IGG3 anti-HLA donor-specific antibodies and graft function in pediatric kidney transplant recipients.

Anti-HLA DSAs are associated with ABMR and graft loss in KT recipients, yet the influence of DSA IgG subclass on outcomes in pediatric KT recipients is not completely understood. We performed a single-center retrospective chart review of pediatric KT recipients with anti-HLA DSAs, aiming to study the association between specific DSA IgG subclasses and graft outcomes, including ABMR and significant graft dysfunction (graft loss or 50% decrease in eGFR). Thirty-six patients (mean age 15.4y) with DSAs initially detected 1 month-14.3 years post-transplantation were followed for a median of 2.8 years. Rates of IgG1, 2, 3, and 4 subclass detection were 92%, 33%, 58%, and 25%, respectively. Twenty-two patients (61%) had clinical ABMR, whereas 19% had subclinical ABMR, and 13 (36%) experienced significant graft dysfunction. Patients with IgG3+ DSAs had a higher risk of graft dysfunction compared with IgG3- patients (52% vs 13%, P = .03). In a multiple Cox proportional regression analysis, the presence of IgG3+ DSA was independently associated with significant graft dysfunction (HR 10.45, 95% CI 1.97-55.55, P = .006). In conclusion, IgG3 subclass DSAs are associated with graft dysfunction and may be useful for risk stratification and treatment decisions in DSA-positive pediatric KT recipients.

Assessing barriers to adherence in routine clinical care for pediatric kidney transplant patients.

Patient-identified barriers to immunosuppressive medications are associated with poor adherence and negative clinical outcomes in transplant patients. Assessment of adherence barriers is not part of routine post-transplant care, and studies regarding implementing such a process in a reliable way are lacking. Using the Model for Improvement and PDSA cycles, we implemented a system to identify adherence barriers, including patient-centered design of a barriers assessment tool, identification of eligible patients, clear roles for clinic staff, and creating a culture of non-judgmental discussion around adherence. We performed time-series analysis of our process measure. Secondary analyses examined the endorsement and concordance of adherence barriers between patient-caregiver dyads. After three methods of testing, the most reliable delivery system was an EHR-integrated tablet that alerted staff of patient eligibility for assessment. Barriers were endorsed by 35% of caregivers (n=85) and 43% of patients (n=60). The most frequently patient-endorsed barriers were forgetting, poor taste, and side effects. Caregivers endorsed forgetting and side effects. Concordance between patient-caregiver dyads was fair (k=0.299). Standardized adherence barriers assessment is feasible in the clinical care of pediatric kidney transplant patients. Features necessary for success included automation, redundant systems with designated staff to identify and mitigate failures, aligned reporting structures, and reliable measurement approaches. Future studies will examine whether barriers predict clinical outcomes (eg, organ rejection, graft loss).

Laparoscopic donor nephrectomy for the pediatric recipient population: Risk factors for adverse outcomes.

Kidney transplantation is the optimal treatment of ESRD in children. Some studies have reported inferior outcomes in recipients of LDN allografts who are ≤ 5 yr of age. We performed a retrospective review of pediatric recipient outcomes of 110 LDN allografts at our institution and examined predictors of adverse outcomes. Subgroup analysis was performed by dividing recipients into three age categories: 0-5 yr, 6-17 yr, and ≥ 18 yr. There was no significant difference between incidences of DGF or ARE between groups. Kaplan-Meier analysis demonstrated 100% allograft survival in 0- to 5-yr-old recipients, nearly reaching statistical significance (p = 0.07) for outcome superior to that of the two older age groups. Pretransplant HD was associated with increased risk of DGF (p = 0.05). Significant risk factors for ARE were recipient weight >15 kg (p = 0.033) and multiple renal arteries (p = 0.047). Previous ARE was associated with an increased risk of allograft failure (p = 0.02). LDN is not associated with increased risk of DGF, ARE, or allograft failure in the youngest recipients. These findings support an aggressive pursuit of preemptive transplantation even in the youngest pediatric allograft recipients.

Efficacy and flexibility impact perceived adherence barriers in pediatric kidney post-transplantation.

The alarming rates of medication nonadherence and its detrimental effect on long-term graft survival in pediatric kidney transplantation has called attention to identifying modifiable factors that promote better adherence and subsequent transplant outcomes. In a sample of 45 adolescent kidney transplant recipients (14.7 ± 3.3 years, 77.8% Caucasian, 39.5% female) and their primary caregivers, study aims included: 1) identifying sociodemographic and medical correlates of both caregiver- and patient-reported general family functioning (i.e., efficacy, flexibility, and communication) and 2) determining the unique contributions of these family functioning indices to perceived posttransplant adherence barriers. During a routine clinic visit, caregivers completed a sociodemographic form and questionnaire on general family functioning. Both caregivers and the adolescents completed a measure on perceived medication adherence barriers. Data identified household income and family structure as persistent correlates of family functioning. Familial efficacy and flexibility contributed significant variance to perceived adherence barriers. Family-based interventions enhancing modifiable family factors, such as flexibility and efficacy, in overcoming medication adherence barriers would likely promote more optimal health outcomes in the pediatric kidney transplant population.

The Improving Renal Outcomes Collaborative: Blood Pressure Measurement in Transplant Recipients.

BACKGROUND AND OBJECTIVES: Hypertension is highly prevalent in pediatric kidney transplant recipients and contributes to cardiovascular death and graft loss. Improper blood pressure (BP) measurement limits the ability to control hypertension in this population. Here, we report multicenter efforts from the Improving Renal Outcomes Collaborative (IROC) to standardize and improve appropriate BP measurement in transplant patients. METHODS: Seventeen centers participated in structured quality improvement activities facilitated by IROC, including formal training in quality improvement methods. The primary outcome measure was the proportion of transplant clinic visits with appropriate BP measurement according to published guidelines. Prospective data were analyzed over a 12-week pre-intervention period and a 20-week active intervention period for each center and then aggregated as of the program-specific start date. We used control charts to quantify improvements across IROC centers. We applied thematic analysis to identify patterns and common themes of successful interventions. RESULTS: We analyzed data from 5392 clinic visits. At baseline, BP was measured and documented appropriately at 11% of visits. Center-specific interventions for improving BP measurement included educating clinic staff, assigning specific team member roles, and creating BP tracking tools and alerts. Appropriate BP measurement improved throughout the 20-week active intervention period to 78% of visits. CONCLUSIONS: We standardized appropriate BP measurement across 17 pediatric transplant centers using the infrastructure of the IROC learning health system and substantially improved the rate of appropriate measurement over 20 weeks. Accurate BP assessment will allow further interventions to reduce complications of hypertension in pediatric kidney transplant recipients.

Protein kinase Czeta: not-so-innocent bystander or unusual suspect in kidney transplant rejection?

Antibodies against non-HLA targets are increasingly recognized in the context of transplant rejection. However, their specific role remains largely elusive, as evidence exists supporting both their occurrence as an epiphenomenon and their actual pathogenicity in the rejection process. Sutherland et al. describe protein kinase Czeta as a novel, non-HLA antigenic target in the setting of graft rejection.

Focal segmental glomerulosclerosis in children: multivariate analysis indicates that donor type does not alter recurrence risk.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS), the second leading cause of end stage renal disease in children, appears to be increasing. Moreover, posttransplantation FSGS recurrence is a major problem, and there is concern that children receiving kidneys from living donors (LD) have increased recurrence risk. METHODS: Data from the United Network for Organ Sharing from 1988 to 2008 were analyzed for number of de novo transplant recipients with a primary diagnosis of FSGS in children 1 to 20 years of age. Poisson regression was used for trend analysis. Univariate and multivariable logistic regression analyses were performed to examine the association of gender, race, human leukocyte antigen matching, age, and donor type with recurrence. RESULTS: Trend analysis of kidney transplantations for FSGS in children (n=2157) showed an increase in cases of 5.8% per year or 209% over 20 years (P<0.0001). Recurrence was reported in 327 (15%) cases overall, with a preponderance for white recipients (P<0.001) in younger age subgroups (P<0.01). Donor type was significant (P=0.02), with recurrence reported in 17% versus 14% of recipients of kidneys from LDs versus deceased donors. Using multivariate analysis, recipients' young age (P=0.02) and white race (P<0.001) were identified as significant risk factors for recurrence, whereas receiving a LD kidney became insignificant. CONCLUSIONS: FSGS as a cause of pediatric end-stage renal disease leading to transplantation is on the rise. FSGS recurrence is highest in young, white children, whereas receiving a LD kidney is not independently associated with increased risk of recurrence.

Nonimmune complications after transplantation.

As posttransplant longevity has increased, nonimmune complications related to the transplant and posttransplant course have emerged as important factors in defining long-term outcomes. The incidence of, and risk factors for these complications may vary by transplanted organ based on immunosuppressive protocols and preexisting risk factors. This article discusses the relevant nonimmune complications associated with posttransplant care, with a focus on risk factors and management strategies.