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Successful Kidney Transplantation from a Cadaveric Donor Unsuitable for Other Centers Due to Acute Renal Failure: A Case Report
Successful Kidney Transplantation from a Cadaveric Donor Unsuitable for Other Centers Due to Acute Renal Failure: A Case Report A. Bilgic, B. Erdogan, A. Kali, M. Buyukbakkal, B. Eser, B. Bozkurt, M. Kilic, and M.D. Ayli ABSTRACT The demand for kidney transplantation due to improved recipient outcomes has stimulated surgeons to expand the criteria for usable donors, but still the use of organs from deceased donors with terminal acute renal failure is uncommon. We report 2 kidney transplant recipients from a cadaveric donor who was not accepted by other centers because of acute renal failure. The donor, a 24-year-old man with an intracerebral hemorrhage, displayed a serum creatinine (SCr) value of 0.6 mg/dL on hospital admission, which increased to 7.3 mg/dL on the fourth hospital day. After the diagnosis of brain death and refusal of the kidneys by other regional centers, we decided to transplant the 2 kidneys. Recipient 1, a 31-year-old man on an 11-year dialysis program, discontinued hemodialysis after 7 days of delayed graft function. The SCr level decreased gradually and was stable at 1.08 mg/dL on postoperative day (POD) 45. The contralateral graft was transplanted into a 30-year-old man (recipient 2) undergoing dialysis treatment for 7 years. After 10 days of delayed graft function, the SCr decreased gradually with continued hemodialysis until POD 24. The SCr level has been stable at 1.34 mg/dL on POD 52. At the end of the third month the SCr levels in recipients 1 and 2 were 1.1 mg/dL and 1.4 mg/dL, respectively. In conclusion, one may safely expand the donor pool with kidneys from deceased donors with acute renal failure (ARF) with good short-term outcomes. HE DEMAND for kidney transplantation has increased dramatically in the past few decades. Waiting lists have increased worldwide, leading to a shortage of organs. The limited supply of cadaver donors suitable for renal transplantation has led physicians to consider alternative strategies to make more organs available. Efforts to increase the number of nonconventional donors include expanded-criteria donors, postcardiac death donors, highrisk behavioral or medical donors, donors with prolonged warm or cold ischemia time, or dual kidneys from donors at the extremes of age.1 However, the utility of these kidneys is presently unclear. Although historically believed to be a relative contraindication to kidney donation and transplantation, increasing interest has focused on the use of kidneys from donors who develop acute renal failure (ARF) or oligo-anuria prior to organ retrieval. Some donor candidates have been rejected because of increased serum creatinine (SCr) levels, although other organs have shown renal function despite high SCr levels. However, potential donors who develop terminal ARF comprise a substantial proportion of discarded kidneys.
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In this work, we have reported 2 kidney transplant recipients from a cadaveric donor who was not accepted by several other centers because of ARF due to acute tubular necrosis. After refusal of the donor kidneys by 11 regional transplantation centers, both were accepted and transplanted into 2 recipients at our center. CASE REPORTS The donor, a 24-year-old man with an intracerebral hemorrhage, suffered a cardio-pulmonary arrest. On hospital admission his blood urea nitrogen (BUN) and SCr were 21 mg/dL and 0.6 mg/dL, respectively. During the follow-up in the intensive care unit, he displayed severe hypotension to 80/50 mm Hg for more than 12 From the Departments of Nephrology (A.B., B.E., A.K., M.D.A.) and General Surgery (B.B., M.K.), Etlik Ihtisas Training and Education Hospital; and the Department of Nephrology (M.B., B.E.), Diskapi Training and Research Hospital, Ankara, Turkey. Address reprint requests to Ayse Bilgic, MD, Etlik Ihtisas Eg˘itim ve Aras¸tirma Hastanesi. Halil Sezai Erkut caddesi, Etlik, Ankara, Turkey. E-mail: [email protected]
0041-1345/12/$–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.04.010
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
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Transplantation Proceedings, 44, 1764 –1766 (2012)
CADAVERIC DONOR hours requiring a dopamine infusion (5 to 15 g/kg/min). His renal function deteriorated progressively with the BUN and SCr levels increasing to 115 mg/dL and 7.3 mg/dL, respectively, on the fourth hospital day. The glomerular filtration rate calculated by the MDRD (The Modification of Diet in Renal Disease) formula was 9.25 mL/min. After the diagnosis of brain death, his kidneys were presented to 11 transplantation centers that refused them. In contrast, we decided to transplant them into 2 waiting list patients. Recipient 1, a 31-year-old man with end-stage renal disease (ESRD) of unknown etiology, had been on peritoneal dialysis for 10 years and hemodialysis (HD) for 1 year. Recipient 2 was a 30-year-old man with ESRD caused by chronic glomerulonephritis who had been on HD for 7 years. The blood types of the donor and the recipients were compatible. Recipient 1 had 4 and recipient 2 had 5 HLA mismatches. Pretransplantation T- and B-lymphocytotoxicity tests were negative. Body weights of the donor, recipient 1, and recipient 2 were 75.0, 60.2, and 75.5 kg, respectively. The left kidney was transplanted to recipient 1; the right kidney was transplanted to recipient 2. The transplantation operations were consecutively performed by the same surgeon with the first operation for recipient 1. The difference in total ischemic time between the 2 recipients was 3 hours and 48 minutes (12 hours and 30 minutes vs 16 hours and 22 minutes, respectively). There were no intraoperative complications. Immunosuppression was induced with basiliximab (20 mg; just before induction of anesthesia and on postoperative day (POD) 4) and methyl-prednisolone (1000 mg; just before the arterial clamp was removed and 250 mg on POD 1. Mycophenolate mofetil (MMF) was started on the POD 1 (2 ⫻ 1 g). The steroid dose was gradually decreased to 5 mg/d at the end of the third month. After 7 days of delayed graft function, the urine output by recipient 1 increased gradually, allowing discontinuation of HD. Tacrolimus (4 mg/d) was prescribed from POD 7 with drug levels maintained between 10 and 15 ng/mL. The SCr level decreased progressively but slowly. At POD 45, the BUN and SCr levels were 55 mg/dL and 1.08 mg/dL, respectively. Recipient 2 experienced 10 days of delayed graft function before the daily urine output achieved adequate levels gradually. Tacrolimus was started on POD 10 showing a drug level of 10 –15 ng/mL. The SCr began to decrease on POD 24 with discontinuation of HD. MMF was switched to mycophenolate sodium because of diarrhea. At POD 52 the BUN and SCr levels were 34 mg/dL and 1.34 mg/dL, respectively. At the end of the third month the SCr level was 1.1 mg/dL in recipient 1 and 1.4 mg/dL in recipient 2 (Fig 1). They experienced no medical problem.
Fig 1. The course of SCr level in recipient 1 and 2.
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DISCUSSION
The demand for cadaveric organs has resulted in the use of marginal donors. Ojo et al reported that patients who received a marginal donor kidney transplant showed a significant survival advantage compared with those remaining on dialysis,2 prompting many centers to expand donor acceptance criteria to include elderly donors as well as, grafts that would have been previously discarded due to arterial hypertension, renal dysfunction, or prolonged ischemia time, or other significant risk factors.3 Many donors without a prior history of kidney disease may experience a variety of renal insults immediately prior to organ recovery, including hypoxic-ischemic injury, exposure to nephrotoxic medications, infection, or rhabdomyolysis. Those injuries have the potential to cause significant renal damage, often leading to acute tubular necrosis and ARF, which may be completely reversible with treatment of the underlying cause.4 It is logical to speculate that kidneys retrieved from donors with acute tubular necrosis may also experience near complete recovery after removal from the donor environment. Indeed potential donors who develop terminal ARF continue to comprise a substantial proportion of discarded donor kidneys.5 We have presented herein 2 cadaveric kidney transplant recipients who displayed good SCr levels at the end of the third month despite a high donor SCr level at the time of donation. Mizutani et al showed that an increased donor SCr level before procurement was less important than the donor SCr levels upon admission.6 Our donors SCr level at the time of procurement was 7.3 mg/dL, whereas his upon admission value was 0.6 mg/dL. A retrospective study compared the outcomes of 170 kidney transplantations from donors accepted after refusal by at least 2 centers due to poor donor or graft quality with a control group.5 The second most common cause for kidney refusal was an abnormal preharvest SCr level (22%). The “marginal donor” group showed comparable results as the control group with respect to chronic and acute rejection; only the rate of primary nonfunction was significantly higher among the “marginal donor” group. A number of recent reports have demonstrated good short-term outcomes with kidneys transplanted from selected donors with either increased SCr levels or ARF. Although the incidence of delayed graft function was high in these studies, the renal function and graft survival were comparable to standard criteria donors.7–10 In 2009, Zuckerman et al performed a 12-month, single-center, retrospective analysis of 25 kidney transplantations from 17 donors with ARF compared with 86 kidneys transplanted from 83 standard criteria donor without ARF.11 Delayed graft function occurred in 8 recipients (32%) in the first group. There was no significant difference between the 2 groups with regard to the incidence of delayed graft function, graft survival, primary nonfunction, or acute rejection episodes. But the duration of delayed graft function was greater among kidneys from donors with ARF.
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Delayed graft function was observed in both recipients 1 and 2, but recipient 2 exhibited a longer period of delayed graft function 7 and 10 days respectively. The recipients exhibited good clinical and laboratory courses after cessation of HD. The SCr value at 3 months after transplantation in recipient 1 was 1.1 mg/dL and in recipient 2 it was 1.4 mg/dL. We believe that the reason for these good shortterm outcomes were the event of increased donor SCr occurring just prior to donation and being potentially reversible. In conclusion, it is largely unknown how many deceased donor kidneys are discarded because of an increased terminal SCr level. In our experience, if the deceased donor is well choosen, the kidneys that suffered from ARF have good short-term outcomes. REFERENCES 1. Port FK, Bragg-Gresham JL, Metzger RA, et al: Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors. Transplantation 74:1281, 2002 2. Ojo AO, Hanson JA, Meier-Kriesche H, et al: Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates. J Am Soc Nephrol 12:589, 2001
BILGIC, ERDOGAN, KALI ET AL 3. Veroux P, Veroux M, Puliatti C, et al: Kidney transplantation from cadaveric donors unsuitable for other centers and older than 60 years of age. Transplant Proc 37:245, 2005 4. Lewers DT, Mathew TH, Maher JF, et al: Long-term follow-up of renal function and histology after acute tubular necrosis. Ann Intern Med 73:523, 1970 5. Dahmane D, Audard V, Hiesse C, et al: Retrospective follow-up of transplantation of kidneys from “marginal” donors. Kidney Int 69:546, 2006 6. Mizutani K, Hattori R, Kato M, et al: Is estimated donor glomerular filtration rate before death a better predictor of decreaseddonor kidney function? Transplant Proc 42:3938, 2010 7. Al Khader AA, Shaheen FA, Attar BA, et al: Successful use of kidneys from deceased donors with acute renal failure. Prog Transplant 17:258, 2007 8. Greenstein SM, Moore N, McDonough P, et al: Excellent outcome using “impaired” standard criteria donors with elevated serum creatinine. Clin Transplant 22:630, 2008 9. Morgan C, Martin A, Shapiro R, et al: Outcomes after transplantation of deceased-donor kidneys with rising serum creatinine. Am J Transplant 7:1288, 2007 10. Anil Kumar MS, Khan SM, Jaglan S, et al: Successful transplantation of kidneys from deceased donors with acute renal failure: three-year results. Transplantation 82:1640, 2006 11. Zuckerman JM, Singh RP, Farney AC, et al: Single center experience transplanting kidneys from deceased donors with terminal acute renal failure. Surgery 146:686, 2009
T
In this work, we have reported 2 kidney transplant recipients from a cadaveric donor who was not accepted by several other centers because of ARF due to acute tubular necrosis. After refusal of the donor kidneys by 11 regional transplantation centers, both were accepted and transplanted into 2 recipients at our center. CASE REPORTS The donor, a 24-year-old man with an intracerebral hemorrhage, suffered a cardio-pulmonary arrest. On hospital admission his blood urea nitrogen (BUN) and SCr were 21 mg/dL and 0.6 mg/dL, respectively. During the follow-up in the intensive care unit, he displayed severe hypotension to 80/50 mm Hg for more than 12 From the Departments of Nephrology (A.B., B.E., A.K., M.D.A.) and General Surgery (B.B., M.K.), Etlik Ihtisas Training and Education Hospital; and the Department of Nephrology (M.B., B.E.), Diskapi Training and Research Hospital, Ankara, Turkey. Address reprint requests to Ayse Bilgic, MD, Etlik Ihtisas Eg˘itim ve Aras¸tirma Hastanesi. Halil Sezai Erkut caddesi, Etlik, Ankara, Turkey. E-mail: [email protected]
0041-1345/12/$–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.04.010
© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1764
Transplantation Proceedings, 44, 1764 –1766 (2012)
CADAVERIC DONOR hours requiring a dopamine infusion (5 to 15 g/kg/min). His renal function deteriorated progressively with the BUN and SCr levels increasing to 115 mg/dL and 7.3 mg/dL, respectively, on the fourth hospital day. The glomerular filtration rate calculated by the MDRD (The Modification of Diet in Renal Disease) formula was 9.25 mL/min. After the diagnosis of brain death, his kidneys were presented to 11 transplantation centers that refused them. In contrast, we decided to transplant them into 2 waiting list patients. Recipient 1, a 31-year-old man with end-stage renal disease (ESRD) of unknown etiology, had been on peritoneal dialysis for 10 years and hemodialysis (HD) for 1 year. Recipient 2 was a 30-year-old man with ESRD caused by chronic glomerulonephritis who had been on HD for 7 years. The blood types of the donor and the recipients were compatible. Recipient 1 had 4 and recipient 2 had 5 HLA mismatches. Pretransplantation T- and B-lymphocytotoxicity tests were negative. Body weights of the donor, recipient 1, and recipient 2 were 75.0, 60.2, and 75.5 kg, respectively. The left kidney was transplanted to recipient 1; the right kidney was transplanted to recipient 2. The transplantation operations were consecutively performed by the same surgeon with the first operation for recipient 1. The difference in total ischemic time between the 2 recipients was 3 hours and 48 minutes (12 hours and 30 minutes vs 16 hours and 22 minutes, respectively). There were no intraoperative complications. Immunosuppression was induced with basiliximab (20 mg; just before induction of anesthesia and on postoperative day (POD) 4) and methyl-prednisolone (1000 mg; just before the arterial clamp was removed and 250 mg on POD 1. Mycophenolate mofetil (MMF) was started on the POD 1 (2 ⫻ 1 g). The steroid dose was gradually decreased to 5 mg/d at the end of the third month. After 7 days of delayed graft function, the urine output by recipient 1 increased gradually, allowing discontinuation of HD. Tacrolimus (4 mg/d) was prescribed from POD 7 with drug levels maintained between 10 and 15 ng/mL. The SCr level decreased progressively but slowly. At POD 45, the BUN and SCr levels were 55 mg/dL and 1.08 mg/dL, respectively. Recipient 2 experienced 10 days of delayed graft function before the daily urine output achieved adequate levels gradually. Tacrolimus was started on POD 10 showing a drug level of 10 –15 ng/mL. The SCr began to decrease on POD 24 with discontinuation of HD. MMF was switched to mycophenolate sodium because of diarrhea. At POD 52 the BUN and SCr levels were 34 mg/dL and 1.34 mg/dL, respectively. At the end of the third month the SCr level was 1.1 mg/dL in recipient 1 and 1.4 mg/dL in recipient 2 (Fig 1). They experienced no medical problem.
Fig 1. The course of SCr level in recipient 1 and 2.
1765
DISCUSSION
The demand for cadaveric organs has resulted in the use of marginal donors. Ojo et al reported that patients who received a marginal donor kidney transplant showed a significant survival advantage compared with those remaining on dialysis,2 prompting many centers to expand donor acceptance criteria to include elderly donors as well as, grafts that would have been previously discarded due to arterial hypertension, renal dysfunction, or prolonged ischemia time, or other significant risk factors.3 Many donors without a prior history of kidney disease may experience a variety of renal insults immediately prior to organ recovery, including hypoxic-ischemic injury, exposure to nephrotoxic medications, infection, or rhabdomyolysis. Those injuries have the potential to cause significant renal damage, often leading to acute tubular necrosis and ARF, which may be completely reversible with treatment of the underlying cause.4 It is logical to speculate that kidneys retrieved from donors with acute tubular necrosis may also experience near complete recovery after removal from the donor environment. Indeed potential donors who develop terminal ARF continue to comprise a substantial proportion of discarded donor kidneys.5 We have presented herein 2 cadaveric kidney transplant recipients who displayed good SCr levels at the end of the third month despite a high donor SCr level at the time of donation. Mizutani et al showed that an increased donor SCr level before procurement was less important than the donor SCr levels upon admission.6 Our donors SCr level at the time of procurement was 7.3 mg/dL, whereas his upon admission value was 0.6 mg/dL. A retrospective study compared the outcomes of 170 kidney transplantations from donors accepted after refusal by at least 2 centers due to poor donor or graft quality with a control group.5 The second most common cause for kidney refusal was an abnormal preharvest SCr level (22%). The “marginal donor” group showed comparable results as the control group with respect to chronic and acute rejection; only the rate of primary nonfunction was significantly higher among the “marginal donor” group. A number of recent reports have demonstrated good short-term outcomes with kidneys transplanted from selected donors with either increased SCr levels or ARF. Although the incidence of delayed graft function was high in these studies, the renal function and graft survival were comparable to standard criteria donors.7–10 In 2009, Zuckerman et al performed a 12-month, single-center, retrospective analysis of 25 kidney transplantations from 17 donors with ARF compared with 86 kidneys transplanted from 83 standard criteria donor without ARF.11 Delayed graft function occurred in 8 recipients (32%) in the first group. There was no significant difference between the 2 groups with regard to the incidence of delayed graft function, graft survival, primary nonfunction, or acute rejection episodes. But the duration of delayed graft function was greater among kidneys from donors with ARF.
1766
Delayed graft function was observed in both recipients 1 and 2, but recipient 2 exhibited a longer period of delayed graft function 7 and 10 days respectively. The recipients exhibited good clinical and laboratory courses after cessation of HD. The SCr value at 3 months after transplantation in recipient 1 was 1.1 mg/dL and in recipient 2 it was 1.4 mg/dL. We believe that the reason for these good shortterm outcomes were the event of increased donor SCr occurring just prior to donation and being potentially reversible. In conclusion, it is largely unknown how many deceased donor kidneys are discarded because of an increased terminal SCr level. In our experience, if the deceased donor is well choosen, the kidneys that suffered from ARF have good short-term outcomes. REFERENCES 1. Port FK, Bragg-Gresham JL, Metzger RA, et al: Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors. Transplantation 74:1281, 2002 2. Ojo AO, Hanson JA, Meier-Kriesche H, et al: Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and wait-listed transplant candidates. J Am Soc Nephrol 12:589, 2001
BILGIC, ERDOGAN, KALI ET AL 3. Veroux P, Veroux M, Puliatti C, et al: Kidney transplantation from cadaveric donors unsuitable for other centers and older than 60 years of age. Transplant Proc 37:245, 2005 4. Lewers DT, Mathew TH, Maher JF, et al: Long-term follow-up of renal function and histology after acute tubular necrosis. Ann Intern Med 73:523, 1970 5. Dahmane D, Audard V, Hiesse C, et al: Retrospective follow-up of transplantation of kidneys from “marginal” donors. Kidney Int 69:546, 2006 6. Mizutani K, Hattori R, Kato M, et al: Is estimated donor glomerular filtration rate before death a better predictor of decreaseddonor kidney function? Transplant Proc 42:3938, 2010 7. Al Khader AA, Shaheen FA, Attar BA, et al: Successful use of kidneys from deceased donors with acute renal failure. Prog Transplant 17:258, 2007 8. Greenstein SM, Moore N, McDonough P, et al: Excellent outcome using “impaired” standard criteria donors with elevated serum creatinine. Clin Transplant 22:630, 2008 9. Morgan C, Martin A, Shapiro R, et al: Outcomes after transplantation of deceased-donor kidneys with rising serum creatinine. Am J Transplant 7:1288, 2007 10. Anil Kumar MS, Khan SM, Jaglan S, et al: Successful transplantation of kidneys from deceased donors with acute renal failure: three-year results. Transplantation 82:1640, 2006 11. Zuckerman JM, Singh RP, Farney AC, et al: Single center experience transplanting kidneys from deceased donors with terminal acute renal failure. Surgery 146:686, 2009