Pediatric Kidney Transplantation

Updated: Jun 30, 2022
  • Author: Rekha Agrawal, MD; Chief Editor: Stuart M Greenstein, MD  more...
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Practice Essentials

In children and adolescents younger than 18 years, the adjusted incidence of end-stage renal disease (ESRD) in the United States in 2019 was 12 cases per million population. Over the decade from 2009 to 2019, the adjusted ESRD incidence in that age group declined by 14.3%. Treatment options include hemodialysis, peritoneal dialysis, and kidney transplantation. Kidney transplantation has become the primary method of treating ESRD in the pediatric population, with 1-year all-cause mortality rates significantly lower than with either form of dialysis. [1] The reported 1- and 5-year patient survival rates are approximately 98% and 94% respectively, while graft survival at 1 and 5 years are 93-95% from living donors and 77-85% from deceased donors. [2]

Unfortunately, the demand for kidney transplants continues to exceed the supply of donor organs. In 2020, 811 pediatric kidney transplantations were performed, but a lack of donor kidneys saw the pediatric transplant waitlist reach 1695 by the end of the year. [3]

Over the past decade, the age of pediatric candidates on the list has shifted, with an increase in those aged 1–5 years (14.9% to 20.9%) and a decrease in those aged 11–17 years (63.4% to 61.9%). However, teenagers still represent the largest group of pediatric kidney transplant recipients. [4] The leading cause of ESRD changes with age: congenital anomalies of the kidney and urinary tract (CAKUT) are most common in children younger than 6 years of age, while focal segmental glomerulosclerosis and glomerulonephritis are more common in older children. [3] Congenital anomalies of the lower urinary tract that lead to ESRD pose significant difficulty for kidney transplantation; treatment of these urologic disorders may require additional procedures, such as open vesicostomy and bladder augmentation. [2]

Table 1. Demographics of pediatric patients awaiting kidney transplant: United States, 2020 [3] (Open Table in a new window)

Patient Characteristic


Age < 1 y


Age 1-5 y


Age 6-10 y


Age 11-17 y










Other or unknown


Table 2 Primary causes of end-stage renal disease (ESRD) in pediatric patients on the kidney transplant waiting list: United States, 2020 [3] (Open Table in a new window)

Cause of Kidney Failure


Focal segmental glomerulosclerosis




Congenital anomalies


Other or unknown


Of current treatment options, kidney transplantation offers children with ESRD the best opportunity for growth and development. Allograft and patient survival both have demonstrated consistent improvement in the 5 decades during which kidney transplantation has been available. This has been the result of improved understanding of the immune response to allografting and the development of increasingly specific strategies to protect a kidney transplant from the body's natural defenses while leaving the recipient protected from infection.

For patient education information, see the Kidney Transplant Directory.



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, and elucidation of the pathophysiology of rejection, starting in the mid-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. [5]  That same year, Carrel reported an improved method of suturing vessels together, work that eventually won him a Nobel Prize. [6]  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. [7]  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. [8]  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. [9]  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. [10]  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. [11]

In the early 1960s, Calne found that a derivative of 6-mercaptopurine (azathioprine) increased the success of experimental kidney transplantation in dogs. [12]  Human use of azathioprine followed, and long-term graft survival from non-identical donor kidneys became a possibility. The success of kidney transplantation increased significantly when Goodwin and Starzl added prednisolone to azathioprine. [13, 14]  Encouraged by this success, transplant centers began performing non-identical 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. [15]  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. [16]  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. [17]  Improvement in graft survival followed the routine use of human leukocyte antigen (HLA) tissue matching [18]  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. [19]  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.



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. [9] 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).

Simplified diagram of the immune response to nonid 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, typified by a gradual obliteration of the lumen of small arteries in the graft caused by endothelial thickening, along with interstitial fibrosis and tubular atrophy. This response occurs more commonly, but not exclusively, in recipients who have experienced an acute rejection. Therefore, these chronic changes may be a long-term consequence of acute rejection, a low-grade indolent immune reaction, toxicity of immunosuppressive medications, or a combination of those processes. [20] Consequently, the term chronic allograft nephropathy is preferred over chronic rejection to describe these chronic changes.



It is critical to 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 candidates for kidney transplantation. Patients with hepatitis- and HIV-related kidney disease may receive a transplant once they no longer have active disease.

Transplantation is also contraindicated in any child with active anti–glomerular basement membrane (GBM) disease (Goodpasture syndrome) with elevated levels of circulating anti-GBM antibodies or active hemolytic-uremic syndrome because those processes can damage an allograft.

Children with renal failure from primary glomerulonephritis, such as focal segmental glomerulosclerosis (FSGS) or membranoproliferative glomerulonephritis, are at increased risk of recurrence following transplantation. Patients with FSGS can receive a transplant once they are no longer nephrotic. These patients undergo medical or surgical nephrectomy before transplantation and thus are not candidates for a preemptive transplant.

Generally, younger children are transplanted once they reach a weight of 10 kg.



Graft survival

The 2018 annual report of the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) demonstrates that graft survival was highest for living-donor recipients younger than 11 years (93.1% at 5 years) and lowest for deceased-donor recipients aged 11–17 years (77.2% at 5 years). The incidence of acute rejection in the first year was 11.4% overall—highest, at 12.5%, for ages younger than 6 years and lowest, at 7.9% for ages 6-10 years. [3]

A study that analyzed North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) data and found that pediatric recipients of young donors (< 5 years) had equivalent patient and graft survival with that of pediatric recipients of ideal donors (6-35 years) and older donors (36-55 years). Estimated glomerular filtration rate of functioning grafts in young donors was comparable to that of ideal donors but better than that of older donors, though primary graft non-function was higher in young donors. The analysis concluded that young donors may be a good option for kidney transplantation in pediatric patients. [21]

Using data from the United Network for Organ Sharing (UNOS) database, one study evaluated the impact of age at transfer to adult-oriented care on renal allograft failure rates. The data noted that graft failures were 58% higher among those who had transferred early (aged < 21 y) compared with those who were transferred late (aged ≥21 y). [22]

Patient survival

The most common causes of death reported for children (0 - 21 y) with ESRD are cardiac arrest cause unknown, withdrawal from dialysis, and sepsis. Cardiovascular disease accounts for a mortality rate of 36% among all pediatric patients with ESRD, 34% in those undergoing dialysis and 11% after transplantation. [23] The youngest children have reported causes similar to those in older children and adolescents. [1]

Managing chronic kidney disease and related cardiovascular morbidity should be an essential component to the care of pediatric transplant patients. Timely identification of any irregularities, such as albuminuria and hypertension, aid in the early detection of renal damage and increase the probability of restoring lost kidney function. [24]

Analysis of NAPRTCS data from 1988 to 2010 on pediatric patients with post-transplant lymphoproliferative disorder (PTLD) showed that in the most recent cases, patient survival was 87.4% at 5 years post-PTLD, compared with 48% cross-sectional survival reported in the 1990s. Recent graft survival post-PTLD was 81.8% at 1 year and 65% at 5 years. Interventions for PTLD included reduction of immunosuppression; use of anti-CD20 antibody, interferon alpha, or antiviral therapy; and surgical reduction. [25]

In a study of 18,911 patients who received a first transplant before age 21 years, mortality was highest in the first year post transplantation. After the first year of the first transplant, mortality rates and age-, sex-, and race-standardized mortality ratios decreased slightly. The age-adjusted all-cause mortality rate decreased by 1% and the cardiovascular mortality rate by 16% for every year after the first post transplantation year; the infection-related mortality rate did not change. Those results suggest that exposure to the "transplantation milieu" does not negatively affect long-term cardiovascular health. [26, 27]