1474 | Short-term Survival in Renal Transplantation from Brain-Death Donors: Focusing on Re- cipients with Diabetes Background Manoochehr Nakhjavani,1 Fatemeh Ghaemi,2 Hamid Ravaghi,3 Mohammad Aghighi,4 Farahnaz Ghaemi5 Corresponding Author: Fatemeh Ghaemi, MD Ministry of Health and Medical Edu- cation, Tehran University of Medical Sciences, Tehran, Iran. Tel: +98 21 88562426 Fax: +98 021 66911294 E-mail: ghaemifatemeh@yahoo. com Received November 2012 Accepted January 2014 1 Department of Endoctrinol- ogy, Tehran University of Medi- cal Sciences, Vali’asr Hospital, Tehran, Iran. 2 Ministry of Health and Medical Education, Tehran University of Medical Sciences, Tehran, Iran. 3 Department of Health Services Management, Health Management and Econom- ics Research Center, School of Health Management and Information Sciences, Iran University of Medical Science, Tehran, Iran. 4 Management Center of Transplantation and Special Diseases, Tehran University of Medical Sciences, Tehran, Iran. 5 Department of Microbiology, Islamic Azad University, Ker- man Branch, Kerman, Iran. KIDNEY TRANSPLANTION Kidney Transplantion Purpose:‎Our‎aim‎was‎to‎evaluate‎short‎term‎survival‎rates‎in‎renal‎transplant‎recipients‎from‎ deceased‎donors,‎while‎focusing‎on‎recipients‎with‎diabetes‎mellitus‎background. Materials and Methods:‎This‎is‎a‎longitudinal‎follow-up‎study‎based‎on‎national‎registry‎of‎ recipients‎in‎Ministry‎of‎Health‎and‎Medical‎Education‎in‎Iran‎from‎2010-11.‎Five‎hundred‎ fifty-five‎recipients,‎226‎(40.8%)‎females‎and‎328‎(59.2%)‎males,‎were‎included‎in‎the‎study.‎ Mean‎(±‎SD)‎age‎of‎the‎recipients‎was‎39‎±‎14‎years.‎Of‎donors‎18.4%‎were‎females‎and‎81.6%‎ were‎males.‎Age‎of‎the‎donors‎was‎33‎±‎14‎years.‎All‎allograft‎recipients‎from‎deceased‎donors‎ enrolled‎in‎the‎study.‎Short-term‎graft‎survival‎(1‎year)‎was‎determined.‎Data‎regarding‎age,‎ gender,‎background‎disease‎and‎cold‎ischemic‎time‎of‎recipients‎and‎donors‎were‎collected‎ from‎the‎organ‎procurement‎units.‎ Results:‎Allografts‎were‎functioning‎in‎499‎(90.1%)‎of‎recipients‎after‎one‎year.‎Of‎recipi- ents‎38‎(6.9%)‎died‎and‎rejection‎of‎transplanted‎kidney‎occurred‎in‎17‎(3.1%)‎cases.‎So,‎ in‎55‎(9.9%)‎cases,‎allografts‎were‎not‎functioning.‎There‎were‎significant‎relationships‎be- tween‎short‎term‎graft‎survival‎of‎donors'‎gender,‎age‎of‎recipients,‎cold‎ischemic‎time‎and‎ level‎of‎clearance‎of‎creatinine‎of‎recipients.‎‎ Conclusion:‎In‎addition‎to‎cold‎ischemic‎time,‎graft‎survival‎can‎be‎affected‎by‎recipients’‎ age.‎There‎are‎some‎other‎considerations‎and‎implications‎regarding‎the‎short‎term‎graft‎sur- vival‎in‎renal‎transplantation‎from‎cadaver‎donors‎which‎are‎discussed‎in‎this‎paper. Keywords:‎graft‎survival;‎kidney‎transplantation;‎tissue‎and‎organ‎procurement;‎survival‎ rate;‎renal‎diabetes‎mellitus. 1475Vol. 11 | No. 02 | March- April 2014 |U R O LO G Y J O U R N A L Survival in Renal Transplantation from Brain-Death Donors | Nakhjavani et al INTRODUCTION Chronic‎renal‎failure‎is‎defined‎as‎glomerular‎filtra-tion‎rate‎>‎60‎mL‎per‎minute‎for‎1.73‎square‎me-ters‎of‎body‎surface‎area‎for‎more‎than‎3‎months,‎ which‎can‎lead‎to‎advanced‎kidney‎disease.(1)‎The‎first‎kid- ney‎transplant‎in‎Iran‎was‎performed‎in‎Shiraz‎in‎1967‎and‎ now‎the‎number‎of‎kidney‎transplants‎in‎Iran‎is‎30‎trans- plants‎per‎1‎million‎people‎in‎each‎year,‎of‎which‎25%‎is‎ from‎brain‎death. According‎to‎the‎report‎of‎the‎Department‎of‎Transplantation‎ and‎Specific‎Diseases‎at‎the‎Ministry‎of‎Health‎and‎Medi- cal‎Education‎(MOHME)‎in‎Iran‎in‎2011,‎the‎number‎of‎new‎ cases‎diagnosed‎with‎end-stage‎renal‎disease‎(ESRD)‎was‎ 4864‎[64‎per‎million‎population‎(pmp)]‎and‎the‎number‎of‎ kidney‎transplantations‎from‎all‎sources‎(living‎related,‎liv- ing‎unrelated,‎decreased‎donors)‎was‎2273‎(30‎pmp).(2)‎The‎ common‎ methods‎ of‎ treating‎ patients‎ with‎ ESRD‎ include‎ hemodialysis,‎peritoneal‎dialysis‎and‎kidney‎transplantation.‎ Kidney‎transplantation‎is‎considered‎the‎most‎effective‎treat- ment‎strategy‎to‎increase‎the‎quality‎of‎life‎for‎recipients.(3) Graft‎sources‎ include‎family‎ living,‎non-family‎ living‎and‎ dead.‎One‎of‎the‎main‎goals‎of‎transplant‎programs‎is‎provid- ing‎a‎suitable‎graft‎for‎each‎patient‎who‎requires‎it.‎Nowa- days,‎ the‎ inadequate‎ number‎ of‎ volunteer‎ donors‎ is‎ con- sidered‎the‎biggest‎obstacle‎to‎achieve‎this‎goal.(4)‎Kidney‎ transplantation‎from‎cadaver‎is‎one‎of‎the‎important‎sources‎ of‎getting‎a‎kidney‎transplant‎in‎treating‎patients‎with‎ESRD.‎ The‎number‎of‎kidney‎transplants‎from‎living‎donor‎and‎ca- daver‎is‎considerably‎various‎across‎different‎countries‎and‎is‎ related‎to‎various‎factors‎including‎specific‎legal,‎cultural‎and‎ religious restrictions.(5) The‎purpose‎of‎renal‎transplant‎is‎to‎prolong‎and‎maintain‎ a‎good‎quality‎of‎life‎for‎recipients‎with‎ESRD;(6)‎it‎is‎more‎ cost‎effective‎and‎it‎allows‎return‎to‎a‎more‎normal‎lifestyle‎ than‎does‎maintenance‎dialysis‎therapy.(7-9) In industrialized countries,‎the‎majority‎of‎organs‎come‎from‎deceased‎donors‎ whereas‎ in‎ countries‎ with‎ lower‎ incomes,‎ the‎ majority‎ of‎ cases‎are‎from‎living‎donors.(10) In both groups, the introduc- tion‎of‎new‎immunosuppressive‎agents‎in‎the‎past‎20‎years,‎ along‎with‎improvements‎achieved‎in‎infection‎prophylaxis‎ strategies,‎have‎resulted‎in‎a‎remarkable‎improvement‎in‎both‎ recipients‎and‎graft‎survival‎rates.‎These‎factors‎have‎made‎ kidney‎transplantation‎as‎the‎treatment‎choice‎for‎recipients‎ with‎ESRSD.(11,12)‎However,‎other‎factors‎such‎as‎age‎and‎ gender‎ of‎ recipients‎ and‎ donors,‎ background‎ diseases‎ and‎ cold‎ ischemic‎ time‎ can‎ affect‎ graft‎ survival‎ rate‎ too.(13-15)‎ Therefore,‎we‎aimed‎to‎evaluate‎the‎short‎term‎graft‎survival‎ rates‎in‎renal‎transplantation‎from‎deceased‎donors‎based‎on‎ data‎in‎MOHME‎registry‎in‎Iran.‎We‎investigated‎the‎survival‎ rates‎of‎kidney‎transplants‎(graft‎survival‎rates)‎from‎brain- death‎cases‎from‎2010‎to‎2011‎in‎Iran. MATERIALS AND METHOD This‎is‎a‎longitudinal‎follow-up‎study‎that‎was‎done‎based‎on‎ MOHME‎registry‎in‎2010‎and‎2011.‎All‎recipients‎who‎had‎ registered‎in‎the‎above‎mentioned‎registry‎and‎had‎received‎ kidney‎allografts‎from‎brain-death‎donors‎were‎included‎in‎ the‎study‎and‎followed-up‎for‎a‎whole‎year.‎The‎following‎ data were collected regarding donors and recipients; short term‎graft‎survival‎ (1‎year),‎age‎of‎ recipients‎and‎donors,‎ gender‎of‎recipients‎and‎donors,‎their‎background‎diseases‎ and‎cold‎ischemic‎time.‎The‎exact‎time‎of‎transplantation‎is‎ considered‎as‎the‎primary‎event,‎and‎the‎onset‎of‎dialysis‎of‎ the‎recipients‎because‎of‎rejection‎as‎well‎as‎the‎death‎of‎the‎ recipients‎are‎considered‎as‎the‎final‎event. There‎were‎595‎cases‎of‎kidney‎transplantation‎in‎2010-2011.‎ Out‎of‎these,‎41‎recipients‎(6.8%)‎were‎excluded‎due‎to‎lack‎ of‎information‎on‎their‎state‎after‎transplantation;‎i.e.‎it‎is‎not‎ clear‎to‎us‎whether‎the‎transplanted‎kidney‎is‎still‎functioning‎ in‎these‎recipients‎or‎not.‎The‎remaining‎554‎cases‎who‎have‎ been‎ transplanted‎ and‎ followed-up‎ in‎ different‎ transplant‎ centers‎from‎the‎beginning‎of‎2010‎to‎the‎end‎of‎2011‎were‎ studied.‎There‎are‎30‎transplant‎units,‎14‎organ‎procurement‎ units‎and‎30‎identification‎units‎in‎different‎hospitals‎all‎over‎ the country. The‎required‎data‎for‎this‎study‎were‎obtained‎from‎MOHME‎ registry.‎ To‎ evaluate‎ the‎ survival‎ rates‎ of‎ recipients‎ from‎ brain-death‎donors,‎creatinine‎level‎was‎determined.‎It‎should‎ be‎noted‎that‎in‎this‎study‎all‎ethical‎standards‎were‎observed.‎ The‎data‎are‎presented‎as‎simple‎number‎(%). RESULTS Of‎study‎subjects‎226‎(40.8%)‎were‎females‎and‎328‎(59.2%)‎ were‎males.‎Mean‎(±‎SD)‎age‎of‎the‎recipients‎was‎39‎±‎14‎ years.‎The‎blood‎groups‎of‎the‎recipients‎in‎this‎study‎were‎ O+‎in‎38.4%,‎A+‎in‎26.3%,‎B+‎in‎21.5%,‎AB+‎in‎9.6%‎and‎ 1476 | Kidney Transplantion negative‎blood‎groups‎in‎4.2%.‎The‎background‎diseases‎are‎ shown‎in‎Table. All‎recipients‎received‎organs‎from‎brain-death‎donors.‎Of‎ donors‎18.4%‎were‎females‎and‎81.6%‎were‎males.‎Mean‎ age‎(±‎SD)‎of‎the‎donors‎was‎33‎±‎14‎years.‎Transplanted‎ kidneys‎were‎functioning‎in‎499‎(90.1%)‎recipients‎in‎1‎year‎ follow-up‎period.‎Of‎recipients‎38‎(6.9%)‎died‎and‎17‎(3.1%)‎ lost‎transplanted‎kidney;‎therefore‎in‎55‎(9.9%)‎of‎cases‎the‎ transplanted‎kidney‎was‎non-functioning. The‎recipients‎who‎experienced‎graft‎loss‎showed‎a‎higher‎ level‎of‎creatinine‎(3.8‎±‎2.5‎mg/dL).‎The‎cold‎ischemic‎time‎ in‎this‎study‎ranged‎from‎4.4‎‎±‎1.6‎to‎6.8‎±‎1.3‎hours.‎Moreo- ver,‎the‎age‎of‎recipients‎who‎suffered‎from‎graft‎loss‎was‎ greater‎than‎the‎average‎age,‎which‎was‎44.2‎±‎14.7‎years.‎ It‎is‎noteworthy‎that‎the‎number‎of‎recipients‎with‎diabetes‎ mellitus‎as‎background‎disease‎(29.4%)‎is‎the‎largest‎com- pared‎to‎other‎background‎diseases.‎Furthermore,‎in‎30‎cases‎ (54.5%)‎out‎of‎55‎where‎the‎transplanted‎kidney‎was‎non- functioning,‎the‎background‎disease‎of‎the‎recipients‎was‎dia- betes‎mellitus.‎Thus,‎we‎may‎say‎that,‎in‎this‎study,‎diabetes‎is‎ the‎most‎common‎background‎disease‎in‎ESRD‎patients‎and‎ also‎the‎largest‎number‎of‎transplantation‎failures‎occurred‎in‎ diabetic patients. DISCUSSION Nowadays,‎survival‎rates‎in‎renal‎transplantation,‎owing‎to‎ recent‎advances,‎appropriate‎follow-up‎and‎the‎use‎of‎immu- nosuppressive‎ drugs,‎ has‎ increased‎ significantly‎ compared‎ with past decades.(11,12)‎The‎present‎study‎was‎an‎attempt‎to‎ examine‎short‎term‎survival‎rate‎in‎renal‎transplant‎recipients‎ from‎brain-death‎donors,‎with‎a‎special‎focus‎on‎recipients‎ with‎diabetes‎mellitus.‎The‎results‎of‎the‎study‎showed‎that‎in‎ 90.1%‎of‎recipients‎the‎transplanted‎kidney‎was‎functioning‎ after‎one‎year.‎Similar‎results‎were‎obtained‎in‎other‎studies.‎ For‎instance,‎the‎study‎by‎Simforoosh‎and‎colleagues‎showed‎ a‎similar‎survival‎rate.(16)‎They‎compared‎short-term‎survival‎ of‎transplanted‎patients‎from‎cadaver‎with‎transplanted‎recip- ients‎of‎living‎people‎and‎concluded‎that‎we‎have‎to‎increase‎ kidney‎transplant‎from‎cadaver.(16)‎In‎another‎study,‎graft‎sur- vival‎from‎cadaver‎was‎82.1%.(17)‎One‎of‎the‎other‎findings‎ of‎the‎present‎study‎was‎that‎recipients‎with‎graft‎loss‎had‎a‎ higher‎level‎of‎creatinine.‎In‎some‎other‎studies‎too,‎survival‎ rates‎of‎recipients‎after‎transplantation‎was‎associated‎with‎ higher‎levels‎of‎creatinine.(18)‎ The‎third‎finding‎of‎this‎study‎is‎that‎the‎number‎of‎recipi- ents‎with‎diabetes‎mellitus‎was‎the‎largest‎compared‎to‎other‎ background‎diseases,‎and‎in‎more‎than‎50%‎of‎the‎patients‎ studied,‎ non-functioning‎ kidney‎ transplants‎ belonged‎ to‎ these‎patients.‎Similar‎results‎were‎reported‎in‎other‎stud- ies.‎Gilbertson‎and‎colleagues,‎for‎instance,‎have‎stated‎that‎ “in‎western‎countries,‎diabetes‎is‎the‎leading‎single‎cause‎of‎ ESRD”.(19)‎In‎another‎study‎in‎2006,‎it‎was‎shown‎that‎“in‎ many‎countries‎such‎as‎the‎United‎States,‎more‎than‎50%‎of‎ patients‎in‎renal‎replacement‎therapy‎programs‎have‎diabetes‎ mellitus‎as‎the‎major‎cause‎of‎their‎renal‎failure”.(20)‎ CONCLUSION Most‎of‎ESRD‎patients‎have‎diabetes‎mellitus‎and‎encoun- ter‎problems‎such‎as‎availability‎of‎the‎required‎organ,‎con- stant‎follow-up,‎immunosuppressive‎therapies,‎mortality‎and‎ morbidity,‎and‎also‎the‎burden‎of‎the‎disease.‎Therefore,‎it‎is‎ highly‎recommended‎to‎prevent‎diabetes‎mellitus‎or‎its‎com- plications‎like‎diabetic‎nephropathy. ACKNOWLEDGMENTS The‎authors‎would‎like‎to‎pay‎highest‎tribute‎to‎the‎donors'‎ families.‎We‎also‎owe‎sincere‎appreciation‎to‎all‎dedicated‎ colleagues‎ in‎ all‎ procurement‎ units‎ and‎ transplant‎ centers‎ countrywide‎for‎their‎precious‎contribution‎by‎timely‎report- ing‎their‎activities‎which‎make‎such‎annual‎surveys‎feasible. CONFLICT OF INTEREST None declared. Table. Background diseases in recipients. Background Disease Frequency no. (%) Diabetes mellitus 163 (29.4) Hypertension 98 (17.6) Glomerulonephritis 94 (16.9) Polycystic Kidney 23 (4.1) Congenital 16 (2.9) Urological diseases 12 (2.2) Unknown 148 (26.8) Total 554 (100) 1477Vol. 11 | No. 02 | March- April 2014 |U R O LO G Y J O U R N A L REFERENCES 1. Bosan IB. Recommendations for early diagnosis of chronic kidney disease. Ann Afr Med. 2007;6:130-6. 2. National Registry Department of Transplantation and Special Dis- ease. Ministry of Health and Medical Education, Iran. 2010. Avail- able from: http://www.irantransplant.org. 3. Abboud O. Incidence, prevalence, and treatment of end-stage renal disease in the Middle East. Ethn Dis. 2006;16:S2-2-4. 4. Foster CE, Weng RR, Smith CV, Imagawa DK. The influence of organ acceptance criteria on long-term graft survival: Outcomes of a kid- ney transplant program. Am J Surg. 2008;195:149-52. 5. Danovitch GM. Handbook of kidney transplantation. Philadelphia, PA: Lippincott Williams & Wilkins; 2009. p. 90-104 6. Ahmadnia H, Shamsa A, Yarmohammadi A, Darabi M, Asl Zare M. Kidney transplantation in older adults: Does age affect graft sur- vival? Urol J. 2005;2:93-96. 7. Kazemeyni SM, Bagheri AR, Heidary AR. Worldwide cadaveric organ donation systems. Urol J. 2004;1:157-64. 8. Feest TG, Rajamahesh J, Byrne C, et al. Trends in adult renal replace- ment therapy in the UK: QJM. 2005;98:21-8. 9. Ballesteros SJ. Indications, morbidity and mortality of the open ne- phrectomy: Analyses of 681 cases and bibliographic review. Arch ESP Urol. 2006;59:59-70. 10. Cusumano A, Garcia-Garcia G, Di GC, et al. End-stage renal disease and its treatment in Latin America in the twenty¬ first century. Ren Fail. 2006;28:631-7. 11. El-Husseini AA, Foda MA, Shokeir AA, Shehab B, Sobh M, Ghoneim M. Determinants of graft survival in pediatric and adolescent live donor kidney transplant recipients: A single center experience. Pediatr Transplant. 2005;9:763-9. 12. Shoskes D, Lapierre C, Cruz-Correra M, et al. Beneficial effects of the bioflavonoids curcumin and quercetin on early function in cadav- eric renal transplantation: A randomized placebo controlled trial. Transplantation. 2005;80:1556-9. 13. Rezaei M, Kazemnejad A, Bardideh A, Mahmoudi M. Factors affect- ing survival in kidney recipients at kermanshah. Urol J. 2004;1:180- 7. 14. Meier-Kriesche HU, Ojo AO, Port FK, Arndorfer JA, Cibrik DM, Ka- plan B. Survival improvement among patients with end-stage renal disease: Trends over time for transplant recipients and wait-listed patients. J Am Soc Nephrol. 2001;12:1293-6. 15. Gillen DL, Stehman-Breen CO, Smith JM, et al. Survival advantage of pediatric recipients of a first kidney transplant among children awaiting kidney transplantation. Am J Transplant. 2008;8:2600-6. 16. Simforoosh N, Gooran S, Tabibi A, Bassiri A, Gharaati MR. Cadaver transplantation in Recent Era: Is cadaveric graft survival similar to living kidney transplantation? IJOTM. 2011;2:168-70. 17. Almasi A, Hassanzade J, Rajaeefard AR, Salahi H. The relationship between graft survival rate of renal transplantation and donor source in transplanted patients at the transplantation center of Namazi Hospital of Shiraz. AMUJ. 2011;14:10-7. 18. Sundaram H, Maureen AM, Wida SC, Christine BT, Barbara AB, Chris- topher PJ. Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int. 2002;62:311-8. 19. Gilbertson DT, Liu J, Xue JL, et al. Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc Nephrol. 2005;16:3736-41. 20. U.S. Renal Data System. USRDS 2006 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, MD: Na- tional Institutes of Health, National Institute of Diabetes and Diges- tive and Kidney Diseases; 2006. Survival in Renal Transplantation from Brain-Death Donors | Nakhjavani et al