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Recent reassessment of the use of race in estimated glomerular filtration rate (eGFR) in adults has instigated questions about the role of race in eGFR expressions for children. Little research has examined the associations of self-reported race with measured GFR (mGFR) adjusting for serum creatinine or cystatin C in children and young adults with chronic kidney disease (CKD). This study examined these associations and evaluated the performance of the previously published "U25" (under the age of 25 years) eGFR equations in a large cohort of children and young adults with CKD.Observational cohort study.Participants in the Chronic Kidney Disease in Children (CKiD) study including 190 Black and 675 non-Black participants contributing 473 and 1,897 annual person-visits, respectively.Self- or parental-reported race (Black, non-Black). Adjustment for serum creatinine or cystatin C, body size, and socioeconomic status.mGFR based on iohexol clearance.Linear regression with generalized estimating equations, stratified by age (6, 6-12, 12-18, and ≥18 years) incorporating serum creatinine or serum cystatin C. Contrasting performance in different self-reported racial groups of the U25 eGFR equations.Self-reported Black race was significantly associated with 12.8% higher mGFR among children in regression models including serum creatinine. Self-reported Black race was significantly associated with 3.5% lower mGFR after adjustment for cystatin C overall but was not significant for those over 12 years. The results were similar after adjustment for body size and socioeconomic factors. The average of creatinine- and cystatin C-based U25 equations was unbiased by self-reported race groups.Small number of children 6 years; lean body mass was estimated.Differences in the creatinine-mGFR relationship by self-reported race were observed in children and young adults with CKD and were consistent with findings in adults. Smaller and opposite differences were observed for the cystatin C-mGFR relationship, especially in the younger age group. We recommend inclusion of children for future investigations of biomarkers to estimate GFR. Importantly, for GFR estimation among those under 25 years of age, the average of the new U25 creatinine and cystatin C equations without race coefficients yields unbiased estimates of mGFR.

RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) guideline on CKD presented an international classification system that ranks patients' risk for CKD progression. Few data on children informed guideline development STUDY DESIGN: Observational cohort study SETTINGS AND PARTICIPANTS: Children aged 1-18 years enrolled in the North American Chronic Kidney Disease in Children (CKiD) cohort study and the European Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. PREDICTOR: Level of estimated glomerular filtration rate (eGFR) and proteinuria (urine protein-creatinine ratio (mg/mg)) at study entry OUTCOME: A composite event of renal replacement therapy, 50% reduction of estimated GFR (eGFR), or eGFR 2.0 at study entry. Six ordered stages with varying combinations of eGFR categories (60-89, 45-59, 30-44 and 15-29 ml/min/1.73m(2)) and UPCR categories (2.0) described the risk continuum. Median times to event ranged from >10 years for eGFR 45-90 and UPCR 2. Children with glomerular disease were estimated to have a 43% shorter time to event than children with nonglomerular disease. Cross-validation demonstrated risk patterns that were consistent across the ten subsample validation models. LIMITATIONS: Observational study, utilized cross validation rather than external validation CONCLUSION: CKD staged by level of eGFR and proteinuria characterizes the timeline of progression and can guide management strategies in children.

Cystatin C (CyC) concentration has been suggested as a marker of middle-molecule accumulation, hemodialysis (HD) adequacy and for estimating residual renal function (RRF), but it has not been studied in pediatric HD. High CyC is associated with increased cardiovascular disease (CVD). We investigated CyC kinetics and the effect of RRF on CyC in a pediatric HD population. A total of 21 HD sessions and 20 interdialytic periods were analyzed in seven patients, age 5–19 years, of whom four were anuric (A) and three were non-anuric (NA). CyC was measured before (preHD) and after (postHD) three standard HD sessions in 1 week and prior to the first session of the following week. We found no difference (p = 0.67) in CyC concentration between preHD CyC (9.85 ± 2.15 mg/l; A vs. NA, p = 0.37) and postHD CyC (10.04 ± 2.83 mg/l; A vs NA, p = 0.28). The weekly average preHD CyC median concentration was 10.14 mg/l (A vs. NA, p = 0.87) and correlated with age (r = 0.808, p = 0.03) and height measurement (r = 0.799, p = 0.03), but not with RRF, single-pool Kt/V, ultrafiltration, HD duration or blood liters processed. Cystatin C is very elevated in children on HD. It does not rise between HD sessions, is not removed by standard HD and remains at steady state; therefore, elimination is extrarenal. Low RRF does not affect CyC elimination. CyC increases with age and height. If a high CyC concentration can be proven to have a causative role in the development of CVD, routine intensified HD regimens in children may be indicated for its removal.

To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.Annualized GFR change in subjects with ARPKD was -1.4 mL/min/1.73 m(2) (-6%), with greater decline in subjects age ≥ 10 years (-11.5%). However, overall rates of GFR decline did not differ significantly in subjects with ARPKD vs controls. There were no significant differences in rates of HTN or left ventricular hypertrophy, but subjects with ARPKD had a greater percent on ≥ 3 blood pressure medications (32% vs 0%, P.0001), more angiotensin-converting enzyme inhibitor use (82% vs 27% vs 36%, P.0005), and less proteinuria (urine protein: creatinine = 0.1 vs 0.6, P.005).This study reports rates of GFR decline, HTN, and proteinuria in a small but well-phenotyped ARPKD cohort. The relatively slow rate of GFR decline in subjects with ARPKD and absence of significant proteinuria suggest that these standard clinical measures may have limited utility in assessing therapeutic interventions and highlight the need for other ARPKD kidney disease progression biomarkers.

Online clearance (OLC) monitor measures conductivity difference between dialysate entering and leaving the dialyser. Derived ionic dialysance (ID) represents effective urea clearance from which Kt/V is calculated, allowing Kt/V monitoring at every treatment without blood sampling. We tested ID accuracy in children and provide recommendations for its use. Using Fresenius machines 2008 K with built-in OLC monitors, we studied 45 hemodialysis (HD) sessions and 168 calculated Kt/V results in 11 patients. Urea distribution volume (V), needed to calculate Kt/V from ID, was estimated using three methods: Mellits and Cheek (MC), KDOQI recommended total body water nomograms (TBWN) and OLC-derived independent from tested HD sessions. Reference spKt/V from pre- and post-HD BUN (Daugirdas) was compared with Kt/V calculated from ID using three different estimated V's. ID was accurate in calculating Kt/V in children when V derived from OLC was used (P = 0.42), with absolute error 0.14 ± 0.12. If TBWN-derived V was used, Kt/V was consistently underestimated by 0.32 ± 0.22. TBWN-derived V can still be recommended for use with OLC for monitoring trend in Kt/V, if underestimation of spKt/V of average 0.3 is accounted for. MC-derived V results in even greater underestimation of spKt/V and therefore cannot be recommended for use with OLC.

A 9-month old girl presented to the emergency room with brown urine and generalized edema. She had been born at full term with normal growth and development. Her parents were unrelated and had no other children. She had been in good health until she developed brown urine 4 days prior to presentation and was noted to have edema 1 day prior to being seen in emergency department. Her physical exam was remarkable for moderate generalized edema, mild pallor, and irritability. Vital signs were within normal limits except for elevated blood pressure (115/63 mmHg). Her urine specimen was turbid and brown. Microscopic exam showed red blood cells (RBC) too numerous to count, 2–5 white blood cells (WBC), and 5–10 squamous epithelial cells per high power field. No RBC casts were seen. Urine protein/creatinine ratio was 17. Renal function panel revealed normal electrolytes, elevated serum creatinine at 0.49 mg/dl (estimated glomerular filtration rate Schwartz 63 ml/min/1.73 m), and low serum albumin at 1.9 g/dl. Complete blood count showed mild anemia with hemoglobin 8.9 g/dl, platelet count 273,000/mm, and WBC 13,900/ mm. Renal ultrasound showed bilaterally enlarged kidneys with increased cortical echogenicity. Chest X-ray was within normal limits. The infant was admitted to the hospital.

To assess depression in children with chronic kidney disease and to determine associations with patient characteristics, intellectual and educational levels, and health-related quality of life (HRQoL).Subjects aged 6-17 years from the Chronic Kidney Disease in Children cohort study completed the Children's Depression Inventory (CDI), Wechsler Abbreviated Scales of Intelligence, Wechsler Individual Achievement Test-II-Abbreviated, and the Pediatric Inventory of Quality of Life Core Scales 4.0. Regression analyses determined associations of CDI score and depression status with subject characteristics, intellectual and educational levels, and HRQoL. A joint linear mixed model and Weibull model were used to determine the effects of CDI score on longitudinal changes in glomerular filtration rate and time to renal replacement therapy.A total of 344 subjects completed the CDI. Eighteen (5%) had elevated depressive symptoms, and another 7 (2%) were being treated for depression. In adjusted analyses, maternal education beyond high school was associated with 5% lower CDI scores (estimate, 0.95; 95% CI, 0.92-0.99). Depression status was associated with lower IQ (99 vs 88; P = .053), lower achievement (95 vs 77.5; P.05), and lower HRQoL by parent and child reports (effect estimates, -15.48; 95% CI, -28.71 to -2.24 and -18.39; 95% CI, -27.81 to -8.96, respectively). CDI score was not related to change in glomerular filtration rate.Children with depression had lower psychoeducational skills and worse HRQoL. Identifying and treating depression should be evaluated as a means of improving the academic performance and HRQoL of children with chronic kidney disease.