eMedicine Specialties > Pediatrics: Surgery > Transplantation
Kidney Transplantation
Updated: Mar 24, 2009
Introduction
Approximately 1 in 65,000 children develops end-stage renal disease (ESRD) each year. Before the 1950s, this condition was essentially untreatable. However, because of advances in surgical techniques and suppression of the immune system, the mortality rate of children with chronic renal failure has dramatically declined. Kidney transplantation has become the primary method of treating ESRD in the pediatric population.
Management of end-stage renal disease in US children aged 0-19 years by age group. Data from US Renal Data Systems, 2008.
For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Kidney Transplant.
History of the Procedure
Until the 1950s, ESRD from any cause was uniformly lethal. Hope for treating renal failure grew with the development of surgical techniques that allowed the anastomosis of blood vessels in the early 20th century.In 1902, Ullman demonstrated the successful autotransplant of a canine kidney to the dog's neck. Following anastomosis of the artery and vein, the kidney made urine.1 That same year, Carrel reported an improved method of suturing vessels together, work that eventually won him a Nobel Prize.2 In 1906, Jaboulay, in whose laboratory Carrel had worked, performed the first human kidney transplant, a xenograft between a pig and human. This kidney made urine for only a short time.3 In 1909, Ernst Unger transplanted an ape's kidney to a young girl with renal failure. The failure of this attempt convinced Unger that a nonsurgical barrier to transplantation existed.4 Other early attempts at the transplantation of kidneys were unsuccessful. Within hours or days, transplanted kidneys became swollen, ceased urine production, became ischemic, and, in some cases, ruptured.
In a series of experiments, Medawar and colleagues demonstrated that skin grafts from nonidentical rabbits were rejected and sloughed by a reaction involving leukocyte invasion of the graft.5 This reaction increased in severity and rapidity when the recipient received a previous transplant from the same donor. Researchers began to look for ways to prevent this response. Ionizing radiation, known to suppress bone marrow production of leukocytes, was used in an attempt to prevent the immune reaction to allografting.
Armed with new information about the immune response to allografting, researchers revived interest in renal transplantation. In 1954, a kidney transplant was performed between identical twins, thus skirting the problems of immune compatibility.6 Several transplants between twins followed. However, the possibility of kidney transplantation for patients with renal failure who did not have a twin donor remained unrealized.7
In the early 1960s, Calne found that a derivative of 6-mercaptopurine (azathioprine) increased the success of experimental kidney transplantation in dogs.8 Human use of azathioprine followed, and long-term graft survival from nonidentical donor kidneys became a possibility. The success of kidney transplantation increased significantly when Goodwin and Starzl added prednisolone to azathioprine.9,10 Encouraged by this success, transplant centers began performing nonidentical living donor kidney transplantation.
Simultaneously, dialysis became available as a pretransplant therapy for patients with ESRD and as a life-preserving measure for recipients of transplants whose kidneys failed. This increased the number of individuals who were candidates for kidney transplantation. Terasaki reported a marked decrease in early allograft failure from hyperacute rejection when a crossmatch between donor lymphocytes and recipient serum was performed.11 A negative crossmatch (no reaction against donor lymphocytes when incubated with recipient serum) indicated that no antibody was present in the recipient, directed against the donor's organ.
In 1968, the Harvard Committee on Irreversible Coma described the features of brain death and made the important observation that patients who had lost basic brainstem function were dead despite the persistence of a heartbeat sustained by artificial ventilator support.12 In 1970, Kansas became the first state to enact legislation defining brain death. Within several years, such statutes were widely established. This provided a legal framework for families to donate the organs of deceased loved ones for use in transplantation. The number of kidney transplants dramatically increased because of the combination of this legislation and the contemporary advances in immunosuppression.
Concurrently, in 1973 the Medicare program in the United States was expanded to provide insurance coverage for patients with ESRD, meaning that individuals were provided renal transplantation or dialysis regardless of their health insurance coverage or their ability to pay. From a relatively rare procedure performed in research centers, kidney transplantation became available in most major cities.
During the 1970s, a 1-year allograft survival rate of 75% was typical for kidneys donated by living relatives; a rate of 50% was typical for organs from cadavers.13 Improvement in graft survival followed the routine use of human leukocyte antigen (HLA) tissue matching14 and the use of antilymphocyte antibodies as a temporary adjunct to immunosuppression regimens. In 1978, Calne reported improvement in allograft survival with the use of a new immunosuppressive agent, cyclosporine.15 Widespread use of cyclosporine led to a dramatic improvement in allograft survival. New protocols incorporating cyclosporine and other drugs have increased the specificity of immunosuppression and decreased the prevalence of infection complications in transplant recipients.
Frequency
Approximately 1200 children (aged 0-19 y) in the United States develop ESRD each year.16 This represents approximately 16 cases per 1 million children.
Etiology
The most common cause of renal failure in children (<19 y) is glomerulonephritis (see Media file 2).
Etiology of end-stage renal disease in children aged 0-18 years by age group. Data from North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Annual Report, 2007.
Other etiologies are demonstrated in all children in Media file 1 and by age group in Media file 2.
Etiology of end-stage renal disease in North American children. Data from Annual Report North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS), 2007.
Etiology of end-stage renal disease in children aged 0-18 years by age group. Data from North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Annual Report, 2007.
Treatment options include hemodialysis, peritoneal dialysis, and renal transplantation. In the late 1990s, about two thirds of children with ESRD received a kidney transplant. Although kidney transplantation is considered to be the management option of choice in children with ESRD, a shortage of available organs has led to a decline in the proportion of patients who receive a kidney transplant (see Media file 3).
Management of end-stage renal disease in US children aged 0-19 years by age group. Data from US Renal Data Systems, 2008.
Pathophysiology
Despite numerous attempts and prolific experimentation, kidney transplantation between nonidentical twins was not successful until the 1960s. Early experimenters understood the outcome of the unmodified response to allografting (ie, a rapid or gradual decrease in urine output and ultimate demise of the transplanted kidney) but not its mechanism.In the 1940s, through a series of elegant animal experiments, Medawar demonstrated that skin grafts between nonidentical rabbits were ultimately sloughed.5 He found that this reaction occurred much more rapidly in animals that had previously been grafted from the same donor and that the process involved a leukocytic infiltration in the allograft. Medawar reasoned that exposure to foreign tissue resulted in an activation of the immune system and that it induced specific memory that allowed rapid reaction to subsequent exposure to similar grafts. Modulation of that response became the goal of transplant investigators in the subsequent decades. Although understanding of the immune response to allografts has dramatically increased over the 50 years since Medawar's experiments, it remains incomplete. The description that follows is a simplified schema intended primarily to assist in the reader's understanding of currently used immunosuppressive agents.
Histocompatibility antigens are glycoproteins found on the cell membrane of all nucleated cells. These antigens (ie, HLAs) widely vary between individuals and are coded by genes located on the short arm of chromosome 6. Following allografting, the recipient is exposed to foreign HLAs from the graft. Macrophages or dendritic cells process these foreign antigens and present them to T-helper lymphocytes. Thus activated, the T-helper lymphocytes produce lymphokines that stimulate maturation of other reactive cells. Interleukin (IL)–2 stimulates production of cytotoxic T lymphocytes. IL-4 induces transformation of B lymphocytes into plasma cells that produce antibody directed specifically against foreign HLAs. In addition, T-helper lymphocytes can be stimulated directly by the secretion of IL-1 from macrophages (see Media file 4).
Simplified diagram of the immune response to nonidentical major histocompatability complex (MHC) antigens. Foreign antigens are processed by macrophages or dendritic cells (antigen-presenting cell) and then presented to T-helper lymphocytes. Release of interleukin-1 from macrophages activates T-helper lymphocytes. Thus activated, these T-helper lymphocytes produce cytokines (interleukin-2) that stimulate production of cytotoxic T lymphocytes, antibody-producing B lymphocytes, and natural killer cells. Diagram provided by David A. Hatch, MD, copyright 2001, used with permission.
Once stimulated, the immune response results in a rapid or gradual attack on the vascular endothelium of the allograft, resulting in rejection. If an individual is exposed to an organ expressing antigens against which the recipient already has developed antibodies, the rejection occurs rapidly. This is called hyperacute rejection, and it can cause swelling, rupture, and loss of the allograft within minutes or hours. Currently used pretransplant cross-matching techniques (between recipient serum and donor lymphocytes) have dramatically reduced the occurrence of this type of rejection.
Stimulated cytotoxic T lymphocytes, specifically directed against the mismatched tissue, and natural killer cells attack target cells, causing acute rejection. This response can vary in severity from mild allograft dysfunction to a dramatic rise in serum creatinine with loss of urine output. Some recipients of transplants experience a gradual reduction in allograft function, called chronic rejection, typified by a gradual obliteration of the lumen of small arteries in the graft caused by endothelial thickening. This response occurs more commonly, but not exclusively, in recipients who have experienced an acute rejection. Therefore, chronic rejection may be a long-term consequence of acute rejection, a low-grade indolent immune reaction, or a combination of both processes.
Relevant Anatomy
See Pathophysiology.
Contraindications
Obtain a thorough history from all potential pediatric recipients of kidney transplants. Children with acute or chronic active infection and those with malignancy are not generally candidates for kidney transplantation. Most centers consider transplantation in a child who has been disease free for 2 years following treatment of cancer.
Transplantation is also contraindicated in any child or family with a history or high likelihood of noncompliance with a prescribed medication regimen. Active systemic lupus erythematosus and Goodpasture disease are also contraindications to transplantation because these processes can damage an allograft. Children with renal failure from focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, systemic lupus erythematosus, hemolytic-uremic syndrome, and Henoch-Schönlein purpura are at increased risk of recurrence following transplantation. Although this increased risk does not necessarily contraindicate transplantation, it can have a significant impact on organ survival and function. Counsel families accordingly.
The success rate of renal transplantation in very young children, especially those younger than 1 year, is significantly less than that in older children. Therefore, carefully evaluate all alternatives for treatment of end-stage renal disease (ESRD). Generally, continuous ambulatory peritoneal dialysis (CAPD) is the preferred method of treatment of children younger than 1 year. However, CAPD may not be possible because of peritoneal scarring. Hemodialysis is difficult in very small children. In such persons, transplantation may be the best option.
More on Kidney Transplantation |
 Overview: Kidney Transplantation |
| Workup: Kidney Transplantation |
| Treatment: Kidney Transplantation |
| Follow-up: Kidney Transplantation |
| Multimedia: Kidney Transplantation |
| References |
| Next Page » |
References
Ullman E. Experimentelle nierentransplantation. In: Wien Klin Wochenschr. Vol 14. 1902:281.
Carrel A. La technique operatoire des anastomoses vasculaires et la transplantation des visceres. Lyon Med. 1902;98:859.
Jaboulay M. Greffe de reins au pli du coude par soudure arte. Bull Lyon Med. 1906;107:575.
Unger E. Nierentransplantation. In: Berlin Dlin Wochenschr. Vol 1. 1909:1057.
Medawar PB. The behaviour and fate of skin autografts and skin homografts in rabbits: A report to the War Wounds Committee of the Medical Research Council. J Anat. Oct 1944;78:176-99. [Medline].
Hume DM, Merrill JP, Miller BF, Thorn GW. Experiences with renal homotransplantation in the human: report of nine cases. J Clin Invest. Feb 1955;34(2):327-82. [Medline].
Murray JE, Merrill JP, Harrison JH. Kidney transplantation between seven pairs of identical twins. Ann Surg. Sep 1958;148(3):343-59. [Medline].
Calne RY, Alexandre GP, Murray JE. A study of the effects of drugs in prolonging survival of homologous renal transplants in dogs. Ann N Y Acad Sci. Oct 24 1962;99:743-61. [Medline].
Goodwin WE, Mims MM, Kaufman JJ. Human renal transplantation III. Technical problems encountered in six cases of kidney homotransplantation. Trans Am Assoc Genitourin Surg. 1962;54:116-25. [Medline].
Starzl TE, Marchioro TL, Waddell WR. The reversal of rejection in human renal homografts with subsequent development of homograft tolerance. Surg Gynecol Obstet. Oct 1963;117:385-95. [Medline].
Terasaki PI, Vredevoe DL, Porter KA, Mickey MR, Marchioro TL, Faris TD, et al. Serotyping for homotransplantation. V. Evaluation of a matching scheme. Transplantation. Nov 1966;4(6):688-99. [Medline].
Cranford RW. Brain death. In: Organ Procurement, Preservation and Distribution in Transplantation. Richmond, Va: UNOS; 1991:23-31.
Banowsky LH. Current results and future expectations in renal transplantation. Urol Clin North Am. May 1983;10(2):337-46. [Medline].
Ting A, Morris PJ. Matching for B-cell antigens of the HLA-DR series in cadaver renal transplantation. Lancet. Mar 18 1978;1(8064):575-7. [Medline].
Calne RY, White DJ, Thiru S, et al. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet. Dec 23-30 1978;2(8104-5):1323-7. [Medline].
USRDS. United States Renal Data System. Available at http://www.usrds.org/. Accessed December 12, 2008.
Traum AZ, Ko DS, Kawai T. The potential for tolerance in pediatric renal transplantation. Curr Opin Organ Transplant. Oct 2008;13(5):489-94. [Medline].
Shapiro R, Scantlebury VP, Jordan ML, et al. Tacrolimus in pediatric renal transplantation. Transplantation. Dec 27 1996;62(12):1752-8. [Medline].
Hocker B, John U, Plank C, et al. Successful withdrawal of steroids in pediatric renal transplant recipients receiving cyclosporine A and mycophenolate mofetil treatment: results after four years. Transplantation. Jul 27 2004;78(2):228-34. [Medline].
Kahan BD, Rajagopalan PR, Hall M. Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group. Transplantation. Jan 27 1999;67(2):276-84. [Medline].
Kim FJ, Ratner LE, Kavoussi LR. Renal transplantation: laparoscopic live donor nephrectomy. Urol Clin North Am. Nov 2000;27(4):777-85. [Medline].
Slakey DP, Wood JC, Hender D, et al. Laparoscopic living donor nephrectomy: advantages of the hand-assisted method. Transplantation. Aug 27 1999;68(4):581-3. [Medline].
Barry JM. Unstented extravesical ureteroneocystostomy in kidney transplantation. J Urol. May 1983;129(5):918-9. [Medline].
Lich R. Recurrent urosepsis in children. Journal of Urology. 1961;86:554.
Gill IS, Hayes JM, Hodge EE, Novick AC. Clean intermittent catheterization and urinary diversion in the management of renal transplant recipients with lower urinary tract dysfunction. J Urol. Nov 1992;148(5):1397-400. [Medline].
Hatch DA, Koyle MA, Baskin LS, et al. Kidney transplantation in children with urinary diversion or bladder augmentation. J Urol. Jun 2001;165(6 Pt 2):2265-8. [Medline].
Whitaker RH. Clinical assessment of pelvic and ureteral function. Urology. Aug 1978;12(2):146-50. [Medline].
Renoult E, Buteau C, Lamarre V, Turgeon N, Tapiero B. Infectious risk in pediatric organ transplant recipients: is it increased with the new immunosuppressive agents?. Pediatr Transplant. Aug 2005;9(4):470-9. [Medline].
Silkensen JR. Long-term complications in renal transplantation. J Am Soc Nephrol. Mar 2000;11(3):582-8. [Medline].
Sia IG, Paya CV. Infectious complications following renal transplantation. Surg Clin North Am. Feb 1998;78(1):95-112. [Medline].
Bock GH, Sullivan EK, Miller D, et al. Cytomegalovirus infections following renal transplantation--effects on antiviral prophylaxis: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol. Dec 1997;11(6):665-71. [Medline].
Granger DK, Burd RS, Schmidt WJ, et al. Incidence and timing of infections in pediatric renal transplant recipients in the cyclosporine era. Transplant Proc. Feb 1994;26(1):64. [Medline].
Cox KL, Lawrence-Miyasaki LS, Garcia-Kennedy R, et al. An increased incidence of Epstein-Barr virus infection and lymphoproliferative disorder in young children on FK506 after liver transplantation. Transplantation. Feb 27 1995;59(4):524-9. [Medline].
Newell KA, Alonso EM, Whitington PF, et al. Posttransplant lymphoproliferative disease in pediatric liver transplantation. Interplay between primary Epstein-Barr virus infection and immunosuppression. Transplantation. Aug 15 1996;62(3):370-5. [Medline].
Green M, Michaels MG, Webber SA, et al. The management of Epstein-Barr virus associated post-transplant lymphoproliferative disorders in pediatric solid-organ transplant recipients. Pediatr Transplant. Nov 1999;3(4):271-81. [Medline].
Ho M, Jaffe R, Miller G, et al. The frequency of Epstein-Barr virus infection and associated lymphoproliferative syndrome after transplantation and its manifestations in children. Transplantation. Apr 1988;45(4):719-27. [Medline].
Broyer M, Tete MJ, Guest G, et al. Varicella and zoster in children after kidney transplantation: long-term results of vaccination. Pediatrics. Jan 1997;99(1):35-9. [Medline].
Furth SL, Sullivan EK, Neu AM, et al. Varicella in the first year after renal transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Transplant. Aug 1997;1(1):37-42. [Medline].
Broyer M, Boudailliez B. Varicella vaccine in children with chronic renal insufficiency. Postgrad Med J. 1985;61 Suppl 4:103-6. [Medline].
Hardy I, Gershon AA, Steinberg SP, LaRussa P. The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group. N Engl J Med. Nov 28 1991;325(22):1545-50. [Medline].
Zamora I, Simon JM, Da Silva ME, Piqueras AI. Attenuated varicella virus vaccine in children with renal transplants. Pediatr Nephrol. Apr 1994;8(2):190-2. [Medline].
Chugh KS, Sakhuja V, Jain S, et al. High mortality in systemic fungal infections following renal transplantation in third-world countries. Nephrol Dial Transplant. 1993;8(2):168-72. [Medline].
Chugh KS, Sakhuja V, Jain S, et al. Fungal infections in renal allograft recipients. Transplant Proc. Oct 1992;24(5):1940-2. [Medline].
Tolkoff-Rubin NE, Rubin RH. Opportunistic fungal and bacterial infection in the renal transplant recipient. J Am Soc Nephrol. Jun 1992;2(12 Suppl):S264-9. [Medline].
Neu AM, Fivush BA. Recommended immunization practices for pediatric renal transplant recipients. Pediatr Transplant. Nov 1998;2(4):263-9. [Medline].
Enke BU, Bokenkamp A, Offner G, et al. Response to diphtheria and tetanus booster vaccination in pediatric renal transplant recipients. Transplantation. Jul 27 1997;64(2):237-41. [Medline].
Mathew JL, El Dib R, Mathew PJ, Boxall EH, Brok J. Hepatitis B immunisation in persons not previously exposed to hepatitis B or with unknown exposure status. Cochrane Database Syst Rev. Jul 16 2008;CD006481. [Medline].
American Academy of Pediatrics. Report of the committee on infectious diseases. Pickering LK, Baker CJ, McMillan M, Long S (Editors). Red Book. 27th Edition. 2006.
Penn I. Incidence and treatment of neoplasia after transplantation. J Heart Lung Transplant. Nov-Dec 1993;12(6 Pt 2):S328-36. [Medline].
Mongeau JG, Clermont MJ, Robitaille P, et al. Study of psychosocial parameters related to the survival rate of renal transplantation in children. Pediatr Nephrol. Oct 1997;11(5):542-6. [Medline].
Birk PE, Matas AJ, Gillingham KJ, et al. Risk factors for chronic rejection in pediatric renal transplant recipients--a single-center experience. Pediatr Nephrol. Aug 1997;11(4):395-8. [Medline].
Pape L, Offner G, Ehrich JH, et al. Renal allograft function in matched pediatric and adult recipient pairs of the same donor. Transplantation. Apr 27 2004;77(8):1191-4. [Medline].
Benfield MR, McDonald R, Sullivan EK, et al. The 1997 Annual Renal Transplantation in Children Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Transplant. May 1999;3(2):152-67. [Medline].
Davis ID, Bunchman TE, Grimm PC, et al. Pediatric renal transplantation: indications and special considerations. A position paper from the Pediatric Committee of the American Society of Transplant Physicians. Pediatr Transplant. May 1998;2(2):117-29. [Medline].
Goldstein SL, Somers MJ, Lande MB, et al. Acyclovir prophylaxis of varicella in children with renal disease receiving steroids. Pediatr Nephrol. Apr 2000;14(4):305-8. [Medline].
Hatch DA, Belitsky P, Barry JM, et al. Fate of renal allografts transplanted in patients with urinary diversion. Transplantation. Oct 1993;56(4):838-42. [Medline].
Whitaker RH. Methods of assessing obstruction in dilated ureters. Br J Urol. Feb 1973;45(1):15-22. [Medline].
Further Reading
Keywords
kidney transplantation, transplant, kidney transplant, end-stage renal disease, ESRD, renal transplant, renal transplantation, kidney donation, dialysis, hemodialysis, glomerulonephritis, histocompatibility antigens, HLAs, kidney rejection, nephrectomy, systemic lupus erythematosus, Goodpasture syndrome, Goodpasture disease, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, hemolytic-uremic syndrome, Henoch-Schönlein purpura, continuous ambulatory peritoneal dialysis, CAPD, treatment, kidney failure, renal failure
