Methods of assessing renal function.

Accurate assessment of renal function is critical for appropriate drug dosing of renally excreted compounds. Glomerular filtration rate (GFR) is considered the best marker of kidney function. Inulin clearance forms the gold standard for measuring GFR, both in adults and in children. The method is invasive, cumbersome, and smaller children require urinary catheterization for accurate timed urine collections. Nuclear medicine methods replaced inulin clearance in the 1970s after (51)Cr EDTA clearance was introduced. Inulin has no plasma protein binding, whereas all commonly used radioisotopes have a small amount of plasma protein binding that leads to lower values. Only iohexol does not have significant plasma protein binding. The underestimation due to plasma protein binding is partially offset by overestimation due to the use of non-compartmental pharmacokinetic modeling of the plasma disappearance of the radioisotope. The problem could be overcome with a urinary nuclear medicine clearance method, but these have not been validated in children. Endogenous markers of GFR include serum creatinine and low molecular weight proteins such as cystatin C and beta-trace protein. Of these, estimation of GFR using cystatin C appears to be the most promising, although its accuracy in pregnancy and in the neonatal period may be limited.

Evaluating Canadian children: WHO, NHANES or what?

AIM: The 2006 World Health Organization (WHO) growth charts have been widely adopted by Canadian dieticians for growth monitoring of Canadian children rather than the National Health and Nutrition Examination Survey (NHANES III) reference data. It has been unclear as to which is the most appropriate. METHODS: We calculated height and weight z-scores of 3086 consecutive patients (1530 female, 49.6%) aged 0-5 years, attending outpatient clinics at a single tertiary care centre using reference data of the latest NHANES survey and the 2006 WHO growth charts. To address age dependency, data were stratified into age groups. Gender dependency was also investigated. RESULTS: Using NHANES III reference intervals, medians of both height z-score (+0.24) and weight z-score (+0.32) were significantly non-zero. The WHO growth charts yielded medians of height z-score (-0.15) and weight z-score (+0.36) respectively, also significantly non-zero. When comparing both reference populations for the entire cohort, Canadian children had significantly different height z-scores whereas weight z-scores did not differ. Age classification revealed a significant age dependency with NHANES III charts yielding higher weight z-scores for up to 8 months and lower z-scores from 8 to 26 months. No significant differences were observed for older than 26 months. Throughout, height z-scores were significantly higher with NHANES III charts across all age groups, with a degree of overestimation higher in younger boys than older ones. CONCLUSION: Our results reveal substantial differences between both reference populations and thus interpretation needs to be done with caution, especially when labelling results as abnormal.

Fibroblast growth factor-23 and calcium phosphate product in young chronic kidney disease patients: a cross-sectional study.

BACKGROUND: Fibroblast growth factor-23 (FGF-23), a novel marker of bone disease in chronic kidney disease (CKD) has been shown to correlate with vascular calcifications. We aimed to describe the effect of the calcium phosphate product (Ca*P) on FGF-23 concentrations in children and young adults without confounding cardiovascular disease. METHODS: Pediatric and young adult patients with CKD stages I-V were recruited in this cross sectional study to measure FGF-23, cystatin C, vitamin D-metabolites and other serum markers of bone metabolism. FGF-23 levels were determined with an enzyme-linked immunosorbent assay. The association between FGF-23 and (Ca*P) was assessed using non-parametric methods. Patients were divided into two age groups, less than 13 years of age and greater than 13 years of age. RESULTS: This cross-sectional study measured serum FGF-23, in 81 patients (42 females, 51.9%) at London Health Sciences Centre, aged 2 to 25 years, with various stages of CKD (Cystatin C estimated glomerular filtration rate, eGFR=10.7-213.0 ml/min). For the whole entire group of patients, FGF-23 levels were found to correlate significantly with age (Spearman r= 0.26, p=0.0198), Cystatin C eGFR (Spearman r=-0.40 p=0.0002), CKD stage (Spearman r=0.457, p<0.0001), PTH (Spearman r=0.330, p=0.0039), ionized calcium (Spearman r=-0.330, p=0.0049), CysC (Spearman r= 0.404, p=0.0002) and 1,25-dihydroxyvitamin D (Spearman r=-0.345, p=0.0034) concentrations. No significant correlation was found between FGF-23 levels and calcium phosphate product (Spearman r= 0.164, p=0.142). Upon classification of patients into two age groups, less than 13 years of age and more than 13 years of age, correlational results differed significantly. FGF-23 correlated with CysC eGFR( Spearman r= -0.633, p<0.0001), CKD stage (Spearman r=0.731, p<0.0001), phosphate (Spearman r= 0.557, p<0.0001), calcium phosphate product (Spearman r=0.534, p<0.0001), 125(OH)2 Vit D (Spearman r=-0.631, p<0.0001), PTH (Spearman r= 0.475, p=0.0017) and ionized calcium (Spearman r= -0.503, p=0.0015) only in the older group. The relationship between FGF-23 and Ca*P for the older group could be expressed by the exponential model FGF-23= 38.15 e0.4625Ca*P. CONCLUSION: Abnormal values of FGF-23 in adolescents and young adults with CKD correlate with Ca* P in the absence of vascular calcifications, and may serve as a biomarker for the risk of cardiovascular calcifications.

The usefulness of cystatin C and related formulae in pediatrics.

Serum creatinine does not share the properties of an ideal marker of glomerular filtration rate (GFR) like inulin, but continues to be the most widely used endogenous marker of GFR. In the search of a better biomarker of GFR, the small molecular weight protein cystatin C has been introduced with features more similar to that of inulin, such as constant production and no non-renal elimination. However,it has not enjoyed widespread use despite its significantly improved diagnostic performance in the detection of impaired GFR and its independence of body composition. A variety of formulae based on either cystatin C or creatinine or both have been developed to estimate GFR. We summarize the currently used methods of GFR measurement, their limitations and analytical errors. The review also summarizes the history, features and the feasibility of cystatin C measurements as well as the most widely used formulae for the estimation of GFR in children. The diagnostic performance of the cystatin C derived eGFR formulae at various levels of GFR is also discussed. An eGFR formula derived from pooled studies analyzing both creatinine and cystatin C, and using a biology-based mathematical approach maybe advantageous.

Are Canadian pediatric nephrology patients really overweight?

AIMS: To assess the influence of height age and short stature on BMI z-scores in children with chronic kidney disease (CKD) in view of the pandemic increase of childhood obesity. MATERIALS: Pediatric nephrology patients older than 2 years of age from 2 tertiary centers in Ontario and age- and gender matched controls from a local reference population. METHODS: We estimated height, weight and body mass index (BMI) z-scores of 705 nephrology patients (319 female) and 4,196 controls aged 2.01 - 19.92 years with chronological and height-adjusted age (corresponding age for a given height plotted on the 50th percentile). The National Health and Nutrition Examination Survey (NHANES III) was used for the z-score Estimation. RESULTS: Chronological age-based patient weight z-scores were significantly heavier than in the NHANES data (median weight z-score +0.29, BMI z-score +0.51; significantly non-zero), not significantly different from height-adjusted age-based BMI z-score (+0.51). The children with kidney problems were shorter (-0.10 SD) than controls. CONCLUSION: The proportion of overweight nephrology patients was similar to matched controls and BMI z-score diminished with worsening GFR.

High prevalence of elevated lead levels in pediatric dialysis patients.

BACKGROUND: After parents raised concerns about potential lead (Pb) contamination of calcium carbonate for treatment of hyperphosphatemia in chronic kidney disease (CKD), we measured blood Pb using high-resolution sector field inductively coupled mass spectrometry in a quality-assurance investigation of ten pediatric dialysis patients (nine on hemodialysis) and six patients before dialysis. METHODS: We assessed the kidney function as cystatin C estimated glomerular filtration rate (eGFR), blood Pb levels, calcium carbonate dose, and standard laboratory parameters, as well as Pb levels in the dialysis feed water. RESULTS: Mean blood Pb concentration in the 16 pediatric CKD patients was 21.1 ± 15.8 µg/l with a maximum of 58 µg/l, which was significantly higher than that of 467 apparently healthy controls (median 6.35 µg/l, interquartile range 4.47, 8.71) and comparable to that of ten adult peritoneal dialysis (PD) patients. Lead levels correlated with red blood cell distribution width, eGFR, and calcium carbonate dose. Pb in dialysate feed water was always <0.00018 mg/l, which is below the accepted limit for water for dialysis of 0.005 mg/l. CONCLUSIONS: We found a high prevalence of elevated Pb levels in pediatric CKD patients that correlated with the calcium carbonate dose and GFR. Lead levels should be monitored in these patients.

Ontario children have outgrown the Broselow tape.

OBJECTIVE: The Broselow Pediatric Emergency Tape (Armstrong Medical Industries, Inc., Lincolnshire, IL) (BT) is a well-established length-based tool for estimation of body weight for children during resuscitation. In view of pandemic childhood obesity, the BT may no longer accurately estimate weight. We therefore studied the BT in children from Ontario in a large recent patient cohort. METHODS: Actual height and weight were obtained from an urban and a rural setting. Children were prospectively recruited between April 2007 and July 2008 from the emergency department and outpatient clinics at the London Health Science Centre. Rural children from junior kindergarten to grade 4 were also recruited in the spring of 2008 from the Avon Maitland District School Board. Data for preschool children were obtained from three daycare centres and the electronic medical record from the Maitland Valley Medical Centre. The predicted weight from the BT was compared to the actual weight using Spearman rank correlation; agreement and percent error (PE) were also calculated. RESULTS: A total of 6,361 children (46.2% female) were included in the study. The median age was 3.9 years (interquartile range [IQR] 1.56-7.67 years), weight was 17.2 kg (IQR 11.6-25.4 kg), and height was 103.5 cm (IQR 82-124.4 cm). Although the BT weight estimate correlated with the actual weight (r  =  0.95577, p < 0.0001), the BT underestimated the actual weight by 1.62 kg (7.1% ± 16.9% SD, 95% CI -26.0-40.2). The BT had an ≥ 10% PE 43.7% of the time. CONCLUSIONS: Although the BT remains an effective method for estimating pediatric weight, it was not accurate and tended to underestimate the weight of Ontario children. Until more accurate measurement tools for emergency departments are developed, physicians should be aware of this discrepancy.

Growth differentiation factor 15: an additional diagnostic tool for the risk stratification of developing heart failure in patients with operated congenital heart defects?

BACKGROUND: Many young adults who have congenital heart defects develop heart failure despite corrective surgeries. Growth differentiation factor 15 (GDF-15) has an established role as a marker for risk stratification and mortality both in patients after acute myocardial infarction and in patients with heart failure. Our aim was to establish a role for GDF-15 for monitoring heart failure in operated congenital heart defects (ACHD). This potential biomarker was validated through comparison with maximal oxygen uptake (VO(2max)) and to another biomarker, N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS: A total of 317 ACHD patients (129 females) with an average age of 26.5 ± 8.5 years (mean ± SD) enrolled in the study. We studied the relation between GDF-15 and NT-proBNP and VO(2max%) (percent predicted for age and gender). The cutoffs for the groups were as follows: NT-proBNP <100, 100 to 300, and >300 pg/mL; VO(2max%) <65%, 65% to 85%, and >85% of predicted normal. RESULTS: Significant differences in mean GDF-15 levels were found between the NT-proBNP <100 and NT-proBNP >300 groups, as well as between the 100 to 300 and the >300 groups. For VO(2max%), significant differences were found in GDF-15 levels between <65% and >85% and between <65% and 65% to 85%, respectively. The lowest mean GDF-15 was found in groups with NT-proBNP <100 pg/mL and VO(2max%) >85%. The highest mean GDF-15 was found in the groups with NT-proBNP >300 pg/mL and VO(2max%) <65%. A subgroup analysis, including 82 patients with operated tetralogy of Fallot, showed that patients in the New York Heart Association I class have significantly lower NT-proBNP and GDF-15 level and markedly higher VO(2max) compared with the patients in higher New York Heart Association class. CONCLUSION: Growth differentiation factor 15 might be used as a surrogate marker for latent heart failure and could help to identify patients with ACHD who are at risk for developing heart failure, even if they are clinically asymptomatic.

Preliminary reference intervals for cystatin C and beta-trace protein in preterm and term neonates.

OBJECTIVE: To determine the reference intervals for serum cystatin C (CysC) and beta-trace protein (BTP) as markers of renal function in preterm and term neonates. DESIGN AND METHODS: Blood samples of 128 neonates (34% female) admitted to the NICU were analyzed to determine the levels of serum creatinine (enzymatically), CysC and BTP (nephelometric, Siemens Health Care). RESULTS: The reference intervals, categorized by age, were reported for the 128 neonates. Median (lower/upper limit) BTP were 1.85 (0.57/3.16) and 1.27 (0.51/2.07) mg/L on days 1 and 3. In keeping with maturation of renal function after birth, CysC and BTP fell from days one to day three after birth, whereas creatinine did not. CONCLUSION: Our data provides reference intervals for the levels of creatinine, CysC, and BTP in neonates on days 1 and 3 after birth and demonstrates that CysC and BTP reflect neonatal renal function, whereas creatinine reflects maternal renal function.

Diagnostic accuracy of cystatin C-based eGFR equations at different GFR levels in children.

BACKGROUND AND OBJECTIVES: The diagnostic accuracy of cystatin C estimated GFR (eGFR) by various cystatin C equations have varied in different studies. We hypothesized that the GFR level of enrolled patients affects the diagnostic accuracy of a cystatin C equation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed 240 consecutively enrolled children at a single Canadian center in a prospective and cross-sectional study. Cystatin C was analyzed with nephelometry, and cystatin C eGFR was estimated by the equations validated in children. GFR was measured by technetium-99m-diethylene-triamine penta-acetic acid (99m)Tc DTPA). RESULTS: We compared various cystatin C equations across GFR strata < 60, < 90, ≥ 135, and ≥ 150 ml/min per 1.73 m² for an accurate prediction and appropriate classification of the measured GFR. The CKiD, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a higher accuracy, estimated by eGFR values within 10% and 30% of the respective (99m)Tc DTPA, in the GFR categories < 60 and < 90 ml/min per 1.73 m², whereas the Bökenkamp, Bouvet, and Filler equations had a greater accuracy in the GFR categories ≥ 135 and ≥ 150 ml/min per 1.73 m². The Bouvet, CKiD, Filler, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a greater sensitivity to classify GFR < 60 and < 90 ml/min per 1.73 m², whereas the Bökenkamp equation had a higher sensitivity for GFR ≥ 135 and ≥ 150 ml/min per 1.73 m². CONCLUSIONS: The diagnostic accuracy of various cystatin C equations varies with GFR. This issue needs consideration while applying these equations in clinical practice and for further research on eGFR equations.

Big mother or small baby: which predicts hypertension?

According to the Barker hypothesis, intrauterine growth restriction and premature delivery adversely affect cardiovascular health in adult life. The association of childhood hypertension as a cardiovascular risk factor and birth weight has been understudied. In a prospective cohort study, the authors evaluated the effect of birth weight, gestational age, maternal prepregnancy body mass index (BMI), and child BMI z score at the time of enrollment on the systolic and diastolic blood pressure (BP) z score in 3024 (1373 women) consecutive outpatient clinic patients aged 2.05 to 18.58 years. The latest National Health and Nutrition Examination Survey (NHANES III) was used to calculate the age-dependent z scores. The median z scores of BMI (+0.48, range -6.96-6.64), systolic BP (+0.41, range -4.50-6.73), and diastolic BP (+0.34, range -3.15-+6.73) were all significantly greater than the NHANES III reference population. Systolic BP z score did not correlate with birth weight or gestational age, but did correlate with maternal prepregnancy BMI (r=.090, P<.0001) and BMI z score (r=.209, P<.0001). Diastolic BP z score positively correlated with birth weight (0.037, P=.044), gestational age (r=.052, P=.005), BMI z score(r=.106, P<.0001), and maternal prepregnancy BMI (r=.062, P=.0007). In contrast to what would be expected from the Barker hypothesis, the authors found no negative correlation between BP z score and birth weight or gestational age. This study suggests that a high BMI, a big mom, and a high birth weight are more important risk factors for hypertension during childhood than low birth weight or gestational age.

Hyperfiltration affects accuracy of creatinine eGFR measurement.

BACKGROUND AND OBJECTIVES: Surrogate markers such as creatinine, cystatin C (CysC), and beta trace protein (BTP) have been used to estimate GFR (eGFR). The accuracy of eGFR may be altered with hyperfiltration and differences in filtration fraction (FF). It is hypothesized that the accuracy of creatinine for eGFR may be affected by hyperfiltration and different effective renal plasma flow (ERPF). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 127 pediatric patients with various renal diseases underwent simultaneous measurements of GFR using 51Cr-EDTA renal scan and ERPF (131I-hippurate clearance) to calculate the FF (FF=GFR/ERPF). The eGFRs were calculated using the commonly used Schwartz (creatinine), Filler (CysC), and Benlamri (BTP) formulas. Agreement of the eGFRs with the measured isotope GFRs was assessed by Bland-Altman plots. Correlation analysis was performed using nonparametric tests to compare FF with eGFR-GFR. RESULTS: The 127 children at a median age (with 25th percentile, 75th percentile) of 11.9 (8.5, 14.9) years had a mean 51Cr EDTA-GFR of 100.6±32.1 ml/min per 1.73 m2 and a median 131I-hippurate clearance (ERPF) of 588 (398,739) ml/min per 1.73 m2. Mean FF was 17.7±4.5% with no correlation between the FF and the error (eGFR-GFR) for CysC and BTP eGFR, whereas there was a significant negative correlation between the error for Schwartz eGFR and FF. CONCLUSIONS: There is a significant negative correlation between the error for the Schwartz eGFR and the FF. CysC and BTP are not affected by differences in FF.

Cystatin C reduction ratio depends on normalized blood liters processed and fluid removal during hemodialysis.

BACKGROUND AND OBJECTIVES: A negative correlation between the weekly standard Kt/V (urea) and serum cystatin C level (CysC) in functionally anephric dialysis patients has been previously demonstrated. Our objective was to measure the per dialysis CysC reduction ratio (CCRR) and to compare it with other indices of dialytic functions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a pilot cross-sectional study of 15 functionally anephric patients on conventional high-flux high-efficiency hemodialysis three times per week, CysC levels were drawn pre-, mid-, and postdialysis over 1 week. CCRR was compared with single-pool Kt/V (Sp Kt/V) using urea kinetic modeling, urea reduction ratio (URR), creatinine reduction ratio (CRR), normalized liters processed (LP/kg), and ultrafiltration volume (UF). Normally distributed data (Shapiro-Wilks test) were described as mean±SD, otherwise as median and interquartile range. RESULTS: The mean pre- and post-CysC levels were 6.0±1.0 and 4.7±1.1 mg/L. The Sp Kt/V and Std Kt/V were 1.5±0.2 and 2.6. The URR, CRR, and CCRR were 70.2%±9.0%, 64.5%±8.2%, and 26.1%±11.8%, respectively. There was no correlation between the CCRR, and the Sp Kt/V, URR, and CRR, whereas CCRR correlated with LP/kg and UF. Multiple regression analysis with these two parameters provided a model that explained 81% of the variance. CONCLUSIONS: Our data suggest that normalized liters processed and ultrafiltration volume explain most of the variance of CCRR. Therefore, CCRR may be an excellent method to monitor dialysis efficiency of low molecular weight proteins.

Random pharmacokinetic profiles of EC-MPS in children with autoimmune disease.

BACKGROUND: : Therapy with mycophenolate mofetil (MMF) has become a valuable therapeutic option in children with autoimmune disease. MMF prescription in children with autoimmune diseases differs from that in transplant recipients in terms of different dosing regimen, and concomitant administration of other immunosuppressive medications. Recently, another formulation of the same active compound, mycophenolic acid (MPA), has become available as enteric-coated Mycophenolate Sodium (EC-MPS). Dosing and pharmacokinetics of EC-MPS in pediatric autoimmune disease have never been studied. METHOD: S: We therefore performed a pilot study on 6 patients, who were treated with EC-MPS. All patients underwent 1-2 full 10-point pharmacokinetic (PK) profiles over a 12-hour dosing interval. We compared the results with that of 22 similar patients on MMF therapy. RESULTS: : Median EC-MPS dose was 724 mg/m2 (range 179-933 mg/m2). The MPA Area-Under-The-(Time-Concentration)-Curves (AUCs) on MMF and EC-MPS were comparable (54.4 mg x h/L on MMF and 44.0 mg x h/L on EC-MPS, n.s., Mann Whitney). After correcting for bioequivalence, the dose-normalized AUCs were also similar on both the formulations. However, PK profiles on EC-MPS were quite random, and time to maximum concentration varied from 30 minutes to 720 minutes. The concentration at six-hour correlated best with the AUC. This was different from a homogenous PK-profile on MPA. CONCLUSIONS: : EC-MPS has a different PK profile from MMF. The data suggest that patients on EC-MPS must undergo a complete PK profile to assess adequate exposure. The 6-hour concentration provides an estimate of the exposure and should be targeted between 3-4 mg/L.

Development of a beta-trace protein based formula for estimation of glomerular filtration rate.

Beta-trace protein (BTP) is a novel marker of glomerular filtration rate (GFR). To date, no pediatric formula for calculating GFR based on BTP has been developed. We measured GFR, serum creatinine and BTP in 387 children who underwent 474 (99m)Tc-diethylene triamine pentaacetic acid renal scans. A BTP-based formula for estimating GFR was derived using stepwise linear regression analysis. A separate control group of 116 measurements in 99 children was used to validate the novel formula. A formula was also developed for each gender. The novel formula is: [formula: see text]. The Spearman rank correlation coefficient between the BTP-derived GFR estimate and the measured GFR was 0.80 [95% confidence interval (CI) 0.76-0.83], which is substantially better than that derived with the Schwartz formula (r = 0.70, 95% CI 0.65-0.74). The Bland-Altman analysis revealed a mean bias of 1.21% [standard deviation (SD) 28%] in the formula development dataset, which was virtually identical to the 1.03% mean bias (29.5% SD) in the validation group and no different from the Schwartz formula bias. The percentage of values within 10% (33.0 vs. 28.3%) and 30% deviation (76.8 vs. 72.6%) were better for BTP-based formula than for the Schwartz formula. Separate formulas according to gender did not perform better than that for the pediatric population. This BTP-based formula was found to estimate GFR with reasonable precision and provided improved accuracy over the Schwartz GFR formula.

Adherence to waiting-time targets for pediatric nephrology clinic referrals.

Waiting times for specialist consultation have not been adequately studied, especially in the pediatric population. The aim of this study was to determine the extent to which pediatric nephrology subspecialty clinic referral waiting times are adhered to with regard to previously determined access targets. Referrals to the pediatric nephrology clinics at Children's Hospital, London, Ontario, Canada, received between October 2007 and November 2008 were retrospectively analyzed. Appointment schedule was allotted by a nephrologist based on the patient's presenting complaint, reported in the referral, in accordance with the previously determined access targets. Adherence to access targets was assessed by the actual clinic visit. There were a total of 250 referrals during the timeframe studied. The median waiting time was 73 (range 0-193) days. Overall, 64% (159/250) of patients met their access target. The median time that patients waited over their access target was 6 (range 0-78) days. Of the patients who did not meet their access targets, 31% (28/91) exceeded their target by 20% or more. Office handling was a component for patients with access target <1 week, whereas availability of clinic space was the main reason for nonadherence to access targets.

Cystatin C levels in functionally anephric patients undergoing dialysis: the effect of different methods and intensities.

BACKGROUND AND OBJECTIVES: Cystatin C, a low molecular weight protein, is produced by nucleated cells, filtered by glomeruli, and degraded by tubules at a constant rate. Its serum concentration has been proposed as a marker of GFR. Its size should make it dialyzable. It is hypothesized that serum cystatin C levels are influenced by the method and intensity of dialysis received. DESIGN: This is a cross-sectional pilot study of cystatin C in functionally anephric dialysis patients. It was measured predialysis in 14 patients on conventional (3 to 5 h, 3 x wk) hemodialysis; eight on nocturnal hemodialysis (three to seven nights, 6 to 8 h); three on daily hemodialysis (6 d, 1(1/2) to 2(1/2) h); and 10 on automated peritoneal dialysis. All had urea kinetic studies and values for single pool Kt/V (Sp Kt/V), standard weekly Kt/V (Std Kt/V), and protein equivalent of nitrogen appearance (nPNA; g/kg/d). C reactive protein (CRP; mg/L) and thyroid stimulating hormone (TSH; mIU/L) were measured as factors known to influence cystatin C. RESULTS: There was no correlation between cystatin C and Sp Kt/V, but there was a significant inverse linear correlation with Std Kt/V and there were significant differences between treatment modalities in cystatin C levels and in Std Kt/V. The estimation of cystatin C was reliable and stable over 3 to 6 wk and its levels uninfluenced by nPNA, CRP, or TSH. CONCLUSION: Serum cystatin C levels are influenced by the method and intensity of dialysis and may have a role in treatment adequacy monitoring.

Body mass does not have a clinically relevant effect on cystatin C eGFR in children.

BACKGROUND: Unlike creatinine, Cystatin C (CysC) is believed to be independent of body composition in both adults and children. Recent findings in adults, suggesting an improved performance of CysC-based estimated glomerular filtration rate (CysC eGFR) by accounting for body mass, necessitated a careful re-evaluation of this issue in children. METHODS: We studied 240 children (median age 11.7 years, range 2-17.9 years, 107 girls), with various kidney diseases, for any change in the relationship between (99)Tc DTPA GFR and CysC eGFR after accounting for body mass. For body mass assessment, body mass index (BMI) z-score was calculated using height-adjusted age, to account for growth retardation secondary to chronic kidney disease. RESULTS: CysC eGFR did not have a significant correlation with BMI z-score (correlation coefficient = 0.06; P = 0.34). Accounting for BMI z-score did not add to the 65% variance in nuclear GFR explained by CysC eGFR. Moreover, it did not change the regression coefficient of 0.85 between CysC eGFR and nuclear GFR either. On Bland & Altman analysis, the bias of 0.05 and standard deviation of 20.39 also did not improve after accounting for BMI z-score in the revised CysC eGFR formula. CONCLUSIONS: In children, body mass exerts a minimal effect on the performance of CysC eGFR estimation.

Limited sampling strategies for sirolimus after pediatric renal transplantation.

SRL has been increasingly used in renal transplantation, but limited sampling approaches for estimation of AUC remain elusive. A post-hoc analysis of 94 PK profiles in 75 patients from four previous studies was performed to generate limited sampling approaches for approximation of AUC based on two to four time points for both BID and OD SRL dosing. AUC was calculated using the trapezoid rule. Stepwise linear regression was performed to generate an abbreviated AUC from the limited sampling approaches. For BID dosing, complete AUC had a strong correlation with the trough levels (r(2) = 0.882, p < 0.0001) and with C2 level (r(2) = 0.9025, p < 0.0001). A three-point and a four-point limited sampling approach showed improved agreement with complete AUC compared with single-point sampling. A convenient and accurate (r(2) = 0.992) four-point limited sampling approach reads: AUC = 10;(1.085 + 0.117 x log C0 + 0.164 x log C1-0.131 x log C2 + 0.823 x log C4). Similarly, complete AUC had a statistically significant correlation with the trough levels (r(2) = 0.549, p < 0.0001) and with C2 level (r(2) = 0.716, p < 0.0001) for OD dosing. The estimation of AUC for OD dosing was improved over single-point sampling (r(2) = 0.951) using the formula: AUC = 10;(1.100 + 0.115 x log C0 + 0.803 x log C4). This study represented the first limited sampling approach for SRL. Further studies are required to determine the optimal SRL target AUC.