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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 21  |  Issue : 2  |  Page : 242-245
Evaluation of factors causing delayed graft function in live related donor renal transplantation


1 Department of Nephrology, Monilek Hospital and Research Center, Jawahar Nagar, Jaipur, India
2 Department of Urology, Monilek Hospital and Research Center, Jawahar Nagar, Jaipur, India
3 Department of Medicine, Monilek Hospital and Research Center, Jawahar Nagar, Jaipur, India

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Date of Web Publication9-Mar-2010
 

   Abstract 

To determine the incidence and determinants of delayed graft function due to post­transplant acute tubular necrosis in live related donor renal transplantation. This is a retrospective study of 337 recipients of live related donor renal graft performed between1986 and 2006. Of these recipients, 24 (7.1%) subjects developed delayed graft function with no evidence of acute rejection, cyclosporin toxicity, vascular catastrophe or obstructive cause and had evidence of acute tubular necrosis (ATN Group). These subjects were compared with recipients (n= 313, 92.9%) who had no clinical or biochemical evidence of ATN. Mean age, and gender distribution of recipients was similar in the two groups (ATN group 35.7 ± 8.3, non-ATN group 34.3 ± 7.5, P= 0.43). Gender distribution of the recipients (men 279, 89.1% vs. 21, 87.5%, P= 0.80) as well as donors (women 221, 70.6% vs. 18, 75.0%, P= 0.75) was also similar. In ATN group as compared with non-ATN group the donor age was significantly greater (56.6 ± 8.3 vs. 46.6 ± 11.2 years, P< 0.0001). There was marginal difference in pre-operative systolic BP (154.5 ± 18.3 vs. 147.4 ± 20.2 mm Hg, P= 0.077) and significant difference in diastolic BP (87.8 ± 9.5 vs. 83.4 ± 11.4 mmHg, P= 0.041). Incidence of multiple renal arteries was similar (16.7% vs. 7.3%, P= 0.22). The warm ischemia time was significantly greater in ATN group (33.3 ± 6.2 min) as compared to non-ATN group (30.4 ± 5.7 min, P= 0.042). Duration of hospital stay was more in ATN group (19.9 ± 6.7 vs. 16.8 ± 8.4 days, P= 0.04) but there was no difference in 1 year survival (284 subjects, 90.7% vs. 21 subjects, 87.5%, P= 0.873). This study shows that greater donor age, higher baseline diastolic BP and greater warm ischemia time are major determinants of delayed graft function due to acute tubular necrosis after related donor renal transplantation.

How to cite this article:
Sharma A K, Tolani S L, Rathi G L, Sharma P, Gupta H, Gupta R. Evaluation of factors causing delayed graft function in live related donor renal transplantation. Saudi J Kidney Dis Transpl 2010;21:242-5

How to cite this URL:
Sharma A K, Tolani S L, Rathi G L, Sharma P, Gupta H, Gupta R. Evaluation of factors causing delayed graft function in live related donor renal transplantation. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2019 Nov 15];21:242-5. Available from: http://www.sjkdt.org/text.asp?2010/21/2/242/60060

   Introduction Top


Delayed graft function is a frequent compli­cation of renal transplantation affecting 2 to 50% of first kidney transplant recipients in dif­ferent centers. [1] The clinical spectrum varies from a slow post-transplant decline of serum crea­tinine to prolonged period of oliguria that mandates dialysis. [1],[2],[3] Delayed graft function is a form of oliguric acute renal failure occurring in post transplant period and is often used synony­mously with acute tubular necrosis. [4] Prolonged dialysis dependency and hospital stay contributes to the overall cost during the post-transplant period. Delayed graft function is associated with an increased risk of premature graft failure and residual graft dysfunction because of the se­quelae of ischemia/reperfusion damage and po­ssibly because of occult mild episodes of acute rejection occurring during that period. [5] The pre­sent retrospective study was conducted with the aim to know the incidence of delayed graft function due to post-transplant acute tubular necrosis in live related donor renal transplan­tation and to understand the various factors responsible for its occurrence.


   Methods Top


This is a retrospective study of 337 recipients of live related donor renal transplantation per­formed at a single centre in India between 1986 and 2006. Only two recipients received second graft. The study included all the recipients ir­respective of their etiology of end stage renal disease. All the recipients received ABO blood group compatible donors with negative tissue cross match and followed the same selection criteria and practically same surgical and me­dical staff was involved in the surgical and me­dical monitoring procedures. All the recipients were given intravenous methyl prednisolone in­traoperatively. Other immunosuppressive drugs used were prednisolone, azathioprine, and cy­closporin, with or without mycophenolate mo­fetil, tacrolimus, sirolimus, everolimus, and in­terleukin-2 receptor blockers. Recipient and do­nor surgeries were performed simultaneously following standard procedures. Laparoscopic do­nor nephrectomy was performed in one donor only. Total ischemia time, i.e., the time bet­ween clamping of renal artery in the donor to the time of releasing of the clamp after arterial anastamosis in the recipient was recorded in all the patients.

All the recipients requiring of dialysis in the first week post-transplant, or decreased urine output (< 30 mL/hour) in first 24 hours, or rising serum creatinine values (decline in creatinine of less than 0.5 mg/dL in first 24 hours) were subjected to ultrasonography, renal cortical and vascular doppler studies, cyclosporin blood le­vels and kidney biopsy if no response to treat­ment was seen. Acute tubular necrosis (ATN) was diagnoses using standard clinical, bioche­mical and histopathological criteria. Acute cel­lular rejections were treated with intravenous methyl prednisolone (1 g daily for three days) and vascular rejections were treated with OK­T3 or anti-thymocyte globulin. Cyclosporin based immunosuppressive regimen was mo­dified in patients with delayed graft function in either of the following ways (i) patients were maintained with reduced doses of cyclosporin, or (ii) patients were switched over from cy­closporin to sirolimus or tacrolimus. Only those recipients who had no evidence of acute rejec­tion or cyclosporin toxicity or vascular catas­trophes or any urological complications were included in the study. The primary end point was the death of the patients.

Statistical analysis for comparison of various clinical and surgical parameters was performed using t-test for numerical variables and chi­square test for ordinal variables. Yates correc­tion was applied when the sample size in a single group was less than 5. P values < 0.05 were considered significant.


   Results Top


Causes of end stage renal disease in the reci­pients included chronic glomerulonephritis in 199 (59.1%), chronic interstitial nephritis in 54 (16.0%), hypertensive glomerulosclerosis in 33 (9.8%), polycystic disease of kidneys in 22 (6.5%), diabetic nephropathy in 21 (6.2%), va­sicoureteric reflux in 3 and other causes in 2 cases.

Patients' characteristics are shown in [Table 1]. It is clear that except higher donor age and diastolic blood pressure in the TN group all the other parameters were similar. The warm is­chemia time was significantly greater in ATN group (33.3 ± 6.2 min) as compared to non­ATN group (30.4 ± 5.7 min, P= 0.042). The only difference in drug therapy was a greater use of daclizumab in ATN group (6 subjects, 25.0%) as compared to non-ATN group (26, 8.3%, P= 0.020). Duration of hospital stay was more in ATN group (19.9 ± 6.7 vs. 16.8 ± 8.4 days, P= 0.01) but there was no difference in 1 year survival (284 subjects, 90.7% vs. 21 sub­jects, 87.5%, P= 0.060).


   Discussion Top


Delayed graft function is a form of post-trans­plant acute renal failure with significant clinical and long term impact on future graft functio­ning. [6] The incidence of delayed graft function in living related donor renal transplantation has been reported to be 4-10%. [7] Different studies have used different criteria of defining delayed graft function therefore resulting in variable reports and the actual incidence being higher than appreciated. Patients with non-oliguric ATN or patients with slowly recovering graft func­tion or patients who needed dialysis for other indications like hyperkalemia has been falsely labeled as delayed graft function. [6]

The term delayed graft function and ATN are often used interchangeably particularly in con­text with cadaver donor transplantation. Post­transplant ATN is essentially caused by ische­mic injury. As the duration of ischemia is not very long in live related donor transplantation the ischemic metabolic changes are reversible. [4] But these metabolic changes may be aggrava­ted by superimposed clinical or sub-clinical re­jections which may remain undetected while patient is on dialysis or by the nephrotoxic ef­fects of immunosuppressive drugs. [8] The inci­dence of delayed graft function is higher in ca­daver transplantation varying from 2 to 50% in different centers. [1],[9] The cadaver kidney is likely to be damaged at every step from procurement to reperfusion. There can be multiple factors in the cadaver donors e.g. underlying disease, vaso­pressors, decreased platelets, disseminated intra­vascular coagulation, catecholamine release, ca­tabolic state of the donor, prolonged ischemia time particularly in non-beating donors. [10] Du­ring ischemia, anaerobic metabolism results in accumulation of lactic acid causing metabolic acidosis. Sodium-potassium pump is affected causing cell diruption. There is irreversible loss of purines from adenosine triphosphate synthe­sis pool and production of oxygen free radicals from hypoxanthine during reperfusion. [11] Reper­fusion injury occurs as a result of restoration of blood in the graft kidney. During reperfusion re-introduction of molecular oxygen in to the tissues occurs which reacts with hypoxanthine and xanthine oxidase and produces superoxide and hydrogen peroxide anions resulting in lipid per-oxidation of the cell membranes. [4],[11] In the present study 24 patients (7.1%) developed ATN similar to other reports. [3]

Various pre-operative factors including donor age, donor hypertension, prolonged anastamosis time, preoperative dialysis with too much ul­trafiltration causing volume contraction in the recipient and pelvic atherosclerosis have been found to promote ischemic injury. Donor age is important in the development of delayed graft function. It has been demonstrated that if the donor age is > 60 years the graft survival dec­reases. [13] In our study the mean age of the do­nors in the ATN group was 56.6 ± 8.3 years as compared to non ATN group which was 46.6 ± 11.2 years. Donor hypertension also plays im­portant role in the development of delayed graft function. [13] Rajgopalan et al demonstrated that recipient's hydration status was an important factor in the development of delayed graft func­tion. They reported that overall incidence of ATN in the group of patients who received sa­line was 7.6% as compared to 53% who did not. [12] Sevel et al demonstrated that female gen­der and high recipient-donor weight ratio were important predictors of development of delayed graft function. [14] This was not observed in the present study. Duration of cold ischemia time is a significant risk factor in the etiology of ATN and an increased ischemia time in cadaver transplantation is the cause of high incidence of ATN. [15] The anastamosis time (warm ischemia time) has also been strongly correlated with de­layed graft function and was identified as the strongest independent predictor of delayed graft function in some studies. [16] In our study the total ischemia time was significantly greater in ATN group as compared to the non-ATN group [Table 1]. Ojo et al demonstrated that the pre­sence of ATN was an important predictive factor for the loss of graft function 5 years after transplantation. [3] On the other hand, Tropp­mann et al reported that presence of ATN had no long term prognostic effect on the transplant survival [17] as observed in the present study.

In conclusion, the present study shows that greater donor age and more warm ischemia time are some of the determinants resulting in ATN post transplantation. A larger sample size is needed to more accurately determine the factors involved in post Transplant ATN.

 
   References Top

1.Marcus JW, Hoitsma AJ, Koene RA. Detrimental effect of acute renal failure on the survival of the renal allograft: Influence of total ischemia time and anastamosis time. Nephrol Dial Transplant 1991;6: 881-6.  Back to cited text no. 1      
2.Jacobs SC, Cho E, Foster C, et al. Laparoscopic donor nephrectomy: The University of Maryland 6­year experience. J Urol 2004;171:47-51.  Back to cited text no. 2  [PUBMED]    
3.Ojo AO, Wolfe RA, Held PA, et al. Delayed graft function: Risk factors and implications for renal allograft survival. Transplantation 1997;6:968-74.  Back to cited text no. 3      
4.Shoskes DA, Halloran PF. Delayed graft function in renal transplantation: Etiology, management and long term significance. J Urol 1996;155:1831-40.  Back to cited text no. 4  [PUBMED]    
5.Howadr RJ, Pfaff WW, Brunsen ME, et al. Delayed graft function is associated with an increased inci­dence of occult rejection and results in poor graft survival. Transplant Proc 1993;25:884.  Back to cited text no. 5      
6.Perico N, Cattaneo D, Sayegh MH, et al. Delayed graft function in kidney transplantation. Lancet 2004; 364:1814-27.  Back to cited text no. 6  [PUBMED]    
7.Senel FM, Karakayali H, Moray G, et al. Delayed graft function: Predictive factors and impact on out­come in living-related kidney transplantation. Ren Fail 1998;20:589-95.  Back to cited text no. 7  [PUBMED]    
8.Cravedi P, Codreanu I, Satta A, et al. Cyclosporin prolongs delayed graft function in kidney transplan­tation: Are rabbit anti-human thymocyte globulins the answer. Nephron Clin Pract 2005;101:65-71.  Back to cited text no. 8      
9.Organ Procurrement Transplant Network. 2004. Available at: http://www.OPTN.org.  Back to cited text no. 9      
10.Darby JM, Stein K, Grenvik A, et al. Approach to management of the heart-beating 'brain- dead' organ donor. JAMA 1989;261:2222.  Back to cited text no. 10  [PUBMED]    
11.McCord JM. Oxygen-derived free radicals in post­ischemic tissue injury. N Engl J Med 1985;312:159.  Back to cited text no. 11  [PUBMED]    
12.Rajagopalan PR, Kay NA, Fitts CT, et al. Preven­tion of ATN after transplantation: Effects of pre­transplantation volume expansion. South Med J 1986; 8:972-4.  Back to cited text no. 12      
13.Cecka JM. The UNOS Scientific Renal Transplant Registry. In: Cecka JM, Terasaki PM. (Eds): Clini­cal Transplantation. Los Angeles. UCLA Tissue Typing Laboratory. 1998; 1-16.  Back to cited text no. 13      
14.Sevel FM, Karakayali H, Moray G, et al. Delayed graft function: Predicting factors and impact on outcome in living related kidney transplantation. Ren Fail 1998;20:589-95.  Back to cited text no. 14      
15.Wynen RM, Booster M, Speatgens C, et al. Long term follow-up of non-heart-beating donor kidneys: Preli­minary results of a retrospective study. Transplant Proc 1993;25:1522.  Back to cited text no. 15  [PUBMED]    
16.Halloran PF, Shoskes DA. Early transplant non-func­tion: Influence on ultimate graft survival and func­tion. In. Solez K, Racussen LC, (Eds): Acute renal failure: diagnosis, treatment and prevention. New York, Mercel Dekkar Inc. 1991;387-397.  Back to cited text no. 16      
17.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.  Back to cited text no. 17  [PUBMED]    

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Correspondence Address:
A K Sharma
Department of Nephrology, Monilek Hospital and Research Center, Sector 4, Jawahar Nagar, Jaipur 302004
India
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PMID: 20228507

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