Pediatric Kidney Transplantation

Updated: Mar 15, 2023
  • Author: Raja Sekhar Dandamudi, 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 kidney disease (ESKD) in the United States in 2020 was 11 cases per million population, down slightly from 13 cases per million population in 2010. [1] Current treatment options for ESKD include hemodialysis, peritoneal dialysis, and kidney transplantation. Of those, kidney transplantation offers children with ESKD the best opportunity for survival, growth, and development. Consequently, kidney transplantation has become the primary method of treating ESKD in the pediatric population, with 1-year all-cause mortality rates significantly lower than with either form of dialysis. [1]

Unfortunately, the demand for kidney transplants continues to exceed the supply of donor organs. In 2020, 715 pediatric kidney transplantations were performed, but a lack of donor kidneys saw the prevalent pediatric transplant waitlist reach 2637 by the end of the year 2020. [2]

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 slight decrease in those aged 11–17 years (63.4% to 61.9%). However, teenagers still represent the largest t proportion of those waiting kidney transplant [3] (See Table 1, below.)

Table 1. Demographics of pediatric patients awaiting kidney transplant: United States, 2020. (OPTN/SRTR Annual Data Report 2020) (Open Table in a new window)

Patient Characteristics Percentage
Age < 1 year 0.3
Age 1-5 years 20.9
Age 6-10 years 17.0
Age 11-17 years 61.9
White 37.1
African American 26.5
Hispanic 31.8
Asian 3.0
Other or unknown 1.5

The leading cause of ESKD 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 (see Table 2, below). [2] Congenital anomalies of the lower urinary tract that lead to ESKD pose significant difficulty for kidney transplantation; treatment of these urologic disorders may require additional procedures, such as open vesicostomy and bladder augmentation. [4]

Table 2. Primary causes of ESKD in pediatric patients on the kidney transplant waiting list: OPTN/SRTR Annual Data Report 2020 (Open Table in a new window)

Etiology of ESKD Percentage
Focal segmental glomerulosclerosis 7.4
Glomerulonephritis 5.1
Congenital anomalies 38.3
Other or unknown 49.2

In pediatric recipients of kidney transplants from deceased donors, the graft failure rate was 1.9% at 6 months and 2.8% at 1 year for transplants in 2018-2019, 6.4% at 3 years for transplants in 2016-2017, 15.2% at 5 years for transplants in 2014-2015, and 32.1% at 10 years for transplants in 2010-2011. The graft failure after living-donor pediatric transplantation was better at 0.8% at 6 months and 1.6% at 1 year for transplants in 2018-2019, 2.7% at 3 years for transplants in 2016-2017, 8.2% at 5 years for transplants in 2014-2015, and 21.7% at 10 years for transplants in 2010-2011. [2] (See Table 3, below.)

Table 3. Graft failure rates in pediatric kidney transplant recipients (Open Table in a new window)


After deceased donor transplant

After living donor transplant

6 months



1 Year



3 years



5 years



10 years



Both allograft and patient survival 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 allograft 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. Further, in children, technical advances in surgical technique, strict perioperative fluid management, and avoidance of small allografts with small vessels have also improved allograft survival.

For patient education information, see the Kidney Transplant Directory.



Until the 1950s, ESKD from any cause was uniformly lethal. Hope for treating kidney 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 successfully autotransplanted a canine kidney to the dog's neck [5] . Later that year, he also conducted dog-to dog allotransplants as well as a dog-to-goat kidney xenotransplants that both produced urine. Ullmann used Payr’s method, whereby the blood vessels are connected by tubes of absorbable magnesium metal.

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. [6, 7]

In 1909, Ernst Unger transplanted an ape's kidney to a young girl with kidney 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 non-identical 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 had received a previous transplant from the same donor. Medawar won the 1960 Nobel Prize in Medicine for this work. 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 allografts.

Armed with new information about the immune response to allograft, researchers revived interest in kidney transplantation. In 1954, Joseph Murray (winner of the 1990 Nobel Prize in Medicine) performed the first successful kidney transplant in Boston 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 kidney failure who did not have a twin donor remained unrealized until 1959, when Gordon Murray in Toronto performed the first successful non-twin sibling transplant. [11, 12]

In the early 1960s, Calne found that a derivative of 6-mercaptopurine (azathioprine) increased the success of experimental kidney transplantation in dogs. [13]   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. [14, 15] Encouraged by this success, transplant centers began performing non–identical living donor kidney transplantation.

Simultaneously, dialysis became available as a pre-transplant therapy for patients with ESKD and as a life-preserving measure for recipients of transplants whose allograft had 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. [16] A negative crossmatch (no reaction against donor lymphocytes when incubated with recipient serum) indicated that the recipient did not harbor antibody 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. [17]

 In 1970, Kansas became the first state in the United States to enact legislation defining brain death. Within several years, such statutes were widely established in other places. 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 ESKD, meaning that individuals were provided kidney 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. [18] Improvement in graft survival followed the routine use of human leukocyte antigen (HLA) tissue matching and the use of anti-lymphocyte antibodies as a temporary adjunct to immunosuppression regimens. [19]

 In 1978, Calne reported improvement in allograft survival with the use of a new immunosuppressive agent, cyclosporine. [20] 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 infectious complications in transplant recipients.



Despite numerous attempts and prolific experimentation, kidney transplantation (except between identical twins) was not successful until the 1960s. Early experimenters understood the outcome of the unmodified response to allograft (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 non-identical rabbits were ultimately sloughed. [21] 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.

 Major histocompatibility complex (MHC) proteins are cell surface proteins that are important for self-recognition, tolerance, and antigen presentation. The key MHC genes are the class I genes (HLA-A, -B, and -C genes), which are expressed on all nucleated cells, and the class II genes (HLA-DP, -DQ, and -DR), which are expressed on antigen-presenting cells (APC): dendritic cells, macrophages, and B-cells. MHC-I is important for intracellular antigen presentation and MHC-II is responsible for presentation of extracellular antigens. MHC mismatch is a risk factor for allograft rejection and MHCs A, B, and DR are used as donor-recipient matching criteria for kidney transplantation.

The immune system lies at the nexus of immune tolerance and graft intolerance. Both innate (non-specific) and adaptive immunity (antigen-specific) activate each other and play key roles in transplant rejection.

Phagocytic leukocytes (neutrophils, monocytes, eosinophils, and basophils), natural killer cells, and dendritic cells form the backbone for innate immunity. Ischemia-reperfusion injury during transplantation recruits neutrophils and macrophages, resulting in release of proteases, free radicals, and pro-inflammatory molecules such as interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-α) within the graft. Macrophages present peptides to alloreactive T cells in peripheral lymph nodes and establish communication between innate and adaptive immunity.

Dendritic cells, macrophages, and B-lymphocytes present peptide fragments of antigens in association with MHC molecules and activate specific T cells. These antigen presenting cells also express costimulatory molecules (B7-1 (CD-80) and B7-2 (CD86) to optimally activate T lymphocytes (interacting with T-cell CD28 receptors). B-cells produce anti-graft antibodies that can act by fixing complement or targeting cells. CD8 T lymphocyte (cytotoxic T cells) cause tissue injury by releasing membrane-damaging proteins such as perforin and granzyme from intracellular granules.

There are subtle differences between adult and pediatric immune responses to the allograft, with greater alloreactivity in adults. Due to thymic atrophy, the thymic response in adults is not as active as it is in children; that leads to changes in the T-cell pool from naive to memory T cells. In children, reduced T-cell effector function, lower titers of anti-HLA antibodies, lower expression of CD40 co-stimulatory ligands, and fewer T- lymphocytes with specific antigen affiliation make the allograft more tolerable, with better post-transplant outcomes. [22]  

Once stimulated, the immune response results in an attack on the vascular endothelium of the allograft, resulting in rejection. The attack may be rapid or gradual. If the allograft expresses antigens against which the recipient has already developed antibodies, rejection occurs rapidly. This is called hyperacute rejection, and it involves swelling, rupture, and loss of the allograft within minutes or hours. Current pre-transplant cross-matching techniques (between recipient serum and donor lymphocytes) have dramatically reduced the occurrence of this type of rejection.

Acute rejection occurs within days or weeks, when stimulated cytotoxic T lymphocytes, specifically directed against the mismatched tissue, and natural killer cells attack target cells. 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 over years, 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. [23] Consequently, the term chronic allograft dysfunction is preferred over chronic rejection to describe these chronic changes.


Indications & Contraindications


Any child with measured or calculated glomerular filtration rate < 20 mL/min/1.732 m2 without hope of recovery or ESKD can be considered for kidney transplantation. Selection criteria in pediatric patients have subtle differences from those in adults. All of the following need to be taken into consideration when determining whether a child is appropriate for rkidney transplantation:

  • Symptoms of uremia
  • Failure to thrive (due to limited caloric intake, impaired growth hormone–activated post-receptor Janus kinase/signal transducer and activator of transcription [JAK/STAT] signaling, and reduced levels of free IGF-1 due to increased inhibitory IGF-binding proteins)
  • Delayed psychomotor development
  • Metabolic bone disease
  • Reliability of the child's social situation


There are few absolute contraindications for kidney transplantation in children. Acute or chronic active infection, active malignancy, unaddressed outflow obstruction, are absolute contraindications due to the need for long-term significant immunosuppression post-transplant. Patients with hepatitis- and HIV-related kidney disease may receive a transplant once they no longer have active disease.

Children with treated malignancy can be eligible for kidney transplant after a disease-free waiting period. The length of time will depend on the type of malignancy. [24]

There can be many relative, and transient, contraindications to kidney transplant. Kidney transplantation should be delayed in those with ongoing active infections, or if the disease responsible for kidney failure is active and rapidly progressive. Transplantation is also deferred in any child with active anti–glomerular basement membrane (GBM) disease with elevated levels of circulating anti-GBM antibodies, active hemolytic-uremic syndrome, active lupus and active anti-neutrophil cytoplasmic antibody (ANCA) vasculitis, because those processes can damage an allograft. Transplantation should not be performed until those conditions have been successfully treated, so that they do not negatively affect the allograft.

Children with kidney 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 may undergo medical or surgical nephrectomy before transplantation and thus are not candidates for a preemptive transplant. Many registry studies suggested obesity as a contraindication at a body mass index (BMI) >35 mg/kg2. [25]  

Transplantation in children with progressive central neurodegenerative disease is not advised, if survival and quality of life are not expected to be substantially improved by transplantation. Non-progressive intellectual, developmental, or cognitive disability are not contraindications for kidney transplantation. Children with developmental delay and their caregivers may benefit from an improved quality of life.

Generally, younger children are transplanted once they reach a length of 65 cm or a weight of 10 kg, to minimize the risk of vascular thrombosis and to accommodate the adult-sized kidney. [26]  

The responsibility for the selection of transplant candidates ultimately lies with the evaluating team, which must assess the risk versus benefit.



For pediatric kidney transplantation dperformed after 2002, patient survival is much greater than graft survival at 10 years (deceased donor recipients: 95% vs. 57%, live donor recipients: 96% vs 78%). [27] In contrast, adults have a much lower patient survival.

Graft survival

The 2018 annual report of the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) notes 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. [2]

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 kidney 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). [28]

Patient survival

Common causes of death in pediatric kidney transplant recipients are cardiovascular issues, infections, and cancer (including post-transplant lymphoproliferative disorder [PTLD]). [29] Cardiovascular disease accounts for a mortality rate of 36% among all pediatric patients with ESKD, 34% in those undergoing dialysis and 11% after transplantation. [30] The youngest children have reported causes similar to those in older children and adolescents. [2]

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 kidney damage and increase the probability of restoring lost kidney function. [31]

Analysis of North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) data from 1988 to 2010 on pediatric patients with 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. [32]

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. [33, 30]