Year : 2010 | Volume
: 21 | Issue : 2 | Page : 242--245
Evaluation of factors causing delayed graft function in live related donor renal transplantation
AK Sharma1, SL Tolani2, GL Rathi2, P Sharma2, H Gupta1, R Gupta3,
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
A K Sharma
Department of Nephrology, Monilek Hospital and Research Center, Sector 4, Jawahar Nagar, Jaipur 302004
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;21:242-245
|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 2021 Oct 24 ];21:242-245
Available from: https://www.sjkdt.org/text.asp?2010/21/2/242/60060
Delayed graft function is a frequent complication of renal transplantation affecting 2 to 50% of first kidney transplant recipients in different centers.  The clinical spectrum varies from a slow post-transplant decline of serum creatinine to prolonged period of oliguria that mandates dialysis. ,, 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.  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.  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.
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 (  The incidence of delayed graft function in living related donor renal transplantation has been reported to be 4-10%.  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. 
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.  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.  The incidence of delayed graft function is higher in cadaver transplantation varying from 2 to 50% in different centers. , 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.  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.  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. , In the present study 24 patients (7.1%) developed ATN similar to other reports. 
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.  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.  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.  Sevel et al demonstrated that female gender and high recipient-donor weight ratio were important predictors of development of delayed graft function.  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.  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.  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.  On the other hand, Troppmann et al reported that presence of ATN had no long term prognostic effect on the transplant survival  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.
|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.|
|2||Jacobs SC, Cho E, Foster C, et al. Laparoscopic donor nephrectomy: The University of Maryland 6year experience. J Urol 2004;171:47-51.|
|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.|
|4||Shoskes DA, Halloran PF. Delayed graft function in renal transplantation: Etiology, management and long term significance. J Urol 1996;155:1831-40.|
|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.|
|6||Perico N, Cattaneo D, Sayegh MH, et al. Delayed graft function in kidney transplantation. Lancet 2004; 364:1814-27.|
|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.|
|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.|
|9||Organ Procurrement Transplant Network. 2004. Available at: http://www.OPTN.org.|
|10||Darby JM, Stein K, Grenvik A, et al. Approach to management of the heart-beating 'brain- dead' organ donor. JAMA 1989;261:2222.|
|11||McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985;312:159.|
|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.|
|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.|
|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.|
|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.|
|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.|
|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.|