Dataset Information

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD.

ABSTRACT: Unlike the case with creatinine, conditions affecting the non-glomerular filtration rate (GFR) determinants of low-molecular-weight serum proteins, ?-trace protein (BTP), ?2-microglobulin (B2M), and cystatin C, are not well characterized.Pooled cross-sectional analysis of 3 studies.3,156 persons with chronic kidney disease from the MDRD (Modification of Diet in Renal Disease) Study, AASK (African American Study of Kidney Disease and Hypertension), and CRIC (Chronic Renal Insufficiency Cohort) Study.Demographic and clinical factors hypothesized to be associated with non-GFR determinants of the filtration markers, selected from literature review and physiologic and clinical considerations.Serum creatinine, BTP, B2M, and cystatin C levels.In multivariable-adjusted errors-in-variables regression models that included adjustment for measured GFR (mGFR) and mGFR measurement error, creatinine level had stronger associations with male sex, black race, and higher urine creatinine excretion than the other filtration markers. BTP was associated less strongly with age, similar in direction with sex, and opposite in direction with race than creatinine level. Like cystatin C, B2M level was associated less strongly with age, sex, and race than creatinine level. BTP, B2M, and cystatin C levels were associated more strongly than creatinine level with other factors, including urine protein excretion and weight for BTP, smoking and urine protein excretion for B2M, and smoking for cystatin C.Findings may not be generalizable to populations without chronic kidney disease, and residual confounding with GFR due to incomplete adjustment for GFR measurement error.Like creatinine, serum levels of low-molecular-weight proteins are affected by conditions other than GFR. Knowledge of these conditions can aid the interpretation of GFR estimates and risk using these markers and guide the use of these filtration markers in developing GFR estimating equations.

SUBMITTER: Liu X

PROVIDER: S-EPMC5123901 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD.

Liu Xun X Foster Meredith C MC Tighiouart Hocine H Anderson Amanda H AH Beck Gerald J GJ Contreras Gabriel G Coresh Josef J Eckfeldt John H JH Feldman Harold I HI Greene Tom T Hamm L Lee LL He Jiang J Horwitz Edward E Lewis Julia J Ricardo Ana C AC Shou Haochang H Townsend Raymond R RR Weir Matthew R MR Inker Lesley A LA Levey Andrew S AS

American journal of kidney diseases : the official journal of the National Kidney Foundation 20160920 6

<h4>Background</h4>Unlike the case with creatinine, conditions affecting the non-glomerular filtration rate (GFR) determinants of low-molecular-weight serum proteins, β-trace protein (BTP), β<sub>2</sub>-microglobulin (B2M), and cystatin C, are not well characterized.<h4>Study design</h4>Pooled cross-sectional analysis of 3 studies.<h4>Setting & participants</h4>3,156 persons with chronic kidney disease from the MDRD (Modification of Diet in Renal Disease) Study, AASK (African American Study of ...[more]

PMID: 27663042

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Project description:Studies in chronic kidney disease populations suggest that the non-glomerular filtration rate (GFR) determinants of serum levels of the low-molecular-weight protein filtration markers cystatin C, ?2-microglobulin (B2M), and beta-trace protein (BTP) are less affected by age, sex, and ethnicity than those of creatinine.Cross-sectional study.Predominantly elderly participants selected from the Age, Gene/Environment Susceptibility Kidney Study (AGES-Kidney; N=683; mean [SD] age, 79 [4] years; GFR, 62 [17]mL/min/1.73 m2) and from the Multi-Ethnic Study of Atherosclerosis Kidney Study (MESA-Kidney; N=273; mean [SD] age, 70.5 [9] years; GFR, 73 [19]mL/min/1.73 m2).Demographic and clinical factors hypothesized to be associated with conditions affecting non-GFR determinants of the filtration markers.Measured GFRs and estimated GFRs (eGFRs) based on creatinine, cystatin C, B2M, and BTP levels (eGFRcr, eGFRcys, eGFRB2M, and eGFRBTP, respectively). Residual associations of factors with eGFR after accounting for measured GFR as the parameter of interest.eGFRcys, eGFRB2M, and eGFRBTP had significantly less strong residual associations with age and sex than eGFRcr in both AGES-Kidney and MESA-Kidney and were not associated with ethnicity (black vs white) in MESA-Kidney. After adjusting for age, sex, and ethnicity, residual associations with most clinical factors were smaller than observed with age and sex. eGFRcys and eGFRB2M, but not eGFRBTP, had significant residual associations with C-reactive protein levels in both studies.Small sample size may limit power to detect associations. Participants may be healthier than the general population.Similar to previous studies in chronic kidney disease, in community-dwelling elders, cystatin C, B2M, and BTP levels are less affected than creatinine level by age and sex and are not affected by ethnicity. Both cystatin C and B2M levels may be affected by inflammation. These findings are important for the development and use of GFR estimating equations based on low-molecular-weight serum proteins throughout the range in GFRs.

Project description:BACKGROUND:Low ankle-brachial index (ABI) is associated with increases in serum creatinine level. Whether low ABI is associated with the development of rapid estimated glomerular filtration rate (eGFR) decline, stage 3 chronic kidney disease (CKD), or microalbuminuria is uncertain. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:Framingham Offspring cohort participants who attended the sixth (1995-1998) and eighth (2005-2008) examinations. PREDICTOR:ABI, categorized as normal (>1.1 to <1.4), low-normal (>0.9 to 1.1), and low (?0.9). OUTCOMES:Rapid eGFR decline (eGFR decline ?3 mL/min/1.73 m(2) per year), incident stage 3 CKD (eGFR <60 mL/min/1.73 m(2)), incident microalbuminuria. MEASUREMENTS:GFR was estimated using the serum creatinine-based CKD-EPI (CKD Epidemiology Collaboration) equation. Urinary albumin-creatinine ratio (UACR) was determined based on spot urine samples. RESULTS:During 9.5 years, 9.0% (232 of 2,592) experienced rapid eGFR decline and 11.1% (270 of 2,426) developed stage 3 CKD. Compared to normal ABI, low ABI was associated with 5.73-fold increased odds of rapid eGFR decline (95% CI, 2.77-11.85; P<0.001) after age, sex, and baseline eGFR adjustment; this persisted after multivariable adjustment for standard CKD risk factors (OR, 3.60; 95% CI, 1.65-7.87; P = 0.001). After adjustment for age, sex, and baseline eGFR, low ABI was associated with a 2.51-fold increased odds of stage 3 CKD (OR, 2.51; 95% CI, 1.16-5.44; P = 0.02), although this was attenuated after multivariable adjustment (OR, 1.68; 95% CI, 0.75-3.76; P = 0.2). In 1,902 free of baseline microalbuminuria, low ABI was associated with increased odds of microalbuminuria after adjustment for age, sex, and baseline UACR (OR, 2.81; 95% CI, 1.07-7.37; P = 0.04), with attenuation upon further adjustment (OR, 1.88; P = 0.1). LIMITATIONS:Limited number of events with low ABI. Outcomes based on single serum creatinine and UACR measurements at each examination. CONCLUSIONS:Low ABI is associated with an increased risk of rapid eGFR decline, suggesting that systemic atherosclerosis predicts a decrease in kidney function.

Project description:Background and objectiveseGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equations on the basis of creatinine, cystatin C, and both (eGFR creatinine-cystatin C) compared with measured GFR by iothalamate clearance and evaluated their non-GFR determinants and associations across 15 cardiovascular risk factors.Design, setting, participants, & measurementsA cross-sectional cohort of 1139 kidney transplant recipients >1 year after transplant was analyzed. eGFR bias, precision, and accuracy (percentage of estimates within 30% of measured GFR) were assessed. Interaction of each cardiovascular risk factor with eGFR relative to measured GFR was determined.ResultsMedian measured GFR was 55.0 ml/min per 1.73 m(2). eGFR creatinine overestimated measured GFR by 3.1% (percentage of estimates within 30% of measured GFR of 80.4%), and eGFR Modification of Diet in Renal Disease underestimated measured GFR by 2.2% (percentage of estimates within 30% of measured GFR of 80.4%). eGFR cystatin C underestimated measured GFR by -13.7% (percentage of estimates within 30% of measured GFR of 77.1%), and eGFR creatinine-cystatin C underestimated measured GFR by -8.1% (percentage of estimates within 30% of measured GFR of 86.5%). Lower measured GFR associated with older age, women, obesity, longer time after transplant, lower HDL, lower hemoglobin, lower albumin, higher triglycerides, higher proteinuria, and an elevated cardiac troponin T level but did not associate with diabetes, smoking, cardiovascular events, pretransplant dialysis, or hemoglobin A1c. These risk factor associations differed for five risk factors with eGFR creatinine, six risk factors for eGFR Modification of Diet in Renal Disease, ten risk factors for eGFR cystatin C, and four risk factors for eGFR creatinine-cystatin C.ConclusionsThus, eGFR creatinine and eGFR creatinine-cystatin C are preferred over eGFR cystatin C in kidney transplant recipients because they are less biased, more accurate, and more consistently reflect the same risk factor associations seen with measured GFR.

Project description:Glomerular filtration rate (GFR) measurements are critical in patients with hepatic cirrhosis but potentially erroneous when based on serum creatinine. New equations for estimated GFR (eGFR) have shown variable performance in cirrhotics, possibly because of inaccuracies in reference methods for measured GFR (mGFR). The primary objective was to compare the performance of 4 improved eGFR equations with a 1-compartment, 2-sample plasma slope intercept 99mTc-DTPA mGFR method to determine whether any of the eGFR calculations could replace plasma 99mTc-DTPA mGFR in patients with cirrhosis. The secondary objective was to test the hypothesis that mGFR using voluntary voided urine collections introduces error compared with plasma-only methods. Methods: Fifty-four patients with hepatic cirrhosis underwent mGFR determinations from 2 plasma samples at 1 and 3 h after intravenous administration of 185 MBq of 99mTc-DTPA. GFR was also generated by a UV/P calculation derived from blood and urine samples. These mGFRs were compared with the eGFRs generated by 4 estimating equations: MDRD (Modified Diet in Renal Disease), CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) (serum creatinine [SCr]), CKD-EPI (cystatin [CysC]), and CKD-EPI (CysC+SCr). eGFRs were compared with mGFRs by Pearson correlation, precision, bias, percentage bias, and accuracy (eGFRs varying by <10% [p10], <20% [p20] or <30% [p30] from the corresponding mGFR). Results: All eGFRs showed poorer performance when the UV/P 99mTc-DTPA mGFR was used as the reference than when the plasma 99mTc-DTPA mGFR was used. When compared with the plasma 99mTc-DTPA mGFR method, the performance of all eGFR equations was superior to most published reports. There was a moderately good positive correlation between eGFRs and mGFRs. When compared with plasma 99mTc-DTPA mGFR, precision of eGFRs was in the range of 14-20 mL/min and showed a negligible bias. Compared with the plasma 99mTc-DTPA mGFR, CKD-EPI (CysC+SCr) showed the best overall performance and accuracy, at 85.19% (p30), 75.93% (p20), and 42.59% (p10). Conclusion: Estimating equations for measuring eGFR performed better than in most published reports, attributable to use of the plasma 99mTc-DTPA mGFR method as a reference. CKD-EPI (CysC+SCr) eGFR showed the best overall performance. However, more discriminating methods may be required when accurate GFR measurements are necessary. mGFR measurements using urine collections may introduce error compared with plasma-only methods.

Project description:Background and objectivesStudies of adults have demonstrated an association between metabolic acidosis, as measured by low serum bicarbonate levels, and CKD progression. We evaluated this relationship in children using data from the Chronic Kidney Disease in Children study.Design, setting, participants, & measurementsThe relationship between serum bicarbonate and a composite end point, defined as 50% decline in eGFR or KRT, was described using parametric and semiparametric survival methods. Analyses were stratified by underlying nonglomerular and glomerular diagnoses, and adjusted for demographic characteristics, eGFR, proteinuria, anemia, phosphate, hypertension, and alkali therapy.ResultsSix hundred and three participants with nonglomerular disease contributed 2673 person-years of follow-up, and 255 with a glomerular diagnosis contributed 808 person-years of follow-up. At baseline, 39% (237 of 603) of participants with nonglomerular disease had a bicarbonate level of ≤22 meq/L and 36% (85 of 237) of those participants reported alkali therapy treatment. In participants with glomerular disease, 31% (79 of 255) had a bicarbonate of ≤22 meq/L, 18% (14 of 79) of those participants reported alkali therapy treatment. In adjusted longitudinal analyses, compared with participants with a bicarbonate level >22 meq/L, hazard ratios associated with a bicarbonate level of <18 meq/L and 19-22 meq/L were 1.28 [95% confidence interval (95% CI), 0.84 to 1.94] and 0.91 (95% CI, 0.65 to 1.26), respectively, in children with nonglomerular disease. In children with glomerular disease, adjusted hazard ratios associated with bicarbonate level ≤18 meq/L and bicarbonate 19-22 meq/L were 2.16 (95% CI, 1.05 to 4.44) and 1.74 (95% CI, 1.07 to 2.85), respectively. Resolution of low bicarbonate was associated with a lower risk of CKD progression compared with persistently low bicarbonate (≤22 meq/L).ConclusionsIn children with glomerular disease, low bicarbonate was linked to a higher risk of CKD progression. Resolution of low bicarbonate was associated with a lower risk of CKD progression. Fewer than one half of all children with low bicarbonate reported treatment with alkali therapy. Long-term studies of alkali therapy's effect in patients with pediatric CKD are needed.

Dataset Information

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD.

Publications

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in CKD.

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