EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Here, we present a case of a deceased-donor kidney transplant. The brain-dead donor had received a massive blood transfusion during cardiopulmonary bypass, which lead to hemolysis, hemoglobinuria, acute kidney injury, and renal replacement therapy. The kidney appeared red after in situ flush. Postoperatively, the recipient developed delayed graft function. Protocol biopsy during the postoperative period revealed the widespread deposition of heme pigment in the renal tubules. Massive blood transfusion and cardiopulmonary bypass surgery are associated with hemolysis and heme pigment deposition in the renal tubules, which subsequently lead to acute kidney injury. Kidneys from such donors appear red and, while this does not preclude transplant, are likely to develop delayed graft function.

Key words : Delayed graft function, Heme pigment, Massive blood transfusion

A 26-year-old male patient received a kidney transplant from a brain-stem dead donor. The recipient had end-stage renal failure secondary to obstructive nephropathy and recurrent pyelo-nephritis. He had been receiving peritoneal dialysis for 18 months before transplant. The kidney was obtained from a 21-year-old male brain-stem dead donor with no significant past medical history. The donor was involved in a traffic accident, had a bilateral massive hemopneumothorax, and required transection of the thoracic aorta. The donor underwent surgery to repair the transected aorta and was placed on cardiopulmonary bypass for 3 hours and 48 minutes, during which he was also transfused with 49 units of packed red blood cells.

After surgery, the donor became progressively oliguric, and ultimately required renal replacement therapy, which consisted of continuous venovenous hemofiltration for 24 hours before procurement. Subsequently, the donor was declared brain dead because of unrecoverable intracranial injuries that were sustained at the time of the accident. The donor’s family consented to donate the kidney for transplant. The liver and kidneys were procured for transplant 3 days after admission and initial surgery and 6 hours and 51 minutes after brain-stem death was declared. Donor serum creatinine on admission was 96 μmol/L, and creatine kinase was 10.47 μkat/L. At the time of donation, the donor was anuric, maintained on continuous venovenous hemo-filtration, and serum creatinine was 676 μmol/L. Both kidneys appeared red or ruddy despite effective in situ and back table flushing (Figure 1A). The recipient received the left kidney, which had a normal anatomy. Human leukocyte antigen mismatches included 1A, 2B, and 0DR. Both the donor and the recipient were cytomegalovirus-negative. The complexion of the kidney remained unchanged despite being back table flushing. The kidney was preserved in cold storage. Standard right iliac fossa extraperitoneal transplant was performed with vascular anastomoses to the external iliac vessels. Surgery was uncomplicated and included a warm ischemia time of 29 minutes and cold ischemia time of 14 hours and 34 minutes. After reperfusion, the kidney was unusually dark red and ruddy despite satisfactory in- and outflow (Figure 1B). The recipient received 30 mg alemtuzumab and 500 mg methylprednisolone at induction, followed by tacrolimus monotherapy immunosuppression with target trough levels of 9 to 14 ng/mL.

After transplant, the recipient was admitted to the intensive care unit to receive 24 hours of invasive ventilation due to type I respiratory failure caused by hospital-acquired pneumonia. The recipient’s serum creatinine was 575 μmol/L before transplant and a peak serum creatinine concentration of 760 μmol/L was measured on postoperative day 5, though peritoneal dialysis was not required. Allograft function slowly improved after postoperative day 5, and serum creatinine plateaued at 440 μmol/L by discharge from the hospital on day 19. Color Doppler ultrasound performed during the postoperative period showed a normal transplant kidney with patent vessels, good perfusion, and no evidence of hydronephrosis or perirenal collection. The resistive index was 0.71 to 0.74. Protocol kidney transplant biopsy on postoperative day 5 showed widespread severe acute tubular injury with many tubules, including luminal occlusion by red-pigmented granular casts (Figure 2). There was no evidence of glomerular thrombi.

The patient was discharged from the hospital on day 19. Graft function was slowly improving, and the patient was dialysis-independent. After discharge, serum creatinine continued to improve. Serum creatinine was 169 μmol/L at 1-year posttransplant, and the patient was still dialysis-independent. The paired right kidney was transplanted at another center and postoperatively developed delayed graft function (DGF) (defined as the number of days required to achieve a creatinine clearance > 10 mL/min, or the need for dialysis within the first 7 days after surgery) that required dialysis for 16 days after surgery. However, at 1-year posttransplant, the kidney is functioning well, and the patient has a serum creatinine concentration of 112 μmol/L and estimated glomerular filtration rate of 47 mL/minute/1.73m². The liver also was transplanted at another center and is functioning well.

Delayed graft function after a renal transplant is a well-recognized condition and affected by several donor and recipient factors.1 Young adults who have sustained trauma are a diminishing source of deceased donor grafts because of improved road safety in the United Kingdom and Europe (56% in 1992 vs 6% in 2013).² These donors often have multiple injuries and receive multiple blood transfusions. Trauma in combination with associated major thoracic vessel disruption is usually instantly fatal. In our case, the donor was successfully resuscitated and underwent surgery to repair aortic disruption. He was placed on cardiopulmonary bypass and received massive blood transfusion. During this process, he sustained acute kidney injury and required renal replacement therapy. Cardio-pulmonary bypass is a known cause of significant intravascular hemolysis, and several studies report the increase in plasma-free hemoglobin.^3-5 In addition to collection, the processing and storing of packed red blood cells is a known cause of hemolysis, although to a much lesser extent,^6-7 and is exaggerated when used in conjunction with cardiopulmonary bypass.

The association between hemoglobinuria and acute kidney injury is well established. Hemoglobin is broken down into heme pigment and globin when released from lysed erythrocytes, and the latter is subsequently broken down into amino acids. The nonproteinaceous heme pigment is believed to injure the kidneys in 3 ways: by causing tubular obstruction; by directly injuring the proximal tubular cells; and by inducing vasoconstriction, thereby reducing blood flow within the outer medulla.^{8 12} Persistent severe hemoglobinuria can lead to the significant deposition of heme pigment in the proximal tubule, thereby leading to acute renal failure.¹³ It is likely that the ruddy discoloration of the kidney was caused by the excessive deposition of heme pigment. Because of the donor’s history of cardiopulmonary bypass and massive transfusion, the ruddy appearance of the kidney most likely represents the tubular deposition of hemoglobinuric casts. Although the donor creatine kinase level was moderately elevated, this is consistent with a traumatic cause of death and, given the characteristic red pigment of the intertubular spaces, the myoglobin casts are most likely a less significant contributing factor.

Kidneys from donors who have received massive transfusions in combination with cardiopulmonary bypass may appear red despite effective flushing. Such kidneys should not be discarded because of poor perfusion. Careful assessment may include biopsy at transplant to assess the degree of pigment deposition in the renal tubules. In most cases, these kidneys can be transplanted and demonstrate good medium-term results. These kidneys usually develop acute kidney injury in the donor and are more likely to develop DGF after transplant, as occurred in both kidneys from the donor described here. In extreme cases with widespread tubular casts, there may be primary nonfunction, though this remains unquantifiable. We believe these kidneys should be used after careful assessment and not discarded outright. Machine perfusion—as opposed to cold storage—may also be beneficial, although this remains untested. Risk-benefit assessments should also take into account the morbidities and mortalities present in patients with chronic kidney disease.¹⁴

Our review of the literature shows that heme pigment nephropathy in the donor kidney caused by cardiopulmonary bypass and massive transfusion, and subsequent outcomes after transplant, have not been previously reported. The transplant surgeon should be aware of the potential adverse outcomes of delayed graft function, suboptimal graft function, and, in extreme cases, primary nonfunction. The dark ruddy complexion of a kidney that has been adequately flushed should alert the surgeon to these possibilities. In our case, both recipients demo-nstrated satisfactory renal function at 1 year after the initial development of DGF and slow graft function.

Cardiopulmonary bypass in conjunction with massive transfusion is associated with hemolysis, heme pigment deposition in the renal tubules, and acute kidney injury. The kidneys from such donors demonstrate a red or ruddy complexion that persists after effective flushing with a preservation solution. Such kidneys should not be discarded or considered poorly perfused. Transplanting such kidneys is associated with delayed graft function, but also satisfactory medium-term graft outcomes.

Volume: 14 Issue: 3 June 2016

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