Performance and Determinants of Serum Creatinine and Cystatin C-Based GFR Estimating Equations in South Asians.

INTRODUCTION: The creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) equation was calibrated for the general Pakistan population (eGFRcr-PK) to eliminate bias and improve accuracy. Cystatin C-based CKD-EPI equations (eGFRcys and eGFRcr-cys) have not been assessed in this population, and non-GFR determinants of cystatin C are unknown. METHODS: We assessed eGFRcys, eGFRcr-cys, and non-GFR determinants of cystatin C in a cross-sectional study of 557 participants (≥40 years of age) from Pakistan. We compared bias (median difference in measured GFR [mGFR] and eGFR), precision (interquartile range [IQR] of differences), accuracy (percentage of eGFR within 30% of mGFR), root mean square error (RMSE), and classification of mGFR <60 ml/min/1.73 m2 (area under the receiver operating characteristic curve [AUC] and net reclassification index [NRI]) among eGFR equations. RESULTS: We found that eGFRcys underestimated mGFR (bias, 12.7 ml/min/1.73 m2 [95% confidence interval {CI} 10.7-15.2]). eGFRcr-cys did not improve performance over eGFRcr-PK in precision (P = 0.52), accuracy (P = 0.58), or RMSE (P = 0.49). Results were consistent among subgroups by age, sex, smoking, body mass index (BMI), and eGFR. NRI was 7.31% (95% CI 1.52%-13.1%; P < 0.001) for eGFRcr-cys versus eGFRcr-PK, but AUC was not improved (0.92 [95% CI 0.87-0.96] vs. 0.90 [95% CI 0.86-0.95]; P = 0.056). Non-GFR determinants of higher cystatin C included male sex, smoking, higher BMI and total body fat, and lower lean body mass. CONCLUSION: eGFRcys underestimated mGFR in South Asians and eGFRcr-cys did not offer substantial advantage compared with eGFRcr-PK. Future studies are warranted to better understand the large bias in eGFRcys and non-GFR determinants of cystatin C in South Asians.

Serum Cystatin C as a Potential Marker for Glomerular Filtration Rate in Patients with Cholangiocarcinoma.

Background: Cholangiocarcinoma (CCA) is the second most common primary hepatobiliary cancer. These patients have meager prognosis and short-term survival. Precise assessment of glomerular filtration rate is a fundamental aspect of clinical care in cancer patients. Cystatin C has been proposed to be superior to creatinine, a well-known marker of renal function. This study aimed to evaluate cystatin C as a marker of GFR calculation in CCA patients. Materials and Methods: One hundred thirty serum samples from CCA patients and 32 from controls were included in this study. Serum cystatin C was measured using immunoturbidity assay. Estimated glomerular filtration rate was calculated by three equations established by chronic kidney disease epidemiology collaboration (based on creatinine and/or cystatin C). Results: Serum cystatin C in CCA patients was higher than that of controls (p=0.0002). Cystatin C was positively correlated with BUN in CCA group (p=0.019). eGFR based on cystatin C and based on both cystatin C and creatinine in CCA was low with significantly different from those of control (p<0.001). Although there was no difference in eGFR using three equations in control, creatinine based eGFR was high with significantly different from eGFR based on cystatin C and on both creatinine and cystatin C in CCA (P=0.000). Proportion in each eGFR stage by three equations showed a high sensitivity with significantly different in CCA (p<0.05). Conclusion: There was a high sensitivity of cys C with significant difference between creatinine and/or cystatin C based eGFR in CCA patients. It should be taken into consideration of mild changes in eGFR by cystatin C which is important in managing drug dosage for CCA patients.

Glomerular filtration rate estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in type 1 diabetes based on genomic ancestry.

BACKGROUND: Black individuals have a great risk of developing chronic kidney disease (CKD) that is associated with high morbimortality, so it is important to classify them into the correct renal function group. Some equations used to estimate glomerular filtration rate (eGFR) divide patients only into two categories: African Americans and non-African Americans. The CKD-EPI equation was tested only in African Americans, and not Black patients from other regions, and takes into consideration self-reported color-race instead of genomic ancestry (GA) to determine the use of the ethnic correction factor. So far, this equation has not been evaluated in admixed populations, such as the Brazilian, using the percentage of GA to decide to apply the correction factor. The purpose of our study was to compare, in patients with type 1 diabetes (T1D), the eGFR calculated without the use of the correction factor, with the values obtained using the correction factor in patients presenting 50% or more of African GA. METHODS: This cross-sectional, multicenter study enrolled 1279 patients from all geographic regions of Brazil. The CKD-EPI equation was used and CKD was defined as eGFR < 60 ml/min. GA were inferred using a panel of 46 AIM-INDEL, afterwards patients presenting an African GA ≥ 50% were selected. RESULTS: Initially, all patients with African GA ≥ 50% (n = 85) were considered as non-African Americans when calculating the eGFR and afterwards the ethnic correction factor was applied to recalculate the eGFR. CKD was present in 23 patients and 56.5% of them were redefined as having normal renal function after using the correction factor, mainly women [11 of the 13 patients (84.6%)], with GFR between 52-59.3 ml/min. CONCLUSIONS: More than half of the patients in the study were reclassified to a normal renal function group, showing that GA may be an important tool to decide between the use of the ethnic correction factor in the CKD-EPI equation in a highly admixed population of patients with T1D. A large-scale study involving GA and eGFR in comparison to reference methods should be conducted to better establish whether or not the ethnic correction factor should be used in highly admixed populations.

Comparison of bias and accuracy using cystatin C and creatinine in CKD-EPI equations for GFR estimation.

BACKGROUND: The directly measured glomerular filtrate rate (mGFR) is the gold standard for kidney function, but it is invasive and costly. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been widely used to estimate GFR, however, the comparative accuracy of estimated GFR (eGFR) using creatinine and cystatin C in CKD-EPI equations remains unclear. We performed this meta-analysis to assess the bias and accuracy of eGFR using equations of CKD-EPIcrea, CKD-EPIcys, and CKD-EPIcrea/cys in adult populations relevant to primary health care. METHODS: Pubmed, Web of Science, EMBASE, and the Cochrane Library were searched from inception until December 2019 for related studies. RESULTS: A total of 35 studies with 23,667 participants, which reported the data on the bias, and/or P30, and/or R were included. The difference in the bias of eGFR using CKD-EPIcys was 4.84 mL/min/1.73 m2 (95% CI, 1.88~7.80) lower than using CKD-EPIcrea, and 1.50 mL/min/1.73 m2 (95% CI, 0.05~2.95) lower than using CKD-EPIcrea/cys. These gaps increased in subgroups of low mGFR (<60 mL/min/1.73 m2). CKD-EPIcrea/cys eGFR achieved the highest accuracy, 7.50% higher than CKD-EPIcrea (95% CI, 4.81~10.18), and 3.21% higher than CKD-EPIcys (95% CI, -0.43~6.85); and the best correlation with mGFR, with Fisher's z transformed R of 1.20 (95% CI, 0.89-1.50). CONCLUSIONS: CKD-EPIcrea/cys and CKD-EPIcys gave less bias and more accurate estimates of mGFR than CKD-EPIcrea. More variables and coefficients could be added in CKD-EPI equations to achieve less bias and more accuracy in future research.

Kidney and vascular function in adult patients with hereditary fructose intolerance.

Objective: Previous studies have shown that patients with hereditary fructose intolerance (HFI) are characterized by a greater intrahepatic triglyceride content, despite a fructose-restricted diet. The present study aimed to examine the long-term consequences of HFI on other aldolase-B-expressing organs, i.e. the kidney and vascular endothelium. Methods: Fifteen adult HFI patients were compared to healthy control individuals matched for age, sex and body mass index. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV) and endothelial function by peripheral arterial tonometry, skin laser doppler flowmetry and the endothelial function biomarkers soluble E-selectin [sE-selectin] and von Willebrand factor. Serum creatinine and cystatin C were measured to estimate the glomerular filtration rate (eGFR). Urinary glucose and amino acid excretion and the ratio of tubular maximum reabsorption of phosphate to GFR (TmP/GFR) were determined as measures of proximal tubular function. Results: Median systolic blood pressure was significantly higher in HFI patients (127 versus 122 mmHg, p = .045). Pulse pressure and cf-PWV did not differ between the groups (p = .37 and p = .49, respectively). Of all endothelial function markers, only sE-selectin was significantly higher in HFI patients (p = .004). eGFR was significantly higher in HFI patients than healthy controls (119 versus 104 ml/min/1.73m2, p = .001, respectively). All measurements of proximal tubular function did not differ significantly between the groups. Conclusions: Adult HFI patients treated with a fructose-restricted diet are characterized by a higher sE-selectin level and slightly higher systolic blood pressure, which in time could contribute to a greater cardiovascular risk. The exact cause and, hence, clinical consequences of the higher eGFR in HFI patients, deserves further study.

GFR estimation in lenalidomide treatment of multiple myeloma patients: a prospective cohort study.

BACKGROUND: The estimated glomerular filtration rate (eGFR) is clinically used to approximate renal function and adapt drug dosage. Multiple myeloma is a hematological disease; its prognosis is largely influenced by renal function. We evaluated two commonly used GFR estimations, CKD-EPI and MDRD (CKD Epidemiology Collaboration; Modification of Diet in Renal Disease) in myeloma patients undergoing treatment with lenalidomide, a renally excreted immunomodulatory drug. METHODS: We prospectively studied 130 myeloma patients receiving lenalidomide treatment at our institution. At baseline and after 3 months, GFR estimations were performed based on the CKD-EPI and MDRD equations. We compared eGFR-dependent CKD staging and lenalidomide dosage assignments. RESULTS: Initially, most patients were classified as CKD stage I/II, using both equations. Comparison of baseline renal function via CKD-EPI and MDRD induced concordance of CKD staging in 83% of patients, while CKD-EPI improved CKD staging in 16% of patients (p = 0.11). CKD-EPI assigned 3% of patients to higher lenalidomide dosing as opposed to MDRD. Both equations showed improved eGFR after 3 months of lenalidomide treatment. CONCLUSIONS: In our multiple myeloma patient cohort, CKD-EPI and MDRD led to similar CKD staging with minor differences in lenalidomide dosage assignment. Consistent with previous studies, eGFR improved under lenalidomide treatment. To standardize GFR estimation in myeloma patients, we suggest using the CKD-EPI equation.

Comparative evaluation of technetium-99m-diethylenetriaminepentaacetic acid renal dynamic imaging versus the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equation for the estimation of GFR.

PURPOSE: We compared the performance of technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) renal dynamic imaging (RDI), the MDRD equation, and the CKD EPI equation to estimate glomerular filtration rate (GFR). METHODS: A total of 551 subjects, including CKD patients and healthy individuals, were enrolled in this study. Dual plasma sample clearance method of 99mTc-DTPA was used as the true value for GFR (tGFR). RDI and the MDRD and CKD EPI equations for estimating GFR were compared and evaluated. RESULTS: Data indicate that RDI and the MDRD equation underestimated GFR and CKD EPI overestimated GFR. RDI was associated with significantly higher bias than the MDRD and CKD EPI equations. The regression coefficient, diagnostic precision, and consistency of RDI were significantly lower than either equation. RDI and the MDRD equation underestimated GFR to a greater degree in subjects with tGFR ≥ 90 ml/min/1.73 m2 compared with the results obtained from all subjects. In the tGFR60-89 ml/min/1.73 m2 group, the precision of RDI was significantly lower than that of both equations. In the tGFR30-59 ml/min/1.73 m2 group, RDI had the least bias, the most precision, and significantly higher accuracy compared with either equation. In tGFR < 30 ml/min/1.73 m2, the three methods had similar performance and were not significantly different. CONCLUSIONS: RDI significantly underestimates GFR and performs no better than MDRD and CKD EPI equations for GFR estimation; thus, it should not be recommended as a reference standard against which other GFR measurement methods are assessed. However, RDI better estimates GFR than either equation for individuals in the tGFR30-59 ml/min/1.73 m2 group and thus may be helpful to distinguish stage 3a and 3b CKD.

Comparison of MDRD, CKD-EPI, and Cockcroft-Gault equation in relation to measured glomerular filtration rate among a large cohort with diabetes.

AIMS: To analyze the performance of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft-Gault (CG), and CG calculated with ideal bodyweight (CG-IBW) equations to estimate glomerular filtration rate (eGFR) based on serum creatinine in a large diabetic population. METHODS: 24,516 adults with type-1-diabetes or type-2-diabetes from the multicenter diabetes prospective follow-up registry DPV were analyzed. We compared eGFR and measured GFR (mGFR) based on 24-h urine collection by calculating mean bias (difference), precision (SD of this difference), accuracy (proportion of eGFR within ±10% of mGFR), Bland-Altman-plots. RESULTS: CG overestimates, whereas MDRD, CKD-EPI, and CG-IBW underestimate. Smallest mean bias and highest accuracy (75.3%) were observed for MDRD compared to the other equations (p<0.0001). MDRD and CKD-EPI estimated most accurately in stages 1 (MDRD:57.7%, CKD-EPI:57.3%) and 2 (MDRD:80.2%, CKD-EPI:80.7%). In stages 3 to 5, highest accuracy was observed for the MDRD (stage 3:82.3%, stage 4:77.8%, stage 5:71.0%). Among younger subjects, accuracy was higher using the CKD-EPI (18-<40years:63.7%, 40-<60years:72.8%). Above age 60years, MDRD estimated most accurately (60-<70years:77.3%, ≥70years:78.8%). In males and females, MDRD estimated most accurately (males:75.3%, females:75.3%). CONCLUSION: In this large diabetic cohort, smallest bias and highest accuracy were observed for the MDRD.

The Chronic Kidney Disease Epidemiology Collaboration equation improves the detection of hyperfiltration in Chinese diabetic patients.

OBJECTIVE: Hyperfiltration confers an increased risk of diabetic nephropathy. Early detection can ensure timely intervention and improved treatment outcomes. Because GFR is known to be affected by hyperglycemia, the aim of this study was to compare the influence of hyperglycemia on GFR estimations calculated by the CKD-EPI equation, the CG equation, and the MDRD equations in estimating hyperfiltration in Chinese diabetic patients. MATERIALS AND METHODS: The performance of the equations, compared with the measured (99)mTc-DTPA glomerular filtration rate was analyzed in 3492 diabetic patients. Bias, precision, and accuracies were compared with respect to HbA1c status. The Bland-Altman method was used to evaluate the agreement among the equations with respect to the mGFR, and the receiver-operating characteristic curve method was used to evaluate diagnostic value of the three equations with respect to the detection of moderate renal failure and hyperfiltration. RESULTS: The mean absolute bias was the smallest for the CKD-EPI equation in the HbA1c < 7.2% cohort, and the highest accuracy within ± 15% and ± 30% was also reached with the CKD-EPI equation in both cohorts. For the detection of hyperfiltration, the CKD-EPI equation exhibited the best performance with the greatest combination of sensitivity and specificity. The biases of the three equations were significantly higher in the HbA1c ≥ 10.5% subgroup compared with the HbA1c < 7.2% cohort. CONCLUSION: The CKD-EPI equation can be used as a screening tool for hyperfiltration and appears to be a more generalizable and accurate equation for estimating GFR in Chinese diabetic patients.

Improved glomerular filtration rate estimation using new equations combined with standardized cystatin C and creatinine in Chinese adult chronic kidney disease patients.

OBJECTIVES: The newly developed glomerular filtration rate (GFR)-estimating equations developed by the CKD-EPI Collaboration and Feng et al. (2013) that are based on standardized serum cystatin C (ScysC), combined/not combined with serum creatinine (Scr), require further validation in China. We compared the performance of four new equations (CKD-EPIcys, CKD-EPIcr-cys, Fengcys, and Fengcr-cys equations) with the CKD-EPI creatinine equation (CKD-EPIcr) in adult Chinese chronic kidney disease (CKD) patients to clarify their clinical application. DESIGN AND METHODS: GFR was measured using the dual plasma sampling (99m)Tc-DTPA method (mGFR) in 252 adult CKD patients enrolled from four centres. Scr and ScysC were measured by standardized assays in a central laboratory. Each equation's performance was assessed using bias, precision, accuracy, agreement, and correct classification of the CKD stage. RESULTS: The measured GFR was 46 [25-83] mL/min per 1.73 m(2). The CKD-EPIcys, CKD-EPIcr-cys and Fengcys equations provided significantly higher accuracy (P15: 38.9%, 39.7%, and 38.9%) than the CKD-EPIcr equation (29.8%). The CKD-EPIcr-cys and Fengcr-cys equations presented higher precision (IQR of the difference, 16.4 and 17.3 mL/min per 1.73 m(2), respectively) and narrower acceptable limits in Bland-Altman analysis (56.6 and 50.8 mL/min per 1.73 m(2), respectively) than single marker-based equations. The CKD-EPIcr-cys equation achieved the highest overall correct proportion (61.5%) in classification of CKD stages. CONCLUSIONS: Combining ScysC and Scr measurements for GFR estimation improves diagnostic performance. The Scr-ScysC equation showed better performance than equations based on either marker alone. The CKD-EPIcr-cys equation showed the best performance for GFR estimation in Chinese adult CKD patients.

Relationship between estimated glomerular filtration rate and biological half-life of 131I. Retrospective analysis in patients with differentiated thyroid carcinoma.

AIM: This retrospective study sought to investigate the relationship between biological half-life (t1/2 biol) of 131I and estimated glomerular filtration rate (eGFR) in patients with thyroid carcinoma. PATIENTS, METHODS: 96 patients with differentiated thyroid carcinoma (69 women, 27 men, mean age 64.0 ± 13.6 years) and diagnostic and therapeutic administration of 131I were considered. Patients with pronounced specific iodine storage were not included in the study. The eGFR was estimated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, the t1/2 biol via dosimetry. Patients were subdivided in groups with normal clearance (NC) (n = 37, 38.5%), medium clearance (MC) (n = 48, 50.0%), and low clearance (LC) (n = 11, 11.5%) (eGFR ≥ 90; 60-89; 15-59 ml/min per 1.73 m2, respectively). The relationship between eGFR and t1/2 biol of 131I was modeled using a power function. RESULTS: The groups significantly differed in terms of age (NC 53.8, MC 68.6, and 78.0 years, respectively), serum creatinine levels (NC: 0.71; MC: 0.85; LC: 1.18 mg/dl), and t1/2 biol (NC: 0.53; MC: 0.71; LC: 1.01 days). The t1/2 biol was significantly influenced only by eGFR, and not by age, gender, or body weight. The relationship between t1/2 biol of 131I and eGFR was described by the formula t1/2 biol = 20.3 · eGFR-0.782. CONCLUSIONS: The calculated relationship between renal function and t1/2 biol of 131I can be used in principle to estimate a dose reduction for patients with renal insufficiency. The model, however, gives erroneous results in individual cases and therefore a routine utilization cannot be recommended. Prospective studies are necessary, based on larger patient numbers and more accurate methods for dose rate measurement and GFR.