Assessment of fluid removal using ultrasound, bioimpedance and anthropometry in pediatric dialysis: a pilot study.

BACKGROUND: Fluid overload is associated with morbidity and mortality in children receiving dialysis. Accurate clinical assessment is difficult, and using deuterium oxide (D2O) to measure total body water (TBW) is impractical. We investigated the use of ultrasound (US), bioimpedance spectroscopy (BIS), and anthropometry to assess fluid removal in children receiving maintenance hemodialysis (HD). METHODS: Participants completed US, BIS, and anthropometry immediately before and 1-2 h after HD for up to five sessions. US measured inferior vena cava (IVC) diameter, lung B-lines, muscle elastography, and dermal thickness. BIS measured the volume of extracellular (ECF) and intracellular (ICF) fluid. Anthropometry included mid-upper arm, calf and ankle circumferences, and triceps skinfold thickness. D2O was performed once pre-HD. We assessed the change in study measures pre- versus post-HD, and the correlation of change in study measures with percent change in body weight (%∆BW). We also assessed the agreement between TBW measured by BIS and D2O. RESULTS: Eight participants aged 3.4-18.5 years were enrolled. Comparison of pre- and post-HD measures showed significant decrease in IVC diameters, lung B-lines, dermal thickness, BIS %ECF, mid-upper arm circumference, ankle, and calf circumference. Repeated measures correlation showed significant relationships between %∆BW and changes in BIS ECF (rrm =0.51, 95% CI 0.04, 0.80) and calf circumference (rrm=0.80, 95% CI 0.51, 0.92). BIS TBW correlated with D2O TBW but overestimated TBW by 2.2 L (95% LOA, -4.75 to 0.42). CONCLUSION: BIS and calf circumference may be helpful to assess changes in fluid status in children receiving maintenance HD. IVC diameter, lung B-lines and dermal thickness are potential candidates for future studies.

Predictors of patency for arteriovenous fistulae and grafts in pediatric hemodialysis patients.

BACKGROUND: Hemodialysis (HD) guidelines recommend permanent vascular access (PVA) in children unlikely to receive kidney transplant within 1 year of starting HD. We aimed to determine predictors of primary and secondary patency of PVA in pediatric HD patients. METHODS: Retrospective chart reviews were performed for first PVAs in 20 participating centers. Variables collected included patient demographics, complications, interventions, and final outcome. RESULTS: There were 103 arterio-venous fistulae (AVF) and 14 AV grafts (AVG). AVF demonstrated superior primary (p = 0.0391) and secondary patency (p = 0.0227) compared to AVG. Primary failure occurred in 16 PVA (13.6%) and secondary failure in 14 PVA (12.2%). AVF were more likely to have primary failure (odds ratio (OR) = 2.10) and AVG had more secondary failure (OR = 3.33). No demographic, clinical, or laboratory variable predicted primary failure of PVA. Anatomical location of PVA was predictive of secondary failure, with radial having the lowest risk compared to brachial (OR = 12.425) or femoral PVA (OR = 118.618). Intervention-free survival was predictive of secondary patency for all PVA (p = 0.0252) and directly correlated with overall survival of AVF (p = 0.0197) but not AVG. Study center demonstrated statistically significant effect only on intervention-free AVF survival (p = 0.0082), but not number of complications or interventions, or outcomes. CONCLUSIONS: In this multi-center pediatric HD cohort, AVF demonstrated primary and secondary patency advantages over AVG. Radial PVA was least likely to develop secondary failure. Intervention-free survival was the only predictor of secondary patency for AVF and directly correlated with overall access survival. The study center effect on intervention-free survival of AVF deserves further investigation.

The first hour refill index: a promising marker of volume overload in children and young adults on chronic hemodialysis.

BACKGROUND: Volume overload is a known risk factor for cardiovascular complications in children on hemodialysis (HD), but a measurable index of volume overload is still lacking. METHODS: We propose a novel index of pre-HD volume overload based on blood volume (BV) monitoring, the first hour refill index (RI), calculated as the ratio between the ultrafiltration rate indexed for body weight during the first HD hour and the percent BV change at the first hour of the treatment. This parameter was retrospectively calculated in 121 sessions in 11 oligoanuric children and young adults on chronic HD, with median age 14.3 years (range 5.4-22.4), and its association with left-ventricular mass index, pre-HD blood pressure, and number of antihypertensive medications was evaluated. RESULTS: The median RI was 2.07 ml/kg/h/%. There was a significant correlation between RI and median LVMI (r 0.66, p = 0.028), which was 53.4 g/m2.7 (45.7-64) in patients with a median RI > 2, and 36.6 g/m2.7 (24.9-47) in those with a median RI < 2 ml/kg/h/% (p = 0.01). The number of antihypertensive drugs per patient was significantly higher in patients with a RI > 2 than in those with a RI < 2 ml/kg/h/% (three vs one per patient; p = 0.02) while blood pressure was not significantly different between the two groups. CONCLUSIONS: The ratio between the ultrafiltration rate per body weight and the BV change during the first hour of a HD session could be a promising index of refill capacity and pre-HD volume overload in children and young adults on chronic HD.

Left ventricular strain and left atrial strain are impaired during hemodialysis in children.

We aimed to investigate intradialytic changes in ventricular and atrial function using speckle tracking echocardiography (STE) in pediatric hemodialysis (HD). Children with HD vintage > 3 months were enrolled, and echocardiography was performed prior to, during, and after HD. STE was analyzed using GE EchoPAC. Left ventricular (LV) global longitudinal strain (GLS), strain rate (Sr), and mechanical dispersion index (MDI) were calculated as the average from 3 apical views; diastolic strain (Ds) and Sr from 4-chamber tracing; left atrial strain (LAS) and Sr from the 4- and 2-chamber views. A total of 15 patients were enrolled at a median age of 12 years (IQR 8, 16) and median HD vintage of 13 months (IQR 9, 25). GLS worsened during HD (- 15.8 ± 2.2% vs - 19.9 ± 1.9%, p < 0.001). Post-HD GLS was associated with BP decrease (coefficient = 0.62, p = 0.01). LV MDI and systolic Sr did not change. LV Ds progressively worsened (- 8.4% (- 9.2, - 8.0) vs - 11.9% (- 13.4, - 10.3), p < 0.001). LAS changes at mid-HD returned to baseline post-HD. Ds, DSr, LAS, LASr were not associated with BV removal or BP decrease (p > 0.1). In conclusions, intradialytic LV strain and LAS changes consistent with subclinical systolic and diastolic dysfunction were observed during HD in children. Changes in Ds, DSr, LAS, and LASr were not associated with BP change or BV removal and may be related to the disease progression. Longitudinal study using these novel indices may unfold the effect of these subclinical changes on long-term cardiovascular health in children requiring chronic HD.

Accesibilidad, disponibilidad y asequibilidad de medicamentos para Niños con Enfermedad Renal Crónica en Guatemala / Access, availability and affordability of medications for children with Advanced Chronic Kidney Disease in Guatemala

El artículo tiene como objetivo analizar la disponibilidad, acceso y asequibilidad de los medicamentos para niños con Enfermedad Renal Crónica (ERC) en tratamiento con hemodiálisis (HD) en un país de bajos a medianos ingresos. Se llevó a cabo un estudio transversal para determinar los medicamentos más utilizados en una unidad de hemodiálisis pediátrica, incluyendo el nombre del medicamento, dosis, frecuencia, forma farmacéutica y vía de administración. Dos farmacias dentro del perímetro del hospital, una pública y una privada, fueron consultadas para determinar el costoy disponibilidad de medicamentos genéricos y de marca. De un total de 30 pacientes de la unidad de hemodiálisis, 22 expedientes fueron revisados. En general 94% de marca se encontraban disponibles en las farmacias consultadas en comparación a un 52% de los medicamentos genéricos. En farmacias públicas, 41% de medicamentos de marca y 29% de medicamentos genéricos se encontraban disponibles. El costo promedio para un mes de tratamiento con medicamentos de marca adquiridos en una farmacia privada era de $495.00 vs $299.00 en una farmacia pública. Para medicamentos genéricos, el costo promedio correspondía a $414.00 y $239.00 en farmacias privadas y públicas respectivamente. En promedio, los medicamentos de marca adquiridos en una farmacia privada requieren 41 días de trabajo en un mes a comparación de 25 días si se adquieren en una farmacia pública. Los medicamentos genéricos adquiridos en farmacias privadas corresponden a 34 días de trabajo vs 20 días en farmacias públicas. En general existió un acceso limitado a medicamentos genéricos y los medicamentos poseen un costo general más elevado a comparación de otros países lo que implica un posible impacto en la adherencia terapéutica y los padecimientos secundarios de la ERC en los pacientes pediátricos en Guatemala. Esta realidad se puede aplicar a otros países de bajos a medianos ingresos.

This article aims to analyze the availability, access, and affordability of medications for children with advanced Chronic Kidney Disease (CKD) treated with hemodialysis (HD) in a low to middle income country (LMIC). A cross- sectional chart review was carried out to determine the most common medications used in an HD pediatric unit, including medication name, dose, frequency, dosage form, and route of administration. Two pharmacies within the hospital perimeter, one public and one private, were consulted to determine medication cost and availability for generic and brand-name equivalents. From 30 patients attending the HD unit, 22 records were reviewed. Overall, 94 % of brand name medications were available at pharmacies consulted, versus and 52% of generic medications. In public pharmacies, 41% of brand name, and 29% of generic medications were available. The average cost for a full month´s treatment for brand name drugs in the private pharmacy was 495.00 USD versus 299.00 USD in the public pharmacy. For generic drugs, the average cost was 414.00 USD, and 239.00 USD in private and public pharmacies respectively. On average, brand-name drugs in the private pharmacy cost 41 days' wages versus 25 in the public pharmacy. Generic drugs in the private pharmacy cost 34 days' wages versus 20 in the public pharmacy. Overall, there was limited access to generic medications, medications had an overall high cost compared to other countries both of which have the potential to impact treatment adherence and overall outcomes of CKD5 pediatric patients in Guatemala. This reality can be translated to other LMIC.

Effect of the decrease in dialysate sodium in pediatric patients on chronic hemodialysis.

Optimal dialysate sodium (dNa) is unknown, with both higher and lower values suggested in adult studies to improve outcomes. Similar studies in pediatric hemodialysis (HD) population are missing. This is the first report of the effect of two constant dNa concentrations in pediatric patients on chronic HD. 480 standard HD sessions and interdialytic periods were studied in 5 patients (age 4-17 years, weight 20.8-66 kg) during a period of 6-11 months per patient. dNa was 140 mEq/L during the first half, and 138 mEq/L during the second half of the study period for each patient. Lowering dNa was associated with improved preHD hypertension, decreased interdialytic weight gain, decreased need for ultrafiltration, lower sodium gradient and was well tolerated despite lack of concordance with predialysis sNa, that was variable. Further studies are needed to verify our findings and to investigate if an even lower dNa may be more beneficial in the pediatric HD population.

Capillary rarefaction: an early marker of microvascular disease in young hemodialysis patients.

BACKGROUND: Pediatric patients with chronic kidney disease (CKD) are at increased risk of early cardiovascular disease and premature death. Abnormalities in microvascular structure and function may presage end-organ damage including vascular calcification and myocardial ischemia associated with disordered mineral metabolism. Early detection of microvascular rarefaction (reduced density of capillaries) may identify at-risk patients and prompt timely therapeutic interventions. Our objective was to study capillary rarefaction in pediatric hemodialysis (HD) patients and to determine possible associations with mineral metabolism and cardiac risk biomarkers. METHODS: Capillary density (CD) was measured by nailfold capillaroscopy in 19 pediatric HD patients and 20 healthy controls. Demographic and biochemical markers were collected at entry and 6-month follow-up. RESULTS: CD was significantly decreased in HD patients compared with controls with a deficit of 24 and 31% at baseline and subsequent follow-up. Maximal CD correlated significantly with intact parathyroid hormone (iPTH) (r = -0.45; P = 0.005), serum calcium (r = -0.38; P = 0.02) and 25(OH) vitamin D levels (r = +0.36; P = 0.03) in HD patients. Capillary functional measures were similar to controls. By multivariate analysis, the primary negative determinants of CD were African American race and hyperparathyroidism; whereas, glomerular disease had a positive influence on capillary rarefaction (R (2) = 64.2% variance; P = 0.001). CONCLUSION: Pediatric HD patients demonstrate a 'structural deficit' in CD but show preserved 'functional integrity'. Capillary rarefaction, an early risk factor of incipient vascular calcification, was strongly associated with biomarkers of altered mineral metabolism. Further studies are warranted to determine the impact of optimizing blood pressure and metabolic control on changes in capillary rarefaction in young CKD patients.

Comparison of cystatin C and Beta-2-microglobulin kinetics in children on maintenance hemodialysis.

Middle-molecules (MM) are not monitored in children on hemodialysis (HD), but are accumulated and increase the risk of cardiovascular disease and mortality. Molecular properties of Cystatin C (CyC), 13 kDa, potentially make it a preferred MM marker over Beta-2-Microglobulin (B2M), 12 kDa. We compared CyC and B2M kinetics to investigate if CyC can be used as preferred MM marker. CyC (mg/L) and B2M (µg/mL) were measured in 21 low-flux HD sessions in seven children. Blood samples were taken at HD start (pre), 1 and 2 hours into HD and at end of HD (post) for all sessions and 60 minutes after the first HD (Eq). PreCyC (9.85 ± 2.15) did not differ (P > 0.05) from postCyC (10.04 ± 2.83). PostB2M (38.87 ± 7.12) was higher (P < 0.05) than preHD B2M (33.27 ± 7.41). There was no change in CyC at 1 and 2 hours into HD, while B2M progressively increased. CyC or B2M changes did not significantly correlate with spKt/V (2.09 ± 0.86), ultrafiltration (4.61 ± 1.98%) or HD duration (218 ± 20 minutes). EqCyC was not different from postCyC (11.07 ± 3.14 vs. 10.71 ± 2.85, P > 0.05), while EqB2M was lower than postB2M (36.48 ± 7.68 vs. 41.09 ± 8.99, P < 0.05). MMs as represented by B2M and CyC are elevated in children on standard HD. Intensified HD modalities would be needed for their removal. B2M is affected by the dialytic process with a rise during HD independent of ultrafiltration and decrease 1 hour after, while CyC remains unchanged. We suggest that CyC be used as preferred marker of MM removal and as a marker of adequacy of intensified HD regimens.