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CHRONIC TRANSPLANT GLOMERULOPATHY - clinical and histological characteristics

CHRONIC TRANSPLANT GLOMERULOPATHY - clinical and histological characteristics. Agnieszka Perkowska-Ptasinska 1 , M. Ciszek, A.L. Urbanowicz, L. Paczek, M. Glyda, A. Debska-Slizien, A. Rydzewski, K. Dziewanowski, M. Myslak and M. Durlik

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CHRONIC TRANSPLANT GLOMERULOPATHY - clinical and histological characteristics

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  1. CHRONIC TRANSPLANT GLOMERULOPATHY- clinical and histological characteristics Agnieszka Perkowska-Ptasinska1, M. Ciszek, A.L. Urbanowicz, L. Paczek, M. Glyda, A. Debska-Slizien, A. Rydzewski, K. Dziewanowski, M. Myslak and M. Durlik 1Transplantation Institute, Warsaw Medical University, Poland

  2. CHRONIC TRANSPLANT GLOMERULOPATHY MORPHOLOGY: double contours of glomerular capillaries, no IF/EM deposits CLINICALLY: proteinuria, hypertension, declining graft function and graft loss Habib 1993; Regele J Am Soc Nephrol 2002; Sijpkens Ki 2004; Gloor AJT 2006; Sis AJT 2007; Gloor AJT 2007; Cosio AJT 2008;

  3. CHRONIC TRANSPLANT GLOMERULOPATHY • rare before 6 months after Tx, • the incidence rises from 1.0-4.0% at 1 year to 20% at 5 years • more common in patients with: • historical or ongoing acute rejection • DSA (especially against HLA II Ag ) • - ABO incompatibility with a donor • - non-HLA reactive Ab (MICA, anti-endothelial cell Ab, • anti-angiotensintype 1 receptor Ab) Dinavahii J AM Soc Nephrol 2011 WillicombeTransplantation 2012 Dragun Curr Opin Organ Transplant. 2012

  4. CHRONIC TRANSPLANT GLOMERULOPATHY Lesions that accompany TG: • PTCitis, • glomerulitis • C4d in PTCs • , Regele J AM Soc Nephrol 2002; Shimizu KI 2002; Aita Clin Transplant 2005; Gloor AJT 2007; Sis AJT 2007, Perkowska Trans Proc 2009 what about the morphology of the interstitium, tubules, arteries, arterioles?

  5. The retrospective study of: • 159 patients with TG and 85 recipients without TG, but with other chronic changes in the graft biopsy (IF/TA and/or chronic vascular lesions) • median observational time: 118 months (range 39-270 months) • median time from Tx to biopsy: 55 months (range 0.4-243 months) • F:102, M:142 • AIM: • to give a detailed morphological characteristics of TG • to search for potential impact of each of studied lesions on graft survival • Methods: • the analysis of clinical and histological (LM) data • including C4d deposition in PTCs and glomeruli (IHC on paraffin sections)

  6. Methods • Light microscopical evaluation based on Banff classification

  7. TG vsnon-TG cases

  8. Correlation between TG and other morphological lesions

  9. probability months graft survival in TG vs non-TG group Non-TG group TG group

  10. probability probability months Patients’ survival months non-TG group without graft loss TG group with graft loss

  11. TG group - graft survival

  12. TG group - graft survival

  13. TG C4d (+)vsTG C4d (-) • No significant difference inthe: • level of proteinuria, • - number of current transplantation, • number of HLA mismatches, • percentage of highly (>50%) immunized recipients, • level of immunosupression, • time interval between Tx and recognition of TG. • donor’s age and sex,

  14. TG C4d (+)vsTG C4d (-)

  15. CONCLUSIONS: TG vs non-TG group differ clinically • TG exerts a negative impact on both recipients’ and grafts’ survival • The earlier TG development is associated with worse prognosis as for the graft survival morphologically • TG is associated with a spectrum of both acute and chronic inflammatory as well as structural changes in glomeruli, tubules, arteries and arterioles. Among these lesions AS without elastica multiplication and glomerular thrombi are independent risk factors for the graft loss • PTC-itis, the presence of neutrophils in PTCs and PTCs’ dilatation are more common in C4d(+) TG cases

  16. CONCLUSIONS: Chronic VASCULAR lesions associated with TG • ARTERIOLAR SUBENDOTHELIAL SCLEROTIZATION • AND • ARTERIOLAR WALL SMCs HYPERTROPHY/HYPERPLASIA • - very few publications, • documented as a feature of thrombotic microangiopathies in native kidneys • (antiphospholipid syndrome,LN, • malignant hypertension, scleroderma,HUS) • Caetano Hypertension 2001 • Nochy J Am Soc Nephrol 1999 • Ruggenenti Am J Kidn Dis 1996

  17. CONCLUSIONS: Chronic VASCULAR lesions associated with TG • ARTERIOSCLEROSIS WITHOUT THE MULTIPLICATION OF ELASTIC LAMINA • (proliferative arteriopathy) • Characteristic for dynamic fibrotic tissue proliferation in the intima typical of inflammatory and thrombotic vasculopathies • in renal transplants: one study??? • Wieczorek AJT 2006 EXERTS NEGATIVE IMPACT ON GRAFT SURVIVAL

  18. CONCLUSIONS • TG is commonly associated with arterial and arteriolar lesions that share the same pathogenesis, evolve on the background of chronic endothelial injury, • most probable Ab-mediated and/or TMA related

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