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Focal Segmental Glomerulosclerosis (FSGS) and the Kidney Transplant Patient

Focal Segmental Glomerulosclerosis (FSGS) and the Kidney Transplant Patient. Cathleen E. Bailey-Vega RN, BSN, CCTC Margaret White RN, BSN, CCTC Ochsner Transplant Center. Causes of ESRD (USRDS per million). Diabetes Mellitus 149 Hypertension 90 Glomerulonephritis 28 Cystic Kidney 8

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Focal Segmental Glomerulosclerosis (FSGS) and the Kidney Transplant Patient

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  1. Focal Segmental Glomerulosclerosis (FSGS)and the Kidney Transplant Patient Cathleen E. Bailey-Vega RN, BSN, CCTC Margaret White RN, BSN, CCTC Ochsner Transplant Center

  2. Causes of ESRD (USRDS per million) Diabetes Mellitus 149 Hypertension 90 Glomerulonephritis 28 Cystic Kidney 8 Other 38 Unknown 14 Missing Disease 5

  3. Focal Segmental Glomerulosclerosis Initially described in 1972 Zimmerman et al induced proteinuria in rats injected with serum from a patient with recurrent FSGS Dantal et al treated patients with recurrent FSGS with protein A immunoadsorption and demonstrated that the material eluted from the protein A column induced proteinuria when injected in rats

  4. Permeability Factor (100% foot process effacement) Idiopathic Autoimmune (T-cell response) Toxins Genetic Abnormalities Infections (HIV, Parvo B-19) Obesicity Heroin Nephropathy Familial Disease Drug Toxicity (pamidronate) Classifications of FSGS: Primary vs. Secondary

  5. Diagnosis • Blood Chemistries • Urinalysis • 24 hour urine for creatinine and protein • Urine for protein/creatinine ratio • Renal Biopsy • Thorough history distinguish rate of onset and symptomatology

  6. Acute on set of nephrotic syndrome Peripheral edema Hypoalbuminemia Nephrotic Range proteinuria HTN Microscopic hematuria Non-nephrotic proteinuria Renal insufficiency Focal sclerosis Hypertrophy Hyperfiltration Renal scarring Symptoms of FSGS: Primary vs. Secondary

  7. Histologic Variants • To make the histologic Dx of FSGS the perihilar, cellular, tip and collapsing variants must be excluded. • Light and Electron microscopy is necessary for accurate Dx. • Light will show mesangial collapse and sclerosis. • Electron will show diffuse fusion of the epithelial cell foot process.

  8. Podocyte-Slit Diaphragm Complex

  9. Injury to visual epithelial cell orpodocyte, which attaches to the glomerular basement membrane by discrete foot process, appears to be the primary problem in most forms of FSGS Barrier to filtration is lost

  10. Prognostic Factors • No Nephrotic Syndrome-85% 10 yr survival • Nephrotic Syndrome- 60-90% 5 yr survival 30-55% 10 yr survival • Massive Proteinuria- progress to ESRD w/in 5 yrs • Interstitial Fibrosis- poor renal survival • Collapsing Variant- worse prognosis (HIV) • Glomerular Tip Lesion- More likely to respond to steroid therapy

  11. Corticosteroids, ACE inhibitors and ARB’s If steroid resistant may try immunosuppressant agents such as: Prograf, CYA, MMF or Rapa Lipid Lower Agents ACE and ARB’s Treat the cause ie:Obesity- wgt loss HIV-HAART, drug toxicity Race may affect response to steroid therapy. Treatment of FSGS: Primary vs. Secondary

  12. Transplant and FSGS Recurrence rate as high as 50% (80% after a re-transplant) Occurs early post-Tx ( Days to 6-12 months) White race is a new recognized risk factor (4) Rapid recurrence is BAD In pediatric patients the benefit of living donation is lost (3,4) Age less that 15 years Rapid clinical course Mesangial proliferation or prior recurrence (1,2) Recurrence is less frequent in blacks (1) Senggutuvan et al Pediatr Nephrol, 1990 (2) Tejani et al, JASN 1992 (3)Baum et al Kidney Int 2001, (4) Abbot et al, Am J Kidney Dis, 2001

  13. Clinical Presentation of FSGS Post Transplant • Rapid onset of proteinuria (1) • More frequent ARF (2) • More frequent rejection (2) • Graft loss is similar among living and cadaver donor recipients (3) • Living donation is not a contra-indication. They DO better • (1)Cheig et al, Kidney Int 1980, (2)Kim et al Kidney Int 1994, (3) Briganti et al N Engl J Med 2002

  14. Potential Treatments • Protein adsorption and plasmapheresis (1) • Plasmapheresis and cyclophosphamida (2) • Preoperative plasmapheresis plus cyclosporine (3) • Early plasmapheresis/ACEi, AIIRB’s (1) Dantal et al N Eng J Med, 1994, (2) Cheong et al Nephro Dial Transplant, 2000

  15. Focal segmental glomerulosclerosis (FSGS) Possible screening Bioassay for a yet-to-be isolated serum protein Possible prophylaxis Plasma exchange or adsorption Incidence 20–40% recurrence, 40–50% graft failure Rationale Although preliminary data suggest that some patients may have a serum protein that correlates with recurrent FSGS after transplantation, no standardized assays are available clinically. Some investigators have suggested that the risk for recurrent FSGS may be reduced with prophylactic plasma exchange. Recommendations (A) Candidates with FSGS should be warned that there is a 20–40% risk of recurrence, and that 40–50% with recurrence lose their grafts. However, the risk of recurrent FSGS need not preclude transplantation. (B) A prior history of graft loss from recurrent FSGS should be considered at least a relative contraindication to living donor transplantation, due to the likelihood of recurrence (up to 80%). (C) Assays for a serum factor to predict recurrent FSGS have not been standardized or validated for clinical practice. (D) There are not yet sufficient data for or against the use of prophylactic plasma exchange or other measures to prevent recurrent FSGS. AJT, 2001

  16. Case Studies on FSGS Post Kidney Transplant

  17. Case # 1 DG 56yo CFOrg DX: FSGS • Rec’d Cad 0antigen mismatch10/30/07 • Sl +Bcell CXM - thymo 100mg x6 d • Bx proven FSGS • Pre-op creat 9.7 on PD since 1/19/05 • Pre-op P/C ratio 6/07-3.64: 10/07 2.2 • Creat on pre-op 9.7 • Creat and P/C ratio decreased daily • Current: Creat 0.9 P/C 0.19 • 11/5/07 begun Diovan (ARB) • NO PLASMAPHERESIS

  18. Case # 2 BF 22yo WmOrg Dx: FSGS (collapsing variant) • massive protenuria treated with cytoxin, cyclosporine and steroids. • PD since 11/04 • LD TX 3/29/06 - CXM • Thymo 100mg x 4 , rapid steroid protocol. (off in 4 days.) • Pre-op P/C not done. Creat 15.0 • Pre-op biopsy 10/04 no segmental sclerosis, near 100% foot process effacement consistent with minimal change disease. • Biopsy 2/05 Collapsing variant of FSGS

  19. Post-Op Course • Kidney function decreased daily but slow • Pt developed peripheral and pulmonary edema .

  20. POD P/C creat Plasmaphesis Med TX • 1 0.9 8.7 N none • 2 2.64 5.0 Y none • 3 10.0 3. 7 Y Biopsy rec. FSGS • 4 11.5 3.4 Y none • 5 7.9 3.0 Y none • 6 9.75 2.5 Y Diovan (ARB) • 7 7.7 2.3 N no changes • 8 8.8 2.1 Y added Altace (ACE) D/C’d on POD 8

  21. Out pt Plasmapheresis M-W-F • 6 days from d/c P/C 1.32 creat 1.8 • 13 days from d/c P/C 1.52 creat 2.3 Plasmapheresis changed to 2x week • 21 days from d/c stopped plasmapheresis P/C 1.32 creat 1.8 • 7 day after stopping pheresis biopsy performed , foot process effacement 40-50% capillary loops with significant decrease from biopsy of 4/1/06 • Current P/C 0.07 creat 1.9 remains on Diovan

  22. Case # 3 TL 55yo Asian FOrg Dx: FSGS • Hemo since 12/04 • CAD kidney 4/21/07 • CXM – • Pre-op P/C 19.4 creat 8.1 • Pre-op Bx 12/03 FSGS 80% globally and segmentally sclerosed glomeruli, focally severe interstitial fibrosis and mod. vasc.sclerosis

  23. POD P/C Creat Plasmaphesis Med TX • 1 4.3 3.8 N none • 3 2.57 1.3 N Lisinopril (ACE) • 5 26.7 1.0 Y same • 6 21.3 1.0 Y Sol. 500mg x 3 biopsy mild cellular and vasc. Rej C4D stains neg. recurrent FSGS • 7 ND 1.5 Y same • 8 5.49 1.6 Y same • 9 7.69 1.6 Y same • 10 4.8 1.6 Y same • 11 4.9 1.4 N Diovan (ARB) • 12 3.7 1.3 N same • 13 2.5 1.4 N D/C’d same • Cur 0.28 0.9 N Diovan /Lisinopril

  24. Case # 4 BR 46yo WMOrg Dx FSGS • Pre-dialysis • Ld transplant 10/15/07 • CXM – • Pre-op P/C 2.83 creat 3.9 • Pre-op biopsy 6/03 changes suggestive of focal and segmental glomeralosclorosis , sub acute and chronic tubulo-interstital nephritis

  25. POD P/C Creat Plasmaphesis Med TX • 1 1.4 2.4 N none • 2 2.79 1.7 N none • 3 3.54 1.4 Y none • 4 3.31 1.3 N biopsy ATN and recurrent FSGS 60% foot process effacement • 5 1.9 1.4 Y none • 6 1.89 1.4 N none • 7 0.49 1.7 Y none • 8 1.21 1.4 Y none • 9 0.45 1.6 N D/C’d none

  26. NO Diovan 2* creatine fluctuations • POD 15 P/C 0.58 creat 2.0 Biopsy + Acute cellular rejection treated with solumedrol 500mg x 3 days. • No further Plasmapheresis • Current P/C 0.08 creat 1.6

  27. Case # 5 LC 61yo CFOrg Dx FSGS • Hemo 9/22/05 • LD with Bil Neph 2* protienuria 8/28/06 • Pre-op creat 5.2 no P/C ratio’s • Creat dropped daily D/C’d POD 4 creat 1.4 • POD 5 readmitted decrease Phos and dehydration D/c’d on POD 8

  28. POD P/C Creat Plasmaphesis Med TX • 9 3.71 2.1 N readmitted • 10 3.0 2.0 N Bx vasc rejection FSGS • 11 3.24 2.0 Y sol 200/ thymo 100 • 12 24* urine pro 2137 creat 2.0 sol/thymo • 13 ND 2.3 N thymo 100 • 14 2.08 2.1 N No thymo • 15 3.8 1.9 N thymo 100 • 16 ND 1.7 N No thymo • 17 3.3 1.8 Y thymo 100 • 18 3.2 1.6 Y No thymo Diovan • 19 3.3 1.5 Y thymo 100 • 20 2.6 1.5 N No thymo

  29. POD P/C Creat Plasmaphesis Med TX • 21 ND 1.5 Y thymo 100 • 22 3.77 1.4 Y No thymo • 23 ND 1.4 Y No thymo • 24 1.56 1.5 D/C’d continue plasma pheresis 3x week Stopped Pod 30. 1.3 2.2 • POD 31 biopsy no ACR • Restarted PP on POD 34 3xweek. • P/C continues to increase runs 3.9-13.11 with intermittent pheresis Creat jumping around 1.8-2.6

  30. 9 weeks PO added Lisinopril • 10 weeks biopsy ACR Sol 400mg x3 days with new pred taper • Week 14 pheresis x 3 • Month 7 pheresis x 3 new pred taper 40 daily P/C 12.3 creat 1.3 • Month 9 Pheresis MWF P/C 14.4 creat 1.7 • Current P/C 10.7 creat 3.2 • Pt considering re-transplant.

  31. Conclusion • Candidates with FSGS should be warned that there is a 20–40% risk of recurrence, and that 40–50 with recurrence lose their grafts. However, the risk of recurrent FSGS need not preclude transplantation. • A prior history of graft loss from recurrent FSGS should be considered at least a relative contraindication to living donor transplantation, due to the likelihood of recurrence (up to 80%). • Assays for a serum factor to predict recurrent FSGS have not been standardized or validated for clinical practice. • There are not yet sufficient data for or against the use of prophylactic plasma exchange or other measures to prevent recurrent FSGS. AJT, 2001

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