Endogenous Filtration Markers Research Articles

Glomerular Filtration Rate Estimation Using β2-Microglobulin and β-Trace Protein in Adults With Solid Tumors: A Prospective Cross-Sectional Study

β2-Microglobulin (B2M) and β-trace protein (BTP) are novel endogenous filtration markers that may improve the accuracy of estimated glomerular filtration rate (eGFR) beyond creatinine and cystatin C (eGFRcr-cys), but they have not been assessed in patients with cancer. Cross-sectional analysis. Prospective cohort of 1,200 patients with active solid tumors recruited between April 2015 and September2017. CKD-EPI equations without race combining B2M and/or BTP with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR). Performance of equations compared with eGFRcr-cys and non-GFR determinants of serum B2M and BTP (SB2M, and SBTP, respectively). Measured GFR (mGFR) was determined using the plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). Bias was defined as the median of the differences between mGFR and eGFR, and 1-P30 was defined as the percentage of estimates that differed by more than 30% from the mGFR (1-P30). Linear regression was used to assess association of clinical and laboratory variables with SB2M, and SBTP after adjustment for mGFR. Mean age and mGFR were 58.8±13.2 SD years and 78.4±21.7 SD mL/min/1.73m2, respectively. Performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys (lesser bias and 1-P30). Performance of 2-marker panel equations was as good as eGFRcr-cys (lesser bias and similar 1-P30). SB2M and SBTP were not strongly influenced by cancer site. Participants may have had better clinical performance status than the general population of patients with solid tumors. B2M and BTP can improve the accuracy of eGFR and may be useful as confirmatory tests in patients with solid tumors, either by inclusion in a multimarker panel equation with creatinine and cystatin C, or by substituting for cystatin C in combination with creatinine. The most accurate method to assess estimate kidney function is estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys). We studied whether using β2-microglobulin (B2M) and/or β-trace protein (BTP) with creatinine with or without cystatin C (2-, 3-, or 4-marker panel eGFR) might be useful in patients with active solid tumors. The performance of the 3-marker and 4-marker panel equations was better than eGFRcr-cys. Performance of 2-marker panel equations was as good as eGFRcr-cys. We conclude that B2M and BTP can improve the accuracy of eGFR and may be useful as a confirmatory test in patients with solid tumors either by inclusion in multimarker panel equation with creatinine and cystatin C or by substituting for cystatin C in combination with creatinine.

Transcutaneous measurement of renal function in two rodent models of obstructive nephropathy

ObjectiveGlomerular filtration rate (GFR) is a key indicator of renal function. In both clinical practice and pre-clinical research, serum levels of endogenous filtration markers, such as creatinine, are often used to estimate GFR. However, these markers often do not reflect minor changes in renal function. In this study, we therefore set out to evaluate the applicability of transcutaneous GFR (tGFR) measurements to monitor the changes in renal function, as compared to plasma creatinine (pCreatinine), in two models of obstructive nephropathy, namely unilateral ureteral obstruction (UUO) or bilateral ureteral obstruction followed by release (BUO-R) in male Wistar rats.ResultsUUO animals showed a significant reduction in tGFR compared to baseline; whereas pCreatinine levels were not significantly changed. In BUO animals, tGFR drops 24 h post BUO and remains lower upon release of the obstruction until day 11. Concomitantly, pCreatinine levels were also increased 24 h after obstruction and 24 h post release, however after 4 days, pCreatinine returned to baseline levels. In conclusion, this study revealed that the tGFR method is superior at detecting minor changes in renal function as compared to pCreatinine measurements.

Differences of Kidney Function Test Results Using Creatinine Clearance Test and Estimated Glomerular Filtration Rate (e-GFR) CKD EPI

Background. Chronic diseases have become one of the world's public health problems in recent decades, and mortality rate are projected to continue to rise. The diagnosis and severity of CKD is based on the results of renal function tests recommended by KDIGO is Glomerulus Filtration Rate (GFR) patients. A simple and inexpensive method is to use endogenous filtration markers to calculate GFR such Creatinine Clearance Test (CCT) or e-GFR CKD EPI formula. Accurate calculation of GFR by CCT and e-LFG CKD-EPI are important to avoid misdiagnosis of CKD. This study aimed to determine if there is any difference in the results between these two methods.
 Method. This study used analytical observational cross-sectional research method. Samples were selected from the population based on inclusion criteria having complete variability data and no exclusion criteria. Analyzed by SPSS software version 28 to check normality using Kolgomorov-Smirnov test, significance test with Mann Whitney and Spearman to check correlation.
 Results. The results of the study of 1257 samples, showing that the data are not normally distributed (p = 0.000), had a significant difference between CCT and e-GFR CKD EPI (p = 0.000) and the correlation is linear and moderate correlation strength (r=0.403) (p=0.000).
 Conclusion. Differences in kidney function test results using CCT and e-GFR CKD-EPI methods in patients who carried out laboratory examinations at the clinical pathology laboratory at Sanglah Hospital, Bali during April 2020–April 2021, was found that there were differences in the results of CCT and e-GFR CKD EPI.

Interpretation of Estimated Glomerular Filtration Rate

Glomerular filtration rate (GFR) plays an important role in the clinical evaluation of renal function, classification, prognosis prediction, and drug dosing in patients with acute or chronic kidney disease . Estimated GFR (eGFR) is calculated based on endogenous filtration markers, such as creatinine and cystatin C. These are useful markers, but it is necessary to understand the clinical settings in which eGFR, calculated using creatinine or cystatin C, may be less accurate. Several equations, including the Cockcroft and Gault, modification of diet in renal disease, and chronic kidney disease-epidemiology collaboration (CKD-EPI) equations, are used to calculate eGFR. The latter is most common because it has high accuracy and can predict prognosis. Recently, a new race-omitting CKD-EPI equation has been developed but further studies are required to determine whether it can be applied in clinical practice and research. Furthermore, careful use of eGFR is needed in acute kidney injury, kidney transplantation, and dialysis patients. Drug dosing must be guided by accurate GFR assessment. In addition to medical care, GFR assessment is also important for public health and research. Therefore, further studies are needed to reevaluate and develop the equations for accurate eGFR calculations.

Comparing Estimated and Measured Glomerular Filtration Rate in Children with Posterior Urethral Valve.

Posterior urethral valve (PUV) is obstructive uropathy that may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children. Glomerular filtration rate (GFR) measurement remains the gold standard for renal function measurement. However, due to its less availability and cumbersome, it is not commonly used, and GFR is estimated utilizing various endogenous filtration markers. This study includes pediatric patients with PUV. We aimed to compare the measured GFR (mGFR) with various creatinine-based estimated GFR methods (eGFR). A single-center retrospective study included 62 treated cases of PUV, postvalve fulguration. The mGFR measured by 99mTc-diethylenetriaminepentaacetate in vitro method and compared with eight eGFR (Schwartz, Cockcroft-Gault [CG], Counahan-Barratt [CB], CKD Epidemiology Collaboration [CKD-EPI], full-age spectrum [FAS] age, FAS height (FAS Ht), Schwartz-Lyon [SL], and Ht independent). Patients were subdivided into different CKD grades and compared with various eGFR. PUV is a common cause of CKD in children and needs special consideration as there is growth retardation associated with it. It decreases creatinine production and thus fallacies in eGFR measurement. There is a requisite to identify and closely monitor the subset of patients with baseline decreased renal function and therefore at risk of developing ESRD. A total of 62 patients were included. Mean age and serum creatinine levels were 8.02 ± 5.53 years and 1.15 ± 0.95 mg/dl (range: 0.4-4.5), respectively. The mean mGFR was 61.6 ± 31.80 mL/min/1.73 m2 and a positive variable correlation was 0.46-0.77 between mGFR and eGFR. Based on mGFR, there were 14 (22.6%), 21 (33.8%), 13 (20.9%), 9 (14.5%), and 5 (8.1%) patients in Grades I-V, respectively. The correct classification of the CKD grades was noted in 25 (40.3%), 16 (25.8%), 32 (51.6%), 16 (25.8%), 25 (40.3%), 27 (43.5%), 26 (41.9%), and 28 (45.2%) patients by Schwartz, CG, CB, CKD-EPI, FAS age, FAS Ht, SL, and Ht-independent equation. The eGFR overestimates GFR at the lower level and underestimates at higher levels. Our results confirm the considerable limitations of various creatinine-based clearance methods for estimating actual GFR. The creatinine clearance-based eGFR should not replace the measurement of the GFR. An initial measure of the mGFR followed by serial follow-up with the eGFR equation may be done. The most accurate eGFR equations are CB for Grade II, SL or Ht independent for Grade III, FAS age for Grade IV, and SL for Grade V CKD.

Serum Uromodulin and All-Cause Mortality in Peritoneal Dialysis Patients: A Chinese Cohort Study

Serum Uromodulin and All-Cause Mortality in Peritoneal Dialysis Patients: A Chinese Cohort Study

Performance of Serum β2-Microglobulin– and β-Trace Protein–Based Panel Markers and 2021 Creatinine- and Cystatin-Based GFR Estimating Equations in Pakistan

Performance of Serum β2-Microglobulin– and β-Trace Protein–Based Panel Markers and 2021 Creatinine- and Cystatin-Based GFR Estimating Equations in Pakistan

Measurement of glomerular filtration rate and its current status in African countries GFR measurement and its status in Africa

Glomerular filtration rate (GFR) is usually estimated rather than measured as this only requires measurement of an endogenous filtration marker. In certain clinical settings a more accurate measure of GFR is essential. The most commonly used endogenous filtration marker is creatinine. Exogenous filtration markers include nonradiopharmaceuticals such as inulin, iohexol and unlabelled iothalamate, or radiopharmaceuticals such as 51Crethylenediaminetetraacetic acid (51Cr-EDTA) and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). Inulin is considered an ideal filtration marker but the clearance of iothalamate, 99mTc-DTPA, 51Cr-EDTA and iohexol have all been shown to have sufficient accuracy for measuring GFR. For radiopharmaceuticals, a well counter is required to measure the amount of activity in patient samples. Iohexol or unlabelled iothalamate require samples to be measured using high performance liquid chromatography with ultraviolet detection (HPLC-UV), liquid chromatography-tandem mass spectrometry (LC-MS/MS) or x-ray fluorescence (XRF). Due to the practical challenges of measuring urinary clearance, measurement of GFR in clinical settings is almost exclusively based on plasma clearance of a filtration marker. This can follow a long-established approach based on the ratio of the tracer administered to the area under the plasma concentration curve. Alternatively, a single plasma sample giving an apparent volume of distribution at a given time point can be used to accurately measure GFR. While techniques exist for the measurement of GFR in a number of African countries, preliminary evidence suggests that facilities are very limited. There is a need for support for both equipment and training to establish GFR measurement facilities in several centres on the continent. Keywords: measured glomerular filtration rate;, mGFR;, Africa

Resolving the Debate: The Future of Using Race in Estimating Kidney Function.

Racial and social unrest witnessed during 2020 ignited a national conversation about the appropriateness of the use of race in health care algorithms and in the estimation of kidney function in particular. The growing concerns over the use of race in kidney function-estimating equations prompted the National Kidney Foundation (NKF) and American Society of Nephrology to launch an effort for change by establishing a task force on reassessing the use of race in diagnosing kidney disease. After nearly a year examining the evidence and obtaining testimony from experts and stakeholders, the task force recommended the immediate implementation of the 2020 Chronic Kidney Disease-Epidemiology creatinine equation refit without race in all US laboratories; increased routine use of cystatin C for confirmation of estimated glomerular filtration rate in clinical decision-making and a call for research on glomerular filtration rate estimation with new endogenous filtration markers and on addressing disparities in health and health care. The NKF and American Society of Nephrology strongly encouraged rapid adoption of these new recommendations. Leadership efforts of the NKF have begun to lay the foundation for national implementation through laboratory engagement, clinician awareness, and patient education.

A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease.

In response to a national call for re-evaluation of the use of race in clinical algorithms, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) established a Task Force to reassess inclusion of race in the estimation of GFR in the United States and its implications for diagnosis and management of patients with, or at risk for, kidney diseases. The Task Force organized its activities over 10 months in phases to ( 1 ) clarify the problem and evidence regarding eGFR equations in the United States (described previously in an interim report), and, in this final report, ( 2 ) evaluate approaches to address use of race in GFR estimation, and ( 3 ) provide recommendations. We identified 26 approaches for the estimation of GFR that did or did not consider race and narrowed our focus, by consensus, to five of those approaches. We holistically evaluated each approach considering six attributes: assay availability and standardization; implementation; population diversity in equation development; performance compared with measured GFR; consequences to clinical care, population tracking, and research; and patient centeredness. To arrive at a unifying approach to estimate GFR, we integrated information and evidence from many sources in assessing strengths and weaknesses in attributes for each approach, recognizing the number of Black and non-Black adults affected. ( 1 ) For US adults (>85% of whom have normal kidney function), we recommend immediate implementation of the CKD-EPI creatinine equation refit without the race variable in all laboratories in the United States because it does not include race in the calculation and reporting, included diversity in its development, is immediately available to all laboratories in the United States, and has acceptable performance characteristics and potential consequences that do not disproportionately affect any one group of individuals. ( 2 ) We recommend national efforts to facilitate increased, routine, and timely use of cystatin C, especially to confirm eGFR in adults who are at risk for or have CKD, because combining filtration markers (creatinine and cystatin C) is more accurate and would support better clinical decisions than either marker alone. If ongoing evidence supports acceptable performance, the CKD-EPI eGFR-cystatin C (eGFRcys) and eGFR creatinine-cystatin C (eGFRcr-cys_R) refit without the race variables should be adopted to provide another first-line test, in addition to confirmatory testing. ( 3 ) Research on GFR estimation with new endogenous filtration markers and on interventions to eliminate race and ethnic disparities should be encouraged and funded. An investment in science is needed for newer approaches that generate accurate, unbiased, and precise GFR measurement and estimation without the inclusion of race, and that promote health equity and do not generate disparate care. This unified approach, without specification of race, should be adopted across the United States. High-priority and multistakeholder efforts should implement this solution.

Measured Glomerular Filtration Rate: The Query for a Workable Golden Standard Technique.

Inulin clearance has, for a long time, been considered as the reference method to determine measured glomerular filtration rates (mGFRs). However, given the known limitations of the standard marker, serum creatinine, and of inulin itself, and the frequent need for accurate GFR estimations, several other non-radioactive (iohexol and iothalamate) and radioactive (51Cr-EDTA, 99mTc-DTPA, 125I iothalamate) exogenous mGFR filtration markers are nowadays considered the most accurate options to evaluate GFR. The availability of 51Cr-EDTA is limited, and all methods using radioactive tracers necessitate specific safety precautions. Serum- or plasma-based certified reference materials for iohexol and iothalamate and evidence-based protocols to accurately and robustly measure GFR (plasma vs. urinary clearance, single-sample vs. multiple-sample strategy, effect of sampling time delay) are lacking. This leads to substantial variation in reported mGFR results across studies and questions the scientific reliability of the alternative mGFR methods as the gold standard to evaluate kidney function. On top of the scientific discussion, regulatory issues are further narrowing the clinical use of mGFR methods. Therefore, this review is a call for standardization of mGFR in terms of three aspects: the marker, the analytical method to assess concentrations of that marker, and the procedure to determine GFR in practice. Moreover, there is also a need for an endogenous filtration marker or a panel of filtration markers from a single blood draw that would allow estimation of GFR as accurately as mGFR, and without the need for application of anthropometric, clinical, and demographic characteristics.

Cystatin-C as Novel Marker of Neonatal Hyperbilirubinemia, in Al-Najaf City, Iraq

Neonatal hyperbilirubinemia results from a readiness for the bilirubin production in neonates and limited their ability to excrete it. The diagnosis of hyperbilirubinemia based on yellow discoloration of the skin and whiteness of eyes, idle in the child's movement and the lack of lactation. The baby seems sick or is difficult to awaken. Serum cystatin-C, is a low molecular protein that belongs to the family of cysteine protease inhibitor, was proposed as an endogenous filtration marker. In this study sixty neonatal patients suffering from hyperbilirubinemia (35 males,25female) were collected from prematurity unit (PU) in Al-Zahra Educational Hospital/Al-Najaf Al-Ashraf during the period from August,2020 to February,2021. A group of 20 randomly (12male, 8female) selected apparently healthy group. After diagnosis of hyperbilirubinemia, the patients were divided into three groups according to age (1-3), (4-7) and (7-9) days. The result reveals that significant increase (p<0.05) in serum cystatin-C in neonatal hyperbilirubinemia as compared with healthy group. The result of study reveals no significant increase(p<0.05) in serum levels of cystatin-C, while the study shows a significant increase (p<0.05) between male and female in serum levels of bilirubin.

Serum creatinine and cystatin C-based estimates of glomerular filtration rate are misleading in acute heart failure.

AimsWe aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation‐based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure.MethodsIn this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty‐eight patients had two sequential GFR measurements 48 h apart. The co‐primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR.ResultsVFI‐based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker‐based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80–0.88, depending on equation used), precision (r 2, range 0.65–0.78) and accuracy (56%–74% of estimates scored within 30% of mGFR). Correlations of 48‐h changes GFR estimates and changes of mGFR were significant (P < 0.05) but weak (Pearson's r, range 0.35–0.39). Observed decreases of eGFR by more than 15% had a low sensitivity (range 38%–46%, depending on equation used) in detecting true worsening mGFR, defined by a >15% decrease in mGFR.ConclusionsIn patients hospitalized for acute heart failure, serum creatinine‐ and cystatin C‐based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure.

POS-055 ESTIMATED VERSUS MEASURED GLOMERULAR FILTRATION RATE IN ACUTE DECOMPENSATED HEART FAILURE

In patients undergoing decongestive therapy for acute heart failure (AHF), endogenous filtration markers such as serum creatinine (SCr) or cystatin C (CysC) are used to monitor kidney function. We tested whether dynamics of endogenous filtration markers and estimated GFR (eGFR) based on these markers appropriately reflect changes of measured GFR (mGFR) patients with AHF.

GFR Estimation Using a Panel of Filtration Markers in Shanghai and Beijing

Rationale & ObjectivesEstimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys) may be less accurate compared to measured GFR (mGFR) in China than in North America, Europe, and Australia due to variation across regions in their non-GFR determinants. The non-GFR determinants of β2-microglobulin (B2M) and β-trace protein (BTP) differ from those of creatinine and cystatin C. Thus, the average eGFR using all 4 markers (eGFRavg) could be more accurate than eGFRcr-cys in China.Study DesignDiagnostic test study.Setting & Participants1,066 participants in Shanghai and Beijing with creatinine and cystatin C and 666 participants with all 4 filtration markers.Tests ComparedIndex tests were previously developed equations for eGFR using creatinine, cystatin C, B2M, and BTP and combinations. The reference test was mGFR using plasma clearance of iohexol. We compared the performance of eGFRavg to eGFRcr-cys using the proportion of participants with errors in eGFR >30% of mGFR (1 − P30) and root mean square error (RMSE) of the regression of eGFR on mGFR on the logarithmic scale. We also compared classification and reclassification of mGFR categories using eGFRavg compared to eGFRcr-cys.OutcomesAccuracy was significantly better for eGFRavg (1 − P30 of 10.4% and RMSE of 0.214) compared to eGFRcr-cys (1 − P30 of 13.8% and RMSE of 0.232; P = 0.004 and P = 0.006, respectively). However, improvements in accuracy did not generally translate into significant improvement in classification or reclassification of mGFR categories.LimitationsStudy population may not be generalizable to clinical settings other than large urban medical centers in China.ConclusionsA panel of endogenous filtration markers including B2M and BTP in addition to creatinine and cystatin C may improve GFR estimation in China. Further study is necessary to determine whether GFR estimation using B2M and BTP can be improved and whether these improvements lead to useful clinical applications.

Development and Validation of Residual Kidney Function Estimating Equations in Dialysis Patients

Rationale & ObjectiveMeasurement of residual kidney function is recommended for the adjustment of the dialysis prescription, but timed urine collections are difficult and prone to errors. Equations to calculate residual kidney function from serum concentrations of endogenous filtration markers and demographic parameters would simplify monitoring of residual kidney function. However, few equations to estimate residual kidney function using serum concentrations of small solutes and low-molecular-weight proteins have been developed and externally validated.Study DesignStudy of diagnostic test accuracy.Setting & Participants823 Chinese peritoneal dialysis (PD) patients (development cohort) and 826 PD and hemodialysis patients from the Netherlands NECOSAD study (validation cohort).Tests ComparedEquations to estimate residual kidney function (estimated clearance [eCl]) using serum creatinine, urea nitrogen, cystatin C, β2-microglobulin (B2M), β-trace protein (BTP), and combinations, as well as demographic variables (age, sex, height, and weight). Equations were developed using multivariable linear regression analysis in the development cohort and then tested in the validation cohort. Equations were compared with published validated equations.OutcomesResidual kidney function measured as urinary clearance (mCl) of urea nitrogen (mClUN) and average of creatinine and urea nitrogen clearance (mClUN-cr).ResultsIn external validation, bias (difference between mCl and eCl) was within ± 1.0 unit for all equations. Accuracy (percent of differences within ± 2.0 units) was significantly better for eClBTP, eClB2M, and eClBTP-B2M than eClUN-cr for both mClUN (78%, 80%, and 81% vs 72%; P < 0.05 for all) and mClUN-cr (72%, 78%, and 79% vs 68%; P < 0.05 for all). The area under the curve for predicting mClUN > 2.0 mL/min was highest for eClB2M (0.853) and eClBTP-B2M (0.848). Results were similar for other validated equations.LimitationsDevelopment cohort only consisted of PD patients, no gold-standard method for residual kidney function measurement.ConclusionsThese results confirm the validity and extend the generalizability of residual kidney function estimating equations from serum concentrations of low-molecular-weight proteins without urine collection.

Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine.

Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk. Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol. Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2 = 0.61). Addition of mGFR did not improve the model. Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined.

Clinical Correlates and Reference Intervals for Cystatin C in a Han Population from Southeast China.

Cystatin C (CysC) is an endogenous filtration marker for estimation of kidney function. This study aimed to define the reference interval (RI) for serum CysC in a southeast Chinese adult population and to explore the variables that affect serum CysC levels. 532 reference individuals (259 male, 273 female, aged 18 - 79 years) were recruited from Guangzhou, China. Multiple regression analysis (MRA) was used to investigate the association between serum CysC levels and clinical factors including age, gender, body mass index, lifestyle, and biochemistry parameters. Reference values were defined using a parametric method according to Clinical and Laboratory Standards Institute guideline (C28A3). The mean serum CysC levels were significantly lower in females than in males (p < 0.001). Serum CysC levels increased with age (~0.047 mg/L increase per decade). MRA demonstrated that serum CysC levels correlated significantly with serum creatinine (Cr), high density lipoprotein (HDL-C), alkaline phosphatase (ALP), albumin (ALB), and uric acid (UA) concentrations, although their relationships were less prominent than those of gender or age. The RIs for serum CysC levels were calculated at 0.73 - 1.17 mg/L for subjects aged 18 - 49 years and at 0.73 - 1.49 mg/L for those aged 50 - 79 years. The RIs for serum CysC were established in a southeast Chinese population. In addition to gender and age, serum Cr, HDL-C, ALP, ALB, and UA also influenced serum CysC levels.

Estimated GFR for Living Kidney Donor Evaluation

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m(2) based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m(2) , suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web-based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.

Biomarkers in chronic kidney disease, from kidney function to kidney damage.

Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m(2). Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.