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Nefritis Lpica

Nefritis LpicaDra Olga Lidia Vera Lastra JSMIDr Gustavo Leal Alegre R4MI

7 de Abril 2016, Ciudad de Mxico

Definicin LESEnfermedad autoinmune en la cual rganos y clulas son daadas por anticuerpos anclados a tejido e inmunocomplejosPrototipo de trastorno autoinmune multisistmico con un amplio espectro de presentaciones clnicasHarrison's Principles of Internal Medicine, 19 ed. 2015EULAR Textbook on Rheumatic Diseases, 2012

EpidemiologaSemin Arthritis Rheum. 2010;39(4):257.Arthritis Care & Research. 2012;64(6):797Lupus. 2006;15(5):308.Dilisis y Trasplante. 2010; 31(1):7-11

EpidemiologaRev Bras Reumatol. 2015;55(1):1-21

Rheum Dis Clin N Am 42 (2016) 63-73

Clinical and Developmental Immunology, Volume 2012

Clinical and Developmental Immunology, Volume 2012

PatogeniaHarrison's Principles of Internal Medicine, 19 ed. 2015

Harrison's Principles of Internal Medicine, 19 ed. 2015

Patogenia NefritisBrenner and Rectors The Kidney. 10 Ed. 2016J Rheumatol. 2003;30(7):1495.

Nature Reviews Nephrology 8, 183-189 (2012)

a | Genetic variants involved in homeostatic cell death (for example, Fas variants) and the rapid clearance of dead cell corpses (for example, C3/4 variants or DNase variants) promote the exposure of nuclear particles to the immune system. b | Nuclear particles resemble viral particles and activate the same viral nucleic acid recognition receptors (for example, TLR7 signaling) on antigen-presenting cells where they elicit autoadjuvant effects. Genetic variants of the signaling elements are recognized risk factors for SLE. Through co-stimulation, the activation of antigen-presenting cells changes the immune interpretation of concomitantly presented antigens of the same particle. c | Polyclonal lymphocyte expansion leads to lymph node and spleen swelling in SLE (as in viral infections). The expansion of autoreactive T cells has multiple effects on the disease process and genetic variants further influence the differentiation of T-helper cells. The complex regulation of lymphocyte activation and expansion is also affected by multiple genetic variants, such as PDCD1, which plays a role in B-cell differentiation, and BLK and BANK1, which are involved in B-cell receptor signaling and B-cell development. Abbreviations: Ag, antigen; BAFF, B-cell activating factor; BANK1, B-cell scaffold protein with ankyrin repeats 1; BLK, B lymphoid tyrosine kinase; C3/4, complement 3/4; CRP, C-reactive protein; IFN, interferon; IL, interleukin; IRAK, interleukin 1 receptor-associated kinase; IRF, interferon regulatory factor; MFG-E8, milk fat globule epidermal growth factor factor 8; MHC, major histocompatibility complex; PDCD1, programmed cell death 1; PTPN22, protein tyrosine phosphatase, non-receptor type 22; SAP, serum amyloid P component; SIGIRR, single immunoglobulin IL-1R-related molecule; SLE, systemic lupus erythematosus; STAT4, signal transducer and activator of transcription 4; TH, T-helper cell; TLR, Toll-like receptor; TNFAIP3, tumor necrosis factor, alpha-induced protein 3; TREG, T-regulatory cell.11

Seminars in Nephrology, Vol 35, No 5, September 2015, pp 444454

Seminars in Nephrology, Vol 35, No 5, September 2015, pp 444454

Nat. Rev. Rheumatol. 6, 1320 (2010).

In situ formation of immune complexes with complement activation and induction of inflammatory mediators results in chemotaxis and activation of inflammatory cells within the kidney and further release of proinflammatory signals and mediators, leading to injury and damage of cellular and structural elements within the renal parenchyma. Permission obtained from Nature Publishing Group Davidson, A. & Aranow, C. Lupus nephritis: lessons from murine models. Nat. Rev. Rheumatol. 6, 1320 (2010).14

Nature Reviews Immunology 13, 738753 (2013)

Glomerular immunopathology often develops from intraglomerular complement activation via the classical (immune complex-related) or alternative (immune complex-independent) complement pathway. Immune complexes can form in different compartments of the glomerulus, which determines the resulting histopathological lesion, as different glomerular cell types are primarily activated in each compartment. The resulting histopathological lesions determine the classification of glomerulonephritis. Immune complex deposition in the mesangium activates mesangial cells, which leads to mesangioproliferative glomerulopathies, such as IgA nephropathy or lupus nephritis class I and II. Subendothelial immune complex deposits activate endothelial cells, as seen in lupus nephritis class III and IV. Subepithelial immune complex deposits preferentially activate the visceral glomerular epithelium that is, podocytes and usually cause massive proteinuria, as these cells are essential for the glomerular filtration barrier. As a result of the poor regeneration of podocytes compared with that of the other glomerular cell types, podocyte loss leads to progressive membranous nephropathy and end-stage renal disease. Primary membranous nephropathy mainly develops from autoimmunity against PLA2R, whereas secondary forms of this nephropathy represent renal manifestations of systemic disorders such as lupus nephritis. Hence, the level of proteinuria is an important prognostic biomarker and predictor of poor outcomes of glomerulopathies. Linear immune complex deposits indicate antibody binding to autoantigens within the glomerular basement membrane (GBM), for example, collagen IV antibodies in anti-GBM disease. Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis develops in the absence of immune complex deposits (known as pauci-immune), as it is driven by both ANCAs and cellular immunity. Complement component C3 glomerulopathies and atypical haemolytic uraemic syndrome (aHUS) develop from the aberrant activation of the alternative complement pathway. The boxes list in order the type of immune deposits, the glomerular structure that is primarily affected, the dominant clinical signs and the related disorders for each mechanism. 3(IV)NC1, non-collagenous 1 (NC1) domain of the 3 chain of type IV collagen; CKD, chronic kidney disease; LAMP2, lysosome-associated membrane protein 2; MPO, myeloperoxidase; PLA2R, secretory phospholipase A2 receptor; PR3, proteinase 3.15

MecanismosPatologa GlomerularPatologa TubulointersticialDepsito de complejos inmunes y activacin del complemento mesangial y subendotelialDepsito de complejos inmunes en vasos periglomerularesActivacin receptor Fc, TLR, y complementoActivacin complementoDepsito subepitelial: Clase VActivacin de clulas endoteliales, molculas de adhesin luminalesExpresin local de citocinas y reclutamiento leucocitarioProduccin local de anticuerpos por clulas BProliferacin endotelial y mesangialCitocinas proapoptticasDao a barrera de filtracin: proteinuria y hematuriaDao tubular: proteinuriaNecrosis de clulas renales con cicatrizacin localAtrofia tubular y vascularInflamacin periglomerularFibrosis intersticial por reparacin insuficienteGlomeruloesclerosis global

J Am Soc Nephrol 24, 2013

Mecanismos de dao glomerular distintos a depsito de inmunocomplejosBrenner and Rectors The Kidney. 10 Ed. 2016


EULAR Textbook on Rheumatic Diseases, 2012

Nefrologia 2012;32(Suppl.1):1-35


Serologa y actividad renalAnticuerpoPrevalenciaAntgenoRelevancia ClnicaAnticuerpos antinucleares98%Antgenos nuclearesMejor prueba de tamizajeAnti DNA de doble cadena70%DNA de doble cadenaEspecfico para LES, correlaciona con actividad renal, vasculitis, y generalAnti SSA30%Complejo proteico para RNA hY, 60KDa y 52kDaAsociado a menor riesgo de nefritisAnti SSB10%Complejo proteico 47 KDa con hY RNAMenor riesgo de nefritisC3, C4--Disminucin asociada a actividad renal

Harrison's Principles of Internal Medicine, 19 ed. 2015

Reumatol Clin. 2010;6(5):268272

Definicin de caso Arthritis Care & Research Vol. 64, No. 6, Junio 2012, pp 797808

Biopsia RenalCurr Opin Nephrol Hypertens. 2005;14(1):1.J Am Soc Nephrol. 2010;21(12):2028.

Correlacin clnico patolgica?Curr Opin Nephrol Hypertens. 2005;14(1):1.J Am Soc Nephrol. 2010;21(12):2028.

Indicaciones de BiopsiaArthritis Care Res (Hoboken). 2012 Jun;64(6):797-808.Nefrologia 2012;32(Suppl.1)1-35

Reporte de biopsiaNefrologia 2012;32(Suppl.1):1-35

Nefrologia 2012;32(Suppl.1):1-35

Nefrologia 2012;32(Suppl.1):1-35

Ejemplo: Femenino de 21 aos con LES MCALaboratorioEGO NormalCr 0.6Anti ds DNA 40C3: 98, C4: 20Biopsia renal MO normalDepsito C1q mesangial

Comprehensive Clinical Nephrology, 4 ed. 2010

Ejemplo:Femenino 23 aos, LES MCA 2008Tratamiento: Cloroquina 150 mg c 24 hrsConsulta de control:EGO con cilindros eritrocitariosCr 0.5, Protenas indetectables, Dep Cr 97 mL minC3: 66, C4:15, anti ds DNA 50Biopsia renal: hipercelularidad mesangialCapilares normales

Comprehensive Clinical Nephrology, 4 ed. 2010

Nefrologia 2012;32(Suppl.1):1-35

Ejemplo:Femenino de 25 aos, LES 6 m dx, HAS 2 meses dxTx: MTX 20 mg/semana, PDN 10 mg/da, amlodipino 5 mg/daAcude por hipertensinEGO: Hematuria, cilindros eritrocitarios, protenas +++Cr 1.1, Protenas 24 hrs: 600 mgC3: 40, C4: 10, anti DS DNA: 300Bx: lesiones focales y segmentarias proliferativas en