Renal transplantation in patients with lupus nephritis - prof. Ayman Refaie
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This document discusses renal transplantation in patients with lupus nephritis. It begins with background on lupus nephritis as a cause of end-stage renal disease. It then covers the pre-transplant workup, including screening for cardiovascular disease, infections, and thrombophilia. The timing of transplantation is discussed, noting most centers recommend 3-6 months of dialysis. Recurrence of lupus nephritis after transplantation is evaluated, finding the rate is low at 2-9%. Outcomes are then reviewed, with graft and patient survival found to be similar to other causes of ESRD. In conclusion, kidney transplantation is a good option for lupus nephritis patients and offers better
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Renal transplantation in patients with lupus nephritis - prof. Ayman Refaie
- 1. 1 Ayman Refaie, MD Chief, Nephrology & Transplantation Unit Urology & Nephrology Center Mansoura-Egypt Renal Transplantation in Patients with Lupus Nephritis
- 2. Agenda Background: Lupus nephritis as a cause of ESRD Pre transplant work up Timing of transplantation Recurrence of LN after transplantation Outcome of LN after transplantation Conclusions
- 3. Agenda • Background: Lupus nephritis as a cause of ESRD • Pre transplant work up • Timing of transplantation • Recurrence of LN after transplantation • Outcome of LN after transplantation • Conclusions
- 5. SLE and Lupus Nephritis: stats The prevalence of SLE is 20 - 150 cases per 100,000 population. 30% to 60% of patients with SLE have renal involvement. 10% to 30% of those with lupus nephritis WHO class III and above will progress to ESRD within15 years from the time of diagnosis. Renal injury is the most important predictor of mortality in patients with SLE. Yap DY, et al. Nephrol Dial Transplant. 2012 Maroz N Am J Med Sci. 2013
- 6. Hesham Elsayed, Saudi J Kidney Dis Transpl 2012 Lupus nephritis as a cause of ESRD among Egyptian population
- 8. Hemodialysis Peritoneal dialysis Renal transplantation
- 9. Patient survival according to the treatment modality Kang SH, et al. The Korean Journal of Internal Medicine 2011 KT HD PD
- 10. Kang SH, et al. The Korean Journal of Internal Medicine 2011 KT HD PD P= 0.02 Patient survival according to the treatment modality
- 11. Kang SH, et al. The Korean Journal of Internal Medicine 2011 KT HD PD NS P= 0.02 Patient survival according to the treatment modality
- 12. Agenda • Background: Lupus nephritis as a cause of ESRD • Pre transplant work up • Timing of transplantation • Recurrence of LN after transplantation • Outcome of LN after transplantation • Conclusions
- 13. SLE candidates for transplantation: special considerations Cardiovascular disease Infections Vascular thrombosis (antiphospholipid Abs) Avascular bone necrosis
- 14. Pre transplant work up: special screening Careful clinical and serological assessment Proper evaluation for coronary artery disease Thrombophilia screen Careful interpretation of Cross match
- 15. Thrombophilia screen in renal transplant candidates with SLE Antiphospholipid antibodies • Lupus anticoagulant • Anticardiolipin antibodies Other hemostatic markers of coagulation • Protein C • Protein S • Anti thrombin III • Factor IV Leiden (History of vascular thrombosis, vascular access closure, spontaneous abortion or preterm delivery)
- 16. The Nightmare
- 17. Barbour et al, Nephrology 19 (2014) 177–185 Antiphospholipid syndrome in renal transplantation: the nightmare
- 18. Anticoagulation protocol of recipients with antiphospholipid antibody syndrome in perioperative periods Choi et al. Medicine (2016) 95:46
- 19. Lupus nephritis posing clinical dilemma in cross-matching • CDC cross match may be false positive if antibodies of auto-immune diseases i.e., SLE, may cause cell lysis. Careful interpretation • Auto-cross-match using recipient’s lymphocytes and serum. • Solid Phase Flow Cytometry Cross-Match (FCXM)
- 20. JOJ Urology & Nephrology, 2017
- 21. Agenda • Background: Lupus nephritis as a cause of ESRD • Pre transplant work up • Timing of transplantation • Recurrence of LN after transplantation • Outcome of LN after transplantation • Conclusions
- 22. Timing of transplantation for LN In most SLE patients that end up on dialysis, a "burn- out" of disease activity is observed. Sometimes disease activity may persist on dialysis. Many centers recommend 3-6 months of dialysis prior to transplantation to reduce disease activity. Both "burn-out" and survival appear to be similar in SLE patients, who are treated with hemodialysis and peritoneal dialysis.
- 23. Arthritis Care & Research, 2015
- 24. Time to graft failure among patients with ESRD attributed to lupus nephritis ALL African-American White Plantinga et al, Arthritis Care & Research, 2015
- 25. Agenda • Background: Lupus nephritis as a cause of ESRD • Timing of transplantation • Pre transplant work up • Recurrence of LN after transplantation • Outcome of LN after transplantation • Conclusions
- 26. Recurrent Lupus Nephritis Rate of recurrent LN is low ( 2 - 9%)
- 27. NATURE CLINICAL PRACTICE NEPHROLOGY
- 29. Clinical characteristics of patients with and without recurrent LN ÇELTİK et al, Nephrology 21 (2016) 601–607
- 30. Risk factors for recurrent LN • Female gender • Younger age (< 33 years) • African American ethnicity • Antiphospholipid autoantibodies
- 31. Diagnosis of RLN • New onset proteinuria or glomerular hematuria • Rapid worsening of previously existing proteinuria • Graft biopsy (LM, IF, EM) • Serology ?
- 32. Treatment of RLN • Do we need further to change immunosuppression regimen? • Usually, NO • Severe proliferative lesions (Steroid … cyclophosphamide … rituximab) ?
- 33. Agenda • Background: Lupus nephritis as a cause of ESRD • Timing of transplantation • Pre transplant work up • Recurrence of LN after transplantation • Outcome of LN after transplantation • Conclusions
- 34. Berden JHM. Kidney Int. 1997;52:538-558
- 36. 1963 - 2012 LN: 744 / 64,160 (1.2%) SLE recipients: 354 (48%) Kidney International, 2016 Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry
- 37. Survival curves for lupus nephritis ESRD and other causes of ESRD in patients on dialysis L Zhang et al. Kidney International (2016) 89, 1337–1345 P = 0.001
- 38. Overall first renal allograft survival curves L Zhang et al. Kidney International (2016) 89, 1337–1345 P = 0.32
- 39. Death-censored first renal allograft survival curves for lupus nephritis ESRD and other causes of ESRD in patients undergoing renal transplantation L Zhang et al. Kidney International (2016) 89, 1337–1345 P = 0.83
- 40. Lupus, 2017 SLE Recipients: 65
- 42. Patient and Graft survival Lupus (2017) 26, 1157–1165
- 44. p= 0.17)
- 45. BioMed Research International, 2014 SLE recipients: 40
- 46. Graft survival rates at 1, 5, and 10 years Cairoli etal, Biomed Res Int, 2014
- 47. Urology & Nephrology Center, Mansoura Thank You Mansoura Experience
- 48. 1976 - 2013 SLE recipients: 23 Controls: 46 (Age, Sex & Tx duration) 2016
- 49. Kidney transplantation in SLE patients: Mansoura UNC Follow up: 15 years • Graft artery or vein thrombosis: 0 • Immunosuppressive protocols: standard • Acute rejection episodes: comparable • Graft function: comparable
- 50. Kidney transplantation in SLE patients: Mansoura UNC Patient & Graft survival (10 years)
- 51. Agenda • Background: Lupus nephritis as a cause of ESRD • Timing of transplantation • Pre transplant work up • Recurrence of LN after transplantation • Impact on patient & graft survival • Conclusions
- 52. Conclusions • kidney transplantation is a good option for patients with ESRD due to LN and offers better survival and lower complication rates than HD and PD. • Graft survival rates at 5 and 10 years in patients with lupus are similar to those in patients with other diseases. • The risk of recurrence is much lower (2- 9%) if compared with other glomerular diseases.
- 53. Conclusions • RLN is not infrequent when patients are evaluated by both protocol and indication biopsies assessed by LM and IF. However, majority of patients do not progress to graft failure. • Measurement of serologic marker such as titers of DNA and complement levels do not help predict disease recurrence. • Thrombophilia screen is recommended in renal transplant candidates with SLE. • Anticoagulation is indicated in recipients with antiphospholipid antibodies.
- 54. Submit your next article to JESNT
- 55. JESNT (2016 & 2017)
Editor's Notes
- In my presentation I will try to cover topics related to renal transplantation for ESRD secondary to LN, and address unique factors that need to be emphasized in this patient population.
- In my presentation I will try to cover topics related to renal transplantation for ESRD secondary to LN, and address unique factors that need to be emphasized in this patient population.
- systemic lupus erythematous is a clinically heterogeneous autoimmune disease that can involve multiple systems, including the skin, joints, heart, lungs, blood, kidneys and, in the most severe cases, the brain.
- .
- Patient survival was higher in the KT group than in the HD group but no significant difference was observed between the HD group and the PD group
- Patient survival was higher in the KT group than in the HD group (p = 0.029, tested by log rank test), but no significant difference was observed between the HD group and the PD group
- Patient survival was higher in the KT group than in the HD group (p = 0.029, tested by log rank test), but no significant difference was observed between the HD group and the PD group
- In my presentation I will try to cover topics related to renal transplantation for ESRD secondary to LN, and address unique factors that need to be emphasized in this patient population.
- A major issue for SLE candidates for transplantation may be the presence of extrarenal complications related either to the disease itself or to previous steroid and/or immunosuppressive therapy. Cardiovascular disease frequently occurs in SLE patients and represents a leading cause of morbidity and mortality Infections are more frequent and severe in SLE patients, particularly in those who have received long term and/or vigorous immunosuppression before transplantation, and also represent the major cause of death especially in children. History of antiphospholipid antibody syndrome (APAS), or solely the presence of these antibodies in SLE patients, increase the risk of graft or other vascular thrombosis. Pretransplant and post-transplant corticosteroid therapy may further exacerbate cardiovascular complications, as well as produce severe osteoporosis and avascular bone necrosis.
- Antiphospholipid syndrome (APS) may occur in isolation or in association with systemic lupus erythematosus (SLE), with the potential to cause renal failure via several distinct pathologies. Renal transplantation in the presence of APS carries a risk of early graft loss from arterial or venous thrombosis, or thrombotic microangiopathy (TMA).
- Transplant renal biopsy on postoperative day 6. Silver Masson trichrome stain shows heterogeneity of glomerular lesions due to recurrent antiphospholipid syndrome. (A) Unaffected glomerulus with patent arterioles. (B) Microthrombi within capillary loops. (C) Ischaemia resulting from afferent arteriolar thrombosis, with wrinkling and retraction of capillary loops. (D) Congestion resulting from efferent arteriolar thrombosis (seen at vascular pole).
- One of the recommended protocols is to change anticoagulation from warfarin to i.v. heparin before surgery and to be maintained until postoperative 4 to 5 day
- And Dr Mohasen el kosi and dr ahmed halawa addressed this issue in an elegant way in this article that was published last year
- …….. and to evaluate a possible recovery of renal function. However, these recommendations are not standardized, and several investigators examined whether duration of time to transplant was associated with risk of graft failure among US LN-ESRD patients. With the exception of these cases, patients should receive renal transplantation as soon as possible, as there is now convincing evidence that the longer the time on dialysis the worse the results, the most successful strategy being represented by a preemptive transplantation
- It was recommend that waiting to transplant patients with ESRD secondary to LN, to allow for quiescence of SLE–related immune activity. However, these recommendations are not standardized, and several investigators examined whether duration of time to transplant was associated with risk of graft failure among US LN-ESRD patients.
- Kaplan-Meier analyses by categorized time to transplant, LN-ESRD patients whose wait time to transplant was <3 months had longer times to graft failure than those whose wait times were >3 months. Race-stratified analyses suggested that this overall pattern held among whites, but not among African Americans.
- In my presentation I will try to cover topics related to renal transplantation for ESRD secondary to LN, and address unique factors that need to be emphasized in this patient population.
- RLN is not infrequent when patients are evaluated by both protocol and indication biopsies assessed by LM and IF. However, majority of patients do not progress to graft failure
- This study examined indication and protocol biopsies in patients with renal failure due to lupus nephritis undergoing kidney transplantation. Out of twelve cases there were two with subclinical recurrence and four with clinical recurrence of their lupus nephritis in the renal transplant.
- -new onset proteinuria or glomerular hematuria should raise the suspicion of RLN. Also, rapid worsening of previously existing proteinuria should also raise the suspicion for RLN, especially with the coexistence of glomerular hematuria -Diagnosis of RLN is made by biopsy and histopathologic evaluation by light microscopy, immunofluorescence and electron microscopy -Measurement of serologic parameters, such as complement levels and titers of anti-double stranded DNA antibodies is not helpful in establishing the diagnosis in the allograft[
- Kidney transplant recipients with recurrent lupus usually do not require any change in the immunosuppressive regimen, as they already receive maintenance therapy for the transplant. Standard immunosuppression with CNIs, MMF and prednisone seems to protect against clinically overt recurrent disease. Severe proliferative lesions in the graft biopsy requires the existing immunosuppressive regimen to be modified. There is not sufficient data to support the use of these agents in RLN, this approach is based upon studies of patients with lupus nephritis involving the native kidney
- In my presentation I will try to cover topics related to renal transplantation for ESRD secondary to LN, and address unique factors that need to be emphasized in this patient population.
- In a retrospective study, the cumulative survival of 165 patients with SLE who underwent kidney transplantation was compared with survival of 21,726 transplant recipients who did not have SLE. Of note, after adjusting for age, patient and renal allograft survival rates in patients with SLE were comparable to rates in the non-SLE population
- Between1963 and 2012, 64,160 individuals started renal replacement therapy (RRT) for ESKD. Of these, 744 individuals (1.2%) had ESKD secondary to lupus Nephritis. 358 (48%) lupus nephritis patients received 404 renal allografts.
- Lupus nephritis was independently associated with higher mortality during dialysis treatment and accordingly patients with lupus nephritis had worse dialysis patient survival
- Overall renal allograft survival rates for the first renal transplant in lupus nephritis patients were similar to those of patients with ESKD due to other causes.
- lupus nephritis was not associated with death censored renal allograft survival
- Both patient and graft survivals after one, three and five years were comparable among lupus nephritis, polycystic kidney disease and diabetes nephropathy with no significant differences.
- Moreover, the glomerular filtration rate was evaluated after one month, six months, one year, and three years as well as after a final registered follow-up, showing non-significant differences among the three groups