Outcomes of Kidney Grafts Refused by One or More Centers and Subsequently Transplanted at a Single United Kingdom Center

Outcomes of Kidney Grafts Refused by One or More Centers and Subsequently Transplanted at a Single United Kingdom Center S. Farid, A. Aldouri, S. Fraser, A. Al-Mukhtar, C. Newstead, A. Lewington, R. Baker, K. Menon, and N. Ahmad ABSTRACT Introduction. The rate-limiting factor in kidney transplantation is the shortage of donor organs with resulting steady increase in patients on the transplant waiting list. In our center we have seen an increase in the use of kidneys refused as unsuitable by one or more centers in the United Kingdom (UK). This study was performed to analyze the outcomes of transplantation from kidneys refused by one or more centers and subsequently transplanted by our institution. Methods. We performed a retrospective analysis using the UK Transplant database of donor grafts refused by one or more centers and subsequently transplanted by us from January 2000 to December 2005. We documented the reason for refusal, donor and recipient factors, incidence of graft rejection, and primary and delayed graft function. Graft function and patient survival at 3 years were compared with standard donor grafts. Results. From January 2000 to December 2005, we performed 623 renal transplantations, including 60 (9.6% from donors who were refused by one or more centers and 402 “standard” donor grafts. The main reasons for initial refusal included: elderly donor 25% (median age, 61 years), better HLA match required 33.3%, anatomical 5%, medical history of donor 6.6%, virology 4.8%, prolonged cold ischemia time 3.3% (median, 33.5 hours), and organ damage 1.6%. The 3-year median creatinine levels of donor grafts refused by multiple centers was 126 ␮mol/L compared with 135 ␮mol/L for standard grafts (P ⫽ .97). Three-year graft and patient survival rates were 86.6% and 96%, for grafts refused by multiple centers and 87% and 95%, for standard grafts, respectively. Upon multivariate analysis none of the above variables were significant predictors of 3-year failure of grafts refused by multiple centers. Conclusions. Nearly 10% of kidney transplants in our center were performed with grafts refused by one or more centers as “unsuitable.” The graft and patient survivals were similar to those of standard grafts. None of the factors for refusal of kidneys by other centers predicted graft failure at 3 years. There may be an element of subjective assessment and subsequently a “cascade effect” involved in refusal of some of these kidneys. HERE continues to be a growing disparity between the demand for and supply of organs for kidney transplantation. The number of transplants performed in the United Kingdom (UK) has remained virtually static over the last 10 years (Fig 1), while the number of patients on the waiting list, waiting time, and patients who succumb on the list continue to increase.1 In the same period the number of cadaveric donors has decreased by approximately 20%.2

T

Waiting time on dialysis before transplantation is an important potential risk factor for subsequent graft loss after transplantation.3 Since a functioning kidney graft From the Department of Renal Transplantation, St. James University Hospital, Leeds, United Kingdom. Address reprint requests to Mr. Niaz Ahmad, MD, FRCS, St. James University Hospital, Beckett Street, Leeds, UK LS9 7TF. E-mail: [email protected]

© 2009 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710

0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.01.088

Transplantation Proceedings, 41, 1541–1546 (2009)

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Transplants Donors Waiting list

6000 5000 4000 3000 2000 1000 Fig 1. Number of donors, transplants, and patients on the active transplant list (April 1996–March 2006).

0 96-97 97-98

98-99

99-00

confers greater survival and quality of life benefit over dialysis,3 there is a high demand for transplantation. Furthermore, the cost benefit of kidney transplantation compared with dialysis over a period of 10 years (the median graft survival) is £241,000 or £24,100 per year for each year the patient has a functioning kidney.4 On January 1, 2007, there were 6200 dialysis patients awaiting transplantation, costing around £190 million per year. If all of these patients received a transplant, the approximate cost would be £40 million per year, representing a £150 million saving per year for the National Health Service.4 The current climate in transplantation demands matching efforts to increase donation rates and maximize organs use. This challenge has seen many centers expand their programs by accepting extended criteria or marginal donor groups with acceptable results.5–7 Transplantation centers continue to update their donor criteria, constantly aware of the balanced risk between expansion and patient safety. However, there remains no homogenous applied UK donor criteria; acceptance of organs continues to show center-tocenter variability. We have seen a year-by-year decrease in the refusal rate of potential donor organs in our center. The present study evaluates the outcome of kidneys refused by one or more other centers and subsequently transplanted by our unit. This observation led to a comprehensive review of our previous acceptance criteria (Table 1). The study also attempted to establish whether the stated reason for refusal had an impact on graft function and/or patient survival. PATIENT AND METHODS We performed a retrospective analysis using the UK Transplant database of all donor grafts refused by one or more centres and subsequently transplanted at our center from January 2000 to December 2005. All transplants were from cadaveric donors and used standard surgical techniques. Standard grafts were defined as patients between 5 and 60 years of age. Donors between 50 and 59 years of age who had at least 2 of the following were excluded from the standard graft group: history of hypertension, terminal donor

00-01

Year

01-02

02-03

03-04

04-05

05-06

creatinine level ⬎130, or cerebrovascular accident as cause of death. In 2000 –2003, the protocol for immunosuppression included methylprednisolone (1 g on induction) and maintenance with cyclosporine, azathioprine, and prednisolone. From 2004, induction immunosuppression was provided by methylprednisilone (1 g) and basiliximab (20 mg preoperatively and on day 4), and maintenance with Tacrolimus (0.05 mg/kg bd) and mycophenolate mofetil (750 mg bd). We recorded the reasons for refusal, donor and recipient factors including donor comorbidity, and predonation creatinine and ischemia times. An acute rejection episode confirmed by biopsy in 9/11 cases was treated with methylprednisolone (500 mg for 3 days) and/or ATG/OKT3. Delayed graft function was defined as a patient requiring dialysis post–renal transplantation (except postoperative dialysis for hyperkalemia). Graft function and patient survival at 3 years were compared with standard donors, which are defined as those between 5 and 60 years of age. We excluded among standard grafts donors who were between 50 and 59 years of age with at least 2 of the following: history of hypertension, terminal creatinine level ⬎130 ␮mol/L, or cerebrovascular accident as a cause of death. Furthermore, we excluded those with gross anatomical abnormalities (eg, horseshoe kidney) or hepatitis B/C.

Statistical Analysis Statistical analysis was performed using SPSS version 13 (SPSS, Chicago, Ill, United States). A Cox regression multivariate analysis was performed in step-wise manner to examine reasons for refusal that impacted graft function and patient survival at 3 years. A P value of .05 or lower was considered to be significant.

RESULTS

During the period January 2000 to December 2005, 60 (9.6%) donor grafts among 623 cadaveric renal transplants were previously refused by one or more centers. The number of patients receiving standard grafts was 402. Donor and recipient demographics of grafts refused by multiple centers are shown in Table 2. Donor medical history specifically related to controlled hypertension and/or non–insulin-dependant diabetes. The median waiting time for all recipients was 426 days. Median retrieval creatinine levels and cold isch-

REFUSED KIDNEY GRAFTS

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Table 1. Criteria for Accepting Cadaveric Donor Kidneys in Our Center Before 2003 Before 2003 A. Offers we normally do not accept a. HbsAg⫹ve, HCV⫹ve, or HIV donors b. Donor malignancy (excluding primary CNS and excised local BCC) c. More than 3 mismatches or 2 DR mismatches d. Poor kidney perfusion e. Non– heart-beating from other centers f. Donor history of drug abuse g. Donor history of abnormal sexual behavior h. Extremes of donor age ⬎65 or ⬍6 y i. Recipient and donor age disparity ⬎30 y j. Projected CIT ⬎24 h k. Adult size kidney for pediatric recipient l. Donor sepsis B. Offers requiring discussion a. Abnormal anatomy b. All pediatric offers c. Damage to the kidney d. Raised creatinine or long-standing hypertension e. Previously transplanted recipients After 2003 A. Offers we normally do not accept a. HbsAg⫹ve, HCV⫹ve, or HIV donors b. Donor malignancy (excluding primary CNS and excised local BCC) B. Offers we would consider after discussion a. More than 3 mismatches or 2 DR mismatches b. Poor kidney perfusion c. Non– heart-beating from other centers d. Donor history of drug abuse e. Donor history of abnormal sexual behavior f. Extremes of donor age ⬎65 or ⬍6 y g. Recipient and donor age disparity ⬎ 30 y h. Projected CIT ⬎24 h i. Adult size kidney for pediatric recipient j. Donor sepsis Abbreviation: BCC, basal cell carcinoma.

emia times (CIT) from donors refused by multiple centers was 79 ␮mol/L (53–153) and 21:15 hours (13:31– 43: 35), respectively. The main reasons for initial refusal (Fig 2) include the following: elderly donor 26.6% (median age, 61 years), Table 2. Donor and Recipient Demographics Overall

Donor

Age (median) Gender PMH

42 Male Hypertension DM Hypertension ⫹ DM White

Ethnicity

Recipient

(8–72) 54% 52% 6% 4%

44.5 Male Hypertension DM

100%

White Asian Black

Abbreviations: PMH, past medical history; DM, diabetes mellitus.

(14–69) 58% 42% 14%

85% 13% 2%

20 15

20 15

6

10

2

5 0

Better HLA match

Age

PMH

CIT*

3

Anatomical

5

Donor size

Fig 2. Reason for graft refusal by one or more centers (n ⫽ 60; years 2000 –2005). Other reasons for refusal: virology (n ⫽ 4), poor function (n ⫽ 1), organ damage (n ⫽ 1), infection (n ⫽ 1), and tumor (n ⫽ 1) (PMH ⫽ past medical history).

better HLA match required 36.6%, medical history of donor 6.6%, prolonged CIT 3.3% (median, 33.5 hours, at time of offer), anatomy 4.8% (accessory arteries, duplex kidney), and organ damage 1.6%. Other factors included virology status 4.8% (CMV-positive and HbcAb ⫹ve), donor size, and “poor donor kidney function” (creatinine level 153 ␮mol/L) 1.6%. For all grafts refused by one or more centers, the overall median 1- and 3-year creatinine values were 120 ␮mol/L and 126 ␮mol/L, respectively, whereas for standard grafts; they were 128 ␮mol/L and 135 ␮mol/L, respectively (P ⫽ .89). Delayed graft function (DGF) was observed in 38% of refused graft versus 28% for standard grafts (P ⫽ .57). The overall 3-year graft and patient survival rates were 86.6% and 96%, respectively, for grafts refused by other centers and 87.7% and 95% for standard grafts respectively (P ⫽ .89). Two patients died with functioning grafts. Primary nonfunction was not observed in the grafts refused by multiple centers and occurred in 2.9% (n ⫽ 12) of standard grafts. Specific outcomes related to each main reason for graft refusal, including donor age, better HLA matching, and past medical history, are shown in Table 3. Higher rates of acute rejection episodes (48%) and elevated creatinine levels at 1 and 3 years (P ⫽ .034 and .041, respectively) were associated with grafts refused on grounds of advanced age. However, these factors did not produce statistically significant effects on graft and patient survivals at 1 and 3 years. The outcomes in the group of donors refused for “better HLA matching” were seen to have the best results. The median mismatch for these grafts in our center was 2. No graft was transplanted with 2 DR mismatches. The acute rejection rate was 10% and 1- and 3-year creatinine values were 104 ␮mol/L and 108 ␮mol/L, respectively. The number of graft losses associated with older donor age, better HLA matching, and donor medical history were 4/8, 2/8, and 0/8, respectively. Other factors associated with subsequent graft loss are shown in Table 4. The number of grafts refused by multiple centers and transplanted before 2004 was 24. They received steroid immunosuppression, and 33 grafts after 2004 did not receive steroid maintenance. Three patients after 2004 who received a donor graft

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refused by multiple centers did receive steroids because they were considered high immunological risk. No statistical difference was seen in terms of acute rejection as well as 1- and 3-year graft function (data not shown). None of the above variables cited for graft refusal was a significant predictor of 3-year graft survivals on multivariate analysis (Table 5). DISCUSSION

To deal with the widening gap between supply and demand of cadaveric organs for renal transplantation, efforts to increase the donor pool with the use of “suboptimal” grafts continue to receive attention. However, centers across the

Table 4. Reason for Refusal and Graft Loss Graft Loss Refusal Factor

Yes

No

Better match Donor age PMH CIT Virology Anatomical Donor size Poor function Organ damage Infection Tumor Total

2 4 0 0 0 1 1 0 0 0 0 8

18 11 6 3 4 2 4 1 1 1 1 52

Table 3. Specific Reason for Refusal and Outcome No. refused on age

n ⫽ 15/60

Donor age (median) Recipient age (median) DGF Primary function Acute rejection 1-y creatinine (␮mol/L) 3-y creatinine (␮mol/L) 1-y GFR (mL/min/1.73 m2)* 3-y GFR (mL/min/1.73 m2)* 1-y patient survival 3-y patient survival

61 (41–72) 51 (36–67) 48% 52% 48% (n ⫽ 7) 143 140 47 48 100% 94%

“Better HLA match required”

n ⫽ 20/60

HLA A mismatch 0,1,2. HLA B mismatch 0,1,2. HLA DR mismatch 0,1,2. Median mismatch DGF Primary function Acute rejection 1-y creatinine (␮mol/L) 3-y creatinine (␮mol/L) 1-y GFR (mL/min/1.73 m2)* 3-y GFR (mL/min/1.73 m2)* 1-y patient survival 3-y patient survival

3, 14, 3 5, 12, 2 7, 13, 0 2 36% 64% 10% (n ⫽ 2) 104 108 75 73 100% 100%

P

.034 .041

.678 .800

No. refused on donor history

n ⫽ 6/60

Hypertension DM Hypertension⫹DM DGF Primary function Acute rejection 1-y creatinine (␮mol/L) 3-y creatinine (␮mol/L) 1-y GFR (mL/min/1.73 m2)* 3-y GFR (mL/min/1.73 m2)* 1-y patient survival 3-y patient survival

4 1 1 0% 100% 16% (n ⫽ 1) 107 116 69 63 100% 100%

Abbreviation: GFR, glomerular filtration rate. *A.S. Levey, T. Greene, J.W. Kusek, G.L. Beck, MDRD Study Group. A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol, 2000 Sept; 11;155A

UK continue to vary in their practices of accepting organs with presumed poor outcomes. Our study showed that grafts that had been refused by one or more centers but subsequently transplanted at our institution experienced satisfactory outcomes. No factor cited for refusal produced a significant adverse outcome on graft survival. Important information was learned, however, from each reason cited for graft refusal. Renal function decreases with age.7 Therefore, it was not surprising to find that donor age (median, 61 years) was a factor affecting graft function after transplantation. Serum creatinine values at 1 and 3 years were significantly higher than those of grafts from younger donors, a finding consistent with published data. However, on subanalysis revealed a significant proportion of these donors displayed hypertension (80%) and a median CIT of 20.5 hours. Careful consideration is thus given to donors older than 60 years of age with hypertension and/or other comorbidity in terms of recipient selection, but they do not present a contraindication to transplantation in our center. We accept that if older donors or those with cardiovascular disease are to be used, the prognosis after transplantation may be more limited. In this regard we preferentially used these donor grafts in carefully selected age-matched recipients (median age, 53 years) with long waiting times. These recipients are aware of the possibility of a suboptimal graft function and have consented for such, as an alternative to prolonged dialysis and extended times on the waiting list. If an elderly donor kidney is to be used then it is of importance to minimize the CIT,8,9 as the risk of graft failure after 3 months increases with every additional hour of CIT. Table 5. Multivariate Analysis of Refusal Factors and Graft Survival Variable

Hazard Ratio

Confidence Interval 95%

P

Donor age Past medical history CIT Better HLA match

2.61 0.62 0.59 1.30

0.57–12.46 0.13–2.89 0.10–1.65 0.24–17.21

.21 .53 .61 .78

REFUSED KIDNEY GRAFTS

In the UK, the allocation of kidneys is a national process and based on HLA matching. The current allocation algorithm gives priority to pediatric recipients, for all 0, 0, and 0 mismatched and all favorably matched (maximum of 1 mismatched antigen at either the HLA-A or HLA-B locus) recipients. Points are accrued for time on the waiting list and sensitization status. It is acknowledged that the net impact of this preferential allocation on the adult renal failure population has been shown by computer modelling to be minimal. Research has shown that outcome is best related to compatibility at the HLA DR locus.10 It has been noted that 1 or 2 mismatches at the HLA A or B locus as compared with a 0 mismatch does not have any statistically significant effect.11 In this study HLA mismatch of transplanted kidneys from the donor group refused by multiple centers was 1 DR mismatch in most cases. Through the current allocation system we are seldom offered a kidney with more than 3 mismatches or 2 DR mismatches. Nevertheless, our unit will accept any number of mismatches for an adult recipient depending on clinical urgency but with concerted effort to optimize DR match. Prolonged CIT has a linear relationship with the occurrence of DGF up to 15 hours, after which every subsequent hour results in an exponential increase in the rate of DGF.12 DGF has important economic implication and impact on early morbidity but the long-term effect of DGF on graft survival and rejection remains unclear. Not all studies agree with DGF as a predictor of poor long-term graft outcomes.13 Although DGF is associated with higher rates of graft loss in the first 6 –12 months, it is not linked during the subsequent longer posttransplantation period.14 Prior to 2003 we did not accept cadaveric kidneys with projected CIT greater than 24 hours at the time of implantation. We have since reviewed our criteria; we accept kidneys with prolonged CIT, making the decision on individual merit. In this study we transplanted kidneys with a CIT of 43 hours (median, 33.5 hours) with favorable outcomes. Donors with hypertension and/or non–insulin-dependent diabetes whose organs were transplanted successfully have all had acceptable outcomes on 3-year follow-up in our study. Kidneys are only accepted from type 2 diabetic donors with absent or minimal proteinuria. Other authors have not found any short- or long-term graft and patient survival differences using kidneys from diabetic compared with nondiabetic donors.15 The precise correlation of arterial hypertension and chronic graft failure remains unclear, but the presence of long-term hypertension in the recipient is a risk factor.16 We continue to note the treatment(s), the number of years of hypertension, and the treatment success when accepting such kidneys and allocating them to recipients. A small number of potential grafts were refused due to concerns regarding infections such as CMV, hepatitis B, and bacterial infections. Because the concern of transferring CMV de novo or inducing CMV reoccurrence has

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decreased with the use of improved prophylaxis regimes.8 We do not refuse such donors. Hepatitis B core antibody (HbcAb)–positive donors have been accepted for seropositive recipients with successful outcomes.6 There is a small risk of transmission with HbcAb-positive donors (1:50).17 We continue to accept such organs after careful consideration. The recipients of these kidneys receive lamivudine prophylaxis and booster hepatitis B virus (HBV) immunization. Bacterial infections continue to be common in the intensive care unit (ICU) setting. Studies have shown that with appropriate antibiotics, transmission of pathogens is minimal and has no adverse outcome on graft function and patient survival.18 In common with all centers, the presence of significant systemic sepsis is an absolute contraindication to transplantation. It is common for centers to reject kidneys on the basis of retrieval damage, anatomy, and perfusion problems. In most of these instances there is much reliance placed on the retrieval surgeons whose experience can be variable. In most cases refusal by one center can lead to a cascade effect with refusal by subsequent centers. We now accept all such potential grafts, assess them on arrival, and, where needed, provide appropriate management to allow implantation, namely, machine perfusion, reflush, and reconstruction of damaged vessels and ureteric structures. Our approach has achieved successful outcomes in this group of donor grafts that would have otherwise been discarded. A further reason cited for graft refusal by centers included unsuspected or uncertain donor tumors (skin, kidney, or certain primary brain tumors). We accept kidneys from donors with central nervous system (CNS) malignancy and treated skin cancer in line with British Transplant Society guidelines. This policy has occasionally resulted in waiting for more than 24 hours for histological confirmation. Donor history of intravenous drug abuse (IVDU) or other high-risk behavior leads to automatic rejection by most units. The specific risk of potential transmission of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and HBV remains low. Serological tests are routinely performed to screen against these infections prior to donation. Some IVDU and homosexuals have clean practices and a track record of voluntary blood tests for infection. Nevertheless, there exists the potential window of a few weeks to several months prior to seroconversion in cases of recently acquired infection. Our center has accepted such donors and performs mandatory HCV RNA polymerase chain reaction (PCR) and more recently HBV DNA PCR prior to implantation. There remains a low theoretical risk of HIV transmission in these circumstances. Effective therapy is available in the form of highly active antiretroviral therapy (HAART). Nevertheless recipients are made aware of the potential and this forms an important part of the consent process. In this study the immunosuppressive regime evolved; we pursued a strategy of steroid avoidance in selected patients. A more detailed analysis of immunosuppressive regimes on

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kidney transplantation outcomes has been previously reported by our institution,19 showing an increased incidence of acute rejection episodes among those with steroid avoidance but no overall difference in graft function or survival. Our results failed to show this observation in those grafts refused by multiple centers, which may reflect the relatively small number of patients in this group. There is not sufficient published literature for firm recommendations or guidelines regarding the acceptance of extended criteria donors. This may be an important factor in the subjective assessment of potential donors by various centers, potentially contributing to a cascade effect on other centers offered the rejected graft. The rejected grafts fall into to one of two broad categories: (1) those rejected due to identifiable, objectively confirmed risk factors, and (2) those rejected on the basis of subjective assessment of the kidney by the retrieving surgeon. It is possible to implant some of the kidneys in the latter category after appropriate risk-benefit analysis and discussion with involved clinicians and recipients. Such considerations should be left to individual centers and recipient circumstances. Kidneys turned down on anatomical grounds should be reassessed by at least one consultant surgeon before or final refusal decision. Based on our experience with such kidneys, we have revised our acceptance/rejection criteria, recommending regular audit of standards a to best utilize this scare resource. ACKNOWLEDGMENTS We thank Clare Ecuyer (Transplant Coordinator) for maintaining and providing the dataset for the study.

REFERENCES 1. United Kingdom Transplant Activity Report. 2005–2006: Available at: http://www.uktransplant.org.uk/ukt/statistics/statistics. jsp. Accessed February 22, 2008 2. Guidelines relating to solid organ transplants from non-heart beating donors: British Transplantation Society. Available at: http://www.bts.org.uk/standards.htm. Accessed November 2004

FARID, ALDOURI, FRASER ET AL 3. Meier-Kriesche HU, Kaplan B: Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes. Paired donor kidney analysis. Transplantation 74:1377, 2002 4. The Cost Effectiveness of Kidney Transplantation: Statement from UK Transplant. Available at http://www.uktransplant.org.uk/ukt. Accessed January 2007 5. Perico N, Ruggenenti P, Scalamogna M, et al: Tackling the shortage donor kidneys; how to use the best that we have. Am J Nephrol 23:245, 2003 6. Lopez-Navidad A, Cabellero F: Extended criteria for organ acceptance. Strategies for achieving organ safety and for increasing the organ pool. Clin Transplant 17:308, 2003 7. Ramos E, Aoun S, Harmon W: Expanding the donor pool: effect on graft outcome. J Am Soc Nephrol 13:2590, 2002 8. Berthoux F: Evaluation and selection of donors. Nephrol Dial Transplant 15:39, 2000 9. Bilgin N, Karakayali H, Moray G, et al: Outcome of renal transplantation from elderly donors. Transplant Proc 30:744, 1996 10. Bryan C, Harell K, Mitchell S, et al: HLA points assigned in cadaveric kidney allocation should be revised: an analysis of HLA class II molecularly typed patients and donors. Am J Transplant 3:459, 2003 11. Su X, Zenios S, Chakkera H, et al: Diminished significance of HLA matching in kidney transplantation. Am J Transplant 4:1501, 2004 12. Irish WD, McCollum DA, Raymond JT, et al: Nomogram for predicting the likelihood of delayed graft function in adult cadaveric renal recipients. J Am Soc Nephrol 14:2967, 2003 13. Perico N, Cattaneo D, Sayegh MH, et al: Delayed graft function in kidney transplantation. Lancet 364:1814, 2004 14. Woo YM, Jardine AG, Clark AF, et al: Early graft function and patient survival following cadaveric renal transplantation. Kidney Int 55:692, 1999 15. Becker YT, Leverson GE, D’Alessandro AM, et al: Diabetic kidneys can safely expand the donor pool. Transplantation 74:141, 2002 16. Frei U, Schindler R, Wieters D, et al: Pre transplant hypertension: a major risk factor for chronic progressive renal allograft dysfunction. Nephrol Dial Transplant 10:1206, 1995 17. Chan PCK, Lok ASF, Cheng IKP, et al: The impact of donor and recipient hepatitis B surface antigen status on liver disease and survival in renal transplant recipients. Transplantation 53:128, 1992 18. Lumbreras C, Sanz F, Gonzalez A, et al: Clinical significance of donor unrecognised bacteraemia in the outcome of solid organ transplant recipients. Clin Infect Dis 33:722, 2001 19. Welberry Smith MP, Newstead C, Ahmad N, Poor tolerance of sirolimus in a steroid avoidance regimen for renal transplantation. Transplantation 85:636, 2008