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Slide Seminar - II Pathology of Renal Transplant

Lorraine Racusen Prof. of Pathology Johns Hopkins Medical School Baltimore, MD. R.K. Gupta Prof & Head Department of Pathology SGPGIMS, Lucknow India. Slide Seminar - II Pathology of Renal Transplant. Slide Seminar- II Pathology of Renal Transplant L Racusen & RK Gupta.

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Slide Seminar - II Pathology of Renal Transplant

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  1. Lorraine Racusen Prof. of Pathology Johns Hopkins Medical School Baltimore, MD R.K. Gupta Prof & Head Department of Pathology SGPGIMS, Lucknow India Slide Seminar - IIPathology of Renal Transplant

  2. Slide Seminar- II Pathology of Renal TransplantL Racusen & RK Gupta • Case 1: 38 years male, 2 yrs post renal transplant biopsy • Case 2: 65 years female, 9 days post renal transplant biopsy • Case 3: 34 years female, 3.2 years post renal transplant with H/O UTI &… • Case 4: 58 yrs male, 6 month post-transplant with colonic perforation • Case 5: 31 Yrs male, 4 yrs post-transplant with duodenojejunal mass

  3. Slide Seminar- II: Pathology of Renal Transplant - Case 1 Case 1 • 38 year old man status post renal transplant 2-3 years before biopsy. • Original disease was Alport’s syndrome, complicated by hypertension. • Presented with palpitations, and was found to have a creatinine of 4.9 mg%. With hydration, his creatinine only fell to 4.1 mg%. • He was biopsied to rule out rejection and other processes in the allograft, and to assess for chronic changes. • There are a variety of processes in this allograft – please identify. • What is the prognosis in the short-term? The long-term? • What special concern is there in a transplant patient with this underlying disease?

  4. Slide Seminar- II: Pathology of Renal Transplant - Case 1

  5. Slide Seminar- II: Pathology of Renal Transplant - Case 1

  6. Slide Seminar- II: Pathology of Renal Transplant - Case 1

  7. Slide Seminar- II: Pathology of Renal Transplant - Case 1

  8. Slide Seminar- II: Pathology of Renal Transplant - Case 1

  9. Slide Seminar- II: Pathology of Renal Transplant - Case 1

  10. Slide Seminar- II: Pathology of Renal Transplant - Case 1

  11. Slide Seminar- II: Pathology of Renal Transplant - Case 1 Case 1 ? Diagnosis

  12. Slide Seminar- II: Pathology of Renal Transplant - Case 1 Case 1 Diagnosis • Acute vascular rejection, Banff Grade 2A, with severe tubulo-interstitial inflammation with C4d positivity

  13. Slide Seminar- II: Pathology of Renal Transplant - Case 1 Case 1 • The biopsy reveals acute rejection, with mild intimal arteritis (v1), Banff type 2A, with a severe tubulointerstitial component (i3, t3). Focal leukocyte margination is noted in glomeruli and peritubular capillaries, mononuclear with occasional neutrophils. Though difficult to assess, chronic changes are significant (ci2-3, ct2-3). • Immunofluorescence reveals diffuse though mild linear capillary staining for C4d – R/O anti-donor antibody. • The patient had been previously treated with OKT3, and had developed anti-OKT3 antibodies, so he was treated with thymoglobulin. There was poor response to therapy, and the patient returned to dialysis within months with a failed allograft.

  14. Slide Seminar- II: Pathology of Renal Transplant - Case 1 Case 1 • In the setting of Banff type 2 rejection, a severe tubulointerstitial component predicts relative resistance to treatment short-term; the same study also demonstrated worse outcome with type 2B than with type 2A rejection, reinforcing the importance of making this distinction on allograft biopsy. • The staining for C4d is diffuse, but only mild, with staining done on frozen tissue using the monoclonal antibody for C4d; the requirement for a positive reading using this technique is for strong staining, so this should be interpreted as below threshold. However, anti-donor antibody should be sought, to rule out an antibody-mediated component. The quite extensive chronic changes portend a poorer long-term (and in this case short-term!) outcome.

  15. Slide Seminar- II: Pathology of Renal Transplant - Case 1 Case 1 References: • Haas M, Kraus ES, Samaniego-Picota M, et al, Acute renal allograft rejection with intimal arteritis: histologic predictors of response to therapy and graft survival. Kidney Int 61:1516-26, 2002 • Racusen LC, Solez K, Colvin RB, et al, The Banff 97 working classification of renal allograft pathology. Kidney Int 55:713-723, 1999 • Racusen LC, Solez K, Colvin R. Fibrosis and atrophy in the renal allograft – Interim report and new directions. Am J Transplant 2:203-6, 2002 • Racusen LC, Halloran PF, Solez K. Banff 2003 meeting report: new diagnostic insights and standards. Am J Transplant 4:1562-6, 2004

  16. Slide Seminar- II: Pathology of Renal Transplant - Case 1 End of Case 1

  17. Slide Seminar- II: Pathology of Renal Transplant - Case 2 Case 2 • 65 year old female had a history of chronic interstitial nephritis and was on dialysis. • She received a living related renal transplant from her daughter 9 days prior to biopsy. • The patient has developed a rise in creatinine after improving function post-operatively. • A biopsy is performed to rule out rejection. What is you diagnosis? Indicate possible underlying etiologies.

  18. Slide Seminar- II: Pathology of Renal Transplant - Case 2

  19. Slide Seminar- II: Pathology of Renal Transplant - Case 2

  20. Slide Seminar- II: Pathology of Renal Transplant - Case 2

  21. Slide Seminar- II: Pathology of Renal Transplant - Case 2

  22. Slide Seminar- II: Pathology of Renal Transplant - Case 2

  23. Slide Seminar- II: Pathology of Renal Transplant - Case 2 Case 2 ? Diagnosis

  24. Slide Seminar- II: Pathology of Renal Transplant - Case 2 Case 2 Diagnosis • Acute vascular rejection, Banff Grade 2B, with no tubulo-interstitial inflammation • Extensive tubulo-toxic change

  25. Slide Seminar- II: Pathology of Renal Transplant - Case 2 Case 2 • The biopsy reveals acute rejection, vascular type, with moderate-to-severe intimal arteries (v2), Banff type 2B, with no significant tubulointerstitial component (i0, t0). • A total of 4 small arteries have intimal arteritis, of varying severity. • There is significant and extensive isometric vacuolization of tubular cells – R/O drug toxicity. • No chronic changes are seen. • There is minimal C4d staining in peritubular capillaries. • She was begun on steroids and thymoglobulin for the rejection; the dose of thymoglobulin had to be decreased due to pancytopenia. • Creatinine fell to 0.9 mg%, then stabilized at 1-1.3 mg%.

  26. Slide Seminar- II: Pathology of Renal Transplant - Case 2 Case 2 Reference: • Racusen LC, Solez K, Colvin RB, et al, The Banff 97 working classification of renal allograft pathology. Kidney Int 55:713-723, 1999

  27. Slide Seminar – I : Pathology of Glomerular Diseases - Case 2 End of Case 2

  28. Slide Seminar- II: Pathology of Renal Transplant - Case 3 Case 3 • 34 year old female S/P deceased donor renal transplant 3.2 years prior to biopsy. The cause of end-stage renal disease is unknown. • She now presents with a rise in creatnine from 1.9 to 2.9 mg%. She has multiple leukocytes in the urine, and history of recent urinary tract infection. • There is some concern that the patient has been non-compliant with her medications. Indicate your diagnosis/diagnoses.

  29. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  30. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  31. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  32. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  33. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  34. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  35. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  36. Slide Seminar- II: Pathology of Renal Transplant - Case 3 Case 3 ? Diagnosis

  37. Slide Seminar- II: Pathology of Renal Transplant - Case 3 Case 3 Diagnosis • Acute cellular rejection, Type IB, with focal acute pyelonephritis • Membranous glomerulonephritis

  38. Slide Seminar- II: Pathology of Renal Transplant - Case 3 Case 3 • The biopsy reveals acute cell-mediated rejection, moderate-to-severe tubulointerstitial type, Banff type IB, with focally severe tubulitis (t3). In addition, there was an area in the cortex with numerous peritubular and intratubular neutrophils, consistent with bacterial infection. In addition, glomeruli show mild increase in mesangial matrix, with very mild glomerulitis (g0-1). While difficult to assess, there appear to be mild-to-moderate chronic changes (ci1-2, ct1-2). • Immunofluorescence studies reveal no C4d staining in peritubular capillaries. However, there is diffuse granular capillary staining for IgG (2-3+), IgM (trace-1+), C3 (1+) and kappa and lambda light chains (2-3+), and C4d (2-3+). • Electron Microscopy reveals subepithelial dense deposits, confirming a diagnosis of early membranous glomerulopathy. Presumably this is a de novo disease, thought the cause of the patient’s end-stage renal disease is unclear. • Membranous glomerulopathy in the allograft may impinge on graft survival, but not invariably. • Pyelonephritis in grafts is not rare – if occurring within the first 3 months, it impacts on graft survival.

  39. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  40. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  41. Slide Seminar- II: Pathology of Renal Transplant - Case 3

  42. Slide Seminar- II: Pathology of Renal Transplant - Case 3 References: • Racusen LC, et al, Banff 97 (see above) • Denton MD, Singh AK. Recurrent and de novo glomerulonephritis in the renal allograft. Semin Nephrol 20:164-75. 2000 • Hariharan S. Long-term kidney transplant survival. Am J Kidney Dis 38:S44-50, 2001 • Seikaly MG. Recurrence of primary disease in children after renal transplantation. Ped Transplant 8:113, 2004 • Giral et al, Acute graft pyelonephrits and long-term kidney graft outcome. Kidney Int 61:1880, 2002

  43. Slide Seminar – I : Pathology of Glomerular Diseases - Case 1 End of Case 3

  44. Slide Seminar- II: Pathology of Renal Transplant - Case 4 Case 4 • 59 Yrs/ Male • Received live related renal allograft 6 months back • Had H/O cyclosporine toxicity and acute cellular rejection • Presented with facial swelling, raised S. creatinine, UTI and sinusitis • Cald well luck surgery performed • Post operative patient developed acute abdominal pain, • X-ray abdomen showed gas under diaphragm and a diagnosis of intestinal perforation was made • Exploratory laprotomy done and colonic perforation repaired • Tissue from maxillary sinus and Colonic resection margins for histopathology

  45. Slide Seminar- II: Pathology of Renal Transplant - Case 4

  46. Slide Seminar- II: Pathology of Renal Transplant - Case 4 Maxillary Sinus

  47. Slide Seminar- II: Pathology of Renal Transplant - Case 4 Maxillary Sinus

  48. Slide Seminar- II: Pathology of Renal Transplant - Case 4 Maxillary Sinus

  49. Slide Seminar- II: Pathology of Renal Transplant - Case 4 Colonic Biopsy

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