Version May 2024
INTRODUCTION — Once the estimated glomerular filtration rate declines to less than 30 mL/min per 1.73 m2 and the child is in stage 4 chronic kidney disease, it is time to start preparing the child and the family/caregiver for renal replacement therapy [1]. Although there have been many advances in conservative kidney replacement therapy, kidney transplantation is the best treatment for children with end-stage kidney disease (ESKD). Kidney allograft and patient survival have increased due to improvements in the care of young patients and advances in immunosuppressive therapy, thereby resulting in reduced frequency and severity of acute rejection. (See "Overview of kidney replacement therapy for children with chronic kidney disease", section on 'Preemptive transplantation as preferred kidney replacement therapy modality' and "Kidney transplantation in children: Immunosuppression".)
This topic will provide an overview of aspects that should be considered in children prior to transplantation. Induction and maintenance immunosuppressive therapy, complications, and outcome of kidney transplantation in children are presented separately. (See "Kidney transplantation in children: Immunosuppression" and "Kidney transplantation in children: Complications" and "Kidney transplantation in children: Outcomes".)
EPIDEMIOLOGY — In the United States, approximately 800 kidney transplants are performed in children below 18 years of age annually [2].
In the United States, the deceased donor kidney allocation policy was revised and the new United States Kidney Allocation System went into effect in December 2014 (see "Kidney transplantation in adults: Organ sharing"). An analysis of data 12 months after implementation showed that transplants for pediatric patients (aged 0 to 17) declined slightly from 4.2 to 3.9 percent [3]. However, pediatric candidates continue to receive priority that provides them greater access to more timely transplants and kidneys that are expected to function longer than in adult candidates. Limited data showed no difference in patient survival but less graft loss under the new system two years after implementation of the Kidney Allocation System [4]. Other countries have also implemented policy changes to prioritize allocation of allografts from deceased donors to pediatric recipients. As an example, such a policy has been in place in France since 1995.
Data from the North American Pediatric Renal Trials and Collaborate Studies (NAPRTCS) registry from 1987 to 2017 provide information regarding recipient characteristics [5].
●Sex – More male children (approximately 60 percent) receive kidney transplants compared with females, primarily due to the higher numbers of males with congenital anomalies of the kidney and urinary tract (CAKUT) that progress to end-stage kidney disease (ESKD).
●Ethnicity – The ethnicity of pediatric recipients has changed over the years, with a decrease in the percentage of White recipients, from a high of 72 percent in 1987 to approximately 50 percent in 2017.
●Underlying primary disease – In the NAPRTCS registry, the most common primary diagnoses occurring in approximately 30 percent of pediatric recipients are due to CAKUT, which include renal aplasia/hypoplasia/dysplasia and obstructive uropathy. Other underlying etiologies include hereditary kidney diseases (eg, polycystic kidney disease, nephronophthisis, cystinosis, congenital nephrotic syndrome, oxalosis, hereditary nephritis, atypical hemolytic uremic syndrome, and Drash syndrome), acquired glomerular disease (eg, focal segmental glomerulosclerosis and secondary glomerulonephritis such as lupus nephritis), reflux nephropathy and pyelo-/interstitial nephritis, and hemolytic uremic syndrome. (See "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Etiology'.)
•Ethnicity – There is some variation in the prevalence of the underlying etiology of pediatric kidney recipients. In Black children, focal segmental glomerulosclerosis is the most common cause of ESKD, whereas CAKUT is the most common etiology in White and Hispanic recipients.
•Age – Etiology also varies with age [5,6]. For example, CAKUT is the primary cause of ESKD in 40 percent of children less than six years of age, whereas it is the etiology in only 20 percent of those between 11 and 17 years of age.
ADVANTAGES OF KIDNEY TRANSPLANTATION — Kidney transplantation is the preferred kidney replacement therapy for children with end-stage kidney disease (ESKD) as patient survival and quality of life are superior for children undergoing transplantation compared with those who remain on dialysis [7,8]. In addition, young children (below six years of age) are more likely to have improved growth after transplantation compared with those undergoing either chronic hemodialysis or peritoneal dialysis [9]. (See "Kidney transplantation in children: Outcomes", section on 'Patient survival' and "Kidney transplantation in children: Outcomes", section on 'Growth after kidney transplantation'.)
PREEMPTIVE TRANSPLANTATION — Children frequently undergo primary or preemptive transplantation, in which transplantation is the first mode of treatment for end-stage kidney disease (ESKD). Preemptive transplants occur more frequently in children than in adults because of the parents'/caregivers' and patients' desire to avoid dialysis when a living donor is available [10]. When performed, this procedure most commonly involves a living donor who is related to the recipient. Children can also be listed for a preemptive deceased donor transplant. Based on the available data, we recommend preemptive kidney transplantation if none of the following contraindications are present and there is a readily available living donor. If there is not an available living donor, we place the child on the active deceased donor waitlist in the chance that they may receive a preemptive transplant before needing dialysis.
Preemptive transplants cannot be performed or are not recommended in the following settings:
●Need for pretransplant nephrectomies (ie, malignant renovascular hypertension, chronic pyelonephritis, or nephrotic syndrome with the associated complications due to hypercoagulability)
●ESKD from autoimmune disease with persistently high titers of autoantibody (ie, antiglomerular basement membrane disease)
●Ongoing active infections
●Underlying kidney disease is still active and associated with rapidly progressive disease (ie, hemolytic uremic syndrome or crescentic glomerulonephritis)
●If the patient or caregivers are not yet able to cope with the regimented care necessary for the transplant recipient as exhibited by nonadherence to their CKD care
Data from the North American Pediatric Renal Trials and Collaborate Studies (NAPRTCS) registry and a study from a single tertiary center reported improved allograft and/or patient survival with preemptive transplantation compared with transplantation while undergoing dialysis in patients with primary kidney transplants [11,12]. Other studies have found that allograft and patient survival and the incidence of rejection were similar in patients transplanted preemptively versus those transplanted while already undergoing dialysis [13-15].
CONTRAINDICATIONS — There are contraindications to kidney transplantation in children, which include:
●Uncontrolled extrarenal malignancies
●Systemic sepsis
●Severe irreversible multisystem organ system failure not correctable by organ transplant
●Severe cardiac or pulmonary dysfunction in a patient who is not a candidate for multiorgan transplantation
●Life-threatening disorder of extrarenal origin that is not correctable by organ transplant
●Elevated levels of circulating antiglomerular basement membrane antibodies (see "Anti-GBM (Goodpasture) disease: Treatment and prognosis" and "Anti-GBM (Goodpasture) disease: Recurrence after transplantation")
Previously, ABO incompatibility and the presence of cytotoxic antilymphocyte antibodies against the donor were contraindications to transplantation; however, subsequent advances with specific protocols have permitted such transplantation in some centers [16]. (See "Kidney transplantation in adults: HLA-incompatible transplantation".)
Human immunodeficiency virus (HIV) infection was traditionally considered an absolute contraindication for transplantation. However, improvements in the long-term prognosis of those with HIV infection have prompted many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection. (See "Kidney transplantation in adults: Kidney transplantation in patients with HIV".)
DELAYED TRANSPLANTATION — Kidney transplantation should be delayed for several months in those with ongoing active infections or if the disease responsible for kidney failure is active and associated with rapidly progressive disease (eg, hemolytic uremic syndrome or crescentic glomerulonephritis). Transplantation should only be performed when there has been successful treatment of these conditions so they do not negatively affect the allograft. Patients with hepatitis B or C infection should not be excluded unless they have active liver disease. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient".)
DONOR CHOICE — The results of kidney transplantation with a living donor are superior to those with a deceased donor [6,8]. A multivariate analysis of United Network for Organ Sharing data showed that even recipients of kidneys from older living donors had a significant long-term allograft survival advantage over those who received a kidney from a young deceased donor [17]. (See "Kidney transplantation in children: Outcomes", section on 'Donor source and age'.)
Advantages associated with living donor kidney transplantation include:
●The incidence of delayed allograft function is lower.
●Long-term allograft survival is higher.
●Dialysis can be avoided or the period on dialysis can be shortened because the time of transplantation is decided in advance. This may limit dialysis-related complications, such as growth impairment.
Despite these advantages, the proportion of living donors varies greatly among countries and regions [18]. Several factors that may explain these differences include the activity level of deceased donor transplant programs in the region or country, cultural variations, and the manner in which parents are solicited for donation.
Living donors should be informed of potential risks. Possible postoperative complications include abscess and hematoma. The incidence of mortality is low for donors. (See "Kidney transplantation in adults: Evaluation of the living kidney donor candidate".)
Despite the general desirability of living donor allografts, a deceased donor may be preferred in settings in which there is a high risk of recurrent disease leading to loss of the allograft, as with rapidly progressive focal glomerulosclerosis. Support for this exception is provided by the finding that long-term survival of living and deceased donor allografts is similar among children with focal glomerulosclerosis [19]. The loss of benefit was associated with recurrent disease.
PRETRANSPLANT EVALUATION — Prior to kidney transplantation, the recipient should undergo the following evaluation and preparation to reduce complications and increase allograft and patient survival.
●Detection of anti-human leukocyte antigen (HLA) antibodies to the donor
●Correction of any significant urinary tract abnormality
●Detection and treatment of any infection prior to transplantation
●Completion of routine childhood immunizations, including varicella vaccine
●Review of whether nephrectomy would be beneficial long-term
Detection and consequences of sensitization — The presence of preformed HLA antibodies are likely to result in severe antibody-mediated rejection and early allograft loss. Several different assays are available to determine the sensitivity (ie, presence of HLA antibodies) of a potential transplant recipient to donor HLA antigens. These assays typically test for the presence of HLA antibodies by testing the serum from the recipient to a panel of HLA antigens or lymphocytes from different donors. (See "Kidney transplantation in adults: HLA-incompatible transplantation", section on 'Approach to the sensitized transplant candidate'.)
The final test of sensitization when a specific donor has been identified is the cross match, which screens for preformed anti-HLA antibodies that would injure the kidney from that specific donor. In the crossmatch, the recipient serum is incubated with the donor's lymphocytes in the presence of complement. (See "Kidney transplantation in adults: HLA-incompatible transplantation", section on 'Approach to the sensitized transplant candidate'.)
Urinary tract abnormalities — The lower urinary tract should be evaluated using a voiding cystourethrogram to detect any abnormality that should be corrected prior to transplantation in patients with history of congenital abnormalities of the kidney and urinary tract (CAKUT) or infection [20-22]. Bladder and urethra abnormalities may be responsible for ureterohydronephrosis of the allograft, thereby increasing the risk of allograft loss. These and other abnormalities may increase the risk of urinary tract infection and, possibly, urosepsis.
Patients with high-grade vesicoureteric reflux or permanent urinary infection should undergo nephroureterectomy to avoid the development of urosepsis. Children with lower tract uropathies (posterior urethral valves, prune-belly syndrome, and neurogenic bladder) and abnormalities of bladder function should be assessed carefully with urodynamic studies. It may be necessary to enlarge the bladder with an intestinal segment in patients with a small pathologic bladder. (See "Prune-belly syndrome" and "Management of posterior urethral valves".)
Infectious disease issues — Steps to prevent infectious complications associated with kidney transplantation are essential. The urinary tract, skin, teeth, and sinuses should be carefully examined for signs of infection or site of chronic infection.
Routine childhood immunizations should be completed, if possible, prior to immunosuppression, particularly if attenuated live virus vaccines are used [23]. Live vaccines, such as varicella and measles, should be administered at least two months prior to transplantation. If vaccination is incomplete, further vaccination should be delayed three to six months after transplantation to maximize immunogenicity and live vaccines are generally contraindicated [24]. Inactivated influenza vaccine can be administered as early as one month after transplantation. (See "Immunizations in solid organ transplant candidates and recipients".)
Native nephrectomy — The need for native nephrectomy is controversial. Loss of residual excretory capacity and erythropoietin production are potential complications of native nephrectomy should the transplant fail.
However, in certain cases, native nephrectomy may be beneficial, although data are limited. These indications include intractable urinary tract infection, high-grade vesicoureteral reflux, severe refractory hypertension, significant polyuria, or persistent nephrosis [25-27]. Native nephrectomy also has been suggested for children with X-Y gonadal dysgenesis and kidney failure (Drash syndrome) as the frequency of Wilms tumor is high if the kidneys are left in place. In addition, native nephrectomy may reduce antihypertensive therapeutic measures [28]. (See "Congenital nephrotic syndrome".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Kidney transplant (The Basics)" and "Patient education: Planning for a kidney transplant (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Preferred treatment for end-stage kidney disease (ESKD) in children – Kidney transplantation is the treatment of choice for children with ESKD because of its superior patient survival rate compared with chronic dialysis. In addition, it is associated with better growth and developmental outcomes. (See 'Advantages of kidney transplantation' above and "Kidney transplantation in children: Outcomes".)
●Underlying etiology of ESKD – The most common cause of ESKD in children who undergo transplantation is congenital anomalies of the kidney and urinary tract (CAKUT; 30 percent), followed by hereditary/genetic kidney diseases and glomerular disorders, particularly focal glomerulosclerosis in Black patients. (See 'Epidemiology' above.)
●Preemptive transplantation – Preemptive transplantation refers to transplantation as the first mode of treatment for ESKD. In most cases, the graft is from a living donor who is related to the recipient. Although it remains uncertain whether preemptive kidney transplantation is associated with better long-term outcome compared with transplantation while undergoing dialysis, this is a common approach for children because of the parents'/caregivers' and patients' desire to avoid dialysis when a living donor is available.
Our approach is to offer preemptive kidney transplantation to suitable transplant candidates if there is a readily available living donor. If there is not an available living donor, we place the patient on the active deceased donor waitlist in the chance that they may receive a transplant before needing dialysis. (See 'Preemptive transplantation' above.)
●Contraindications for transplantation – There are few contraindications for kidney transplantation as the modality of choice for kidney replacement therapy in children with ESKD. These include sepsis, uncontrolled extrarenal malignancies, irreversible multiorgan failure, severe cardiac and pulmonary dysfunction not corrected by organ transplant, underlying life-threatening disorder not corrected by kidney transplant, elevated levels of antiglomerular basement membrane antibodies, and recent history of nonadherence to medical care. (See 'Contraindications' above.)
●Delayed transplantation – Transplantation is delayed for children with active infections or if the underlying cause of ESKD is active and associated with rapidly progressive disease (eg, hemolytic uremic syndrome). Transplantation is performed when there has been successful treatment of these conditions. (See 'Delayed transplantation' above.)
●Donor choice – Graft survival is typically superior with a living donor versus a deceased donor allograft. Despite the general desirability of living donor allografts, a deceased donor may be preferred in settings in which there is a high risk of recurrent disease leading to loss of the allograft, as with rapidly progressive focal glomerulosclerosis. (See 'Donor choice' above.)
●Pretransplant evaluation – Pretransplant evaluation and preparation are key components for a successful transplant in the pediatric recipient and include the following (see 'Pretransplant evaluation' above):
•Detection of anti-human leukocyte antigen (HLA) antibodies to the donor
•Correction of any significant urinary tract abnormality
•Detection and treatment of any infection prior to transplantation
•Completion of routine childhood immunizations
•Review of whether nephrectomy would be beneficial long term
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