EXPERIMENTAL AND CLINICAL TRANSPLANTATION

There have been several studies exploring the viability of kidneys procured from extended criteria donors with acute kidney injury. Previous publications have evaluated the long-term outcomes of kidneys after acute kidney injury. We describe the case of 2 transplants from a donor with acute renal failure after a motor vehicle accident. The donor required 11 days of venovenous hemodialysis before procurement. There have not been any previous reports of donations following such a prolonged period of dialysis. The kidneys were shared across organ procurement organization service areas and had cold ischemia times of 32 hours and 26 hours. Both recipients had delayed graft function. One recipient had several complications that required multiple readmission for treatment. At last follow-up, both transplanted organs were functioning adequately and producing urine. This case report presents a novel opportunity to understand the extent of possible kidney transplant after acute kidney injury.

Key words : Acute kidney injury donor, Delayed graft function, Donation after circulatory death

Transplant centers are increasingly expanding the criteria of acceptable organs for transplant in an effort to meet the growing demand; this includes donors with acute kidney injury (dAKI). Previous studies have correlated increasing severity of Acute Kidney Injury Network (AKIN) stages 1, 2, and 3 with progressively higher rates of delayed graft function (DGF) and kidney discard.¹ Moreover, a review in the United Kingdom indicated increased rates of primary nonfunction with AKIN stage 3 kidneys.² However, other analyses of kidneys procured from dAKI have validated comparable long-term outcomes in 1-year graft survival, as well as estimated glomerular filtration rate (eGFR), and biopsy results for interstitial fibrosis and tubular atrophy.³ Several publications have cataloged successful transplant of kidneys from specifically selected AKIN donors.^4,5 In this report, we have detailed the case of organ procurement and transplant of kidneys from a donor with severe AKI who required prolonged hemodialysis for 11 days. There have not been any previous accounts of successful transplant with such an extended period of hemofiltration.

Donor
The donor was a 41-year-old man with donation after cardiac death who had previously required 11 days of hemodialysis to treat his kidney injury. He had a body mass index (BMI, calculated as patient’s weight in kg divided by the square of body height in m) of 27.4, and he was from a different organ procurement organization donor service area. He was admitted after sustaining severe injuries in a motor vehicle accident. Initial creatinine was 1.05 mg/dL, the kidney donor profile index (KDPI) was 37%, and he tested positive for cytomegalovirus and negative for Epstein-Barr virus. During the hospital course, he required venovenous hemodialysis for 11 days for treatment of AKI secondary to rhabdomyolysis.

The peak creatinine was 4.55 mg/dL, and the final creatinine was 3.23 mg/dL; creatine kinase was 10?582 U/L. Despite the severity of injury and need for hemodialysis, renal biopsy at procurement showed no vessel or interstitial injury in either kidney; global glomerulosclerosis of 5% was observed in the left kidney and 1% in the right. Urinalysis did not show any casts. Both kidneys were visually inspected and placed on a perfusion pump with a resistance of 0.30 mm Hg/mL/min and flow of 108 mL/min.

Recipient 1
The first recipient was a 60-year-old Asian man with end-stage renal disease secondary to immunoglobulin A nephropathy. His BMI was 32, and he was on hemodialysis for 2 years with an estimated posttransplant survival of 41%. Previous medical history was significant for hypertension, gout, hyperlipidemia, peripheral vascular disease, history of deep venous thrombosis, and positive tests for both cytomegalovirus and Epstein-Barr virus. Cold ischemia time (CIT) was 32 hours, and pump time was 10.3 hours. There were no operative complications; graft perfusion was verified by ultrasonography. Immunosuppression was started using tacrolimus, mycophenolate, and prednisone. Postoperative course was significant for DGF, which required 2 treatments of hemodialysis. The recipient was discharged on postoperative day 3 with a creatinine level of 10.93 mg/dL. At 2-month follow-up, he was dialysis independent and making adequate urine with a creatinine level of 1.74 mg/dL.

Recipient 2
The second recipient was a 61-year-old non-Hispanic white man with end-stage renal disease secondary to hypertension and diabetes mellitus. His BMI was 27, and he had been on hemodialysis for 6 years, with an estimated posttransplant survival of 90% and at the top of the wait list. Medical history included chronic heart failure, hyperlipidemia, cytomegalovirus negative, and Epstein-Barr virus positive. Cold ischemia time was 26 hours, and pump time was 17 hours and 30 minutes. Transplant was affected by profuse bleeding from the donor kidney biopsy site. Good graft perfusion was verified by ultrasonography.

His postoperative course was significant for several complications that led to multiple protracted hospital stays. Transfusion was required to ameliorate a low hemoglobin level. Delayed graft function was treated with multiple treatments of hemodialysis.

Recipient 2 later presented with systemic hypotension and sepsis that required treatment with antibiotics, and he briefly needed vasopressors. A computed tomography scan of the abdomen and pelvis demonstrated a hematoma at the transplant site, as well as findings suspicious of a pseudoaneurysm along the cortex of the transplanted kidney, presumably secondary to the biopsy. Treatment was initiated with fluid boluses and multiple units of blood. Lasix renal scan showed perfusion of the kidney and minimal excretion consistent with acute tubular necrosis and DGF. He was discharged on postoperative day 18 in stable condition after receiving 2 more units of blood.

Recipient 2 was readmitted 3 days later for shortness of breath, diaphoresis, and syncope that occurred 1 day after a prolonged hemodialysis session. He received multiple units of blood during admission, and ultrasonography showed resolution of the pseudoaneurysm noted on the previous admission. He was dialysis independent during the stay and was discharged on postadmission day 10.

Two months after the transplant, recipient 2 was making adequate urine with a creatinine level of 1.35 mg/dL. However, at the 3-month follow-up, he was admitted with a creatinine level of 3.14 mg/dL and hydronephrosis that required nephrostomy tube placement. He was readmitted with sepsis due to gram-negative bacteremia, later found to be carbapenem-resistant Enterobacteriaceae, that necessitated antibiotic management. During the hospital stay, bilateral lower extremity deep vein thrombosis required treatment with anticoagulants.At the last follow-up, he was making 1 L of urine per hour from the transplanted kidney and his creatinine level was 1.5 mg/dL.

Several groups have investigated the use of kidneys procured from donors with reversible AKI; those studies predominantly focused on renal injury caused by rhabdomyolysis. Generally, the parameters for AKI emphasized creatinine kinase greater than 1000 U/L, presence of urine myoglobin,⁶ and terminal creatinine greater than 2.0 mg/dL.³

A retrospective analysis of kidney transplants with AKI in the United Kingdom demonstrated increasing rates of DGF and graft discard with progressive AKI stages, as well as lower 6-month eGFR in recipients with DGF.² Another publication explained that, while DGF was more common in kidneys with AKI, the 1-year postoperative eGFR, graft survival time, and proportion of interstitial fibrosis and tubular atrophy were similar to those shown in the standard donor group.³

A prospective trial with kidneys from 7 donors with acute renal failure due to rhabdomyolysis concluded that, although 3 of 10 recipients had DGF, all of them attained normal graft function at 1-month posttransplant.⁶

This case report is particularly unique because of a confluence of risk factors in the donor. Previous literature has included donors that required hemodialysis prior to procurement; however, the longest course of hemofiltration was 4 days.⁵ Our case is the first instance of successful organ procurement and transplant with an organ that required 11 days of dialysis.

Another complicating factor in this instance was the prolonged CIT for the recipients, which was 32 hours and 26 hours, with pump times of 10.3 hours and 17.5 hours, respectively. Current literature on the impact of CIT on renal graft function suggests that graft failure rates increase with CIT, especially after 22 hours.⁷ The risks for graft failure and mortality increase with each additional hour of CIT.⁸ Another group investigating CIT and focusing on renal transplant outcomes in donors with AKI did not yield a statistically significant difference with CIT up to 15 hours.⁹

The decision-making process that resulted in the kidneys being considered viable for transplant is particularly important in this case. First, donor youth, good health without any preexisting medical conditions, and injury by rhabdomyolysis were important factors. More importantly, biopsy investigation revealed excellent histological findings with minimal injury. Furthermore, healthy appearance upon visual inspection at the time of procurement, along with good flow and resistance metrics after placement on perfusion pump, increased the likelihood of good transplant outcome. The confluence of all these factors qualified the kidneys as acceptable for transplant and increased surgeon confidence in transplant of the organs.

One of the concerning factors in recipient 2 was the development of the cortical pseudoaneurysm due to donor graft biopsy. These findings, along with the low hemoglobin and unstable status, were particularly alarming in the postoperative period. The subsequent resolution of the radiological findings supported our conservative approach in management. It is important to note that the blood loss anemia was not related to dAKI.

The treatment course for recipient 2 was further complicated by the incidence of infection with carbapenem-resistant Enterobacteriaceae. There were several risk factors for developing an infection with Klebsiella, including multiple prolonged hospital admissions. Solid-organ transplant is also an independent risk factor for developing an infection with carbapenem-resistant Enterobacteriaceae.¹⁰ Although recipient 2 was able to successfully recover from the infection, an analysis of kidney transplant recipients with carbapenem-resistant Enterobacteriaceae infection demonstrated a 46% mortality rate.¹¹

This case report presents a novel opportunity to understand the extent of possible kidney transplant after AKI. The donor had severe AKI due to a motor vehicle accident and required 11 days of hemodialysis. He had a terminal creatinine of 3.23 mg/dL and creatinine kinase of 10?582 U/L. Kidney donation was still possible because it is believed that kidney injury secondary to rhabdomyolysis is temporary and resolves in the days to weeks following the insult. The clinician’s decision-making process with rigorous donor and recipient selection is paramount in the transplant of organs with acute injury. Postoperative management of DGF is important in restoring normal graft function.

Volume: 19 Issue: 11 November 2021

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