For three decades, the international Banff classification has been the gold standard for kidney allograft rejection diagnosis, but this system has become complex over time with the integration of ...multimodal data and rules, leading to misclassifications that can have deleterious therapeutic consequences for patients. To improve diagnosis, we developed a decision-support system, based on an algorithm covering all classification rules and diagnostic scenarios, that automatically assigns kidney allograft diagnoses. We then tested its ability to reclassify rejection diagnoses for adult and pediatric kidney transplant recipients in three international multicentric cohorts and two large prospective clinical trials, including 4,409 biopsies from 3,054 patients (62.05% male and 37.95% female) followed in 20 transplant referral centers in Europe and North America. In the adult kidney transplant population, the Banff Automation System reclassified 83 out of 279 (29.75%) antibody-mediated rejection cases and 57 out of 105 (54.29%) T cell-mediated rejection cases, whereas 237 out of 3,239 (7.32%) biopsies diagnosed as non-rejection by pathologists were reclassified as rejection. In the pediatric population, the reclassification rates were 8 out of 26 (30.77%) for antibody-mediated rejection and 12 out of 39 (30.77%) for T cell-mediated rejection. Finally, we found that reclassification of the initial diagnoses by the Banff Automation System was associated with an improved risk stratification of long-term allograft outcomes. This study demonstrates the potential of an automated histological classification to improve transplant patient care by correcting diagnostic errors and standardizing allograft rejection diagnoses.ClinicalTrials.gov registration: NCT05306795 .
Peritoneal dialysis is the most commonly prescribed dialysis modality for infants and young children with kidney failure worldwide. Provision of high-quality care for the pediatric patient on chronic ...peritoneal dialysis requires a multidisciplinary approach and a strong collaboration with the patient and their caregiver. This article not only reviews current recommendations and advances in the care of pediatric patients on peritoneal dialysis with a focus on the provision of high-quality care and improvement in outcomes, but it also draws attention to health care disparities that exist locally and globally.
In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis ...CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study.
Plasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR.
Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2).
In children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.
Exposure to Bisphenol A (BPA) and phthalates is ubiquitous among adults and children in the United States. Among children and adolescents, those with chronic kidney disease (CKD) are potentially at ...greater risk of adverse effects from BPA and phthalate exposure. The objective of this study was to evaluate BPA and phthalate exposure among children with CKD and evaluate associations with three measures of kidney function.
Cross sectional study.
The CKD population was represented by the Chronic Kidney Disease in Children (CKiD) Study, a multicenter, prospective cohort study of children with impaired kidney function in the US. The main outcome was assessment of the relationship between chemical exposures and clinical laboratory findings at enrollment into CKiD. Data collected at baseline from participants 1 to 17 years old (N = 538) were analyzed. Urinary BPA and phthalate levels were evaluated at this time point. Data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative pediatric population, were used for comparison to the CKiD cohort.
Urinary BPA and phthalate levels in the CKiD population were consistently lower than levels detected in healthy children. Additionally, BPA was not significantly associated with blood pressure, proteinuria, or estimated glomerular filtration rate (eGFR). Within the CKiD population, for select individual and combined phthalates, there was an inverse relationship with the urinary protein:creatinine ratio (LMW phthalates, − 9.53% change; 95% CI: − 14.21, − 4.21; p = 0.001), and in most cases, a positive relationship with eGFR (LMW phthalates, a 3.46 unit increase in eGFR, 95% CI: 1.85, 5.07; p < 0.001).
Lack of longitudinal data, limited assessment of diet and nutritional status.
In the study cohort, children with CKD did not have increased exposure to BPA and phthalates. Longitudinal studies with repeated measures are likely to be more informative about the possible health effects of prolonged exposure to BPA and phthalates in pediatric patients with CKD.
•Exposure to bisphenol A and phthalates is lower in children with CKD than healthy controls.•Exposure to bisphenol A has no effect on kidney function in children with CKD.•Exposure to select phthalates is associated with increased GFR in children with CKD.•The long-term impact of these environmental chemicals requires further study.
As patients with chronic kidney disease (CKD) transition from pediatric nephrology care to adult care, their kidney function is clinically assessed by estimated glomerular filtration rate (eGFR) ...using both pediatric and adult equations, which may not be congruent. Here we evaluated commonly used eGFR equations and directly measured iohexol GFR (iGFR) among participants between ages 18 and 26 with a diagnosis of pediatric CKD in the Chronic Kidney Disease in Children (CKiD) cohort. The bedside serum creatinine (SCr)-only equation (CKiDSCr), the SCr-only CKD-EPI (CKD-EPISCr), the cystatin C (Cys)-only CKD-EPI (CKD-EPICys) and the combined SCr and Cys CKD-EPI (CKD-EPISCr-Cys) were compared with a) 279 measured iGFRs obtained from 187 participants and b) 548 eGFRs from the SCr and Cys-based CKiD equation (CKiDSCr-Cys) obtained from 219 participants. Among emerging adults with a median iGFR of 49 ml/min/1.73m2, the CKiDSCr-Cys equation had low bias (+1.5 ml/min/1.73m2) and high correlation (0.94), while CKiDSCr underestimated iGFR and CKiDSCr-Cys (–5.6 and –7.4 ml/min/1.73m2, respectively) and CKD-EPISCr had an overestimation bias (+8.2 and +6.1 ml/min/1.73m2, respectively). However, the CKD-EPICys and CKD-EPISCr-Cys exhibited strong agreement with both iGFR and CKiDSCr-Cys. GFR may also be validly estimated in this population by taking the simple average of CKiDSCr and CKD-EPISCr (average bias +1.3 compared to iGFR and -0.6 compared to CKiDSCr-Cys). Clinicians should be aware that individually the pediatric and adult SCr-based estimates of GFR had large discrepancies among emerging adults with pediatric CKD. Thus, when cystatin C is not available, we recommend the average of pediatric and adult SCr-based eGFR as a valid tool for clinical use.
Carnitine metabolism and homeostasis is significantly altered in patients receiving maintenance dialysis. Current literature in the adult and pediatric dialysis populations suggest a high prevalence ...of carnitine deficiency, which may lead to erythropoietin-resistant anemia, cardiomyopathy, and muscle weakness. However, the results of pediatric dialysis studies are limited and have not provided the evidence necessary to support strong recommendations or guidelines pertaining to carnitine management. The characteristics and function of carnitine, the definition and consequences of deficiency, a brief overview of recent adult studies, and current studies on carnitine supplementation in pediatric hemodialysis (HD) and peritoneal dialysis (PD) populations are discussed in this review.
Background: Exit site infections are a risk factor for the development of peritonitis in patients on long-term peritoneal dialysis. Visual assessments of an exit site utilising currently available ...tools (Twardowski and Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS)) are necessary to objectively characterise the appearance of an exit site. The aim of this study was to assess the interobserver agreement of exit site evaluations utilising both exit site scoring tools. Methods: Exit site evaluations were independently performed by two evaluators during outpatient visits at 13 sites within the Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease collaborative. The frequency and percentage of evaluations where both reviewers agreed were calculated. A sub-analysis was performed looking at evaluations where disagreement occurred. Results: A total of 371 paired exit site evaluations were collected over 6 months. For the majority of evaluations (range: 78%–97% Twardowski, 78%–97% MEPPS), both reviewers agreed that no abnormality was present across all domains. When the analysis was restricted to evaluations where at least one reviewer noted an abnormality, interobserver agreement fell across all domains (range: 31%–61% Twardowski, 56%–66% MEPPS). Disagreements more commonly occurred regarding the presence versus absence of an abnormality, rather than a difference in the severity of an abnormality. Conclusions: Whereas interobserver agreement is high when the appearance of a peritoneal dialysis catheter exit site is characterised as ‘normal’, interobserver disagreement is common when the appearance of the exit site is ‘abnormal’. Further work is warranted to improve interobserver agreement of exit site assessments and to identify domains conferring an increased risk of infection.
Young age has been associated with poorer control of hypertension in children with chronic kidney disease (CKD). Using data from the CKiD Study (Chronic Kidney Disease in Children), we examined the ...relationship between age, hypertensive blood pressure (BP) recognition, and pharmacologic BP control in children with nondialysis-dependent CKD.
Participants included 902 CKiD Study participants with CKD stages 2 to 4. A total of 3550 annual study visits met inclusion criteria and participants were stratified by age (0 to <7, ≥7 to <13, ≥13 to ≤18 years). Generalized estimating equations to account for repeated measures were applied to logistic regression analyses to evaluate the association of age with unrecognized hypertensive BP and medication use.
Children <7 years of age had a higher prevalence of hypertensive BP and a lower prevalence of antihypertensive medication use compared with older children. At visits where participants <7 years of age had hypertensive BP readings, 46% had unrecognized, untreated hypertensive BP compared with 21% of visits for children ≥13 years of age. The youngest age group was associated with higher odds of unrecognized hypertensive BP (adjusted odds ratio, 2.11 95% CI, 1.37-3.24) and lower odds of antihypertensive medication use among those with unrecognized hypertensive BP (adjusted OR, 0.51 95% CI, 0.27-0.996).
Children younger than 7 years of age with CKD are more likely to have both undiagnosed and undertreated hypertensive BP. Efforts to improve BP control in young children with CKD are needed to minimize development of cardiovascular disease and slow CKD progression.
Background
Cardiovascular disease (CVD) is the most common cause of mortality in chronic kidney disease (CKD). Children with early-onset CKD arguably experience the greatest lifetime CVD burden. We ...utilized data from the Chronic Kidney Disease in Children Cohort Study (CKiD) to evaluate two pediatric CKD cohorts: congenital anomalies of the kidney and urinary tract (CAKUT) and cystic kidney disease for CVD risks and outcomes.
Methods
CVD risk factors and outcomes including blood pressures, left ventricular hypertrophy (LVH), left ventricular mass index (LVMI), and ambulatory arterial stiffness index (AASI) scores were evaluated.
Results
Forty-one patients in the cystic kidney disease group were compared to 294 patients in the CAKUT group. Cystic kidney disease patients had higher cystatin-C levels, despite similar iGFR. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) indexes were higher in the CAKUT group, but a significantly higher proportion of cystic kidney disease patients was on anti-hypertensive medications. Cystic kidney disease patients had increased AASI scores and a higher incidence of LVH.
Conclusions
This study provides a nuanced analysis of CVD risk factors and outcomes including AASI and LVH in two pediatric CKD cohorts. Cystic kidney disease patients had increased AASI scores, higher incidence of LVH, and higher rates of anti-hypertensive medication use which could imply a greater burden of CVD despite similar GFR. Our work suggests that additional mechanisms may contribute to vascular dysfunction in cystic kidney disease, and that these patients may need additional interventions to prevent the development of CVD.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Traditional and nontraditional cardiovascular disease risk factors are highly prevalent in children with chronic kidney disease (CKD). We examined the longitudinal association of adiposity with ...cardiac damage among children with CKD and explored whether this association was modified by sex.
Prospective cohort study.
Children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study at 49 pediatric nephrology centers across North America.
Age- and sex-specific body mass index (BMI) z score.
Age- and sex-specific left ventricular mass index (LVMI) z score and left ventricular hypertrophy (LVH).
Longitudinal analyses using mixed-effects models to estimate sex-specific associations of BMI z scores with LVMI z score and with LVH, accounting for repeated measurements over time.
Among 725 children with 2,829 person-years of follow-up, median age was 11.0 years and median estimated glomerular filtration rate was 52.6mL/min/1.73m2. Nearly one-third of both boys and girls were overweight or obese, median LVMI z score was 0.18 (IQR: −0.67, 1.08), and 11% had LVH. Greater BMI z scores were independently associated with greater LVMI z scores and greater odds of LVH. For each 1-unit higher BMI z score, LVMI z score was 0.24 (95% CI, 0.17-0.31) higher in boys and 0.38 (95% CI, 0.29-0.47) higher in girls (Pinteraction = 0.01). For each 1-unit higher BMI z score, the odds of LVH was 1.5-fold (95% CI, 1.1-2.1) higher in boys and 3.1-fold (95% CI, 1.8-4.4) higher in girls (Pinteraction = 0.005).
Not all children had repeated measurements. LVH is a surrogate and not a hard cardiac outcome. The observational design limits causal inference.
In children, adiposity is independently associated with the markers of cardiac damage, LVMI z score and LVH. This association is stronger among girls than boys. Pediatric overweight and obesity may therefore have a substantial impact on cardiovascular risk among children with CKD.
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