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Impact of Graft Infection on Long-Term Survival After Kidney Transplant
Impact of Graft Infection on Long-Term Survival After Kidney Transplant a _ A. Zukowska , K. Kotfisb, M. Kaczmarczykc, J. Biernawskab, Ł. Szydłowskib, T. Sulikowskid, A. Sierockad, d b, _ J. Pawlus , R. Bohatyrewicze, and M. Zukowski * a Clinical Microbiology, Teaching Hospital No 2, Pomeranian Medical University, Szczecin, Poland; bDepartment of Anesthesiology, Intensive Care, and Acute Poisoning, Pomeranian Medical University, Szczecin, Poland; cDepartment of Laboratory Diagnostic and Molecular Medicine, Pomeranian Medical University, Szczecin, Poland; dClinic of General and Transplant Surgery, Pomeranian Medical University, Szczecin, Poland; and eClinic of Anesthesiology and Intensive Care, Pomeranian Medical University, Szczecin, Poland
ABSTRACT Background. Patients undergoing transplantation procedures are at a high risk of developing infections because of the need for immunosuppression. Infections presenting directly after renal transplantation greatly influence the overall success of the procedure. The aim of this study was to evaluate the influence of postoperative infection on the length of survival after renal transplant. Methods. In 2009 a multicenter prospective trial evaluating the factors that influence the occurrence of postoperative infective complications was published by the authors. That study reported that 25 out of 232 recipients of a renal transplant were diagnosed with an infection. The present study shows the effect of postoperative infection on the length of survival after renal transplantation during a 15-year observation period. Statistical methods involved monofactorial and multifactorial Kaplan-Meier analysis for the length of survival and the Cox proportional hazards model for mortality prediction. A P value of <.05 was considered to indicate statistical significance. Results. The analysis demonstrated that the lifespan of renal transplant recipients was decreased in those with postoperative infection, at both year 10 of the observation period (P ¼ .013) and 15 years after transplantation (P ¼ .012). Moreover, it was ascertained that an infection in the postoperative period was an independent risk factor increasing the mortality after renal transplantation: P ¼ .026; hazard ratio 2.90 (95% confidence interval, 1.13e7.41). Conclusions. The occurrence of an infection in the postoperative period significantly decreases the lifespan of a renal transplantation recipient.
K
IDNEY transplantation is a treatment of choice for endstage renal disease patients. The number of transplanted kidneys has increased during the past decade, and the survival rate of graft recipients has improved. A nosocomial infection in the postoperative period remains an important problem of modern surgery [1]. Patients undergoing transplantation procedures are at a high risk of developing infections owing to the need for immunosupression, so nosocomial infections in the early post-transplantation period impose a difficult problem for the kidney transplantation team [2]. Infections presenting directly after renal transplantation greatly influence the overall success of the procedure, because
they increase not only morbidity and mortality, but also the cost and length of hospitalization [3,4]. Despite many published studies, the influence of the nosocomial infection in the post-transplantation period on the long-term outcomes of grafts remains unclear [5,6]. The aim of the present study was to evaluate the influence of postoperative infection on the length of survival after renal transplant. _ *Address correspondence to Maciej Zukowski, Department of Anesthetics and Intensive Care, Pomeranian Medical University, ców Wlkp. 72, 70-111 Szczecin, Poland. E-mail: Al Powstan [email protected]
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.08.018
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2752
Transplantation Proceedings, 46, 2752e2754 (2014)
IMPACT OF GRAFT INFECTION
2753
1,0 0,9
without graf t inf ection graf t inf ection
0,8
Surv iv al probabilit y
0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0 -0,1 0
20
40
60
80
100
120
140
Months
METHODS In the year 2009 a multicenter prospective trial evaluating the factors that influence the occurrence of postoperative infective complications was published by the authors of this study. In that trial, 232 kidney recipients were examined for occurrence of septic complications, including septicemia, pneumonia, peritonitis, and graft infection. All kidneys were taken from 146 multiorgan donors, including 28 female and 118 male patients, with the age range from 8 to 58 years (mean 32.5 10.9). We concluded that mean arterial pressure (MAP) <70 mm Hg and systemic vascular resistance index
Fig 1. Kaplan-Meier survival curve: recipients with and without graft infection in 10-year observation period (P ¼ .013).
(SVRI) <1,200 dyne$s/cm5$m2 among organ donors predicted greater occurrence of septic complications and increased mortality among kidney transplant recipients. That study reported that 25 out of 232 recipients of a renal transplant were diagnosed with an infection. In the present study, we assessed the effect of postoperative infection on the length of survival after renal transplantation during a 15-year observation period. In the analysis we included the donors’ data of age, sex, and cause of death and the recipients’ data including age, sex, cause of renal failure, prior hemodialysis period, donor-recipient sex mismatch, and post-transplantation course (occurrence of delayed graft function
1,0 without graf t inf ection graf t inf ection
0,9 0,8
Surv iv al probabilit y
0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0 -0,1
Fig 2. Kaplan-Meier survival curve: recipients with and without graft infection in 15-year observation period (P ¼ .012).
0
20
40
60
80
100 Months
120
140
160
180
200
_ ZUKOWSKA, KOTFIS, KACZMARCZYK ET AL
2754 [DGF], episodes of acute rejection, and time and number of hemodialysis after transplantation). We analyzed the influence of the episodes of postoperative infection on the long-term survival in a 15-year observation period. We analyzed infection all together and in subgroups, including septicemia, pneumonia, peritonitis, urinary tract infection, and graft infection. Statistical methods involved monofactorial and multifactorial Kaplan-Meier analysis for the length of survival and the Cox proportional hazards model for mortality prediction. A P value of <.05 was considered to indicate statistical significance.
RESULTS
There was no statistically significant difference in the donors’ mean age, sex, or cause of death between the infection group and the noninfection group. Recipients’ data and postoperative parameters did not show significant difference between the 2 groups. The most common infection site was pneumonia (n ¼ 11), followed by graft infection (n ¼ 10), urinary tract infection (n ¼ 2), septicemia (n ¼ 1), and peritonitis (n ¼ 2). A Kaplan-Meier analysis demonstrated that the lifespan of renal transplant recipients was decreased in those with postoperative graft infection, at both year 10 of the observation period (P ¼ .013; Fig 1) and 15 years after transplantation (P ¼ .012; Fig 2). Moreover, in the univariate Cox regression proportional hazards model, it was ascertained that an infection in the postoperative period was an independent risk factor increasing the mortality after renal transplantation: P ¼ .012; hazard ratio, 3.29 (95% confidence interval, 1.29e8.38). We did not find statistically significant influence of other analyzed parameters on the long-term survival after kidney transplantation (Table 1). DISCUSSION
In this study, nosocomial infections were defined as an independent risk factor for increasing mortality after renal transplantation, a result that is similar to other those of previously published studies. We conclude that graft infection strongly affects the lifespan of patients after kidney transplantation. A limitation of the present study is the fact
Table 1. Univariate Cox Regression Proportional Hazards Model Risk Factor
P Value
HR (95% CI)
Donor age Donor sex Cause of donor’s death Recipient age Recipient sex Donor-recipient sex mismatch Cause of recipient’s renal failure Time of hemodialysis before transplantation Delayed graft function Acute rejection Occurrence of postoperative infection Time of hemodialysis after transplantation Number of hemodialysis after transplantation
.466 .335 .988 .682 .712 .958 .988 .559
0.98 1.38 0.99 0.99 1.06 1.02 0.99 0.99
(0.95e1.02) (0.71e2.67) (0.54e1.82) (0.98e1.01) (0.75e1.51) (0.48e2.15) (0.48e2.03) (0.97e1.01)
.334 .318 .012 .777 .891
1.34 0.73 3.29 1.01 1.01
(0.74e2.43) (0.39e1.36) (1.29e8.38) (0.96e1.05) (0.92e1.09)
Abbreviations: HR, hazard ratio; CI, confidence interval.
that the criteria of infection were not clearly defined, and we did not collected microbiologic culture results. Despite these limitations, it has been clearly shown that all 10 recipients with the graft infection in the postoperative period died within 6 years after transplantation. REFERENCES [1] Linares L, Cervera C, Cofán F, et al. Epidemiology and outcomes of multiple antibiotic-resistant bacterial infection in renal transplantation. Transplant Proc 2007;39:2222e4. [2] Ferraresso M, Berardinelli L. Nosocomial infection in kidney transplant recipients: a retrospective analysis of a single-center experience. Transplant Proc 2005;37:2495e6. [3] Zukowski M, Kotfis K, Biernawska J, et al. Graft infection in kidney recipients and its relation to transplanted kidney function. Transplant Proc 2011;43:2997e9. [4] Kasiske BL, Gaston RS, Gourishankar S, et al. Long-term deterioration of kidney allograft function. Am J Transplant 2005;5: 1405e14. [5] Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007;357:2601e14. [6] Gómez EG, Hernández JP, López FJ, et al. Long-term Allograft survival after kidney transplantation. Transplant Proc 2013;45:3599e602.
ABSTRACT Background. Patients undergoing transplantation procedures are at a high risk of developing infections because of the need for immunosuppression. Infections presenting directly after renal transplantation greatly influence the overall success of the procedure. The aim of this study was to evaluate the influence of postoperative infection on the length of survival after renal transplant. Methods. In 2009 a multicenter prospective trial evaluating the factors that influence the occurrence of postoperative infective complications was published by the authors. That study reported that 25 out of 232 recipients of a renal transplant were diagnosed with an infection. The present study shows the effect of postoperative infection on the length of survival after renal transplantation during a 15-year observation period. Statistical methods involved monofactorial and multifactorial Kaplan-Meier analysis for the length of survival and the Cox proportional hazards model for mortality prediction. A P value of <.05 was considered to indicate statistical significance. Results. The analysis demonstrated that the lifespan of renal transplant recipients was decreased in those with postoperative infection, at both year 10 of the observation period (P ¼ .013) and 15 years after transplantation (P ¼ .012). Moreover, it was ascertained that an infection in the postoperative period was an independent risk factor increasing the mortality after renal transplantation: P ¼ .026; hazard ratio 2.90 (95% confidence interval, 1.13e7.41). Conclusions. The occurrence of an infection in the postoperative period significantly decreases the lifespan of a renal transplantation recipient.
K
IDNEY transplantation is a treatment of choice for endstage renal disease patients. The number of transplanted kidneys has increased during the past decade, and the survival rate of graft recipients has improved. A nosocomial infection in the postoperative period remains an important problem of modern surgery [1]. Patients undergoing transplantation procedures are at a high risk of developing infections owing to the need for immunosupression, so nosocomial infections in the early post-transplantation period impose a difficult problem for the kidney transplantation team [2]. Infections presenting directly after renal transplantation greatly influence the overall success of the procedure, because
they increase not only morbidity and mortality, but also the cost and length of hospitalization [3,4]. Despite many published studies, the influence of the nosocomial infection in the post-transplantation period on the long-term outcomes of grafts remains unclear [5,6]. The aim of the present study was to evaluate the influence of postoperative infection on the length of survival after renal transplant. _ *Address correspondence to Maciej Zukowski, Department of Anesthetics and Intensive Care, Pomeranian Medical University, ców Wlkp. 72, 70-111 Szczecin, Poland. E-mail: Al Powstan [email protected]
0041-1345/14 http://dx.doi.org/10.1016/j.transproceed.2014.08.018
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2752
Transplantation Proceedings, 46, 2752e2754 (2014)
IMPACT OF GRAFT INFECTION
2753
1,0 0,9
without graf t inf ection graf t inf ection
0,8
Surv iv al probabilit y
0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0 -0,1 0
20
40
60
80
100
120
140
Months
METHODS In the year 2009 a multicenter prospective trial evaluating the factors that influence the occurrence of postoperative infective complications was published by the authors of this study. In that trial, 232 kidney recipients were examined for occurrence of septic complications, including septicemia, pneumonia, peritonitis, and graft infection. All kidneys were taken from 146 multiorgan donors, including 28 female and 118 male patients, with the age range from 8 to 58 years (mean 32.5 10.9). We concluded that mean arterial pressure (MAP) <70 mm Hg and systemic vascular resistance index
Fig 1. Kaplan-Meier survival curve: recipients with and without graft infection in 10-year observation period (P ¼ .013).
(SVRI) <1,200 dyne$s/cm5$m2 among organ donors predicted greater occurrence of septic complications and increased mortality among kidney transplant recipients. That study reported that 25 out of 232 recipients of a renal transplant were diagnosed with an infection. In the present study, we assessed the effect of postoperative infection on the length of survival after renal transplantation during a 15-year observation period. In the analysis we included the donors’ data of age, sex, and cause of death and the recipients’ data including age, sex, cause of renal failure, prior hemodialysis period, donor-recipient sex mismatch, and post-transplantation course (occurrence of delayed graft function
1,0 without graf t inf ection graf t inf ection
0,9 0,8
Surv iv al probabilit y
0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0 -0,1
Fig 2. Kaplan-Meier survival curve: recipients with and without graft infection in 15-year observation period (P ¼ .012).
0
20
40
60
80
100 Months
120
140
160
180
200
_ ZUKOWSKA, KOTFIS, KACZMARCZYK ET AL
2754 [DGF], episodes of acute rejection, and time and number of hemodialysis after transplantation). We analyzed the influence of the episodes of postoperative infection on the long-term survival in a 15-year observation period. We analyzed infection all together and in subgroups, including septicemia, pneumonia, peritonitis, urinary tract infection, and graft infection. Statistical methods involved monofactorial and multifactorial Kaplan-Meier analysis for the length of survival and the Cox proportional hazards model for mortality prediction. A P value of <.05 was considered to indicate statistical significance.
RESULTS
There was no statistically significant difference in the donors’ mean age, sex, or cause of death between the infection group and the noninfection group. Recipients’ data and postoperative parameters did not show significant difference between the 2 groups. The most common infection site was pneumonia (n ¼ 11), followed by graft infection (n ¼ 10), urinary tract infection (n ¼ 2), septicemia (n ¼ 1), and peritonitis (n ¼ 2). A Kaplan-Meier analysis demonstrated that the lifespan of renal transplant recipients was decreased in those with postoperative graft infection, at both year 10 of the observation period (P ¼ .013; Fig 1) and 15 years after transplantation (P ¼ .012; Fig 2). Moreover, in the univariate Cox regression proportional hazards model, it was ascertained that an infection in the postoperative period was an independent risk factor increasing the mortality after renal transplantation: P ¼ .012; hazard ratio, 3.29 (95% confidence interval, 1.29e8.38). We did not find statistically significant influence of other analyzed parameters on the long-term survival after kidney transplantation (Table 1). DISCUSSION
In this study, nosocomial infections were defined as an independent risk factor for increasing mortality after renal transplantation, a result that is similar to other those of previously published studies. We conclude that graft infection strongly affects the lifespan of patients after kidney transplantation. A limitation of the present study is the fact
Table 1. Univariate Cox Regression Proportional Hazards Model Risk Factor
P Value
HR (95% CI)
Donor age Donor sex Cause of donor’s death Recipient age Recipient sex Donor-recipient sex mismatch Cause of recipient’s renal failure Time of hemodialysis before transplantation Delayed graft function Acute rejection Occurrence of postoperative infection Time of hemodialysis after transplantation Number of hemodialysis after transplantation
.466 .335 .988 .682 .712 .958 .988 .559
0.98 1.38 0.99 0.99 1.06 1.02 0.99 0.99
(0.95e1.02) (0.71e2.67) (0.54e1.82) (0.98e1.01) (0.75e1.51) (0.48e2.15) (0.48e2.03) (0.97e1.01)
.334 .318 .012 .777 .891
1.34 0.73 3.29 1.01 1.01
(0.74e2.43) (0.39e1.36) (1.29e8.38) (0.96e1.05) (0.92e1.09)
Abbreviations: HR, hazard ratio; CI, confidence interval.
that the criteria of infection were not clearly defined, and we did not collected microbiologic culture results. Despite these limitations, it has been clearly shown that all 10 recipients with the graft infection in the postoperative period died within 6 years after transplantation. REFERENCES [1] Linares L, Cervera C, Cofán F, et al. Epidemiology and outcomes of multiple antibiotic-resistant bacterial infection in renal transplantation. Transplant Proc 2007;39:2222e4. [2] Ferraresso M, Berardinelli L. Nosocomial infection in kidney transplant recipients: a retrospective analysis of a single-center experience. Transplant Proc 2005;37:2495e6. [3] Zukowski M, Kotfis K, Biernawska J, et al. Graft infection in kidney recipients and its relation to transplanted kidney function. Transplant Proc 2011;43:2997e9. [4] Kasiske BL, Gaston RS, Gourishankar S, et al. Long-term deterioration of kidney allograft function. Am J Transplant 2005;5: 1405e14. [5] Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007;357:2601e14. [6] Gómez EG, Hernández JP, López FJ, et al. Long-term Allograft survival after kidney transplantation. Transplant Proc 2013;45:3599e602.