Incidence and Etiology

The incidence of ESRD in pediatric patients in the USA in 2006 according to the USRDS annual report varies by age group (Table 530-1). There is an adjusted incident rate of 14.4 per million population for ages 0 to 19 yr.

Table 530-1 INCIDENT RATES OF REPORTED ESRD IN THE USA

ESRD, end-stage renal disease.

www.usrds.org.

* Rates are adjusted for sex and race.

The etiology of ESRD in children varies significantly by age (Table 530-2). Congenital, hereditary, and cystic diseases cause ESRD in more than 52% of children 0 to 4 yr of age, whereas glomerulonephritis and focal segmental glomerulosclerosis (FSGS) account for 38% of cases of ESRD in patients 10 to 19 yr of age. The most common diagnosis in children with transplanted kidneys is structural disease (49%), followed by various forms of glomerulonephritis (14%) and FSGS (12%). Children also often start ESRD therapy with a higher estimated glomerular filtration (eGFR) rate than do adults; in 2001, approximately 50% of patients 0 to 19 yr of age had an eGFR >10 mL/min, compared to approximately 38% in patients 20 yr old.

Table 530-2 COMMON CAUSES OF ESRD IN PEDIATRIC TRANSPLANT RECIPIENTS (N = 9854)

ESRD, end-stage renal disease; MPGN, membranoproliferative glomerulonephritis.

web.emmes.com/study/ped.

Indications

Almost all children with ESRD are considered to be candidates for renal transplantation. There are very few absolute contraindications for pediatric kidney transplantation. Relative contraindications include children with preexisting metastatic malignancy or HIV. Patients with remission of malignancy off maintenance treatment for a minimum of 2 yr may be reconsidered on an individual basis for transplantation, with close post-transplantation surveillance. Similarly, patients with autoimmune diseases resulting in ESRD are candidates for transplantation after a period of immunologic quiescence of the primary disease for a period of at least 1 year before transplantation. Another relative contraindication includes severe neurologic dysfunction, but the wishes of the parents and the potential for rehabilitation must be considered.

Renal transplantation is considered for any child when renal replacement therapy is indicated. In children, dialysis may be required for a period before transplantation to optimize nutritional and metabolic conditions, to achieve an appropriate size in small children, or to keep a patient stable until a suitable donor is available. For young infants, a recipient may need to weigh at least 8-10 kg to minimize the risk for vascular thrombosis and to accommodate an adult-sized kidney. This can require a period of dialysis support until the child is at least 12 to 18 mo of age. Transplantation with an adult-sized kidney has been successful in children who weighed <10 kg or were <6 mo of age.

Preemptive transplantation (i.e., transplantation without prior dialysis) continues to account for approximately 25% of all pediatric renal transplants, based mostly on a desire by the child and the family to avoid dialysis. There may be a small benefit in allograft outcome if transplantation occurs without prior dialysis, which might relate to a lower incidence of infections and cardiovascular risk factors. Preemptive renal transplant should be considered when GFR is <10-15 mL/min/1.73 m² and with symptomatic ESRD or rapidly declining GFR and need for dialysis within 6 to 12 mo. The rates of preemptive transplantation differ moderately for different age groups, being 20% for recipients aged ≤2 yr, 24% for 2-5 yr, 28% for 6-12 yr, and 22% for 13-17 yr.

Characteristics of Donors and Recipients

Data from the 2007 Scientific Registry of Transplant Recipients (SRTR) showed that approximately 2/3 of transplants are performed in children 11-17 yr of age, 17% are done in patients 6-12 yr of age, and 17% are in patients 1-5 yr of age.

Almost half of all pediatric kidney transplants come from living donors. From 1998 to 2003, 58% of pediatric transplants had come from living donors. According to the USRDS, for children ranging from 0-19 yr of age, there were 29 live donor transplants and 27 cadaver donor transplants per 100 dialysis patient–years. These figures are more than double the corresponding rates for adults. The highest rates of transplantation are in the 5-9-yr-old group, with 40 live donor transplants and 46 cadaver donor transplants performed per 100 dialysis patient-years.

The Organ Procurement and Transplantation Network (OPTN) provides preference for children waiting for a deceased donor renal transplant. Owing to improved outcomes in deceased donor pediatric transplantation using donors 5-35 yr of age, OPTN in 2005 implemented a pediatric kidney allocation policy that gave priority for kidneys from deceased donors <35 yr of age. These kidneys were assigned to recipients <18 yr, after 0 mismatch transplants, recipients with a panel reactive antibody (PRA) >80, or candidates receiving a kidney with a nonrenal origin. This policy shortened the wait time for children versus adults and is associated with improved outcomes.

From the 2008 North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) annual report, 48% of transplants in the registry were from deceased donors and 52% from living donors. Data from the OPTN/Scientific Registry of Transplant Recipients (SRTR) 2007 annual report show that in 2004 there were an equal number of living and deceased donor kidney transplants; recipients of living donor kidneys dropped to 47% in 2005 and declined even further to 35% in 2006.

Living donor kidney transplantation graft survival has improved over the years, and from 2003 to 2007 the graft survival rate in living donor renal transplants was 96.1%, unchanged from the 1999-2002 rate of 95.9%. Graft survival rates for deceased donors from 2003-2007 are 94.4%, also improved from 92.7% in 1999-2002.

For children awaiting deceased donor renal transplants the goals are to minimize waiting times, transplanting kidneys into children 0-6 yr of age within 6 mo, children 7-12 yr within 12 mo, and children 12-18 yr within 18 mo.

Evaluation and Preparing for Transplantation

The team approach includes evaluations by a transplant surgeon, nephrologist, nutritionist, social worker, psychologist, financial counselor, pretransplant nurse, and dialysis nurse (if the patient is on dialysis). Patients have a complete evaluation and discussions are undertaken with the patient and family as to what to expect with transplantation and during the post-transplant course.

Primary renal disease can recur in a number of renal diseases, but it is not a contraindication to transplantation. Recurrent disease in the renal graft accounts for graft loss in almost 7% of primary transplantations and 10% in repeat transplantations.

With focal segmental glomerulosclerosis (FSGS) and primary oxalosis, patients are at risk for major renal function impairment with recurrence of disease. The NAPRTCS database has found that grafts in ∼20-30% of patients with the diagnosis of FSGS fail because the disease recurs. In patients with the original disease of FSGS whose grafts fail, the mean time to failure is 17 months. Alport syndrome can recur as an antiglomerular basement membrane (anti-GBM) glomerulonephritis in approximately 3-4% of patients after transplantation and lead to graft loss. Histologic evidence of recurrence of membranoproliferative glomerulonephritis (MPGN) type I varies widely, from 20% to 70%, and graft loss can occur in ≤30% of cases. Histologic recurrence of MPGN type II disease occurs in virtually all cases, with graft loss in ≤50% cases. Histologic recurrence with mesangial IgA deposits is common and occurs in about half of the patients with IgA nephropathy and in about 30% of patients with Henoch-Schönlein purpura. Congenital nephrotic syndrome rarely recurs after transplantation, though patients can develop anti-nephrin antibodies and present with nephrotic syndrome. Some cases (∼25%) of nephrotic syndrome after transplantation are likely de novo. Membranous nephropathy occurs very rarely in children. The recurrence rate after kidney transplantation for patients who have been treated for Wilms tumor is about 13%.

Owing to the high risk of developing Wilms tumor, patients with Denys-Drash syndrome should undergo bilateral nephrectomy before transplantation. Other indications for bilateral native nephrectomies include hyposthenuria with polyuria, significant proteinuria, and severe hypertension resistant to medical management. Nephrectomies are also indicated in cases such as autosomal polycystic kidney disease, where more room may be needed to place the transplanted kidney and to create space in the abdominal cavity to improve feeding tolerability and the infant’s ability to thrive.

Failure to maintain adequate perfusion of the adult-sized kidney, secondary to a “perfusion steal” by the native kidneys, results in a histologic picture of “chronic” acute tubular necrosis and a negative impact on graft function.

Urologic problems such as vesicoureteral reflux, posterior urethral valves, abnormal urinary bladders, and/or neurogenic bladders should be addressed before surgery. Malformations and voiding abnormalities (e.g., neurogenic bladder, bladder dyssynergia, remnant posterior urethral valves, and urethral strictures) should be identified and repaired if possible. Children with urologic disease and renal dysplasia often require multiple operations to optimize urinary tract anatomy and function. Such procedures include ureteric reimplantation to correct vesicoureteral reflux, bladder augmentation or reconstruction, creation of a vesicocutaneous fistula by using the appendix to provide a simple, continent, and cosmetically acceptable way for intermittent catheterization (Mitrofanoff procedure), and excision of duplicated systems or ectopic ureteroceles that could cause recurrent infections. There are reports of excellent outcomes often being achieved in posterior urethral valve bladders by following a staged procedure of initial valve resection to limit any injury to the posterior urethra, and bladder rehabilitation, without the requirement of augmentation, by a process of regimented double voiding.

A comprehensive nutritional assessment needs to be done to ensure that optimal nutritional status is achieved before transplant. Many children with ESRD and especially those on dialysis require nutritional supplements to provide them with sufficient protein and calories. Infants and young children on dialysis often require nasogastric or gastric tube feedings to overcome decreased oral intake from nausea and anorexia due to uremia. Optimal outcomes result from transplanting adult-sized kidneys from living donors when the child weighs ≥10 kg.

Even with careful management of nutrition and bone health in children with kidney disease, most of these children have poor linear growth and are candidates for growth hormone therapy. Aggressive nutritional support is essential. Early gastrostomy or nasogastric tube feeding is often employed to improve caloric intake and promote growth, especially in children started on dialysis therapy at a young age. Linear growth tends to improve after transplantation in children with growth potential. Eighty-one percent of children receiving transplants grow better because they are no longer uremic. For children who continue to have poor growth velocity after transplantation, growth hormone can be restarted after the first post-transplant year due to potential risk for rejection if used early after transplant. Steroid-free immunosuppressant protocols show promise for normalization of linear growth after transplantation. Bone disease needs to be evaluated for and treated before transplantation. Secondary hyperparathyroidism needs to be treated before transplant to avoid post-transplant urinary phosphate wasting and hypercalcemia. High calcium phosphorus product before transplantation leads to vascular stiffness and calcifications, increasing the patient’s risk for cardiovascular disease.

Even in pediatric patients, cardiovascular disease is the leading cause of death in most ESRD mortality statistics. In the USA, >25% of the mortality in children on maintenance dialysis is due to cardiovascular disease. Cardiac death is the leading cause of death in young patients after transplant in childhood. Therefore, evaluation of cardiac function is required before proceeding with a kidney transplant in a pediatric patient to be sure that patient has sufficient cardiac function to tolerate the large fluid load that accompanies kidney transplantation. All patients being evaluated for kidney transplant have at least an echocardiogram and electrocardiogram. Hypertension is common and can result from fluid overload and/or intrinsic native renal disease. Blood pressure needs to be under optimal control before transplant. If blood pressure cannot be controlled with medical management, bilateral nephrectomy may need to be performed before transplant to control the hyper-reninemic response from the failing kidneys.

Anemia needs to be treated before transplantation. Most patients are on erythropoietin, folate, and iron to maintain goals for hemoglobin levels between 11 and 12 g/dL. Blood transfusions should be avoided owing to concerns for sensitizing the patient to HLA antigens before transplant. If a blood transfusion is required, patients should receive cytomegalovirus (CMV)-negative, leuko-reduced red blood cells. Blood should not be irradiated owing to concerns for trauma to the cells and potential for increased antigen exposure.

Evaluation for venous thrombosis and hypercoagulable states is important before renal transplantation. From the NAPRTCS 2008 report of renal transplants from 2000-2007, the third leading cause of graft failure was vascular thrombosis at 10%, and the leading causes were chronic (34.9% ) and acute (13.1%) rejection. Risk factors for graft thrombosis include surgical technique, perfusion and reperfusion injury of graft, young donor age (<2 yr), young recipient (<5 yr), cold ischemia time >24 hr, arterial hypotension, prior history of peritoneal dialysis, and/or hypoperfusion of adult kidney transplant in a small child. Particularly in the young recipient, before transplant, there needs to be evaluation for thrombosis of iliac vessels or inferior vena cava if the patient has had previous surgery or central line placement. Femoral line catheterizations greatly increase the risk for inferior vena cava thrombosis. Children who have large protein losses such as from nephrotic syndrome and/or peritoneal dialysis can be at increased risk for thrombosis due to protein loss such as protein S, C, and antithrombin III. Doppler ultrasound, computed tonographic angiography (CTA), and magnetic resonance angiography (MRA) have all been used to evaluate vessels. MRA has been used less owing to the concern of exposure to gadolinium and nephrogenic systemic fibrosis. In patients with renal compromise receiving contrast media, intravenous hydration is needed before and after the study for patients with residual renal function, acidosis should be corrected before giving contrast, and N-acetyl cysteine should be administered before and after the CT angiogram to reduce the risk of contrast nephropathy. If the patient is on dialysis, dialysis clearance can be done after contrast administration; hemodialysis is the optimal method for clearance.

Infections need to be identified and treated before transplantation. Infectious disease screening includes a complete history of household contacts with treatment for active or latent tuberculosis, vaccine history for varicella and pertussis, travel history within the past 2 yr and/or if there was significant time spent in another country, history of bacille Calmette-Guérin (BCG), animal and/or insect exposure, sexual activity, and consumption of high-risk foods such as unpasteurized products. Screening includes tuberculosis skin test (PPD), CMV IgG, Epstein-Barr virus (EBV) antibody panel, varicella titer, measles antibody, hepatitis B serologies, hepatitis C antibody, HIV, and toxoplasmosis. Additional testing for patients who lived in or visited the central valleys of California, Utah, Nevada, Arizona, and/or New Mexico includes Coccidioides immunodiffusion. Patients from the Ohio River valley should also have histoplasma antibody checked. Patients from Mexico should have Coccidioides immunodiffusion, histoplasma antibody, and ova and parasite screen to evaluate for Strongyloides. Those from South America should have Coccidioides immunodiffusion, histoplasma antibody, and toxoplasma antibody. Sexually active patients should also be screened for syphilis, gonorrhea, HIV, and chlamydia.

Immunizations need to be up to date before transplantation. All live vaccines need to be given before transplantation because these vaccines should not be given to immunosuppressed patients. Therefore, MMR and varicella should be given before transplant and antibody titers should be checked to monitor for response. MMR may be given as early as 6 mo of age. Inhaled influenza vaccine should not be given to transplant patients, family members, or health care providers.

Psychiatric evaluation should be performed before transplant to evaluate patients’ and their families’ ability to cope with the stressors that accompany caring for a child with a kidney transplant. A psychologist should also evaluate the patient and their caregivers for depression, substance abuse, and/or noncompliance so that problems can be identified and managed before kidney transplantation. If noncompliance is identified or anticipated, interventions should be in place before transplantation. These should include social and psychiatric interventions, where possible.

Children need 2 ABO blood types checked before being listed for a kidney transplant and a donor should be sought who shares HLA-A, HLA-B, and/or HLA-DR antigens. The 2008 NAPRTCS data have shown increased risk for rejection and graft failure with 2-DR mismatch compared to a 0-DR mismatch. The recipient’s blood is also checked to see if the patient is sensitized. Patients can become sensitized by prior transplant, blood transfusions, sepsis, and/or pregnancy.

Immunosuppression

Most pediatric kidney transplant centers employ a combination of drug therapy consisting of a calcineurin inhibitor and corticosteroids with or without an antiproliferative agent. The NAPRTCS reported that in 2003, approximately 80% of transplanted patients were receiving a 3-drug regimen at 6 months after transplantation. The rationale for this combination therapy in children is to provide effective immunosuppression and at the same time minimize the toxicity of any single drug.

Fluid Management in Infants and Small Children

Maintenance of adequate blood flow to an adult-sized kidney in an infant or small child is crucial to avoid acute tubular necrosis (ATN) and graft loss from vascular thrombosis and primary nonfunction. The recipient aortic blood flow in early after transplantation of an adult sized kidney more than doubles from pretransplant aortic blood flow. The maximum blood flow that can be obtained in an adult-sized kidney transplanted into a small child is approximately 2/3 of what was in the donor. Therefore, a low blood flow state such as with hypovolemia or hypotension increases the risk for ATN, graft thrombosis, and graft nonfunction. In the postoperative period, patients are maintained on high fluid volumes.

Close attention is paid to blood pressure and hydration status in the operating room in an attempt to reduce the incidence of delayed graft function (DGF). Typically, a central venous catheter is inserted to monitor the central venous pressure (CVP) throughout the operation. To achieve adequate renal perfusion, a CVP of 12-15 cm H₂O should be achieved before removing the vascular clamps; a higher CVP may be desirable in the case of a small infant receiving an adult-sized kidney. Dopamine is usually started in the operating room at 2 to 3 µg/kg/min, increased if required, and continued for 24-48 hr postoperatively. It is used to facilitate diuresis and perhaps to affect renal vasodilatation. The mean arterial blood pressure is kept >65-70 mm Hg by adequate hydration with a crystalloid solution and 5% albumin, and, if necessary, by using dopamine at higher doses. A blood transfusion with packed red blood cells may be required in very small recipients because the hemoglobin can drop as a result of sequestration of ∼150-250 mL of blood in the transplanted kidney. Mannitol and/or furosemide may be given before removing the vascular clamps to increase the effective circulatory volume and facilitate diuresis. Mannitol can also act as a free-radical scavenger, and together with renal dose dopamine it is a critical factor for minimizing the ischemia-reperfusion injury in steroid-avoidance regimens. After the transplanted kidney starts to produce urine, volume replacement should be immediately started with normal saline.

Infants continue to receive aggressive fluid management by nasogastric or gastrostomy tube feedings of at least 2500 mL/m²/day for ≥6 mo after transplant or longer if the child is unable to take in sufficient volume. This aggressive fluid management showed 30 mL/min greater GFR in infants who received adult-sized kidneys and who were maintained on this higher fluid requirement than infants who were not.

Renal Biopsy

Renal biopsy is the gold standard for diagnosis of acute allograft dysfunction. The role of protocol biopsies is still not well established, although preliminary data from adult studies suggest that graft outcome may be improved by detecting early pathology. Additionally, this can give valuable information for monitoring drug nephrotoxicity. A few studies document the efficacy of protocol biopsies in pediatric renal transplantation. In protocol biopsies, pathologic findings as described by the Banff classification do not correlate as well as expected with the clinical course.

Rejection

Hyperacute rejection occurs immediately when the kidney is transplanted and is due to preformed antibodies against the donor HLA, ABO, or other antigens. Hyperacute rejection is rare. The only treatment is removal of the graft.

Acute cellular rejection needs to be identified and treated early. Diagnosis of acute rejection in the very young transplant recipient is often not straightforward. Because most small children receive adult-sized kidneys, an elevation in serum creatinine may be a late sign of rejection as a result of the large renal reserve compared with the body mass. Thus, significant allograft dysfunction may be present with little or no increase in the serum creatinine level. One of the earliest and most sensitive signs of rejection is the development of hypertension along with low-grade fever. In children, any increase in serum creatinine, especially if it is accompanied by hypertension, should be considered a symptom of acute rejection until proved otherwise. Late diagnosis and treatment of rejection are associated with higher incidence of resistant rejections and graft loss. Genomic studies in pediatric kidney transplantation have demonstrated molecular heterogeneity for different acute rejection episodes, not distinguishable by pathologic grading, but with a key evolving role for B cells as antigen-presenting cells for aggressive T cell–mediated recalcitrant rejection. These studies emphasize the need for mechanistic counterparts to ongoing clinical trials in organ transplantation, to better study and identify surrogate markers for monitoring diagnosis and prognosis of acute rejection.

Chronic rejection is the leading cause of graft loss and primarily results from immune and nonimmune injuries such as hypertension, diabetes, and hyperlipidemia. Children often have a gradual decline in their renal function and often have fixed proteinuria and hypertension. Despite initial excitement about the potential of MMF and sirolimus mitigating chronic graft injury, this has not translated readily into observable clinical benefits.

Graft Survival

Five-yr graft survival is higher in living-donor recipients compared to grafts from deceased donors. The OPTN/SRTR 2007 annual report gives graft survival at 5 yr (2000-2005) for living-donor kidney transplant as 88.% for recipients 1-5 yr of age, 84.6% for those 6-10 yr of age, and 74.4% for those 11-17 yr of age. Survival in deceased-donor recipients was 74.4% for those 1-5 yr of age, 72.1% for those 6-10 yr of age, and 63% for those 11-17 yr of age.

From the NAPRTCS data, graft survival rates of pediatric kidney transplants has improved since 1987 with 1-yr survival rates during 2003-2006 of 95.7% for living-donor transplants and 95% for deceased-donor transplants. Children <10 yr of age have the best long-term graft and patient survival rates of all transplant recipients. Graft survival in adolescent patients is the lowest of all the age groups. It is well known that noncompliance is a difficult problem in this age group. Other risk factors for graft failure are race, previous transplant history, history of multiple blood transfusions, HLA-B matches, sex, and transplant year. About 25% of pediatric kidney transplants are preemptive. Graft survival for living and deceased donor kidneys is significantly better in the preemptive group compared to patients who are on dialysis first. The 3 most common causes of graft failure include chronic rejection (34.9%) of graft failures, acute rejection (13%), and vascular thrombosis (10.1%). About 6.4% had graft failure due to recurrence of primary disease (NAPRTCS 2007). The NAPRTCS 2003-2007 data showed the probability of the first rejection at 12 mo being 8.7% for the living donor and 17.7% for the deceased donor.

Graft survival is significantly worse in the presence of ATN in either donor group. ATN is defined by NAPRTCS as requiring the use of dialysis within the first transplant week. NAPRTCS 2008 data reports a 5.1% delay in graft function in living donor renal transplants compared to the ATN rate of 16.4% in children who received deceased donor transplant.

Complications with Immunosuppression Infections

Since the mid-1990s, with new immunosuppressive agents, the incidence of acute rejection has decreased, but the incidence of infections after transplantation has been increasing.

Pneumonia and urinary tract infection (UTI) are the most common post-transplant bacterial infections. UTIs can progress rapidly to urosepsis and may be confused with episodes of acute rejection. Trimethoprim-sufamethoxazole is used for UTI antibiotic prophylaxis as well as PCP prophylaxis for at least the first 6 mo after transplant. Opportunistic infections associated with unusual organisms usually do not occur until after the first month after transplantation.

The herpes viruses (CMV, herpes virus, varicella zoster, and EBV) pose a special problem in view of their common occurrence in children. Many young children have not yet been exposed to these viruses, and because they lack protective immunity, their predisposition to serious primary infection is high. The incidence of CMV seropositivity is about 30% in children >5 yr of age and rises to about 60% in teenagers. Thus, the younger child is at a greater potential risk for serious infection when a CMV-positive donor kidney is transplanted. About half the children are seronegative for EBV, and infection occurs in about 75% of these patients. Most EBV infections are clinically silent. PTLD in children, as in adults, may be related to EBV infection in the presence of vigorous immunosuppression. The incidence of these infections is higher in children who receive antibody induction therapy and after treatment of acute rejection, and, where available, prophylactic therapy is advisable. It has also been shown in children that subclinical replication of these viruses is much higher in regimens with maintenance steroids, versus protocols with complete steroid avoidance, and that even subclinical viral replication can have a detrimental effect on the incidence of acute rejection and graft function. Antiviral prophylaxis with gancyclovir and valganciclovir for 3-12 mo after transplantation, especially in the higher-risk groups (recipient negative, donor positive), have been effective in reducing the incidence of clinical CMV disease. Serial surveillance for these viruses by quantitative PCR for viral load in the peripheral blood has also allowed educated minimization of immunosuppression with resultant reduction in viral burden.

Polyomavirus nephropathy (PVN) is emerging as an important cause of allograft dysfunction; almost 1/3 of children have BK viruria, although allograft dysfunction is observed in lower numbers (∼5%). The increased incidence of PVN is thought to be the result of more-potent immunosuppressive regimens. A renal biopsy, with identification of polyoma by immunoperoxidase staining, may be required to make the diagnosis with certainty. Reducing immunosuppression is the main form of therapy, and cidofovir and leflunomide are used as adjunctive therapies.

It is important to monitor for post-transplant lymphoproliferative disease with routine exams for lymphadenopathy, hepatosplenomegaly, and EBV screen. A schematic plan to monitor for EBV, CMV, and PTLD is provided in Figure 530-1.

Figure 530-1 Surveillance for cytomegalovirus and Epstein-Barr virus infections after pediatric kidney transplantation.

Hypertension, hyperlipidemia, and post-transplant diabetes mellitus are other potential complications of immunosuppressant medications that need to be monitored for and treated when necessary.

Nonadherence with immunosuppressive medications is one of the most important and one of the most elusive problems facing the medical team. At least half of the pediatric deceased donor transplant recipients demonstrated significant medication nonadherence in the post-transplantation period by using as an assessment direct reporting to the medical team. This figure exceeded 60% in adolescents. Because direct reporting of nonadherence can significantly underestimate its true incidence, this analysis points out the potential magnitude of the problem. Nonadherence appears to be the principal cause of graft loss in 10% to 15% of all pediatric kidney transplant recipients; for patients with retransplants, this figure might exceed 25%. Risk factors that suggest an increased propensity toward medication nonadherence include female sex, adolescent age, family instability, insufficient emotional support, lower social economic class, and maladaptive behavior. Currently available methods to measure adherence are crude and provide only a general estimate.

Though growth improves after transplantation, chronic steroid use does not allow a child to reach full potential height. The precise mechanism by which steroids impair skeletal growth is unknown. Steroids could reduce the release of growth hormone, reduce insulin growth factor (IGF) activity, impair growth cartilage directly, decrease calcium absorption, or increase renal phosphate wasting. The use of recombinant growth hormone (rhGH) in pediatric renal transplant recipients significantly improves growth velocity and SDS. An allograft GFR of <60 mL/min/l.73 m² is associated with poor growth and low IGF levels; optimal growth occurs with a GFR >90 mL/min/1.73 m². Graft function is the most important factor after a high corticosteroid dosage in the genesis of post-transplantation growth failure. Steroid minimization and withdrawal protocols have demonstrated growth benefits, and the steroid avoidance data in children show significant catch-up growth at 5 yr after transplantation. These factors have even greater weight than for age and gender-matched peers. It is thus likely that with a well-functioning kidney and no maintenance steroids, children might now be able to realize their full height potential.

Long-Term Outcome

With advances in transplant care and treatment modalities and with diligent attention to the pediatric patient’s psychosocial, educational, vocational, and developmental rehabilitation, the social and emotional functioning of the child and the child’s family appears to return to pre-illness levels within a year of successful transplantation. Renal transplantation leads to improvement in linear growth in children. School function tests improve after renal transplantation. Most patients can reenter school and social activities after a short recovery time of 4-6 wk after surgery. A 3-yr follow-up shows that nearly 90% of children are in their appropriate school or job placement positions. Surveys of 10-year survivors of pediatric kidney transplants report that most patients consider their health to be good, and they engage in appropriate social, educational, and sexual activities while experiencing a very good to excellent quality of life.