A review of ferric citrate clinical studies, and the rationale and design of the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) trial.

2022

2022 Mar 02

1432-198X

<p>Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3-4 (ClinicalTrials.gov Identifier NCT04741646).</p>

10.1007/s00467-022-05492-7

Pediatr Nephrol

35237863

Design and Methods of the Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS) Study in Children.

2021

e791

2021 Dec

2373-8731

<p>Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients.</p>

<p><strong>Methods: </strong>Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (-normalized mRNA, and ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure.</p>

<p><strong>Results: </strong>To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted.</p>

<p><strong>Conclusions: </strong>Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection.</p>

10.1097/TXD.0000000000001244

Transplant Direct

34805493