Leishmaniosi e patologia renale

Transcription

1 Leishmaniosi e patologia renale George Lubas Prof. di Clinica Medica Veterinaria Dipl. European College Veterinary Internal Medicine Ass. Dipl. European College Veterinary Clinical Pathology 1 Canine leishmaniasis (CanL) ZoonoCc parasicc disease (enzoocc in the Mediterranean basin) caused by intracellular protozoan Leishmania infantum. Characterized by heterogeneous clinical presentacon in which renal pathologic condicons are ojen the principal cause of death. Pierantozzi et al, JAAHA Master Nefrologia 7 feb 14, G Lubas 1

2 CanL & nephropathy Mainly characterized by glomerular damage Primarily apributed to intra- glomerular deposicon of circulacng immune complexes formed by organism ancgens and the ancbodies produced against it. 3 CanL & glomerular lesions Glomerular lesions histologically classified as: membranous glomerulo- nephrics, membranoproliferacve glomerulonephrics, mesangial glomerulonephrics, focal segmental glomerulosclerosis. D Amico, Bazzi. Kidney Int Master Nefrologia 7 feb 14, G Lubas 2

3 CanL & renal damage Renal damage in CanL is thought to be a mulcfactorial process that is caused by immune complex deposicon; however, recent study has also highlighted the role of T lymphocytes and adhesion molecules. Immune complex deposicon can be the consequence of persistent ancgenemia and circulacng immune complexes; the process typically triggers the accvacon of the complement system and causes acute injury to the glomerular capillaries and mesangium. Aresu et al, Vet Path, CanL & pathogenesis of renal damage The pathogenesis of the renal damage in Leishmania infeccon is not well defined; both a type III hypersensicvity mechanism and the involvement of CD4þ T cells have been proposed. The glomerular proliferacon papern has also been apributed to an inhibicon of mesangial cells apoptosis and the migracon of inflammatory cells into the glomerular tuj. 6 Master Nefrologia 7 feb 14, G Lubas 3

4 Glomerulopathy & proteinuria Glomerulopathy that characterizes renal involvement in CanL causes proteinuria and renal failure. Results of previously published studies carried out on dogs in the USA with naturally occurring chronic renal failure suggest that persistent proteinuria is associated with greater frequency of renal morbidity and mortality due to both renal and extrarenal causes 7 Pathogenesis of glomerulonephrics Immune- mediated associated with IC deposicon/in situ formacon in the glomeruli (Ig and complement) Nonimmune- mediated may be inflammatory or noninflammatory 8 Master Nefrologia 7 feb 14, G Lubas 4

5 IC in the glomerulus 1. Ag- Ab equivalence soluble circulacng IC are trapped in the glomerulus 2. Ab excess IC tends to be large and insoluble and are removed by phagocycc cells 3.Ag excess - IC do not readily bind complement and are less likely to produce immunological injury 9 IC in the glomerulus Factors affeccng deposicon of IC 1. Size of the IC 2. Charge of the IC 3. Removal of the IC by phagocytosis 4. Damage of the basement membrane itself IC locacon of deposicon/ formacon 1. Subepithelial usually small IC 2. Subendothelial usually large or negacvely charged IC 3. Intramembranous Ag planted in the GBM 4. Mesangium mesangial cells remove large IC and deposit them in the mesangium 10 Master Nefrologia 7 feb 14, G Lubas 5

6 IC deposicon and severity of disfunccon Subepithelial BM thickening and minimal inflammatory cell infiltracon proteinuria may be severe Subendothelial recruitment of inflammatory cells and BM thickening moderate proteinuria Mesangial hypercellularity and mesangial matrix accumulacon may be asymptomacc 11 Proteinuria and prognosis Moreover, the risk of developing adverse outcomes increases as the magnitude of proteinuria increases Nevertheless, regardless of the role of proteinuria as a mediator of renal injury, it is an important marker both for increased risk of adverse outcomes and for response to renoproteccve intervencons. 12 Master Nefrologia 7 feb 14, G Lubas 6

7 Prevalence of CanL renal damage Prevalence of renal disease in dogs with leishmaniasis ( %) (Cortadellas et al., JVIM, 2006; Ruiz de Ybáñez et al., Vet Parasitol, 2009) is higher than the prevalence of renal disease in dogs without leishmaniasis (<=15% in dogs over 10 years old) (Price, Comp Clin Path, 2002). IniCally, infected dogs could have moderate to severe proteinuria in absence of azotemia, but as glomerular disease progresses to tubulo- intersccal lesions, azotemia and end- stage renal failure could be developed (Zatelli et al., AJVR, 2003). 13 Commento arccolo JVIM 14 Master Nefrologia 7 feb 14, G Lubas 7