ESRD Transplantation Flashcards
- Recognize that the kidney transplantation is an important consideration for kidney replacement therapy and that it may be the therapy of choice for some patients.
diabetics get the biggest benefit, they also have the greatest mortality
adds survival of approx 10 years depending on recipients age and improves quality of life greatly (more energy, freedom)
- Describe the non immune and immune mechanisms of injury that contribute to the pathophysiology of kidney transplantation.
vascular or urinary blockage, reperfusion injury
acute rejection 3 signals
signal 1 antigen present cell from the recipient recognizes donor antigen (CNI)
signal 2 costimulator (anti proliferative)
signal 3 inflammatory cytokines (steroids, antibodies ie. IL-2 blocker)
side effects of try include dyslipidemia
- What are the important determinants of early and late kidney transplant function?
phase I: warm ischemia (in donor), cold ischemia (preservation) and reperfusion injury in recipient (ATN like)
phase II: Hyper acute (preformed Ab against) ABO or HLA (avoid trsnpt)
antibody-mediated: ie. vasculitis (plasma exchange +IVIG)
cellular: activated T-cells cause parenchymal injury, tissue mismatch (immunosuppression)
phase III: chronic immune and non-imune factors (macrophages, T and B cells, fibroplasia)
- Name three phases of response elicited by kidney transplants if the transplant acts as a source of foreign proteins.
phase I: innate inflammation (complement, cytokines, adhesion molecules) resulting in delayed graft function
phase II: Ag specific and cellular immunity (T cells, antibodies) resulting in acute rejection
phase III: tissue remodeling (lymph, plasma cells, fibroblasts, PMN)
- Recognize that immunosuppressants inhibit each of the three immune signals involved in transplant rejection.
calcinurin inhibitors (cyclosporin A, tacrolimus)
anti proliferative (azathioprine, mycophenolate, sirolimus, everolimus)
steroids (prednisone)
antibodies (IL-2 receptor blockers, thyomoglobin, alemtuzumab)
List factors that may preclude a candidate from renal transplant.
- unresolved malignancy
- severe peripheral vascular disease
- life expectancy <5y
- controversy (HIV, hepatitis, other end stage organ disease CAD, COPD etc)
- non-adherance
Contrast HLA-class I and II antigens.
class I present intra-cellular derived peptides (expressed on most cells) HLA-A,B and C
class II present extracellular derived peptides (expressed on B-cells, activated T-cells)
Discuss surgical complications of kidney transplant.
Arterial: thrombosis and stenosis
Venous: thrombosis
Urological/Fluid collection: obstruction (blood clot or lymphocele- hydronephrosis), stenosis, leak
When and how does tubulointerstital and vascular injury occur? (cell mediated)
(acute)
tubulointerstitial infiltrate and edema occur in acute cellular rejection due to infiltration by mononuclear cells and destruction of tubules leading to arteritis and necrosis
vascular injury manifests with transmural lymphocytic infiltrate
require biopsy to differentiate vascular or tissue damage
When and how does peritubular capillarities or glomerulitis occur? (antibody mediated)
antibodies are deposited in peritubular capillaries resulting complement activation (C4d metabolite) during the acute antibody mediated rejection
Is chronic rejection pathogenesis Ag dependent or independent? Characterize the type of injure in chronic rejection.
poorly understood but assumed to depend on BOTH Ag dependent and Ag independent mechanisms
characterized by fibrosis and chronic vascular injury; glomerular sclerosis and arteriosclerosis are signs of chronic rejection
Comment on the likelihood of recurrence in the following diseases: DM nephrophaty MPGN FSGS IgA HUS
DM (100%) takes time to develop
MPGN (90-100%) depending on type
FSGS (30%) and it can be hard to control
IgA (25%) but it may take longer than the life of the graph
HUS (30%) and can be severe although treatable
