Renal Transplant Flashcards
Not a candidate if…
o Unresolved malignancy (require 5 years disease free)
o Severe peripheral vascular disease
o Life expectancy <5 years
o Areas of controversy: HIV, hepatitis, other end stage organ disease
o Non-compliance
Surgical complications of transplant
Arterial
Thrombosis
• Present: acute oliguria, both prerenal and intrarenal acute kidney dysfunction
Stenosis
• Presents with HT, compromised renal perfusion, RAAS activation
Venous
o Thrombosis
Urological o Obstruction: clot, lymphocele o Stenosis: donor issues, blood supply, infectious o Leak (rare)
Fluid collection o Hydronephrosis (may be from ureteral stricture)
List the phases of host response
Phase 1: Innate nonspecific inflammation
Phase 2: Antigen specific immunity
Phase 3: Tissue remodeling
Describe Phase 1
Immediate nonspecific inflammation Warm ischemia in donor • Goal < 30 min Cold ischemia (preservation) • Goal <18 hours Reperfusion injury (in recipient) • Similar to ATN • Due to cytokine release
Effects of ischemia on kidney:
• Ischemia targets tubular epithelial cells and endothelium → damages cytoskeleton → loss of brush border; sloughing into tubular lumen → casts, obstruction → reduced GFR → azotemia and delayed graft function
• Loss of brush border and cell polarity → sodium excretion reduced
• Ischemia activates complement and upregulates inflammatory receptors → vasoconstriction, platelet trapping, RBC and WBCs in vessel lumen, inflamed tissue → hypoxia in medulla
• Production of acute-phase cytokines (TNF-alpha, interferon-γ)
Timing: 0-72 hours
Outcome = delayed graft function; needs dialysis for 1st seven days
Describe Phase 2
Antigen specific immunity
o From reaction of recipient’s immune system to donor cells (involves lymphocytes, plasma cells)
o Timing: 0-10 days
o Presents: acute kidney dysfunction, Na+ excretion, mild proteinuria, sterile pyuria
o Outcome: acute rejection
o Requires immunosuppressive drugs
Describe Phase 3
Tissue remodeling -Involves: lymphocytes, plasma cells, fibroblasts, macrophages -Medicated by cytokines -Both antigen dependent and independent -Timing: months to years Outcome: chronic failure
List the types of rejection
Hyperacute
Acute: Ab-mediated and Cellular
Chronic
Hyperacute rejection
Occurs min-hours Mediators: preformed ab's against ABO or HLA molecules Incidence = rare Pathology: graft thrombosis Prevent: Cross-matching Therapy: avoid transplant
Acute rejection
Ab-mediated rejection (any time after transplant)
Mediated by memory ab’s
Incidence: less common
Pathology: vasculitis, C4d deposition in PERItubular capillaries
Prevention: avoid risk factors
Therapy: plasma exchange and IVIG
Cellular rejection (any time after transplant)
Mediated by activated T cells
Incidence: more common
Pathology = parenchymal injury: tubuloinerstitial inflitrate and edema, Vascular injury: transmural lymphocyte infiltrate
Prevention: tissue typing
Therapy: immunosuppression
Chronic rejection
Duration = months to years
Mediated by macrophages, T and B cells, fibroblasts
Incidence = universal
Pathology: accelerated graft arteriosclerosis and glomerulosclerosis (Due to smooth muscle proliferation and narrowing of lumen)
Prevention: immune AND Non0=-immune measures
Immune factors:
-poor HLA matching, previous sensitization
-delayed graft function
-suboptimal immunosuppression
-patient noncompliance
Result = episodes of subacute and acute rejection
NONimmune factors:
-older donor or poor graft quality
-brain-death, preservation, or ischemic injury
-HT
-hyperlipidemia
-chronic toxic effects of cyclosporine or tacrolimus
No real therapy
Describe Class I and II HLA
Class I HLA:
• On surface of all nucleated cells
• Interacts with cytotoxic CD8+ T cells
Class II HLA:
• On cell surface of antigen presenting cells and activated T cells
• Interacts with helper CD4+ cells
Recognize that immunosuppressants inhibit each of the three immune signals involved in transplant rejection.
1) TCR/CD3: Calcineurin signaling
o Inhibited by cyclosporine, Tacrolimus
2) CD28 costimulatory pathway
3) CD25 and IL-2 = mTOR pathway
o Inhibited by Sirolimus, Everolimus
Disease recurrence after transplant
- DM nephropathy: 100% but takes time
- MPGN: 60-100% depending on type
- FSGS: 30% and can be hard to control
- IgA: 30% but takes time
- HUS: 30% and can be severe
List the types of drugs used in transplant
Calcineurin inhibitors
Anti-proliferative
-Steroids
-Antibodies
Describe calcineurin inhibitors
Cyclosporine A:
-targets T cells
Tacrolimus:
-targets T and B cells
Complications from both:
- viral (CMV) and bacterial infections
- malignancies
- HT
- dyslipidemia
- diabetes
- renal scarring
