The Differentiation Pattern And Therapy Based On Water-Fluid Retention For Cardiorenal Syndrome With Volume Overload And Clinical Study Of Nourishing Yin And Draining Water Method

1.Literature research and clinical experienceA progressively deeper understanding of heart-associated edema has been achieved throughout thousands of years of TCM(traditional Chinese medicine)development.Huangdi’s Internal Classic(《皇帝内经》,Huang-di-nei-jing)first described the symptoms of edema associated with heart failure,and advanced the pathogenesis,location and treatment of edema;Treatise on Cold Damage and Miscellaneous Diseases(《伤寒杂病论》,Shang-han-za-bing-lun)compiled in the Eastern Han Dynasty first established the water differentiation in the five zang organs method and the name of heartwater disease(congestive heart failure),and systematically elaborated water retention disease,pattern,treatment and formulamedicinal;the Sui and Tang Dynasties saw a deepening knowledge of the course,diet,pattern differentiation and treatment of heartwater disease;the etiology,pathogenesis and treatment of edema in the Song,Jin and Yuan Dynasties were a continuation of previous viewpoints with different emphasis on the lung,spleen and kidney;in the Ming and Qing Dynasties,the simultaneous treatment of water and blood principle was proposed.On the basis of medical practitioners’ inheritance and development through the ages,the systematic theories of modern Chinese medicine on the etiology,pathogenesis,diagnosis and treatment of heartwater disease have been developed.Based on medical practitioners’ inheritance and development through the ages,Professor ZHOU YUPING proposed water-fluid retention as an important TCM pathological product and an etiological factor of cardiorenal syndrome(CRS).Considering the deficiency of qi,blood,yin,yang and healthy qi,he categorized heartwater disease into six different patterns:water-fluid retention,qi deficiency with water retention,yang deficiency with water retention,qi stagnation with water retention,yin deficiency with water retention,and blood stasis with water retention;and gives a balanced treatment according to the pathogenesis,progression and priority of the disease.2.Clinical StudyBackground:2 Cardio-renal Syndrome(CRS)refers to congestive heart failure(CHF)induced progressive renal function impairment.CRS patients with volume overload are critically ill with high mortality,and diuretic treatment is limited,which is one of the urgent medical burdens to be solved.Modified Polyporus Decoction(猪苓汤,Zhuling Tang)from Treatise on Cold Damage(《伤寒论》,shang-han-lun),the whole prescription nourishes Yin and eliminates dampness with sweet and mild flavors,fills deficiency and ascends Qi with pungent and bitter flavors.It is effective to treat the patients with depression of Qi activity and Yin Deficiency with Water Retention.Objective:To investigate the effects of modified Polyporus Decoction(猪苓汤,Zhuling Tang),the typical formula of the nourishing yin and draining water method,on urinary ions,urinary AQP2,changes in plasma volume,and cardiorenal functions and symptoms in patients with cardiorenal syndrome with volume overload manifesting as yin deficiency with water retention pattern,and explore the preliminary action mechanism of the modified Polyporus Decoction for improving water retention through the AVP-AQP2 pathway.Methods:A total of 64 cases of patients with cardiorenal syndrome of volume overload manifesting as yin deficiency with water retention pattern were included in the clinical observation study using a single-center,prospective,randomized,parallel group design.They were randomly divided into the treatment group and the control group with 32 cases each.The control group received basic western therapy and the treatment group was treated with modified Polyporus Decoction and basic western therapy for 7-10 days.Urinary ion,diuretic efficiency,cardiac and renal function,symptoms and overall efficacy were compared between the two groups before and after treatment.Results:(1)There were no significant differences in age,sex,history of tobacco and alcohol use,course of heart failure,complications,baseline cardiac and renal function,and previous oral administration between the treatment group and the control group(P>0.05),indicating that the two groups were comparable.(2)Urine ion level:UNa ion concentration in control group decreased after treatment(P<0.05),and UNa excretion in treatment group was better than that in control group(P<0.05).The improvement effect of FENa in treatment group was better than that in control group(P<0.05).(3)Diuretic efficiency:The average 24h net loss and 24h urine volume of treatment group were higher than those of control group(P<0.05).(4)Changes of heart and kidney function:NT-proBNP in treatment group and control group was decreased,and the treatment group was better than the control group(P<0.05).In patients with baseline eGFR 60-90 mL/min/1.73m2,the improvement of blood Cr in treatment group was better than that in control group(P<0.05).(5)TCM symptom score:The total score of TCM symptom score,asthma,edema and oliguria scores of the treatment group and the control group were all lower than before treatment,and the treatment group had better symptom improvement effect than the control group(P<0.05).(6)Overall efficacy:TCM symptom integral effective rate in the treatment group was higher than that in the control group,and the difference between the groups was statistically significant(P<0.05).The reduction rate of loop diuretic in treatment group was higher than that in control group,and the difference between groups was statistically significant(P<0.05).(7)Hospital stay and prognosis:there were no significant differences in hospital stay and 14-day mortality between the two groups(P>0.05).(8)Mechanical study:There were no significant differences in urinary AQP2,serum CPP and AQP/CR between the two groups before and after treatment(P>0.05).Conclusion:The results of this study showed that modified Polyporus Decoction combined with basic western therapy can effectively promote urinary sodium and chloride excretion in patients with CRS with volume overload,enhance diuretic efficiency,further improve the action of loop diuretics,prevent the combined and overdosing use of diuretics,improve patients’ cardiorenal functions in a certain degree,alleviate CRS symptoms,and improve overall efficacy.However,the action mechanism for improving water retention has remained unclear,which requires further animal experiments to verify.