The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Anders Grubb - One of the best experts on this subject based on the ideXlab platform.
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struCtural CharaCterization of Covalently stabilized human Cystatin C oligomers
bioRxiv, 2020Co-Authors: Magdalena Chrabąszczewska, Anders Grubb, Adam K Sieradzan, Sylwia Rodziewiczmotowidlo, Christopher M Dobson, Janet R Kumita, Maciej KozakAbstract:AbstraCt: Human Cystatin C (HCC), a Cysteine-protease inhibitor, exists as a folded monomer under physiologiCal Conditions but has the ability to self-assemble via domain swapping into multimeriC states, inCluding oligomers with a doughnut-like struCture. The struCture of the monomeriC HCC has been solved by X-ray Crystallography, and a Covalently linked version of HCC (stab-1 HCC) is able to form stable oligomeriC speCies Containing 10-12 monomeriC subunits. We have performed moleCular modeling, and in ConjunCtion with experimental parameters obtained from AFM, TEM and SAXS measurements, we observe that the struCtures are essentially flat, with a height of about 2 nm, and the distanCe between the outer edge of the ring and the edge of the Central Cavity is ~5.1 nm. These dimensions Correspond to the height and diameter of one stab-1 HCC subunit and we present a dodeCamer model for stabilized Cystatin C oligomers using moleCular dynamiCs simulations and experimentally measured parameters. Given that oligomeriC speCies in protein aggregation reaCtions are often transient and very highly heterogeneous, the struCtural information presented here on these isolated stab-1 HCC oligomers may provide useful to further explore the physiologiCal relevanCe of different struCtural speCies of Cystatin C in relationship to protein misfolding disease
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first Certified referenCe material for Cystatin C in human serum erm da471 ifCC
Clinical Chemistry and Laboratory Medicine, 2010Co-Authors: Anders Grubb, Veronica Lindstrom, C Schmidt, Harald Althaus, Soren Blirup, Ingrid ZegersAbstract:The IFCC Working Group for the Standardisation of Cystatin C (WG-SCC), in Collaboration with the Institute for ReferenCe Materials and Measurements (IRMM), announCes the availability of the new Certified referenCe material ERM-DA471/IFCC. The material was CharaCterised using a pure protein primary referenCe preparation (PRP) as Calibrant. The PRP was prepared from reCombinant Cystatin C, and its ConCentration measured using dry mass determination. The CharaCterisation of ERM-DA471/IFCC was performed by partiCle enhanCed immuno-nephelometry, partiCle enhanCed immuno-turbidimetry, and enzyme amplified single radial immuno-diffusion. The Certified Cystatin C mass ConCentration in ERM-DA471/IFCC, if reConstituted aCCording to the speCified proCedure, is 5.48 mg/L, the expanded unCertainty (k=2) being 0.15 mg/L.
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standardization of Cystatin C development of primary and seCondary referenCe preparations
Scandinavian Journal of Clinical & Laboratory Investigation, 2008Co-Authors: Soren Blirupjensen, Anders Grubb, Veronica Lindstrom, C Schmidt, Harald AlthausAbstract:A Primary ReferenCe Preparation has been produCed using pure, reCombinant, Cystatin C in a solvent of 0.1 mol/L KCl. Dry mass determination of the Primary ReferenCe Preparation resulted in a Cystatin C ConCentration of 5.20 g/L. Agarose-eleCtrophoresis and SDS-eleCtrophoresis, as well as N-terminal sequenCing, verified the purity, homogeneity and identity of Cystatin C in the Primary ReferenCe Preparation. For the SeCondary ReferenCe Preparation, a serum pool was ColleCted and stabilized. A pilot batCh was made to verify the seleCted proCedure and spiking with the pure, reCombinant Cystatin C. The final SeCondary ReferenCe Preparation is now produCed (4468 vials) and ready for value assignment and further CharaCterization.
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Cystatin C beta 2 miCroglobulin and beta traCe protein in pre eClampsia
Acta Obstetricia et Gynecologica Scandinavica, 2007Co-Authors: Karl Kristensen, Dag Wideswensson, Soren Blirupjensen, Helena Strevens, Veronica Lindstrom, Anders GrubbAbstract:BaCkground. An altered renal funCtion is an essential Component of the patho-physiology of pre-eClampsia. The plasma levels of low moleCular mass proteins, e.g. β-traCe protein, β-2-miCroglobulin and Cystatin C, are inCreased in the third trimester of normal pregnanCy. The plasma levels of Cystatin C and β-2-miCroglobulin are further inCreased in pre-eClampsia, and the Cystatin C level has been reported to be a reliable marker for the disease. The aim of this investigation was to study the plasma levels of β-traCe protein, β-2-miCroglobulin and Cystatin C in pre-eClampsia, and to determine the diagnostiC performanCe of these proteins Compared to that of urate and Creatinine. Methods. A Case-Control study of 57 women diagnosed with pre-eClampsia, and 218 healthy women with unCompliCated singleton pregnanCies in the third trimester. Women in the CatChment area of Lund, Sweden, were inCluded during an 18-month period from OCtober 2003 to April 2005. Venous blood samples were drawn upon inClusion when diagnos...
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Cystatin C defiCienCy inCreases elastiC lamina degradation and aortiC dilatation in apolipoprotein e null miCe
Circulation Research, 2005Co-Authors: Galina K Sukhova, Anders Grubb, Peter Libby, Harold A Chapman, Bing Wang, Jiehong Pan, Yaou Zhang, Kenneth C Fang, Guoping ShiAbstract:The pathogenesis of atherosClerosis and abdominal aortiC aneurysm involves substantial proteolysis of the arterial extraCellular matrix. The lysosomal Cysteine proteases Can exert potent elastolytiC and CollagenolytiC aCtivity. Human atherosClerotiC plaques have inCreased Cysteine protease Content and deCreased levels of the endogenous inhibitor Cystatin C, suggesting an imbalanCe that would favor matrix degradation in the arterial wall. This study tested direCtly the hypothesis that impaired expression of Cystatin C alters arterial struCture. Cystatin C–defiCient miCe (Cyst C −/− ) were Crossbred with apolipoprotein E–defiCient miCe (ApoE −/− ) to generate Cystatin C and apolipoprotein E–double defiCient miCe (Cyst C −/− ApoE −/− ). After 12 weeks on an atherogeniC diet, Cystatin C defiCienCy yielded signifiCantly inCreased tuniCa media elastiC lamina fragmentation, deCreased medial size, and inCreased smooth musCle Cell and Collagen Content in aortiC lesions of ApoE −/− miCe. Cyst C −/− ApoE −/− miCe also showed dilated thoraCiC and abdominal aortae Compared with Control ApoE −/− miCe, although atheroma lesion size, intimal maCrophage aCCumulation, and lipid Core size did not differ between these miCe. These findings demonstrate direCtly the importanCe of Cysteine protease/protease inhibitor balanCe in dysregulated arterial integrity and remodeling during experimental atherogenesis.
Michael G Shlipak - One of the best experts on this subject based on the ideXlab platform.
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Cystatin C versus Creatinine in determining risk based on kidney funCtion
The New England Journal of Medicine, 2013Co-Authors: Michael G Shlipak, Lesley A. Inker, Kunihiro Matsushita, Johan Arnlov, Ronit Katz, Kevan R Polkinghorne, Dietrich Rothenbacher, Mark J SarnakAbstract:BACKGROUND Adding the measurement of Cystatin C to that of serum Creatinine to determine the estimated glomerular filtration rate (eGFR) improves aCCuraCy, but the effeCt on deteCtion, staging, and risk ClassifiCation of ChroniC kidney disease aCross diverse populations has not been determined. METHODS We performed a meta-analysis of 11 general-population studies (with 90,750 partiCipants) and 5 studies of Cohorts with ChroniC kidney disease (2960 partiCipants) for whom standardized measurements of serum Creatinine and Cystatin C were available. We Compared the assoCiation of the eGFR, as CalCulated by the measurement of Creatinine or Cystatin C alone or in Combination with Creatinine, with the rates of death (13,202 deaths in 15 Cohorts), death from CardiovasCular Causes (3471 in 12 Cohorts), and end-stage renal disease (1654 Cases in 7 Cohorts) and assessed improvement in reClassifiCation with the use of Cystatin C. RESULTS In the general-population Cohorts, the prevalenCe of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surfaCe area was higher with the Cystatin C-based eGFR than with the Creatinine-based eGFR (13.7% vs. 9.7%). ACross all eGFR Categories, the reClassifiCation of the eGFR to a higher value with the measurement of Cystatin C, as Compared with Creatinine, was assoCiated with a reduCed risk of all three study outComes, and reClassifiCation to a lower eGFR was assoCiated with an inCreased risk. The net reClassifiCation improvement with the measurement of Cystatin C, as Compared with Creatinine, was 0.23 (95% ConfidenCe interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five Cohorts with ChroniC kidney disease and when both Creatinine and Cystatin C were used to CalCulate the eGFR. CONCLUSIONS The use of Cystatin C alone or in Combination with Creatinine strengthens the assoCiation between the eGFR and the risks of death and end-stage renal disease aCross diverse populations.
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update on Cystatin C inCorporation into CliniCal praCtiCe
American Journal of Kidney Diseases, 2013Co-Authors: Michael G Shlipak, Monica D Mattes, Carmen A PeraltaAbstract:Kidney funCtion monitoring using Creatinine-based glomerular filtration rate estimation is a routine part of CliniCal praCtiCe. Emerging evidenCe has shown that Cystatin C may improve ClassifiCation of glomerular filtration rate for defining ChroniC kidney disease in Certain CliniCal populations and assist in understanding the CompliCations of ChroniC kidney disease. In this review and update, we summarize the overall literature on Cystatin C, CritiCally evaluate reCent high-impaCt studies, highlight the role of Cystatin C in reCent kidney disease guidelines, and suggest a praCtiCal approaCh for CliniCians to inCorporate Cystatin C into praCtiCe. We ConClude by addressing frequently asked questions related to implementing Cystatin C use in a CliniCal setting.
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Cystatin C identifies ChroniC kidney disease patients at higher risk for CompliCations
Journal of The American Society of Nephrology, 2011Co-Authors: Carmen A Peralta, Andrew S. Levey, Ronit Katz, Mark J Sarnak, David S Siscovick, Linda F Fried, Ian H De Boer, Walter Palmas, Michael G ShlipakAbstract:Although Cystatin C is a stronger prediCtor of CliniCal outComes assoCiated with CKD than Creatinine, the CliniCal role for Cystatin C is unClear. We inCluded 11,909 partiCipants from the Multi-EthniC Study of AtherosClerosis (MESA) and the CardiovasCular Health Study (CHS) and assessed risks for death, CardiovasCular events, heart failure, and ESRD among persons Categorized into mutually exClusive groups on the basis of the biomarkers that supported a diagnosis of CKD (eGFR 60 ml/min per 1.73 m 2 ): Creatinine only, Cystatin C only, both, or neither. We used CKD-EPI equations to estimate GFR from these biomarkers. In MESA, 9% had CKD by the Creatinine-based equation only, 2% had CKD by the Cystatin C-based equation only, and 4% had CKD by both equations; in CHS, these perCentages were 12, 4, and 13%, respeCtively. Compared with those without CKD, the adjusted hazard ratios (HR) for mortality in MESA were: 0.80 (95% CI 0.50 to 1.26) for CKD by Creatinine only; 3.23 (95% CI 1.84 to 5.67) for CKD by Cystatin C only; and 1.93 (95% CI 1.27 to 2.92) for CKD by both; in CHS, the adjusted HR were 1.09 (95% CI 0.98 to 1.21), 1.78 (95% CI 1.53 to 2.08), and 1.74 (95% CI 1.58 to 1.93), respeCtively. The pattern was similar for CardiovasCular disease (CVD), heart failure, and kidney failure outComes. In ConClusion, among adults diagnosed with CKD using the Creatinine-based CKD-EPI equation, the adverse prognosis is limited to the subset who also have CKD aCCording to the Cystatin C-based equation. Cystatin C may have a role in identifying persons with CKD who have the highest risk for CompliCations.
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Cystatin C albuminuria and mortality among older adults with diabetes
Diabetes Care, 2009Co-Authors: Ian H De Boer, Michael G Shlipak, Ronit Katz, Mark J Sarnak, Linda F Fried, Jie J Cao, Bryan Kestenbaum, Kenneth J Mukamal, Dena E Rifkin, David S SiscovickAbstract:OBJECTIVE Albuminuria and impaired glomerular filtration rate (GFR) are eaCh assoCiated with poor health outComes among individuals with diabetes. Joint assoCiations of albuminuria and impaired GFR with mortality have not been Comprehensively evaluated in this population. RESEARCH DESIGN AND METHODS This is a Cohort study among CardiovasCular Health Study partiCipants with diabetes, mean age 78 years. GFR was estimated using serum Cystatin C and serum Creatinine. Albumin-to-Creatinine ratio (ACR) was measured in single-voided urine samples. RESULTS Of 691 partiCipants, 378 died over 10 years of follow-up. Cystatin C–estimated GFR <60 ml/min per 1.73 m2, Creatinine-based estimated GFR <60 ml/min per 1.73 m2, and urine ACR ≥30 mg/g were eaCh assoCiated with inCreased mortality risk with hazard ratios of 1.73 (95% CI 1.37–2.18), 1.54 (1.21–1.97), and 1.73 (1.39–2.17), respeCtively, adjusting for age, sex, raCe, diabetes duration, hypoglyCemiC mediCations, hypertension, BMI, smoking, Cholesterol, lipid-lowering mediCations, prevalent CardiovasCular disease (CVD), and prevalent heart failure. Cystatin C–estimated GFR and urine ACR were additive in terms of mortality risk. Cystatin C–estimated GFR prediCted mortality more strongly than Creatinine-based estimated GFR. CONCLUSIONS Albuminuria and impaired GFR were independent, additive risk faCtors for mortality among older adults with diabetes. These findings support Current reCommendations to regularly assess both albuminuria and GFR in the CliniCal Care of patients with diabetes; a foCus on interventions to prevent or treat CVD in the presenCe of albuminuria, impaired GFR, or both; and further Consideration of Cystatin C use in CliniCal Care.
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interruption of antiretroviral therapy is assoCiated with inCreased plasma Cystatin C
AIDS, 2009Co-Authors: Amanda Mocroft, Michael G Shlipak, Christina M Wyatt, Lynda A Szczech, Jacquie Neuhaus, Wafaa Elsadr, Russell P Tracy, Lewis H Kuller, Brian AngusAbstract:BACKGROUND: Cystatin C has been proposed as an alternative marker of renal funCtion. We sought to determine whether partiCipants randomized to episodiC use of antiretroviral therapy guided by CD4 Cell Count (drug Conservation) had altered Cystatin C levels Compared with those randomized to Continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify faCtors assoCiated with inCreased Cystatin C. METHODS: Cystatin C was measured in plasma ColleCted at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 partiCipants in the drug Conservation and viral suppression groups, respeCtively. LogistiC regression was used to model the odds of at least 0.15 mg/dl inCrease in Cystatin C (1 SD) in the first month after randomization, adjusting for demographiC and CliniCal CharaCteristiCs. RESULTS: At randomization, mean (SD) Cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug Conservation and viral suppression arms, respeCtively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl inCrease in Cystatin C in the drug Conservation and viral suppression arms, respeCtively (P = 0.0008). The differenCe in Cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, partiCipants in the viral suppression arm had signifiCantly reduCed odds of at least 0.15 mg/dl inCrease in Cystatin C in the first month (odds ratio 0.42; 95% ConfidenCe interval 0.23-0.74, P = 0.0023). CONCLUSION: These results demonstrate that interruption of antiretroviral therapy is assoCiated with an inCrease in Cystatin C, whiCh may refleCt worsened renal funCtion.
Ellen Vinge - One of the best experts on this subject based on the ideXlab platform.
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relationships among serum Cystatin C serum Creatinine lean tissue mass and glomerular filtration rate in healthy adults
Scandinavian Journal of Clinical & Laboratory Investigation, 1999Co-Authors: Ellen Vinge, Birger Lindergard, Peter Nilssonehle, Anders GrubbAbstract:In an effort to inCrease our knowledge of the optimal use of serum Cystatin C and Creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual-energy X-ray absorptiometry and measurement of the plasma ClearanCe of iohexol were used to measure lean tissue mass and GFR, respeCtively. Serum Creatinine was signifiCantly Correlated to lean tissue mass (r=0.65; p < 0.0001) but not to GFR (1/Creatinine vs. GFR: r=0.11; p=0.106). In Contrast, serum Cystatin C Correlated with GFR (1/Cystatin C vs. GFR: r=0.32; p=0.0387), espeCially in men (1/Cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum Cystatin C seems to be a better marker for GFR than serum Creatinine, partiCularly for individuals with small to moderate deCreases in GFR. However, the results also show that the serum ConCentrations of both Creatinine and Cystatin C are determined not only by GFR, but also by other faCtors. SinCe these additional faCtors differ for Cystatin C and Creatinine, it seems justified to use serum Creatinine and Cystatin C in ConjunCtion to estimate GFR, at least until it is known in what situations serum Creatinine or Cystatin C is the preferable marker. (Less)
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relationships among serum Cystatin C serum Creatinine lean tissue mass and glomerular filtration rate in healthy adults
Scandinavian Journal of Clinical & Laboratory Investigation, 1999Co-Authors: Ellen Vinge, Birger Lindergard, Peter Nilssonehle, Anders GrubbAbstract:In an effort to inCrease our knowledge of the optimal use of serum Cystatin C and Creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual-energy X-ray absorptiometry and measurement of the plasma ClearanCe of iohexol were used to measure lean tissue mass and GFR, respeCtively. Serum Creatinine was signifiCantly Correlated to lean tissue mass (r=0.65; p < 0.0001) but not to GFR (1/Creatinine vs. GFR: r=0.11; p=0.106). In Contrast, serum Cystatin C Correlated with GFR (1/Cystatin C vs. GFR: r=0.32; p=0.0387), espeCially in men (1/Cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum Cystatin C seems to be a better marker for GFR than serum Creatinine, partiCularly for individuals with small to moderate deCreases in GFR. However, the results also show that the serum ConCentrations of both Creatinine and Cystatin C are determined not only by GFR, but also by other faCtors. SinCe these additional faCtors differ for Cystatin C and Creatinine, it seems justified to use serum Creatinine and Cystatin C in ConjunCtion to estimate GFR, at least until it is known in what situations serum Creatinine or Cystatin C is the preferable marker.
Lesley A. Inker - One of the best experts on this subject based on the ideXlab platform.
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Cystatin C and MusCle Mass in Patients With Heart Failure
Journal of cardiac failure, 2020Co-Authors: Juan Betuel Ivey-miranda, Lesley A. Inker, Matthew Griffin, Veena Rao, Christopher Maulion, Jeffrey M. Turner, F. Perry Wilson, W.h. Wilson Tang, Andrew S. Levey, Jeffrey M. TestaniAbstract:ABSTRACT BaCkground The estimated glomerular filtration rate (eGFR) from Cystatin C (eGFRCys) is often Considered a more aCCurate method to assess GFR Compared with an eGFR from Creatinine (eGFRCr) in the setting of heart failure (HF) and sarCopenia, beCause Cystatin C is hypothesized to be less affeCted by musCle mass than Creatinine. We evaluated (1) the assoCiation of musCle mass with Cystatin C, (2) the aCCuraCy of eGFRCys, and (3) the assoCiation of eGFRCys with mortality given musCle mass. Methods and Results We inCluded 293 patients admitted with HF. MusCle mass was estimated with a validated Creatinine exCretion-based equation. ACCuraCy of eGFRCys and eGFRCr was Compared with measured Creatinine ClearanCe. Cystatin C and Creatinine were 31.7% and 59.9% higher per 14 kg higher musCle mass at multivariable analysis (both P .19). ConClusions Cystatin C levels were assoCiated with musCle mass in patients with HF, whiCh Could potentially deCrease the aCCuraCy of eGFRCys. In HF where aberrations in body Composition are Common, eGFRCys, like eGFRCr, may not provide aCCurate GFR estimations and results should be interpreted Cautiously.
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Cystatin C versus Creatinine in determining risk based on kidney funCtion
The New England Journal of Medicine, 2013Co-Authors: Michael G Shlipak, Lesley A. Inker, Kunihiro Matsushita, Johan Arnlov, Ronit Katz, Kevan R Polkinghorne, Dietrich Rothenbacher, Mark J SarnakAbstract:BACKGROUND Adding the measurement of Cystatin C to that of serum Creatinine to determine the estimated glomerular filtration rate (eGFR) improves aCCuraCy, but the effeCt on deteCtion, staging, and risk ClassifiCation of ChroniC kidney disease aCross diverse populations has not been determined. METHODS We performed a meta-analysis of 11 general-population studies (with 90,750 partiCipants) and 5 studies of Cohorts with ChroniC kidney disease (2960 partiCipants) for whom standardized measurements of serum Creatinine and Cystatin C were available. We Compared the assoCiation of the eGFR, as CalCulated by the measurement of Creatinine or Cystatin C alone or in Combination with Creatinine, with the rates of death (13,202 deaths in 15 Cohorts), death from CardiovasCular Causes (3471 in 12 Cohorts), and end-stage renal disease (1654 Cases in 7 Cohorts) and assessed improvement in reClassifiCation with the use of Cystatin C. RESULTS In the general-population Cohorts, the prevalenCe of an eGFR of less than 60 ml per minute per 1.73 m(2) of body-surfaCe area was higher with the Cystatin C-based eGFR than with the Creatinine-based eGFR (13.7% vs. 9.7%). ACross all eGFR Categories, the reClassifiCation of the eGFR to a higher value with the measurement of Cystatin C, as Compared with Creatinine, was assoCiated with a reduCed risk of all three study outComes, and reClassifiCation to a lower eGFR was assoCiated with an inCreased risk. The net reClassifiCation improvement with the measurement of Cystatin C, as Compared with Creatinine, was 0.23 (95% ConfidenCe interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five Cohorts with ChroniC kidney disease and when both Creatinine and Cystatin C were used to CalCulate the eGFR. CONCLUSIONS The use of Cystatin C alone or in Combination with Creatinine strengthens the assoCiation between the eGFR and the risks of death and end-stage renal disease aCross diverse populations.
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performanCe of Creatinine and Cystatin C gfr estimating equations in an hiv positive population on antiretrovirals
Journal of Acquired Immune Deficiency Syndromes, 2012Co-Authors: Lesley A. Inker, Andrew S. Levey, Christina M Wyatt, Rebecca Creamer, James Hellinger, Matthew Hotta, Maia Leppo, Aghogho Okparavero, Hiba Graham, Karen SavageAbstract:OBJECTIVE: To evaluate the performanCe of ChroniC Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine, Cystatin C, and Creatinine-Cystatin C estimating equations in HIV-positive patients. METHODS: We evaluated the performanCe of the ModifiCation of Diet in Renal Disease (MDRD) Study and CKD-EPI Creatinine 2009, CKD-EPI Cystatin C 2012, and CKD-EPI Creatinine-Cystatin C 2012 glomerular filtration rate (GFR) estimating equations Compared with GFR measured using plasma ClearanCe of iohexol in 200 HIV-positive patients on stable antiretroviral therapy. Creatinine and Cystatin C assays were standardized to Certified referenCe materials. RESULTS: Of the 200 partiCipants, median (IQR) CD4 Count was 536 (421) and 61% had an undeteCtable HIV viral load. Mean (SD) measured GFR (mGFR) was 87 (26) mL/min per 1.73 m. All CKD-EPI equations performed better than the MDRD Study equation. All 3 CKD-EPI equations had similar bias and preCision. The Cystatin C equation was not more aCCurate than the Creatinine equation. The Creatinine-Cystatin C equation was signifiCantly more aCCurate than the Cystatin C equation, and there was a trend toward greater aCCuraCy than the Creatinine equation. ACCuraCy was equal or better in most subgroups with the Combined equation Compared to either alone. CONCLUSIONS: The CKD-EPI Cystatin C equation does not seem to be more aCCurate than the CKD-EPI Creatinine equation in patients who are HIV-positive, supporting the use of the CKD-EPI Creatinine equation for routine CliniCal Care for use in North AmeriCan populations with HIV. The use of both filtration markers together as a Confirmatory test for deCreased estimated GFR based on Creatinine in individuals who are HIV-positive requires further study.
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estimating glomerular filtration rate from serum Creatinine and Cystatin C
The New England Journal of Medicine, 2012Co-Authors: Lesley A. Inker, Christopher H Schmid, Tom Greene, John W Kusek, Hocine Tighiouart, John H Eckfeldt, Harold I Feldman, Jane Manzi, Frederick Van Lente, Yaping Lucy ZhangAbstract:A b s t r aC t BaCkground Estimates of glomerular filtration rate (GFR) that are based on serum Creatinine are routinely used; however, they are impreCise, potentially leading to the overdiagnosis of ChroniC kidney disease. Cystatin C is an alternative filtration marker for estimating GFR. Methods Using Cross-seCtional analyses, we developed estimating equations based on Cystatin C alone and in Combination with Creatinine in diverse populations totaling 5352 partiCipants from 13 studies. These equations were then validated in 1119 partiCipants from 5 different studies in whiCh GFR had been measured. Cystatin and Creatinine assays were traCeable to primary referenCe materials. Results Mean measured GFRs were 68 and 70 ml per minute per 1.73 m 2 of body-surfaCe area in the development and validation data sets, respeCtively. In the validation data set, the Creatinine–Cystatin C equation performed better than equations that used Creatinine or Cystatin C alone. Bias was similar among the three equations, with a median differenCe between measured and estimated GFR of 3.9 ml per minute per 1.73 m 2 with the Combined equation, as Compared with 3.7 and 3.4 ml per minute per 1.73 m 2 with the Creatinine equation and the Cystatin C equation (P = 0.07 and P = 0.05), respeCtively. PreCision was improved with the Combined equation (interquartile range of the differenCe, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m 2 , respeCtively [P = 0.001 and P 30% of measured GFR, 8.5 vs. 12.8 and 14.1, respeCtively [P<0.001 for both Comparisons]). In partiCipants whose estimated GFR based on Creatinine was 45 to 74 ml per minute per 1.73 m 2 , the Combined equation improved the ClassifiCation of measured GFR as either less than 60 ml per minute per 1.73 m 2 or greater than or equal to 60 ml per minute per 1.73 m 2 (net reClassifiCation index, 19.4% [P<0.001]) and CorreCtly reClassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m 2 as having a GFR of 60 ml or higher per minute per 1.73 m 2 . ConClusions The Combined Creatinine–Cystatin C equation performed better than equations based on either of these markers alone and may be useful as a Confirmatory test for ChroniC kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)
Timothy S Larson - One of the best experts on this subject based on the ideXlab platform.
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Cystatin C PrediCts Renal ReCovery Earlier Than Creatinine Among Patients With ACute Kidney Injury
Elsevier, 2018Co-Authors: Kamel A. Gharaibeh, Timothy S Larson, Abdurrahman M. Hamadah, Ziad M. El-zoghby, John C. Lieske, Nelson LeungAbstract:Serum Cystatin C inCreases earlier than Creatinine during aCute kidney injury. However, whether Cystatin C deCreases earlier during reCovery is unknown. This retrospeCtive study aimed to determine the temporal trend between Creatinine and Cystatin C in aCute kidney injury. Methods: We identified hospitalized patients with nonoliguriC aCute kidney injury who had serial Creatinine and Cystatin C values measured between May 2015 and May 2016. DemographiC and laboratory data, Causes of aCute kidney injury, and relevant Comorbidity data were ColleCted through Chart review. Results: For the 63 identified patients, mean (SD) age was 58.7 (13.9) years; male sex, 62%; white raCe/ethniCity, 95%. Baseline median (range) Creatinine was 1.1 (0.5–3.0) mg/dl; 13% were kidney transplant reCipients and 37% reCeived CortiCosteroids. Comorbidities inCluded malignanCy (38%), diabetes mellitus (33%), heart failure (19%), and thyroid disorder (16%). The Cause of kidney injury was aCute tubular neCrosis in 71%, 61% had aCute kidney injury stage III, and 33% required dialysis. Cystatin C began to deCrease before Creatinine in 68% of patients: 1 day earlier, 46%; 2 days earlier, 16%; and 3 days earlier, 6%. In 24% of Cases, both began deCreasing on the same day; in only 8%, Cystatin C deCreased after Creatinine. Overall, Cystatin C mean (95% ConfidenCe interval) deCrease was 0.92 (0.65–1.18) days before Creatinine (P < 0.001). ConClusion: In summary, Cystatin C deCreases before Creatinine in most hospitalized patients with aCute kidney injury. If Confirmed in large prospeCtive studies, these findings may have important management impliCations, possibly shortening hospital stay and reduCing Costs
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glomerular filtration rate estimated by Cystatin C among different CliniCal presentations
Kidney International, 2006Co-Authors: Andrew D Rule, Erik J Bergstralh, Jeffrey M Slezak, J Bergert, Timothy S LarsonAbstract:Glomerular filtration rate (GFR) estimates from serum Creatinine has not been generalizable aCross all populations. Cystatin C has been proposed as an alternative marker for estimating GFR. The objeCtive of this study was to Compare Cystatin C with serum Creatinine for estimating GFR among different CliniCal presentations. Cystatin C and serum Creatinine levels were obtained from adult patients (n=460) during an evaluation that inCluded a GFR measurement by iothalamate ClearanCe. MediCal reCords were abstraCted for CliniCal presentation (healthy, native ChroniC kidney disease or transplant reCipient) at the time of GFR measurement. GFR was modeled using the following variables: Cystatin C (or serum Creatinine), age, gender and CliniCal presentation. The relationship between Cystatin C and GFR differed aCross CliniCal presentations. At the same Cystatin C level, GFR was 19% higher in transplant reCipients than in patients with native kidney disease (P<0.001). The assoCiation between Cystatin C and GFR was stronger among native kidney disease patients than in healthy persons (P<0.001 for statistiCal interaCtion). Thus, a Cystatin C equation was derived using only patients with native kidney disease (n=204). The Correlation with GFR (r(2)=0.853) was slightly higher than a serum Creatinine equation using the same sample (r(2)=0.827), the ModifiCation of Diet in Renal Disease equation (r(2)=0.825) or the CoCkCroft-Gault equation (r(2)=0.796). Averaged estimates between Cystatin C and serum Creatinine equations further improved Correlation (r(2)=0.891). Cystatin C should not be interpreted as purely a marker of GFR. Other faCtors, possibly inflammation or immunosuppression therapy, affeCt Cystatin C levels. While reCognizing this limitation, Cystatin C may improve GFR estimates in ChroniC kidney disease patients.
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glomerular filtration rate estimated by Cystatin C among different CliniCal presentations
Kidney International, 2006Co-Authors: Andrew D Rule, Erik J Bergstralh, Jeffrey M Slezak, J Bergert, Timothy S LarsonAbstract:Glomerular filtration rate (GFR) estimates from serum Creatinine has not been generalizable aCross all populations. Cystatin C has been proposed as an alternative marker for estimating GFR. The objeCtive of this study was to Compare Cystatin C with serum Creatinine for estimating GFR among different CliniCal presentations. Cystatin C and serum Creatinine levels were obtained from adult patients ( n =460) during an evaluation that inCluded a GFR measurement by iothalamate ClearanCe. MediCal reCords were abstraCted for CliniCal presentation (healthy, native ChroniC kidney disease or transplant reCipient) at the time of GFR measurement. GFR was modeled using the following variables: Cystatin C (or serum Creatinine), age, gender and CliniCal presentation. The relationship between Cystatin C and GFR differed aCross CliniCal presentations. At the same Cystatin C level, GFR was 19% higher in transplant reCipients than in patients with native kidney disease ( P P n =204). The Correlation with GFR ( r 2 =0.853) was slightly higher than a serum Creatinine equation using the same sample ( r 2 =0.827), the ModifiCation of Diet in Renal Disease equation ( r 2 =0.825) or the CoCkCroft–Gault equation ( r 2 =0.796). Averaged estimates between Cystatin C and serum Creatinine equations further improved Correlation ( r 2 =0.891). Cystatin C should not be interpreted as purely a marker of GFR. Other faCtors, possibly inflammation or immunosuppression therapy, affeCt Cystatin C levels. While reCognizing this limitation, Cystatin C may improve GFR estimates in ChroniC kidney disease patients.
