Nefropatía lúpica
Resumen
El compromiso renal es frecuente en el lupus eritematoso sistémico (28%-74%), constituyendo en algunas series el factor que se vincula a la mayor morbimortalidad asociada a la enfermedad. En su patogenia participan el depósito de inmunocomplejos, la activación del complemento, linfocitos B, T y múltiples citocinas. Se puede manifestar clínicamente con cualquier síndrome nefrológico, desde alteraciones mínimas del sedimento urinario a enfermedad renal crónica extrema. La biopsia renal está indicada en todas las circunstancias en que se sospeche el daño renal así como frente a cambios clínico-evolutivos en pacientes con nefropatía lúpica conocida. El tratamiento se planifica en función de la presentación clínica, lesión histológica predominante, compromiso extrarrenal, edad, comorbilidades y preferencias del paciente. Algunos factores como el retraso en el diagnóstico, la edad de presentación, características raciales, formas proliferativas, valor de creatinina y proteinuria al debut se vinculan a progresión hacia enfermedad renal crónica extrema. Se revisan los principales aspectos vinculados a la epidemiología, presentación clínica, lesión histológica y estrategias diagnósticas y terapéuticas en la nefropatía lúpica.
Citas
(2) Cervera R, Khamashta MA, Hughes GR. The Euro-lupus project: epidemiology of systemic lupus erythematosus in Europe. Lupus 2009; 18(10):869-74.
(3) Pons-Estel BA, Catoggio LJ, Cardiel MH, Soriano ER, Gentiletti S, Villa AR, et al; Grupo Latinoamericano de Estudio del Lupus. The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics”. Medicine (Baltimore) 2004; 83(1):1-17.
(4) Mazzuchi N, Acosta N, Caorsi H, Schwedt E, Di Martino LA, Mautone M, et al. Frecuencia de diagnóstico y presentación clínica de las glomerulopatías en el Uruguay. Nefrología 2005; 25(2):113–20.
(5) Danila MI, Pons-Estel GJ, Zhang J, Vilá LM, Reveille JD, Alarcón GS. Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort. Rheumatology (Oxford) 2009; 48(5):542-5.
(6) European Working Party on Systemic Lupus Erythematosus; Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003; 82(5):299-308.
(7) Ottati G. Sobrevida de la Nefropatía Lúpica en Uruguay. En: VIII Congreso Uruguayo de Nefrología, 27-29 setiembre 2012, Montevideo.
(8) Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349(16):1526-33.
(9) Yung S, Chan TM. Autoantibodies and resident renal cells in the pathogenesis of lupus nephritis: getting to know the unknown. Clin Dev Immunol 2012; 2012:139365.
(10) Fenton KA, Rekvig OP. A central role of nucleosomes in lupus nephritis. Ann N Y Acad Sci 2007; 1108:104-13.
(11) Sinico RA, Rimoldi L, Radice A, Bianchi L, Gallelli B, Moroni G. Anti-C1q autoantibodies in lupus nephritis. Ann N Y Acad Sci 2009; 1173:47-51.
(12) Fenton K, Fismen S, Hedberg A, Seredkina N, Fenton C, Mortensen ES, et al. Anti-dsDNA antibodies promote initiation, and acquired loss of renal Dnase1 promotes progression of lupus nephritis in autoimmune (NZBxNZW) F1 mice. PLoS One 2009; 4(12):e8474.
(13) Apostolidis SA, Lieberman LA, Kis-Toth K, Crispín JC, Tsokos GC. The dysregulation of cytokine networks in systemic lupus erythematosus. J Interferon Cytokine Res 2011; 31(10):769-79.
(14) Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki KG, Iniotaki A, et al. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: an open-label trial. Arthritis Rheum 2005; 52(2):501-13.
(15) Vilaysane A, Chun J, Seamone ME, Wang W, Chin R, Hirota S, et al. The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J Am Soc Nephrol 2010; 21(10):1732-44.
(16) LUMINA Study Group; Bastian HM, Roseman JM, McGwin G Jr, Alarcón GS, Friedman AW, Fessler BJ, et al. LUpus in MInority populations: nature vs nurture. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus 2002; 11(3):152-60.
(17) Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, de Ramon Garrido E, Danieli MG, et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann Rheum Dis 2010; 69(1):61-4.
(18) Christopher-Stine L, Siedner M, Lin J, Haas M, Parekh H, Petri M, et al. Renal biopsy in lupus patients with low levels of proteinuria. J Rheumatol 2007; 34(2):332-5.
(19) Ruiz Irastorza G, Espinosa G, Frutos MA, Jiménez Alonso J, Praga M, Pallarés L, et al. Diagnóstico y tratamiento de la nefritis lúpica. documento de consenso del Grupo de Enfermedades Autoinmunes Sist{emicas (GEAS) de la Sociedad Española de Medicina Interna (SEMI) y de la Sociedad Española de Nefrología (SEN). Nefrología 2012; 32(Supl 1):1–35.
(20) Silva-Fernández L, Andreu-Sánchez JL, Ginzler EM. Tratamiento actual de la nefirtis lúpica: ¿cúal es la mejor opción? Rev Clín Esp 2008; 208(3):138–41.
(21) Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004; 15(2):241-50.
(22) McCluskey RT. Lupus nephritis. Pathol Annu 1970; 5:125–44.
(23) Yung S, Tsang RC, Sun Y, Leung JK, Chan TM. Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: implications on tubulointerstitial inflammation in lupus nephritis. J Am Soc Nephrol 2005; 16(11):3281–94.
(24) Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4(2):295-306.
(25) Asherson RA, Cervera R. The antiphospholipid syndrome: multiple faces beyond the classical presentation. Autoimmun Rev 2003; 2(3):140–51.
(26) Sangle SR, D’Cruz DP, Abbs IC, Khamashta MA, Hughes GR. Renal artery stenosis in hypertensive patients with antiphospholipid (Hughes) syndrome: outcome following anticoagulation. Rheumatology (Oxford) 2005; 44(3):372–7.
(27) Silvariño R, Sant F, Espinosa G, Pons-Estel G, Solé M, Cervera R, et al. Nephropathy associated with antiphospholipid antibodies in patients with systemic lupus erythematosus. Lupus 2011; 20(7):721-9.
(28) European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association; Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, et al. Joint European League against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 2012; 71(11):1771-82.
(29) Silvariño R, Sato EI. Factores de riesgo para aterosclerosis en enfermedades autoinmunitarias. Rev Méd Urug 24(2):118-32.
(30) Silvariño R, Alonso J. Alteraciones del perfil lipídico en las enfermedades autoinmunes sistemáticas. Arch Med Interna (Montevideo) 2008; 30(4):114-9.
(31) Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf 2014; 37(4):201-11.
(32) Ruiz-Irastorza G, Danza A, Khamashta M. Glucocorticoid use and abuse in SLE. Rheumatology (Oxford) 2012; 51(7):1145-53.
(33) Ruiz-Irastorza G, Danza A, Perales I, Villar I, Garcia M, Delgado S, et al. Prednisone in lupus nephritis: how much is enough? Autoimmun Rev 2014; 13(2):206-14.
(34) Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta MA. Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69(1):20-8.
(35) Grupo Latino Americano de Estudio del Lupus Eritematoso (Gladel); Shinjo SK, Bonfá E, Wojdyla D, Borba EF, Ramirez LA, Scherbarth HR, et al. Antimalarial treatment may have a time-dependent effect on lupus survival: data from a multinational Latin American inception cohort. Arthritis Rheum 2010; 62(3):855-62.
(36) Kasitanon N, Fine DM, Haas M, Magder LS, Petri M. Hydroxychloroquine use predicts complete renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis. Lupus 2006; 15(6):366-70.
(37) Barber CE, Geldenhuys L, Hanly JG. Sustained remission of lupus nephritis. Lupus 2006; 15(2):94-101.
(38) Pons-Estel GJ, Alarcón GS, McGwin GJr, Danila MI, Zhang J, Bastian HM, et al. Protective effect of hydroxychloroquine on renal damage in patients with lupus nephritis: LXV, data from a multiethnic US cohort. Arthritis Rheum 2009; 61(6):830-9.
(39) Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2010; 62(6):775-84.
(40) Durán-Barragán S, McGwin G Jr, Vilá LM, Reveille JD, Alarcón GS. Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus—results from LUMINA (LIX): a multiethnic US cohort. Rheumatology (Oxford) 2008; 47(7):1093-6.
(41) Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics; Bertsias G, Ioannidis JP, Boletis J, Bombardieri S, Cervera R, Dostal C, et al. EULAR recommendations for the management of systemic lupus erythematosus: report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 2008; 67(2):195-205.
(42) Caorsi de la Fuente HM. Tratamiento de la nefropatía lúpica. Arch Med Interna (Montevideo) 2004; 26(3/4):77-82.
(43) Appel GB, Contreras G, Dooley MA, Ginzler EM, Isenberg D, Jayne DL, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol 2009; 20(5):1103-12.
(44) Bao H, Liu ZH, Xie HL, Hu WX, Zhang HT, Li LS. Successful treatment of class V+IV lupus nephritis with multitarget therapy. J Am Soc Nephrol 2008; 19(10):2001–10.
(45) Ward MM. Changes in the incidence of endstage renal disease due to lupus nephritis in the United States, 1996-2004. J Rheumatol 2009; 36(1):63–7.
(46) Collaborative Study Group; Korbet SM, Schwartz MM, Evans J, Lewis EJ. Severe lupus nephritis: racial differences in presentation and outcome. J Am Soc Nephrol 2007; 18(1):244–54.
(47) Bihl GR, Petri M, Fine DM. Kidney biopsy in lupus nephritis: look before you leap. Nephrol Dial Transplant 2006; 21(7):1749–52.
(48) Mok CC. Membranous nephropathy in systemic lupus erythematosus: a therapeutic enigma. Nat Rev Nephrol 2009; 5(4):212–20.
(49) Contreras G, Pardo V, Cely C, Borja E, Hurtado A, De La Cuesta C, et al. Factors associated with poor outcomes in patients with lupus nephritis. Lupus 2005; 14(11):890-5.
(50) Greloni G, Scolnik M, Marin J, Lancioni E, Quiroz C, Zacariaz J, et al. Value of repeat biopsy in lupus nephritis flares. Lupus Sci Med 2014; 1(1):e000004.
(51) Houssiau FA, Vasconcelos C, D’Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheum 2002; 46(8):2121-31.