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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2013  |  Volume : 24  |  Issue : 2  |  Page : 243-246
Risk factors and consequences of delayed graft function


1 Department of Internal Medicine A, Charles Nicolle Hospital, Tunis, Tunisia
2 Department of Urology, Charles Nicolle Hospital, Tunis, Tunisia
3 Laboratory of Immunology (LR03SP01), Charles Nicolle Hospital, Tunis, Tunisia

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Date of Web Publication26-Mar-2013
 

   Abstract 

The impact of delayed graft function (DGF) on the outcome of renal transplantation remains controversial. We analyzed the risk factors for DGF and its impact on graft and patient survival. A total of 354 renal transplants performed between June 1986 and April 2000 were analyzed. Variables analyzed included donor and recipient age, method and duration of renal replacement therapy, HLA mismatch, cold and warm ischemia times, biopsy-confirmed acute rejection, length of stay in the hospital, serum creatinine at the end of first hospitalization as well as graft and patient survival at one, three, five and ten years. The study patients were divided into two groups: patients with DGF (G1) and those without DGF (G2). DGF occurred in 50 patients (14.1%), and it was seen more frequently in patients transplanted from deceased donors (60% vs. 40%, P <0.0001). The cause of DGF was acute tubular necrosis, seen in 98% of the cases. Univariate analysis showed a statistically significant difference between the two groups G1 and G2 in the following parameters: average duration on dialysis (52.3 vs. 36.4 months, P = 0.006), HLA mismatch (44.9% vs. 32.11% P = 0.015), donor age (35.9 vs. 40.2 years, P = 0.026), cold ischemia time (23 vs. 18.2 h, P = 0.0016), warm ischemia time (41.9 vs. 38.6 mn, P = 0.046), length of stay in the hospital during first hospitalization (54.7 vs. 33.2 days, P <0.0001), serum creatinine at the end of first hospitalization (140 vs. 112 μmol/L, P <0.0001) and at three months following transplantation (159 vs. 119 μmol/L, P = 0.0002). Multivariate analysis revealed the following independent risk factors for DGF: deceased donor (RR = 13.2, P <0.0001) and cold ischemia time (RR = 1.17, P = 0.008). The graft survival at one, three, five and ten years was 100%, 93%, 88.3% and 78.3% in G1 versus 100%, 95.9% 92.8% and 82.3% in G2; there was no statistically significant difference. The patient survival at one, three, five and ten years was 100%, 91.3%, 83.6% and 74.4% in G1 versus 100%, 95.9%, 94% and 82.6% in G2 with a statistically significant difference (P = 0.04). Prolonged cold ischemia time and transplantation of kidneys from deceased donors were the main risk factors for DGF in our study. Also, DGF significantly affected patient survival but had no influence on graft survival.

How to cite this article:
Ounissi M, Cherif M, Abdallah TB, Bacha M, Hedri H, Abderrahim E, Goucha R, Kheder A, Slama RB, Derouiche A, Chebil M, Bardi R, Sfar I, Gorgi Y. Risk factors and consequences of delayed graft function. Saudi J Kidney Dis Transpl 2013;24:243-6

How to cite this URL:
Ounissi M, Cherif M, Abdallah TB, Bacha M, Hedri H, Abderrahim E, Goucha R, Kheder A, Slama RB, Derouiche A, Chebil M, Bardi R, Sfar I, Gorgi Y. Risk factors and consequences of delayed graft function. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Feb 21];24:243-6. Available from: http://www.sjkdt.org/text.asp?2013/24/2/243/109564

   Introduction Top


Delayed graft function (DGF) is a frequent and well known complication of renal transplantation, which occurs in 30% of cadaver kidney allografts and has no curative treatment. [1] It is characterized essentially by acute ischemic tubular necrosis. It has bad economic implications due to the need for prolonged patient hospitalization and possibly the need for hemodialysis sessions. DGF also increases the risk of acute allograft rejection and may affect long-term graft survival. [1],[2] Many risk factors have been identified including donor hemodynamic compromise or prolonged cold ischemia time. Additionally, the incidence of DGF remains high due to the frequent use of marginal donors due to organ shortage.

The aim of this study is to review the risk factors for occurrence of DGF and its impact on long-term graft and patient survival.


   Patients and Methods Top


DGF is usually defined as the necessity of dialysis during the first week after transplantation. [1],[2] Acute rejection episodes (AR) are diagnosed based on clinical symptoms and confirmed by kidney biopsy.

Data from 354 patients who underwent renal transplantation between June 1986 and April 2008 were analyzed retrospectively. Variables analyzed included donor age, recipient age, method and duration of renal replacement therapy, HLA mismatch, cold and warm ischemia times, biopsy-confirmed acute rejection, length of hospital stay, serum creatinine at the end of first hospitalization and at three, six and 12 months following transplantation as well as the graft and patient survival rates at one, three, five and ten years in recipients with (G1) and without DGF (G2).

Patients with vascular thrombosis of the kidney immediately after transplantation, recurrence of focal and segmental glomerulosclerosis (FSGS), death during the first week after surgery and primary non-functioning kidney were not analyzed for DGF.

Statistical analysis was made using the Stat view Software 5.0. Categorical variables were compared using the unpaired Student's t-test. Nominal variables were compared using Chi square. The graft and patient survival rates were computed using the actuarial method and comparison was performed using the log rank test. The level of statistical significance was set at 5%.


   Results Top


A total of 354 patients were included in the study with a mean age of 32.2 ± 9.3 years. There were 121 females (34.2%) and 233 males (65.8%). The source of the allograft was from living donors (LD) in 293 cases (82.8%) and deceased donors (DD) in 61 cases (17.2%). DGF was seen in 50 patients (14.1%). Twenty of these patients were transplanted from LD (40%) and 30 from DD (60%); the difference was statistically significant (P <0.0001).

In 98% of the cases (49 patients), the DGF was related to acute tubular necrosis (ATN) and in 2% (one patient) it was due to cortical necrosis. The demographic and clinical characteristics of the study patients are given in [Table 1]. Multivariate analysis of clinical variables revealed deceased donor as an independent risk factors of DGF [RR = 13.2 (6.7-25.9) P <0.0001].
Table 1: Demographic and clinical characteristics of the study patients.

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In deceased donor transplants, cold ischemia time increases the risk of DGF by a factor of 1.17 (1.04-1.3) with a P = 0.008. The graft survival at 1, 3, 5 and 10 years was 100%, 93%, 88.3% and 78.3% in G1 versus 100%, 95.9%, 92.8% and 82.3% in G2, without any statistically significant difference [Figure 1].
Figure 1: Actuarial allograft survival in the groups of patients with and without delayed graft function (DGF).

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The patient survival at one, three, five and ten years was 100%, 91%, 83% and 74.4% in G1 versus 100%, 95.9%, 94% and 82.6% in G2 patients; the difference was statistically significant (P = 0.04) [Figure 2].
Figure 2: Actuarial patient survival in the groups of patients with and without delayed graft function (DGF).

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   Discussion Top


DGF is high on the list of immediate post-operative complications following kidney transplantation. Defined as the need for dialysis in the first week after surgery, DGF occurs in 20-50% of patients receiving a first cadaver graft. [1],[2] It is usually the result of ischemic damage to the graft before or during harvesting, and is further aggravated by the perfusion injury.

DGF was seen in only 14.1% of our patients, and this is probably because the majority of transplants in our study patients were from LD. The mean duration of first hospitalization was significantly longer in the group with DGF. The same results were reported by Marcen and others. [3] Factors related to the donor and pre-renal, renal or post-renal transplant factors related to the recipient can contribute to DGF. [4] From experimental studies, both ischemia and reperfusion in ischemically damaged kidneys after hypothermic preservation activate a complex sequence of events that sustain renal injury and play a pivotal part in the development of DGF. [4],[5] In our study, univariate analysis showed that donor age and mean duration of cold and warm ischemia are risk factors for DGF. Multivariate analysis showed that only cadaveric graft and the mean duration of cold ischemia are risk factors for DGF.

The long-term effect of DGF on graft survival could ultimately be explained by the subsequent reduction of the nephron mass leading to hyperfiltration, glomerular hypertension, nephrosclerosis and chronic decline of graft function. [5],[6],[7] The role of DGF on graft survival is controversial. Troppman et al have suggested that DGF without rejection may have no impact on long-term graft survival. [8] Henk et al have reported that DGF influences graft function but not graft survival. [9] Other studies have suggested that graft survival in patients with or without DGF is the same if no AR occurs, but is lower in patients with both DGF and AR when compared with patients with DGF alone. [10],[11],[12] However, these results are still controversial and some authors having reported that AR and DGF were independent risk factors for allograft survival. [13],[14],[15],[16]

In our study, DGF affected patient survival and not graft survival. The patient survival at three, five and ten years was statistically lower in the group with DGF, which is consistent with other reports in the literature. [17]

Finally, recent advances in the pathophysiology of DGF point toward the importance of ischemia-reperfusion injury mechanisms and some interventions that may reduce this injury are under investigation. They include the use of new solutions to improve organ preservation and the use of some anti-oxidant and anti-inflammatory drugs. [1]

DGF is frequent in our kidney transplanted patients. Cold ischemia time and deceased donor are important independent predictors. There is no correlation between DGF and the acute rejection rate or graft survival. However, patient survival is significantly better in patents without DGF.

 
   References Top

1.Szwarc I, Garrigue V, Delmas S, Deleuze S, Chong G, Mourad G. Delayed graft function: A frequent but still unsolved problem in renal transplantation. Néphrol Thér 2005;1:325-34.  Back to cited text no. 1
    
2.Giral-Classe M, Hourmant M, Cantarovich D, et al. Delayed graft function of more than six days strongly decreases long term survival of transplant kidneys. Kidney Int 1998;54:972-8.  Back to cited text no. 2
    
3.Marcén R, Orofino L, Pascual J, et al. Delayed graft function does not reduce the survival of renal transplant allografts. Transplantation 1998; 66:461-6.  Back to cited text no. 3
    
4.Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet 2004;364:1814-27.  Back to cited text no. 4
    
5.Land W, Messmer K. The impact of ischemia/ reperfusion injury on specific and non specific early and late chronic events after organ transplantation. Transplant Rev 1996;10:108-27.  Back to cited text no. 5
    
6.Brenner BM. Nephron underdosing: A programmed cause of chronic allograft failure. Am J Kidney Dis 1993;21:66-72.  Back to cited text no. 6
    
7.Sanfilippo F, Vaughn WK, Spees EK, Lucas BA. The detrimental effects of delayed graft function in cadaver donor renal transplantation. Transplantation 1984;38:643-8.  Back to cited text no. 7
    
8.Troppmann C, Gillingham KJ, Gruessner RW, et al. Delayed graft function in the absence of rejection has no long term impact. Transplantation 1996;61:1331-7.  Back to cited text no. 8
    
9.Boom H, Mallat MJ, de Fijter JW, Zwinderman AH, Paul LC. Delayed graft function influences renal function, but not survival. Kidney Int 2000;58:859-66.  Back to cited text no. 9
    
10.Troppmann C, Gillingham KJ, Benedetti E, et al. Delayed graft function, acute rejection and outcome after cadaver renal transplantation. Transplantation 1995;59:962-8.  Back to cited text no. 10
    
11.Halloran PF, Aprile MA, Farewell V, et al. Early function as the principal correlate of graft survival. Transplantation 1998;46:223-8.  Back to cited text no. 11
    
12.Halloran PA, Farewell V. Factors influencing early renal function in cadaver kidney transplant. Transplantation 1988;45:122-7.  Back to cited text no. 12
    
13.Feldman HI, Gayner R, Berlin JA, et al. Delayed function reduces renal allograft survival independent of acute rejection. Nephrol Dial Transplant 1996;11:1306-13.  Back to cited text no. 13
    
14.Humar A, Johnson EM, Payne WD, et al. Effect of initial graft function on renal allograft rejection and survival. Clin Transplant 1997;11:623-7.  Back to cited text no. 14
    
15.Najarian JS, Gillingham KJ, Sutherland DE, Reinsmoen NL, Payne WD, Matas AJ. The impact of the quality of initial graft function on cadaver kidney transplants. Transplantation 1994; 57:812-6.  Back to cited text no. 15
    
16.Heitig A. Delayed graft function. Néphrol Thér 2008;5:184-7.  Back to cited text no. 16
    
17. Sáinz MM, Toro JC, Poblete HB, Perez LF, Nicovani VH, Carrera MG. Incidence and factors associated with delayed graft function in renal transplantation in Carlos Van Buren Hospital, January 2000 to June 2008. Transplant Proc 2009;41:2655-8.  Back to cited text no. 17
    

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Correspondence Address:
Mondher Ounissi
Department of Internal Medicine A, Charles Nicolle Hospital, Tunis
Tunisia
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DOI: 10.4103/1319-2442.109564

PMID: 23538345

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