Application of GFR estimating equations to children with normal, near-normal, or discordant GFR.

BACKGROUND: The objective was to determine the extent that eGFR formulas correspond to measured plasma iohexol clearance (iGFR) in children with normal or near normal kidney function, particularly how different eGFR formulas yield discordant results. METHODS: iGFR from 2 (iGFR-2pt) and 4 (iGFR-4pt) time points along with creatinine and/or cystatin C-based eGFR were measured in children with mild CKD, stages 1-2. eGFR was calculated using 6 equations: 3 under 25 (U25) formulas from the Chronic Kidney Disease in Children (CKiD) study, the full age-combined cystatin C (cysC) and creatinine spectrum (FAS-combined), the European Kidney Function Consortium (EKFC-creatinine) equation, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-epi) cysC-based equation. RESULTS: Twenty-nine children were included, of which 22 had discordant creatinine vs. cystatin C-based eGFR by ≥ 15mL/min/1.73 m2. Overall, the FAS-combined had the least bias, while the U25 most accurately identified children with an eGFR < 90 mL/min/1.73 m2. When Cr-eGFR was ≥ 15 mL/min higher than CysC-eGFR, the U25 creatinine eGFR was closest to iGFR-4pt. When CysC eGFR was higher, the U25-combined was closest to iGFR-4pt. CONCLUSION: The formulas that most closely approximated the measured GFR varied depending on the pattern of discordant eGFR results. Based on the results, we recommend using the CKiD U25-combined formula to screen for children with a low GFR. Either the CKiD U25-combined or FAS-combined would be recommended for changes in eGFR longitudinally. However, because all formulas were discordant from the iGFR-4pt in over a third of participants, further refinement of pediatric eGFR formulas is needed at the normal/near-normal range. A higher resolution version of the Graphical abstract is available as Supplementary information.

Recalibration of cystatin C using standardized material in Siemens nephelometers.

BACKGROUND: Cystatin C is a key GFR biomarker. Recently, Siemens recalibrated the assay based on certified reference material ERM-DA471/IFCC. The NIH-funded longitudinal chronic kidney disease in children (CKiD) study has > 3000 cystatin C measurements based on a pre-IFCC calibrator provided by Siemens. Since cystatin C values for CKiD are now standardized to IFCC certified reference material, it is important to relate the IFCC-calibrated results to the previous values so that there are no discontinuous results. METHODS: We diluted cystatin C ERM-DA471/IFCC (5.48 mg/L) into buffer and compared results with predicted ones. We then updated the cystatin C application on our BN II nephelometer to provide results based on pre-IFCC and IFCC calibrations of CKiD specimens simultaneously. We assayed 51 previously analyzed sera and 62 fresh additional specimens. RESULTS: The predicted concentrations from the IFCC standard were consistently 17% higher than the measured values using the pre-IFCC calibration (y = 1.1686x). Similarly, the re-run and fresh sample concentrations were 17% higher via the IFCC calibration than by the pre-IFCC calibration (y = 1.168x). There was very high reliability in the measurements using the previous calibration for re-run specimens (0.99) and for 33 pristine specimens using IFCC calibration (0.99). CONCLUSIONS: We confirm the recalibration proposed by Siemens. To convert pre-IFCC results to IFCC-calibrated concentrations, the value is multiplied by 1.17. Conversely, one divides IFCC-calibrated results by 1.17 to estimate GFR via previously published pre-IFCC CKiD eGFR equations. For older adolescents, cystatin C has already been standardized and can be directly applied to the CKD-EPI equations.

Renal Response to a Protein Load in Healthy Young Adults as Determined by Iohexol Infusion Clearance, Cimetidine-Inhibited Creatinine Clearance, and Cystatin C Estimated Glomerular Filtration Rate.

OBJECTIVE: Renal reserve (RR) measures the increase in glomerular filtration rate (GFR) in response to a protein load; lack of RR could indicate subclinical kidney disease but such a test is not routinely used in clinical practice. The purpose of this study was to compare a meat versus liquid protein load in a cystatin C-based (Cys-C) RR test using cimetidine-inhibited creatinine clearance (Cr Cl) and iohexol infusion clearance (Io Cl) for validation. The design was cross-sectional analysis and the setting was a Clinical Research Center. SUBJECTS: Participants (N = 16), mean (standard deviation [SD]) age 22 (2) years, had normal health and blood pressure without proteinuria. INTERVENTION: Participants 1 to 8 received a beef burger (1 g/kg protein) and participants 9 to 16 received a ProCel shake (1-1.5 g/kg protein). MAIN OUTCOME MEASURE: RR defined as the difference in stimulated versus baseline GFR. RESULTS: Baseline GFR (SD) in mL/minute/1.73 m2 averaged 103.0 (15.6) for Cr Cl, 94.8 (7.9) for Io Cl, and 117.0 (6.0) for Cys-C estimated GFR (eGFR). Mean RR (SD) for the burger group (N = 8, mL/minute/1.73 m2) was 16.6 (12.3) for Cr Cl (P = .006); 7.2 (3.7) for Io Cl (P < .001), and 4.9 (2.6) for Cys-C eGFR (P = .001). Mean RR for the shake group (N = 8) was 15.8 (5.8) for Cr Cl (P < .001), 10.1 (7.8) for Io Cl (P = .008), and 2.4 (2.9) for Cys-C eGFR (P = .05). CONCLUSION: Protein loading stimulates Io Cl and Cr Cl after a beef or milk-based protein load. The change in Cys-C eGFR is significant but smaller for the shake and burger group, which may be due to the dilutional effect of water loading or the length of Cys-C half-life in the blood.

Mind over chronic pain: A meta-analysis of cognitive restructuring in chronically ill adults.

OBJECTIVE: This meta-analysis synthesizes research on the impact of cognitive restructuring on chronic pain intensity, aiming to integrate diverse methodologies and findings while evaluating potential moderators. METHODS: Following PRISMA guidelines, we systematically searched multiple databases (PubMed, Web of Science, JSTOR, Sage, Social Science Research Network, PsycArticles, ScienceDirect, and Education Resources Information Center) until July 2023. Studies involving adults (≥18 years) diagnosed with chronic conditions who underwent cognitive restructuring to reduce chronic pain intensity, were included. Eligible studies compared this intervention with a control group. We excluded studies incorporating cognitive restructuring within broader interventions, lacking statistical data, or not written in English. Study quality was assessed using the Cochrane Risk of Bias tool (RoB 2). RESULTS: After reviewing 18,312 studies, we selected 11 studies published between 1991 and 2022, involving 693 participants with chronic conditions. A significant large overall effect size was found (d = 0.94, 95% CI 0.48 to 1.40). Moderation analyses revealed significant differences based on sex and study quality, with effects less pronounced among females and more substantial in higher-quality studies. CONCLUSION: Despite limitations such as statistical instability due to a small number of studies in certain moderator categories and methodological variability, this meta-analysis highlights the robust effects of cognitive restructuring on chronic pain intensity. The findings are valuable for guiding power calculations and future research expectations. Clinically, these results support the significant effect of cognitive restructuring in both individual and group settings, regardless of age, particularly when facilitated by teams that include psychologists.

Rapid assessment of renal reserve in young adults by cystatin C.

BACKGROUND: The kidney can increase glomerular filtration rate (GFR) in response to a protein load (renal reserve). In a pilot study of healthy young adults we examined renal reserve using changes in serum cystatin C (cysC). METHODS: Glomerular filtration rate was obtained using iohexol single slope plasma disappearance. To stimulate GFR, subjects ingested a beefburger containing 60 grams of protein. CysC was measured by immunonephelometry before and 125-141 minutes after protein loading. RESULTS: All subjects were found to have a normal iohexol plasma disappearance GFR with a mean of 104.6 ± 9.9 mL/min per 1.73 m(2). CysC decreased in each subject after the meat meal. Baseline cysC-based estimated GFR was 98.1 ± 9.1 mL/min per 1.73 m(2) with a mean increase of 12.0 ± 5.2 (p = 0.0003). CONCLUSIONS: Our study showed a consistent decrease in serum cysC and increase in cysC-based estimated GFR following a protein load in young adults. Further studies are needed using renal clearance methods to confirm that cysC accurately determines renal reserve in patients with and without chronic kidney disease.

Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C.

The Chronic Kidney Disease in Children study is a cohort of about 600 children with chronic kidney disease (CKD) in the United States and Canada. The independent variable for our observations was a measurement of glomerular filtration rate(GFR) by iohexol disappearance (iGFR) at the first two visits 1 year apart and during alternate years thereafter. In a previous report, we had developed GFR estimating equations utilizing serum creatinine, blood urea nitrogen, height, gender, and cystatin C measured by an immunoturbidimetric method; however, the correlation coefficient of cystatin C and GFR(0.69) was less robust than expected. Therefore, 495 samples were re-assayed using immunonephelometry. The reciprocal of immunonephelometric cystatin C was as well correlated with iGFR as was height/serum creatinine (both 0.88). We developed a new GFR estimating equation using a random 2/3 of 965 person-visits and applied it to the remaining 1/3 as a validation data set. In the validation dataset, the correlation of the estimated GFR with iGFR was 0.92 with high precision and no bias; 91 and 45% of eGFR values were within 30 and 10% of iGFR, respectively. This equation works well in children with CKD in a range of GFR from 15 to 75 ml/min per 1.73 m2. Further studies are needed to establish the applicability to children of normal stature and muscle mass, and higher GFR.

Cross-Sectional and Longitudinal Performance of Creatinine- and Cystatin C-Based Estimating Equations Relative to Exogenously Measured Glomerular Filtration Rate in HIV-Positive and HIV-Negative Persons.

BACKGROUND: Reliable estimates of glomerular filtration rate (GFR) are important in the clinical management of HIV-positive patients. Data on the performance of widely used estimating equations (eGFR) relative to exogenously measured GFR are sparse in this population. METHODS: We evaluated cross-sectional and longitudinal accuracy and bias of eGFR, based on creatinine and cystatin C, relative to disappearance of infused iohexol from plasma (iGFR) in a cohort of participants followed annually for up to 7 years. RESULTS: A total of 222 HIV-positive and 139 HIV-negative participants contributed 1240 visits with valid iGFR and eGFR measures. Estimated GFR based on both creatinine and cystatin C performed the best. Estimated GFR based on creatinine alone overestimated iGFR by 9 mL·min·1.73 m on average and was significantly less accurate in HIV-positive than HIV-negative individuals. The performance of equations based on either creatinine alone or cystatin C alone were significantly affected by participant factors (eg, non-suppressed HIV RNA, nadir CD4 count, hepatitis C virus coinfection). The average iGFR slope was -4% per year in HIV-positive participants. In both HIV-positive and HIV-negative participants, eGFR slope measures were generally unbiased but inaccurate, with only 60%-74% of observations falling within ±5% points of iGFR slope. CONCLUSIONS: Both creatinine and cystatin C have limitations as GFR indices in HIV-positive individuals. Estimated GFR based on both creatinine and cystatin C performed best in our study and may be preferred in HIV-positive persons with kidney disease or comorbidities that place them at high risk for kidney disease.

Estimating kidney function in HIV-infected adults in Kenya: comparison to a direct measure of glomerular filtration rate by iohexol clearance.

BACKGROUND: More than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population. METHODS: We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated. RESULTS: The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm(3). Median measured GFR was 115 mL/min/1.73 m(2). Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60-90 mL/min/1.73 m(2) (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions. CONCLUSIONS: Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m(2), in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations.