Tonsillectomy and steroid pulse (TSP) therapy for patients with IgA nephropathy: a nationwide survey of TSP therapy in Japan and an analysis of the predictive factors for resistance to TSP therapy
Tonsillectomy and steroid pulse (TSP) therapy for patients with IgA nephropathy: a nationwide survey of TSP therapy in Japan and an analysis of the predictive factors for resistance to TSP therapy
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DOI：
10.1007/s10157-009-0179-1
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发表时间：
2009-10-01
影响因子：
2.3
通讯作者：
Watanabe, Tsuyoshi
中科院分区：
文献类型：
--
作者：
Miura, Naoto;Imai, Hirokazu;Watanabe, Tsuyoshi
Hotta等人（Am J Kidney Dis 38:736-742, 2001）基于约50%的患者达到尿异常临床缓解（CR）的数据，提出扁桃体切除术和类固醇脉冲（TSP）治疗IgA肾病是一种根治性治疗方法。作为初步调查，我们向日本848家医院发送了问卷和信件，每家医院在2006年10月至12月期间聘请了一名日本肾病学会会员，以收集有关TSP治疗IgA肾病患者的患病率和疗效的信息。作为二次调查，我们收集了来自低和高cr率组的数据，以确定哪些因素预测TSP治疗的耐药。2000年至2006年间，共有2746名患者接受了TSP治疗。通过测量TSP治疗后6个月和12个月的尿标准计算，CR率分别为32.0%（347/ 1085）和45.6%（452/991）。对30家医院进行TSP治疗的至少10名患者的分析显示，CR率从10%以下到100%不等。对10家医院的二次调查显示，在每家医院修正了CR率后，患者可分为三组：低CR率（4家医院122例）、中CR率（4家医院78例）和高CR率（2家医院103例）。所有患者（303例）的CR率为54.1%。比较低cr率组和高cr率组的患者资料显示，Wakai等人描述的发病年龄（年，P = 0.05）、蛋白尿量（g/d, P = 0.02）、总蛋白（g/dl, P = 0.02）、病理分级（P = 0.009）和预后评分有显著差异[Nephrol Dial Transplant， 21:2800- 2808,2006, (P = 0.04)]。单变量分析表明有显著区别non-CR和CR子组治疗持续时间从诊断到茶匙(6.9 + / - 6.8和5.3 + / - 5.2年;P = 0.02),大量蛋白尿(1.5 + / - 1.6和0.8 + / - 0.8克/天,P < 0.0001),血清肌酐(0.99 + / - 0.40和0.87 + / - 0.34 mg / dl; P = 0.006),病理等级(P = 0.0006),和Wakai et al预后评分系统(37.4 + / - 17.8和28.1 + / - 15.1;P < 0.0001)。多因素logistic分析显示，对TSP治疗的耐药性取决于发病年龄、蛋白尿量、血尿分级和病理分级，预测TSP治疗耐药性的评分可由公式得出：[(-0.0330)x（年龄）+ (0.4772)x log（蛋白尿量）- (0.0273)x（血尿分级：0、1、2和3）+ (0.7604)x（病理分级：1、2、3和4）- 0.1894]。受试者工作特征（ROC）曲线显示，耐药评分大于-0.02的患者易耐TSP治疗（敏感性69%，特异性75%，阳性似然比2.76）。TSP治疗有望带来泌尿异常的CR，但不幸的是，治疗后1年的平均CR率约为50%。对TSP治疗耐药的预测因素有发病年龄、蛋白尿量、血尿分级和病理分级。本研究提示，早期或轻中度IgA肾病患者在接受TSP治疗后容易达到CR，而晚期或重症患者则容易出现TSP治疗耐药。
Tonsillectomy and steroid pulse (TSP) therapy was proposed as a curative treatment for IgA nephropathy by Hotta et al. (Am J Kidney Dis 38:736-742, 2001) based on data that about 50% of patients achieved clinical remission (CR) of urinary abnormalities.As a primary survey, we sent a questionnaire and letter to 848 hospitals in Japan, each of which employed a Fellow of the Japanese Society of Nephrology between October and December of 2006, in order to gather information about the prevalence and efficacy of TSP therapy for patients with IgA nephropathy. As a secondary survey, we collected data from both low- and high-CR-rate groups to determine which factors predicted resistance to TSP therapy.A total of 2,746 patients received TSP therapy between 2000 and 2006. The CR rates, calculated by measuring urinary criteria 6 and 12 months after TSP therapy, were 32.0% (347/1,085) and 45.6% (452/991), respectively. Analysis of the 30 hospitals in which TSP therapy had been performed on at least ten patients revealed that the CR rates varied from below 10% to 100%. A secondary survey of ten hospitals revealed that, after correction of the CR rate from each hospital, patients could be categorized into three groups: those with a low CR rate (122 patients in four hospitals), a middle CR rate (78 patients in four hospitals), and a high CR rate (103 patients in two hospitals). The CR rate of all patients (N = 303) was 54.1%. A comparison of patient data between the low- and high-CR-rate groups showed a significant difference in age at onset (years; P = 0.05), amount of proteinuria (g/day; P = 0.02), total protein (g/dl; P = 0.02), pathological grade (P = 0.009), and prognostic score as described by Wakai et al. [Nephrol Dial Transplant 21:2800-2808, 2006, (P = 0.04)]. Univariate analysis revealed that there was a significant difference between non-CR and CR subgroups in duration from diagnosis until TSP therapy (6.9 +/- A 6.8 versus 5.3 +/- A 5.2 years; P = 0.02), amount of proteinuria (1.5 +/- A 1.6 versus 0.8 +/- A 0.8 g/day; P < 0.0001), serum creatinine (0.99 +/- A 0.40 versus 0.87 +/- A 0.34 mg/dl; P = 0.006), pathological grade (P = 0.0006), and Wakai et al.'s prognostic score (37.4 +/- A 17.8 versus 28.1 +/- A 15.1; P < 0.0001). A multivariate logistic analysis demonstrated that resistance to TSP therapy depends on age at onset, amount of proteinuria, hematuria grade, and pathological grade, and a score predicting resistance to TSP therapy could be derived by the formula: [(-0.0330) x (age) + (0.4772) x log (amount of proteinuria) - (0.0273) x (hematuria grade: 0, 1, 2, and 3) + (0.7604) x (pathological grade: 1, 2, 3, and 4) - 0.1894]. A receiver operating characteristic (ROC) curve showed that patients with a resistance score of greater than -0.02 easily resist TSP therapy (sensitivity 69%, specificity 75%, positive likelihood ratio 2.76).TSP therapy shows promise as a treatment that can bring about CR of urinary abnormalities, but unfortunately the average CR rate is about 50% at 1 year after treatment. Predictive factors for resistance to TSP therapy are age at onset, amount of proteinuria, hematuria grade, and pathological grade. The present study suggests that patients with either early-stage or mild to moderate IgA nephropathy easily achieve CR following TSP therapy, whereas patients with late-stage or severe disease are prone to TSP therapy resistance.