by
Joseph G. Maliakkal;
M. John Hicks;
Mini Michael;
David T. Selewski;
Katherine Twombley;
Michelle N. Rheault;
Meredith Seamon;
Jason M. Misurac;
Cheryl L. Tran;
Loretta Reyes;
Joseph T. Flynn;
Ali M. Onder;
Alexandru R. Constantinescu;
Vaishali Singh;
Cynthia Pan;
Abiodun Omoloja;
Qiang Wu;
William E. Smoyer;
Guillermo Hidalgo;
Scott E. Wenderfer
There is no evidence-based definition for diagnosing crescentic glomerulonephritis. The prognostic implications of crescentic lesions on kidney biopsy have not been quantified. Our objective was to determine risk factors for end-stage kidney disease (ESKD) in patients with glomerulonephritis and crescents on kidney biopsy. A query of the Pediatric Nephrology Research Consortium’s Pediatric Glomerulonephritis with Crescents registry identified 305 patients from 15 centers. A retrospective cohort study was performed with ESKD as the primary outcome.
Median age at biopsy was 11 years (range 1–21). The percentage of crescents was 3–100% (median 20%). Etiologies included IgA nephropathy (23%), lupus (21%), IgA vasculitis (19%) and ANCA-associated GN (13%), post-infectious GN (5%), and anti-glomerular basement membrane disease (3%). The prevalence of ESKD was 12% at one year and 16% at last follow-up (median = 3 years, range1–11). MediantimetoESKDwas100days. RiskfactorsforESKDincluded%crescents,presence of fibrous crescents, estimated GFR, and hypertension at biopsy. For each 1% increase in %crescents, therewasa3%decreaseinlogoddsof1-yearrenalsurvival(p = 0.003)anda2%decreaseinlogodds of renal survivalat last follow-up(p < 0.001). Thesefindings providean evidencebase for enrollment criteria for crescentic glomerulonephritis in future clinical trials.
Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD). Arginine, the endogenous precursor for nitric oxide synthesis, is produced in the kidneys. Arginine bioavailability contributes to endothelial and myocardial dysfunction in CKD. Plasma from 129X1/SvJ mice with and without CKD (5/6th nephrectomy), and banked plasma from children with and without CKD were analyzed for amino acids involved in arginine metabolism, ADMA, and arginase activity. Echocardiographic measures of myocardial function were compared with plasma analytes. In a separate experiment, a non-specific arginase inhibitor was administered to mice with and without CKD. Plasma citrulline and glutamine concentrations correlated with multiple measures of myocardial dysfunction. Plasma arginase activity was significantly increased in CKD mice at 16 weeks vs. 8 weeks (p = 0.002) and ventricular strain improved after arginase inhibition in mice with CKD (p = 0.03). In children on dialysis, arginase activity was significantly increased vs. healthy controls (p = 0.04). Increasing ADMA correlated with increasing RWT in children with CKD (r = 0.54; p = 0.003). In a mouse model, and children, with CKD, arginine dysregulation correlates with myocardial dysfunction.
Sickle cell disease (SCD) is the most common hemoglobinopathy in the United States and vaso-occlusive pain episodes (VOE) are the leading cause of hospitalizations and emergency department (ED) visits1. There are limited therapies for acute management of VOE that directly target the underlying etiology for sickle-related pain therefore treatment is largely symptomatic. Moderate-to-severe pain is typically treated with parenteral hydration, opioids, and hospitalization to achieve adequate pain control.
by
Mark R Hanudel;
Marciana L Laster;
Anthony A Portale;
Aditi Dokras;
Raymond P Quigley;
German Lozano A Guzman;
Joshua J Zaritsky;
Nicole A Hayde;
Frederick J Kaskel;
Mark M Mitsnefes;
Jorge A Ramirez;
Peace D Imani;
Poyyapakkam R Srivaths;
Amy J Kogon;
Michelle R Denburg;
Tom D Blydt-Hansen;
Loretta Reyes;
Larry Greenbaum;
Darcy K Weidemann;
Bradley A Warady;
David A Elashoff;
Susan R Mendley;
Tamara Isakova;
Isidro B Salusky
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).