Download Renal Allograft Dysfunction - Beth Israel Deaconess Medical Center

APPROACH TO RENAL ALLOGRAFT DYSFUNCTION
Allen Repp, M.D.
October 11, 2002
Description
 Renal allograft dysfunction is the most common complication of renal transplantation
 Risk factors for diminished allograft survival include prior cadaveric transplantation, evidence of
prior sensitization, higher degrees of HLA mismatch, donor ages <5 or >60, occurrence of
delayed graft function, allograft dysfunction at discharge from transplantation, and episodes of
acute rejection
 1 year survival of 1st allograft is approximately 86% for cadaveric and 92% for living-related
(although there is consider variability between transplant centers)
 Time after transplantation provides the framework for consideration of the causes of allograft
dysfunction, since the prevailing causes vary with the time after transplantation.
Immediate Post-Transplantation (1 week)
 Delayed graft function (DGF) represents renal failure persisting after transplantation and is
usually defined as oliguria or requirement for dialysis in the first week of transplantation
 Major Causes:
 Post-ischemic acute tubular necrosis (ATN) = most common cause of delayed graft
function
 Risk factors: cold ischemia time > 24 hours with cyclosporine induction, prior
sensitization, and use of bioincompatible membranes and/or ultrafiltration within 24 hours
of transplant
 Biopsy: sloughed and swollen tubular epithelial cells with scalloping of epithelial cells
 Hyperacute rejection = rare, and usually avoidable cause of immediate allograft dysfunction
 Often diagnosed intra-operatively when the transplant kidney becomes mottled and
cyanotic, with absence of blood flow on Doppler
 Usually caused by unrecognized ABO incompatibility or anti-HLA class I antibodies
(positive T cell cross match)
 Biopsy: intrarenal coagulopathy with thrombi of small arteries and glomeruli, and renal
cortical necrosis
 Accelerated rejection = episode of rejection occurring 2-5 days post-transplant
 Can occur with or without delayed graft function
 Attributed to prior sensitization to donor antigens or by anti-HLA class II antibodies
(positive B cell mismatch)
 Biopsy: cellular rejection with interstitial infiltrate with mononuclear cells and eosinophils
and disruption of basement membrane by infiltrating cells, and/or vascular rejection with
capillary endothelial swelling, arteriolar fibrinoid necrosis, and fibrin thrombi in glomerular
capillaries
 Atheroembolic disease and thrombosis
 Atheroemboli can derive from donor’s aorta at time of organ procurement or from
recipients vascular system at time of transplantation
 Thrombosis can occur in setting of graft rejection (aka secondary thrombosis), or rarely in
the absence of rejection (aka primary thrombosis), associated with increased donor age,
longer cold ischemia time, presence of anti-phospholipid antibodies, and
hypersensitization
 Evaluation:
 Perform ultrasound to assess urinary leak or obstruction
 In high risk patients proceed to biopsy quickly (day 3-5) to evaluate for rejection
 In low risk patients proceed to biopsy on day 7-10
 Treatment is based on biopsy findings -- pulse dose methylprednisolone for predominantly
cellular rejection or OKT3 for predominantly vascular rejection
 If no evidence of rejection on initial biopsy but delayed graft function persists, repeat biopsy is
warranted
Beth Israel Deaconess Medical Center Residents’ Report
Early Post-Transplantation (1-12 Weeks)
 Initial allograft function followed by early renal insufficiency
 Major Causes:
 Acute rejection = most common cause of allograft dysfunction during the early posttransplant period
 Once occurred in 50-60% renal transplant patients, now estimated to occur in 15-25%
 Heralded by diminished urine output and increasing blood pressure
 Biopsy: similar to hyperacute rejection with attempts made to distinguish cellular rejection
from vascular rejection
 Cyclosporine or tacrolimus (FK506) toxicity
 Both of these calcineurin inhibitors are nephrotoxic through a variety of mechanisms and
can lead to oliguric ATN, HUS-like syndrome (rare), and chronic progressive renal dz
 Important to distinguish from acute rejection, as the management is obviously completely
different
 Urinary tract obstruction
 Prerenal azotemia secondary to volume depletion
 Infection – Polyoma virus (BK type) interstitial nephritis and CMV-mediated renal disease
 Recurrence of primary disease such as focal glomerulosclerosis, HUS-TTP, or anti-GBM
disease
 Drug induced acute interstitial nephritis
 Evaluation:
 Check UA for evidence of recurrent disease or infection
 Check plasma cyclosporine levels. If elevated (>150 ng/mL), decrease dose and re-evaluate
in 1-2 days
 Renal US to exclude obstruction or urinary leak
 Biopsy to evaluate for acute rejection. If rejection present, treat with corticosteroids
Late Acute Dysfunction (>12 weeks)
 Acute allograft dysfunction occurring more than 3 months post transplant
 Major Causes:
 Prerenal azotemia secondary to volume depletion
 Cyclosporine or tacrolimus toxicity
 Acute rejection (consider in the setting of decreasing immunosuppressive doses or medical
non-compliance)
 Urinary tract obstruction
 Recurrence of primary disease
 Renal artery stenosis (associated with HTN)
 Infections – CMV or human polyoma virus type BK associated interstitial nephritis
 Evaluation:
 Replete intravascular volume and repeat creatinine measurement
 Check plasma cyclosporine levels. If elevated (>150 ng/mL), decrease dose and re-evaluate
in 1-2 days
 Renal US to exclude obstruction or urinary leak
 Renal biopsy
Late Chronic Dysfunction
 Slowly progressive renal insufficiency over a period of months to years
 Major Causes:
 Chronic allograft nephropathy / chronic rejection
 Cyclosporine nephrotoxicity
 Hypertensive nephrosclerosis
 Infections – CMV and polyomavirus
 Recurrence of primary disease – e.g., focal glomerulosclerosis, membranoproliferative GN,
IgA nephropathy, diabetic nephropathy
 Evaluation:
 Often difficult to determine cause of chronic allograft dysfunction, even with biopsy
 No available treatment for chronic allograft nephropathy except for decreasing cyclosporine
dosage as indicated and controlling blood pressure
Beth Israel Deaconess Medical Center Residents’ Report