Malnutrition and immune cell subsets in children undergoing kidney transplantation.

BACKGROUND: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immune system responds to the insult of both immunosuppression and allotransplantation is unknown. We examined the relationship of nutritional status with post-transplant outcomes and characterized the peripheral immune cell phenotypes of children from the Immune Development of Pediatric Transplant (IMPACT) study. METHODS: Ninety-eight patients from the IMPACT study were classified as having obesity, undernutrition, or normal nutrition-based pre-transplant measurements. Incidence of infectious and alloimmune outcomes at 1-year post-transplantation was compared between nutritional groups using Gray's test and Fine-Gray subdistribution hazards model. Event-free survival was estimated by Kaplan-Meier method and compared between groups. Differences in immune cell subsets between nutritional groups over time were determined using generalized estimating equations accounting for the correlation between repeated measurements. RESULTS: We did not observe that nutritional status was associated with infectious or alloimmune events or event-free survival post-transplant. We demonstrated that children with obesity had distinct T-and B-cell signatures relative to those with undernutrition and normal nutrition, even when controlling for immunosuppression. Children with obesity had a lower frequency of CD8 Tnaive cells 9-month post-transplant (p < .001), a higher frequency of CD4 CD57 + PD1- T cells, and lower frequencies of CD57-PD1+ CD8 and CD57-PD1- CD8 T cells at 12-month transplant (p < .05 for all). CONCLUSIONS: Children with obesity have distinct immunophenotypes that may influence the tailoring of immunosuppression.

Relationship between antithymocyte globulin, T cell phenotypes, and clinical outcomes in pediatric kidney transplantation.

Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Pediatric Transplant (IMPACT) study, we compared T cell phenotypes after ATG or non-ATG induction. We examined the effects of ATG on the early clinical outcomes of alloimmune events (development of de novo donor specific antibody and/or biopsy proven rejection) and infection events (viremia/viral infections). Long-term patient and graft outcomes were examined using the Scientific Registry of Transplant Recipients. After ATG induction, although absolute counts of CD4 and CD8 T cells were lower, patients had higher percentages of CD4 and CD8 memory T cells with a concomitant decrease in frequency of naïve T cells compared to non-ATG induction. In adjusted and unadjusted models, ATG induction was associated with increased early event-free survival, with no difference in long-term patient or allograft survival. Decreased CD4+ naïve and increased CD4+ effector memory T cell frequencies were associated with improved clinical outcomes. Though immunologic parameters are drastically altered with ATG induction, long-term clinical benefits remain unclear in pediatric patients.

Renal allograft loss due to renal vascular thrombosis in the US pediatric renal transplantation.

BACKGROUND: Renal vascular thrombosis (RVT) is a major cause of early allograft loss in the first year following pediatric kidney transplantation. We examined recent trends in allograft loss due to RVT and identified associated risk factors. METHODS: We identified 14,640 kidney-only transplants performed between 1995 and 2014 with follow-up until June 30, 2016, in 13,758 pediatric patients aged < 19 years from the US Renal Data System. We examined the 1-year incidence of allograft loss due to RVT by year of transplant, and plotted the trend over time. Cox proportional hazards models were used to investigate the relationship between year of transplant as well as recipient, donor, and transplant characteristics with allograft loss due to RVT. RESULTS: The incidence of allograft loss due to RVT consistently declined among pediatric kidney transplant performed between 1995 and 2014. Among transplants performed between 1995 and 2004, 128/7542 (1.7%) allografts were lost due to RVT compared to 53/7098 (0.8%) among transplants performed between 2005 and 2014; average 1-year cumulative incidence was 1.5% (95% CI, 1.3-1.9%) and 0.6% (95% CI, 0.5-0.8%), respectively. Increased risk for allograft loss due to RVT was associated with en bloc kidney transplantation (HR, 3.42; 95% CI 1.38-8.43) and cold ischemia time ≥ 12 h (HR, 1.78; 95% CI, 1.15-2.76). Interestingly, these risk factors were more prevalent in the latter decade. CONCLUSIONS: The incidence of allograft loss due to RVT significantly and continuously declined among pediatric kidney transplants performed between 1995 and 2014. The causes for this improvement are unclear in the present analysis.

Phase I study of single-dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients.

Belatacept is an intravenously infused selective T cell costimulation blocker approved for preventing organ rejection in renal transplant recipients aged ≥18 years. This phase I trial examined the pharmacokinetics and pharmacodynamics (percentage CD86 receptor occupancy [%CD86RO]) of a single dose of belatacept (7.5 mg/kg) administered to kidney transplant recipients aged 12-17 years receiving a stable calcineurin inhibitor-based immunosuppressive regimen. Nine adolescents (mean age 15.1 years) who were seropositive for Epstein-Barr virus were enrolled; all completed the 6-month study. Pharmacokinetics suggested relatively low variability of exposure (coefficients of variation for maximum observed serum concentration [Cmax ] and area under the serum concentration-time curve from time zero extrapolated to infinity [AUC0-INF ] were 20% and 25%, respectively). Mean half-life (T1/2 ) occurred 7.2 days postinfusion. Belatacept total body clearance was 0.48 mL/h/kg, and volume of distribution at steady-state (Vss ) was low at 0.09 L/kg. Compared with historical data from healthy adult volunteers administered a single dose of belatacept 10 mg/kg and adult kidney transplant recipients administered multiple doses of belatacept 5 mg/kg, pharmacokinetic values for adolescents were similar, indicating consistency across adolescent and adult populations. Mean %CD86RO increased with increasing belatacept concentration, indicating a direct relationship between pharmacokinetics and pharmacodynamics. Four patients reported 7 serious adverse events; none was considered related to belatacept. These data will inform belatacept dose selection in future studies of adolescent kidney transplant recipients.

Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs.

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF-related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF-related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty-eight (24%) patients had MMF-related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non-depleting induction, UGT2B7-900A>G (rs7438135) was associated with increased risk of MMF-related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF-related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte-depleting induction. IMPDH1 may influence time course of leukopenia after transplant.

Ofatumumab for the treatment of childhood nephrotic syndrome.

BACKGROUND: Ofatumumab is a humanized anti-CD20 monoclonal antibody that has recently garnered interest as a potential therapeutic agent for nephrotic syndrome. We report our center's experience in administering ofatumumab to five pediatric patients with idiopathic nephrotic syndrome. METHODS: Between March 2015 and November 2016, five patients were treated with ofatumumab. One patient had post-transplant recurrent focal segmental glomerulosclerosis (FSGS) which had been resistant to plasmapheresis and numerous immunosuppressive agents. Four patients had nephrotic syndrome in their native kidneys, one with initial steroid-resistant disease and the others with subsequent development of steroid resistance. Two of the patients were treated with a desensitization protocol after experiencing hypersensitivity reactions to ofatumumab. RESULTS: One patient did not complete ofatumumab treatment due to infusion reactions. Of the four remaining patients, three achieved complete remission after treatment, and one achieved partial remission. One of the patients achieving complete remission represents the first reported case of successful treatment of post-transplant recurrent FSGS using ofatumumab. Two patients who received ofatumumab with our desensitization protocol were able to complete their treatments after initially experiencing hypersensitivity reactions. CONCLUSIONS: Ofatumumab may be an effective treatment for refractory childhood nephrotic syndrome and post-transplant recurrent FSGS. A desensitization protocol may be helpful to address hypersensitivity reactions.

Premature T Cell Senescence in Pediatric CKD.

An individual's immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regarding the variability of T cell maturation in children with renal disease is available. In this study, we compared the T cell phenotype in children with renal failure (n=80) with that in healthy children (n=20) using multiparameter flow cytometry to detect markers of T cell maturation, exhaustion, and senescence known to influence immune function. We correlated data with the degree of renal failure (dialysis or nondialysis), prior immunosuppression use, and markers of inflammation (C-reactive protein and inflammatory cytokines) to assess the influence of these factors on T cell phenotype. Children with renal disease had highly variable and often markedly skewed maturation phenotypes, including CD4/CD8 ratio reversal, increased terminal effector differentiation in CD8+ T cells, reduction in the proportion of naïve T cells, evidence of T cell exhaustion and senescence, and variable loss of T cell CD28 expression. These findings were most significant in patients who had experienced major immune insults, particularly prior immunosuppressive drug exposure. In conclusion, children with renal disease have exceptional heterogeneity in the T cell repertoire. Cognizance of this heterogeneity might inform risk stratification with regard to the balance between infectious risk and response to immunosuppressive therapy, such as that required for autoimmune disease and transplantation.

Physical Activity and Kidney Injury in Pediatric and Young Adult Kidney Transplant Recipients.

OBJECTIVES: To quantify physical activity and grip strength in pediatric kidney transplant recipients and describe attitudes about exercise and exercise counseling given concerns about allograft injury. STUDY DESIGN: This was a cross-sectional analysis of 101 kidney transplant recipients (7-21 years old) >6 months post-transplant. Patients completed the Physical Activity Questionnaire (PAQ). Grip strength was measured with a dynamometer. We asked about activity limitations and provider counseling. Univariate analysis and multiple linear regression were used to determine independent predictors of PAQ score and grip strength z score. RESULTS: We enrolled 101 of 122 eligible patients. Median PAQ score was 2.2 (range 0-5) and was lower compared with controls (P < .001). The average grip strength z score was -1.1 and -0.7 in the right and left hand, respectively. Predictors of lower grip strength were younger age (P = .036), non-African American race (P = .029), lower height z score (P = .010), and longer percentage of lifetime with kidney disease (P = .029). Although 49% and 67% limited exercise before and after transplant, respectively, 67% reported increased activity after transplant. By parent report, provider counseling included limiting certain activities (71%) and encouraging regular exercise (45%). CONCLUSION: Physical activity and grip strength are low after kidney transplant. Patients perceive an emphasis on exercise limitations rather than the benefits of regular exercise. Interventions that encourage physical activity may be beneficial.

New-onset diabetes after kidney transplant in children.

The development of new-onset diabetes after kidney transplantation (NODAT) is associated with reduced graft function, increased cardiovascular morbidity and lower patient survival among adult recipients. In the pediatric population, however, the few studies examining NODAT have yielded inconsistent results. Therefore, the true incidence of NODAT in the pediatric population has been difficult to establish. The identification of children and adolescents at risk for NODAT requires appropriate screening questions and tests pre- and post-kidney transplant. Several risk factors have been implicated in the pathogenesis of NODAT and post-transplant glucose intolerance, including African American race, obesity, family history of diabetes and the type of immunosuppressant regimen. Moreover, uremia per se results in a state of insulin resistance that increases the risk of developing diabetes post-transplant. When an individual becomes glucose intolerant, early lifestyle modification and antihyperglycemic measures with tailoring of the immunosuppressant regimen should be implemented to prevent the development of NODAT. For the child or adolescent with NODAT, antihyperglycemic therapy should be prescribed in order to achieve optimal glycemic control, ultimately reducing complications and improving overall allograft and patient survival. In this article, we review the risk factors, screening methods, diagnosis, management and outcome of children and adolescents with NODAT and post-kidney transplant glucose intolerance.

Routine transplant Doppler ultrasonography following pediatric kidney transplant.

The utility and cost-effectiveness of routine transplant renal DU as a screening test in the immediate postoperative period following pediatric renal transplantation has not been systematically evaluated. Our center's transplant protocol includes a routine DU on postoperative day 3, unless an earlier DU was obtained for a specific indication. We retrospectively evaluated 113 consecutive pediatric renal transplant recipients. Indication for DU (routine vs. non-routine), timing, results, and graft outcome data were collected. We determined whether the DU result affected patient management. Eighty routine DU examinations were evaluated. Thirty (37.5%) of the 80 routine DUs had abnormalities. Most abnormalities were minor and did not require intervention. One patient with a dysfunctional bladder had mild hydronephrosis; this led to a decision to increase the frequency of bladder catheterization. This was the only intervention based upon the routine DUs. Twenty percent of routine DUs revealed abnormalities that led to a follow-up study, but none of these studies led to an intervention. The incremental cost of each DU exceeded $1080 and the incremental cost-effectiveness ratio for a documented change in management exceeded $86, 400. Our results suggest that routine post-transplant DU is not cost-effective in pediatric renal allograft recipients.

Chylous ascites complicating pediatric renal transplantation.

BACKGROUND: Chylous ascites (CA) is an unusual complication of pediatric abdominal surgery which can be difficult to manage. Little data are available to guide therapy. CASE-DIAGNOSIS/TREATMENT: We describe the presentation, clinical course and management of two patients, a 7-year-old boy and 2.5-year-old girl, who experienced CA following intraperitoneal renal transplantation. Both cases failed medical management, and the patients required surgical intervention. One required a peritoneovenous shunt while the other required an external abdominal drain. Both patients eventually experienced resolution of the CA and excellent long-term renal function. CONCLUSIONS: These case descriptions highlight the challenges of optimizing nutrition while controlling chylous output. We also review some of the risk factors associated with CA and draw attention to the consideration of this diagnosis in any renal transplant recipient with post-operative abdominal distention and ascites.

Linear growth in pediatric renal transplant recipients receiving sirolimus.

SRL is a potent macrolide immunosuppressive agent that can be used as maintenance therapy for prevention of rejection and avoidance of CNI nephrotoxicity. However, animal studies indicate that SRL may inhibit skeletal and muscle growth. We analyzed linear growth in 25 children, age 1-15 yr old, maintained on SRL to determine whether SRL is detrimental to linear growth. Height z-scores at baseline were compared with those at 24 months. We also compared linear growth in children receiving SRL to patients maintained on TAC. Height z-scores over 24 months did not significantly change in the SRL group as a whole. Z-scores improved in 13 of 25 patients (52%). Children with improved z-scores were significantly younger than patents who did not display improved growth: 6 ± 5 yr vs. 11 ± 4 yr (p < 0.05). Height z-scores in SRL and TAC-based patients were no different initially and at 24 months, and a similar number of patients in each group displayed improved height scores. Height z-scores improved in 52% of patients on SRL and occurred predominantly in younger patients for the initial 24 months of treatment. Linear growth in SRL patients was also similar to the results in TAC-based patients. Therefore, our data did not identify a significant adverse effect of SRL on growth.

Five-year experience using sirolimus-based, calcineurin inhibitor-free immunosuppression in pediatric renal transplantation.

From December 2003 to December 2008, we employed a protocol for withdrawing TAC and converting to SRL in a cohort of low-risk renal pediatric transplant recipients. We report our experience in these children with respect to graft survival, AR episodes, renal function, and adverse events. All patients received basiliximab induction and TAC, MMF, and prednisone. Criteria for conversion to SRL included first transplants without histologic evidence for AR on three-month surveillance biopsies. Patient exclusion criteria included AR prior to or before surveillance biopsies, polyoma (BK) virus nephropathy, a history of nephrotic syndrome, or multiple organ transplants. Fifty-one of 137 patients who received transplants from December 2003 to December 2008 met criteria for withdrawal of TAC and were converted to SRL. SRL was discontinued in 11 children because of adverse events within 12 months after conversion. Among the remaining 40 patients, actuarial graft survival was 91% at five yr. AR occurred in 13% of patients within one yr after conversion. Complications from SRL included aphthous ulcers (30%); viremia with BK virus (20%), EBV (13%), and CMV (3%); proteinuria (7%); elevated cholesterol (7%); diabetes mellitus (2%); thrombocytopenia (2%); erectile dysfunction (2%); and lymph edema (2%). SRL was discontinued in 20%, predominantly for aphthous ulcers. Our experience with SRL-based immunosuppression demonstrates that a CNI-free regimen can be successful in lower-risk patients meeting our selection criteria. Aphthous ulcers and BK virus viremia were the most prevalent adverse events.

Recovery of renal function and survival after continuous renal replacement therapy during extracorporeal membrane oxygenation.

OBJECTIVE: To assess the outcome of pediatric patients supported by concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). DESIGN, SETTING, AND PATIENTS: Acute kidney injury is associated with mortality in ECMO patients. CRRT in patients on ECMO provides an efficient and potentially beneficial method of acute kidney injury management. Concern that concomitant CRRT use increases the risk of developing anuria and chronic renal failure limits its use in some centers. We hypothesized that development of chronic renal failure is rare with concurrent ECMO and CRRT. We evaluated the outcomes of 154 ECMO/CRRT patients cared for over 10 yrs at a referral pediatric medical center. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 68 (44%) ECMO/CRRT survivors, 45 were assigned a pediatric risk, injury, failure, loss and end-stage (referred to as "pRIFLE") score at CRRT initiation. Seventeen (38%) patients met the criteria for Risk, 15 (33%) for Injury, and 10 (22%) for Failure. Two Failure patients later met End stage criteria. Of all survivors, 18 (26%) required ongoing renal replacement therapy (15 required continuous veno-venous hemofiltration, two required peritoneal dialysis, and one patient required intermittent hemodialysis) post ECMO discontinuation. Renal recovery occurred in 65 (96%) of 68 patients before discharge. One neonatal patient had sepsis-induced renal injury on transfer, but had normal creatinine 1 month later. Two pediatric patients with vasculitis and primary renal disease at presentation (both meeting Failure criteria) developed end-stage renal disease. One received peritoneal dialysis and subsequent renal transplant. The other has diminished function without need for renal replacement therapy. CONCLUSION: In the absence of primary renal disease, chronic renal failure did not occur after concurrent use of CRRT with ECMO. Concern for precipitating chronic renal failure by using CRRT during ECMO is not substantiated by this large single-center experience. Consistent with previous reports, mortality is higher in patients receiving concomitant CRRT and ECMO compared with those receiving ECMO alone. Mortality is similar to patients requiring CRRT who are not on ECMO. Additional studies are warranted to determine the optimal role of CRRT use in ECMO patients.

Prevalence of clinical rejection after surveillance biopsies in pediatric renal transplants: does early subclinical rejection predispose to subsequent rejection episodes?

We analyzed rates of both SCR and CR in children receiving SB at three months post-transplant to determine if SCR predisposed patients to acute CR. Acute rejection was defined according to Banff criteria to include borderline classification or higher. All cases of SCR and CR were treated with anti-rejection protocols. Between October 2004 and July 2008, 89 SB were performed at three months post-transplant. Twenty-six cases of SCR were detected (29%). Sixteen patients experienced 22 episodes of biopsy-proven CR occurring after SB, including seven episodes following SCR and 15 after normal SB. The onset of CR varied from one to 27 months after SB and occurred at similar intervals for cases with SCR and normal SB. The percentage of patients remaining free of CR at 30 months post-transplant was similar in patients with SCR and normal SB. Renal function and graft survival at 30 months also were no different between patients with SCR and those with normal SB. Early-SCR, when treated with rejection protocols, is not a prognostic indicator for subsequent CR episodes.

Successful outcome after early combined liver and en bloc-kidney transplant in an infant with primary hyperoxaluria type 1: a case report.

PH1 is a metabolic disorder characterized by urolithiasis and the accumulation of oxalate crystals in the kidneys and other organs. Although patients often first present with renal failure, PH1 results from a deficiency of the hepatic peroxisomal enzyme AGT. Ultimately only liver transplantation will cure the underlying metabolic defect. Herein, we report the case of a three-month-old male infant diagnosed with PH and treated using a combined liver and en bloc-kidney transplant from a single donor. At the time of transplant, the patient was 11 months old and weighed 7.9 kg. He received a full size liver graft and en bloc kidneys from a two-yr-old donor. At 36 months post-transplant, the patient is steadily growing with normal renal and hepatic function. This is one of the first reports of successful liver and en bloc-kidney transplantation with abdominal compartment expansion by PTFE for the infantile form of PH1 in a high risk child before one yr of age. Prompt diagnosis and early referral to a specialized center for liver and kidney replacement offer the best chance for survival for infants with this otherwise fatal disease.

Atypical hemolytic uremic syndrome responsive to steroids and intravenous immune globulin.

Atypical hemolytic uremic syndrome remains a challenge to diagnose and treat, with significant acute morbidity and risk for progression to end stage renal disease. Treatment strategies center on plasma exchange but do not necessarily affect the progression of disease. We report the case of a patient with atypical HUS resulting from a mutation in the complement pathway who responded to treatment with steroids and IVIG, therefore avoiding transfusion or plasma exchange.

Understanding the pathway between the transplant experience and health-related quality of life outcomes in adolescents.

Developments in solid organ transplantation have resulted in improved survival for children with advanced kidney, liver, and heart disease; however, concerns have been raised regarding the quality of life of survivors. This study examined HRQOL in adolescent transplant recipients. We examined the influence of demographic, treatment regimen, and family factors on physical and mental health domains of HRQOL. The current single-center investigation involved 68 solid organ transplant recipients and their parents. All families participated in a structured interview to collect information on demographics, characteristics of the adolescents' disease and treatment regimen, family functioning, and HRQOL for parents and adolescents. Using hierarchical regression analyses, predictive models of physical functioning and mental health outcomes for adolescent transplant recipients were developed for parent-proxy and adolescent self-report. Perceived frequency of medication side-effects and family conflict significantly contributed to adolescent physical functioning and mental health outcomes. Taken together, transplant consequences and family environment significantly impact physical and mental health outcomes in adolescent transplant recipients. Our findings demonstrate the need for pharmacological considerations and psychological interventions to address these areas.

Tacrolimus withdrawal and conversion to sirolimus at three months post-pediatric renal transplantation.

UNLABELLED: Nephrotoxicity caused by CNI may adversely affect long-term graft outcomes. For this reason, we have adopted a protocol for withdrawing TAC and converting to SRL at three months post-renal transplantation. All recipients received basiliximab induction and TAC, MMF, and prednisone. Patients without acute rejection by surveillance biopsy at three months were eligible for SRL conversion. RESULTS: From August 2004 to September 2006, TAC was withdrawn and replaced by SRL in 30 first transplant recipients, who were followed for six to 39 months (mean 18 +/- 8). Renal function did not improve significantly after SRL conversion (p = 0.25). Acute rejection occurred in three patients (10%) at five to 12 months after CNI withdrawal. There were no occurrences of wound healing problems, pneumonitis or post-transplant lymphoproliferative disease. Thrombocytopenia and diabetes each occurred in one patient. Four patients received treatment for hypercholesterolemia. CNI withdrawal and replacement with SRL was an effective regimen in children who did not display biopsy evidence of acute rejection at three months post-transplant. While these early results are promising, the ultimate benefit of this protocol to enhance the long-term renal function and graft survival requires ongoing follow-up.

Surveillance renal transplant biopsies and subclinical rejection at three months post-transplant in pediatric recipients.

UNLABELLED: Subclinical acute rejection (SCR) has been increasingly recognized in adult renal transplant recipients with the advent of surveillance biopsies. However, in children, surveillance biopsies are not routinely performed at most centers. Therefore, the incidence, predisposing factors, treatment, and clinical outcomes of SCR remain unclear in children. From August 2004 to December 2005, we performed 36 protocol biopsies at three months post-transplantation. All patients had received induction therapy with basiliximab and were maintained on prednisone, MMF, and tacrolimus. Sixteen cases of SCR were detected by biopsy (44%). Age, gender, race, donor source, or serum creatinine did not discriminate between children with SCR and those with normal biopsies. All cases of SCR were treated with high doses of methylprednisolone. At one yr post-transplant, renal function was similar in children with SCR to those with normal surveillance biopsies (p = 0.62). Because of the high incidence of SCR, the maintenance dose of MMF was increased by 50% in 20 children transplanted after December 2005. This resulted in a significant decline in the incidence of SCR from 44 to 15% (p < 0.05). However, the incidence of polyomavirus (BK) viremia also increased significantly in these children (p < 0.005). CONCLUSION: A high incidence of SCR was found on surveillance biopsies at three months post-transplant and could not be predicted by age, gender, race, donor source, or serum creatinine. The occurrence of SCR declined significantly by increasing the dose of MMF, but resulted in an increase in BK viremia. We conclude that surveillance biopsies provide valuable information in the management of pediatric renal transplant recipients. Increasing immunosuppression to avoid SCR should be weighed against the risk for infection.