非大量蛋白尿狼疮肾炎患者肾脏病理严重程度的危险因素分析
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摘要
目的研究影响非大量蛋白尿(24h蛋白尿<3. 5 g)狼疮肾炎(LN)患者肾脏病理严重程度的危险因素以及预后情况。方法纳入2004年1月1日至2018年3月31日于华中科技大学同济医学院附属同济医院行肾脏穿刺活检确诊为LN并且起始24h蛋白尿<3. 5 g的患者作为研究对象,记录患者肾活检时相关临床信息,并行规律随访。对所有患者肾活检时的病理切片进行重新阅片,采用统一标准进行评分,根据患者肾脏病理严重程度分为病理轻组和病理重组。采用Log-rank检验比较两组的缓解率差异。采用Logistic回归方程分析影响非大量蛋白尿LN患者肾脏病理严重程度的危险因素。结果共纳入95例非大量蛋白尿LN患者,以女性为主,平均年龄(32. 4±1. 1)岁,其中有随访者共79人。肾脏病理轻组43例,肾脏病理重组52例,病理轻组患者血红蛋白、血清IgA水平均高于病理重组(P <0. 05),而血氯水平显著低于病理重组(P <0. 05)。随访结果显示,病理轻组患者的远期(大于6个月)累积完全缓解率大于病理重组(P <0. 05)。多因素Logistic回归结果提示,年龄(OR=1. 219,95%CI:1. 043～1. 425,P <0. 05)、SLEDAI-2K评分(OR=1. 202,95%CI:1. 025～1. 411,P <0. 05)、起始蛋白尿定量(OR=3. 793,95%CI:1. 058～13. 595,P <0. 05)、血清IgA水平(OR=0. 222,95%CI:0. 063～0. 781,P <0. 05)是肾脏病理重的独立危险因素。结论老龄、高SLEDAI-2K评分、高起始蛋白尿定量和低血清IgA水平可能与非大量蛋白尿LN患者的肾脏病理较重相关。
Objective To explore the renal pathology-related factors of non-nephrotic-range proteinuria of biopsy-proven lupus nephritis( LN) patients and their prognosis. Methods We prospectively observed non-nephrotic-range proteinuria patients with biopsy-proven LN in Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology between Jan. 1,2004 and July 31,2018. All related baseline clinical data were recorded and regular follow-up was performed. The pathological sections of all patients were re-read and scored according to uniform criteria.According to the severity of renal pathology,the patients were divided into two groups: mild pathologic damage group and severe pathologic damage group. Log-rank test was used to compare the difference of remission rate between the mild pathologic damage group and severe pathologic damage group. Logistic regression equation was used to analyze the renal pathology-related risk factors. Results Ninety-five non-major proteinuria LN patients( female: 83. 2%,mean age: 32. 4 years) were enrolled,including79 follow-ups. There were 43 cases of mild renal pathologic damage group and 52 cases of severe renal pathologic damage group. Hemoglobin and serum IgA levels were significantly higher in mild pathologic group than in severe pathologic damage group( P < 0. 05). The follow-up results showed that the cumulative complete remission rate in the mild pathologic damage group was significantly higher than that in the severe pathologic damage group( P < 0. 05). Multivariate logistic regression results indicated age( OR = 1. 219,95% CI: 1. 043 to 1. 425,P < 0. 05),SLEDAI-2 K score( OR = 1. 202,95% CI: 1. 025 to 1. 411,P < 0. 05),initial proteinuria( OR = 3. 793,95% CI: 1. 058 to 1. 595,P < 0. 05),and serum IgA levels( OR = 0. 222,95% CI: 0. 063 to 0. 781,P < 0. 05) were independent renal pathology-related risk factors. Conclusions Older,high SLEDAI-2 K scores,high initial proteinuria and low serum IgA levels may be associated with severe renal pathologic damage in patients with non-nephrotic-range proteinuria LN.
Objective To explore the renal pathology-related factors of non-nephrotic-range proteinuria of biopsy-proven lupus nephritis( LN) patients and their prognosis. Methods We prospectively observed non-nephrotic-range proteinuria patients with biopsy-proven LN in Tongji Hospital affiliated to Tongji Medical College,Huazhong University of Science and Technology between Jan. 1,2004 and July 31,2018. All related baseline clinical data were recorded and regular follow-up was performed. The pathological sections of all patients were re-read and scored according to uniform criteria.According to the severity of renal pathology,the patients were divided into two groups: mild pathologic damage group and severe pathologic damage group. Log-rank test was used to compare the difference of remission rate between the mild pathologic damage group and severe pathologic damage group. Logistic regression equation was used to analyze the renal pathology-related risk factors. Results Ninety-five non-major proteinuria LN patients( female: 83. 2%,mean age: 32. 4 years) were enrolled,including79 follow-ups. There were 43 cases of mild renal pathologic damage group and 52 cases of severe renal pathologic damage group. Hemoglobin and serum IgA levels were significantly higher in mild pathologic group than in severe pathologic damage group( P < 0. 05). The follow-up results showed that the cumulative complete remission rate in the mild pathologic damage group was significantly higher than that in the severe pathologic damage group( P < 0. 05). Multivariate logistic regression results indicated age( OR = 1. 219,95% CI: 1. 043 to 1. 425,P < 0. 05),SLEDAI-2 K score( OR = 1. 202,95% CI: 1. 025 to 1. 411,P < 0. 05),initial proteinuria( OR = 3. 793,95% CI: 1. 058 to 1. 595,P < 0. 05),and serum IgA levels( OR = 0. 222,95% CI: 0. 063 to 0. 781,P < 0. 05) were independent renal pathology-related risk factors. Conclusions Older,high SLEDAI-2 K scores,high initial proteinuria and low serum IgA levels may be associated with severe renal pathologic damage in patients with non-nephrotic-range proteinuria LN.
引文
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[33]Ryan MJ,Mc Lemore GR Jr,Hendrix ST.Insulin resistance and obesity in a mouse model of systemic lupus erythematosus[J].Hypertension,2006,48(5):988-993.
[2]Musa R,Qurie A.Lupus Nephritis[M].StatPearls Publishing LLC,2018.
[3]Hahn BH,Mc Mahon MA,Wilkinson A,et al.American College of Rheumatology guidelines for screening,treatment,and management of lupus nephritis[J].Arthritis Care Res(Hoboken),2012,64(6):797-808.
[4]Guo Q,Lu X,Miao L,et al.Analysis of clinical manifestations and pathology of lupus nephritis:a retrospective review of 82 cases[J].Clin Rheumatol,2010,29(10):1175-1180.
[5]Tsai YG,Lee CY,Lin TY,et al.CD8(+)Treg cells associated with decreasing disease activity after intravenous methylprednisolone pulse therapy in lupus nephritis with heavy proteinuria[J].Plo SOne,2014,9(1):e81344.
[6]Desai N,Cimbaluk D,Lewis EJ,et al.Proteinuria in membranous lupus nephritis:the pathology is in the podocyte[J].Lupus,2013,22(5):461-468.
[7]Hochberg MC.Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus[J].Arthritis Rheum,1997,40(9):1725.
[8]Weening JJ,D'Agati VD,Schwartz MM,et al.The classification of glomerulonephritis in systemic lupus erythematosus revisited[J].JAm Soc Nephrol,2004,15(2):241-250.
[9]Chan TM.Histological reclassification of lupus nephritis[J].Curr Opin Nephrol Hypertens,2005,14(6):561-566.
[10]Gonzalo E,Toldos O,Martinez-Vidal MP,et al.Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis[J].Arthritis Res Ther,2012,14(3):R126.
[11]Shariati-Sarabi Z,Ranjbar A,Monzavi SM,et al.Analysis of clinicopathologic correlations in Iranian patients with lupus nephritis[J].Int J Rheum Dis,2013,16(6):731-738.
[12]Hsu CY,Chiu WC,Yang TS,et al.Age-and gender-related longterm renal outcome in patients with lupus nephritis[J].Lupus,2011,20(11):1135-1141.
[13]Donadio JV Jr,Hart GM,Bergstralh EJ,et al.Prognostic determinants in lupus nephritis:a long-term clinicopathologic study[J].Lupus,1995,4(2):109-115.
[14]Tang Z,Chen D,Yang S,et al.Late onset lupus nephritis:analysis of clinical manifestations and renal pathological features in Chinese patients[J].Rheumatol Int,2011,31(12):1625-1629.
[15]Al Arfaj AS,Khalil N,Al Saleh S.Lupus nephritis among 624 cases of systemic lupus erythematosus in Riyadh,Saudi Arabia[J].Rheumatol Int,2009,29(9):1057-1067.
[16]Bombardier C,Gladman DD,Urowitz MB,et al.Derivation of the SLEDAI.A disease activity index for lupus patients[J].Arthritis Rheum,1992,35(6):630-640.
[17]Gladman DD,Ibanez D,Urowitz MB.Systemic lupus erythematosus disease activity index 2000[J].J Rheumatol,2002,29(2):288-291.
[18]Romero-Diaz J,Isenberg D,Ramsey-Goldman R.Measures of adult systemic lupus erythematosus:updated version of British Isles Lupus Assessment Group(BILAG 2004),European Consensus Lupus Activity Measurements(ECLAM),Systemic Lupus Activity Measure,Revised(SLAM-R),Systemic Lupus Activity Questionnaire for Population Studies(SLAQ),Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K),and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index(SDI)[J].Arthritis Care Res(Hoboken),2011,63(Suppl 11):S37-46.
[19]Sato JO,Corrente JE,Saad-Magalhaes C.Correlation between the Modified Systemic Lupus Erythematosus Disease Activity Index2000 and the European Consensus Lupus Activity Measurement in juvenile systemic lupus erythematosus[J].Lupus,2016,25(13):1479-1484.
[20]Ahn SS,Park Y,Jung SM,et al.Serum leucine-rich alpha2-glycoprotein is elevated in patients with systemic lupus erythematosus and correlates with disease activity[J].Clin Chim Acta,2018,486:253-258.
[21]Bakema JE,van Egmond M.The human immunoglobulin A Fc receptor FcalphaRI:a multifaceted regulator of mucosal immunity[J].Mucosal Immunol,2011,4(6):612-624.
[22]Woof JM,Kerr MA.The function of immunoglobulin A in immunity[J].J Pathol,2006,208(2):270-282.
[23]Pasquier B,Launay P,Kanamaru Y,et al.Identification of FcalphaRI as an inhibitory receptor that controls inflammation:dual role of FcRgamma ITAM[J].Immunity,2005,22(1):31-42.
[24]Bartoe JL,Nathanson NM.Differential regulation of leukemia inhibitory factor-stimulated neuronal gene expression by protein phosphatases SHP-1 and SHP-2 through mitogen-activated protein kinase-dependent and-independent pathways[J].J Neurochem,2000,74(5):2021-2032.
[25]Wilton JM.Suppression by Ig A of Ig G-mediated phagocytosis by human polymorphonuclear leucocytes[J].Clin Exp Immunol,1978,34(3):423-428.
[26]Nikolova EB,Russell MW.Dual function of human Ig A antibodies:inhibition of phagocytosis in circulating neutrophils and enhancement of responses in IL-8-stimulated cells[J].J Leukoc Biol,1995,57(6):875-882.
[27]Hammarstrom L,Vorechovsky I,Webster D.Selective Ig A deficiency(SIgAD)and common variable immunodeficiency(CVID)[J].Clin Exp Immunol,2000,120(2):225-231.
[28]Robins G,Howdle PD.Advances in celiac disease[J].Curr Opin Gastroenterol,2005,21(2):152-161.
[29]Zhang Z,Xu X,Fan H,et al.Higher serum chloride concentrations are associated with acute kidney injury in unselected critically ill patients[J].BMC Nephrol,2013,14:235.
[30]Suetrong B,Pisitsak C,Boyd JH,et al.Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients[J].Crit Care,2016,20(1):315.
[31]Wilcox CS.Regulation of renal blood flow by plasma chloride[J].J Clin Invest,1983,71(3):726-735.
[32]Yunos NM,Bellomo R,Hegarty C,et al.Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults[J].JAMA,2012,308(15):1566-1572.
[33]Ryan MJ,Mc Lemore GR Jr,Hendrix ST.Insulin resistance and obesity in a mouse model of systemic lupus erythematosus[J].Hypertension,2006,48(5):988-993.