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

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).

Case report: a 5-year-old with new onset nephrotic syndrome in the setting of COVID-19 infection.

BACKGROUND: This is a case report of an asymptomatic SARS-CoV-2 infection associated with new-onset nephrotic syndrome in a pediatric patient. This is the third case of new-onset nephrotic syndrome in children associated with SARS-CoV-2 infection, but is the first case report describing a new-onset nephrotic syndrome presentation in a patient who had asymptomatic COVID-19 infection. CASE PRESENTATION: This is a case of a previously healthy 5 year old female who presented with new-onset nephrotic syndrome in the setting of an asymptomatic COVID-19 infection. She presented with progressive edema, and laboratory findings were significant for proteinuria and hypercholesterolemia. She was treated with albumin, diuretics, and corticosteroid therapy, and achieved clinical remission of her nephrotic syndrome within 3 weeks of treatment. Though she was at risk of hypercoagulability due to her COVID-19 infection and nephrotic syndrome, she was not treated with anticoagulation, and did not develop any thrombotic events. CONCLUSIONS: Our case report indicates that SARS-CoV-2 infection could be a trigger for nephrotic syndrome, even in the absence of overt COVID-19 symptoms.

Chronic kidney disease impacts health-related quality of life of children in Uganda, East Africa.

BACKGROUND: Limited data exist about causes of chronic kidney disease (CKD) and impact on health-related quality of life (HRQoL) in African children. We evaluated types of kidney disease in Ugandan children 0-18 years and compared HRQoL in children with CKD or with benign or resolving kidney disease (non-CKD) to assess predictors of HRQoL. METHODS: Demographic, socioeconomic, and clinical data were obtained for this cross-sectional study. Pediatric Quality of Life Core Scale™ (PedsQL) was used to survey 4 domains and overall HRQoL. CKD and non-CKD scores were compared using unpaired t test. HRQoL predictors were evaluated using linear and logistic regression analyses. RESULTS: One hundred forty-nine children (71 CKD, 78 non-CKD; median age 9 years; male 63%) had the following primary diseases: nephrotic syndrome (56%), congenital anomalies of the urinary tract (CAKUT) (19%), glomerulonephritis (17%), and other (8%). CAKUT was the predominant etiology (39%) for CKD; 63% had advanced stages 3b-5. Overall HRQoL scores were significantly lower for CKD (57 vs. 86 by child report, p < 0.001; 63 vs. 86 by parent proxy report, p < 0.001). Predictors of lower HRQoL were advanced CKD stages 3b-5, primary caregiver non-parent, vitamin D deficiency, and anemia. CONCLUSION: Like other parts of the world, CAKUT was the main cause of CKD. Most CKD children presented at late CKD stages 3b-5. Compared with non-CKD, HRQoL in CKD was much lower; only two-thirds attended school. Vitamin D deficiency and anemia were potentially modifiable predictors of low HRQoL. Interventions with vitamin D, iron, and erythropoietin-stimulating agents might lead to improved HRQoL.

Peritoneal dialysis catheter outcomes in infants initiating peritoneal dialysis for end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) although rare among infants presents many management challenges. We sought to evaluate factors associated with PD catheter failure among infants initiated on chronic PD. METHODS: A retrospective chart review of all children under two years of age who had PD catheters placed for initiation of chronic PD from 2002 to 2015. Data was extracted for catheter related events occurring within 12 months of catheter placement. Cox and Poisson regression models were used to delineate factors associated catheter complications. RESULTS: Twenty-five infants with median age 18 days had PD catheters placed for chronic dialysis. Common complications included leakage around the exit site (31%), blockage (26%), migration or malposition (23%), catheter-related infections (18%), and other complications (2%). Predictors of initial PD catheter failure were age less than one month at catheter placement (hazard ratio (HR) 7.77, 95% CI, 1.70-35.39, p = 0.008), use of catheter within three days of placement (HR 5.67, 95% CI, 1.39-23.10, p = 0.015) and presence of a hernia (HR 8.64, 95% CI, 1.19-62.36, p = 0.033). In an adjusted Poisson regression model, PD catheter use within three days of placement was the only predictor of any catheter complication over the12 months of follow up. CONCLUSIONS: Use of PD catheters within three days of placement was associated with catheter failure. We recommend that when possible, catheters should be allowed to heal for at least three days prior to use to reduce risk of complications and improve catheter survival.

Acute kidney injury and its association with in-hospital mortality among children with acute infections.

BACKGROUND: We investigated prevalence of acute kidney injury (AKI) at hospitalization and its association with in-hospital mortality among Ugandan children hospitalized with common acute infections, and predictors of mortality among AKI children. METHODS: We enrolled 2,055 children hospitalized with primary diagnoses of acute gastroenteritis, malaria, or pneumonia. Serum creatinine, albumin, electrolytes, hemoglobin, and urine protein were obtained on admission. Participants were assessed for AKI based on serum creatinine levels. Demographic and clinical data were obtained using a primary care provider survey and medical chart review. Logistic regression was used to determine predictors of in-hospital mortality. RESULTS: A total of 278 (13.5%) of children had AKI on admission; for 76.2%, AKI was stage 2 (98/278) or stage 3 (114/278) defined as serum creatinine >2- or 3-fold above normal upper limit for age, respectively. AKI prevalence was particularly high in gastroenteritis (28.6%) and underweight children (20.7%). Twenty-five percent of children with AKI died during hospitalization, compared to 9.9% with no AKI (adjusted odds ratio (aOR) 3.5 (95% CI, 2.2-5.5)). In-hospital mortality risk did not differ by AKI stage. Predictors of in-hospital mortality among AKI children included primary diagnosis of pneumonia, aOR 4.5 (95% CI, 1.8-11.2); proteinuria, aOR = 2.1 (95% CI, 1.0-4.9) and positive human immunodeficiency virus (HIV) status, aOR 5.0 (95% CI, 2.0-12.9). CONCLUSIONS: Among children hospitalized with gastroenteritis, malaria, or pneumonia, AKI at admission was common and associated with high in-hospital mortality.

Human immunodeficiency virus infection and cerebral malaria in children in Uganda: a case-control study.

BACKGROUND: Human immunodeficiency virus (HIV)-1 infection increases the burden of malaria by increasing susceptibility to infection and decreasing the response to malarial treatment. HIV-1 has also been found to suppress the immune system and predispose to severe forms of malaria in adults. There is still a paucity of data on the association between HIV-1 infection and cerebral malaria in children. The aim of this study was to determine whether HIV-1 infection is a risk factor for cerebral malaria in children. METHOD: We conducted an unmatched case-control study, in which 100 children with cerebral malaria were compared with 132 with uncomplicated malaria and 120 with no malaria. In stratified analyses we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age. RESULTS: HIV-1 infection was present in 9% of children with cerebral malaria compared to 2.3% in uncomplicated malaria (age-adjusted odds ratio (aOR) 5.94 (95% confidence interval (CI) 1.36-25.94, p = 0.012); and 2.5% in children with no malaria (aOR 3.85 (95% CI0.99-14.93, p = 0.037). The age-adjusted odds of being HIV-positive among children with cerebral malaria compared to the control groups (children with uncomplicated malaria and no malaria) was 4.98 (95% CI 1.54-16.07), p-value = 0.003. CONCLUSIONS: HIV-1 infection is associated with clinical presentation of cerebral malaria in children. Clinicians should ensure that children diagnosed with HIV infection are initiated on cotrimoxazole prophylaxis as soon as the diagnosis is made and caretakers counselled on the importance of adherence to the cotrimoxazole towards reducing the risk of acquiring P.falciparum malaria and associated complications such as cerebral malaria. Other malaria preventive measures such as use of insecticide-treated mosquito nets should also be emphasized during counselling sessions.