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FACTORS TO BE CONSIDERED

  • What are the identifiable causes of allograft failure?

  • Is the patient going to outlive the failing allograft?

  • Is the patient retransplantable?

  • Is there a reason to interrupt immunosuppression?

  • How to modify immunosuppression

  • How to preserve remaining allograft function

  • Management of end-stage renal disease (ESRD) in prior kidney recipient

  • Preparing for a retransplant

  • Retransplantation and follow-up care

CAUSES OF FAILING RENAL ALLOGRAFT

  • Who are the innocent bystanders? Who is at fault here?

  • Is it the kidney? Is it the recipient? Is it the medical team?

  • Is it just an unavoidable outcome?

FAILING ALLOGRAFT: IMMUNOLOGICAL CONSIDERATIONS

  • Chronic rejection

  • Antibody-mediated rejection

  • High immunological risk transplant

  • Human leukocyte antigen (HLA) mismatch

  • Suboptimal immunosuppression

  • Suboptimal adherence to treatment

  • Sensitized recipient

RECIPIENT OF A SUBOPTIMALLY FUNCTIONING KIDNEY

  • Injury during organ recovery

  • Prolonged ischemia time

  • Loss of renal parenchyma due to small accessory vessels

  • Preexisting diseases in donor kidney

  • Significant donor–recipient age and size mismatch

  • Mechanical-vascular/urological issues

  • Suboptimal surgical techniques

  • Genetically destined to fail faster (ApoL1)

FAILING ALLOGRAFT: INFECTIONS

  • Recurrent urinary infections, BK virus (BKV), adenovirus

  • Recurrence of kidney disease: focal segmental glomerulosclerosis (FSGS), IgA, lupus, hemolytic uremic syndrome (HUS), oxalosis

  • Intentional reduction in immunosuppression

  • BKV, cytomegalovirus (CMV)

  • Posttransplant lymphoproliferative disorder (PTLD)

  • Malignancy

  • Major/recurrent/opportunistic infections

OUTCOME FOLLOWING FAILED RENAL ALLOGRAFT

  • Successful transplantation tries to achieve improved longevity and quality of life

  • Causes of mortality following failed renal allograft:

    • Cardiac (36%)

    • Infectious (17%)

ALLOGRAFT NEPHRECTOMY, CESSATION OF IMMUNOSUPPRESSION, AND IMMEDIATE DIALYSIS INITIATION

  • Primary nonfunction

  • Early allograft failure

  • Vascular event: arterial or venous thrombosis

  • Hyper-acute rejection

  • Early refractory acute rejection

  • Prevents graft rupture and hemorrhage

ALLOGRAFT PRESERVATION, CONTINUATION OF IMMUNOSUPPRESSION, AND DELAYED DIALYSIS INITIATION

  • Allograft loss more than 1–2 years after transplant:

    • Preserve residual allograft function: survival advantage1

    • Prevents graft intolerance syndrome/inflammatory state

    • Minimizes allosensitization

ALLOGRAFT PRESERVATION: CONTINUATION OF IMMUNOSUPPRESSION

  • Prevents reactivation of autoimmune diseases: irritable bowel disease (IBD), systemic lupus erythematosus (SLE), vasculitides

  • Cardiovascular, infectious, metabolic complications

  • Increased risk of cancers: skin, non-Hodgkin lymphoma (NHL), and Kaposi

ALLOGRAFT FUNCTION PRESERVATION: STRATEGIES

  • Optimization of immunosuppression

  • Calcineurin inhibitor (CNI) minimization

  • Costimulatory blockade

  • Managing chronic antibody-mediated rejection (AMR)

  • Ensuring vascular adequacy

  • Managing cardiovascular (CV) and chronic kidney disease (CKD) risk factors: diabetes mellitus (DM), hypertension (HTN), hypersensitivity lung disease (HLD)

  • Optimizing bladder function

  • Nutrition, sleep, exercise, body weight

  • Avoiding nephrotoxic agents: nonsteroidal anti-inflammatory drugs (NSAIDs), tobacco, cocaine, contrast media

ALLOGRAFT NEPHRECTOMY

  • Early allograft loss (<12 months): twice as likely to undergo allograft nephrectomy in United States Renal Data System (USRDS) cohort2

  • Fourfold likely to have nephrectomy in ...

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