- Email: [email protected]
Illinois Statewide Dual Kidney Transplantation Experience—Are We Appropriately Selecting Kidneys?
Transplantation/Vascular Surgery
Illinois Statewide Dual Kidney Transplantation Experience— Are We Appropriately Selecting Kidneys? Cory M. Hugen,* Anthony J. Polcari, Ronald Skolek, Martin F. Mozes and John E. Milner From the Department of Urology, Loyola University Medical Center, Maywood (CMH, AJP, JEM), and Gift of Hope, Itasca (RS, MFM), Illinois
Abbreviations and Acronyms CIT ⫽ cold ischemia time DCD ⫽ donation after cardiac death DGF ⫽ delayed graft function DKT ⫽ dual kidney transplant DM ⫽ diabetes mellitus DSA ⫽ donation service area ECD ⫽ expanded criteria donor GS ⫽ glomerulosclerosis HTN ⫽ hypertension MP ⫽ machine perfusion OPO ⫽ organ procurement organization SKT ⫽ single kidney transplant Submitted for publication December 16, 2010. Study received institutional review board approval. * Correspondence: Department of Urology, Loyola University Medical Center, Fahey Center, Room 244, Maywood, Illinois 60153 (telephone: 708-216-5100; FAX: 708-216-8991; e-mail: [email protected]).
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Purpose: Dual kidney transplantation is a technique that some transplant centers have adopted to increase organ use. We investigated whether kidneys that were recovered and discarded were similar to those kidneys used for dual kidney transplantation. Materials and Methods: We reviewed all kidneys recovered, biopsied and placed on machine perfusion in the state of Illinois from January 2002 to October 2009. We selected those kidneys used in dual kidney transplant, and compared their characteristics to those of kidneys that were recovered and biopsied but ultimately discarded. The immediate and 1-year outcomes of the dual kidney transplant recipients were analyzed. Results: During the study period 60 dual transplants were performed while 94 kidney pairs were discarded. Overall donors from the used group had a lower mean creatinine clearance, older mean patient age, lower percentage of glomerulosclerosis, higher final flow rate and lower resistance. However, the comparison between those kidneys used successfully with 1-year graft survival and those discarded demonstrated only 3 less favorable parameters among the discarded group, namely a higher percentage of glomerulosclerosis (18.5% vs 13.9%, p ⫽ 0.024), a higher degree of interstitial fibrosis and a higher final resistance (0.39 vs 0.31, p⬍0.001). Conclusions: The considerable overlap in demographics, histology and perfusion parameters between used and discarded kidneys suggests that many kidneys that were recovered and discarded could have been used in dual kidney transplantation with acceptable outcomes. This highlights the need for further study of how kidneys are selected and used. Key Words: kidney transplantation, perfusion, graft survival SINCE the Crystal City report was published proposing guidelines to maximize the use of organs recovered from deceased donors,1 there has been an increase in the number of patients consented for organ donation, kidneys recovered and kidneys ultimately transplanted. Although the total number of kidneys recovered in the last decade has increased by nearly 4,000 over the
number from the prior decade, the proportion of these kidneys that are ultimately discarded has also increased significantly from 10% in 1998 to 17% in 2007.2 A factor which has likely contributed to this phenomenon is the increased recovery of DCD and ECD kidneys.3 Studies examining the factors that determine whether a kidney is used
0022-5347/11/1863-0996/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 186, 996-1000, September 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.04.084
AND
RESEARCH, INC.
DUAL KIDNEY TRANSPLANTATION
or discarded have found that biopsy findings, the use of machine perfusion and the donation service area from which the kidney originates all have a role in the selection process.4 Some studies have reported that kidneys with a higher percentage of glomerulosclerosis on biopsy are associated with worse outcomes,5,6 but other studies have not corroborated these findings.7,8 Thus, there is no clear consensus regarding the importance of GS in kidney selection. Additionally, kidneys placed on MP have been shown to have a lower incidence of DGF,9 increased use10 and improved 1-year graft outcomes.11 Dual kidney transplantation, a technique that some transplant centers have adopted to increase organ use, has traditionally been performed when pediatric kidneys are offered for an adult patient or when it is believed that a single kidney would not suffice due to the marginal status of the donor. Recent studies have shown that DKT provides excellent long-term outcomes even when performed with kidneys classified as DCD or ECD.7,12,13 Despite numerous studies demonstrating that patients who undergo kidney transplantation have improved survival and quality of life compared with those who remain on dialysis14 even when marginal kidneys are used,15 thousands of kidneys are recovered and then discarded each year. All agree we must increase our efforts to maximally use the existing supply of deceased donor kidneys. To determine whether those kidneys ultimately discarded could possibly have been used successfully with DKT, we examined the Illinois statewide experience of DKT, and compared the characteristics of kidney pairs used for DKT with those of kidneys that were recovered, biopsied and perfused but then discarded.
MATERIALS AND METHODS With institutional review board approval a review of all kidneys recovered and subsequently placed on MP in the state of Illinois from January 2002 to October 2009 was performed. Information was extracted from a database which is maintained prospectively by the organ procurement organization serving the entire state of Illinois. This OPO served 8 transplant centers during the study period. Donor demographic and clinic data were entered into the database as recorded by the OPO transplant coordinator at the time of donation. Creatinine clearance was calculated using the Cockcroft-Gault equation. Recipient followup information was reported from the transplant center to the OPO at 1 week, 1 month, 6 months and 1 year. Restricted access to this database was granted by the OPO director. All kidney pairs used for DKT were identified. The donor demographics, kidney biopsy results and MP parameters were analyzed. The characteristics of these kidneys were then compared with available organs that were biopsied and perfused but ultimately discarded. To see if there were differences between the discarded pairs and
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those used successfully in DKT, we selected only recipients with functioning grafts after 1 year of followup. The donor demographics, kidney biopsy results and MP parameters of these proven kidneys were compared with those that were discarded. All biopsies were reviewed by a single pathologist employed by the OPO. GS was reported as a raw percentage in the original database, and for the purposes of analysis the kidneys were categorized into group 1— 0% to 5%, group 2— 6% to 10%, group 3—11% to 15%, group 4 —16% to 20%, group 5—21% to 25% and group 6 — greater than 25% GS. Arteriolosclerosis was reported as none, mild, moderate or severe. Interstitial fibrosis was reported by the pathologist as none, mild, moderate or severe, and kidneys were analyzed according to these groupings. All kidneys included in this analysis were placed on MP according to the OPO protocol to place all DCD and ECD kidneys on MP or at the discretion of the OPO medical director. Kidneys were perfused using a LifePort® Kidney Transporter or RM3 (Waters Medical Systems, Rochester, Minnesota) perfusion machine. Statistical analysis was performed using SPSS® 16.0 for Windows. Bivariate analyses included chi-square tests of association and t tests, with results considered significant at p ⬍0.05.
RESULTS During the study period 60 DKTs (120 kidneys) were performed and 94 pairs (188 kidneys) were discarded. The donor demographic and clinical data as well as the kidney biopsy results and perfusion parameters are detailed in table 1. Mean ⫾ SD cold ischemia time for the used group was 26.3 ⫾ 7.5 hours. A total of 15 (25%) DKT recipients experienced DGF, defined as the need for some form of renal replacement therapy in postoperative week 1. Overall donors from the discarded group had a higher mean admission creatinine clearance (87.4 vs 76.9, p ⫽ 0.008) and a younger mean age (57 vs 62, p ⬍0.001) than those in the used group. There were no significant differences in initial and final creatinine levels, the proportion of patients with HTN and DM, or biopsy findings of interstitial fibrosis and arteriolosclerosis between the groups. However, those in the used group did have a lower mean percentage of glomerulosclerosis (14.7 ⫾ 12.1 vs 18.5 ⫾ 17.9, p ⫽ 0.042), higher final flow rate and lower resistance. There were 58 recipients (97%) with a complete set of 1-year followup data. Of these patients 50 (87%) were alive off dialysis, 4 (7%) were alive on dialysis and 4 (7%) were deceased. The mean serum creatinine of the 50 patients off dialysis was 10.69 ⫾ 0.68 mg/dl at 1 year. A comparison between those kidneys used successfully with 1-year graft survival and those discarded is presented in table 2. We found that all parameters were similar between the groups except younger donor age (57 vs 62, p ⫽ 0.001), higher admission creatinine clearance (87.4 vs 76.6,
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Table 1. Demographic, biopsy and pulsatile perfusion parameters of all kidneys Used No. of kidneys Mean ⫾ SD pt age Mean ⫾ SD Cr: Initial Final Clearance No. history of HTN (%) No. DM more than 5 yrs (%) No. interstitial fibrosis (%): None Mild Moderate Severe No. arteriolosclerosis (%): None Mild Moerate Severe Mean ⫾ SD % GS No. % GS (%): 0–5 6–10 11–15 16–20 21–25 Greater than 25 Mean ⫾ SD initial flow Mean ⫾ SD initial resistance Mean ⫾ SD final flow Mean ⫾ SD final resistance
120 62
⫾ 10
Discarded 188 57
⫾ 13
1.05 ⫾ 0.38 1.39 ⫾ 0.76 76.9 ⫾ 24.8 78 (65) 24 (20)
1.27 ⫾ 1.53 1.57 ⫾ 0.94 87.4 ⫾ 38.1 134 (71) 28 (15)
23 (19) 84 (70) 13 (11) 0
37 (20) 105 (57) 40 (22) 1
p Value ⬍0.001* 0.129* 0.081* 0.008* 0.258† 0.276† 0.055†
0.79† 32 (26) 39 (33) 41 (34) 8 (7) 14.7 ⫾ 12.1
44 (24) 54 (30) 69 (37) 16 (9) 18.5 ⫾ 17.9
27 (22.5) 26 (21.7) 21 (17.5) 17 (14.2) 10 (8.3) 19 (15.8) 78.8 ⫾ 36.3 0.52 ⫾ 0.28 114 ⫾ 32 0.30 ⫾ 0.10
45 (23.9) 33 (17.6) 20 (10.6) 18 (9.6) 18 (9.6) 54 (28.7) 75.0 ⫾ 38.2 0.61 ⫾ 0.35 105 ⫾ 40 0.39 ⫾ 0.20
0.042†
0.38* 0.016* 0.031* ⬍0.001*
* t Test comparing sample means. † Chi-square test comparing sample proportions.
p ⫽ 0.011), higher final resistance (0.39 vs 0.31, p⬍0.001), a higher degree of interstitial fibrosis (p ⫽ 0.018) and a higher mean percentage of GS (18.5% vs 13.9%, p ⫽ 0.024) among those kidneys discarded. When patients with more than 25% GS on biopsy were excluded from analysis, the mean percent GS in the used group was 10.86% ⫾ 7.3% vs 9.97% ⫾ 7.7% in the discard group (p ⫽ 0.39).
DISCUSSION The widening gap between organ supply and demand is among the most challenging issues facing the transplant community today. One part of the solution to this complex problem is to maximally use the existing kidney supply without compromising recipient outcomes. DKT has been used to this end in select cases with excellent results. In our study there was a 25% rate of DGF, 87% 1-year graft survival and 93% 1-year patient survival among recipients of DKT, which compared favorably to other series,7,12,13 and to national United Network for Organ Sharing averages for single kidneys of 89% and 94%, respectively. Furthermore, kidney pairs
discarded within the same OPO had many characteristics similar to those which were transplanted successfully, suggesting that there is opportunity for improved use. When we compared all kidneys used for DKT with those discarded there were some significant differences with regard to biopsy results and perfusion parameters, implying that these variables were used in the selection process. However, when we compared only kidneys that survived 1 year with those that were discarded, many of these differences disappeared. The characteristics that differed significantly were age, admission creatinine clearance, interstitial fibrosis severity, glomerulosclerosis amount and final resistance. The statistical difference in glomerulosclerosis between the 2 groups disappeared when we excluded kidneys with more than 25% GS. Surprisingly, age and admission creatinine clearance were actually less favorable among the used group. DKT has been used increasingly in the last decade, often using ECD kidneys. While it has been shown that ECD kidneys may have nearly equivalent results to standard criteria donors in highly Table 2. Demographic, biopsy and pulsatile perfusion parameters of kidney used with 1-year graft survival and of those discarded Used No. kidneys Mean ⫾ SD pt age Mean ⫾ SD Cr: Initial Final Clearance No. history of HTN (%) No. DM more than 5 yrs (%) No. interstital fibrosis (%): None Mild Moderate Severe No. arteriolosclerosis (%): None Mild Moderate Severe Mean ⫾ SD % GS No. % GS (%): 0–5 6–10 11–15 16–20 21–25 Greater than 25 Mean ⫾ SD initial flow Mean ⫾ SD initial resistance Mean ⫾ SD final flow Mean ⫾ SD final resistance
100 62
⫾ 10
Discarded 188 57
⫾ 13
1.06 ⫾ 0.40 1.42 ⫾ 0.79 76.6 ⫾ 24.3 68 (68) 14 (14)
1.27 ⫾ 1.53 1.57 ⫾ 0.94 87.4 ⫾ 38.1 134 (71.3) 28 (14.9)
20 (20) 72 (72) 8 (8) 0
37 (20) 105 (57) 40 (22) 1 (1)
p Value 0.001* 0.117* 0.192* 0.011* 0.56† 0.84† 0.018†
0.39† 32 (32) 31 (31) 31 (31) 6 (6) 13.9 ⫾ 11.9
44 (24) 54 (30) 69 (37) 16 (9) 18.5 ⫾ 17.9
25 (25) 22 (22) 15 (15) 16 (16) 10 (10) 12 (12) 75.2 ⫾ 33.7 0.55 ⫾ 0.30 111 ⫾ 31 0.31 ⫾ 0.10
45 (23.9) 33 (17.6) 20 (10.6) 18 (9.6) 18 (9.6) 54 (28.7) 75.0 ⫾ 38.2 0.61 ⫾ 0.35 105 ⫾ 40 0.39 ⫾ 0.20
* t Test comparing sample means. † Chi-sqaure test comparing sample proportions.
0.024†
0.96* 0.13* 0.18* 0.⬍001*
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selected recipients,16 not all patients meet these rigorous selection criteria and would not likely do well with a single ECD kidney. However, these patients may benefit from a dual transplant with 2 ECD kidneys. Several investigators have reported on their experiences with DKT in these situations. Andres et al reported excellent results with DKT in recipients older than 75 years or those 60 to 74 years old with transplant biopsy demonstrating GS greater than 15%.17 Remuzzi et al reported nearly equivalent early results in a case-control study comparing recipients receiving DKT or SKT as determined by a biopsy scoring system.18 A followup study with long-term outcomes was recently reported in which the authors found that recipients of kidneys from donors older than 60 years old who underwent SKT (8 recipients) or DKT (54 recipients) fared as well as recipients of SKT from donors younger than 60 years old and better than SKT recipients from donors older than 60 years who did not undergo biopsy.19 Additionally, 2 large studies analyzing United Network for Organ Sharing data have reported excellent results with DKT.13,20 Despite these data and the familiarity of more centers with DKT, many kidneys are still being discarded. Sung et al found that the DSA from which an ECD kidney originates is an independent predictor of discard,4 suggesting that DSAs have different thresholds for using ECD kidneys. This may be partly explained by the wide variability in wait times between DSAs and, thus, the need to use ECD kidneys.21 Because many kidneys in areas where ECDs are less likely to be used are discarded, it is possible that these kidneys could be used for DKT in other DSAs experienced with DKT. Another factor limiting the growth of DKT is a lack of published guidelines about which kidneys should be used in DKT and which recipients are most likely to benefit. There is no consensus regarding the importance of biopsy results, MP parameters or recipient demographics in determining success after renal transplantation. While some studies have evaluated scoring systems,22,23 donor glomerular filtration rate24 and donor creatinine clearance25 to help guide selection for DKT, individual
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transplant centers are faced with this decision likely based on limited experience and guided only by a novel series of literature. Thus, kidneys which probably could be used with successful outcomes are overlooked and discarded. As the collective experience grows and more literature becomes available, the role of DKT will continue to be refined. Some limitations of the current study should be addressed. Patients were not selected to undergo DKT by any standard selection criteria but instead underwent DKT based on the decision at each individual center. The inherent selection bias incurred with this sort of allocation system cannot be underestimated. In addition, the decision to discard kidneys may have been related to donor and recipient characteristics not reported in the database. For example, potential infectious issues or high risk behaviors in the donor, rather than biopsy results or perfusion parameters alone, could have affected the selection decision. In addition, the mean CIT is longer than ideal, especially considering that these ECD kidneys are already of poorer quality. The prolonged CIT may partially be explained by the allocation system used for these kidneys. Most kidneys were initially offered as single kidneys and, when rejected, were then offered as a pair. The CIT could potentially be lowered by initially offering the kidneys as a pair. Finally, while the DKTs performed were shown to have good short-term outcomes, the argument in favor of using the discarded kidneys would be strengthened by 5-year outcomes on par with standard criteria donor transplants.
CONCLUSIONS We have demonstrated that within a single OPO, DKT performed using ECD and DCD kidneys results in acceptable 1-year outcomes. In addition, many kidneys that were recovered and eventually discarded were similar to those kidneys used for DKT with good outcomes. This finding suggests that more transplants could be performed with the existing supply of deceased donor kidneys, and could help alleviate the widening gap between kidney supply and demand.
REFERENCES 1. Rosengard BR, Feng S, Alfrey EJ et al: Report of the Crystal City meeting to maximize the use of organs recovered from the cadaver donor. Am J Transplant 2002; 2: 701.
3. Metzger RA, Delmonico FL, Feng et al: Expanded criteria donors for kidney transplantation. Am J
2. Scientific Registry of Transplant Recipients, 2008 Annual Report, Tables 3.1 and 3.3. Available at http://optn.transplant.hrsa.gov/ar2008/Chapter_ II_AR_CD.htm?cp⫽3#10. Accessed May 7, 2010.
4. Sung RS, Christensen LL, Leichtman AB et al: Determinants of discard of expanded criteria donor kidneys: impact of biopsy and machine perfusion. Am J Transplant 2008; 8: 783.
Transplant 2003; 3: 114.
5. Gaber LW, Moore LW, Alloway RR et al: Glomerulosclerosis as a determinant of posttransplant function of older donor renal allografts. Transplantation 1995; 60: 334. 6. Randhawa PS, Minervini MI, Lombardero M et al: Biopsy of marginal donor kidneys: correlation of histologic findings with graft dysfunction. Transplantation 2000; 69: 1352.
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7. Tan JC, Alfrey EJ, Dafoe DC et al: Dual-kidney transplantation with organs from expanded criteria donors: a long-term follow-up. Transplantation 2004; 78: 692. 8. Pokorna E, Vitko S, Chadimova M et al: Proportion of glomerulosclerosis in procurement wedge renal biopsy cannot alone discriminate for acceptance of marginal donors. Transplantation 2000; 69: 36. 9. Wight JP, Chilcott JB, Holmes MW et al: Pulsatile machine perfusion vs. cold storage of kidneys for transplantation: a rapid and systematic review. Clin Transplant 2003; 4: 293. 10. Schold JD, Kaplan B, Howard RJ et al: Are we frozen in time? Analysis of the utilization and efficacy of pulsatile perfusion in renal transplantation. Am J Transplant 2005; 5: 1681. 11. Moers C, Smits JM, Maathuis MH et al: Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 2009; 360: 7. 12. Alfrey EJ, Boissy AR and Lerner SM: Dual-kidney transplants: long-term results. Transplantation 2003; 75: 1232. 13. Gill J, Cho YW, Danovitch GM et al: Outcomes of dual adult kidney transplants in the United States: an analysis of the OPTN/UNOS database. Transplantation 2008; 85: 62.
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14. Wolfe RA, Ashby VB, Milford EL et al: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999; 341: 1725. 15. Ojo AO, Hanson JA, Meier-Kriesche H et al: Survival in recipients of marginal cadaveric donor kidneys compared with other recipients and waitlisted transplant candidates. J Am Soc Nephrol 2001; 12: 589. 16. Stratta RJ, Rohr MS, Sundberg AK et al: Increased kidney transplantation utilizing expanded criteria deceased organ donors with results comparable to standard criteria donor transplant. Ann Surg 2004; 239: 688. 17. Andres A, Morales JM, Herrero JC et al: Double versus single renal allografts from aged donors. Transplantation 2000; 69: 2060. 18. Remuzzi G, Grinyo J, Ruggenenti P et al: Early experience with dual kidney transplantation in adults using expanded donor criteria. Double Kidney Transplant Group. J Am Soc Nephrol 1999; 10: 2591. 19. Remuzzi G, Cravedi P, Perna A et al: Long-term outcome of renal transplantation from older donors. N Engl J Med 2006; 354: 343.
20. Bunnapradist S, Gritsch HA, Peng A et al: Dual kidneys from marginal adult donors as a source for cadaveric renal transplantation in the United States. J Am Soc Nephrol 2003; 14: 1031. 21. Sung RS, Guidinger MK, Lake CD et al: Impact of the expanded criteria donor allocation system on the use of expanded criteria donor kidneys. Transplantation 2005; 79: 1257. 22. Nyberg SL, Baskin-Bey ES, Kremers W et al: Improving the prediction of donor kidney quality: deceased donor score and resistive indices. Transplantation 2005; 80: 925. 23. Wolters HH, Palmes D, Heidenreich S et al: Longterm follow-up of double kidney transplantation using a score for evaluation of marginal donors. Transpl Int 2005; 18: 453. 24. Snanoudj R, Rabant M, Timsit MO et al: Donorestimated GFR as an appropriate criterion for allocation of ECD kidneys into single or dual kidney transplantation. Am J Transplant 2009; 9: 2542. 25. Singh D, Kiberd B and Lawen J: Can the outcome of older donor kidneys in transplantation be predicted? An analysis of existing scoring systems. Clin Transplant 2004; 18: 351.
Illinois Statewide Dual Kidney Transplantation Experience— Are We Appropriately Selecting Kidneys? Cory M. Hugen,* Anthony J. Polcari, Ronald Skolek, Martin F. Mozes and John E. Milner From the Department of Urology, Loyola University Medical Center, Maywood (CMH, AJP, JEM), and Gift of Hope, Itasca (RS, MFM), Illinois
Abbreviations and Acronyms CIT ⫽ cold ischemia time DCD ⫽ donation after cardiac death DGF ⫽ delayed graft function DKT ⫽ dual kidney transplant DM ⫽ diabetes mellitus DSA ⫽ donation service area ECD ⫽ expanded criteria donor GS ⫽ glomerulosclerosis HTN ⫽ hypertension MP ⫽ machine perfusion OPO ⫽ organ procurement organization SKT ⫽ single kidney transplant Submitted for publication December 16, 2010. Study received institutional review board approval. * Correspondence: Department of Urology, Loyola University Medical Center, Fahey Center, Room 244, Maywood, Illinois 60153 (telephone: 708-216-5100; FAX: 708-216-8991; e-mail: [email protected]).
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Purpose: Dual kidney transplantation is a technique that some transplant centers have adopted to increase organ use. We investigated whether kidneys that were recovered and discarded were similar to those kidneys used for dual kidney transplantation. Materials and Methods: We reviewed all kidneys recovered, biopsied and placed on machine perfusion in the state of Illinois from January 2002 to October 2009. We selected those kidneys used in dual kidney transplant, and compared their characteristics to those of kidneys that were recovered and biopsied but ultimately discarded. The immediate and 1-year outcomes of the dual kidney transplant recipients were analyzed. Results: During the study period 60 dual transplants were performed while 94 kidney pairs were discarded. Overall donors from the used group had a lower mean creatinine clearance, older mean patient age, lower percentage of glomerulosclerosis, higher final flow rate and lower resistance. However, the comparison between those kidneys used successfully with 1-year graft survival and those discarded demonstrated only 3 less favorable parameters among the discarded group, namely a higher percentage of glomerulosclerosis (18.5% vs 13.9%, p ⫽ 0.024), a higher degree of interstitial fibrosis and a higher final resistance (0.39 vs 0.31, p⬍0.001). Conclusions: The considerable overlap in demographics, histology and perfusion parameters between used and discarded kidneys suggests that many kidneys that were recovered and discarded could have been used in dual kidney transplantation with acceptable outcomes. This highlights the need for further study of how kidneys are selected and used. Key Words: kidney transplantation, perfusion, graft survival SINCE the Crystal City report was published proposing guidelines to maximize the use of organs recovered from deceased donors,1 there has been an increase in the number of patients consented for organ donation, kidneys recovered and kidneys ultimately transplanted. Although the total number of kidneys recovered in the last decade has increased by nearly 4,000 over the
number from the prior decade, the proportion of these kidneys that are ultimately discarded has also increased significantly from 10% in 1998 to 17% in 2007.2 A factor which has likely contributed to this phenomenon is the increased recovery of DCD and ECD kidneys.3 Studies examining the factors that determine whether a kidney is used
0022-5347/11/1863-0996/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 186, 996-1000, September 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.04.084
AND
RESEARCH, INC.
DUAL KIDNEY TRANSPLANTATION
or discarded have found that biopsy findings, the use of machine perfusion and the donation service area from which the kidney originates all have a role in the selection process.4 Some studies have reported that kidneys with a higher percentage of glomerulosclerosis on biopsy are associated with worse outcomes,5,6 but other studies have not corroborated these findings.7,8 Thus, there is no clear consensus regarding the importance of GS in kidney selection. Additionally, kidneys placed on MP have been shown to have a lower incidence of DGF,9 increased use10 and improved 1-year graft outcomes.11 Dual kidney transplantation, a technique that some transplant centers have adopted to increase organ use, has traditionally been performed when pediatric kidneys are offered for an adult patient or when it is believed that a single kidney would not suffice due to the marginal status of the donor. Recent studies have shown that DKT provides excellent long-term outcomes even when performed with kidneys classified as DCD or ECD.7,12,13 Despite numerous studies demonstrating that patients who undergo kidney transplantation have improved survival and quality of life compared with those who remain on dialysis14 even when marginal kidneys are used,15 thousands of kidneys are recovered and then discarded each year. All agree we must increase our efforts to maximally use the existing supply of deceased donor kidneys. To determine whether those kidneys ultimately discarded could possibly have been used successfully with DKT, we examined the Illinois statewide experience of DKT, and compared the characteristics of kidney pairs used for DKT with those of kidneys that were recovered, biopsied and perfused but then discarded.
MATERIALS AND METHODS With institutional review board approval a review of all kidneys recovered and subsequently placed on MP in the state of Illinois from January 2002 to October 2009 was performed. Information was extracted from a database which is maintained prospectively by the organ procurement organization serving the entire state of Illinois. This OPO served 8 transplant centers during the study period. Donor demographic and clinic data were entered into the database as recorded by the OPO transplant coordinator at the time of donation. Creatinine clearance was calculated using the Cockcroft-Gault equation. Recipient followup information was reported from the transplant center to the OPO at 1 week, 1 month, 6 months and 1 year. Restricted access to this database was granted by the OPO director. All kidney pairs used for DKT were identified. The donor demographics, kidney biopsy results and MP parameters were analyzed. The characteristics of these kidneys were then compared with available organs that were biopsied and perfused but ultimately discarded. To see if there were differences between the discarded pairs and
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those used successfully in DKT, we selected only recipients with functioning grafts after 1 year of followup. The donor demographics, kidney biopsy results and MP parameters of these proven kidneys were compared with those that were discarded. All biopsies were reviewed by a single pathologist employed by the OPO. GS was reported as a raw percentage in the original database, and for the purposes of analysis the kidneys were categorized into group 1— 0% to 5%, group 2— 6% to 10%, group 3—11% to 15%, group 4 —16% to 20%, group 5—21% to 25% and group 6 — greater than 25% GS. Arteriolosclerosis was reported as none, mild, moderate or severe. Interstitial fibrosis was reported by the pathologist as none, mild, moderate or severe, and kidneys were analyzed according to these groupings. All kidneys included in this analysis were placed on MP according to the OPO protocol to place all DCD and ECD kidneys on MP or at the discretion of the OPO medical director. Kidneys were perfused using a LifePort® Kidney Transporter or RM3 (Waters Medical Systems, Rochester, Minnesota) perfusion machine. Statistical analysis was performed using SPSS® 16.0 for Windows. Bivariate analyses included chi-square tests of association and t tests, with results considered significant at p ⬍0.05.
RESULTS During the study period 60 DKTs (120 kidneys) were performed and 94 pairs (188 kidneys) were discarded. The donor demographic and clinical data as well as the kidney biopsy results and perfusion parameters are detailed in table 1. Mean ⫾ SD cold ischemia time for the used group was 26.3 ⫾ 7.5 hours. A total of 15 (25%) DKT recipients experienced DGF, defined as the need for some form of renal replacement therapy in postoperative week 1. Overall donors from the discarded group had a higher mean admission creatinine clearance (87.4 vs 76.9, p ⫽ 0.008) and a younger mean age (57 vs 62, p ⬍0.001) than those in the used group. There were no significant differences in initial and final creatinine levels, the proportion of patients with HTN and DM, or biopsy findings of interstitial fibrosis and arteriolosclerosis between the groups. However, those in the used group did have a lower mean percentage of glomerulosclerosis (14.7 ⫾ 12.1 vs 18.5 ⫾ 17.9, p ⫽ 0.042), higher final flow rate and lower resistance. There were 58 recipients (97%) with a complete set of 1-year followup data. Of these patients 50 (87%) were alive off dialysis, 4 (7%) were alive on dialysis and 4 (7%) were deceased. The mean serum creatinine of the 50 patients off dialysis was 10.69 ⫾ 0.68 mg/dl at 1 year. A comparison between those kidneys used successfully with 1-year graft survival and those discarded is presented in table 2. We found that all parameters were similar between the groups except younger donor age (57 vs 62, p ⫽ 0.001), higher admission creatinine clearance (87.4 vs 76.6,
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Table 1. Demographic, biopsy and pulsatile perfusion parameters of all kidneys Used No. of kidneys Mean ⫾ SD pt age Mean ⫾ SD Cr: Initial Final Clearance No. history of HTN (%) No. DM more than 5 yrs (%) No. interstitial fibrosis (%): None Mild Moderate Severe No. arteriolosclerosis (%): None Mild Moerate Severe Mean ⫾ SD % GS No. % GS (%): 0–5 6–10 11–15 16–20 21–25 Greater than 25 Mean ⫾ SD initial flow Mean ⫾ SD initial resistance Mean ⫾ SD final flow Mean ⫾ SD final resistance
120 62
⫾ 10
Discarded 188 57
⫾ 13
1.05 ⫾ 0.38 1.39 ⫾ 0.76 76.9 ⫾ 24.8 78 (65) 24 (20)
1.27 ⫾ 1.53 1.57 ⫾ 0.94 87.4 ⫾ 38.1 134 (71) 28 (15)
23 (19) 84 (70) 13 (11) 0
37 (20) 105 (57) 40 (22) 1
p Value ⬍0.001* 0.129* 0.081* 0.008* 0.258† 0.276† 0.055†
0.79† 32 (26) 39 (33) 41 (34) 8 (7) 14.7 ⫾ 12.1
44 (24) 54 (30) 69 (37) 16 (9) 18.5 ⫾ 17.9
27 (22.5) 26 (21.7) 21 (17.5) 17 (14.2) 10 (8.3) 19 (15.8) 78.8 ⫾ 36.3 0.52 ⫾ 0.28 114 ⫾ 32 0.30 ⫾ 0.10
45 (23.9) 33 (17.6) 20 (10.6) 18 (9.6) 18 (9.6) 54 (28.7) 75.0 ⫾ 38.2 0.61 ⫾ 0.35 105 ⫾ 40 0.39 ⫾ 0.20
0.042†
0.38* 0.016* 0.031* ⬍0.001*
* t Test comparing sample means. † Chi-square test comparing sample proportions.
p ⫽ 0.011), higher final resistance (0.39 vs 0.31, p⬍0.001), a higher degree of interstitial fibrosis (p ⫽ 0.018) and a higher mean percentage of GS (18.5% vs 13.9%, p ⫽ 0.024) among those kidneys discarded. When patients with more than 25% GS on biopsy were excluded from analysis, the mean percent GS in the used group was 10.86% ⫾ 7.3% vs 9.97% ⫾ 7.7% in the discard group (p ⫽ 0.39).
DISCUSSION The widening gap between organ supply and demand is among the most challenging issues facing the transplant community today. One part of the solution to this complex problem is to maximally use the existing kidney supply without compromising recipient outcomes. DKT has been used to this end in select cases with excellent results. In our study there was a 25% rate of DGF, 87% 1-year graft survival and 93% 1-year patient survival among recipients of DKT, which compared favorably to other series,7,12,13 and to national United Network for Organ Sharing averages for single kidneys of 89% and 94%, respectively. Furthermore, kidney pairs
discarded within the same OPO had many characteristics similar to those which were transplanted successfully, suggesting that there is opportunity for improved use. When we compared all kidneys used for DKT with those discarded there were some significant differences with regard to biopsy results and perfusion parameters, implying that these variables were used in the selection process. However, when we compared only kidneys that survived 1 year with those that were discarded, many of these differences disappeared. The characteristics that differed significantly were age, admission creatinine clearance, interstitial fibrosis severity, glomerulosclerosis amount and final resistance. The statistical difference in glomerulosclerosis between the 2 groups disappeared when we excluded kidneys with more than 25% GS. Surprisingly, age and admission creatinine clearance were actually less favorable among the used group. DKT has been used increasingly in the last decade, often using ECD kidneys. While it has been shown that ECD kidneys may have nearly equivalent results to standard criteria donors in highly Table 2. Demographic, biopsy and pulsatile perfusion parameters of kidney used with 1-year graft survival and of those discarded Used No. kidneys Mean ⫾ SD pt age Mean ⫾ SD Cr: Initial Final Clearance No. history of HTN (%) No. DM more than 5 yrs (%) No. interstital fibrosis (%): None Mild Moderate Severe No. arteriolosclerosis (%): None Mild Moderate Severe Mean ⫾ SD % GS No. % GS (%): 0–5 6–10 11–15 16–20 21–25 Greater than 25 Mean ⫾ SD initial flow Mean ⫾ SD initial resistance Mean ⫾ SD final flow Mean ⫾ SD final resistance
100 62
⫾ 10
Discarded 188 57
⫾ 13
1.06 ⫾ 0.40 1.42 ⫾ 0.79 76.6 ⫾ 24.3 68 (68) 14 (14)
1.27 ⫾ 1.53 1.57 ⫾ 0.94 87.4 ⫾ 38.1 134 (71.3) 28 (14.9)
20 (20) 72 (72) 8 (8) 0
37 (20) 105 (57) 40 (22) 1 (1)
p Value 0.001* 0.117* 0.192* 0.011* 0.56† 0.84† 0.018†
0.39† 32 (32) 31 (31) 31 (31) 6 (6) 13.9 ⫾ 11.9
44 (24) 54 (30) 69 (37) 16 (9) 18.5 ⫾ 17.9
25 (25) 22 (22) 15 (15) 16 (16) 10 (10) 12 (12) 75.2 ⫾ 33.7 0.55 ⫾ 0.30 111 ⫾ 31 0.31 ⫾ 0.10
45 (23.9) 33 (17.6) 20 (10.6) 18 (9.6) 18 (9.6) 54 (28.7) 75.0 ⫾ 38.2 0.61 ⫾ 0.35 105 ⫾ 40 0.39 ⫾ 0.20
* t Test comparing sample means. † Chi-sqaure test comparing sample proportions.
0.024†
0.96* 0.13* 0.18* 0.⬍001*
DUAL KIDNEY TRANSPLANTATION
selected recipients,16 not all patients meet these rigorous selection criteria and would not likely do well with a single ECD kidney. However, these patients may benefit from a dual transplant with 2 ECD kidneys. Several investigators have reported on their experiences with DKT in these situations. Andres et al reported excellent results with DKT in recipients older than 75 years or those 60 to 74 years old with transplant biopsy demonstrating GS greater than 15%.17 Remuzzi et al reported nearly equivalent early results in a case-control study comparing recipients receiving DKT or SKT as determined by a biopsy scoring system.18 A followup study with long-term outcomes was recently reported in which the authors found that recipients of kidneys from donors older than 60 years old who underwent SKT (8 recipients) or DKT (54 recipients) fared as well as recipients of SKT from donors younger than 60 years old and better than SKT recipients from donors older than 60 years who did not undergo biopsy.19 Additionally, 2 large studies analyzing United Network for Organ Sharing data have reported excellent results with DKT.13,20 Despite these data and the familiarity of more centers with DKT, many kidneys are still being discarded. Sung et al found that the DSA from which an ECD kidney originates is an independent predictor of discard,4 suggesting that DSAs have different thresholds for using ECD kidneys. This may be partly explained by the wide variability in wait times between DSAs and, thus, the need to use ECD kidneys.21 Because many kidneys in areas where ECDs are less likely to be used are discarded, it is possible that these kidneys could be used for DKT in other DSAs experienced with DKT. Another factor limiting the growth of DKT is a lack of published guidelines about which kidneys should be used in DKT and which recipients are most likely to benefit. There is no consensus regarding the importance of biopsy results, MP parameters or recipient demographics in determining success after renal transplantation. While some studies have evaluated scoring systems,22,23 donor glomerular filtration rate24 and donor creatinine clearance25 to help guide selection for DKT, individual
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transplant centers are faced with this decision likely based on limited experience and guided only by a novel series of literature. Thus, kidneys which probably could be used with successful outcomes are overlooked and discarded. As the collective experience grows and more literature becomes available, the role of DKT will continue to be refined. Some limitations of the current study should be addressed. Patients were not selected to undergo DKT by any standard selection criteria but instead underwent DKT based on the decision at each individual center. The inherent selection bias incurred with this sort of allocation system cannot be underestimated. In addition, the decision to discard kidneys may have been related to donor and recipient characteristics not reported in the database. For example, potential infectious issues or high risk behaviors in the donor, rather than biopsy results or perfusion parameters alone, could have affected the selection decision. In addition, the mean CIT is longer than ideal, especially considering that these ECD kidneys are already of poorer quality. The prolonged CIT may partially be explained by the allocation system used for these kidneys. Most kidneys were initially offered as single kidneys and, when rejected, were then offered as a pair. The CIT could potentially be lowered by initially offering the kidneys as a pair. Finally, while the DKTs performed were shown to have good short-term outcomes, the argument in favor of using the discarded kidneys would be strengthened by 5-year outcomes on par with standard criteria donor transplants.
CONCLUSIONS We have demonstrated that within a single OPO, DKT performed using ECD and DCD kidneys results in acceptable 1-year outcomes. In addition, many kidneys that were recovered and eventually discarded were similar to those kidneys used for DKT with good outcomes. This finding suggests that more transplants could be performed with the existing supply of deceased donor kidneys, and could help alleviate the widening gap between kidney supply and demand.
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