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. See the image below.
For excellent patient education resources, see eMedicineHealth'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.  That same year, Carrel reported an improved method of suturing vessels together, work that eventually won him a Nobel Prize.  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.  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.  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.  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.  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. 
In the early 1960s, Calne found that a derivative of 6-mercaptopurine (azathioprine) increased the success of experimental kidney transplantation in dogs.  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.  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.  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.  Improvement in graft survival followed the routine use of human leukocyte antigen (HLA) tissue matching  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.  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.
Approximately 1200 children (aged 0-19 y) in the United States develop ESRD each year.  This represents approximately 16 cases per 1 million children.
The most common cause of renal failure in children (< 19 y) is glomerulonephritis (see image below).
Other etiologies are demonstrated in all children in the first image below and by age group in the second image below.
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 below).
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.  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 below).
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. 
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.
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