The utility of surveillance biopsies in pediatric kidney transplantation.

BACKGROUND: Surveillance biopsies (SBs) are performed in some pediatric kidney transplant programs, based on data obtained in earlier immunosuppressive eras that the treatment of subclinical acute rejection results in better graft survival. The benefit of SBs for patients on modern immunosuppression regimens is unclear. We have therefore evaluated the clinical utility of SBs in a population of children receiving a kidney transplant. METHODS: We have performed SBs at 3, 6 and 12 months post-transplantation as standard of care at our institution since 2013 in patients on a regimen of rabbit anti-thymocyte globulin, tacrolimus, mycophenolate and rapid steroid taper (RST; steroids maintained in some exceptions). We reviewed pathology reports of 82 SBs from 34 transplants in 34 children for all abnormal findings and adequacy of specimens. Clinical records were reviewed for changes in management resulting from SB findings and for significant procedure complications. RESULTS: Of the 82 biopsies, 41 (50%) had abnormal findings separate from fibrosis, including five Banff Grade I rejections, ten borderline rejections, six calcineurin-inhibitor nephrotoxicity, four BK-virus nephropathy, five recurrent disease and three acute pyelonephritis. Moderate or more fibrosis was present in nine of the 82 (11%) biopsies. Management changes due to SB findings occurred in nine cases (11.0%). The proportion of abnormal findings or management changes did not differ between the RST or steroid-based groups. Patients performing clean intermittent catheterization showed inflammatory changes often read as rejection, but were managed differently. Three biopsies were deemed inadequate. No significant complications occurred. CONCLUSIONS: A high percentage of the SBs performed under modern immunosuppression showed abnormal findings even when fibrosis was excluded. However, management changes due to the SB findings were less frequent, although they occurred in a clinically meaningful percentage of cases. Complications or inadequate specimens were rare.

Using an interactive water bottle to target fluid adherence in pediatric kidney transplant recipients: a pilot study.

Hydration is important post-renal transplant to maintain adequate renal perfusion and graft function. Adherence to fluid recommendations is challenging given barriers to staying hydrated. There are no studies of adherence to fluid intake recommendations following pediatric renal transplant. Through this pilot study, we sought to determine whether the use of a commercially available interactive water bottle would lead to better adherence to recommended fluid intake and improved kidney functioning post-transplant relative to standard of care. Participants included 32 youth ages 7-19 ≥1 month post-kidney transplant randomized to the intervention (HydraCoach(®) water bottle) or standard education control group. Laboratory records were reviewed for serum chemistries (Na, BUN, creatinine) at baseline and one-month follow-up, and participants recorded daily fluid intake for 28 days. Those in the intervention group were significantly more likely to meet or exceed their fluid target, but this did not translate into better kidney functioning. Participants in the intervention group largely reported satisfaction with the water bottle and were likely to continue its use. While an interactive water bottle providing real-time feedback may be a promising intervention to help pediatric kidney transplant patients meet fluid goals, it did not appear to impact kidney function.

Single-center experience in pediatric renal transplantation using thymoglobulin induction and steroid minimization.

Our center has offered thymoglobulin induction with steroid minimization to our pediatric renal transplant patients for the last 10 yr. Steroid minimization or avoidance has shown favorable results in survival, kidney function, and growth in previous studies of pediatric patients. We report our experience with this protocol over the past 10 yr with respect to patient/graft survival, acute rejection episodes, renal function, linear growth, bone density, cardiovascular risk factors, and opportunistic infections. A retrospective chart review was performed for pediatric renal transplant patients on the steroid-minimized protocol between January 2002 and December 2011 on an intention to treat basis. Patient demographics, height, weight, serum creatinine, iGFR, biopsies, and survival data were collected. Height and weight z-scores were calculated with EpiInfo 7, using the CDC 2000 growth charts. Survival was calculated using Kaplan-Meier analysis. eGFR was calculated using the original and modified Schwartz equations. Forty-four pediatric patients were identified, aged 13 months to 19 yr. Five-yr survival was 95.5% for males and 94.4% for females. Only five patients had biopsy-proven ACR, two of which were at more than 12 months post-transplantation. Height delta z-scores from transplant to one, three, and five yr were 0.34, 0.38, and 0.79, respectively. Weight delta z-scores from transplant to one, three, and five yr were 0.87, 0.79, and 0.84, respectively. Mean original Schwartz eGFR was 84.3 ± 15.8 mL/min/1.73 m(2) , modified Schwartz eGFR was 59.3 ± 11.5 mL/min/1.73 m(2) , and iGFR was 64.2 ± 8.5 mL/min/1.73 m(2) at three yr. Of 18 subjects who had a bone density exam, none had a z-score less than -2 on DEXA exam at one-yr post-transplantation. Fifty-one percent of patients were on antihypertensives at the time of transplant compared with 43% at one-yr post-transplantation. Three yr post-transplantation, the average LDL was <100 mg/dL, and average total cholesterol was <200 mg/dL. There were no clinical episodes of EBV or CMV infection. A steroid-minimized protocol with thymoglobulin induction is safe and provides favorable improvement in linear growth, stable graft function, stable or improved cardiovascular risk factors, and normal bone density in pediatric renal transplant patients.

Measuring family management of transplant tasks: the transplant responsibility questionnaire.

Little is known about how parents and youth perceive their roles in post-transplant management and how this relates to post-transplant adherence. The goals of this study are to (1) describe a new measure, the TRQ, (2) to describe parent and child performance on the TRQ, and to (3) determine the relationship between the TRQ and adherence. We hypothesized that older youth would describe higher post-transplant self-care behaviors, parents would underestimate youth self-care, and greater parent involvement would be associated with better adherence. Participants included 59 parent-child dyads. Inclusion criteria included: (i) youth aged 7-18 yr and (ii) at least three months post-kidney or post-liver transplant. Parents and youth completed the TRQ, and adherence was measured by s.d. of sequential immunosuppressant blood levels. Youth perceived greater levels of self-care than their parents perceived. Older youth reportedly engaged in more self-care than younger youth. Less than 25% of the sample was non-adherent, and non-adherence was unrelated to performance on the TRQ. The TRQ may have utility as a clinical tool to address areas for improvement in youth self-care. The high degree of parental involvement likely explains the high degree of adherence in this sample.

Limitations of cyclosporine C2 monitoring in pediatric heart transplant recipients.

Monitoring CSA levels at two h after dosing (C2) has been shown effective in providing adequate CSA-based immunosuppression in clinical trials in adult transplant recipients, but there is limited data regarding C2 monitoring in pediatric transplant recipients. Given the differences in CSA pharmacokinetics between children and adults, a cohort of stable pediatric transplant recipients was converted from monitoring CSA trough (C0) to C2 levels, to establish the clinical utility and safety of C2 monitoring. After an abbreviated AUC(0-5) to establish baseline exposure, subsequent CSA dosing was adjusted based on C2 levels. Additional evaluation included monitoring for rejection, changes in CSA dose, toxicity, serum chemistries, and infection. Twelve heart transplant recipients were enrolled, with mean age 4.8 yr (range: 0.6-14.0). All patients received microemulsified CSA (Neoral((R)); Novartis Pharmaceuticals, East Hanover, NJ, USA) twice daily. Baseline CSA dose was 5.39 +/- 2.05 mg/kg/day (mean +/- s.d.), with mean C0 = 267 +/- 112, C2 = 1065 +/- 565, and AUC(0-5) = 3817 +/- 1435. Only seven participants showed clear CSA peak levels at two h, with five exhibiting delayed peaks at three to five h post-dose. These seven participants completed 48 wk of study, with mean CSA dose decreasing to 4.55 +/- 3.61 mg/kg/day, maintaining mean C2 599 +/- 211 (vs. target C2 = 800). No significant change in serum creatinine was observed, although GFR increased from 76.9 to 107.6 mL/min/1.73 m(2) (p = 0.11). Five patients failed to achieve target C2 levels (>800) during the first four wk, despite comparable AUC values, and were maintained on trough monitoring (C0). Mean systolic and diastolic blood pressures fell slightly, three minor infections were noted during the study period, and one episode of acute rejection occurred, despite stable CSA dosing. Nearly 50% of stable pediatric transplant recipients failed to achieve adequate peak C2 CSA levels during conversion from C0 to C2 monitoring. Age-dependent differences in CSA absorption and/or clearance pharmacokinetics may explain these findings.

Progressive chronic kidney disease after pediatric lung transplantation.

The development of chronic kidney disease (CKD) was evaluated in a large cohort of pediatric lung transplant recipients. Retrospective chart review identified 125 patients undergoing first lung transplant at St. Louis Children's Hospital and surviving 1 year. Mean age at transplant was 10.3 +/- 0.55 years, while mean time after transplant was 4.9 years. Serum creatinine nearly doubled from baseline 0.48 mg/dL +/- 0.02 (n = 125) to 0.87 mg/dL +/- 0.04 (n = 120) at 1 year, and tripled to 1.39 mg/dL +/- 0.15 (n = 23) by 7 years after transplant. The glomerular filtration rate (GFR), as estimated by the Schwartz formula, decreased from baseline 163 +/- 5.9 mL/min/1.73 m(2) (n = 109) to 88 +/- 2.5 (n = 104), reaching 69 +/- 9.0 (n = 6) by 10 years (p < 0.01). Seven patients developed end-stage kidney disease, and by 5 years after transplant, 38% of patients reached GFR < 60 mL/min. Older age at transplant and primary diagnosis of cystic fibrosis (CF) were both associated with decreased renal survival by Kaplan-Meier (KM) analysis. In summary, pediatric lung transplant recipients experience significant loss of renal function over time, as observed in other solid organ transplant recipients, and is most dramatic in adolescents.

Cytomegalovirus disease after prophylaxis with oral ganciclovir in renal transplantation: the importance of HLA-DR matching.

This study assessed the incidence of cytomegalovirus (CMV) disease and associated outcomes after oral ganciclovir prophylaxis in renal transplantation. A retrospective analysis was performed of all adult renal transplant recipients at a single transplant center transplanted between August 16, 1996, and December 31, 2000. CMV disease prophylaxis included ganciclovir 1000 mg orally thrice daily prescribed for 90 d in D-/R+ cases and 180 d in D+/R- and D+/R+ cases. Forty (9.1%) of 470 patients studied were diagnosed with CMV disease, which varied significantly by CMV serostatus and number of HLA-DR matches. The highest incidence of disease, 26.2%, was in D+/R- patients with zero HLA-DR matches. Five-year graft survival was 56.8% with CMV disease compared with 79.1% without (P < 0.001). Five-year graft survival with CMV disease was 75.9% with one or two HLA-DR matches versus 16.2% with zero HLA-DR matches (P < 0.001). CMV remains an important factor in long-term graft survival after oral ganciclovir prophylaxis. However, we have observed that the adverse impact of CMV disease on graft survival is apparent only in patients with zero HLA-DR matches. These results call for the development of new CMV disease prophylaxis and treatment strategies in patients with zero HLA-DR matches. In addition, organ allocation policies discouraging combining CMV-seropositive donors and zero HLA-DR matches may be worth consideration.