Transplantation is infrequently offered to older persons. Fewer than 5% of those aged ≥ 65 yr begun on dialysis therapy will receive a transplant (1,2). For those selected, the survival rate is favorable (3,4). Case control studies show a survival advantage for transplantation over dialysis, even for those aged over 60 yr of age (2,5), yet kidney transplantation remains controversial for older patients because of the ethical issues surrounding the allocation of scarce organs and the scientific doubts about the efficacy and cost-effectiveness of transplantation in this age group. Many clinicians view dialysis as a stable strategy with an acceptable survival and few short-term risks. In contrast, transplantation, though associated with longer life expectancy and better quality of life, is viewed as having significant risks of short-term morbidity and mortality. The purpose of this study was to use decision analytic modeling to quantify clinical and economic tradeoffs for an older patient considering transplantation.
Materials and Methods
The study examined a theoretical cohort of nondiabetic patients aged 65 yr or more who were stable on dialysis at the time of the decision. Patients were assumed to be medically fit for transplantation and were excluded if they had ongoing malignancy, active cardiovascular disease, or a chronic infective condition. Additional models were constructed for patients who were known to be diabetic at the time of being placed on the waiting list for transplantation and for those with known cardiovascular disease.
The two treatment strategies were transplantation and continued dialysis. Dialysis was defined as thrice weekly in-center hemodialysis, as this is the most common treatment modality used. Similarly, we assumed that patients who opted for transplantation would be transplanted with a cadaveric graft, in accordance with common practice in North America. Although immunosuppression regimens differ widely, we assumed that routine therapy included cyclosporin, prednisone, and mycophenolate mofetil (MMF) with substitution or addition of antilymphocyte products or tacrolimus as necessary. Patients who received a graft could return to the dialysis health state but were assumed not to undergo transplantation twice.
The major clinical events associated with transplantation and with dialysis were summarized using a Markov model programmed in Decision Maker, version 7.0 (6). This technique involves identifying clinically important events and defining them as health “states.” A theoretical cohort of patients cycles from one health state to another, in cycles set at 3 mo, until the time of death.
The model assumed that all patients remained on dialysis until the time of transplantation or, if not transplanted, until death (Figure 1). The model contained six health states: dialysis; transplant; acute rejection (AR); transplant-related complication; AR plus transplant-related complication; and death. The dialysis and transplantation health states include all aspects of health and costs associated with long-term chronic care. Specific dialysis-related complications were not modeled, as the theoretical cohort of patients were considered suitable for transplantation surgery and were therefore assumed to be at low risk for complications. Patients in the dialysis strategy were at zero risk of transplant-related complications.
A small proportion of transplanted patients entered the death health state at the time of transplantation surgery, reflecting perioperative mortality. Those who survived the perioperative period were at risk of developing one or more episodes of AR, transplant-related complication, or a combination of AR and complication. In addition, within each cycle, transplant patients were at risk of sudden death or the resumption of dialysis because of graft loss.
Probabilities were set so that the risk of developing acute rejection was maximal in the first few months, falling exponentially to less than 2% per year by 2 yr. The occurrence of either AR or a complication was assumed to increase the risk of death and the risk of graft loss. Although complications may arise for a variety of clinical reasons, transplant-related complications were grouped as one health state for the purposes of the model. As complications are more common after acute rejection, the overall rate of complications was maximal in the first 2 yr and then fell to a baseline level thereafter.
Four assumptions about mortality were made: perioperative mortality was the same for all patients; mortality related to dialysis was assumed to be constant over time; mortality risk was increased in transplant patients in the presence of either AR or a complication; and the hazard of death was assumed to be additive when a patient had both acute rejection and a complication.
Diabetic patients were considered to be at increased risk of postoperative complications, cardiovascular disease, and death when compared with nondiabetic patients. Drug-induced diabetes was considered as a separate complication in a small proportion of those who received a transplant. We assumed that drug-induced diabetes was life-long, occurred at the time of transplantation, and brought with it the risks of increased mortality and complications described for patients with long-standing diabetes.
The base case assumed that there was a 2-yr delay between the decision to proceed with transplant and harvesting a suitable organ. In practice, however, patients can either proceed with transplantation with an organ from a live donor or be wait-listed for a cadaveric transplant (3,4). Therefore, subsequent analyses with a wait-time of 0 and 4 yr were also performed. Patients with zero wait-time were assumed to have had a living donor organ and therefore incurred extra costs of organ acquisition. During the wait-listing period, the costs, probabilities, and utilities were those of dialysis patients plus additional costs of the transplant work-up. Thus, the overall benefits and risks of transplantation included those from the time spent on the waiting list as well as those incurred after transplantation. Death while waiting for a suitable organ was also anticipated in a proportion of patients.
As patients with end-stage renal failure were expected to be dialysis-dependent for life, the time horizon used for the analysis was the lifetime of the patient. The outcome was measured as life expectancy, both with and without quality-adjustment. Cost-effectiveness was estimated as the incremental cost incurred for each additional quality-adjusted life year (QALY).
Probability values were derived from the literature following a formal MEDLINE search for studies published between 1991 and 2000. When no single study reported the exact probability of an event, an estimate was obtained by combining data from several sources. When multiple studies reported different probability estimates, the studies that most closely represented the population of interest were chosen (e.g., those that focused on an over 65-yr-old population with first cadaveric graft). If multiple studies were relevant, a mean value was calculated and used as the baseline estimate. Data from multiple studies were used to estimate a clinically plausible range for each variable that was used in sensitivity analyses (Table 1).
Life Expectancy for Transplant Patients
Mortality data for dialysis and transplant patients were taken from the United States Renal Data Systems (USRDS). Estimates of transplant and dialysis mortality were validated against published data and that from the Canadian Organ Replacement Register (CORR) (3,7).
We estimated mortality rates in transplant recipients by summing the age-standardized mortality rate (ASR) for the general population and the disease-specific mortality rate for transplantation (8–10):
We calculated the transplant-specific mortality rate by subtracting the ASR for 65-yr-olds from the overall mortality rate reported by the USRDS for 65-yr-old renal transplant recipients. Thus, the predicted overall mortality rate for each age included both an age-specific general mortality rate and an age-independent transplant mortality rate.
Life Expectancy for Dialysis Patients
Dialysis mortality was estimated from the USRDS mortality rate of wait-listed dialysis patients (11). Patients had been selected as being suitable for transplantation, screened, and then placed on the waiting list. The disease-specific mortality rate for dialysis patients who were otherwise suitable for transplantation was calculated by subtracting the age-specific mortality rate for 65-yr-olds in the general population from the overall mortality rate of wait-listed dialysis patients aged 65 to 70 yr old (8,9,11).
The probability of acute rejection was taken from USRDS data and reported rejection rates with MMF treatment (12,13). Additional studies were used to derive the clinically plausible range (1,14–22). Infection rates were estimated from data specifically relating to older patients and from that relating to the large immunosuppressive trials (12,23,24). Other studies were used to establish the clinically plausible range of values (12,15,17,25–27). The relative risk of developing a complication after therapy for acute rejection was estimated by calculating the mean rate reported in six studies that examined the effects of two or more antirejection drug regimens and reported complication rates (28–33). The probability of graft loss was derived directly from USRDS graft survival rates in >65-yr-old patients (4,34). The increased risk of graft loss or death after acute rejection was estimated from one series that reported the reasons for and exact numbers of grafts lost in an elderly cohort of patients (14). The increased risk of death after a complication was estimated on the basis of the assumption that the risk of death after a complication was higher than after acute rejection. The clinically plausible range of values was calculated using data from those studies used to estimate the clinical risk of a complication (12,15,17,25–27). The risk of drug-induced diabetes was estimated by calculating the mean rate reported in several studies (25,35–46).
Utility estimates were derived from the literature. A MEDLINE search revealed seven studies reporting the utility of dialysis or transplantation using the time tradeoff or the standard gamble methods (47–53). One study was clearly superior to others because of its long-term prospective design (it followed dialysis patients through until the time of transplantation) and the specific inclusion of older patients (51). Time tradeoff values reported for patients aged 60 yr or more were used as the baseline estimates. The utility associated with a good transplant (i.e., no dysfunction or comorbidity) and a bad transplant (i.e., multiple problems requiring admission and changes in therapy) were also reported. These, together with information from other reports, were used to determine the clinically plausible range (Table 1) (47–53). No data were available on the disutility associated with an episode of rejection, posttransplant complications, or hospitalization for transplant surgery. The analysis assumed a utility of zero for the whole period of hospitalization associated with rejection episodes, complications, or the initial surgery. The duration of hospitalization was estimated from USRDS data on hospitalization and from the Toronto hospital administrative database for the years 1996/7.
Economic Assumptions and Data
The perspective taken was that of the third-party payer. Costs were estimated from published data (35,51,54–68). Where appropriate, costs were converted to 1999 US dollars by using the median 1999 exchange rate and the Bureau of Labor Statistics Consumer Price Index (69,70). Health outcomes and costs were discounted at 3% per year (71).
We used Medicare data to estimate the annual cost of both transplantation and dialysis (4,72). Although more accurate cost estimates are available for individual strategies, none of these studies utilize the same methods to derive costs for both transplantation and dialysis. We acknowledge that current reimbursement levels for dialysis may underestimate the true costs of providing this service and would introduce a bias favoring dialysis. However, we believe that using comparably costing methodology for transplantation and dialysis is essential in estimating marginal costs across strategies and that introducing a bias against transplantation was acceptable. Estimates for the annual cost of dialysis, transplant surgery, and transplantation follow-up were $50,829, $62,217, and $9,792, respectively.
Newer immunosuppressive medications, including MMF and tacrolimus, are more commonly used now than in the period from which the cost estimates were drawn. Therefore, the cost of transplant follow-up was increased by an estimated $6027 per year, to include the costs of additional, optional treatment with MMF (65,68). The cost of transplant work-up, transplant surgery, and graft failure were also estimated from Medicare data (4,72).
No data were available from Medicare for the costs of acute rejection or transplant-related complications. One study, comparing the costs associated with different immunosuppressive regimens, reported the cost of all complications (by type of complication) and both inpatient and outpatient rejection (60). These were used to estimate costs associated with acute rejection and complications. The clinically plausible range of costs was estimated from all published data available (4,51,58–60,62–65,73–76) (Table 1).
Transplant survival was modeled to within 0.2% of that reported by the USRDS (4). The modeled transplant survival rates were compared with Canadian data taken from the CORR database (5-yr mortality rate: 34.57%, 34.50%, and 32.00% for model, USRDS, and CORR data, respectively).
Both cadaveric and living donor transplantation increased life expectancy (LE) and quality-adjusted LE (QALE) for patients of all ages and comorbidity subgroups (Tables 2 and 3). A 65-yr-old patient without comorbidity gained 1.2 yr of life and approximately 1.1 QALY with transplantation. Gains in LE and QALE were smaller for patients with diabetes and cardiovascular disease. No age threshold was observed (Table 3). Otherwise, healthy patients continued to gain QALY with transplantation even at the age of 80 yr.
The analysis showed that transplantation improved health outcomes at an increased cost (Figure 2). Cadaveric transplantation remained favorable only in those of a relatively young age (<70 yr) without comorbidity. Diabetic patients incurred about twofold higher costs with transplantation than with dialysis because of a higher rate of complications (the additional life years gained from transplantation when aged 65 yr at the time of transplantation equaled 0.7 yr at an incremental cost/QALY of $138,660). Similar results were seen for those transplanted if they had cardiovascular disease (0.7 life-years gained at an incremental cost/QALY of $110,327 when aged 65 yr).
Effect of Increased Wait-Listing Interval
The time to transplantation was varied from 0 to 6 yr to reflect the range of possible waiting times. The results showed the survival advantage decreased considerably with increased waiting time. Transplantation, performed without delay, appeared economically attractive (incremental cost/QALY, <$30,000) for 65-yr-old patients. In patients over the age of 80 yr, the incremental cost per QALY was higher compared with those aged ≤ 65 yr, but it remained favorable when compared with the costs associated with providing life-saving dialysis care (incremental cost/QALY for transplantation, $50,000 for those aged 80 yr). Waiting list times of more than 2 yr were associated with a dramatic increase in cost-effectiveness ratios (incremental cost/QALY: $15 000, $68 000, and $193,600 for wait-listed times of 0, 2, and 4 yr, respectively). At 6.7 yr, the QALE of dialysis for a 65 yr-old equaled that of transplantation (Table 3). Transplantation remained economically attractive for a nondiabetic 65-yr-old patient only if a transplant became available within 22 mo of wait-listing.
One-way sensitivity analyses were performed for all probability, utility, and mortality estimates. The model was said to be sensitive to the variable if the value at which the QALE was equal with either strategy fell within the plausible range. The results were highly sensitive to the duration of time spent on the waiting list (threshold, 6.7 yr). The threshold for the dialysis mortality rate was significantly lower than the clinically plausible range, thus minimizing the likelihood that an error in the estimate would influence the model results (threshold, 1% per year mortality rate on dialysis). The hypothesis that perioperative mortality rates would increase with age, and therefore limit usefulness of transplantation, was tested by sensitivity analysis. No threshold was found.
With regard to cost-effectiveness, the model was tested across the range of plausible values. Sensitivity analysis shows that the analysis is moderately sensitive to the utility of transplantation. The results were not sensitive to other variables (Figure 3).
Transplantation has been shown to be superior to dialysis in younger populations (7,11). This study focused on those patients aged more than 65 yr and had no upper age limit. The study has two principal findings. The first is that transplantation offers substantial gains in both LE and QALE for older patients. The benefits are shown to be higher in those receiving a transplant immediately (as with living donor transplantation), than those who are transplanted after a prolonged wait time. As wait-listed times increase, the clinical benefits of transplantation as a treatment strategy for management of the older person with end-stage renal disease decrease dramatically. These data would promote the use of living donor transplants for the older patient. The second finding is that, in comparison with other accepted medical therapies (e.g., coronary artery bypass surgery or the use of enoxaparin DVT prophylaxis), cadaveric transplantation is economically attractive for otherwise healthy patients up to age 70 yr and in the younger elderly with some comorbidity (77–79).
In older patients, our data show that transplantation compared with dialysis continues to increase LE at an advanced age, but it does so at increased cost. The data also show that for the older patient the attractiveness of transplantation is highly sensitive to the time spent waiting for the transplant. As no consensus exists for the level at which a cost-effectiveness ratio is economically attractive, the interpretation of our results may vary among readers. Azimi and Welch (80) have shown that most authorities support additional expenditures associated with cost-effectiveness ratios of ≤$61,500/QALY but that they draw different conclusions about cost-effectiveness ratios within the range $61,500 and $11,600,000/QALY. On this basis, we would suggest that transplantation is significantly more attractive for patients aged 65 yr in a center where the wait-listed time is ≤2 yr or for patients aged up to 80 yr where a living donor program exists.
In comparison with previous studies, we focused on the implications of transplantation in the older population. Although one may argue that other disease-specific and comorbidity-associated factors may influence survival with transplantation in patients over 70 yr old, we have attempted to adjust for these factors by using age-standardized mortality rates, wide sensitivity analyses, and separate analyses for populations with CV disease and diabetes. In fact, older age may be associated with benefits with respect to transplantation. For example, acute rejection appears to be reduced in older patients because of a less active immune system (1,13,81,82). Although the elderly do not appear to be at lower risk of infection or chronic graft rejection with standard immunosuppressive regimens, future regimens at modified doses may decrease complications in this age group and increase the graft survival. Dialysis vintage, gender, and race are not adjusted for in this analysis. Thus, in the case of black patients, particularly women, one may expect a higher gain from transplantation than for white patients of the same age and comorbidity profile.
Most analyses in younger patients have shown that transplantation offers prolonged survival and cost savings compared with dialysis treatment (51,59,60,62,65,73,83). Using our model, a patient aged 55 yr who was transplanted after a 2-yr period on the waiting list could expect prolongation of LE by 1.1 yr (estimated LE of 9.2 yr and 8.0 yr with transplantation and dialysis, respectively). Cost-effectiveness after a 2-yr wait for a cadaveric organ showed an incremental cost of $55,237/QALY with transplantation. In contrast to our findings, others have suggested that transplantation results in a longer LE at lower costs (51,62,73). One reason for this discrepancy is potential overestimation of costs and marginal underestimation of survival benefits in younger patients with this model, because utilities for transplantation and dialysis rates and consequences (e.g., death) of acute rejection and infections, hospitalization duration, and costs were derived from data specifically relating to patients aged ≥65 yr. Also, incremental costs per QALY increased with increased time on the waiting list, suggesting that, regardless of age, longer wait times significantly impact on the cost-benefits of transplantation.
The results of our analysis are somewhat conservative because of some assumptions made in the model. First, Medicare charges tend to underestimate the actual costs of providing dialysis care to the standards currently recommended (54,84). In addition, the costs of acute rejection or transplant-related complications reflect those cases, requiring hospitalization rather than those managed in an outpatient setting. These assumptions result in an overestimation of the costs of transplantation and an underestimation of the costs of dialysis. Second, the analysis used pessimistic utilities for the complications of transplantation, again resulting in a bias that favors dialysis. In contrast, the time costs for patients on hemodialysis, in terms of both lost leisure and productivity, are only captured within the utility value for current health thus favoring transplantation.
Renal transplantation has been controversial in older patients. From the clinician’s viewpoint, our results confirm that many older patients may benefit from renal transplantation. However, liberalizing transplant criteria may introduce problems. First, ethical arguments against the allocation of scarce cadaveric organs to older patients may still prevail. Second, advocating that older patients should be accepted for transplantation would only increase the number of potential recipients for each cadaveric organ harvested and thus further prolong the wait-list. We acknowledge that our study does not address the issues of equity or rationing and that individual healthcare providers will need to develop their policies on the basis of local availability. We do, however, advocate financing transplantation, particularly living donor transplantation, in this population.
In conclusion, renal transplantation offers significant LE gains for well-selected patients aged ≤70 yr, with the young elderly having the most economically favorable profile. Transplantation centers should consider the substantial health benefits that could accrue to the elderly in formulating equitable transplant policies. Potential benefits from transplantation would have to be evaluated within the context of local wait-listed times and the local availability of organs.
Funding in the form of a Research Fellowship to SVJ has been provided by the Ontario Government.
1. Albrechtson D, Leivestad T, Sodal G, Bentdal O, Berg KG, Brekke I, Fauchald P, Flatmark A, Jakobsen A, Lien B, Nordal K, Pfeffer P, Thorsby E, Soreide O: Kidney transplantation in patients older than 70 years of age. Transplant Proc 27: 86–88, 1995
2. Schaubel D, Desmeules M, Mao Y, Jeffery J, Fenton SS: Survival experience among elderly end-stage renal disease patients. Transplantation 60: 1389–1394, 1995
3. Canadian Institute for Health Information. Annual Report 1999, Dialysis and Transplantation, Canadian Organ Replacement Register. 1999. Ottawa, Ontario. Volume 1
4. National Institute of Diabetes and Digestive and Kidney Diseases: U.S: Renal data systems, Annual Data Report (on CD). Researchers Guide, reference tables and ADR slides Ann Arbor MI, United States Renal Data System Coordinating Center, 2000
5. Wolfe RA, Ashby EL, Milford EL, Ojo AO, Ettenger RE, Agodoa LYC, Held PJ, Port FK: Patient survival for wait-listed dialysis versus cadaveric renal transplant patients in the US. J Am Soc Nephrol 8: 708, 1997
6. Sonnenberg FA, Beck R: Markov models in medical decision making: a practical guide. Med Decis Making 13: 322–338, 1993
7. Rabbat CG, Thorpe KE, Russell JD, Churchill DN: Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario. Canada. J Am Soc Nephrol 11: 917–922, 2000
8. Beck JR, Kassirer JP, Pauker SG: The convenient approximation of life expectancy (The “DEALE”). I. Validation of the method. Am J Med 73: 883–888, 1982
9. Beck JR, Pauker SG, Gottlieb JE, Klein K, Kassirer JP: A convenient approximation of life expectancy (The “DEALE”). II: Use in medical decision making. Am J Med 73: 889–897, 1982
10. David P and Millar, W: Life tables, Canada and provinces and Health reports - Supplement no. 13. 84–537-XPB. 1995. Statistics Canada
11. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Eng J Med 341: 1725–1730, 1999
12. The Tricontinental mycophenylate mofetil renal transplantation study group: A blinded, randomized clinical trial of mycophenylate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 61: 1029–1037, 1996
13. Sullivan SD, Garrison LP, Best JH, and members of the US Renal Transplant Mycophenolate Mofetil study group: The cost effectiveness of mycophenolate mofetil in the first year after primary cadaveric transplant. J Am Soc Nephrol 8: 1592–1598, 1997
14. Cole EH, Farewell VT, Aprile M, Cattran DC, Pei YP, Fenton SS, Zaltzman J, Cardella CJ: Renal transplantation in older patients: the University of Toronto experience. Ger Nephrol Urol 5: 85–92, 1995
15. Riera L, Seron D, Castelao AM, Grino JM, Franco E, Bover J, Vigues L, Alsina J, Serrallach N: Renal transplantation in cyclosporin-treated patients over age 50. Transplant Proc 24: 122–123, 1992
16. Morales JM, Munoz MA, Campo C, Andres A, Araque A, Alamo C, Praga M, Ortuno T, Hernandez E, Rodicio JL: Renal transplantation in older patients with double therapy with optional change to cyclosporin monotherapy: long term results. Transplant Proc 26: 2511–2512, 1994
17. Andreu J, de la Torre M, Oppenheimer F, Campistol, JM, Ricart MJ, Vilardell J, Talbot R, Carretero P: Renal transplantation in elderly recipients. Transplant Proc 24: 120–121, 1992
18. Morris GE, Jamieson NV, Small J, Evans DB, Calne SR: Cadaveric renal transplantation in elderly recipients: Is it worthwhile ? Nephrol Dial Transplant 6: 887–892, 1991
19. MacDonell RC, Van Buren DH, Richie RE, Johnson HK, Nylander WA, Hledlerman JH, Ynares CM, Trusler LA, Green WF, Crowe DA: Kidney transplantation at extremes of age: CsA eliminates the increased risk in recipients </= 5 or >/= 55 years. Transplant Proc 26: 2518–2521, 1994
20. Spanish Monotherapy Study Group: Cyclosporine monotherapy versus OKT3 and cyclosporin versus prednisone and cyclosporine as induction therapy in older renal transplant patients: a multicenter randomized study. Transplant Proc 26: 2522–2524, 1994
21. Lundgren G, Persson NH, Albrechtson D, Brynger H, Flatmark A, Frodin L, Groth CG, Lindholm A, Weibull H: Recipient age- an important factor for the outcome of cadaver renal transplantation in patients treated with cyclosporine. Transplant Proc 21: 1653–1654, 1989
22. Kock B, Kuhlback B, Ahonen J: Kidney transplantation in patients over 60 years of age. Scand J Urol Nephrol 54: 203–205, 1980
23. Meier-Kreische HU, Ojo A, Hanson J, Cibrik D, Lake K, Agodoa LY, Leichtman A, Kaplan B: Increased immunosuppressive vulnerability in elderly renal transplant recipients. Transplantation 69: 885–889, 2000
24. Meier-Kreische HU, Friedman G, Jacobs M, Mulgaonkar S, Vaghela M, Kaplan B: Infectious complications in geriatric renal transplant patients: comparison of two immunosuppressive protocols. Transplantation 68: 1496–1502, 1999
25. Mayer AD, Dmitrewski J, Squifflet J, Besse T, Grabensee B, Klein B, Eigler FW, Heeman U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RWG, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JLR, Talbot D, Neumayer H, Hauser I, Ericzon B, Brattrstrom C, Claesson K, Muhlbacher F, Pohanka E: Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporin in the prevention of renal allograft rejection. Transplantation 64: 436–443, 1997
26. Papadakis J, Brown CB, Cameron JS, Adu D, Bewick M, Donaghey R, Ogg CS, Rudge C, Williams DG, Taube D: High versus “low” dose corticosteroids in recipients of cadaveric kidneys: prospective controlled trial. BMJ (Clin Research Ed) 286: 1097–1100, 1983
27. Stratta RJ, Taylor RJ, Sindhi R, Sudan D, Jerius JT, Gill IS: Analysis of early readmissions after combined pancreas-kidney transplantation. Am J Kidney Dis 28: 867–877, 1996
28. A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. Ortho Multicenter Transplant Study Group. N Eng J Med 313: 337–342, 1985
29. Midtvedt K, Tafjord AB, Hartmann A, Eide TC; Holdaas H; Nordal KP; Draganov B; Sodal G.; Leivestad T, Fauchald P: Half dose of OKT3 is efficient in treatment of steroid-resistant renal allograft rejection. Transplantation 62: 38–42, 1996
30. Woodle ES, Thistlethwaite JR, Gordon JH, Laskow D, Deierhoi MH, Burdick J, Pirsch JD, Sollinger H, Vincenti F, Burrows L, Schwartz B, Danovitch GM, Wilkinson AH, Shaffer D, Simpson MA, Freeman RB, Rohrer RJ, Mendez R, Aswad S, Munn SR, Wiesner RH, Delmonico FL, Neylan J, Whelchel J: A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group. Transplantation 62: 594–599, 1996
31. Jordan M, Shapiro R, Vivas CA, Scantlebury VP; Rhandhawa P; Carrieri G; McCauley J; Demetris AJ; Tzakis A, Fung J, Simmons RL, Hakala TR, Starzl TE: FK506 “rescue” for resistant rejection of renal allografts under primary cyclosporine immunosuppression. Transplantation 57: 860–865, 1994
32. Siegel RR, Aquino HC, Luke RG, Schmidt R: Minimising the risks of treating acute allograft rejection. Proc Eur Dial Trans Assoc 11: 351–356, 1975
33. Matas AJ, Tellis VA, Quinn T, Glichlick D, Soberman R, Weiss R, Karwa G, Veith FJ: ALG treatment of steroid-resistant rejection in patients receiving cyclosporine. Transplantation 41: 579–583, 1986
34. Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D: Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Eng. J Med 342: 605–612, 2000
35. Fryer JP, Granger DK, Leventhal JR, Gillingham K, Najarian JS, Matas AJ: Steroid-related complications in the cyclosporine era. Clinical Transplant 8: 224–229, 1994
36. Tornatore KM, Biocevich DM, Reed KA, Tousley K, Gray V, Singh JP, Murray BM, Venuto RC: Post-transplant diabetes mellitus and methylprednisolone pharmacokinetics in African-American and Caucasian renal transplant recipients. Clinical Transplant 9: 289–296, 1995
37. Saxena S, Dash SC, Guleria S, Mittal R, Agarwal SK, Tiwari SC, Mehta SN: Post transplant diabetes mellitus in live related renal allograft recipients: a single centre experience. J Assoc Physicians India 44: 472–479, 1996
38. Filler G, Amendt P, von Bredow MA, Ehrich JH: Transient diabetes mellitus and peripheral insulin resistance following Tacrolimus intoxication in a child after renal transplantation. Nephrol Dial Transplant 12: 334–336, 1997
39. Kim YS, Kim MS, Kim SI, Lim SK, Lee HY, Han DS, Park K: Post-transplantation diabetes is better controlled after conversion from prednisone to deflazacort: a prospective trial in renal transplants. Transpl Int 10: 197–201, 1997
40. Isoniemi HM, Ahonen J, Tikkanen MJ, van Willebrand EO, Krogerus L, Eklund BH, Hockerstedt KV, Salmela KE, Hayry PJ: Long-term consequences of different immunosuppressive regimens for renal allografts. Transplantation 55: 494–499, 1993
41. Vesco L, Busson M, Lang P: Characteristics of postrenal transplant diabetes mellitus. Transplant Proc 27: 2465–2466, 1995
42. Hjelmesaeth J, Hartmann A, Kofstad J, Stenstrom J, Leivestad T, Egeland T, Fauchald P: Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age. Transplantation 64: 979–983, 1997
43. Sakhuja V, Sharma UK, Jha V, Minz M, Chugh KS: High incidence of posttransplant diabetes mellitus in renal transplant recipients on triple-drug immunosuppression. Transplant Proc 27: 2728–2730, 1995
44. Lee HC, Nam MS, Nam SY, Cha BS, Lee JH, Song YD, Lee EJ, Lim SK, Kim KR, Kim YS, Park K, Huh KB: Posttransplant diabetes mellitus after renal transplantation in Korea. Transplant Proc 28: 1159–1160, 1996
45. Tanabe K, Koga S, Takahashi K, Sonda K, Tokumoto T, Babazono T, Yagisawa T, Toma H, Kawai T, Fuchinoue S, Teraoka S, Ota K: Diabetes mellitus after renal transplantation under FK 506 (tacrolimus) as primary immunosuppression. Transplant Proc 28: 1304–1305, 1996
46. Lanerolle RD, de Abrew K, Fernando DJ, Sheriff MH: Post-renal transplant diabetes in Sri Lanka. Transplant Proc 28: 1945–1947, 1996
47. Churchill DN, Torrance GW, Taylor DW, Barnes CC, Ludwin D, Shimizu A, Smith EKM: Measurement of quality of life in end-stage renal disease: the time trade off approach. Clin Invest Med 10: 14–20, 1987
48. Douzdjian V, Bunke CM, Ferrara D, Silvestri G: A utility-based decision analysis model for treatment of type I diabetics with ESRD: dialysis versus kidney transplant versus kidney-pancreas transplant. J Am Soc Nephrol 8: 680A, 1997
49. Laupacis A, Wong C, Churchill DN, The Canadian Erythropoietin Study Group: The use of generic and specific quality of life measures in haemodialysis patients treated with erythropoeitin. Control Clin Trials 12: 168S–179S, 1991
50. Laupacis A, Muirhead N, Keown P, Wong C: A disease-specific questionnaire for assessing quality of life in patients on hemodialysis. Nephron 60: 302–306, 1992
51. Laupacis A, Keown P, Pus N, Ferguson B, Wong C, Muirhead N: A study of the quality of life and cost-utility of renal transplantation. Kidney Int 50: 235–242, 1996
52. Russell JD, Beecroft ML, Ludwin D, Churchill DN: The quality of life in renal transplantation - a prospective study. Transplantation 54: 656–660, 1992
53. Churchill DN, Wallace JE, Ludwin D, Beecroft ML, Taylor DW: A comparison of evaluative indices of quality of life and cognitive function in hemodialysis patients. Control Clin Trials 12: 159S–167S, 1991
54. Goeree R, Manalich J, Grootendorst P, Beecroft ML, Churchill DN: Cost analysis of dialysis treatments for end-stage renal disease (ESRD). Clinical & Investigative Medicine - Medecine Clinique et Experimentale 18: 455–464, 1995
55. Khan IH, MacLeod AM: Towards cost-effective dialysis therapy in Europe: the need for a multidisciplinary approach. Nephrol Dial Transplant 12: 2483–2485, 1998
56. Bruns F, Seddon P, Saul M, Zeidel M: The cost of caring for end-stage kidney disease patients: an analysis based on hospital financial transaction records. J Am Soc Nephrol 9: 884–890, 1998
57. Garella S: The costs of dialysis in the USA. Nephrol Dial Transplant 12 Suppl 1: 10–21, 1997
58. Cogny-Van Weydevelt F, Ngohou C, Pontefract R, Bacquaert-Dufour K, Riberi P: Hemodialysis and transplantation cost-effectiveness analysis. Transplant Proc 28: 2838–2838, 1996
59. Madrigal G: Cost estimate of kidney transplants in Costa Rica: Comparison to chronic dialysis. Transplant Proc 26: 121–121, 1994
60. Shield CF3, Jacobs RJ, Wyant S, Das A: A cost-effectiveness analysis of OKT3 induction therapy in cadaveric kidney transplantation. Am J Kidney Dis 27: 855–864, 1996
61. Kiberd BA: Should hepatitis C-infected kidneys be transplanted in the United States? Transplantation 57: 1068–1072, 1994
62. Eggers PW: Comparison of treatment costs between dialysis and transplantation. Semin Nephrol 12: 284–289, 1992
63. Lenisa L, Castoldi R, Socci C, Motta F, Ferrari G, Spotti D, Caldara R, Secchi A, Pozza G, Di Carlo V: Cost-effective treatment for diabetic end-stage renal disease: dialysis, kidney, or kidney-pancreas transplantation? Transplant Proc 27: 3108–3113, 1995
64. Prichard SS: The costs of dialysis in Canada. Nephrol Dial Transplant 12 Suppl 1: 22–24, 1997
65. Sullivan SD, Garrison LP, Best JH, and members of the US Renal Transplant Mycophenylate Mofetil study group: The cost effectiveness of mycophenylate mofetil in the first year after primary cadaveric transplant. J Am Soc Nephrol 8: 1598 1997
66. Neylan JF, Sullivan EM, Prendergast MM, Steinwald AB, Goss TF, FK506 kidney transplant study group: An economic assessment of post-transplant hospitalizations among kidney transplant patients receiving tacrolimus versus cyclosporin immunosuppressive therapy. The International Congress of Immunosuppression, Orlando 1998
67. Morris-Stiff G, Richards T, Baboolal K, Balaji V, Ostrowski K, Moore R, Darby C, Lord R, and Jurewicz, A: Pharmaco-economic study of tacrolimus and neoral in cadaveric renal transplantation. The British Transplantation Society, Dublin 1998
68. Oliveira, D: Economic analysis of Prograf (tacrolimus) and cyclosporin in the prevention of kidney allograft rejection. New Horizons in Kidney Transplantation 1: 12–15, 1997
69. Internet address: http:/www/oanda.com/cgi_bin/ncc
70. Bureau of Labor Statistics. 1998
71. Krahn M, Gafni A: Discounting in the economic evaluation of health care interventions. Med Care 31: 403–418, 1993
72. Evans RW, Kitzmann DJ: An economic analysis of kidney transplantation. Surg Clin North Am 78: 149–174, 1998
73. Karlberg I, Nyberg G: Cost-effectiveness studies of renal transplantation. Int J Technol Assess Health Care 11: 611–622, 1995
74. Mallick NP: The costs of renal services in Britain. Nephrol Dial Transplant 12 Suppl 1: 25–28, 1997
75. Department of Health and Human Services, Health Care Financing Administration Bureau of Data Management and Strategy Office of Research and Demonstrations. Health Care Financing. End Stage Renal Disease. 1997. Baltimore, MD
76. Levine DZ: Would you deny this patient dialysis? Am J Kidney Dis 31: 131–132, 1998
77. Naimark D, Naglie G, Detsky AS: The meaning of life expectancy: what is a clinically significant gain? J Gen Intern Med 9: 702–707, 1994
78. O’Brien BJ, Anderson DR, Goeree R: Cost-effectiveness of enoxaparin versus warfarin prophylaxis against deep-vein thrombosis after total hip replacement. Can Med Assoc J 150: 1083–1090, 1994
79. Weinstein MC, Stason WB: Cost-effectiveness of interventions to prevent or treat coronary heart disease. Ann Rev Public Health 6: 41–63, 1985
80. Azimi NA, Welch HG: The effectiveness of cost-effectiveness analysis in containing costs. J Gen Intern Med 13: 664–669, 1998
81. Ismail N, Hakim R, Helderman JH: Renal replacement therapies in the elderly: Part II renal transplantation. Am J Kidney Dis 23: 1–15, 1994
82. Jassal SV, Opelz G, Cole E: Transplantation in the elderly: A review. Ger Nephrol Urol 7: 157–165, 1997
83. Manninen DL, Evans RW: The costs and outcomes of kidney transplantation according to initial immunosuppressive drug protocol. Clin Transplant 269: 275, 1987
84. National Kidney Foundation- Dialysis Outcomes Quality Initiative Guidelines. 1997. Washington, National Kidney Foundation
85. Velez RL, Brinker KR, Vergne-Marinin PJ, Nesser DA, Long DL, Trevino G, Dickerman RM, Helfsick GB: Renal transplantation with cyclosporine in the elderly population. Transplant Proc 23: 1749–1752, 1991
86. Parfrey PS, Hutchinson TA, Harvey C, Guttman RD: Transplantation versus dialysis in diabetic patients with renal failure. Am J Kidney Dis 5: 112–116, 1985
87. Rao KV: The influence of preexisting vascular disease on the outcome of renal transplantation in diabetic patients. Nephron 48: 74–75, 1988
88. Basadonna G, Matas AJ, Gillingham K, Sutherland DE, Payne WD, Dunn DL, Gores PF, Gruessner RW, Arrazola L, Najarian JS: Kidney transplantation in patients with type I diabetes: 26-year experience at the University of Minnesota. Clin Transplant 227: 235, 1992
89. Kasiske BL, Guijarro C, Massy ZA, Wiederkehr MR, Ma JZ: Cardiovascular disease after renal transplantation. J Am Soc Nephrol 7: 158–165, 1996
90. Peters TG, Jones KW, Walker GW, Charlton RK, Antonucci LE, Repper SM, Hunter RDS: Living-unrelated kidney donation: a single center experience. Clinical Transplant 13: 108–112, 1999