激素及免疫抑制剂治疗原发性肾小球疾病的疗效观察
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摘要
肾小球病系指一组有相似的临床表现(如血尿、蛋白尿、高血压等),但病因、发病机制、病理改变、病程和预后不尽相同,病变主要累及双肾肾小球的疾病。目前各国家,各地区对同种病理类型的肾小球疾病治疗方法不尽相同,故对各种类型肾小球肾炎需用何种治疗需要分析大量的资料,进行大量的工作。
本课题以肾小球疾病患者(主要包括慢性肾小球肾炎及原发性肾病综合征的患者,也包括未行肾活检穿刺术的患者)为研究对象,将临床表现及临床诊断相同的患者随机分组,对比糖皮质激素(以下简称激素)和/或免疫抑制剂治疗的效果及副作用,针对行肾活检的病例,根据是否应用激素和/或免疫抑制剂对比治疗效果,结果表明,肾病综合征患者在激素治疗组和对照组间疗效缓解率比较具有显著性差异,尿蛋白的减少或血浆蛋白的回升均好于对照组。两组不良反应发生率有显著性差异。针对激素治疗无效或复发的难治性肾病综合征加用环磷酰胺冲击治疗,可快速有效地控制病情,加快难治性NS的缓解,不良反应少,无严重副作用发生。慢性肾小球肾炎患者在治疗组与对照组疗效缓解率比较具有显著性差异,尿蛋白、尿红细胞的减少均好于对照组。激素加免疫抑制剂治疗组不良反应少,不影响继续治疗及疗效缓解。临床表现为慢性肾小球肾炎的患者行肾活检后根据相同病理类型比较对照组及治疗组疗效,两组间具有显著性差异。116例行肾活检的病例,按照病理类型不同进行逐个比较,应用激素或免疫抑制剂治疗为一组,单纯应用基础治疗为二组,相关病理类型两组缓解率对比均有显著性差异。
本课题的研究方法与结果将为肾小球疾病的个体化治疗的研究及指导临床工作提供重要循证资料。
Objective Currently believe that the majority of primary or secondary glomerular diseases are mediated by the immune response of inflammatory disease. Thus, hormones and immunosuppressive drugs in the treatment of glomerular diseases occupy an important position. Numerous studies show that a reasonable application of hormone and / or immunosuppressive agents for the treatment of glomerular diseases standardized, can effectively control the progress of glomerular disease, reduce end-stage renal diseases. Primary glomerular disease, because of its unknown etiology, the pathological symptoms similar to those between the types and the pathogenesis is not clear, the diagnosis and treatment have brought a lot of inconvenience, but On the same kinds of pathological types of glomerular disease, all countries, all regions have different treatment methods. Therefore we focused on patients with primary glomerular disease hormone and / or immunosuppressant treatment efficacy , side effects and other related aspects of systematic review and analysis during 2 years in renal medicine in our hospital, hoping for further research clinical work, as well as providing important guidance to relevant information. Materials and Methods 160 cases of patients treated in kidney Section in our hospital from 2006 to 2008, the clinical diagnosis are consistent with chronic glomerulonephritis and nephrotic syndrome, exclusion of secondary glomerular diseases group, 72 cases of male, 88 cases of female, average age 37 years old, two persons less than the 14-year-old (9-year-old and 12-year-old), were not related. Of which 97 cases of chronic glomerulonephritis, 63 cases of primary nephrotic syndrome, renal biopsy in 116 cases, not done in 44 cases of renal biopsy.Pathological type showed mesangial proliferative glomerulonephritis of 33 cases, focal segmental glomerulosclerosis in 25 cases ,10 cases of minimal change nephropathy, 17 cases of membranous nephropathy, 28 cases of IgA nephropathy, mesangial capillary glomerulonephritis in 1 case, crescentic glomerulonephritis in 1 case,1 case for glomerular necrosis.All cases will be divided according to clinical manifestation of nephrotic syndrome and chronic glomerulonephritis group, are in line with the internal medicine of the sixth printing plate to develop the diagnostic criteria, and without the application of glucocorticoid contraindication.63 cases of primary NS patients, A group of 15 cases, the treatment given to the foundation. 48 cases of group B, patients were given based therapy plus hormone therapy (methylprednisolone sodium succinate 500mg / d, the impact of the treatment of three days, then oral prednisone acetate tablets changed by 1mg / kg ? d). 97 cases of chronic glomerulonephritis, C group 64 cases, to give basic treatment.33 cases of group D, patients were given hormone (prednisolone acetate oral tablets, 40mg/d) At the same time, plus immunosuppressive agents (leflunomide) treatment. Observation and comparison of the urine, 24 h urinary protein, plasma albumin changes, and to monitor the general situation of adverse reactions recorded before and after treatment . In addition, hormone therapy for refractory or relapsing nephrotic syndrome, including nine cases of methylprednisolone pulse therapy and then to oral hormone therapy, but after eight weeks does not work, there are 12 cases of relapse after remission cases. (including biopsy examination 12 cases, minimal change nephropathy two cases, mesangial proliferative glomerulonephritis 1 case,4 cases of membra- nous nephropathy, focal segmental glomerulosclerosis in 2 cases, IgA nephropathy in 2 cases, crescentic glomerulonephritis 1 cases), plus the impact of treatment with cyclophosphamide. Result The results of this study show that patients with nephrotic syndrome of the hormone therapy group and the control group after treatment compared with a remission rate of significant difference,,and the reduction of urine protein or serum albumin are better than the pick-up in the control group. Two groups the incidence of adverse reactions have significant differences. Application of the impact of a three-day prednisolone sodium succinate, and then oral prednisone acetate in treatment of eight weeks, is still invalid or relapse after remission of refractory nephrotic syndrome cases continues to increase with cyclophosphamide treatment, the course of treatment was found to be effective to eliminate or reduce proteinuria and improve serum albumin, adverse reactions in small and difficult to relapse. Patients with chronic glomerulonephritis treated group and control group after treatment compared with a remission rate of significant difference, urine protein, urine red blood cells are better than the reduction in the control group, and the hormone treatment group plus immunosuppressant had no significant adverse events, and did not affect the continued efficacy of the treatment and mitigation. Clinical diagnosis of chronic glomerulonephritis patients with renal biopsy, as compared with the same pathological type of the control group and treatment group effect, between the two groups showed a significant difference. 116 cases of a routine biopsy, carried out in accordance with the different pathological types by comparison. The treatment of hormone or immunosuppressive agents as the first group, the basis of treatment for the second group, , Respectively, of the remission rate of pathological types of comparison, in which mesangial proliferative glomerulonephritis, focal segmental glomerulonephritis, IgA nephropathy, membranous nephropathy were significantly different, but minimal change nephrotic group no significant difference in remission rates. Conclusions This study showed that patients with nephrotic syndrome for 3 consecutive days using high-dose intravenous methylprednisolone sodium succinate, and then the application of adequate oral prednisone acetate tablets by 1mg/kg ? d, results show that the hormone therapy group from onset time was shorter than in the control group, clinical symptoms and signs improved significantly, thereby greatly reducing the length of stay, At the same time, in reducing symptoms and can quickly play the role of immune suppression and anti-inflammatory, the effective reduction of proteinuria, serum albumin increased, reducing the chance of infection, a low incidence of adverse reactions,so this is a safe and effective treatment. In addition, the study shows that medium amount of hormone (prednisolone acetate oral tablets, 40mg/d) plus immunosuppressive drugs (leflunomide) for the control of chronic nephritis have a role in proteinuria, with a total effective rate was 90.91%, significantly lower urinary protein and urinary red blood cell levels, and adverse reactions occurred, it can be used as treatment a choice of chronic nephritis. Refractory nephrotic syndrome for the use of high-dose CTX therapy can control the disease quickly and efficiently to speed up the relief of refractory NS, the total effective rate was 76.19%, before and after the impact of urinary protein, plasma albumin, creatinine, blood urea nitrogen values were significantly different, with no serious side-effects. However, the observation and study of the subject was limited by the time, so the application of hormone and / or immunosuppressant treatment of long-term efficacy and adverse reactions has yet to be observed and recorded for further follow-up and research.
本课题以肾小球疾病患者(主要包括慢性肾小球肾炎及原发性肾病综合征的患者,也包括未行肾活检穿刺术的患者)为研究对象,将临床表现及临床诊断相同的患者随机分组,对比糖皮质激素(以下简称激素)和/或免疫抑制剂治疗的效果及副作用,针对行肾活检的病例,根据是否应用激素和/或免疫抑制剂对比治疗效果,结果表明,肾病综合征患者在激素治疗组和对照组间疗效缓解率比较具有显著性差异,尿蛋白的减少或血浆蛋白的回升均好于对照组。两组不良反应发生率有显著性差异。针对激素治疗无效或复发的难治性肾病综合征加用环磷酰胺冲击治疗,可快速有效地控制病情,加快难治性NS的缓解,不良反应少,无严重副作用发生。慢性肾小球肾炎患者在治疗组与对照组疗效缓解率比较具有显著性差异,尿蛋白、尿红细胞的减少均好于对照组。激素加免疫抑制剂治疗组不良反应少,不影响继续治疗及疗效缓解。临床表现为慢性肾小球肾炎的患者行肾活检后根据相同病理类型比较对照组及治疗组疗效,两组间具有显著性差异。116例行肾活检的病例,按照病理类型不同进行逐个比较,应用激素或免疫抑制剂治疗为一组,单纯应用基础治疗为二组,相关病理类型两组缓解率对比均有显著性差异。
本课题的研究方法与结果将为肾小球疾病的个体化治疗的研究及指导临床工作提供重要循证资料。
Objective Currently believe that the majority of primary or secondary glomerular diseases are mediated by the immune response of inflammatory disease. Thus, hormones and immunosuppressive drugs in the treatment of glomerular diseases occupy an important position. Numerous studies show that a reasonable application of hormone and / or immunosuppressive agents for the treatment of glomerular diseases standardized, can effectively control the progress of glomerular disease, reduce end-stage renal diseases. Primary glomerular disease, because of its unknown etiology, the pathological symptoms similar to those between the types and the pathogenesis is not clear, the diagnosis and treatment have brought a lot of inconvenience, but On the same kinds of pathological types of glomerular disease, all countries, all regions have different treatment methods. Therefore we focused on patients with primary glomerular disease hormone and / or immunosuppressant treatment efficacy , side effects and other related aspects of systematic review and analysis during 2 years in renal medicine in our hospital, hoping for further research clinical work, as well as providing important guidance to relevant information. Materials and Methods 160 cases of patients treated in kidney Section in our hospital from 2006 to 2008, the clinical diagnosis are consistent with chronic glomerulonephritis and nephrotic syndrome, exclusion of secondary glomerular diseases group, 72 cases of male, 88 cases of female, average age 37 years old, two persons less than the 14-year-old (9-year-old and 12-year-old), were not related. Of which 97 cases of chronic glomerulonephritis, 63 cases of primary nephrotic syndrome, renal biopsy in 116 cases, not done in 44 cases of renal biopsy.Pathological type showed mesangial proliferative glomerulonephritis of 33 cases, focal segmental glomerulosclerosis in 25 cases ,10 cases of minimal change nephropathy, 17 cases of membranous nephropathy, 28 cases of IgA nephropathy, mesangial capillary glomerulonephritis in 1 case, crescentic glomerulonephritis in 1 case,1 case for glomerular necrosis.All cases will be divided according to clinical manifestation of nephrotic syndrome and chronic glomerulonephritis group, are in line with the internal medicine of the sixth printing plate to develop the diagnostic criteria, and without the application of glucocorticoid contraindication.63 cases of primary NS patients, A group of 15 cases, the treatment given to the foundation. 48 cases of group B, patients were given based therapy plus hormone therapy (methylprednisolone sodium succinate 500mg / d, the impact of the treatment of three days, then oral prednisone acetate tablets changed by 1mg / kg ? d). 97 cases of chronic glomerulonephritis, C group 64 cases, to give basic treatment.33 cases of group D, patients were given hormone (prednisolone acetate oral tablets, 40mg/d) At the same time, plus immunosuppressive agents (leflunomide) treatment. Observation and comparison of the urine, 24 h urinary protein, plasma albumin changes, and to monitor the general situation of adverse reactions recorded before and after treatment . In addition, hormone therapy for refractory or relapsing nephrotic syndrome, including nine cases of methylprednisolone pulse therapy and then to oral hormone therapy, but after eight weeks does not work, there are 12 cases of relapse after remission cases. (including biopsy examination 12 cases, minimal change nephropathy two cases, mesangial proliferative glomerulonephritis 1 case,4 cases of membra- nous nephropathy, focal segmental glomerulosclerosis in 2 cases, IgA nephropathy in 2 cases, crescentic glomerulonephritis 1 cases), plus the impact of treatment with cyclophosphamide. Result The results of this study show that patients with nephrotic syndrome of the hormone therapy group and the control group after treatment compared with a remission rate of significant difference,,and the reduction of urine protein or serum albumin are better than the pick-up in the control group. Two groups the incidence of adverse reactions have significant differences. Application of the impact of a three-day prednisolone sodium succinate, and then oral prednisone acetate in treatment of eight weeks, is still invalid or relapse after remission of refractory nephrotic syndrome cases continues to increase with cyclophosphamide treatment, the course of treatment was found to be effective to eliminate or reduce proteinuria and improve serum albumin, adverse reactions in small and difficult to relapse. Patients with chronic glomerulonephritis treated group and control group after treatment compared with a remission rate of significant difference, urine protein, urine red blood cells are better than the reduction in the control group, and the hormone treatment group plus immunosuppressant had no significant adverse events, and did not affect the continued efficacy of the treatment and mitigation. Clinical diagnosis of chronic glomerulonephritis patients with renal biopsy, as compared with the same pathological type of the control group and treatment group effect, between the two groups showed a significant difference. 116 cases of a routine biopsy, carried out in accordance with the different pathological types by comparison. The treatment of hormone or immunosuppressive agents as the first group, the basis of treatment for the second group, , Respectively, of the remission rate of pathological types of comparison, in which mesangial proliferative glomerulonephritis, focal segmental glomerulonephritis, IgA nephropathy, membranous nephropathy were significantly different, but minimal change nephrotic group no significant difference in remission rates. Conclusions This study showed that patients with nephrotic syndrome for 3 consecutive days using high-dose intravenous methylprednisolone sodium succinate, and then the application of adequate oral prednisone acetate tablets by 1mg/kg ? d, results show that the hormone therapy group from onset time was shorter than in the control group, clinical symptoms and signs improved significantly, thereby greatly reducing the length of stay, At the same time, in reducing symptoms and can quickly play the role of immune suppression and anti-inflammatory, the effective reduction of proteinuria, serum albumin increased, reducing the chance of infection, a low incidence of adverse reactions,so this is a safe and effective treatment. In addition, the study shows that medium amount of hormone (prednisolone acetate oral tablets, 40mg/d) plus immunosuppressive drugs (leflunomide) for the control of chronic nephritis have a role in proteinuria, with a total effective rate was 90.91%, significantly lower urinary protein and urinary red blood cell levels, and adverse reactions occurred, it can be used as treatment a choice of chronic nephritis. Refractory nephrotic syndrome for the use of high-dose CTX therapy can control the disease quickly and efficiently to speed up the relief of refractory NS, the total effective rate was 76.19%, before and after the impact of urinary protein, plasma albumin, creatinine, blood urea nitrogen values were significantly different, with no serious side-effects. However, the observation and study of the subject was limited by the time, so the application of hormone and / or immunosuppressant treatment of long-term efficacy and adverse reactions has yet to be observed and recorded for further follow-up and research.
引文
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[2] Tumlin JA, Lohavichan V, Hennigar R. Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide J . Nephrol Dial Transplant, 2003, 18(7): 1321-1329.
[3] Pozzi C,AndrulliS,Del VecchioL ,et al.Corticosteroid effect- iveness in IgA nephropathy:Long term results of a randomized, controlled trial J .J Am Soc Nephrol ,2004,15(1):157-163.
[4]陈晓农,陈楠.原发性肾病综合征的药物治疗[J].世界临床药物,2004, 25(2): 76-88.
[5]邵淑芹,免疫抑制剂在治疗肾小球疾病中的应用进展,潍坊医学院学报, 2006,28(1):54.
[6] Hauser LA,Renders L ,Radeke HH,et al.Mycophenolate mofetil inhibits ratand human mesangial leuproliferation by guanosine depletion J .Ne phrol Dial Transplant ,1999,14:98-102.
[7]刘浩,刘志红,黄海东等.霉酚酸酯及地塞米松对血管内皮细胞功能的影响.肾脏病与透析移植杂志,2000 ,9(1) :48-50.
[8]傅君舟,杨京芝,李剑文等.霉酚酸酯联合低分子肝素治疗难治性肾病综合征.中华肾脏病杂志,2002,18(3) :227～228.
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