摘要
研究背景中医药防治慢性肾衰竭(chronic renal failure, CRF)在缓解临床症状、提高生活质量、保护残余肾功能、延缓早中期肾衰进展、推迟进入透析和肾移植时间等方面具有较好疗效和独特优势。广东省中医院肾病重点专科作为全国优秀中医肾病重点专科和国家中医药管理局“十一五”重点病种慢性肾衰中医诊疗方案研究的牵头单位,领导全国30家肾病重点专科,对目前各中心正在实施的诊疗方案进行梳理、总结,形成一个优化的具有中医特色和优势的慢性肾衰(非透析期)中医诊疗方案。研究目的本研究对已形成的慢性肾衰(非透析期)中医诊疗方案进行前瞻性、大样本的临床验证和疗效评价研究,初步评价该方案对非透析期CRF患者的临床症状、肾功能、相关并发症、生活质量等方面的疗效情况,为该方案的进一步多中心临床研究及行业内推广应用提供研究基础和依据。
方法采用前瞻性研究方法,入选符合纳入标准的140例非透析期CRF患者,按照慢性肾衰(非透析期)中医诊疗方案连续治疗3个疗程(每个疗程2个月),观察治疗前后临床症状积分、肾功能(血肌酐、血尿素氮、血尿酸)、血清白蛋白、血红蛋白、血脂(总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白)、纤维蛋白原、血钙和磷的变化,进行疗效评定；采用CKD-EPI公式估算GFR(eGFR)作为主要疗效评价指标,制定肾功能疗效评价标准；采用翻译、改良后KDQOL-SFTM1.3量表,对非透析期CRF患者进行信度和效度的检测,于治疗前后各调查一次,进行生活质量评价。
结果①慢性肾衰竭的中医病机属本虚标实之证,本虚证以脾肾气虚证居首位(52.90%,73/138),其次分别为气阴两虚证(18.84%)、脾肾阳虚证(13.77%)、阴阳两虚证和肝肾阴虚证(各为7.25%)。标实证多以兼证形式存在的,占所有标实证型的55.80%(77/138)；其中以血瘀证及其兼证最常见(73.19%),其次为湿热及其兼证(37.68%)。年龄和CKD分期对CRF本虚证的分布有显著影响；CKD分期对CRF标实证的分布有显著影响。②慢性肾衰(非透析期)中医诊疗方案对CRF患者的临床症状有较好改善作用,症状积分下降率由高至低依次为：倦怠乏力(38.60%)、大便情况(31.70%)、腹胀(31.40%)、畏寒肢冷(30.90%)、水肿(29.10%)、腰膝酸软(28.20%)、恶心(26.90%)、头晕(23.40%)、纳呆(23.30%)、呕吐(21.40%)、夜尿频多(10.60%)；症状改善总有效率达85.51%。男性和女性、各年龄段、各主要原发疾病、CKD各期、各中医证型的症状积分均有显著降低(P<0.05)；症状改善有效率方面：脾肾气虚证优于阴阳两虚证和脾。肾阳虚证,单个标实证优于多个标实证,湿热证、湿热兼血瘀证优于浊毒兼血瘀证(P<0.05)。③该方案能显著提升CRF患者的eGFR,降低SCr、UA(P<0.05)；以GFR下降<2 ml/(min·1.73m2·年)作为治疗有效判定标准,得出该方案对CRF患者的肾功能改善总有效率为76.92%。不同性别、65岁以下患者、慢性肾炎、CKD 3期和4期、脾肾气虚证、气阴两虚证、肝肾阴虚证、湿热证、血瘀证的eGFR均有显著升高(P<0.05)；肾功能改善有效率方面：女性显著高于男性,45岁以下患者显著高于65岁以上患者,慢性肾炎显著优于糖尿病肾病,CKD 3期显著高于CKD 5期,脾肾气虚证显著优于阴阳两虚、脾肾阳虚证,气阴两虚证显著优于脾肾阳虚证,单个标实证显著优于多个标实证,湿热证优于浊毒兼血瘀证(P<0.05)。④该方案能显著提高CRF患者的ALB和Hb(P<0.05),尤其对男性、45岁以下、慢性肾炎、脾肾气虚证、湿热兼血瘀证和湿浊兼血瘀证患者的营养状况改善更为全面。⑤该方案能显著降低CRF患者的TC、LDL(P<0.05),尤其对慢性肾炎、脾肾气虚证和湿热兼血瘀证患者的血脂调节作用更优。⑥该方案能显著降低CRF患者的Fib(P<0.05),对男性和女性、45岁以上、各主要原发病、CKD各期患者均有改善作用(P<0.05)；对脾肾气虚证、脾肾阳虚证和气阴两虚证等本虚证,以及湿热兼血瘀证、湿浊兼血瘀证、浊毒兼血瘀证等多个标实兼证患者的Fib亦有显著改善(P<0.05)。⑦该方案能显著降低CRF患者血磷、升高血钙,尤其对65岁以下、脾肾气虚证患者疗效更全面(P<0.05)；在CKD 3期和4期以降低血磷为主,而CKD 5期既能降低血磷,同时也升高血钙。⑧翻译、改良后的KDQOL-SFTM1.3全量表Cronbach's a系数为-0.954,分半信度为0.899；各条目与其所属维度评分呈显著正相关关系(P<0.01),有70项相关系数r>0.5,占88.61%(70／79)。KDTA量表提取11个公因子,累计方差贡献率达72.73%,应用方差最大旋转后所得结果与量表理论构想基本一致。⑨单因素分析提示,影响CRF(非透析期)生活质量的因素包括：性别、年龄、原发病、CKD分期、中医证候、受教育程度、工作情况、医疗费别等。多元线性回归分析提示,影响SF-36生理健康(PCS)的因素有：症状积分、Hb、CKD分期、性别;影响SF-36心理健康(MCS)的因素有：症状积分、医疗费别；影响肾脏病相关领域(KDTA)生活质量的因素有：eGFR、工作情况、受教育程度、Hb。⑩该方案对CRF患者的生活质量有显著改善作用,这种作用可能并不完全依赖于肾功能的改善。对于部分肾功能改善无效的患者,中医药可以发挥辨证论治和整体调节的优势,改善临床症状、提高生活质量。该方案对于男性和女性、各年龄段、各主要原发疾病、CKD各期、脾肾气虚证和气阴两虚证、各标实证型(除浊毒兼血瘀证之外)患者的生活质量评分均有全面提升作用(包括SF-36的生理健康和心理健康、肾脏病相关的生活质量)(P<0.05)。
结论慢性肾衰(非透析期)中医诊疗方案能够有效缓解CRF患者的临床症状；能够有效保护患者的肾功能,延缓肾衰快速进展；能够有效改善患者的营养状况和血脂、凝血、钙磷等代谢情况,减少CRF某些并发症发生和发展；能够全面提高患者生活质量,包括生理健康、心理健康和肾脏病相关领域的生活质量；且使用较为安全,无严重副作用。改良后KDQOL-SFTM1.3量表具有较好信度和效度,可初步用于国内CRF(非透析期)的生活质量评价研究。
Backgroound
Traditional Chinese Medicine (TCM) have good therapeutic effectiveness and unique advantages of prevention and treatment of Chronic Renal Failure (CRF), such as easing the symptoms, improving the quality of life (QOL), protecting residual renal function, slowing progress in early and medium stage, deferring to dialysis or renal transplantation.
As the national first-rank key specialty of TCM and leading units of key disease entity study on CRF treatment scheme of State Chinese Medicine Administration Bureau in the Eleventh Five-year Plan Period, Nephropathy Key Specialty of Guangdong Provincail Hospital of TCM leaded 30 domestic hospitals to comb and summarize their current diagnosis and treatment scheme on CRF (Non-dialysis), and form a optimization scheme of diagnosis and treatment on CRF (Non-dialysis), with the characteristic and advantages of TCM.
Objective
Prospective and large samples clinic trial was used in our study to primarily evaluate the therapeutic efficiency of Chinese medical diagnosis and treatment scheme on CRF (Non-dialysis), in terms of symptoms, renal function, complications, quality of life (QOL), etc. The study will provide the foundation and evidence for the further multicenter clinic trial and popularization and application of the scheme.
Methods
One hundred and forty patients who were eligible for the inclusion criteria were enrolled in this prospective study. Two months was one period of treatment, and all patients were treated by Chinese Medical Diagnosis and Treatment Scheme on CRF(Non-dialysis) for 3 periods. The therapeutic effects were compared before and after treatment with the changes of symptom scores, serum creatinine (SCr), blood urea nitrogen (BUN), uric acid (UA), albumin (Alb), hemoglobin (Hb), serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fibrinogen (Fib), serum calcium (Ca) and phosphorus (P). Therapeutic effectiveness evaluation criteria of renal function was decided by glomerular filtration rate (GFR), as the main index of effectiveness evaluation, estimated with CKD-EPI formula.
Kidney Disease Quality of Life Short Form, Version 1.3 (KDQOL-SFTM1.3) questionnaire was translated and modified, and then used in the patients with CRF (Non-dialysis) to test the reliability and validity and evaluate the quality of life (QOL).
Result
①The TCM pathogenesis of CRF was attributive to primary deficiency and secondary excess. With respect to the primary deficiency syndrome, spleen and kidney Qi deficiency (SKQD) was the most common type, accounted for 52.90% of all the types; followed by both Qi and Yin deficiency (QYD) (18.84%), spleen and kidney Yang deficiency (SKYD) (13.77%), both Yin and Yang deficiency (YYD) (7.25%), liver and kidney Yin deficiency (LKYD) (7.25%). The secondary excess syndrome mostly emerged in form of several syndrome associatively, accounted for 55.80% of all the types. Blood stasis syndrome (BSS) and its accompanied syndromes were dominant in all excess syndrome types, accounted for 73.19%, followed by dampness heat syndrome (DHS) and its accompanied syndromes (37.68%). Age and stage of CKD had siginificant effect on the deficiency syndrome distribution, Stage of CKD had also siginificant effect on the excess syndrome distribution.
②Chinese medical diagnosis and treatment scheme for CRF (Non-dialysis) could relieve clinical symptom of patients with CRF (Non-dialysis).
The order of reduction rates of symptom scores was tiredness and inertia (38.60%), defecation (31.70%), abdominal distention (31.40%), aversion to cold and cold extremities (30.90%), edema (29.10%), ache of waist andknee (28.20%), nausea (26.90%), dizziness (23.40%), anorexia (23.30%), vomiting (21.40%), frequent Night urination (10.60%), from high to low. The total effective rate of improvement in clinical symptoms was 85.51%. The clinical symptom scores reduced markedly in different gender, each age phases, each primary diseases, stagesⅢ～Ⅴof CKD and each TCM syndrome types after treatment (P<0.05).
In terms of the effective rate of improvement in clinical symptoms, SKQD was superior to YYD and SKYD, the single secondary excess syndrome was superior to the accompanied secondary excess syndrome, and DHS and dampness heat accompanied by blood stasis (DHABS) was superior to turbidity toxin accompanied by blood stasis (TTABS) (P<0.05).
③The scheme could noticeably raise eGFR, and reduce SCr, UA in CRF patients (Non-dialysis). According to the criteria for evaluating therapeutic effect of kidney function with GFR droping less than 2 ml/(min·1.73m2) per year, the total effective rate of improvement in kidney function by the scheme was 76.92%. There were significant increases of eGFR in male and female, patients under 65 years old, chronic glomerulonephritis, stagesⅢandⅣof CKD, QYD, LKYD, DHS, BSS after treatment (P<0.05).
In terms of the effective rate of improvement in kidney function, female was markedly higher than male, patients less 45 years old than patients over 65 years old, chronic glomerulonephritis (CGN) than diabetic nephropathy (DN), patients in stage III of CKD than stage V of CKD, SKQD than YYD and SKYD, QYD than SKYD, the single secondary excess syndrome than the accompanied secondary excess syndrome, DHS than TTABS (P<0.05).
④The scheme could significantly raise ALB and Hb in CRF patients (Non-dialysis) after treatment (P<0.05), especially in male, patients under 45 years old, chronic glomerulonephritis (CGN), SKQD, DHABS and TTABS, with overall improvement of the nutritional status both in Hb and ALB.
⑤The scheme could obviously reduce TC and LDL in CRF patients (Non-dialysis) after treatment (P<0.05), especially in patients of CGN, SKQD and DHABS, with better adjustment of the hyperlipidemia both in LDL and TC.
⑥The scheme could significantly drop Fib level after treatment in CRF patients (Non-dialysis) of different gender, over 45 years old, each primary diseases, stagesⅢ～Ⅴof CKD, SKQD, SKYD, QYD, DHABS, DHABS and TTABS (P <0.05).
⑦The scheme could distinctly decrease serum P and increase serum Ca in CRF patients (Non-dialysis) after treatment (P<0.05), especially in patients under 65 years old, SKQD, with overall improvement of calcium- phosphorus metabolic disorder. Serum P can lower in stagesⅢ～Ⅴof CKD mainly, while serum Ca can rise in stages V of CKD.
⑧The translated and modified KDQOL-SFTM1.3 showed good reliability and validity. Cronbach's alpha coefficient of full scale was 0.954, spilit reliability was 0.899; Each item in the scale had significant correlation with its belonged dimension (P<0.05), and the correlation coefficient of 70 items were over 0.5, account for 88.61 percentage of all 79 items (70/79). Eleven common factors were extracted from KDTA scale through exploratory principal component analysis and explaining 72.73% variance. The structure of the scale after varimax rotation was similar to the theory construction.
⑨The single factor analysis showed that the factors influencing the overall quality of life (QOL) in CRF patients (Non-dialysis) involved gender, age, primary diseases, stages of CKD, syndrome of TCM (primary deficiency syndrome and secondary excess syndrome), educational level, working condition, medical payment and so on. The multiple regressive analysis revealed that the factors influencing the QOL of Physical Component Summary (PCS) of SF-36 scale included symptom scores, Hb, stages of CKD, gender; the factors influencing the QOL of Mental Component Summary (MCS) of SF-36 scale included symptom scores, medical payment; the factors influencing the QOL of Kidney Disease Targeted Areas (KDTA) included eGFR, working condition, educational level, Hb.
⑩The scheme could significantly improve quality of life (QOL) of CRF patients (Non-dialysis) (P<0.05), which might not completely depend on the improvement of renal function; Some patients with poor improvement in kidney function could also have improvement in clinical symptoms and enhancement in QOL through the treatment based on syndrome differentiation and overall adjustment of TCM. The QOL of patients in different gender, age phases, primary diseases, stagesⅢ～Ⅴof CKD, SKQD, QYD, each of the secondary excess syndromes (excepting TTABS) could have overall improvement in PCS and MCS of SF-36 scale as well as in KDTA scale (P<0.05).
Conclusion
Chinese medical diagnosis and treatment scheme for CRF (Non-dialysis) could effectively relieve the clinical symptoms; protect residual renal function with postponing the CRF rapid process; improve the nutritional status, the metabolism of lipid and calcium-phosphorus, and the hypercoagulant state, thus decreasing the occurance and development of some complications; but safely and without severe side-effects. The scheme could also improve the QOL all sidedly, involving PCS and MCS of SF-36 scale as well as KDTA scale. The translated and modified KDQOL-SFTM1.3 showed good reliability and validity in individuals with CRF (Non-dialysis), as a result, it could be used to evaluate the quality of life in domestic CRF (Non-dialysis) patients initially.
引文
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