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Does Delayed Graft Function in the First Kidney Transplant Influence Graft Outcome in a Subsequent Transplant?
Does Delayed Graft Function in the First Kidney Transplant Influence Graft Outcome in a Subsequent Transplant? K.K. Sureshkumar and R.J. Marcus
ABSTRACT Background. In kidney transplantation, delayed graft function (DGF) portends adverse graft and patient outcomes. It is unclear whether DGF in the first kidney transplant would adversely impact the outcome of a subsequent transplant. Methods. Utilizing data from the Organ Procurement and Transplant Network, we identified patients ⱖ 18 years of age who underwent at least two deceased donor kidney transplantation (DDKT) between 1987 and 2010. Patients were then divided into two groups based on whether or not they developed DGF in the first transplant (1st TXP DGF group and 1st TXP no-DGF group). Unadjusted and adjusted graft survivals (Cox regression) between the groups were compared. Results. A total of 10,628 patients were identified who received more than one DDKT (3672 patients in the 1st TXP DGF group and 6956 patients in the 1st TXP no-DGF group). A higher incidence of DGF was observed with the second transplant in patients who had DGF in the first transplant (34% vs 26%, P ⫽ .001). Unadjusted graft survival for the second transplant was superior in the 1st TXP no-DGF group (P ⫽ .002). After correction for confounding variables, DGF in the first transplant did not have significant adverse impact on the graft survival of the second transplant (hazard ratio 1.2 with 95% confidence interval 0.96 –1.09, P ⫽ .44). Conclusions. In patients undergoing more than one DDKT, DGF in the first transplant is associated with higher incidence of DGF in the subsequent transplant but did not have independent adverse influence on the outcome of that graft. ELAYED GRAFT FUNCTION (DGF) in deceased donor kidney transplantation (DDKT) is associated with increase in hospital length of stay, acute rejection episodes, and cost of care.1 Long-term allograft survival is also adversely affected, and there is now evidence for adverse recipient outcome as well.2 Several donor-, recipient-, and transplant-related factors contribute to the development of DGF. Many recipients will eventually undergo more than one kidney transplantation. It is unclear whether the development of DGF in a first transplant in such patients will have any adverse impact on the outcome in a subsequent transplant. The objectives of the current study were to identify the incidence of DGF in a second DDKT in renal transplant recipients who experienced DGF in their first DDKT as well as to evaluate the impact of DGF in the first transplant on the outcome of the subsequent transplant.
D
PATIENTS AND METHODS Using Organ Procurement and Transplant Network/United Network of Organ Sharing standard transplant analysis and research files, we identified patients ⱖ 18 years of age who underwent at least two DDKT between 1987 and 2010. Recipients of multiorgan transplant were excluded from the analysis. Patients were divided into two groups based on whether or not they developed DGF in the first transplant (1st TXP DGF group and 1st TXP no-DGF group). DGF was defined as the need for dialysis within the first week of transplantation. Unadjusted and adjusted graft survivals were compared between the two groups. A Cox regression model From the Division of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA. Address reprint requests to K.K. Sureshkumar, MD, FRCP (Glasg), FASN, Division of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh PA15212. E-mail: ksureshk@ wpahs.org
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2011.06.036
Transplantation Proceedings, 43, 2499 –2501 (2011)
2499
2500
SURESHKUMAR AND MARCUS
was constructed to adjust for factors known to impact graft outcome. The confounding variables included in the model were as follows: donor-related factors (age, expanded criteria donor [ECD] kidneys, death from cerebrovascular accident); recipient-related factors (age, African-American race, diabetes mellitus, peak panel reactive antibodies, human leukocyte antigen [HLA] mismatches); and factors related to second transplant (cold ischemia time, DGF).
RESULTS
Demographic characteristics of the two groups are shown in Table 1. A total of 10,628 patients were identified who underwent more than one DDKT. Of these patients, 3672 were in the 1st TXP DGF group and 6956 in the 1st TXP no-DGF group. Recipients in the 1st TXP DGF group were slightly older, had higher proportion of males and AfricanAmericans, had higher HLA mismatches, and had longer cold ischemia time. A higher proportion of patients in this group also required dialysis before first and second transplantations. There was a higher incidence of DGF in the second transplant in patients who experienced DGF in the first transplant (34% vs 26%, P ⫽ .001). Unadjusted graft survival for the second transplant was superior in the 1st TXP no-DGF group (P ⫽ .002). However, adjusted graft survivals (after correcting for confounding variables) were similar between the 1st TXP DGF and no-DGF groups (P ⫽ .44, Fig 1). In the Cox regression model, DGF in the first transplant did not have any significant adverse impact on the graft survival for the second transplant (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.96 –1.09, P ⫽ .44). The strongest three predictors of poor graft survival for the second transplant were DGF in the second transplant (HR 1.84, 95% CI 1.73–1.96, P ⬍ .001), ECD kidney status (HR 1.34, 95% Table 1. Demographic Characteristics of the Second Transplant
Number of patients Donor age (y) Donor death from CVA (%) ECD kidney (%) Recipient age (y) Recipient gender (M/F), % Recipient African-American race (%) Recipient diabetes (%) Peak PRA (%) HLA mismatches Dialysis before first transplant (%) Dialysis before second transplant (%) Cold ischemia time (h)
DGF in First Transplant Group
No DGF in First Transplant Group
P Value
3672 35 ⫾ 16 38 9 45 ⫾ 13 64/36 31
6956 35 ⫾ 16 37 9 44 ⫾ 13 59/41 25
.496 .146 .942 .007 .001 ⬍.001
14 40 ⫾ 39 3.2 ⫾ 1.9 94
14 43 ⫾ 39 3.0 ⫾ 2.0 87
.539 .006 .001 .001
92 19 ⫾ 10
88 18 ⫾ 10
.001 .002
DGF, delayed graft function; CVA, cerebrovascular accident; ECD, expanded criteria donor; PRA, panel-reactive antibody; HLA, human leukocyte antigen.
Fig 1. Adjusted graft survival of delayed graft function (DGF) in first transplant (1st TXP DGF) group (1) versus no DGF in first transplant (1st TXP no-DGF) group (2).
CI 1.20 –1.49, P ⬍ .001); and recipient African-American race (HR 1.26, 95% CI 1.17–1.34, P ⬍ .001).
DISCUSSION
Our study showed an increase in the incidence of DGF in the second kidney transplant in patients who underwent two DDKT and experienced DGF in the first transplant. Even though the unadjusted graft survival was superior for the second transplant in patients who did not experience DGF in the first transplant, graft survival in the adjusted model was not influenced by DGF in the first transplant. In previous registry analysis, DGF in a current transplant was found to independently predict 5-year graft loss with a relative risk of 1.53 in DDKT recipients.1 A recent systematic review and meta-analysis showed a 41% increase in risk of graft loss at 3.2-year follow-up in patients who experienced DGF.3 Initial nephron destruction and non-immunemediated inflammation and scarring induced by DGF were implicated in long-term allograft loss.1 DGF was also found to increase the risk for death with functioning graft in both deceased and living donor kidney transplant recipients.2,4 Even though the development of DGF in the current transplant by far was the strongest predictor of adverse graft outcome, with an impressive 84% relative risk for graft failure in our study, the influence of DGF from previous transplant did not spill over into the current transplant outcome in multivariate analysis. There was a correlation between maintenance dialysis before first transplant and the risk for DGF development for the primary transplant. Pretransplant dialysis duration has been shown to be a risk factor for reduced graft survival in previous analysis.5 We conclude that the negative impact of the development of DGF in a current transplant should not influence
DGF AND SUBSEQUENT TRANSPLANTS
the graft outcome of a DDKT the recipient may receive in the future. REFERENCES 1. Ojo AO, Wolfe RA, Held PJ, et al: Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 63:968, 1997 2. TapiaWala SN, Tinckam KJ, Cardella CJ, et al: Delayed graft function and the risk for death with a functioning graft. J Am Soc Nephrol 21:153, 2010
2501 3. Yarlagadda SG, Coca SG, Formica RN Jr, et al: Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis. Nephrol Dial Transplant 24:1039, 2009 4. Narayanan R, Cardella CJ, Cattran DC, et al: Delayed graft function and the risk of death with graft function in living donor kidney transplant recipients. Am J Kidney Dis 56:961, 2010 5. Meier-Kriesche H-U, Kaplan B: Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation 74:1377, 2002
ABSTRACT Background. In kidney transplantation, delayed graft function (DGF) portends adverse graft and patient outcomes. It is unclear whether DGF in the first kidney transplant would adversely impact the outcome of a subsequent transplant. Methods. Utilizing data from the Organ Procurement and Transplant Network, we identified patients ⱖ 18 years of age who underwent at least two deceased donor kidney transplantation (DDKT) between 1987 and 2010. Patients were then divided into two groups based on whether or not they developed DGF in the first transplant (1st TXP DGF group and 1st TXP no-DGF group). Unadjusted and adjusted graft survivals (Cox regression) between the groups were compared. Results. A total of 10,628 patients were identified who received more than one DDKT (3672 patients in the 1st TXP DGF group and 6956 patients in the 1st TXP no-DGF group). A higher incidence of DGF was observed with the second transplant in patients who had DGF in the first transplant (34% vs 26%, P ⫽ .001). Unadjusted graft survival for the second transplant was superior in the 1st TXP no-DGF group (P ⫽ .002). After correction for confounding variables, DGF in the first transplant did not have significant adverse impact on the graft survival of the second transplant (hazard ratio 1.2 with 95% confidence interval 0.96 –1.09, P ⫽ .44). Conclusions. In patients undergoing more than one DDKT, DGF in the first transplant is associated with higher incidence of DGF in the subsequent transplant but did not have independent adverse influence on the outcome of that graft. ELAYED GRAFT FUNCTION (DGF) in deceased donor kidney transplantation (DDKT) is associated with increase in hospital length of stay, acute rejection episodes, and cost of care.1 Long-term allograft survival is also adversely affected, and there is now evidence for adverse recipient outcome as well.2 Several donor-, recipient-, and transplant-related factors contribute to the development of DGF. Many recipients will eventually undergo more than one kidney transplantation. It is unclear whether the development of DGF in a first transplant in such patients will have any adverse impact on the outcome in a subsequent transplant. The objectives of the current study were to identify the incidence of DGF in a second DDKT in renal transplant recipients who experienced DGF in their first DDKT as well as to evaluate the impact of DGF in the first transplant on the outcome of the subsequent transplant.
D
PATIENTS AND METHODS Using Organ Procurement and Transplant Network/United Network of Organ Sharing standard transplant analysis and research files, we identified patients ⱖ 18 years of age who underwent at least two DDKT between 1987 and 2010. Recipients of multiorgan transplant were excluded from the analysis. Patients were divided into two groups based on whether or not they developed DGF in the first transplant (1st TXP DGF group and 1st TXP no-DGF group). DGF was defined as the need for dialysis within the first week of transplantation. Unadjusted and adjusted graft survivals were compared between the two groups. A Cox regression model From the Division of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA. Address reprint requests to K.K. Sureshkumar, MD, FRCP (Glasg), FASN, Division of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh PA15212. E-mail: ksureshk@ wpahs.org
© 2011 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/–see front matter doi:10.1016/j.transproceed.2011.06.036
Transplantation Proceedings, 43, 2499 –2501 (2011)
2499
2500
SURESHKUMAR AND MARCUS
was constructed to adjust for factors known to impact graft outcome. The confounding variables included in the model were as follows: donor-related factors (age, expanded criteria donor [ECD] kidneys, death from cerebrovascular accident); recipient-related factors (age, African-American race, diabetes mellitus, peak panel reactive antibodies, human leukocyte antigen [HLA] mismatches); and factors related to second transplant (cold ischemia time, DGF).
RESULTS
Demographic characteristics of the two groups are shown in Table 1. A total of 10,628 patients were identified who underwent more than one DDKT. Of these patients, 3672 were in the 1st TXP DGF group and 6956 in the 1st TXP no-DGF group. Recipients in the 1st TXP DGF group were slightly older, had higher proportion of males and AfricanAmericans, had higher HLA mismatches, and had longer cold ischemia time. A higher proportion of patients in this group also required dialysis before first and second transplantations. There was a higher incidence of DGF in the second transplant in patients who experienced DGF in the first transplant (34% vs 26%, P ⫽ .001). Unadjusted graft survival for the second transplant was superior in the 1st TXP no-DGF group (P ⫽ .002). However, adjusted graft survivals (after correcting for confounding variables) were similar between the 1st TXP DGF and no-DGF groups (P ⫽ .44, Fig 1). In the Cox regression model, DGF in the first transplant did not have any significant adverse impact on the graft survival for the second transplant (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.96 –1.09, P ⫽ .44). The strongest three predictors of poor graft survival for the second transplant were DGF in the second transplant (HR 1.84, 95% CI 1.73–1.96, P ⬍ .001), ECD kidney status (HR 1.34, 95% Table 1. Demographic Characteristics of the Second Transplant
Number of patients Donor age (y) Donor death from CVA (%) ECD kidney (%) Recipient age (y) Recipient gender (M/F), % Recipient African-American race (%) Recipient diabetes (%) Peak PRA (%) HLA mismatches Dialysis before first transplant (%) Dialysis before second transplant (%) Cold ischemia time (h)
DGF in First Transplant Group
No DGF in First Transplant Group
P Value
3672 35 ⫾ 16 38 9 45 ⫾ 13 64/36 31
6956 35 ⫾ 16 37 9 44 ⫾ 13 59/41 25
.496 .146 .942 .007 .001 ⬍.001
14 40 ⫾ 39 3.2 ⫾ 1.9 94
14 43 ⫾ 39 3.0 ⫾ 2.0 87
.539 .006 .001 .001
92 19 ⫾ 10
88 18 ⫾ 10
.001 .002
DGF, delayed graft function; CVA, cerebrovascular accident; ECD, expanded criteria donor; PRA, panel-reactive antibody; HLA, human leukocyte antigen.
Fig 1. Adjusted graft survival of delayed graft function (DGF) in first transplant (1st TXP DGF) group (1) versus no DGF in first transplant (1st TXP no-DGF) group (2).
CI 1.20 –1.49, P ⬍ .001); and recipient African-American race (HR 1.26, 95% CI 1.17–1.34, P ⬍ .001).
DISCUSSION
Our study showed an increase in the incidence of DGF in the second kidney transplant in patients who underwent two DDKT and experienced DGF in the first transplant. Even though the unadjusted graft survival was superior for the second transplant in patients who did not experience DGF in the first transplant, graft survival in the adjusted model was not influenced by DGF in the first transplant. In previous registry analysis, DGF in a current transplant was found to independently predict 5-year graft loss with a relative risk of 1.53 in DDKT recipients.1 A recent systematic review and meta-analysis showed a 41% increase in risk of graft loss at 3.2-year follow-up in patients who experienced DGF.3 Initial nephron destruction and non-immunemediated inflammation and scarring induced by DGF were implicated in long-term allograft loss.1 DGF was also found to increase the risk for death with functioning graft in both deceased and living donor kidney transplant recipients.2,4 Even though the development of DGF in the current transplant by far was the strongest predictor of adverse graft outcome, with an impressive 84% relative risk for graft failure in our study, the influence of DGF from previous transplant did not spill over into the current transplant outcome in multivariate analysis. There was a correlation between maintenance dialysis before first transplant and the risk for DGF development for the primary transplant. Pretransplant dialysis duration has been shown to be a risk factor for reduced graft survival in previous analysis.5 We conclude that the negative impact of the development of DGF in a current transplant should not influence
DGF AND SUBSEQUENT TRANSPLANTS
the graft outcome of a DDKT the recipient may receive in the future. REFERENCES 1. Ojo AO, Wolfe RA, Held PJ, et al: Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 63:968, 1997 2. TapiaWala SN, Tinckam KJ, Cardella CJ, et al: Delayed graft function and the risk for death with a functioning graft. J Am Soc Nephrol 21:153, 2010
2501 3. Yarlagadda SG, Coca SG, Formica RN Jr, et al: Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis. Nephrol Dial Transplant 24:1039, 2009 4. Narayanan R, Cardella CJ, Cattran DC, et al: Delayed graft function and the risk of death with graft function in living donor kidney transplant recipients. Am J Kidney Dis 56:961, 2010 5. Meier-Kriesche H-U, Kaplan B: Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation 74:1377, 2002