背景:免疫球蛋白G4相关疾病(IgG4-RD)是一种基于全身性免疫反应性的纤维炎性疾病。免疫球蛋白G4相关性肾病(IgG4-RKD)是一个经常被忽视的诊断。本研究旨在描述IgG4-RKD,并检查与IgG4-RD的肾脏结局相关的因素。方法:我们研究了2012年1月至2020年12月的前瞻性IgG4-RKD队列,并进行了密切随访。收集并分析肾活检的临床病理资料。我们旨在探讨长期肾脏结局和疾病复发的独立危险因素。在12个月时eGFR<45ml/min/1.73m2的患者被定义为具有差的结果。结果:纳入的42例IgG4-RKD患者的平均年龄为58.5±8.7岁(男女比例=5:1)。IgG4-RD反应指数(RI)为12.2±3.3。共有66.7%的患者出现急性肾脏疾病或急性慢性肾脏疾病。8例患者(19.0%)出现肾病性蛋白尿,和9(21.4%)有高滴度的IgG4自身抗体,包括抗中性粒细胞胞浆抗体和抗磷脂酶A2受体。对40例患者进行了肾活检。37例(90.0%)患者诊断为IgG4相关性肾小管间质性肾炎,其中19例(47.5%)并发肾小球疾病(膜性肾病[MN],n=3;新月体肾小球肾炎[CrGN],n=11;糖尿病肾病,n=3;MN和CrGN,n=2)。IgG4-RDRI与血清C3密切相关(R=-0.509,P=0.001),C4(R=-0.314,P=0.049)级,外周血嗜酸性粒细胞计数(PBEC;R=0.377,P=0.024),RI评分中未包含的因素.相关分析显示,IgG4-RDRI(R=0.422,P=0.007),受累器官(R=0.452,P=0.003),C3(R=-0.487,R=0.002)与1个月时血清肌酐下降百分比相关。然而,多变量回归分析未能确定任何可以预测短期肾脏恢复和IgG4-RKD复发的临床病理参数。29个变量中有10个,最重要的,通过最小绝对收缩和选择算子(LASSO)回归分析确定。通过多因素logistic回归分析,血清IgG4较高(OR=0.671,P=0.010),IgG1(OR=1.396,P=0.049),IgG3(OR=19.154,P=0.039),和红细胞沉降率(ESR;OR=1.042,P=0.032)是长期预后不良的独立因素。常规免疫抑制药物和/或利妥昔单抗处方,83.3%的病人,肾功能改善。重复肾脏活检证实了两名免疫抑制治疗患者的间质性炎症缓解。然而,疾病复发率高达31.0%。结论:我们强烈建议在活动性IgG4-RD中进行肾活检,尤其是有蛋白尿和肾功能不全的时候,因为应该评估并发肾小球受累和活动性间质炎症。较高的血清IgG1、IgG3和ESR是长期肾脏预后不良的独立因素;然而,升高的IgG4预测良好的肾脏预后,适当及时的免疫抑制剂治疗有助于达到较好的预后。
Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic immunoreactivity-based fibro-inflammatory disease. Immunoglobulin G4-related kidney disease (IgG4-RKD) is a frequently overlooked diagnosis. This
study aimed to describe IgG4-RKD and examine the factors relevant to the renal outcomes of IgG4-RD. Methods: We studied a prospective IgG4-RKD cohort between January 2012 and December 2020 with close follow-up. Clinicopathologic data at kidney biopsy were collected and analyzed. We aimed to explore independent risk factors for long-term renal outcome and disease relapse. Patients with an eGFR<45 ml/min per 1.73m2 at 12 months were defined as having poor outcomes. Results: The included 42 patients with IgG4-RKD had a mean age of 58.5 ± 8.7 years (male-to-female ratio = 5:1). The IgG4-RD responder index (RI) was 12.2 ± 3.3. A total of 66.7% of the patients presented with acute on kidney disease or acute on chronic kidney disease. Eight patients (19.0%) showed nephrotic-range proteinuria, and nine (21.4%) had high-titer IgG4-autoantibodies, including antineutrophil cytoplasmic antibody and anti-phospholipase A2 receptor. A kidney biopsy was conducted in 40 patients. Thirty-seven (90.0%) patients were diagnosed with IgG4-related tubulointerstitial nephritis, and 19 (47.5%) of them had concurrent glomerular diseases (membranous nephropathy [MN], n = 3; crescentic glomerulonephritis [CrGN], n = 11; diabetic kidney disease, n = 3; and both MN and CrGN, n = 2). IgG4-RD RI had a close relationship with serum C3 (R = -0.509, P = 0.001), C4 (R = -0.314, P = 0.049) levels, and peripheral blood eosinophil count (PBEC; R = 0.377, P = 0.024), factors that were not included in RI scores. Correlation analysis disclosed that IgG4-RD RI (R = 0.422, P = 0.007), organs involved (R = 0.452, P = 0.003), and C3 (R = -0.487, R = 0.002) were correlated with the percentage decrease of serum creatinine at 1 month. However, multivariate regression analysis failed to identify any clinicopathological parameters that could predict short-term renal restoration and IgG4-RKD relapse. Ten out of 29 variables, of most importance, were identified by the least absolute shrinkage and selection operator (LASSO) regression analysis. By multivariate logistic regression a higher serum IgG4 (OR = 0.671, P = 0.010), IgG1 (OR = 1.396, P = 0.049), IgG3 (OR = 19.154, P = 0.039), and erythrocyte sedimentation rate (ESR; OR = 1.042, P = 0.032) were found to be independent factors for poor long-term outcome. Conventional immunosuppressive medications and/or rituximab were prescribed, and in 83.3% of the patients, the kidney function improved. Repeat kidney biopsies confirmed the remission of interstitial inflammation in two patients under immunosuppressive therapy. However, the disease relapse rate was as high as 31.0%. Conclusions: We strongly recommend a kidney biopsy in active IgG4-RD, especially when there is proteinuria and renal dysfunction, because concurrent glomerular involvement and active interstitial inflammation should be assessed. A higher serum IgG1, IgG3, and ESR were independent factors for the poor long-term renal outcome; however, elevated IgG4 predicted a good renal prognosis, and appropriate and timely immunosuppressive therapy can help achieve a better prognosis.