eGFR values and selected renal urine biomarkers in preterm neonates with uncomplicated clinical course.

BACKGROUND: Diagnosing acute kidney injury (AKI) in preterm newborns, who are particularly susceptible to renal damage, is a serious challenge as there is no definite consensus about the diagnostic criteria. OBJECTIVES: The objective of this study was to measure the values for selected urinary biomarkers and estimated glomerular filtration rate (eGFR) among a population of preterm infants with uncomplicated clinical course as well as to determine whether these markers depend on birth weight (BW), gestational age (GA), postnatal age (PNA), or gender. MATERIAL AND METHODS: The prospective study was carried out in neonatal intensive care unit (NICU). The evaluation included 57 children that were divided into 3 categories according to BW: low birth weight (LBW) - 1501-2500 g (22 infants); very low birth weight (VLBW) - 1000-1500 g (25 infants); and extremely low birth weight (ELBW) - 750-999 g (10 infants). Urine samples were collected daily between the 4th and 28th day of life for measurements of creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and human kidney injury molecule 1 (hKIM1). RESULTS: The values of the 3 urine tubular biomarkers, serum creatinine and eGFR were taken in substantially healthy preterm infants with normal kidney function at 4 time intervals during the neonatal period. Their correlations were determined and a multivariable regression analysis was carried out with respect to BW, GA, PNA, and gender. Trends of the studied markers in terms of PNA and BW were also assessed with the Jonckheere-Terpstra test. CONCLUSIONS: Glomerular and tubular function in preterm neonates during the 1st month of life is significantly influenced by BW, GA, PNA, and gender.

Factors affecting mortality in children requiring continuous renal replacement therapy in pediatric intensive care unit.

BACKGROUND: Acute kidney injury (AKI) occurs in up to 30% of pediatric intensive care unit (PICU) patients and is associated with a high mortality rate. OBJECTIVES: The objective of the study was to evaluate factors associated with the outcome and to identify the prognostic factors in children receiving continuous renal replacement therapy (CRRT). MATERIAL AND METHODS: This was a retrospective, single-center study, including 46 patients. RESULTS: Logistic regression analysis demonstrated significant effects on patient survival exerted by the percentage of fluid overload (FO%) (odds ratio (OR): 1.030; p = 0.044). In the group of patients with FO% < 25%, the mortality was 33.3%, and in the FO% ≥ 25% group, the mortality was 67.9% (p < 0.001). The probability of death without multi-organ failure (MOF) was 13%, while with MOF it was 74%. There was no difference in the duration of hospitalization between the CRRT patients (mean: 21.9 days) and the general population of children hospitalized in PICU in the same period (n = 3,255; mean: 25.4 days); however, a significant difference was noted in mortality between the 2 groups of patients (54% vs 6.5%; p < 0.001). CONCLUSIONS: The mortality of PICU CRRT patients is more than 8-fold higher than the mortality of the total PICU population. Coexisting MOF increases the mortality almost 6 times. The mortality of children with FO% ≥ 25% was more than 2-fold higher than the mortality of children with FO% < 25%.

Filter Size Not the Anticoagulation Method is the Decisive Factor in Continuous Renal Replacement Therapy Circuit Survival.

BACKGROUND/AIM: As continuous renal replacement therapy (CRRT) has emerged as a standard therapy in pediatric intensive care units (PICU), many related issues that may have an impact on circuit survival have gained in importance. Objective of the study was an evaluation of factors associated with circuit survival, including anticoagulation (ACG). METHODS: Retrospective study that included 40 patients, who in total received 7636 hours of CRRT during 150 sessions (84 filters, 4260 hours with heparin anticoagulation (Hep-ACG); 66 filters, 3376 hours with regional citrate anticoagulation (RCA)). RESULTS: The Kaplan-Meier analysis of the total circuit survival time depending on the type of ACG did not demonstrate a significant difference between Hep-ACG and RCA. The percentage of clotted filters was significantly higher in case of smaller filters (HF20: 58.8%; ST60: 29.5%; ST100: 15.8%), and their lifetime was significantly lower regardless of ACG (the mean and median lifetime for HF20: 38.7/27.0 h; for ST60: 54.1/72.0 h., for ST100: 62.1/72.0 h, respectively). CONCLUSIONS: Irrespectively of filter size, filter clotting occurs within the first 24 hours after the initiation of CRRT. Most commonly, clotting affects small filters, and their lifetime is significantly shorter as compared to larger filters regardless of the type of the ACG.

Reference ranges and impact of selected confounders on classic serum and urinary renal markers in neonatal period.

PURPOSE: Renal injury in term and pre-term neonates may be an antecedent to chronic kidney disease in the child's further life. The aim of the paper was to compile a reference range for selected serum and urinary renal markers in the neonatal period for full-term (FT) and pre-term (PT) newborns. MATERIAL AND METHODS: The prospective study included 23 FT infants (birth weight - BW≥2500g and gestational age - GA≥37Hbd) and 32 PT children (BW<2500g and GA<37Hbd) in good general condition, without acute kidney injury (AKI) or sepsis. Between the 4th and 28th DOL, urinary concentrations of the studied renal markers (uCr, uNa, uOsm) were determined on a daily basis, while serum creatinine (SCr) was assessed minimum every 48-72h. RESULTS: The mean GA and BW of the FT and PT infants were respectively as follows: 38.5±1.7Hbd; 3433±495.2g and 32.7±2.6Hbd; 1836.7±419.8g. For serum glomerular (SCr, eGFR) and tubular markers (FENa, RFI), the median values with normal ranges were compiled. For urinary renal markers (uCr, uNa, uOsm) and those values standardized for kg of body weight, percentile tables for 4-28DOL were elaborated. CONCLUSIONS: The study has resulted in determining the normal ranges of serum glomerular and tubular renal markers, as well as percentile tables of selected urinary renal parameters during the neonatal period. The percentile tables may prove to be helpful for further standardization of other urinary parameters per urinary creatinine in neonatal population.

Can We Further Improve the Quality of Nephro-Urological Care in Children with Myelomeningocele?

Myelomeningocele (MMC) results from a failure of normal neural tube fusion in early fetal development. Retrospective, observational study of medical data of 54 children treated in Pediatric Nephrology and Urology Clinics for five years was performed. The following data were analyzed: serum creatinine, eGFR, urine analysis, renal scintigraphy (RS), renal ultrasound, and urodynamics. Mean age of studied population: 12.3 years, median of eGFR at the beginning and at the end of survey was 110.25 and 116.5 mL/min/1.73 m² accordingly. Median of frequency of urinary tract infections (fUTI): 1.2 episodes/year. In 24 children: low-pressure, in 30 children: high-pressure bladder was noted. Vesicouretral reflux (VUR) was noted in 23 children (42.6%). fUTI were more common in high-grade VUR group. High-grade VURs were more common in group of patients with severe renal damage. At the end of the survey 11.1% children were qualified to higher stages of chronic kidney disease. Renal parenchyma damage progression in RS was noted in 22.2% children. Positive VUR history, febrile recurrent UTIs, bladder wall trabeculation, and older age of the patients constitute risk factors of abnormal renal scans. More than 2.0 febrile, symptomatic UTIs annually increase by 5.6-fold the risk of severe renal parenchyma damage after five years.

Modification of the Schwartz equations for children increases their accuracy at eGFR > 60 mL/min/1.73 m(2).

AIM: Estimation of eGFR in children with normal kidney function using the Schwartz equations results in underestimating real GFR. MATERIALS AND METHODS: We propose modification of three Schwartz equations - two based on creatinine concentration (eGFRScrBS bedside) and (eGFRScr) and one 3-marker based on creatinine, urea and cystatin C concentrations (eGFRS3M). The iohexol test (reference method) was performed 417 times in 353 children >2 years with mean GFR: 98 ± 31.6 ml/min/1.73m(2). The assessment included also the Filler and Zappitelli equations. The modification was performed using methods: (1) based on equation, eGFRcor = a [eGFR - T] + T, where T = 50, if eGFR > T, and a equals for: eGFRScrBS 1.4043, for eGFRScr 2.0048, for eGFRS3M 1.2951, and (2) based on correction of all coefficients of the original equation. RESULTS: For comparison of all the results and for children with GFR< 60, 60-90, 90-135 and > 135 ml/min/1.73m(2) the correlation coefficient, relative error (RE) and root mean square relative error (RMSRE) was employed and revealed improvement of RE from 25.9 to 6.8 and 3.9% (depending on the correction method) for eGFRScr; from 19 to 8.1 and 3.9% for eGFRScrBS and: from 11.6% to 2.0 and 2.3% for eGFRS3M (respectively). The RMSRE values changed from 30 to 21.3 and 19.8% for eGFRScr, from 25.1 to 21.6 and 19.8% for eGFRScrBS and from 19.1 to 15.8 and 15.3 % for eGFRS3M. CONCLUSIONS: Modifications of Schwartz equations at GFR > 60 ml/min/1.73m(2) significantly improves the accuracy of calculating eGFR. The 3-markers equation is more accurate and should be employed frequently.

Which equations should and which should not be employed in calculating eGFR in children?

PURPOSE: We assessed the reliability of calculating eGFR in children as compared to the iohexol disappearance test (GFR-I), which was performed 417 times in 353 children aged 2 and more. MATERIAL/METHODS: eGFR was estimated with equations based on serum creatinine: Schwartz (1: eGFR-Scr), Cockroft-Gault (2: eGFR-CG) and MDRD (3: eGFR-MDRD), and on creatinine clearance (4: eGFR-U), or relying on serum cystatin C: Hoeck (5: eGFR-H), Bokenkamp (6: eGFR-B) and Filler (7: eGFR-F), and on the three Schwartz markers (8: eGFR-S3M). Mean relative error (RE), correlation (R), Bland-Altman analysis and accuracy of GFR-I were studied in all patients and in subgroups: at GFR<60ml/min/1.73m(2); in children aged ≤12 and >12. RESULTS: The results by eGFR-Scr, eGFR-S3M demonstrated no statistical difference to GFR-I at GFR<60ml/min/1.73m(2), but underestimated eGFR at higher filtration values by 11.6±15.1% and 19.1±16.4, respectively (p<0.0000). The eGFR-B, eGFR-F and eGFR-MDRD equations illustrated important overestimation of reference GFR results (RE: 84±44.2%; 29.5±27.9%, 35.6±62%; p<0.0000 for all). The MDRD and C-G formulas showed statistically better consistency in children aged >12. A good agreement was achieved by the eGFR-H equation (5.1±21.9%; p<0.0000; R=0.78). CONCLUSIONS: (1) Schwartz equations show a good conformity at GFR<60ml/min/1.73m(2), but underestimate the results at higher GFR values. (2) The Bokenkamp equation with original coefficient should not be employed in children. (3) The use of the Hoeck formula in all children and C-G and MDRD formula in children aged >12 is possible. (4) The error of eGFR calculations increases at higher GFR values.

Acute kidney injury in a single pediatric intensive care unit in Poland: a retrospective study.

BACKGROUND/AIMS: The recent improvements of management of patients in pediatric intensive care units (PICU) are associated with improved outcome. However, this decrease in mortality is associated with an increased number of children with acute kidney injury (AKI), especially in patients with multiorgan failure. METHODS: The report presents a retrospective analysis of 25 cases of AKI (assessed based on the pRIFLE criteria) in PICU within 7 years. RESULTS: AKI was diagnosed in 1.24% of all hospitalized children. AKI percentage duration (as compared to the total hospitalization time) in the children who died vs. the survivors was 79.55% vs. 46.19%, respectively (p<0.05). The mortality rate of AKI patients was 40% which was 4.4-times higher as compared to the total mortality rate in PICU. The final cumulative survival ratio (FCSR) of patients meeting the oliguria criterion (which was met in 48% of AKI patients) was 37% vs. 49% in non-oliguric children. Averaged urine output values in the first week of hospitalization in the deceased vs. survivors were 1.49 vs. 2.57 ml/kg/h, respectively (p<0.05). CONCLUSIONS: Oliguria should not be considered as a sensitive parameter for AKI diagnosing in children below one year of age. A decreased mean urine output in the first week of PICU hospitalization (less than 1.4 ml/kg/h) should be considered as a poor prognostic factor. In many cases AKI was diagnosed too infrequently and too late.

Analytical solution of multicompartment solute kinetics for hemodialysis.

Objective. To provide an exact solution for variable-volume multicompartment kinetic models with linear volume change, and to apply this solution to a 4-compartment diffusion-adjusted regional blood flow model for both urea and creatinine kinetics in hemodialysis. Methods. A matrix-based approach applicable to linear models encompassing any number of compartments is presented. The procedure requires the inversion of a square matrix and the computation of its eigenvalues λ , assuming they are all distinct. This novel approach bypasses the evaluation of the definite integral to solve the inhomogeneous ordinary differential equation. Results. For urea two out of four eigenvalues describing the changes of concentrations in time are about 10(5) times larger than the other eigenvalues indicating that the 4-compartment model essentially reduces to the 2-compartment regional blood flow model. In case of creatinine, however, the distribution of eigenvalues is more balanced (a factor of 10(2) between the largest and the smallest eigenvalue) indicating that all four compartments contribute to creatinine kinetics in hemodialysis. Interpretation. Apart from providing an exact analytic solution for practical applications such as the identification of relevant model and treatment parameters, the matrix-based approach reveals characteristic details on model symmetry and complexity for different solutes.

Serum interleukin 6 levels as an early marker of acute kidney injury on children after cardiac surgery.

BACKGROUND: Cardiosurgical operations in cardiopulmonary bypass (CPB) constitute a risk of acute kidney injury (AKI). OBJECTIVES: The aim of the study was an assessment of AKI risk in children within the first 24 hours after CPB cardiac surgery, evaluating serum interleukin 6 (sIL6). MATERIAL AND METHODS: The study included 47 children with congenital heart disease operated in CPB. Blood samples were taken before the procedure (0 hour) as well as at 2, 6, 12, 18 and 24 hours after the operation. RESULTS: AKI was confirmed in 19 children. The mean sIL6 concentration in the AKI compared with non-AKI group was: 180.6 vs. 93.7; p = 0.0017. The maximum sIL6 in the AKI group was obtained at 2 hrs after CPB (350.36 pg/ml). Logistic regression analysis for AKI development depending on the value of sIL6 at 2 hrs after CPB proved that every rise of sIL6 by 100 pg/ml increased the chance of AKI development by 70% (p = 0.0161). With every circulatory arrest time prolongation by 10 minutes for a given sIL6 concentration, the chance of AKI development increased by 47% (p = 0.0407). AKI risk at 2 hrs after CPB, for a sIL6 cut-off point amounting to 185 pg/ml, increased more than 3-fold (AUROC - 68%). CONCLUSIONS: Determining sIL6 in children after cardiosurgical operations at 2 hrs after the procedure constitutes a good, yet not a perfect marker of AKI risk development. Nomograms of the constant risk values of AKI were worked out presenting the ranges of values in relation to serum IL6 concentrations and the child's body mass, age and the time of circulatory arrest.

[Early markers of acute kidney injury in newborns]. / Wczesne markery ostrego uszkodzenia nerek w okresie noworodkowym.

The incidence of acute kidney injury (AKI) at neonatal intensive care units (NICU) is estimated as 6-24%. Traditional AKI markers i.e. serum creatinine (SCr) concentration, fractional sodium exertion, urine sodium concentration and renal failure index--are low sensitivity and low specificity markers but beside remain very late ones. Serum creatinine concentration arises 48 hours after renal tissue damage. The paper presents contemporary knowledge concerning concentration reference ranges of some early AKI biomarkers (NGAL, hKIM1, OPN, IL18)--either in term or preterm newborns. The most current reports about chosen AKI biomarkers in newborns with uncomplicated clinical course and in children with AKI within the course of sepsis or after cardiopulmonary bypass surgery--were discussed. Disposing of the reliable clinical data referring to early AKI biomarkers constitutes a valuable aid for clinicians who having got to know about the actual risk possess the time for proper clinical interventions.

Relationship between kinetics of albumin-bound bilirubin and water-soluble urea in extracorporeal blood purification.

BACKGROUND: The purpose of the study was to examine the relationship between urea and conjugated bilirubin kinetics during extracorporeal liver support (ELS) therapy and to determine the dose of therapy for urea and conjugated bilirubin as markers for water-soluble and protein-bound solutes, respectively. METHODS: Kinetics of urea and bilirubin were described by standard two-compartment models with central clearance, constant intercompartment clearance, constant generation rate and constant volume. While the concentration of urea was assumed as equilibrated between compartments at the beginning of ELS therapy, the concentration of conjugated bilirubin between compartments was assumed to follow the partition of albumin between plasma and interstitial spaces. Treatment dose was calculated as removed solute mass and fractional solute removal. RESULTS: Seven patients were studied during 15 treatments lasting at least 6 h. Bilirubin distribution volume of 14.8 ± 5.4 L was not different from urea extracellular water volume of 15.0 ± 2.8 L. The correspondence between models was used to predict the mass of bilirubin removed based on extracellular volume obtained from urea kinetics, average data from bilirubin kinetics, as well as selected treatment and patient information. The prediction of bilirubin mass removed based on this reduced information was not different from the mass of solute removed based on complete bilirubin kinetic analysis. CONCLUSIONS: The correspondence between kinetics of urea and conjugated bilirubin can be used to identify the bilirubin distribution volume from urea kinetic analysis. This information is then useful to estimate and predict the solute removal of conjugated bilirubin in ELS.

Correlation between fat mass and blood pressure in healthy children.

Obesity is a well-known risk factor for arterial hypertension. The aim of this study was to analyze which surrogate marker of adiposity, i.e., body mass index (BMI) or fat mass (FM), as measured by bioimpedance analysis (BIA), best correlated with blood pressure in healthy children. Body weight, height, and casual blood pressure (BP) were measured in 193 healthy children (103 boys), aged 8-16 years. Body composition was determined by BIA. The correlation between BMI and age was linear, whereas the correlation between percentage of FM and age was nonlinear and it was different in boys and girls. Blood pressure standard deviation scores (SDS) correlated with FM SDS (BIA) over the entire normal range (systolic: r = 0.26, p = 0.002; diastolic: r = 0.33, p < 0.01). An evaluation of the children based on BP (three groups: BP < 50th percentile, 50th < BP > 95th percentile; BP > 95th percentile) revealed that hypertensive children had a higher BMI (17.6 vs. 19.4 vs. 26.2 kg/m(2), respectively) and a greater FM (14.0 vs. 16.8 vs. 30.2%, respectively). In conclusion, the divergence in FM in healthy boys and girls can be determined by BIA but not by BMI. In healthy children, BP within the entire normal range correlated with FM, children with established hypertension presented with a significantly higher FM. The study points to FM as an important determinant of BP pressure in obese and non-obese children.

[GFR estimation based upon cystatin C concentration as a substance marker--proposal of a new formula]. / Wyznaczanie GFR na podstawie stezenia cystatyny C jako substancji markerowej--propozycja nowego wzoru.

Glomerular filtration rate (GFR) estimation is very important for evaluation of kidney function. Its calculation is based upon a 24 hour urine collection and serum creatinine concentration values or on the basis of developed for this purpose numerous formulas with special attention dedicated to the abbreviated MDRD formula and Cockcroft-Gault formulas for adults and Schwartz et al. and Counahan et al. formulas for children. Future expectations are related to GFR estimation based on serum cystatin C concentration and formulas specially developed for this cause. The aim of the study was the comparative analysis of GFR results based on Filler's and Lapage's, Grubb's et al. and Schwartz's et al. formulas and reference values obtained in 93 patients after measuring iohexol concentration after its single injection. Significant differences between the results obtained from employed formulas for high, as well as for low values of GFR were shown, respectively. Serial calculations were performed allowing to finding out a new prescription for GFR calculation. A new formula for GFR calculation based on cystatin C concentration: GFR = -7.28+82.29 x C(-1) was proposed.

[Body mass index (BMI) or bioimpedance analysis (BIA) --which method enables a better assessment of fat mass in children?]. / Wskaznik masy ciala (BMI) czy analiza bioimpedancji elektrycznej (BIA)--która metoda pozwala lepiej ocenic zawartosc tkanki tluszczowej u dzieci?

A comparison of accuracy between electrical bioimpedance analysis (BIA) and body mass index (BMI) for fat mass evaluation in children was the aim of the study. One-hundred and ninety three healthy children (90 females, 103 males) were enrolled. The mean age of the studied population was 11.8 years (+/- 2.2), mean weight equalled to 42.6 (+/- 12.8) kg and mean height-151.1 (+/- 13.5) cm. BIA measurments were performed by multifrequency (1; 5; 50; 100 kHz) BIA 2000M analyzer using BIANOSTIC electrods. Calculations of free fat mass and fat mass were performed using Nutri 4 Data Input Software (Germany). The LMS method for percentile charts of FFM and FM acording to height has been applied and results for boys and girls were drawn separatelly. Percentile charts of FM and BMI were compared. Different shape of curves of FM content and BMI for boys during puberty was noticed. BIA allows for precise fat mass content evaluation in children and its use should be disseminated.

[Does daily hemodialysis influence urea kinetic modeling (UKM) coefficients?--Preliminary report]. / Czy hemodializa codzienna wplywa na zmiane wspólczynników modelowania kinetycznego dializy?--Doniesienie wstepne.

Large number of data shows beneficial effects of implementing daily hemodialysis (DH) upon the outcome in patients dialysed previously in 3 times a week hemodialysis (3H) schedule. The mechanisms responsible for this phenomenon are still unclear, despite the time of low-flux DH sessions is shortened almost by half. Evaluation of the effect of doubling the number of hemodialyses per week upon so called cellular clearance (intercompartmental diffusion coefficient, Kc) computed in 2 pool-model was main aim of this study. 6 chronically dialysed patients (previously 3x per week) were subjected to DH. Based upon output data from UKM and weekly KT/V, the time for each DH session was computed, with no change in Kd (dialyser clearance). Kc was estimated from double-pool volume variable model equations and rebound. By the use of almost similar dialyser clearances in 16 conventional and 29 DH modeling sessions, estimated Kc values had been found non significantly higher in DH: (323.16; S.D. 187.86 vs. 268.80; S.D. 104.09 ml/min; p=0,68). Mean ultrafiltration/pre-dialysis body weight ratio (UFR/BW1) was 4,97 (S.D. 2.27)% in conventional hemodialysis and 3.66 (S.D. 1.46)% in DH. Mean dialysis index Kt/V values had decreased in DH (0.79; S.D. 0.17, vs. 1,34 (S.D. 0.26). Mean UFR/W1 ratio correlated negatively with Kc either in conventional or in DH (r=-0.653; p = 0.006 and r=-0.552; p=0.0036, respectively). Statistically significant negative correlation between Kt/V and Kc was found only in DH subjects (r=-0.466, p =0.010). The authors concluded, that increased Kc observed in patients subjected to DH may be responsible for better dialysis efficacy in patients switched into this treatment modality.

[New measurement techniques in biology and medicine: atomic force microscopy (part III)]. / Nowe techniki pomiarowe w biologii i medycynie: mikroskopia sit atomowych (czesc III).

Biological samples can be investigated with atomic force microscopy (AFM) in either of two imaging modes: contact mode or tapping mode. Applications of fluid tapping mode AFM in biology and medical sciences are constantly growing and the data obtained with this technique are improving, especially in terms of resolution. Even dynamic processes can be observed almost as they would occur in vivo. AFM is a proven imaging technique that has recently gained attention in biomaterials due to its ability to analyze surface properties, non-destructively at nanometer-level resolution in ambient air or in fluid environments.