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Renal transplantation in elderly patients
Renal Transplantation in Elderly Patients A.I. Sa´nchez-Fructuoso, D. Prats, P. Naranjo, C. Ferna´ndez, B. Avile´s, and A. Barrientos
T
HE EVER-INCREASING age of the population of the developed world and advances in medical science and technology have permitted the offer of dialysis and subsequent renal transplant to patients of advanced age. However, several investigations have demonstrated lower graft survival in elderly patients and patient death as the main cause of graft loss.1–3 The present study describes a retrospective review of cadaveric renal transplants (RTs) performed at this centre and compares graft function and outcome in a large group of elderly and younger recipients. A cutoff age of 55 years was established to permit comparison with most previously published data.1 MATERIALS AND METHODS The RT records of 511 patients were reviewed. Data corresponded to 156 (30.5%) RT patients .55 years (group 1) and 355 (69.5%) younger patients (group 2). The RTs were performed during the period from 1980 to 1997 and recipients were subjected to similar posttransplant treatment. Kaplan–Meier time-to-event curves for graft and patient survival were used. Graft failure was defined as return to dialysis or death of the recipient with a nonfunctioning kidney. The combined influence of various risk factors on graft and patient survival (donor age, recipient age, sequential therapy, percent cytotoxic antibodies, HLA compatibility, time of cold ischaemia, time of posttransplant acute tubular necrosis [ATN], cytomegalovirus) was estimated by fitting data to Cox’s relative risk (RR) regression model (CI 95%).
RESULTS
First-time hospitalisation was slightly higher in group 1 (21.9 6 1.8 vs 20.2 6 0.8 days; P 5 .08). The time of posttransplant ATN was similar in both groups (3.99 6 0.62 vs 5.11 6 0.50 days). Mean serum creatinine and creatinine clearance were similar in both groups (group 1: 1.53 6 0.07 mg/dL and 62.64 6 2.41 mL/min; group 2: 1.58 6 0.04 mg/dL and 67.18 6 1.82 mL/min, respectively; P 5 .550 and P 5 .139, respectively). The number of rejection episodes recorded in group 1 was minor (0.35 6 0.05 vs 0.71 6 0.05 for mean number of episodes per patient; P 5 .000). For groups 1 and 2, respectively 0.19 6 0.04 and 0.35 6 0.03 of the rejection episodes were corticosensitive (P 5 .001), whereas 0.17 6 0.03 and 0.35 6 0.04 were corticoresistant (P , .000). The incidence of cytomegalovirus infection was 76.8% in
group 1 vs 48.3% in group 2 (P 5 .000). Tumours were diagnosed in 13.3% of the group 1 patients, and 8.2% of the patients in group 2 (P 5 .09). Graft survival at 1, 5, and 10 years was 88%, 87.2%, and 77.4% in group 1 and 80%, 72.9%, and 57.8% in group 2, respectively (P 5 .008). The inclusion of patients who died with a functioning graft as undergoing graft failure, reduced graft survival values to 83.4%, 70.1% and 36.2% in group 1 and to 75.7%, 63.4%, and 47.5% in group 2 at 1, 5, and 10 years, respectively (P 5 .243). In group 1, 24 RTs were lost (15.4%) vs 100 (28.2%) in group (P 5 .001). In group 1, 17 patients died with a functional kidney. When these patients were included as having undergone graft loss, death represented the major cause of transplant loss (41.5%). In group 2, 44 patients died with a functioning kidney, representing 30.5% of graft losses. An increased risk of graft loss was associated with (Cox’s model): cytotoxic antibodies .25% (RR 5 1.87 [1.00 to 3.50], P 5 .06); time posttransplant ATN .1 day (RR 5 1.66 [0.92 to 2.99], P 5 .09); donor age .55 years (RR 5 3.32 [1.67 to 6.62], P 5 .003); and a second or third transplant (RR 5 2.13 [0.97 to 4.65], P 5 0.07). Patient survival at 1, 5, and 10 years was 91.5%, 76.0%, and 44.7% in group 1 and 93.1%, 85.0%, and 74.5% in group 2, respectively (P 5 .033). Thirty (19.2%) patients died in group 1, whereas 50 (14.06%) died in group 2 (P 5 .832). Sepsis was the most common cause of death in both groups. An increased risk of death was associated with: recipient age .55 years (RR 5 2.24 [1.25 to 4.01], P 5 .007), cytomegalovirus infection (RR 5 1.83 [0.90 to 3.70], P 5 .09); and cytomegalovirus disease (RR 5 2.30 [1.19 to 4.46], P 5 .01). DISCUSSION
In Spain, 5 of 10 patients with CRF receiving treatment are over the age of 60 years and 1 in 10 is over 75.4 The mean age of those receiving hospital dialysis increased from 48.9 years in 1984 to 56.6 years in 1991. Consequently, the mean From the Nephrology Department, H Universitario San Carlos, Madrid, Spain. Address reprint requests to Dr A.J. Sa´nchez-Fructuoso, Hospital Clinico San Carlos, Servico de Nefrologia c/Martin Lagos S/N, 28040 Madrid, Spain.
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/98/$19.00 PII S0041-1345(98)00619-8
Transplantation Proceedings, 30, 2277–2278 (1998)
2277
2278
age of RT patients also increased from 37.2 years (1984) to 42.7 years (1991).5 To date, elderly patients have been excluded from RT waiting lists for several reasons although the most determining factors include scarcity of donors and the poor results obtained in the short term (mainly in the 1970s) in elderly patients using traditional immunosuppressive regimes. However, the current most relevant factor is, perhaps, donor scarcity, because the effect of recipient age on the outcome of RT has been minimised by the introduction of cyclosporine, the use of low-dose corticosteroids, the improved management of pre- and postsurgical complications, and the adequate selection of patients. This is supported by the findings of the present report and those of other investigators.5–7 The current graft survival rate in Spain at 5 years (from 1987 to 1992) is 68.9% for patients over 60 years.5 This value is similar to the value presently reported and slightly higher than that quoted by the EDTA (58.5%)3 and others.1 Consistent with the findings of Opelz,6 no differences in graft survival were found with respect to younger patients. It has been proposed that the similarity in graft survival rates between the two patient age groups reported by other investigators is due to the lack of inclusion of patients who die with a functional kidney as patients undergoing graft loss.1 This factor was taken into account in the present study and no decrease in survival rate with age was found. Similar observations have been reported by Tesi et al.7 Also in agreement with other reports,1,8 –10 the main causes of death in the elderly patient group were infection and cardiac disease. The present review confirms the lower incidence of rejection episodes in elderly patients with respect to younger patients described by other investigators.7,8,11
SA´NCHEZ-FRUCTUOSO, PRATS, NARANJO ET AL
It may be concluded that greater medical experience in the management of RT patients and advances in the diagnosis and treatment of associated conditions have led to the substantial improvement of both patient and graft survival in the elderly to reach levels similar to those of younger patients. The lower incidence of rejection that occurs in older patients may lead to the possibility of reduced immunosuppression. This would lower the risk of infection, which currently represents the main cause of death.
REFERENCES 1. Cole EH, Farewell VT, Aprile M, et al: Geriat Nephrol Urol 5:85, 1995 2. Ismail N, Hakim RM, Helderman JH: Am J Kidney Dis 23:1, 1994 3. Valderrabano F, Jones EHP, Mallick NP: Nephrol Dial Transplant 10(suppl 5):1, 1995 4. Go ´mez Campedra´ FJ, Tejedor A, et al: Nefrologia 14:136, 1994 5. Barrio V: Nefrologia 16:307, 1996 6. Opelz G: UNOS Newsletter 4:12, 1992 7. Tesi RJ, Elkhammas EA, Davies EA, et al: Lancet 343:461, 1994 8. Pirsch JD, Stratto RJ, Armburst MJ, et al: Transplantation 47:259, 1989 9. Shaw B, First MR, Mundo R, et al: Am J Kidney Dis 12:516, 1988 10. Koka P, Cecka JM. In Terasaki PI (ed): Clinical Transplants 1990. Los Angeles, Calif: UCLA Tissue Typing Laboratory; 1991, p 437 11. Ost L, Groth CG, Lindholm B, et al: Transplantation 30:339, 1989
T
HE EVER-INCREASING age of the population of the developed world and advances in medical science and technology have permitted the offer of dialysis and subsequent renal transplant to patients of advanced age. However, several investigations have demonstrated lower graft survival in elderly patients and patient death as the main cause of graft loss.1–3 The present study describes a retrospective review of cadaveric renal transplants (RTs) performed at this centre and compares graft function and outcome in a large group of elderly and younger recipients. A cutoff age of 55 years was established to permit comparison with most previously published data.1 MATERIALS AND METHODS The RT records of 511 patients were reviewed. Data corresponded to 156 (30.5%) RT patients .55 years (group 1) and 355 (69.5%) younger patients (group 2). The RTs were performed during the period from 1980 to 1997 and recipients were subjected to similar posttransplant treatment. Kaplan–Meier time-to-event curves for graft and patient survival were used. Graft failure was defined as return to dialysis or death of the recipient with a nonfunctioning kidney. The combined influence of various risk factors on graft and patient survival (donor age, recipient age, sequential therapy, percent cytotoxic antibodies, HLA compatibility, time of cold ischaemia, time of posttransplant acute tubular necrosis [ATN], cytomegalovirus) was estimated by fitting data to Cox’s relative risk (RR) regression model (CI 95%).
RESULTS
First-time hospitalisation was slightly higher in group 1 (21.9 6 1.8 vs 20.2 6 0.8 days; P 5 .08). The time of posttransplant ATN was similar in both groups (3.99 6 0.62 vs 5.11 6 0.50 days). Mean serum creatinine and creatinine clearance were similar in both groups (group 1: 1.53 6 0.07 mg/dL and 62.64 6 2.41 mL/min; group 2: 1.58 6 0.04 mg/dL and 67.18 6 1.82 mL/min, respectively; P 5 .550 and P 5 .139, respectively). The number of rejection episodes recorded in group 1 was minor (0.35 6 0.05 vs 0.71 6 0.05 for mean number of episodes per patient; P 5 .000). For groups 1 and 2, respectively 0.19 6 0.04 and 0.35 6 0.03 of the rejection episodes were corticosensitive (P 5 .001), whereas 0.17 6 0.03 and 0.35 6 0.04 were corticoresistant (P , .000). The incidence of cytomegalovirus infection was 76.8% in
group 1 vs 48.3% in group 2 (P 5 .000). Tumours were diagnosed in 13.3% of the group 1 patients, and 8.2% of the patients in group 2 (P 5 .09). Graft survival at 1, 5, and 10 years was 88%, 87.2%, and 77.4% in group 1 and 80%, 72.9%, and 57.8% in group 2, respectively (P 5 .008). The inclusion of patients who died with a functioning graft as undergoing graft failure, reduced graft survival values to 83.4%, 70.1% and 36.2% in group 1 and to 75.7%, 63.4%, and 47.5% in group 2 at 1, 5, and 10 years, respectively (P 5 .243). In group 1, 24 RTs were lost (15.4%) vs 100 (28.2%) in group (P 5 .001). In group 1, 17 patients died with a functional kidney. When these patients were included as having undergone graft loss, death represented the major cause of transplant loss (41.5%). In group 2, 44 patients died with a functioning kidney, representing 30.5% of graft losses. An increased risk of graft loss was associated with (Cox’s model): cytotoxic antibodies .25% (RR 5 1.87 [1.00 to 3.50], P 5 .06); time posttransplant ATN .1 day (RR 5 1.66 [0.92 to 2.99], P 5 .09); donor age .55 years (RR 5 3.32 [1.67 to 6.62], P 5 .003); and a second or third transplant (RR 5 2.13 [0.97 to 4.65], P 5 0.07). Patient survival at 1, 5, and 10 years was 91.5%, 76.0%, and 44.7% in group 1 and 93.1%, 85.0%, and 74.5% in group 2, respectively (P 5 .033). Thirty (19.2%) patients died in group 1, whereas 50 (14.06%) died in group 2 (P 5 .832). Sepsis was the most common cause of death in both groups. An increased risk of death was associated with: recipient age .55 years (RR 5 2.24 [1.25 to 4.01], P 5 .007), cytomegalovirus infection (RR 5 1.83 [0.90 to 3.70], P 5 .09); and cytomegalovirus disease (RR 5 2.30 [1.19 to 4.46], P 5 .01). DISCUSSION
In Spain, 5 of 10 patients with CRF receiving treatment are over the age of 60 years and 1 in 10 is over 75.4 The mean age of those receiving hospital dialysis increased from 48.9 years in 1984 to 56.6 years in 1991. Consequently, the mean From the Nephrology Department, H Universitario San Carlos, Madrid, Spain. Address reprint requests to Dr A.J. Sa´nchez-Fructuoso, Hospital Clinico San Carlos, Servico de Nefrologia c/Martin Lagos S/N, 28040 Madrid, Spain.
© 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
0041-1345/98/$19.00 PII S0041-1345(98)00619-8
Transplantation Proceedings, 30, 2277–2278 (1998)
2277
2278
age of RT patients also increased from 37.2 years (1984) to 42.7 years (1991).5 To date, elderly patients have been excluded from RT waiting lists for several reasons although the most determining factors include scarcity of donors and the poor results obtained in the short term (mainly in the 1970s) in elderly patients using traditional immunosuppressive regimes. However, the current most relevant factor is, perhaps, donor scarcity, because the effect of recipient age on the outcome of RT has been minimised by the introduction of cyclosporine, the use of low-dose corticosteroids, the improved management of pre- and postsurgical complications, and the adequate selection of patients. This is supported by the findings of the present report and those of other investigators.5–7 The current graft survival rate in Spain at 5 years (from 1987 to 1992) is 68.9% for patients over 60 years.5 This value is similar to the value presently reported and slightly higher than that quoted by the EDTA (58.5%)3 and others.1 Consistent with the findings of Opelz,6 no differences in graft survival were found with respect to younger patients. It has been proposed that the similarity in graft survival rates between the two patient age groups reported by other investigators is due to the lack of inclusion of patients who die with a functional kidney as patients undergoing graft loss.1 This factor was taken into account in the present study and no decrease in survival rate with age was found. Similar observations have been reported by Tesi et al.7 Also in agreement with other reports,1,8 –10 the main causes of death in the elderly patient group were infection and cardiac disease. The present review confirms the lower incidence of rejection episodes in elderly patients with respect to younger patients described by other investigators.7,8,11
SA´NCHEZ-FRUCTUOSO, PRATS, NARANJO ET AL
It may be concluded that greater medical experience in the management of RT patients and advances in the diagnosis and treatment of associated conditions have led to the substantial improvement of both patient and graft survival in the elderly to reach levels similar to those of younger patients. The lower incidence of rejection that occurs in older patients may lead to the possibility of reduced immunosuppression. This would lower the risk of infection, which currently represents the main cause of death.
REFERENCES 1. Cole EH, Farewell VT, Aprile M, et al: Geriat Nephrol Urol 5:85, 1995 2. Ismail N, Hakim RM, Helderman JH: Am J Kidney Dis 23:1, 1994 3. Valderrabano F, Jones EHP, Mallick NP: Nephrol Dial Transplant 10(suppl 5):1, 1995 4. Go ´mez Campedra´ FJ, Tejedor A, et al: Nefrologia 14:136, 1994 5. Barrio V: Nefrologia 16:307, 1996 6. Opelz G: UNOS Newsletter 4:12, 1992 7. Tesi RJ, Elkhammas EA, Davies EA, et al: Lancet 343:461, 1994 8. Pirsch JD, Stratto RJ, Armburst MJ, et al: Transplantation 47:259, 1989 9. Shaw B, First MR, Mundo R, et al: Am J Kidney Dis 12:516, 1988 10. Koka P, Cecka JM. In Terasaki PI (ed): Clinical Transplants 1990. Los Angeles, Calif: UCLA Tissue Typing Laboratory; 1991, p 437 11. Ost L, Groth CG, Lindholm B, et al: Transplantation 30:339, 1989