单独应用血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体拮抗剂治疗特发性膜性肾病患者的预后及其影响因素分析
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摘要
目的探讨单独应用血管紧张素转换酶抑制剂(ACEI)或血管紧张素Ⅱ受体拮抗剂(ARB)治疗的特发性膜性肾病(IMN)患者的预后及影响因素。方法选取2011年12月至2016年12月于中国医科大学附属盛京医院肾内科经肾穿刺活检诊断为IMN患者85例,均只接受ACEI或ARB治疗,完全缓解、部分缓解者纳入缓解组,开始接受糖皮质激素和/或免疫抑制剂治疗者纳入未缓解组,比较2组患者基本资料、生化指标和肾脏病理结果 ,评估IMN患者单独应用ACEI/ARB治疗的预后影响因素。结果缓解组46例,其中完全缓解29例,部分缓解17例;未缓解组39例。缓解组<60岁患者比例、eGFR水平高于未缓解组[89.1%(41/46)比66.7%(26/39),(138±29)ml/(min·1.73 m~2)比(120±28)ml/(min·1.73 m~2)],未缓解组合并糖尿病比例、血清胱抑素C水平高于缓解组[20.5%(8/39)比2. 2%(1/46),(1. 04±0. 32)mg/L比(0. 91±0.17)mg/L],未缓解组的间质炎性细胞浸润评分高于缓解组,补体C3沉积程度低于缓解组,差异均有统计学意义(均P<0. 05)。Logistic多因素回归分析结果提示,具有糖尿病病史、血清胱抑素C水平升高是影响IMN患者预后的独立危险因素(比值比=408.862、46.973,95%置信区间:4.447～37 590.022、3.091～713.836,均P<0.01)。结论单独ACEI/ARB治疗可使部分IMN患者达到缓解,既往有糖尿病病史以及高胱抑素C血症可能影响患者预后,应根据患者的情况选择个体化的治疗方案。
Objective To investigate the prognosis and related factors of idiopathic membranous nephropathy(IMN) treated with angiotensin converting enzyme inhibitor/angiotensin Ⅱ receptor blocker( ACEI/ARB).Methods From December 2011 to December 2016, 85 IMN patients diagnosed by renal biopsy in Shengjing Hospital of China Medical University were enrolled. All patients were treated with ACEI/ARB alone. According to the therapeutic response, they were divided into remission group and no remission group; the no remission group was treated with glucocorticoids and/or immunosuppressants subsequently. Basic information, biochemical indexes and pathological results were compared between groups. Prognostic factors of IMN patients treated by ACEI/ARB were analyzed. Results There were 46 patients in the remission group(29 complete remission, 17 partial remission) and39 patients in the no remission group. Proportion of patients under 60 years old and estimated glomerular filtration rate in the remission group were higher than those in the no remission group[89. 1%(41/46) vs 66.7%(26/39),(138 ±29)ml/(min ·1. 73 m~2) vs(120 ±28)ml/(min ·1.73 m~2) ]. Proportion of patients with diabetes and level of serum cystatin C in the no remission group were higher than those in the remission group [20.5%(8/39) vs2.2%(1/46),(1.04 ±0.32)mg/L vs(0.91 ±0. 17)mg/L]. The no remission group had higher interstitial inflammatory cell infiltration score and lower complement C3 sedimentation degree(all P < 0. 05). Logistic multivariate regression analysis showed that diabetes history and high serum cystatin C level were independent risk factors of the prognosis of IMN(dds ratio =408.862, 46.973; 95% confidence interval: 4.447-37 590.022,3.091-713.836; P < 0. 01). Conclusions Monotherapy with ACEI/ARB can relieve IMN in some patients.Diabetes history and high serum cystatin C level may have adverse affect the therapeutic response of IMN.
Objective To investigate the prognosis and related factors of idiopathic membranous nephropathy(IMN) treated with angiotensin converting enzyme inhibitor/angiotensin Ⅱ receptor blocker( ACEI/ARB).Methods From December 2011 to December 2016, 85 IMN patients diagnosed by renal biopsy in Shengjing Hospital of China Medical University were enrolled. All patients were treated with ACEI/ARB alone. According to the therapeutic response, they were divided into remission group and no remission group; the no remission group was treated with glucocorticoids and/or immunosuppressants subsequently. Basic information, biochemical indexes and pathological results were compared between groups. Prognostic factors of IMN patients treated by ACEI/ARB were analyzed. Results There were 46 patients in the remission group(29 complete remission, 17 partial remission) and39 patients in the no remission group. Proportion of patients under 60 years old and estimated glomerular filtration rate in the remission group were higher than those in the no remission group[89. 1%(41/46) vs 66.7%(26/39),(138 ±29)ml/(min ·1. 73 m~2) vs(120 ±28)ml/(min ·1.73 m~2) ]. Proportion of patients with diabetes and level of serum cystatin C in the no remission group were higher than those in the remission group [20.5%(8/39) vs2.2%(1/46),(1.04 ±0.32)mg/L vs(0.91 ±0. 17)mg/L]. The no remission group had higher interstitial inflammatory cell infiltration score and lower complement C3 sedimentation degree(all P < 0. 05). Logistic multivariate regression analysis showed that diabetes history and high serum cystatin C level were independent risk factors of the prognosis of IMN(dds ratio =408.862, 46.973; 95% confidence interval: 4.447-37 590.022,3.091-713.836; P < 0. 01). Conclusions Monotherapy with ACEI/ARB can relieve IMN in some patients.Diabetes history and high serum cystatin C level may have adverse affect the therapeutic response of IMN.
引文
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[8] Polanco N, Gutiérrez E, Rivera F, et al. Spontaneous remission of nephrotic syndrome in membranous nephropathy with chronic renal impairment[J]. Nephrol Dial Transplant, 2012,27(1):231-234,DOI:10. 1093/ndt/gfr285.
[9] Huh H, Lee H, Lee JP, et al. Factors affecting the long-term outcomes of idiopathic membranous nephropathy[J]. BMC Nephrol,2017,18(1):104. DOI:10.1186/s12882-017-0525-6.
[10] Polanco N, Gutiérrez E, CovarsíA, et al. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy[J].J Am Soc Nephrol, 2010,21(4):697-704. DOI:10. 1681/ASN. 2009080861.
[11] Cattran DC, Kim ED, Reich H, et al. Membranous nephropathy:quantifying remission duration on outcome[J]. J Am Soc Nephrol,2017,28(3):995-1003. DOI:10.1681/ASN. 2015111262.
[12] Couser WG. Primary membranous nephropathy[J]. Clin J Am Soc Nephrol. 2017,12(6):983-997. DOI:10.2215/CJN. 11761116.
[13] Hoxha E, Harendza S, Pinnschmidt H, et al. PLA2R antibody levels and clinical outcome in patients with membranous nephropathy and non-nephrotic range proteinuria under treatment with inhibitors of the renin-angiotensin system[J]. PLoS One, 2014,9(10):e110681. DOI:10. 1371/journal. pone.0110681.
[14] Li L, Zhang X, Li Z, et al. Renal pathological implications in type 2diabetes mellitus patients with renal involvement[J]. J Diabetes Complications, 2017,31(I):114-121. DOI:10. 1016/j. jdiacomp.2016. 10.024.
[15] Liu S, Guo Q, Han H, et al. Clinicopathological characteristics of non-diabetic renal disease in patients with type 2 diabetesmellitus in a northeastern Chinese medical center:a retrospective analysis of273 casesv[J]. Int Urol Nephrol, 2016,48(10):1691-1698.DOI:10.1007/s11255-016-1331-y.
[16] Grubb A, Bj(o|¨)rk J, Nyman U, et al. Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation[J]. Scand J Clin Lab Invest, 2011,71(2):145-149. DOI:10.3109/00365513.2010.546879.
[2] Hladunewich MA, Troyanov S, Calafati J, et al. The natural history of the non-nephrotic membranous nephropathy patient[J]. Clin J Am Soc Nephrol, 2009,4(9):1417-1422. DOI:10. 2215/CJN.01330209.
[3] Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimateglomerular filtration rate[J]. Ann Intern Med, 2009,150(9):604-612.
[4] Austin HA 3rd, Muenz LR, Joyce KM, et al. Diffuse proliferative lupus nephritis:identification of specific pathologic features affecting renaloutcome[J]. Kidney Int, 1984,25(4):689-695.
[5] Schieppati A, Mosconi L, Pema A, et al. Prognosis of untreated patients with idiopathic membranous nephropathy[J]. N Engl J Med, 1993,329(2):85-89. DOI:10.1056/NEJM199307083290203.
[6] Howman A, Chapman TL, Langdon MM, et al. Immunosuppression for progressive membranous nephropathy:a UK randomised controlled trial[J]. Lancet. 2013,381(9868):744-751. DOI:10.1016/S0140-6736(12)61566-9.
[7] Sprangers B, Bomback AS, Cohen SD, et al. Idiopathic membranous nephropathy:clinical and histologic prognostic features and treatment patterns over time at a tertiary referral center[J]. Am J Nephrol, 2012,36(1):78-89. DOI:10.1159/000339628.
[8] Polanco N, Gutiérrez E, Rivera F, et al. Spontaneous remission of nephrotic syndrome in membranous nephropathy with chronic renal impairment[J]. Nephrol Dial Transplant, 2012,27(1):231-234,DOI:10. 1093/ndt/gfr285.
[9] Huh H, Lee H, Lee JP, et al. Factors affecting the long-term outcomes of idiopathic membranous nephropathy[J]. BMC Nephrol,2017,18(1):104. DOI:10.1186/s12882-017-0525-6.
[10] Polanco N, Gutiérrez E, CovarsíA, et al. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy[J].J Am Soc Nephrol, 2010,21(4):697-704. DOI:10. 1681/ASN. 2009080861.
[11] Cattran DC, Kim ED, Reich H, et al. Membranous nephropathy:quantifying remission duration on outcome[J]. J Am Soc Nephrol,2017,28(3):995-1003. DOI:10.1681/ASN. 2015111262.
[12] Couser WG. Primary membranous nephropathy[J]. Clin J Am Soc Nephrol. 2017,12(6):983-997. DOI:10.2215/CJN. 11761116.
[13] Hoxha E, Harendza S, Pinnschmidt H, et al. PLA2R antibody levels and clinical outcome in patients with membranous nephropathy and non-nephrotic range proteinuria under treatment with inhibitors of the renin-angiotensin system[J]. PLoS One, 2014,9(10):e110681. DOI:10. 1371/journal. pone.0110681.
[14] Li L, Zhang X, Li Z, et al. Renal pathological implications in type 2diabetes mellitus patients with renal involvement[J]. J Diabetes Complications, 2017,31(I):114-121. DOI:10. 1016/j. jdiacomp.2016. 10.024.
[15] Liu S, Guo Q, Han H, et al. Clinicopathological characteristics of non-diabetic renal disease in patients with type 2 diabetesmellitus in a northeastern Chinese medical center:a retrospective analysis of273 casesv[J]. Int Urol Nephrol, 2016,48(10):1691-1698.DOI:10.1007/s11255-016-1331-y.
[16] Grubb A, Bj(o|¨)rk J, Nyman U, et al. Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation[J]. Scand J Clin Lab Invest, 2011,71(2):145-149. DOI:10.3109/00365513.2010.546879.