(0.8%).There were 2905 patients who had visited nephrology-related departments at least once during the follow-up in this hospital,among which,2419 patients were assigned to the CM group,while 486 patients with no such prescription were assigned to the non-CM group.After applying PSM to the clinical data of patients in the CM group and the non-CM group to balance the distribution of the covariates,a total of 966 patients(483 in the CM group and 483 in the non-CM group)were enrolled.Till February 1st 2018,a total of 41 initiated dialysis,6 received kidney transplants,250 patients developed CKD progression,40 patients died,and 105 entered ESRD in CM group.As to the non-CM group,34 patients started dialysis,21 received kidney transplants,274 patients met CKD progression,and 60 patients died.There was no statistically significant difference(p=0.47)in the cumulative incidence of RRT between the CM group(10.5%)and the non-CM group(11.1%).Kaplan-Meier analysis showed that the risk of CKD progression was significantly lower in the CM group than in the non-CM group in the duration of the seven-year observation(HR 0.75,95%CI 0.63-0.89,p=0.001).The cumulative incidence of ESRD in the Chinese Herbal Medicine group was 39.5%,with no significant difference from the non-CM group(p=0.86),suggesting that traditional Chinese medicine intervention did not increase the risk of ESRD in stage 3-4 CKD patients.Among the patients with 1-2 years and 2-4 years follow-up,the risk of progression of CKD was consistently lower in the CM group(p=0.008,0.007,respectively).However,when the follow-up period exceeded four years,the risk of CKD progression was not significantly different between the two groups.According to the duration of the use of prescribed Chinese medicine,the CM group patients were divided into four subgroups(1-29 days,29-87 days,88-377 days,and>378 days).The results showed that the occurrence of CKD progression was lower in the above groups than in the non-CM group,but only when the duration of CM intervention reached 378 days could a statistically significant difference be observed between CM and non-CM group(p<0.001).What's more,patients receiving Chinese herbal decoction(CHD)treatment based on TCM syndrome differentiation had a significantly lower occurrence of CKD progression,the hazard ratios of which were as follows:patients received CHD:HR 0.82,95%CI 0.68-0.99,patients received Chinese patent medicine + CHD:HR 0.64,95%CI 0.35-1.17,the difference was statistically significant(p<0.05).Patients with Cordyceps(including Jinshuibao Capsules and Bailing Capsules)(HR 0.81,95%CI 0.66-0.99,p<0.05),and Haikun Shenxi Capsules(HR 0.79,95%CI 0.63-0.99,p<0.05)showed lower risk of CKD progression.Between 2010 and 2017,the overall mortality was significantly lower in the CM group than in the non-CM group(HR 0.58,95%CI 0.39-0.86,p=0.007).Sensitivity analysis of the cumulative incidence of CKD progression was performed in both groups.Among patients over 65 years old,male,with hypertension,combined hyperlipidemia,and Charlson score no less than 4 points,CM intervention combined with conventional Western medicine is more conducive to delaying the progression of CKD,compared with western conventional treatment alone.Conclusion:In our hospital,more than 80%of patients received Chinese medicine treatment after stage 3-4 CKD diagnosis.Contrary to current opinion,Chinese medicine intervention is associated with significantly lower risk of CKD progression and overall mortality in CKD 3-4 patients,compared with conventional western medicine treatment.Additionally,Chinese medicine intervention did not increase the occurrence of ESRD or the initiation of RRT.Among patients treated with Chinese herbal formula based on TCM syndrome differentiation,the risk of CKD progression was significantly lower,compared with patients receiving patent CM without TCM syndrome differentiation.Therefore,individualized Chinese medicine treatment based on TCM syndrome differentiation might improve the efficacy of Chinese medicine on CKD. |
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