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Postoperative Course and Delayed Graft Function

CASE 34-1, QUESTION 5: G.P. is admitted to the transplant ward for initial post-transplantation

management. His urine output during the next 3 hours has decreased from 300 to 40 mL/hour. He is receiving

IV fluids at a rate equivalent to his urine output. He received 3 L of fluids in the operating room. His blood

pressure is 140/83 mm Hg, heart rate is 87 beats/minute, and temperature is 36.9°C; he has no signs of

dehydration. His BUN is 56 mg/dL and his SCr is 12.8 mg/dL. Another dose of furosemide 100 mg IV

increased his urine output to 140 mL/hour, but his urine output returned to less than 40 mL/hour in a few hours.

Fluids and IV furosemide were given again with similar results. Renal ultrasound indicates no urine leaks, fluid

collections, or ureteral obstruction. A diethylenetriamine penta-acetic acid renal scan indicates good perfusion,

but decreased accumulation and clearance. During the next 2 days, G.P.’s BP is 150/93 mm Hg, weight is 76

kg (4 kg higher than pretransplantation), urine output has fallen to less than 200 mL/day, and relevant laboratory

values are as follows:

BUN, 85 mg/dL

SCr, 13.2 mg/dL

K, 5.8 mEq/L

The decision is made to institute hemodialysis. What has happened to G.P.’s renal function? What is the most

likely diagnosis?

The initial renal function after kidney transplantation can reflect excellent,

moderate, or delayed graft function. In recipients with excellent function, a good

diuresis begins immediately and continues; the serum creatinine rapidly declines to

less than 2.5 mg/dL within the first few days after transplantation. Most living-related

transplants and between 30% and 50% of deceased donor transplants generally

experience this pattern. Kidney transplant recipients with moderate or slow graft

function usually experience a slower decline in serum creatinine, which stabilizes

within the first week. Recipients with delayed graft function usually have anuria or

oliguria, require dialysis in the early period, and take days to weeks to recover.

Delayed graft function is most common in recipients of organs from deceased

transplant donors, occurring in between 10% and 50% of cases.

29 The diagnosis of

delayed graft function is based on clinical, laboratory, and diagnostic criteria that

may vary among centers. Traditionally, delayed graft function has been defined as the

need for dialysis within the first 7 days post-transplant. Slow graft function is another

term that has been used to describe a lag in improvement and does not involve

dialysis. Delayed graft function is influenced by the donor (age, condition of organ,

prolonged ischemic time), intraoperative conditions (hypotension, fluid imbalance,

ischemia or reperfusion injury), and recipient characteristics such as prior

transplantation, postoperative hypovolemia or hypotension, and use of nephrotoxic

drugs.

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In G.P., poor urine output in the first hours after transplantation and subsequent

oliguria, the exclusion of other causes of acute tubular necrosis, the results of the

renal scan, the lack of improvement in BUN and serum creatinine, and the need for

dialysis are indicative of delayed graft function. Delayed graft function reduces

kidney long-term graft survival, increases the risk of acute rejection, and influences a

patient’s early management by requiring dialysis, increasing the length of hospital

stay, and increasing the costs of therapy. It also may make the assessment of acute

rejection more difficult because the patient already has impaired renal function. In

delayed graft function, a renal biopsy may be obtained if no improvement in serum

creatinine is seen by day 7.

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CASE 34-1, QUESTION 6: What adjustments should be made in G.P.’s immunosuppressive regimen at this

time? Are there any therapies that can prevent or treat delayed graft function?

The adverse renal effects of CNIs may contribute to the onset of delayed graft

function as well as prolong its duration. Therefore, tacrolimus may be discontinued

temporarily or its dose significantly reduced. Because of this effect, some protocols

do not include CNIs, use them only in low doses for the first week, or delay their use

until kidney function improves. These protocols often include antibodies and provide

more intense immunosuppression early after transplantation when the risk of delayed

graft function and acute rejection is highest. Rabbit antithymocyte globulin is

commonly used in patients with delayed graft function because it may shorten the

duration and the need for dialysis when compared with the CNI. Another potential

option would be to use basiliximab, which has been shown to reduce acute rejection

rates and extend the time to first rejection. One concern with the use of basiliximab is

that a CNI may be required sooner than with rabbit antithymocyte globulin because

this agent does not provide as long a duration of protection from rejection. One

should also confirm that MPA doses be maintained and continue prednisone taper. In

G.P., rabbit antithymocyte globulin would be administered for 5 to 10 days,

depending on improvement in his SCr and urine output, along with his current

regimen of prednisone and mycophenolate. A typical dose would be 1.5 mg/kg/day or

every other day, depending on his CD3

+

level, and WBC and platelet counts.

Tacrolimus will not be started until his SCr decreases.

Recent studies have focused developing therapies that prevent or reverse delayed

graft function, with mixed results. There are several therapies being tested within this

context, which include therapies to inhibit p53 (I5NP), complement (eculizumab),

TLR2 (OPN-305), and hepatocyte growth factor (BB3). Other therapies that have

been tested include alteplase, etanercept, ischemic preconditioning, erythropoietin,

and dopamine, with the later showing reduced dialysis requirements but none

demonstrating improved graft survival. As this is a common and important clinical

dilemma, it continues to be a significant area of research and discovery.

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