CysC-based Equations Research Articles

Comparison of estimated GFR using cystatin C versus creatinine in pediatric kidney transplant recipients

BackgroundAn accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients.MethodsCysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1–18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland–Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging.ResultsBias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate—both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland–Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%).ConclusionsIn this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Estimating the Glomerular Filtration Rate in Pediatric Patients With Neurogenic Bladder: A Comparison Between Creatinine- and Cystatin C-Equations.

Background and objective Patients with neurogenic bladder (NB) are at a higher risk of developing chronic kidney disease (CKD). Due to their lower muscle mass, the estimated glomerular filtration rate (eGFR) based on creatinine (Cr) may be overestimated and delay the diagnosis of renal failure. This study compared eGFR calculated with different equations based on Cr and/or cystatin C (CysC) in children with NB, and the differences between patients with lower muscle mass (underdeveloped lower limbs) and those with independent gait (less muscle depletion). Methods We calculated the eGFR inpediatric patients with NB and CKD stages 1 and 2 by using the following equations: Chronic Kidney Disease in Children equation for serum creatinine (CKiD-Cr), CKiD-CysC, CKiD combined-Cr/CysC, Zappitelli-CysC, and Zappitelli combined-Cr/CysC. Results We evaluated a total of 47 patients, 74.5% with CKD stage 1, with a median age of 14.1 years. Of these participants, 59.6% had lipo/myelomeningocele. The CKiD-Cr and CysC-based equations led to significantly lower calculated eGFR ​​(p<0.05), specifically CKiD-CysC (p<0.001), Zappitelli-CysC (p<0.001), CKiD-Cr/CysC (p<0.001), and Zappitelli combined-Cr/CysC (p<0.05). When CKiD-CysC was used, 68% of the patients moved to a more advanced CKD stage. In patients without independent gait, with lower muscle mass (55.3%), the median eGFR calculated using the CKiD-Cr and CKiD combined-Cr/CysC equations was significantly higher (p<0.05). However, there were no differences between the two groups when using the other CysC-based equations. Conclusion In patients with NB and poor muscle mass, the CKiD-Cr equation may overestimate renal function. CysC-based equations seem more reliable in these patients, especially in those with greater muscular atrophy.

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

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. 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. Twenty-nine children were included, of which 22 had discordant creatinine vs. cystatin C-based eGFR by ≥ 15mL/min/1.73m2. Overall, the FAS-combined had the least bias, while the U25 most accurately identified children with an eGFR < 90 mL/min/1.73m2. 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. 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.

#4671 ESTIMATED GLOMERULAR FILTRATION RATE USING CYSTATIN C AND CREATININE IN CHILDREN WITH NEUROGENIC BLADDER – IMPACT OF DEMOGRAPHICS AND PROTEINURIA

Abstract Background and Aims There is a high-risk of progressive chronic kidney disease (CKD) in patients with neurogenic bladder (NB) and early detection of estimated glomerular filtration rate (eGFR) reduction is essential, preventing delayed diagnosis. Creatinine-based formulas can overestimate eGFR in these patients due to decreased muscle mass. This study aims to compare eGFR calculated by different equations using serum creatinine (Cr) and/or cystatin C (CysC), in children with NB, and analyse the influence of demographic variables and proteinuria. Methods Data on pediatric patients with NB and CKD stage 1 and 2, based on eGFR calculated by the CKiD-Cr formula, were collected from January 2009 to December 2022, in a Pediatric Nephrology Unit from a tertiary hospital. The eGFR was calculated using CKiD CysC, Schwartz combined Cr/CysC, Zapitelli-CysC and Zapitelli combined Cr/CysC formulas. Proteinuria was defined by urine protein-to-creatinine ratio greater than 0.2 (mg/mg). Results Fifty patients were evaluated, with a median (25th-75th percentile) age of 14.2 (9.0-16.7) years, 48% (n = 24) female, with a median height of 142 (119.8-154.3) cm, mostly below to 5th percentile (64%, n = 32) and a median body mass index of 20.5 (15.5-26.7) kg/m2, 58% (n = 29) of patients had lipo/myelomeningocele and 76% (n = 38) were classified as stage 1 CKD. The median eGFR (ml/min/1.73m2) calculated by different formulas was: CKiD-Cr 108.1 (89.2-129.6); CKiD-CysC 77.1 (59.7-87.7), CKiD- Cr/CysC 86.6 (67.4-98.1); Zapitelli-CysC 83.3 (63.3-95.7) and Zapitelli combined- Cr/CysC 101.4 (75.5-121.2). When compared to CKiD-Cr, all the CysC-based formulas showed significantly lower values of eGFR (p&amp;lt;0.01). No statistical differences were obtained in eGFR calculated by CKiD-Cr and CKiD-CysC equations regarding age, sex, percentile of height or body mass index. In patients without independent gait (wheelchair or orthosis), with more muscle atrophy and underdeveloped lower limbs (54%, n = 27), the eGFR calculated by CKiD- Cr equation was higher than in the patients who are ambulatory (119.0 (102.8-150.0) vs 91.6 (64.5-111.8); p&amp;lt;0.01). On the other hand, there were no differences regarding eGFR obtained by CKiD-CysC in those two groups of patients (p = 0.640). Proteinuria was detected in 39% (n = 15) of the patients with stage 1 CKD and of these 87% (n = 13) had CKD upstaging using CKiD-CysC equation. In addition, the difference between the median Cr-eGFR and CysC-eGFR was significantly higher in the group of patients with proteinuria (53.0 (36.2-59.7) vs 32.6 (13.4-45.9); p = 0.007). Proteinuria was significantly higher in the group of children with more muscle atrophy, without independent gait (wheelchair or orthosis) compared to ambulatory (0.30 (0.12-0.43) vs 0.12 (0.06-0.20); p = 0.021). Conclusions In pediatric patients with NB and poor muscle mass Cr-based formulas can overestimate eGFR and delay the diagnosis and correct staging of CKD. In these patients CysC-based equations seem to be more reliable in assessing kidney function. In children with NB proteinuria appears to be a possible early and sensitive marker of CKD progression, mostly in those with more muscle depletion.

Wide-ranging performance of different eGFR equations in stage determination of Chronic Kidney Disease patients from endemic areas for CKD in Sri Lanka

Background: Chronic kidney disease of unknown etiology (CKDu) is a public health issue at epidemic proportions in North Central, Uwa and other provinces of Sri Lanka. The initial diagnosis and stage determination of the disease are based on estimated glomerular filtration rate (eGFR), and urine albumin to creatinine ratio (UACR) particularly at community level screening. In this context, harmony and performance of pertaining equations were verified. Methods: Three hundred and ninety-nine (399) volunteer CKD patients were recruited from select CKDu high prevalence areas (Padaviya, Girandurukotte, and Mahiyanganaya). Performance of kidney dysfunction determinants; serum creatinine (SCr), and serum Cystatin C (CysC), as well as markers; UACR, and eGFR variants; SCr based MDRD, SCr based EPI, serum CysC based EPI and SCr and CysC based EPI were scrutinized in terms of kidney disease improving global outcomes (KDIGO) heat-map guidelines. Results: Notable deviation was observed between SCr-based and CysC-based equations at early development of the disease (stage G1) suggesting that the latter may tend to under estimate disease development initially. UACR successfully confirmed diagnosis from eGFR equations including G1 proteinuric subjects (G1). Conclusions: Comparative study of marker performances should improve eGFR based identification of initial CKDu cases in Sri Lanka.

Measurement and Estimation of Glomerular Filtration Rate in Children With Neurogenic Bladder: A Prospective Study

ObjectiveTo evaluate the performance of different equations used to estimate glomerular filtration rate (GFR) in children with neurogenic bladder (NB). MethodsThe GFR measured with the technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) dual-plasma sample clearance method was defined as the true GFR (tGFR). The Chronic Kidney Disease in Children (CKiD) equation for serum creatinine (Scr) and/or cystatin C (Cys C) was used for GFR calculation. Estimated GFR (eGFR) using CKiDScr, CKiDCys C, and CKiDScr+Cys C equations was compared with tGFR in children with NB. ResultsIn total, 458 children with NB were prospectively enrolled in this study. The mean tGFR was 73.84 ± 18.54 ml/min/1.73 m2, mean eGFRScr was 77.94 ± 18.38 ml/min/1.73 m2, mean eGFRCys C was 74.20 ± 17.64 ml/min/1.73 m2, and mean eGFRScr+Cys C was 75.70 ± 18.07 ml/min/1.73 m2. The correlation between the Scr-based equation and 99mTc-DTPA clearance method was low (r = 0.648). The Cys C-based equations exhibited the strongest correlations: CKiDCys C (r=0.891) and CKiDScr+Cys C (r = 0.879). The overall prevalence of chronic kidney disease (CKD) was 20.7%, 19.7%, 17.5%, and 12.4% according to tGFR, eGFRCys C, eGFRCys C+Scr and eGFRScr, respectively. The area under the curve (AUC) for the Receiver operating characteristic (ROC) curve of the CKiDCys C equation was the highest (AUCCKiDcys = 0.956). ConclusionThe Cys C-based CKiD equation was the most accurate for estimating GFR compared with 99mTc-DTPA clearance method in children with NB. The CKiDScr equation overestimated the GFR. The CKiDCys C equation can be used to detect initial stages of CKD in children with NB.

Comparison of Cystatin C and Creatinine-Based Equations with Measured Glomerular Filtration Rate in a Diverse Pediatric Population.

Accurate assessment of kidney function is essential for early detection of kidney damage. While measured glomerular filtration rate (mGFR) is occasionally used as a reference, estimated GFR (eGFR) from serum creatinine- and cystatin C (CysC)-based equations are routinely used in clinical practice as a reliable and less invasive approach. In pediatric populations, CysC-based equations provide a closer approximation as they are independent of body composition. Limited information is available on the performance of CysC-based equations in comparison with mGFR with tracers other than iohexol. Therefore, the goal of our study was to evaluate how eGFR, based on several CysC- and creatinine-based equations, with and without race correction, relates to mGFR in a diverse pediatric population. A total of 43 patients (7 months to 21 years) from diverse race/ethnicity were retrospectively studied to compare the mGFR from multiple blood sample collections after intravenous tracer injection (Tc-99mDTPA) with eGFR using 9 equations. Deming regression analyses were performed to assess correlation between the mGFR and eGFRs. The average mGFR for this cohort was 95.0 mL/min/1.73 m2. Race-corrected (RC) equations gave overestimated eGFR across all ethnic groups, with the lowest bias for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) CysC-creatinine (34.14 mL/min/1.73 m2). The best correlations to mGFR, percentage of eGFR within 30% of mGFR (P30), and lowest biases were from non-race-corrected (NRC) equations Chronic Kidney Disease in Children (CKiD) (0.6460, 65.1%, 2.86 mL/min/1.73 m2), CKD-EPI CysC (0.6858, 69.8%, 11.01 mL/min/1.73 m2), and Schwartz CysC (0.6876, 79.1%, -14.00 mL/min/1.73 m2). Overall, CysC-based equations without race correction provide a good approximation of mGFR and a less invasive alternative to monitoring kidney function in pediatric population, irrespective of race/ethnicity.

Assessment of Cystatin C-Based GFR Estimating Equations as a Novel Reliable Biomarker for Renal Pathology Diagnosis in Patients with Mild to Severe Tubular Affection

Background and Objective: Serum creatinine, a commonly used biomarker in determining glomerular filtration rate (GFR) and chronic kidney disease (CKD) stage, is highly variable biologically and does not rise until > 50% of renal function (RF) impairment occurs. Also, its production is not constant & is affected by many factors as muscle mass, age, inflammation. On the other hand, Cystatin C shows more stable production making it more suitable for assessment of kidney function. Also, It has been shown that the progression of CKD to renal failure, even in glomerular diseases, correlated better with the degree of tubular damage and interstitial fibrosis. So, our aim was to investigate the relation between kidney function assessed by different cystatin (Cys-C)-based estimated glomerular filtration rate (eGFR) in comparison to the gold standard Iohexol (Ioh) based measured (m)GFR in relation to the pathological degree of tubular damage in renal biopsy. To our knowledge, this is the first study that evaluates the relation of (Cys-C)-based eGFR to tubulointerstitial fibrosis in renal biopsy. Methods: This cross-sectional study was performed on 20 CKD cases who attended the Nephrology Department at Ain Shams University, where a renal biopsy was obtained, and individuals were allocated into two groups: group A (GA) with mild tubular affection (TA) and group B (GB) with moderate to severe TA. All participants were referred for measure-ment of GFR using Iohexol (Ioh) together with serum Cys-C level and eGFR was calculated using different Cys-C-based GFR estimating equations, which were further compared using Multivariate Linear Regression and Bland-Altman analyses. Results: Our results revealed a substantial statistical difference among the two studied groups regarding Hb, s creatinine, urea. GB had significantly lower levels for both eGFR and mGFR (82, 93, 115, or 115) ml/min/1.73m2, Vs. GA (200, 123, 162 or 124) ml/min/1.73m2, according to GFR_iohexol, Stevens, Grubb, and CKD_EPI_CYST equations, respectively, p 0.05. A significant correlation between CKD-EPI CYST and mGFR_Iohexol (Ioh) for GA was found (R = 0.601, p = 0.030), where there was a non-substantial relation between any of the used equations and the mGFR in category B (p > 0.05). There was no independent association between the eGFR results and Iohexol clearance. Stevens eGFR had the highest-level bias 33.9 compared with CKD_EPI_CYST (28) and Grubb eGFR (22.85). Conclusion: eGFR by CysC-based equations underestimate GFR in comparison to GFR-iohexol. There is significant correlation between eGFR by CysC-based equations and the gold standard GFR-iohexol only in mild degree of tubular affection and only with CKD-EPI-CYST equation. Stevens equation showed the highest bias while Grubb equation showed the least bias. Although cystatin-based equations have demonstrated a high level of correlation with measured GFR, they are still regarded as imprecise and cannot be established as equal to measured GFR or as a gold standard for GFR estimate.

Estimating Glomerular Filtration Rate in Cirrhosis Using Creatinine-Based and Cystatin C-Based Equations: Systematic Review and Meta-Analysis.

Accurate estimation of kidney function in cirrhosis is crucial for prognosis and decisions regarding dual-organ transplantation. We performed a systematic review/meta-analysis to assess the performance of creatinine-based and cystatin C (CysC)-based eGFR equations compared with measured GFR (mGFR) in patients with cirrhosis. A total of 25 studies (n = 4565, 52.0 years, 37.0% women) comprising 18 equations met the inclusion criteria. In all GFR equations, the creatinine-based equations overestimated GFR (standardized mean difference, SMD, 0.51; 95% confidence interval [CI], 0.31-0.71) and CysC-based equations underestimated GFR (SMD, -0.3; 95% CI, -0.60 to -0.02). Equations based on both creatinine and CysC were the least biased (SMD, -0.14; 95% CI, -0.46 to 0.18). Chronic kidney disease-Epi-serum creatinine-CysC (CESC) was the least biased but had low precision and underestimated GFR by -3.6 mL/minute/1.73 m2 (95% CI, -17.4 to 10.3). All equations significantly overestimated GFR (+21.7 mL/minute/1.73 m2 ; 95% CI, 17.7-25.7) at GFR <60 mL/minute/1.73 m2 ; of these, chronic kidney disease-Epi-CysC (10.3 mL/minute/1.73 m2 ; 95% CI, 2.1-18.4) and GFR Assessment in Liver Disease (12.6 mL/minute/1.73 m2 ; 95% CI, 7.2-18.0) were the least biased followed by Royal Free Hospital (15 mL/minute/1.73 m2 ; 95% CI, 5.5-24.6) and Modification of Diet in Renal Disease 6 (15.7 mL/minute/1.73 m2 ; 95% CI, 10.6-20.8); however, there was an overlap in the precision of estimates, and the studies were limited. In ascites, overestimation of GFR was common (+8.3 mL/minute/1.73 m2 ; 95% CI, -3.1 to 19.7). However, overestimation of GFR by 10 to 20 mL/minute/1.73m2 is common in patients with cirrhosis with most equations in ascites and/or kidney dysfunction. A tailored approach is required especially for decisions regarding dual-organ transplantation.

Effect of Cystatin C on Vancomycin Clearance Estimation in Critically Ill Children Using a Population Pharmacokinetic Modeling Approach.

Vancomycin is eliminated by glomerular filtration, but current approaches to estimate kidney function in children are unreliable. The authors sought to compare the suitability of cystatin C (CysC)-based glomerular filtration rate equations with the most commonly used creatinine-based equation, bedside Schwartz, to estimate vancomycin clearance (CL). This prospective observational study enrolled critically ill patients (2-18 years) receiving intravenous vancomycin at the Children's Hospital of Philadelphia during December 2015-November 2017. Vancomycin levels were collected during clinical care and at 3 times during a single dosing interval. Plasma CysC was measured within 24 hours before intravenous vancomycin (baseline) initiation or immediately after enrollment and along with the third pharmacokinetic sample. Nonlinear mixed effects modeling was performed using NONMEM software. Covariate selection was used to test model fit with inclusion of the estimated glomerular filtration rate (eGFR) on CL using bedside Schwartz versus various published CysC-based equations. In total, 83 vancomycin levels were obtained from 20 children. The median age was 12.7 years; 6 patients were women. A 1-compartment model best described the data; CL was allometrically scaled to 0.75. During covariate selection, inclusion of the eGFR calculated using a CysC-based equation significantly improved model fit [reduction in objective function value (OFV) range: -17.191 to -18.704] than bedside Schwartz ([INCREMENT]OFV -12.820). Including the full age spectrum equation, an eGFR equation based on both creatinine and CysC, led to the largest OFV reduction (-22.913); female sex was also a significant covariate of CL in the model. Final model pharmacokinetic indices were CL = 0.29 L/h/kg and volume of distribution = 0.48 L/kg. CysC-based equations help better estimate vancomycin CL than bedside Schwartz in critically ill children.

Prognostic Value of Cystatin C-Derived Estimated Glomerular Filtration Rate in Patients with Acute Heart Failure

Background: Renal function is closely related to cardiac function and an important prognostic marker in heart failure. Objective: We aimed to test the prognostic value of cystatin C (cysC)-derived estimated glomerular filtration rates (eGFR) in comparison with eGFRs from creatinine solely based equations in patients with acute heart failure (AHF). Methods: This study included 262 patients (65.8 ± 14.9 years old, 126 male) with AHF. Prognostic value of the eGFRs, from cysC-based equations chronic kidney disease epidemiology collaboration (CKD-EPI-cysC and CKD-EPI-creatinine [cr]-cysC equations) were compared with eGFRs calculated from serum creatinine levels only (Modification of Diet in Renal Disease [MDRD]-4 and CKD-EPI-cr equations). Prognosis was evaluated with the composite of all-cause mortality and hospitalization for heart failure within 1 year. Results: During the follow-up period (mean follow-up period, 264.0 ± 136.1 days), 67 (25.6%) events occurred. Estimated GFR using CKD-EPI-cysC was the best for predicting 1-year outcome using receiver operating characteristic curve analysis (area under curve 0.585, 0.607, 0.669, and 0.652 for eGFRs from MDRD-4, CKD-EPI-cr, CKD-EPI-cysC, and CKD-EPI-cr-cysC respectively). The Kaplan-Meier survival curve analysis showed that only the eGFRs classification from the equations based on cysC significantly predicted 1-year outcome in patients with AHF. Conclusions: Estimated GFRs calculated with cysC predicted the prognosis more accurately in patients with AHF than the eGFRs from creatinine only equations.

Evaluation of cystatin C-derived glomerular filtration rate equations in Chinese population

ABTRACTGlomerular filtration rate (GFR) has become the best indicator for assessing renal function. This study aims to validate the existing cystatin C (CysC)-derived estimated glomerular filtration rate (eGFR) equations in Chinese patients to explore whether the reported CysC-derived eGFR formulas could be applied to the Chinese population. This study validated the equations in a population totaling 1816 inpatients. We calculated eGFR by different CysC-derived equations, then compared with the mGFR. Equation performance was assessed by bias (mean difference between mGFR and eGFR), precision (inter-quartile range of difference) and accuracy (mainly, accuracy within 30% [P30]). All equations expressed poor performance in dialysis patients (n = 345), and the performance for non-dialysis patients (n = 1471) were significantly greater than that in dialysis patients. Feng and Pei equations had higher P30 (50.82% and 49.73%, respectively) than the widely used CKD-EPICysC (41.10%) and MacIsaac equations (48.23%), and the distribution of eGFR values is more similar to the distribution of mGFR in non-dialysis patients. Similar trends showed in mGFR, sex, age, and BMI subgroups. However, no equation met the guideline standard of P30 ≥ 75%. Our results suggest that the published CysC-based eGFR equations are not suitable for dialysis patients, and the accuracy of equations for non-dialysis patients significantly better than the dialysis ones. Moreover, Feng and Pei equation showed better performance in non-dialysis patients.

Cystatin C as a novel predictor of preterm labor in severe preeclampsia.

BackgroundThe most common cause of acute kidney injury (AKI) in pregnancy is preeclampsia. Serum cystatin C (CysC) is a potential biomarker of early kidney damage as its levels are not disturbed by volume status changes in pregnancy, and serum CysC levels could serve as a replacement for conventionally used creatinine. In this study, we investigated the serum levels of CysC in severe preeclampsia cases and the associations between CysC levels and poor obstetric outcomes.MethodsOur cohort included severe preeclampsia patients with a normal serum creatinine level. Creatinine was measured to calculate estimated glomerular filtration rate (eGFR) based on the Cockcroft and Gault, Modification of Diet in Renal Disease Study (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, while CysC was measured to calculated eGFR based on a CysC-based equation. We then evaluated the correlations between serum CysC level, eGFR, and obstetric outcomes.ResultsTwenty-six patients were evaluated of which 38.5% delivered preterm and 30.8% had low-birth weight babies. Unlike creatinine-based eGFR and CysC-based eGFR, serum CysC demonstrate significant negative correlation with gestational age. Receiver operating characteristic curve analysis indicated that serum CysC is a potential biomarker of preterm delivery with a cut-off serum level of 1.48 mg/L with 80% sensitivity and 75% specificity.ConclusionGFR estimation using CysC is likely to be inaccurate in pregnancy. However, we found a significant correlation between preterm delivery and serum CysC level. Our results suggest that serum CysC level has the potential to predict preterm delivery in severe preeclampsia patients.

Prospective Comparison of Equations Based on Creatinine and Cystatin C for the Glomerular Filtration Rate Estimation in Chinese Renal Transplant Recipients

BackgroundCurrently, there is no dedicated equation to estimate glomerular filtration rate (GFR) for transplanted kidneys. This study aimed to compare the performance of serum creatinine (Scr)- and cystatin C (CysC)-based equations in Chinese renal transplant recipients. MethodsA total of 252 stable renal transplant recipients were enrolled in this study. The plasma clearance of 99mTc-DTPA (rGFR) was used as a reference standard. The Scr, CysC, and rGFR of the patients were measured on the same day. The bias, precision, accuracy (percentage of estimates within 10%, 30%, and 50% of rGFR), and agreements of 8 Scr and 5 CysC eGFR equations were assessed. The factors affecting the accuracy were also evaluated. ResultsAmong the Scr-based equations, the Japanese Society of Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) equation had the best overall performance with a bias of −6.2 mL/min/1.73 m2, and 96.1% of its estimates were within 30% of the rGFR. For the CysC-based equations, the Filler equation had the best performance with a bias of −3.9 mL/min/1.73 m2, and 93.7% of its estimates were within 30% of the rGFR. Overall, the CysC-based equations showed better performance than the Scr-based equations. In addition, significant differences were observed between bias and gender and between bias and rGFR value in some equations, whereas transplantation time and immunosuppressive regimens were not correlated with the bias. ConclusionThe JSN-CKDI equation provides the best estimation of the GFR equations, and the CysC-based equations performed better than the Scr-based equations in this population.

Monitoring the estimated glomerular filtration rate (eGFR) in patients with small-cell lung cancer during chemotherapy: equations based on serum creatinine or cystatin C?

This study compared the differences between the estimated glomerular filtration rate (eGFR) calculated by several equations based on serum creatinine (Scr) and cystatin C (CysC) concentrations for monitoring renal function in patients with small-cell lung cancer (SCLC) during chemotherapy. Seventy-one patients with SCLC were retrospectively analyzed. The eGFR before and after each chemotherapy cycle was calculated by the following equations: the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, the modification of diet in renal disease (MDRD) equation, the Cockcroft-Gault (CG) equation, and five CysC-based equations. The patients were compared among the different eGFR groups. The mean decreases in eGFRCKD-EPI (-2.25±9.89ml/min/1.73m2) between each treatment cycle were more significant than the decreases in eGFRCG (-0.46±10.17ml/min/1.73m2), eGFRMDRD (-0.48±9.79ml/min/1.73m2), and five calculated eGFRCysC (p<0.05). Single-/multiparameter analyses showed that patients with a higher body mass index (BMI>23) and receiving more treatment cycles (>3) were at increased risk for developing renal impairment with an eGFR less than 60ml/min/1.73m2 during chemotherapy. The eGFR calculated by the CKD-EPI equation changed more significantly between each chemotherapy cycle than did the eGFR from the other equations based on Scr or CysC in patients with SCLC. Oncologists should pay more attention to the renal function of specific patient groups during treatment.

Validation of cystatin C-based equations for evaluating residual renal function in patients on continuous ambulatory peritoneal dialysis.

Residual renal function needs to be assessed frequently in patients on continuous ambulatory peritoneal dialysis (CAPD). A commonly used method is to measure creatinine (Cr) and urea clearance in urine collected over 24 h, but collection can be cumbersome and difficult to manage. A faster, simpler alternative is to measure levels of cystatin C (CysC) in serum, but the accuracy and reliability of this method is controversial. Our study aims to validate published CysC-based equations for estimating residual renal function in patients on CAPD. Residual renal function was measured by calculating average clearance of urea and Cr in 24-h urine as well as by applying CysC- or Cr-based equations published by Hoek and Yang. We then compared the performance of the equations against the 24-h urine results. In our sample of 255 patients ages 47.9 ± 15.6 years, the serum CysC level was 6.43 ± 1.13 mg/L. Serum CysC level was not significantly associated with age, gender, height, weight, body mass index, hemoglobin, intact parathyroid hormone, normalized protein catabolic rate or the presence of diabetes. In contrast, serum CysC levels did correlate with peritoneal clearance of CysC and with levels of prealbumin and high-sensitivity C-reactive protein. Residual renal function was 2.56 ± 2.07 mL/min/1.73 m 2 based on 24-h urine sampling, compared with estimates (mL/min/1.73 m 2 ) of 2.98 ± 0.66 for Hoek's equation, 2.03 ± 0.97 for Yang's CysC-based equation and 2.70 ± 1.30 for Yang's Cr-based equation. Accuracies within 30%/50% of measured residual renal function for the three equations were 29.02/48.24, 34.90/56.86 and 31.37/54.90. The three equations for estimating residual renal function showed similar limits of agreement and differed significantly from the measured value. Published CysC-based equations do not appear to be particularly reliable for patients on CAPD. Further development and validation of CysC-based equations should take into account peritoneal clearance of CysC and other relevant factors.

Estimation of Glomerular Filtration Rate (GFR) Using Serum Cystatin C and Creatinine Has Poor Precision and Accuracy in Adults with HbSS Sickle Cell Disease

Introduction: Renal damage is a progressive complication of sickle cell disease (SCD) that begins with hyerfiltration in childhood followed by decline in glomerular filtration rate (GFR) and chronic renal failure in up to 12% of HbSS adults. Albuminuria is a marker of glomerular damage but does not predict GFR. Serum creatinine (SCr) is typically low in SCD despite glomerular damage, in part because tubular dysfunction leads to increased creatinine secretion. Cystatin C (CysC) is a low molecular weight protein, eliminated exclusively by glomerular filtration, and correlates with GFR in children and adults with chronic kidney disease (CKD). Previously, estimated GFR (eGFR) has been compared to measured GFR (mGFR) using equations that incorporate CysC and SCr in young children with SCD; however no studies have examined the precision or accuracy of GFR formulas in adults and older children with SCD.Methods: Adults and children ≥10 years with HbSS and albuminuria (albumin/creatinine ratio ≥30 mg/g) who were on hydroxyurea therapy for ≥6 months were enrolled on a trial of losartan therapy to determine effects on albuminuria and renal hemodynamics. GFR was measured by urinary clearance of intravenous iohexol at baseline and 2 time points subsequent to starting losartan. Serum creatinine and CysC were measured using standard clinical laboratory techniques. For subjects age ≥18 years, eGFR was calculated using 3 CysC-based equations that have high accuracy in adults with CKD:(1) eGFR = 76.7 x [CysC(mg/L)]-1.19;(2) eGFR = 127.7 x [CysC(mg/L)]-1.17 x age-0.13 x 0.91(female) x 1.06(African American);(3) eGFR = 177.6 x [SCr(mg/dL)]-0.65 x [CysC(mg/L)]-0.57 x age-0.20 x 0.80(female) x 1.11(African American).In subjects <18 years, eGFR was calculated by:(1) modified Schwartz formula, eGFR = height in cm x 0.41/SCr(mg/dL), and(2) CKiD Schwartz formula: eGFR = 39.1 x [height (m)/SCr]0.516 x [1.8/CysC (mg/L)]0.294 x [30/BUN (mg/dL)]0.169 x 1.099(male) x [height(m)/1.4]0.188.The relation of serum CysC with mGFR was determined by Pearson's correlation. Bias was assessed as the median difference between eGFR and mGFR, and precision as the interquartile range (IQR) for the difference. Accuracy was assessed as the percent of estimates within 10% (P10), 30% (P30) and 50% (P50) of mGFR.Results: In 15 subjects (4 female, 1 <18 years), there were 33 iohexol GFR measurements (15 prior to losartan, 18 on losartan). Eight (53%) had macroalbuminuria (ACR >300 mg/g). Mean SCr was 0.58 mg/dL, mean CysC was 0.74 mg/L (normal 0.5 - 1.0 mg/L), and mean mGFR was 106.9 ml/min/1.73 m2 (range 68 - 147). Four (27%) subjects had stage 2 CKD (GFR <90 ml/min/1.73 m2) measured at 7 time points prior to losartan. CysC correlated inversely with mGFR (r= -0.58, p=0.0003) (Figure) and was higher in those with stage 2 CKD vs. stage 1 (mean 0.95 vs. 0.68 mg/L, p=0.0013). CysC was above laboratory-defined normal range in 2/26 (7%) with stage 1 CKD and 3/7 (43%) with stage 2 CKD (p=0.052). For subjects ≥18 years (31 measurements), bias, precision, and accuracy of all 3 equations is shown in the Table. Bias tended to be less for measurements taken while on losartan; however this was not a significant difference for any eGFR equation. For the 1 subject <18 years (2 measurements), the modified Schwartz formula had less bias than the CKiD formula (12.4 vs. 83.7 ml/min/1.73 m2). Table 1Bias - ml/min/1.73 m2 (95% CI)Precision - IQR ml/min/1.73 m2 (95% CI)P10 - %P30 - %P50 - %Equation 121.9 (-7.8, 29.8)50.1 (6.3, 66.6)12.961.396.7Equation 233.5 (-4.7, 47.6)58.0 (12.4, 81.5)16.151.674.2Equation 364.3 (51.7, 80.0)42.2 (8.4, 76.9)9.716.138.7Conclusions: In adults with HbSS, the equation that best estimated GFR incorporated serum CysC alone without age, sex, race, or SCr; however accuracy and precision of all equations was unacceptably low and tended to overestimate GFR. Equation 3 which incorporated SCr had the greatest positive bias. Cystatin C correlates with GFR in SCD, and is elevated more frequently in stage 2 CKD, thus it remains an important marker of renal impairment in this population. As direct GFR measurement is not practical in the general clinical setting, further studies are needed to develop eGFR equations with improved accuracy for the SCD population. DisclosuresOff Label Use: Losartan was given to patients for treatment of sickle cell nephropathy, defined as albuminuria with albumin/creatinine ratio >30 mg/g. Losartan is FDA approved for diabetic nephropathy and hypertension, but has no indications for sickle nephropathy.

Evaluation of Serum Cystatin C as a Marker of Early Renal Impairment in Patients with Liver Cirrhosis

Background. Serum cystatin C (CysC) was proposed as an effective reflection of the glomerular filtration rate (GFR). However, its role in patients with liver cirrhosis has not been extensively verified especially in the detection of early RI. Patients and Methods. Seventy consecutive potential candidates for living donor liver transplantation with serum creatinine (Cr) <1.5 mg/dL were included. CysC, Cr, and estimated GFR [creatinine clearance (CCr), Cockcroft-Gault formula (C-G), MDRD equations with 4 and 6 variables, CKD-EPI-Cr, CKD-EPI-CysC, and CKD-EPI-Cr-CysC] were all correlated to isotopic GFR. Early RI was defined as GFR of 60–89 mL/min/1.73 m2. Results. Patients were 25.7% and 74.3% Child-Pugh classes B and C, respectively. GFR was ≥90, 60–89, and 30–59 mL/min/1.73 m2 in 31.4%, 64.3%, and 4.3% of the patients, respectively. All markers and equations, except C-G, were significantly correlated to GFR with CKD-EPI-Cr-CysC formula having the highest correlation (r = 0.474) and the largest area under the ROC curve (0.808) for discriminating early RI. At a cutoff value of 1.2 mg/L, CysC was 89.6% sensitive and 63.6% specific in detecting early RI. Conclusion. In patients with liver cirrhosis, CysC and CysC-based equations showed the highest significant correlation to GFR and were measures that best discriminated early RI.

G.P.173: Are current formulas for estimated glomerular filtration rate reliable in children and adolescents with Duchenne muscular dystrophy?

Improved life expectancy and the need to monitor renal safety of new therapies have fueled interest in renal function in patients with Duchenne muscular dystrophy (DMD). We assessed the usefulness of estimated glomerular filtration rate (eGFR) formulas based on serum creatinine (sCr) and/or cystatin C (CysC) in children and adolescents with DMD. DMD patients have low sCr values since they have less muscle mass. SCr-based formulas may therefore have limitations. CysC, being independent of muscle mass, may serve as a valuable alternative for eGFR in DMD. In a prospective cross-sectional study, 18 patients (5–22 years) underwent 51 Cr-EDTA for GFR measurement (mGFR), blood and urine analysis. Values for renal clearance obtained with sCr-based, CysC-based and sCr/CysC-based eGFR formulas were compared to mGFR. Median mGFR was 128 ml/min/1.73 m 2 . Nine patients had a mGFR >P90 (135 ml/min/m 2 ). Because of very low sCr values (mean ± SD: 0.16 ± 0.07 mg/dL), sCr-based and sCr/CysC-based formulas overestimate GFR. Mean eGFR ± SD was 464.0 ± 264.1 ml/min/1.73 m 2 for Schwartz, 464.2 ± 269.4 ml/min/1.73 m 2 for Flanders Metadata, 178.7 ± 61.1 ml/min/1.73 m 2 for height-independent and 479.9 ± 327.0 ml/min/1.73 m 2 for the Q (height) equation. CysC values (0.78 ± 0.13 mg/L) are within normal adult reference ranges. However, sCr/CysC-based formulas result in mean eGFR ± SD of 154.2 ± 34.7 ml/min/1.73 m 2 for Zappitelli and 169.2 ± 43.7 ml/min/1.73 m 2 for Bouvet. Concerning CysC-based equations the mean eGFR ± SD was 153.8 ± 60.3 ml/min/1.73 m 2 for Larsson, 125.4 ± 21.9 ml/min/1.73 m 2 for Filler and 105.4 ± 19.1 ml/min/1.73 m 2 for Zappitelli. This study demonstrates that sCr-based and sCr/CysC-based formulas should not be used for eGFR in DMD. However, even though mGFR and CysC-based equations showed a better agreement, more research is needed to confirm the preliminary findings that CysC-based equations are suitable for eGFR in DMD patients.

Comparison of seven kinds of calculation methods on glomerular filtration rate in patients with chronic kidney disease

Objective: The objective was to compare the diagnostic value of seven kinds of calculation methods on glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD). Materials and Methods: A total of 120 cases with CKD and 120 normal people were included in this study. They were grouped according to the GFR results estimated by the plasma clearance of 99m technetium-diethylene-triamine-pentaacetate. Serum cystatin C (Cys C) concentrations were detected by enzyme-linked immunosorbent assay. GFR and serum creatinine (SCr) was simultaneously analyzed using Automatic Biochemistry Analyzer. Estimated GFR (eGFR) was detected with seven kinds of calculation methods. Results: Modification of diet in renal disease (MDRD) equations obtained significantly lower GFR in group CKD2, while Cockcroft-Gault (CG) equation obtained significantly lower GFR in group CKD3. There were no statistical differences between four Cys C-based equations (GFR estimated via cystatin [Cys-eGFR] formula) and GFR from CKD1 to CKD5. In the groups CKD2 and CKD3, GFRs detected by four kinds of formula Cys-eGFR were all superior to that by CG and MDRD. For the CKD patients with GFR <60 mL/min/1.73 m 2 , four kinds of receiver operating characteristic (ROC) curve area of Cys-eGFR were more than GFR estimated via creatinine (Cr-eGFR) formula, the differences were statistically significant. For those with GFR <30 mL/min/1.73 m 2 , the comparative results of ROC curve area had no statistical difference. Conclusion: Cys-eGFR is a more accurate equation for estimating GFR than CG and MDRD equation, but not superior to Cr-eGFR, which based on SCr in advanced chronic renal failure patients.