- Email: [email protected]
Laparoscopic kidney donation from patients older than 60 years1
Laparoscopic Kidney Donation from Patients Older than 60 Years Stephen C Jacobs, MD, FACS, J Robert Ramey, MD, Geoffrey N Sklar, MD, Stephen T Bartlett, MD, FACS The current study seeks to determine if the efficacy and safety of laparoscopic donor nephrectomy holds true when performed in patients older than 60 years of age. STUDY DESIGN: Medical records of 42 renal donors older than 60 years were reviewed compared with younger controls carefully matched for gender, race, nephrectomy side, auxiliary recipient procedures, and date of surgery. RESULTS: Preoperative baseline serum creatinine was identical in both groups (0.9 ⫾ 0.2 mg/dL) although controls had a slightly higher (NS) creatinine clearance (106.9 ⫾ 19.1 versus 100.0 ⫾ 35.5 mL/m). Operatively, there was no substantial difference between groups in operative time, warm ischemia time, estimated blood loss, number or size of ports used, and length of incision needed for removal of kidney. Intraoperative and postoperative complication rates were also equivalent between old and young donors. Postnephrectomy serum creatinine was identical. There was no increased length of hospitalization for older donors and they tended to require less morphine sulfate patient-controlled anesthesia. Recipient renal function was slightly better in the younger kidneys early and the difference became statistically significant at 6 to 12 months, but the magnitude of the improvement is not clinically important. CONCLUSIONS: Laparoscopic donor nephrectomy may be performed safely in patients older than 60 years of age. There was no increase in complication rates or length of hospital stay. Older donors did not have a greater increase in serum creatinine after donation compared with donors younger than 40 years of age, nor did recipients of these older kidneys have clinically significantly higher serum creatinine than recipients of kidneys from donors less than 40 years old. ( J Am Coll Surg 2004;198:892–897. © 2004 by the American College of Surgeons) BACKGROUND:
donor nephrectomy appears to increase the likelihood that a living donor will be identified.2,3 Laparoscopically procured kidneys have been shown to provide equivalent recipient outcomes and donor safety when compared with the traditional open surgical technique.4-8 Laparoscopic donation has been shown to reduce postoperative pain, shorten hospitalization, allow a faster return to work, and provide improved cosmetic results,4-9 possibly decreasing disincentives to donation.2,3 The potential donor pool may now include previously excluded groups, including donors older than the traditional range. The impact of age on donor well-being, recipient graft function, and graft survival needs to be assessed. A well-described, age-associated decline in renal function results from a combination of structural and functional alterations to the kidney parenchyma and its vasculature.10 Renal vessels develop atherosclerotic occlusions along with intimal and medial thickening of the smaller vessels. Additionally, glomeruli undergo progressive sclerosis producing a decrease in glomerular surface
As the waiting list of patients for cadaver renal allografts grows longer, living related donation has become an increasingly popular option. Renal transplantation from living donors yields improvements in both overall recipient and graft survival when compared with cadaveric allografts. Although open donor nephrectomy is a relatively safe procedure, the gap between the number of organs needed and the number of patients awaiting renal transplantation continues to increase. With goals of reducing donor morbidity and encouraging increased numbers of living donor volunteers, transplantation centers introduced laparoscopic donor nephrectomy programs.1 The availability of laparoscopic No competing interests declared.
Received October 16, 2003; Revised February 16, 2004; Accepted February 18, 2004. From the Department of Surgery, Divisions of Urology (Jacobs, Ramey, Sklar) and Transplantation (Bartlett), University of Maryland School of Medicine, Baltimore, MD. Correspondence address: Stephen C Jacobs, MD, 22 S Greene St, Baltimore, MD 21201.
© 2004 by the American College of Surgeons Published by Elsevier Inc.
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ISSN 1072-7515/04/$30.00 doi:10.1016/j.jamcollsurg.2004.02.018
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Table 1. Preoperative Characteristics of Elderly Kidney Donors
Characteristic
Age (y) Creatinine (mg%) CrCl (mL/min) HLA match First-degree relative (%) Weight (kg) Height (in) BMI (kg/m2) Race (% Caucasion)
Controls (n ⴝ 42)
> 60 y (n ⴝ 42)
Male controls (n ⴝ 24)
Men > 60 y (n ⴝ 24)
Female controls (n ⴝ 18)
Women > 60 y (n ⴝ 18)
33.0 ⫾ 5.0 0.9 ⫾ 0.2 106.9 ⫾ 19.1 3.0 ⫾ 1.5 67 80.1 ⫾ 17.2 67.1 ⫾ 4.2 28.0 ⫾ 5.1 83
64.5 ⫾ 3.9 0.9 ⫾ 0.2 100.0 ⫾ 35.5 2.8 ⫾ 1.8 50 79.7 ⫾ 12.8 67.5 ⫾ 3.6 27.1 ⫾ 4.4 83
34.5 ⫾ 4.5 1.0 ⫾ 0.2 111.0 ⫾ 22.3 3.1 ⫾ 1.5 63 86.1 ⫾ 15.1 69.6 ⫾ 2.7 27.9 ⫾ 4.5 82
65.3 ⫾ 3.9 1.0 ⫾ 0.2 99.2 ⫾ 23.1 2.8 ⫾ 1.5 41 84.1 ⫾ 11.2 69.7 ⫾ 2.0 26.8 ⫾ 3.7 82
31.0 ⫾ 5.2 0.8 ⫾ 0.1 103.9 ⫾ 16.2 2.9 ⫾ 1.5 72 72.1 ⫾ 17.0 63.9 ⫾ 3.5 28.0 ⫾ 5.9 83
63.4 ⫾ 3.8 0.8 ⫾ 0.1 101.0 ⫾ 48.1 2.7 ⫾ 2.1 64 73.9 ⫾ 12.7 64.6 ⫾ 3.2 27.5 ⫾ 5.4 83
Data are mean ⫾ SD except where percentages as indicated. BMI, body mass index; CrCl, creatinine clearance.
area and the total number of functional nephrons. Functional losses include a decrease in both renal blood flow and glomerular filtration rate and impaired sodium retention and concentrating ability. Older kidneys might be expected to be at greater risk when subjected to the peritransplantation insults as ischemia and rejection. This raises concerns about the interaction of the decreased renal reserve capacity that comes with the normal aging process and the conditions of laparoscopic surgery. Studies of cadaveric renal allografts generally indicate that older kidneys have poorer longterm graft survival.11-18 The United Network for Organ Sharing registry clearly shows a stepwise decline in cadaver graft survival with donor ages more than 50 years.19 This deleterious effect of advanced donor age has not been seen in studies of living related donor nephrectomy performed through an open approach.20 So the current study was undertaken to determine whether the benefits of laparoscopic donor nephrectomy may safely be extended to donors older than age 60 with acceptable graft outcomes. METHODS From March 1996 to March 2002, 42 transperitoneal laparoscopic donor nephrectomies were performed on living donors older than 60 years at the University of Maryland Medical Center. This comprised 5.7% of the laparoscopic donor nephrectomies performed in the time period. Donor preoperative evaluation was by standard protocol.21 Donors older than age 50 years routinely undergo cardiac stress testing. Retrospective chart reviews were performed (IRB exemption No. 1202916). The preoperative, operative, and postoperative data
from the aged donors were compared with data from a carefully matched control group of 42 donors less than 40 years of age. Ancillary protocols specific to the institution logistically affecting the donors include simultaneous cadaver pancreas and living donor renal transplantation and pretransplant recipient plasmapheresis for high plasma reactive antibodies. Each elderly donor had a matched control chosen from a pool of 369 laparoscopic renal donors less than 40 years old. The controls were not chosen randomly: each elderly donor had a control chosen in order by race, gender, nephrectomy side, date of surgery, and participation in ancillary protocols. Statistical analysis was with software SPSS for Windows version 6.1.3. (SPSS Inc). Data expressed are as mean ⫾ SD. RESULTS Matching of the controls to aged donors was very close. Each group comprised 18 women and 24 men with identical racial profiles (1 Asian, 6 African American, 35 Caucasian). Six donors were entered in the simultaneous cadaver pancreas living kidney transplant protocol and one donor was enrolled in the high plasma reactive antibodies protocol in each group. Date of surgery was close. In the series, the control donor nephrectomies were 10 ⫾ 13 operations separated from their matched donor (28 ⫾ 39 days). There were two right nephrectomies in the aged donors and only one right nephrectomy in the control group. Preoperative comparison of the donors is found in Table 1. Baseline serum creatinine was identical in both the aged and control groups (0.9 ⫾ 0.2 mg/dL), although controls had a slightly higher creatinine clearance. The donor–recipient rela-
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Table 2. Operative Data
Operative time (min) Warm ischemia time (s) Estimated blood loss (mL) 12-mm ports 5-mm ports Incision length (cm)
Controls
> 60 y
Male controls
Men > 60 y
Female controls
Women > 60 y
201.7 ⫾ 55.1 170.3 ⫾ 95.9 112 ⫾ 121 1.5 ⫾ 1.1 2.0 ⫾ 0.9 6.6 ⫾ 1.0
210.2 ⫾ 51.2 195.6 ⫾ 99.8 157 ⫾ 266 1.4 ⫾ 1.1 2.0 ⫾ 0.9 6.8 ⫾ 1.9
194.5 ⫾ 43.2 174.5 ⫾ 120.9 147 ⫾ 145 1.4 ⫾ 1.0 2.0 ⫾ 0.8 6.7 ⫾ 1.2
208.5 ⫾ 40.9 205.2 ⫾ 123.1 110 ⫾ 103 1.4 ⫾ 1.0 2.2 ⫾ 0.9 6.9 ⫾ 2.4
211.6 ⫾ 68.6 165.0 ⫾ 53.2 85 ⫾ 91 1.7 ⫾ 1.2 1.9 ⫾ 1.0 6.5 ⫾ 0.8
212.1 ⫾ 62.7 183.7 ⫾ 61.5 401 ⫾ 157 1.4 ⫾ 1.2 1.9 ⫾ 0.8 6.8 ⫾ 0.9
Data are mean ⫾ SD. There were no statistical differences with regard to gender of the donor.
tionships and HLA matching were similar. The size of the donors was similar. Caucasians made up a larger percentage (83%) of the 2 groups than the percentage in our overall laparoscopic donor experience (68%). Operatively, there were no substantial differences between the groups with regard to operative time, warm ischemia time, estimated blood loss, number or size of ports used, and length of incision needed for removal of kidney (see Table 2). Intraoperative and postoperative complication rates were also equivalent between the elderly and younger control donors (see Table 3). Of donors older than 60 years, 9.5% experienced intraoperative complications, similar to the intraoperative complications seen in donors less than 40 years old (21%). Postoperative complications occurred in 21% and 11.9% of donors, respectively. Conversion to open donor nephrectomy was similar and occurred in one donor older than age 60 years (2.3%). Postoperatively there was no increased length of hospitalization for older donors and they required less morphine sulfate patient-controlled analgesia (Table 4). Serum creatinine levels during postoperative hospitalization were identical between the groups. Bowel function returned in the two groups at the same time: liquid diets were tolerated at 1 day and regular diets were tolerated at 2 days. With respect to recipient graft function (Fig. 1), there was a nonsignificant trend toward increased recipient serum creatinine with kidneys from the older donors (1.9 ⫾ 1.2 mg/dL versus 1.6 ⫾ 0.9 mg/dL at 1 week).
There was also a slight increase in delayed graft function with older kidneys (4.7% versus 2.4%). Graft survival at 1 year was 86% for kidneys from older donors and 100% for kidneys from younger controls. DISCUSSION Concerns over using kidneys from elderly donors comes primarily from the cadaver transplantation experience. Rao and colleagues10 found no difference in overall recipient survival at 1, 2, or 3 years post-transplantation using cadaver kidneys older than 50 years, but did note substantially lower graft survival at years 2 and 3 with these older organs. Additionally, measurements of creatinine clearance indicated a slight but notable impairment in both the short- and longterm renal function of these recipients. Subsequent reports substantiated the adverse impact of donor age on cadaver graft longterm function.11-18 Because of the shortage of available organs, cadaver grafts from elderly donors continue to be used regularly, though two elderly kidneys may be transplanted together in an effort to provide more renal mass.19 Living related renal donor programs have also expanded the traditional age range upward. Sumrani and colleagues22 evaluated the impact of age on the outcomes of open living donor nephrectomy. Comparing recipients of kidneys older than 55 years with those younger than 55 years, they found similar graft and patient survival rates and equal incidence of rejection between the
Table 3. Complications Seen in Elderly Donors Intraoperative complications Controls
Pneumothorax Splenic laceration (n ⫽ 2) Adrenal hemorrhage Extraction incision enlarged Branch renal artery injury (n ⫽ 2)
Postoperative complications < 60 y
Controls
< 60 y
Conversion (stapler misfire) Splenic laceration Bradycardia Extraction incision enlarged —
Urinary retention (n ⫽ 2) Umbilical hernia Epididymitis Atelectasis —
Urinary retention (n ⫽ 5) Delayed ileus (n ⫽ 2) Pancreatitis Atelectasis —
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Table 4. Postoperative Data
Hospital stay (h) Morphine sulfate, mg Creatinine, mg% Preop creatinine/postop creatinine
Controls
> 60 y
Male controls
Men > 60 y
Female controls
Women > 60 y
61.6 ⫾ 20.3 76.0 ⫾ 45.0* 1.4 ⫾ 0.3 1.4
64.9 ⫾ 21.4 49.7 ⫾ 65.4* 1.4 ⫾ 0.3 1.5
60.1 ⫾ 24.1 66.5 ⫾ 41.4 1.5 ⫾ 0.2 1.7
63.2 ⫾ 21.3 45.2 ⫾ 43.3 1.5 ⫾ 0.2 1.5
62.7 ⫾ 14.3 87.1 ⫾ 47.8 1.2 ⫾ 0.2 1.1
67.2 ⫾ 21.8 56.3 ⫾ 93.5 1.2 ⫾ 0.2 1.4
*p ⫽ 0.05. Conversion to open surgery donor excluded from analysis. Postop, postoperative; preop, preoperative.
two groups. Older kidney recipients had elevated serum creatinine levels in the early post-transplantation period. Renal function then remained stably elevated for the course of followup, with the slope of recipient serum creatinine versus time similar regardless of donor age. The current series also shows a nonstatistically significant initial trend toward increased serum creatinine in recipients of kidneys older than 60 years at 1-week followup. But this elevation resolved by 1-month posttransplantation and no significant difference in serum creatinine was noted between groups for the remainder of the 2-year followup. Concerns have been raised about the quality of organs harvested by transperitoneal laparoscopic donor nephrectomy because of physiologic alterations produced by insufflation of the abdomen with carbon dioxide. Most important among these is the potential ischemia produced by decreased renal perfusion secondary to increased intraabdominal pressure. London and colleagues23 demonstrated that exposure to prolonged pneumoperitoneum during nephrectomy in a porcine model produces a 70% reduction in renal blood flow, oliguria, and a significant decrease in postoperative creatinine clearance in euvolemic controls receiving maintenance doses of IV fluid support (3 mL/kg/h of isotonic saline). They were able to prevent these effects of pneu-
moperitoneum with aggressive isotonic intravascular volume expansion (20 mL/kg bolus ⫹ 15 mL/kg/h 0.45% NaCl). Previous human series of laparoscopic donor nephrectomy have not identified any specific effects of pneumoperitoneum on graft function, but the number of confounding variables is great and the issue has not been carefully examined. Procurement teams have been monitoring and maintaining appropriate intravascular volume and urine output throughout the laparoscopic experience. But it is possible that older kidneys, with their decreased reserve capacity, are more susceptible to the effects of increased intraabdominal pressure associated with laparoscopic nephrectomy. This represents a potential source of the transient, early rise in serum creatinine seen in this study with recipients of kidneys older than 60 years. Older patients are at increased risk for perioperative complications when compared with the general population. Yet, when Johnson and colleagues24 investigated the complications and risks associated with open living related donor nephrectomy, multivariate analysis indicated that age of more than 50 years was not an independent risk factor for complications. Age did, on the other hand, appear to be an independent risk factor for prolonged hospitalization. Other risk factors for increased complications identified by this study were male
Figure 1. Recipient graft function of kidneys from older donors. Shaded bar, older than 60 years; white bar, control.
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gender (versus female) and body mass index ⱖ30 kg/m.22 The current series revealed a decrease in the narcotic requirements of male donors older than 60 years, which appears to be primarily because of very low usage in men of this age group. The decreased usage of morphine sulfate patient-controlled analgesia was expected as older patients have been reported to generally require lower doses of narcotics.25 In a small series (n ⫽ 6), Hsu and colleagues26 reported that elderly donors tolerated laparoscopic donor nephrectomy well and recipient function was satisfactory. The results of the current study show donors older than 60 years are comparable to other recently published series on laparoscopic nephrectomy in younger donors for operating time, estimated blood loss, intraoperative complication rate, and conversion to open donor nephrectomy. Postoperatively these older donors did not experience increased complications. Urinary retention requiring recatheterization (11.9%) and prolonged ileus (4.8%) were the most common postoperative complications. In followup of living related open nephrectomy donors Sesso and colleagues18 found that donors experience an increase in serum creatinine, but it does not appear to be related to age at donation and no patient developed overt renal disease after donor nephrectomy. Compensatory renal hypertrophy does continue to occur in the elderly, though to a lesser extent than that seen in the young.27 The current study does not show a difference between genders in immediate postdonation serum creatinine levels, though Sesso and colleagues18 did find a larger drop in glomerular filtration rate associated with female gender. Longterm followup data are not available to assess the renal function of the remaining kidney in our older donors. In a large series from India, Kumar and colleagues28 evaluated 112 elderly open nephrectomy donors and found no increase in morbidity and mortality related to age. The donors averaged 57 years of age, but did range up to 81 years. A Swedish study on the longterm effects of renal donation has indicated that after 20 years kidney donors appear to live longer than the general population of that country.29 Although this likely represents a selection bias, with only the healthiest patients being allowed to donate, it importantly illustrates that there is no longterm increase in mortality post-donor nephrectomy. Donors also did not experience any deaths secondary to renal disease, renal cancer, or other damage to the remaining kidney and the age-
J Am Coll Surg
associated decline in renal function of donors was similar to that seen in normal healthy subjects.30 This analysis indicates equivalent recipient outcomes and donor safety with laparoscopic donor nephrectomy in donors older than 60 years of age compared with those younger than 40 years, the more traditional source of living renal donors. Additionally, our data show that the benefits of laparoscopy, namely decreased pain and postoperative hospital stays, are applicable to this older group of donors as well. These encouraging findings are likely the result of the relative health and lack of comorbid conditions in our older donor cohort, which serves to underscore the necessity of comprehensive predonation screening in this population. The graft life expectancy of older living donor kidneys will not be as long as younger living donor kidneys, but it may approach or surpass that of cadaver kidneys in some patients, particularly poorly HLA-matched recipients or elderly recipients. Further, many renal transplant recipients, especially elderly or vasculopathic renal failure patients, do not have life expectancies as long as the graft life expectancies of young living donor kidneys. Currently only 4% of living renal donors in the United States are 60 years of age or older.30 In view of the fact that laparoscopic live donor nephrectomy appears as safe in donors over 60 years as in younger donors, expansion of the pool of potential related and unrelated donors to include those older than 60 years will help alleviate the current organ shortfall. Author Contributions
Study conception and design: Jacobs, Bartlett Acquisition of data: Ramey Analysis and interpretation of data: Jacobs, Sklar Drafting of manuscript: Jacobs, Sklar Critical revision: Bartlett Statistical expertise: Sklar Supervision: Jacobs REFERENCES 1. Schulam PG, Kavoussi LR, Cheriff AD, et al. Laparoscopic live donor nephrectomy: the initial 3 cases. J Urol 1996;155:1857– 1859. 2. Ratner LE, Hiller J, Sroka M, et al. Laparoscopic live donor nephrectomy removes disincentives to live donation. Trans Proc 1997;29:3402–3403. 3. Schweitzer EJ, Wilson J, Jacobs S, et al. Increased rates of donation with laparoscopic donor nephrectomy. Ann Surg 2000;232: 392–400.
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4. Jacobs SC, Cho E, Dunkin BJ. Laparoscopic donor nephrectomy: current role in renal allograft procurement. Urology 2000;55:807–811. 5. London E, Rudich S, McVicar J, et al. Equivalent renal allograft function with laparoscopic versus open live donor nephrectomies. Transplant Proc 1999;31:258–260. 6. Fabrizio MD, Ratner LE, Montgomery RA, Kavoussi LR. Laparoscopic live donor nephrectomy. Urol Clin North Am 1999; 26:247–256. 7. Jacobs SC, Cho E, Dunkin BJ, et al. Laparoscopic live donor nephrectomy: the University of Maryland 3 year experience. J Urol 2000;164:1494–1499. 8. Brown SL, Biehl TR, Rawlins MC, Hefty T. Laparoscopic live donor nephrectomy: a comparison with the conventional open approach. J Urol 2001;165:766–769. 9. Leventhal JR, Deeik RK, Joehl RJ, et al. Laparoscopic live donor nephrectomy—is it safe? Transplantation 2000;70:602–606. 10. Rao KV, Kasiske BL, Odlund MD, et al. Influence of cadaver donor age on posttransplant renal function and graft outcome. Transplantation 1990;49:91–95. 11. Sumrani N, Delaney V, Ding Z, et al. Renal transplantation from elderly living donors. Transplantation 1991;51:305–309. 12. Morales JM, Campo C, Hernandez E, et al. Influence of donor and recipient age on graft survival rate after renal transplantation with a protocol of low CyA doses. Transplant Proc 1991;23: 2622–2623. 13. 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 2002;74: 1281–1286. 14. Tomal H, Tanabe K, Tokumoto T, et al. Time-dependent risk factors influencing the long-term outcome in living renal allografts: donor age is a crucial risk factor for long-term graft survival more than 5 years after transplantation. Transplantation 2001;72:940–947. 15. Carter JT, Lee CM, Weinstein R, et al. Evaluation of the older cadaveric kidney donor: the impact of donor hypertension and creatinine clearance on graft performance and survival. Transplantation 2002;70:765–771. 16. Segoloni GP, Messina M, Triolo G, et al. Impact of donor age in kidney transplantation. Transplant Proc 1991;23:2620–2621.
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17. Pirsch JD, D’Alessandro AM, Sollinger HW, et al. The effect of donor age, recipient age, and HLA match on immunologic graft survival in cadaver renal transplant recipients. Transplantation 1992;53:55–59. 18. Sesso R, Whelton PK, Klag MJ. Effect of age and gender on kidney function in renal transplant donors: a prospective study. Clin Nephrol 1993;40:31–37. 19. Johnson LB, Kuo PC, Dafoe DC, et al. Double adult renal allografts: a technique for expansion of the cadaveric kidney donor pool. Surgery 1996;120:580–584. 20. Organ Procurement and Transplantation Network. Available at: http://www.optn.org/latestData/rptStrat.asp. 21. Kasiske BL, Ravenscraft M, Ramos EL, et al. The evaluation of living renal transplant donors: clinical practice guidelines. J Am Soc Nephrol 1996;7:2288. 22. Sumrani N, Daskalakis P, Miles AM, et al. The influence of age on function of renal allografts from live related donors. Clin Nephrol 1993;39:260–264. 23. London ET, Ho HS, Neuhaus AMC, et al. Effect of intravascular volume expansion on renal function during prolonged CO2 pneumoperitoneum. Ann Surg 2000;231:195–201. 24. Johnson EM, Remucal MJ, Gillingham KJ, et al. Complications and risks of living donor nephrectomy. Transplantation 1997; 64:1124–1128. 25. Egbert AM, Parks LH, Short LM, Burnett ML. Randomized trial of postoperative patient-controlled analgesia vs intramuscular narcotics in frail elderly men. Arch Int Med 1990;150: 1897–1903. 26. Hsu TH, Su LM, Ratner LE, Kavoussi LR. Laparoscopic donor nephrectomy in the elderly patient. Urology 2002;60:398–401. 27. Velosa JA, Offord KP, Schroeder DR. Effect of age, sex and glomerular filtration rate on renal function outcome of living kidney donors. Transplantation 1995;60:1618–1621. 28. Kumar A, Verma BS, Srivastava A, et al. Long-term followup of elderly donors in a live related renal transplant program. J Urol 2000;163:1654–1668. 29. Fehrman-Ekholm I, Elinder C, Stenbeck M, et al. Kidney donors live longer. Transplantation 1997;64:976–978. 30. Mandal AK, Snyder JJ, Gilbertson DT, et al. Does cadaver donor renal transplantation ever provide better outcomes than live donor renal transplantation? Transplantation 2003;75:494–500.
donor nephrectomy appears to increase the likelihood that a living donor will be identified.2,3 Laparoscopically procured kidneys have been shown to provide equivalent recipient outcomes and donor safety when compared with the traditional open surgical technique.4-8 Laparoscopic donation has been shown to reduce postoperative pain, shorten hospitalization, allow a faster return to work, and provide improved cosmetic results,4-9 possibly decreasing disincentives to donation.2,3 The potential donor pool may now include previously excluded groups, including donors older than the traditional range. The impact of age on donor well-being, recipient graft function, and graft survival needs to be assessed. A well-described, age-associated decline in renal function results from a combination of structural and functional alterations to the kidney parenchyma and its vasculature.10 Renal vessels develop atherosclerotic occlusions along with intimal and medial thickening of the smaller vessels. Additionally, glomeruli undergo progressive sclerosis producing a decrease in glomerular surface
As the waiting list of patients for cadaver renal allografts grows longer, living related donation has become an increasingly popular option. Renal transplantation from living donors yields improvements in both overall recipient and graft survival when compared with cadaveric allografts. Although open donor nephrectomy is a relatively safe procedure, the gap between the number of organs needed and the number of patients awaiting renal transplantation continues to increase. With goals of reducing donor morbidity and encouraging increased numbers of living donor volunteers, transplantation centers introduced laparoscopic donor nephrectomy programs.1 The availability of laparoscopic No competing interests declared.
Received October 16, 2003; Revised February 16, 2004; Accepted February 18, 2004. From the Department of Surgery, Divisions of Urology (Jacobs, Ramey, Sklar) and Transplantation (Bartlett), University of Maryland School of Medicine, Baltimore, MD. Correspondence address: Stephen C Jacobs, MD, 22 S Greene St, Baltimore, MD 21201.
© 2004 by the American College of Surgeons Published by Elsevier Inc.
892
ISSN 1072-7515/04/$30.00 doi:10.1016/j.jamcollsurg.2004.02.018
Jacobs et al
Vol. 198, No. 6, June 2004
Donor Nephrectomy after Age 60
893
Table 1. Preoperative Characteristics of Elderly Kidney Donors
Characteristic
Age (y) Creatinine (mg%) CrCl (mL/min) HLA match First-degree relative (%) Weight (kg) Height (in) BMI (kg/m2) Race (% Caucasion)
Controls (n ⴝ 42)
> 60 y (n ⴝ 42)
Male controls (n ⴝ 24)
Men > 60 y (n ⴝ 24)
Female controls (n ⴝ 18)
Women > 60 y (n ⴝ 18)
33.0 ⫾ 5.0 0.9 ⫾ 0.2 106.9 ⫾ 19.1 3.0 ⫾ 1.5 67 80.1 ⫾ 17.2 67.1 ⫾ 4.2 28.0 ⫾ 5.1 83
64.5 ⫾ 3.9 0.9 ⫾ 0.2 100.0 ⫾ 35.5 2.8 ⫾ 1.8 50 79.7 ⫾ 12.8 67.5 ⫾ 3.6 27.1 ⫾ 4.4 83
34.5 ⫾ 4.5 1.0 ⫾ 0.2 111.0 ⫾ 22.3 3.1 ⫾ 1.5 63 86.1 ⫾ 15.1 69.6 ⫾ 2.7 27.9 ⫾ 4.5 82
65.3 ⫾ 3.9 1.0 ⫾ 0.2 99.2 ⫾ 23.1 2.8 ⫾ 1.5 41 84.1 ⫾ 11.2 69.7 ⫾ 2.0 26.8 ⫾ 3.7 82
31.0 ⫾ 5.2 0.8 ⫾ 0.1 103.9 ⫾ 16.2 2.9 ⫾ 1.5 72 72.1 ⫾ 17.0 63.9 ⫾ 3.5 28.0 ⫾ 5.9 83
63.4 ⫾ 3.8 0.8 ⫾ 0.1 101.0 ⫾ 48.1 2.7 ⫾ 2.1 64 73.9 ⫾ 12.7 64.6 ⫾ 3.2 27.5 ⫾ 5.4 83
Data are mean ⫾ SD except where percentages as indicated. BMI, body mass index; CrCl, creatinine clearance.
area and the total number of functional nephrons. Functional losses include a decrease in both renal blood flow and glomerular filtration rate and impaired sodium retention and concentrating ability. Older kidneys might be expected to be at greater risk when subjected to the peritransplantation insults as ischemia and rejection. This raises concerns about the interaction of the decreased renal reserve capacity that comes with the normal aging process and the conditions of laparoscopic surgery. Studies of cadaveric renal allografts generally indicate that older kidneys have poorer longterm graft survival.11-18 The United Network for Organ Sharing registry clearly shows a stepwise decline in cadaver graft survival with donor ages more than 50 years.19 This deleterious effect of advanced donor age has not been seen in studies of living related donor nephrectomy performed through an open approach.20 So the current study was undertaken to determine whether the benefits of laparoscopic donor nephrectomy may safely be extended to donors older than age 60 with acceptable graft outcomes. METHODS From March 1996 to March 2002, 42 transperitoneal laparoscopic donor nephrectomies were performed on living donors older than 60 years at the University of Maryland Medical Center. This comprised 5.7% of the laparoscopic donor nephrectomies performed in the time period. Donor preoperative evaluation was by standard protocol.21 Donors older than age 50 years routinely undergo cardiac stress testing. Retrospective chart reviews were performed (IRB exemption No. 1202916). The preoperative, operative, and postoperative data
from the aged donors were compared with data from a carefully matched control group of 42 donors less than 40 years of age. Ancillary protocols specific to the institution logistically affecting the donors include simultaneous cadaver pancreas and living donor renal transplantation and pretransplant recipient plasmapheresis for high plasma reactive antibodies. Each elderly donor had a matched control chosen from a pool of 369 laparoscopic renal donors less than 40 years old. The controls were not chosen randomly: each elderly donor had a control chosen in order by race, gender, nephrectomy side, date of surgery, and participation in ancillary protocols. Statistical analysis was with software SPSS for Windows version 6.1.3. (SPSS Inc). Data expressed are as mean ⫾ SD. RESULTS Matching of the controls to aged donors was very close. Each group comprised 18 women and 24 men with identical racial profiles (1 Asian, 6 African American, 35 Caucasian). Six donors were entered in the simultaneous cadaver pancreas living kidney transplant protocol and one donor was enrolled in the high plasma reactive antibodies protocol in each group. Date of surgery was close. In the series, the control donor nephrectomies were 10 ⫾ 13 operations separated from their matched donor (28 ⫾ 39 days). There were two right nephrectomies in the aged donors and only one right nephrectomy in the control group. Preoperative comparison of the donors is found in Table 1. Baseline serum creatinine was identical in both the aged and control groups (0.9 ⫾ 0.2 mg/dL), although controls had a slightly higher creatinine clearance. The donor–recipient rela-
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Table 2. Operative Data
Operative time (min) Warm ischemia time (s) Estimated blood loss (mL) 12-mm ports 5-mm ports Incision length (cm)
Controls
> 60 y
Male controls
Men > 60 y
Female controls
Women > 60 y
201.7 ⫾ 55.1 170.3 ⫾ 95.9 112 ⫾ 121 1.5 ⫾ 1.1 2.0 ⫾ 0.9 6.6 ⫾ 1.0
210.2 ⫾ 51.2 195.6 ⫾ 99.8 157 ⫾ 266 1.4 ⫾ 1.1 2.0 ⫾ 0.9 6.8 ⫾ 1.9
194.5 ⫾ 43.2 174.5 ⫾ 120.9 147 ⫾ 145 1.4 ⫾ 1.0 2.0 ⫾ 0.8 6.7 ⫾ 1.2
208.5 ⫾ 40.9 205.2 ⫾ 123.1 110 ⫾ 103 1.4 ⫾ 1.0 2.2 ⫾ 0.9 6.9 ⫾ 2.4
211.6 ⫾ 68.6 165.0 ⫾ 53.2 85 ⫾ 91 1.7 ⫾ 1.2 1.9 ⫾ 1.0 6.5 ⫾ 0.8
212.1 ⫾ 62.7 183.7 ⫾ 61.5 401 ⫾ 157 1.4 ⫾ 1.2 1.9 ⫾ 0.8 6.8 ⫾ 0.9
Data are mean ⫾ SD. There were no statistical differences with regard to gender of the donor.
tionships and HLA matching were similar. The size of the donors was similar. Caucasians made up a larger percentage (83%) of the 2 groups than the percentage in our overall laparoscopic donor experience (68%). Operatively, there were no substantial differences between the groups with regard to operative time, warm ischemia time, estimated blood loss, number or size of ports used, and length of incision needed for removal of kidney (see Table 2). Intraoperative and postoperative complication rates were also equivalent between the elderly and younger control donors (see Table 3). Of donors older than 60 years, 9.5% experienced intraoperative complications, similar to the intraoperative complications seen in donors less than 40 years old (21%). Postoperative complications occurred in 21% and 11.9% of donors, respectively. Conversion to open donor nephrectomy was similar and occurred in one donor older than age 60 years (2.3%). Postoperatively there was no increased length of hospitalization for older donors and they required less morphine sulfate patient-controlled analgesia (Table 4). Serum creatinine levels during postoperative hospitalization were identical between the groups. Bowel function returned in the two groups at the same time: liquid diets were tolerated at 1 day and regular diets were tolerated at 2 days. With respect to recipient graft function (Fig. 1), there was a nonsignificant trend toward increased recipient serum creatinine with kidneys from the older donors (1.9 ⫾ 1.2 mg/dL versus 1.6 ⫾ 0.9 mg/dL at 1 week).
There was also a slight increase in delayed graft function with older kidneys (4.7% versus 2.4%). Graft survival at 1 year was 86% for kidneys from older donors and 100% for kidneys from younger controls. DISCUSSION Concerns over using kidneys from elderly donors comes primarily from the cadaver transplantation experience. Rao and colleagues10 found no difference in overall recipient survival at 1, 2, or 3 years post-transplantation using cadaver kidneys older than 50 years, but did note substantially lower graft survival at years 2 and 3 with these older organs. Additionally, measurements of creatinine clearance indicated a slight but notable impairment in both the short- and longterm renal function of these recipients. Subsequent reports substantiated the adverse impact of donor age on cadaver graft longterm function.11-18 Because of the shortage of available organs, cadaver grafts from elderly donors continue to be used regularly, though two elderly kidneys may be transplanted together in an effort to provide more renal mass.19 Living related renal donor programs have also expanded the traditional age range upward. Sumrani and colleagues22 evaluated the impact of age on the outcomes of open living donor nephrectomy. Comparing recipients of kidneys older than 55 years with those younger than 55 years, they found similar graft and patient survival rates and equal incidence of rejection between the
Table 3. Complications Seen in Elderly Donors Intraoperative complications Controls
Pneumothorax Splenic laceration (n ⫽ 2) Adrenal hemorrhage Extraction incision enlarged Branch renal artery injury (n ⫽ 2)
Postoperative complications < 60 y
Controls
< 60 y
Conversion (stapler misfire) Splenic laceration Bradycardia Extraction incision enlarged —
Urinary retention (n ⫽ 2) Umbilical hernia Epididymitis Atelectasis —
Urinary retention (n ⫽ 5) Delayed ileus (n ⫽ 2) Pancreatitis Atelectasis —
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Table 4. Postoperative Data
Hospital stay (h) Morphine sulfate, mg Creatinine, mg% Preop creatinine/postop creatinine
Controls
> 60 y
Male controls
Men > 60 y
Female controls
Women > 60 y
61.6 ⫾ 20.3 76.0 ⫾ 45.0* 1.4 ⫾ 0.3 1.4
64.9 ⫾ 21.4 49.7 ⫾ 65.4* 1.4 ⫾ 0.3 1.5
60.1 ⫾ 24.1 66.5 ⫾ 41.4 1.5 ⫾ 0.2 1.7
63.2 ⫾ 21.3 45.2 ⫾ 43.3 1.5 ⫾ 0.2 1.5
62.7 ⫾ 14.3 87.1 ⫾ 47.8 1.2 ⫾ 0.2 1.1
67.2 ⫾ 21.8 56.3 ⫾ 93.5 1.2 ⫾ 0.2 1.4
*p ⫽ 0.05. Conversion to open surgery donor excluded from analysis. Postop, postoperative; preop, preoperative.
two groups. Older kidney recipients had elevated serum creatinine levels in the early post-transplantation period. Renal function then remained stably elevated for the course of followup, with the slope of recipient serum creatinine versus time similar regardless of donor age. The current series also shows a nonstatistically significant initial trend toward increased serum creatinine in recipients of kidneys older than 60 years at 1-week followup. But this elevation resolved by 1-month posttransplantation and no significant difference in serum creatinine was noted between groups for the remainder of the 2-year followup. Concerns have been raised about the quality of organs harvested by transperitoneal laparoscopic donor nephrectomy because of physiologic alterations produced by insufflation of the abdomen with carbon dioxide. Most important among these is the potential ischemia produced by decreased renal perfusion secondary to increased intraabdominal pressure. London and colleagues23 demonstrated that exposure to prolonged pneumoperitoneum during nephrectomy in a porcine model produces a 70% reduction in renal blood flow, oliguria, and a significant decrease in postoperative creatinine clearance in euvolemic controls receiving maintenance doses of IV fluid support (3 mL/kg/h of isotonic saline). They were able to prevent these effects of pneu-
moperitoneum with aggressive isotonic intravascular volume expansion (20 mL/kg bolus ⫹ 15 mL/kg/h 0.45% NaCl). Previous human series of laparoscopic donor nephrectomy have not identified any specific effects of pneumoperitoneum on graft function, but the number of confounding variables is great and the issue has not been carefully examined. Procurement teams have been monitoring and maintaining appropriate intravascular volume and urine output throughout the laparoscopic experience. But it is possible that older kidneys, with their decreased reserve capacity, are more susceptible to the effects of increased intraabdominal pressure associated with laparoscopic nephrectomy. This represents a potential source of the transient, early rise in serum creatinine seen in this study with recipients of kidneys older than 60 years. Older patients are at increased risk for perioperative complications when compared with the general population. Yet, when Johnson and colleagues24 investigated the complications and risks associated with open living related donor nephrectomy, multivariate analysis indicated that age of more than 50 years was not an independent risk factor for complications. Age did, on the other hand, appear to be an independent risk factor for prolonged hospitalization. Other risk factors for increased complications identified by this study were male
Figure 1. Recipient graft function of kidneys from older donors. Shaded bar, older than 60 years; white bar, control.
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gender (versus female) and body mass index ⱖ30 kg/m.22 The current series revealed a decrease in the narcotic requirements of male donors older than 60 years, which appears to be primarily because of very low usage in men of this age group. The decreased usage of morphine sulfate patient-controlled analgesia was expected as older patients have been reported to generally require lower doses of narcotics.25 In a small series (n ⫽ 6), Hsu and colleagues26 reported that elderly donors tolerated laparoscopic donor nephrectomy well and recipient function was satisfactory. The results of the current study show donors older than 60 years are comparable to other recently published series on laparoscopic nephrectomy in younger donors for operating time, estimated blood loss, intraoperative complication rate, and conversion to open donor nephrectomy. Postoperatively these older donors did not experience increased complications. Urinary retention requiring recatheterization (11.9%) and prolonged ileus (4.8%) were the most common postoperative complications. In followup of living related open nephrectomy donors Sesso and colleagues18 found that donors experience an increase in serum creatinine, but it does not appear to be related to age at donation and no patient developed overt renal disease after donor nephrectomy. Compensatory renal hypertrophy does continue to occur in the elderly, though to a lesser extent than that seen in the young.27 The current study does not show a difference between genders in immediate postdonation serum creatinine levels, though Sesso and colleagues18 did find a larger drop in glomerular filtration rate associated with female gender. Longterm followup data are not available to assess the renal function of the remaining kidney in our older donors. In a large series from India, Kumar and colleagues28 evaluated 112 elderly open nephrectomy donors and found no increase in morbidity and mortality related to age. The donors averaged 57 years of age, but did range up to 81 years. A Swedish study on the longterm effects of renal donation has indicated that after 20 years kidney donors appear to live longer than the general population of that country.29 Although this likely represents a selection bias, with only the healthiest patients being allowed to donate, it importantly illustrates that there is no longterm increase in mortality post-donor nephrectomy. Donors also did not experience any deaths secondary to renal disease, renal cancer, or other damage to the remaining kidney and the age-
J Am Coll Surg
associated decline in renal function of donors was similar to that seen in normal healthy subjects.30 This analysis indicates equivalent recipient outcomes and donor safety with laparoscopic donor nephrectomy in donors older than 60 years of age compared with those younger than 40 years, the more traditional source of living renal donors. Additionally, our data show that the benefits of laparoscopy, namely decreased pain and postoperative hospital stays, are applicable to this older group of donors as well. These encouraging findings are likely the result of the relative health and lack of comorbid conditions in our older donor cohort, which serves to underscore the necessity of comprehensive predonation screening in this population. The graft life expectancy of older living donor kidneys will not be as long as younger living donor kidneys, but it may approach or surpass that of cadaver kidneys in some patients, particularly poorly HLA-matched recipients or elderly recipients. Further, many renal transplant recipients, especially elderly or vasculopathic renal failure patients, do not have life expectancies as long as the graft life expectancies of young living donor kidneys. Currently only 4% of living renal donors in the United States are 60 years of age or older.30 In view of the fact that laparoscopic live donor nephrectomy appears as safe in donors over 60 years as in younger donors, expansion of the pool of potential related and unrelated donors to include those older than 60 years will help alleviate the current organ shortfall. Author Contributions
Study conception and design: Jacobs, Bartlett Acquisition of data: Ramey Analysis and interpretation of data: Jacobs, Sklar Drafting of manuscript: Jacobs, Sklar Critical revision: Bartlett Statistical expertise: Sklar Supervision: Jacobs REFERENCES 1. Schulam PG, Kavoussi LR, Cheriff AD, et al. Laparoscopic live donor nephrectomy: the initial 3 cases. J Urol 1996;155:1857– 1859. 2. Ratner LE, Hiller J, Sroka M, et al. Laparoscopic live donor nephrectomy removes disincentives to live donation. Trans Proc 1997;29:3402–3403. 3. Schweitzer EJ, Wilson J, Jacobs S, et al. Increased rates of donation with laparoscopic donor nephrectomy. Ann Surg 2000;232: 392–400.
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