Progress made toward equitable transplantation in children and young adults with kidney disease.

Racial disparities in pediatric kidney transplantation have been well described over the last two decades and include disparities in preemptive transplantation, waitlisting, time from activation to transplantation, living donation, and graft outcomes. Changes to the organ allocation system including the institution of Share 35 in 2005 and the Kidney Allocation System (KAS) of 2014 have resulted in resolution of some, but not all racial-ethnic disparities. Despite overall improvements in time from waitlist activation to transplant, disparities remain in preemptive transplantation, time to waitlisting, and living donor transplantation. Although improving under the KAS, racial disparities remain in graft survival as well. Racial disparity in kidney transplant access and graft survival is an international problem within pediatric nephrology. Although the racial group affected may differ, various minoritized pediatric groups across the world are affected by transplant disparities. Social determinants of health including financial access, language barriers, and the presence of a healthy living donor play a role in mediating these disparities. Further investigation is needed to better understand and intervene upon modifiable social, biological, and cultural factors driving the remaining disparity in transplant outcomes.

Associations between anemia and FGF23 in the CKiD study.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in chronic kidney disease-mineral bone disorder and is associated with CKD progression and cardiovascular morbidity. Factors related to CKD-associated anemia, including iron deficiency, can increase FGF23 production. This study aimed to assess whether anemia and/or iron deficiency are associated with increased circulating concentrations of FGF23 in the large, well-characterized Chronic Kidney Disease in Children (CKiD) study cohort. METHODS: Hemoglobin concentrations, iron parameters, C-terminal (total) FGF23, intact FGF23, and relevant covariables were measured in cross-sectional analysis of CKiD study subjects. RESULTS: In 493 pediatric patients with CKD (median [interquartile range] age 13 [9, 16] years), the median estimated glomerular filtration rate was 48 [35, 61] ml/min/1.73 m2, and 103 patients (21%) were anemic. Anemic subjects had higher total FGF23 concentrations than non-anemic subjects (204 [124, 390] vs. 109 [77, 168] RU/ml, p < 0.001). In multivariable linear regression modeling, anemia was independently associated with higher total FGF23, after adjustment for demographic, kidney-related, mineral metabolism, and inflammatory covariables (standardized ß (95% confidence interval) 0.10 (0.04, 0.17), p = 0.002). In the subset of subjects with available iron parameters (n = 191), iron deficiency was not associated with significantly higher total FGF23 concentrations. In the subgroup that had measurements of both total and intact FGF23 (n = 185), in fully adjusted models, anemia was significantly associated with higher total FGF23 (standardized ß (95% CI) 0.16 (0.04, 0.27), p = 0.008) but not intact FGF23 (standardized ß (95% CI) 0.02 (-0.12, 0.15), p = 0.81). CONCLUSIONS: In this cohort of pediatric patients with CKD, anemia was associated with increased total FGF23 levels but was not independently associated with elevated intact FGF23, suggesting possible effects on both FGF23 production and cleavage. Further studies are warranted to investigate non-mineral factors affecting FGF23 production and metabolism in CKD.

Sclerostin, Osteocytes, and Wnt Signaling in Pediatric Renal Osteodystrophy.

The pathophysiology of chronic kidney disease-mineral and bone disorder (CKD-MBD) is not well understood. Specific factors secreted by osteocytes are elevated in the serum of adults and pediatric patients with CKD-MBD, including FGF-23 and sclerostin, a known inhibitor of the Wnt signaling pathway. The molecular mechanisms that promote bone disease during the progression of CKD are incompletely understood. In this study, we performed a cross-sectional analysis of 87 pediatric patients with pre-dialysis CKD and post-dialysis (CKD 5D). We assessed the associations between serum and bone sclerostin levels and biomarkers of bone turnover and bone histomorphometry. We report that serum sclerostin levels were elevated in both early and late CKD. Higher circulating and bone sclerostin levels were associated with histomorphometric parameters of bone turnover and mineralization. Immunofluorescence analyses of bone biopsies evaluated osteocyte staining of antibodies towards the canonical Wnt target, ß-catenin, in the phosphorylated (inhibited) or unphosphorylated (active) forms. Bone sclerostin was found to be colocalized with phosphorylated ß-catenin, which suggests that Wnt signaling was inhibited. In patients with low serum sclerostin levels, increased unphosphorylated "active" ß-catenin staining was observed in osteocytes. These data provide new mechanistic insight into the pathogenesis of CKD-MBD and suggest that sclerostin may offer a potential biomarker or therapeutic target in pediatric renal osteodystrophy.

Addressing Structural Racism in Pediatric Clinical Practice.

Structural racism is the inequitable allocation of various social determinants of health to different communities. Exposure to this and other discrimination levied from intersectional identities is the primary driver of disproportionately adverse health outcomes for minoritized children and their families. Pediatric clinicians must vigilantly identify and mitigate racism in health care systems and delivery, assess for any impact of patient and family exposure to racism and direct them to appropriate health resources, foster an environment of inclusion and respect, and ensure that all care is delivered through a race-conscious lens with the utmost cultural humility and shared decision-making.

Racial-ethnic diversity in ambulatory blood pressure monitoring in children with chronic kidney disease.

BACKGROUND: Black adults with chronic kidney disease (CKD) have higher rates of hypertension as compared to White adults with CKD. Little is known of how race and ethnicity associate with the prevalence of hypertension in pediatric CKD patients. The aim was to compare ambulatory blood pressure monitoring (ABPM) results for patients with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study across racial-ethnic groups. METHODS: Patients from the CKiD study who identified as non-Hispanic White, non-Hispanic Black, or Hispanic were included to analyze differences in ABPM results across these racial-ethnic groups. The outcomes were fitted using 3 progressively adjusted models. RESULTS: This study included 501 CKiD participants with at least one successful ABPM study. Compared to White participants, Black participants had 4.2 mmHg higher mean sleep systolic blood pressure and 2.7 mmHg higher mean sleep diastolic blood pressure (p = 0.001 and p = 0.004, respectively). Additionally, Black participants had higher odds of abnormal wake systolic load (OR 1.88, 1.21-2.91, p = 0.005), wake diastolic load (OR 1.68, 1.03-2.73, p = 0.04), sleep systolic load (OR 2.19, 1.36-3.5, p = 0.001), sleep diastolic load (OR 2.01, 1.28-3.15, p = 0.002), systolic non-dipping (OR 2.02, 1.31-3.10, p = 0.001), and diastolic non-dipping (OR 2.69, 1.60-4.51, p < 0.001). Compared to White participants, Hispanic participants demonstrated only a lower sleep diastolic load (OR 0.54, 0.31-0.95, p = 0.03). CONCLUSIONS: Black children with CKD have higher absolute nocturnal blood pressures and higher rates of abnormal dipping. Further studies are needed to determine the etiology of these differences and the clinical implications of racial-ethnic differences in ABPM outcomes within the pediatric CKD population. A higher resolution version of the Graphical abstract is available as Supplementary information.

Seeking justice, equity, diversity and inclusion in pediatric nephrology.

Inequity, racism, and health care disparities negatively impact the well-being of children with kidney disease. This review defines social determinants of health and describes how they impact pediatric nephrology care; outlines the specific impact of systemic biases and racism on chronic kidney disease care and transplant outcomes; characterizes and critiques the diversity of the current pediatric nephrology workforce; and aims to provide strategies to acknowledge and dismantle bias, address barriers to care, improve diversity in recruitment, and strengthen the pediatric nephrology community. By recognizing historical and current realities and limitations, we can move forward with strategies to address racism and bias in our field and clinical practices, thereby cultivating inclusive training and practice environments.

Genetic Variants Associated With Mineral Metabolism Traits in Chronic Kidney Disease.

CONTEXT: Chronic kidney disease (CKD) causes multiple interrelated disturbances in mineral metabolism. Genetic studies in the general population have identified common genetic variants associated with circulating phosphate, calcium, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23). OBJECTIVE: In this study we aimed to discover genetic variants associated with circulating mineral markers in CKD. METHODS: We conducted candidate single-nucleotide variation (SNV) analysis in 3027 participants in the multiethnic Chronic Renal Insufficiency Cohort (CRIC) to determine the associations between SNVs and circulating levels of mineral markers. RESULTS: SNVs adjacent to or within genes encoding the regulator of G protein-coupled signaling 14 (RGS14) and the calcium-sensing receptor (CASR) were associated with levels of mineral metabolites. The strongest associations (P < .001) were at rs4074995 (RGS14) for phosphate (0.09 mg/dL lower per minor allele) and FGF23 (8.6% lower), and at rs1801725 (CASR) for calcium (0.12 mg/dL higher). In addition, the prevalence of hyperparathyroidism differed by rs4074995 (RGS14) genotype (chi-square P < .0001). Differential inheritance by race was noted for the minor allele of RGS14. Expression quantitative loci (eQTL) analysis showed that rs4074995 was associated with lower RGS14 gene expression in glomeruli (P = 1.03 × 10-11) and tubules (P = 4.0 × 10-4). CONCLUSION: We evaluated genetic variants associated with mineral metabolism markers in a CKD population. Participants with CKD and the minor allele of rs4074995 (RGS14) had lower phosphorus, lower plasma FGF23, and lower prevalence of hyperparathyroidism. The minor allele of RGS14 was also associated with lower gene expression in the kidney. Further studies are needed to elucidate the effect of rs4074995 on the pathogenesis of disordered mineral metabolism in CKD.

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).

Race and Ethnicity Predict Bone Markers and Fracture in Pediatric Patients With Chronic Kidney Disease.

Studies in healthy children have shown racial-ethnic differences in bone markers and bone outcomes including fractures. At present, limited studies have evaluated the impact of race and ethnicity on bone markers and fractures within the pediatric chronic kidney disease (CKD) population. In a cohort study of 762 children between the ages of 1.5 years and 18 years, with CKD stages 1 to 4 from the CKD in children (CKiD) cohort, the relationship between racial-ethnic group and bone markers (parathyroid hormone [PTH], 25-hydroxyvitamin D [25-OHD], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and C-terminal fibroblast growth factor [FGF23]) was determined using linear mixed models. Additionally, logistic regression was used to evaluate racial-ethnic differences in prevalent fracture upon study entry. Black race was associated with 23% higher PTH levels (confidence interval [CI], 2.5% to 47.7%; p = .03), 33.1% lower 25-OHD levels (CI, -39.7% to -25.7%; p < .0001), and no difference in C-terminal FGF23 or 1,25(OH)2 D levels when compared to whites. Hispanic ethnicity was associated with 15.9% lower C-terminal FGF23 levels (CI, -28.3% to -1.5%; p = .03) and 13.8% lower 25-OHD levels (CI, -22.2% to -4.5%; p = .005) when compared to whites. Black and Hispanic children had 74% (odds ratio [OR] 0.26; CI, 0.14 to 0.49; p = .001) and 66% (OR 0.34; CI, 0.17 to 0.65; p < .0001) lower odds of any fracture than white children at study entry, respectively. Race and ethnicity are associated with differences in bone markers and despite lower 25-OHD levels, both black and Hispanic children with CKD reported a lower prevalent fracture history than white children. The current findings in the CKD population are similar to racial-ethnic differences described in healthy children. Additional studies are needed to better understand how these differences might impact the management of pediatric CKD-MBD. © 2020 American Society for Bone and Mineral Research (ASBMR).

Association of age with risk of first and subsequent allograft failure and mortality among young kidney transplant recipients in the USA - a retrospective cohort study.

Adolescent age may be a high-risk period for kidney allograft failure. However, the knowledge on this topic is limited mostly to the first transplant. Among 20 960 patients aged ≤21 years at the first kidney transplantation from the US Renal Data System, we evaluated the association of age at the first kidney transplant with risk for the first and subsequent graft failures (1st, 2nd, and 3rd) using the conditional risk set model for recurrent time-to-event data. The median age was 15 (interquartile range: 9-18) years, and 18% received transplants twice or more during a median follow-up of 9.7 years. The risk for graft failures was highest in 16 to <18 years old with an adjusted hazard ratio (aHR) of 1.93 (95% CI, 1.73-2.15; reference: <3 years). When separately analyzed, the highest risk was observed in 17, 19, and 21 years old for the first, second, and third transplant, respectively. Those 16 to <18 years were also strongly associated with the highest risk for death after returning to dialysis (aHR, 4.01; 95% CI, 2.82-5.71). Adolescent recipients remain at high risk for allograft failure for a long time, which may result in high mortality risk, even though they surpass this high-risk period soon after the first transplant.

Primary causes of kidney disease and mortality in dialysis-dependent children.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) is associated with a slower progression to end-stage renal disease (ESRD) in pre-dialysis patients. However, little is known about the associated mortality risks after transitioning to dialysis. METHODS: This retrospective cohort study included 0-21 year-old incident dialysis patients from the United States Renal Data System starting dialysis between 1995 and 2016. We examined the association of CAKUT vs. non-CAKUT with all-cause mortality, using Cox regression adjusted for case mix variables. We also examined the mortality risk associated with 14 non-CAKUT vs. CAKUT ESRD etiologies and under stratification by estimated glomerular filtration rate (eGFR). RESULTS: Among 25,761 patients, the median (interquartile range) age was 17 (11-19) years, and 4780 (19%) had CAKUT. CAKUT was associated with lower mortality, with an adjusted hazard ratio (aHR) of 0.72 (95%CI, 0.64-0.81) (reference: non-CAKUT). In age-stratified analyses, CAKUT vs. non-CAKUT aHRs (95%CI) were 0.66 (0.54-0.80), 0.56 (0.39-0.80), 0.66 (0.50-0.86), and 0.97 (0.80-1.18) among patients < 6, 6-< 13, 13-< 18, and ≥ 18 years at dialysis initiation, respectively. Among non-CAKUT ESRD etiologies, the risk of mortality associated with primary glomerulonephritis (aHR, 0.93; 95%CI 0.80-1.09) and focal segmental glomerulosclerosis (aHR, 0.89; 95%CI, 0.75-1.04) were comparable or slightly lower compared to CAKUT, whereas most other primary causes were associated with higher mortality risk. While the CAKUT group had lower mortality risk compared to the non-CAKUT group patients with eGFR ≥5 mL/min/1.73m2, CAKUT was associated with higher mortality in patients with eGFR < 5 mL/min/1.73 m2. CONCLUSIONS: CAKUT is associated with lower mortality among children < 18 years old, but showed comparable mortality with non-CAKUT among patients ≥ 18 years old. ESRD etiology should be considered in risk assessment for children initiating dialysis.

Unraveling the osteocyte in CKD-MBD post-renal transplantation.

Changes in indices of mineral metabolism, bone protein expression, and bone turnover were assessed between pre- and post-renal transplant bone biopsies obtained 12 months apart. Circulating sclerostin and fibroblast growth factor 23 (FGF-23) levels decreased, and a low bone turnover state was highly prevalent on follow-up. In contrast, bone sclerostin expression increased, whereas FGF-23 bone expression was unchanged/decreased. These findings underscore the limitations of circulating biomarkers and the critical role of bone biopsy to understand osteocyte biology in chronic kidney disease-mineral bone disorder.

Serum albumin and hospitalization among pediatric patients with end-stage renal disease who started dialysis therapy.

BACKGROUND: Hypoalbuminemia is a strong predictor of hospitalization and mortality among adult dialysis patients. However, data are scant on the association between serum albumin and hospitalization among children new to dialysis. METHODS: In a retrospective cohort study of children 1-17 years old with end-stage renal disease receiving dialysis therapy in a large US dialysis organization 2007-2011, we examined the association of serum albumin with hospitalization frequency and total hospitalization days using a negative binomial regression model. RESULTS: Among 416 eligible patients, median (interquartile range) age was 14 (10-16) years and mean ± SD baseline serum albumin level was 3.7 ± 0.8 g/dL. Two hundred sixty-six patients (64%) were hospitalized during follow-up with an incidence rate of 2.2 (95%CI, 1.9-2.4) admissions per patient-year. There was a U-shaped association between serum albumin and hospitalization frequency; hospitalization rates (95%CI) were 2.7 (2.2-3.2), 1.9 (1.5-2.4), 1.6 (1.3-1.9), and 2.7 (1.7-3.6) per patient-year among patients with serum albumin levels < 3.5, 3.5- < 4.0, 4.0- < 4.5, and ≥ 4.5 g/dL, respectively. Case mix-adjusted hospitalization incidence rate ratios (IRRs) (95%CI) were 1.63 (1.24-2.13), 1.32 (1.10-1.58), and 1.25 (1.06-1.49) at serum albumin levels 3.0, 3.5, and 4.5 g/dL, respectively (reference: 4.0 g/dL). Similar trends were observed in hospitalization days. These associations remained robust against further adjustment for laboratory variables associated with malnutrition and inflammation. CONCLUSIONS: Both high and low serum albumin were associated with higher hospitalization in children starting dialysis. Because the observed association is novel and not fully explainable especially for high serum albumin levels, interpreting the results requires caution and further studies are needed to confirm and elucidate this association before clinical recommendations are made.

Racial differences in bone histomorphometry in children and young adults treated with dialysis.

BACKGROUND: Healthy African-Americans are known to have greater bone mineral density and decreased risk of fracture when compared to Caucasians. In fact, comparisons of bone histomorphometry in healthy South African children and adults reveal greater cortical thickness in Black subjects as compared to White. How these differences are reflected in the bone of American children and young adults on dialysis is unknown. METHODS: Using tetracycline-labeled, iliac crest bone biopsies obtained in prior research protocols in pediatric and young adult dialysis patients, we compared trabecular and cortical parameters between non-Hispanic African-American subjects and non-Hispanic Caucasian subjects matched by age and gender. A linear regression model controlled for trabecular turnover and mineralization was used to further investigate the association of race with cortical thickness. RESULTS: The matched cohort consisted of 52 subjects-26 African-American and 26 Caucasian. Turnover, mineralization and volume parameters in trabecular bone did not show significant differences between racial groups. Characterizing subjects by renal osteodystrophy type did not show a statistically significant difference although Caucasian patients had double the prevalence of mineralization defects. Consistent with this was a trend toward better mineralization parameters in African-Americans including shorter osteoid maturation time and lower osteoid volume. A sub-cohort of patients with cortical measures demonstrated greater median (IQR) cortical thickness in African-Americans (541 µm [354, 694]) than in Caucasians (371 µm [336, 446], p = 0.08). In a linear regression model controlling for trabecular turnover and mineralization, African-American subjects had 36.2% (95% CI 0.28 to 85.1%, p = 0.048) greater cortical thickness as compared to White subjects. There was no significant difference in cortical porosity. CONCLUSIONS: Although likely limited by sample size, our findings suggest that, similar to findings in populations of normal children, African-American race in pediatric and young adults on dialysis is associated with greater cortical thickness. Additionally, there was a trend toward greater mineralization defects in Caucasian children. Both findings require further exploration with larger patient samples in order to thoroughly explore these racial differences and the implications on CKD-MBD treatment.

Estimated GFR at Dialysis Initiation and Mortality in Children and Adolescents.

RATIONALE & OBJECTIVE: The association of estimated glomerular filtration rate (eGFR) at dialysis therapy initiation with mortality among adult dialysis patients has been greatly debated, with some studies showing no benefit from early dialysis therapy initiation. However, this association has not been well investigated in pediatric dialysis patients. The objective of this study was to evaluate the mortality risk associated with eGFR at dialysis therapy initiation in children and adolescents with kidney failure. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 9,963 incident dialysis patients aged 1 to 17 years in the US Renal Data System registry (1995-2016). PREDICTOR: eGFRs at dialysis therapy initiation calculated using the pediatric-specific bedside Schwartz equation (<5, 5-<7, 7-<9, 9-<12, and ≥12mL/min/1.73m2). OUTCOME: Time to all-cause death. ANALYTICAL APPROACH: Cox proportional hazards regression adjusted for case-mix variables, height, body mass index, hemoglobin level, and serum albumin level. RESULTS: Median eGFR was 7.8 (IQR, 5.6-10.5) mL/min/1.73m2 and median age was 13 (IQR, 9-16) years. 696 deaths were observed during the median follow-up of 1.4 (IQR, 0.7-2.7) years, and overall crude mortality rate was 31 per 1,000 patient-years. There appeared to be a trend toward higher mortality risk across higher eGFRs at dialysis therapy initiation. Compared with eGFRs of 7 to <9mL/min/1.73m2, eGFRs <5 and ≥12mL/min/1.73m2 were associated with lower and higher mortality, with adjusted HRs of 0.57 (95% CI, 0.43-0.74) and 1.31 (95% CI, 1.05-1.65), respectively. In age-stratified analysis, there were consistent relationships among patients 6 years and older while the eGFR-mortality association was attenuated among patients younger than 6 years (Pinteraction = 0.002). LIMITATIONS: Possible errors in eGFRs due to methods for serum creatinine measurement. Unmeasured confounders related to eGFR at dialysis therapy initiation. CONCLUSIONS: Higher eGFR at dialysis therapy initiation was associated with higher mortality risk. Further studies of eGFR at initiation are needed in pediatric dialysis patients, especially among those younger than 6 years.

Racial-ethnic differences in chronic kidney disease-mineral bone disorder in youth on dialysis.

BACKGROUND: Studies in healthy pediatric populations and adults treated with dialysis demonstrate higher parathyroid hormone (PTH) and lower 25-hydroxyvitamin D levels in African-Americans. Despite these findings, African-Americans on dialysis demonstrate greater bone strength and a decreased risk of fracture compared to the Caucasian dialysis population. The presence of such differences in children and young adult dialysis patients is unknown. METHODS: Differences in the markers of mineral and bone metabolism (MBM) were assessed in 661 incident dialysis patients (aged 1 month to < 21 years). Racial-ethnic differences in PTH, calcium, phosphate, and total alkaline phosphatase (AP) activity were analyzed over the first year of dialysis using multivariate linear mixed models. RESULTS: African-American race predicted 23% higher serum PTH (95% CI, 4.7-41.3%) when compared to Caucasian patients, while Hispanic ethnicity predicted 17.5% higher PTH (95% CI, 2.3-38%). Upon gender stratification, the differences in PTH were magnified in African-American and Hispanic females: 38% (95% CI, 14.8-69.8%) and 28.8% (95% CI, 4.7-54.9%) higher PTH compared to Caucasian females. Despite higher PTH values, African-American females persistently demonstrated up to 10.9% lower serum AP activity (95% CI, - 20.6-- 0.7%). CONCLUSIONS: There are racial-ethnic differences in the markers of MBM. Higher PTH is seen in African-American and Hispanic children and young adults on dialysis with a magnification of this difference amongst the female population. There is a need to consider how factors like race, ethnicity, and gender impact the goal-targeted treatment of MBM disorders.

Kidney Disease Among African Americans: A Population Perspective.

End-stage kidney disease and earlier stages of chronic kidney disease (CKD) represent one of the most dramatic examples of racial/ethnic disparities in health in our nation. African Americans are 3 times more likely to require renal replacement therapy then their non-Hispanic white counterparts. This article describes CKD-related disparities linked to a variety of clinical, socioeconomic, and cultural factors, as well as to select social determinants of health that are defined by social positioning and often by race within the United States. Our advancing understanding of these issues has led to improvements in patient outcomes and is narrowing the gap in disparities across most aspects of CKD and CKD risk factors. There are also extensive data indicating similar improvements in quality measures for patients on dialysis therapy. This article also reviews the state of CKD in African Americans from a population perspective and provides recommendations for the way forward.

Non-renal-Related Mechanisms of FGF23 Pathophysiology.

PURPOSE OF REVIEW: We will review non-renal-related mechanisms of fibroblast growth factor 23 (FGF23) pathophysiology. RECENT FINDINGS: FGF23 production and metabolism may be affected by many bone, mineral, and kidney factors. However, it has recently been demonstrated that other factors, such as iron status, erythropoietin, and inflammation, also affect FGF23 production and metabolism. As these non-mineral factors are especially relevant in the setting of chronic kidney disease (CKD), they may represent emerging determinants of CKD-associated elevated FGF23 levels. Moreover, FGF23 itself may promote anemia and inflammation, thus contributing to the multifactorial etiologies of these CKD-associated comorbidities. CKD-relevant, non-mineral-related, bidirectional relationships exist between FGF23 and anemia, and between FGF23 and inflammation. Iron deficiency, anemia, and inflammation affect FGF23 production and metabolism, and FGF23 itself may contribute to anemia and inflammation, highlighting complex interactions that may affect aspects of CKD pathogenesis and treatment.

Clinical experience with the use of ferric citrate as a phosphate binder in pediatric dialysis patients.

BACKGROUND: Ferric citrate, an iron-based phosphate binder, has been shown to improve both hyperphosphatemia and iron deficiency in adult chronic kidney disease patients, but its use in the pediatric dialysis population has not been described. METHODS: This is a retrospective analysis of 11 unselected pediatric dialysis patients who received ferric citrate as a phosphate binder between 2015 and 2017. Time-averaged laboratory values were compared pre- and post-ferric citrate initiation using the Wilcoxon signed-rank test. RESULTS: The median age of this cohort was 13 years old (range 4-17 years old). Five patients were on hemodialysis, and six patients were on peritoneal dialysis. The median duration of ferric citrate therapy was 214 days (range 39-654 days), with a median time-averaged ferric citrate dose of 3.5 tablets per day (range 1.5-8.4 tablets per day). Compared to the pre-ferric citrate period, ferric citrate treatment was associated with decreased serum phosphate (6.5 to 5.2 mg/dl, p = 0.014), decreased phosphate age-related standard deviation score (SDS) (2.3 to 0.9, p = 0.019), increased transferrin saturation (26 to 34%, p = 0.049), increased ferritin (107 to 230 ng/ml, p = 0.074), and maintenance of hematocrit. CONCLUSIONS: In pediatric dialysis patients, ferric citrate may be able to concurrently lower phosphate levels and treat iron deficiency. However, larger studies are needed to further evaluate safety and efficacy in the pediatric chronic kidney disease population.