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Annals of Internal Medicine May 2009Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically...
BACKGROUND
Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values.
OBJECTIVE
To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
DESIGN
Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates.
SETTING
Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006.
PARTICIPANTS
8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES.
MEASUREMENTS
GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age.
RESULTS
In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%).
LIMITATION
The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR.
CONCLUSION
The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use.
PRIMARY FUNDING SOURCE
National Institute of Diabetes and Digestive and Kidney Diseases.
Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Creatinine; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Nutrition Surveys; Prevalence; Reproducibility of Results; United States
PubMed: 19414839
DOI: 10.7326/0003-4819-150-9-200905050-00006 -
Blood Advances Jul 2022The reduced-intensity conditioning regimen, fludarabine and melphalan, is frequently used in allogeneic hematopoietic stem cell transplantation (HSCT). Melphalan and the...
The reduced-intensity conditioning regimen, fludarabine and melphalan, is frequently used in allogeneic hematopoietic stem cell transplantation (HSCT). Melphalan and the active metabolite of fludarabine, F-ara-A, are excreted via the kidneys. Existing methods to assess clearance in this setting are based on serum creatinine, which has known limitations for glomerular filtration rate (GFR) estimation in patients with malignancy. Measured GFR (mGFR) may better predict drug dosing to mitigate toxicity and increase the chances of successful engraftment. The primary objective of this study was to assess the association between mGFR and risk for nonrelapse mortality (NRM) in patients who have undergone allogeneic HSCT receiving conditioning with fludarabine and melphalan. In the 109 included patients, mGFR <65 mL/min/1.73 m2 predicted a significantly higher rate of overall NRM (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.35; P = 04) and 1-year incidence of infection (HR, 2.63; 95% CI, 1.54-4.55; P < .001) in addition to a significantly lower 2-year survival (P = .019). Kidney function estimated via estimated GFR (eGFR) and estimated creatinine clearance did not correlate with posttransplant outcomes. These results suggest that mGFR is a promising approach for assessing clearance in patients who have undergone allogeneic HSCT and may be preferred to standard creatinine-based eGFR strategies.
Topics: Creatinine; Graft vs Host Disease; Humans; Iothalamic Acid; Melphalan; Retrospective Studies; Vidarabine
PubMed: 35522968
DOI: 10.1182/bloodadvances.2021006395 -
Kidney International Reports Nov 2023In clinical practice, kidney (dys)function is monitored through creatinine-based estimations of glomerular filtration rate (eGFR: Modification of Diet in Renal Disease...
INTRODUCTION
In clinical practice, kidney (dys)function is monitored through creatinine-based estimations of glomerular filtration rate (eGFR: Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). Creatinine is recognized as a late and insensitive biomarker of glomerular filtration rate (GFR). The novel biomarker proenkephalin (PENK) may overcome these limitations, but no PENK-based equation for eGFR is currently available. Therefore, we developed and validated a PENK-based equation to assess GFR.
METHODS
In this international multicenter study in 1354 stable and critically ill patients, GFR was measured (mGFR) through iohexol or iothalamate clearance. A generalized linear model with sigmoidal nonlinear transfer function was used for equation development in the block-randomized development set. Covariates were selected in a data-driven fashion. The novel equation was assessed for bias, precision (mean ± SD), and accuracy (eGFR percentage within ±30% of mGFR, P30) in the validation set and compared with MDRD and CKD-EPI.
RESULTS
Median mGFR was 61 [44-81] ml/min per 1.73 m. In order of importance, PENK, creatinine, and age were included, and sex or race did not improve performance. The PENK-based equation mean ± SD bias of the mGFR was 0.5 ± 15 ml/min per 1.73 m, significantly less compared with MDRD (8 ± 17, < 0.001) and 2009 CKD-EPI (5 ± 17, < 0.001), not reaching statistical significance compared with 2021 CKD-EPI (1.3 ± 16, = 0.06). The P30 accuracy of the PENK-based equation was 83%, significantly higher compared with MDRD (68%, < 0.001) and 2009 CKD-EPI (76%, < 0.001), similar to 2021 CKD-EPI (80%, 0.13).
CONCLUSION
Overall, the PENK-based equation to assess eGFR performed better than most creatinine-based equations without using sex or race.
PubMed: 38025210
DOI: 10.1016/j.ekir.2023.08.006 -
Journal of Personalized Medicine Sep 2021Inulin clearance has, for a long time, been considered as the reference method to determine measured glomerular filtration rates (mGFRs). However, given the known... (Review)
Review
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 (Cr-EDTA, Tc-DTPA, I iothalamate) exogenous mGFR filtration markers are nowadays considered the most accurate options to evaluate GFR. The availability of Cr-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.
PubMed: 34683089
DOI: 10.3390/jpm11100949 -
Kidney International Reports Nov 2022The validity of a timed urine collection is typically judged by measurement of urine creatinine excretion, but prevailing limits may be unreliable. We sought to...
INTRODUCTION
The validity of a timed urine collection is typically judged by measurement of urine creatinine excretion, but prevailing limits may be unreliable. We sought to empirically derive population-based limits of excretion for evaluating the validity of a timed urine collection.
METHODS
Covariate and 24-hour urine data were obtained from 3582 participants in the Chronic Renal Insufficiency Cohort (CRIC) study, 814 participants in the Modification of Diet in Renal Disease (MDRD) study, 1010 participants in the Jackson Heart Study (JHS), and 8536 participants in the Prevention of Renal Vascular End Stage Disease (PREVEND) study. Weight, height, age, sex, and serum creatinine concentrations were evaluated as potential predictors of urine creatinine excretion using Akaike Information Criteria, R-squared values, and deviance. Bias and precision of the fitted models were assessed by analyses of residuals. Agreement between 24-hour creatinine clearance and I-iothalamate clearance was assessed before and after exclusion of potentially invalid urine samples.
RESULTS
A best-fitting model to predict 24-hour urine creatinine excretion among the 9199 discovery cohort members included sex-specific terms for weight, height, and age (R-squared = 0.328). This model had a median bias of +4.3 mg creatinine/day (95% confidence interval -5.6, +13.3 mg/day) in 4599 validation cohort members, and 82% of observed values were within 30% of predicted model. Serum creatinine concentrations only marginally improved model precision but reduced bias in persons with advanced chronic kidney disease (CKD).
CONCLUSION
The limits of urine creatinine excretion derived here represent the most valid and representative data for appraising the adequacy of a timed urine collection.
PubMed: 36531868
DOI: 10.1016/j.ekir.2022.08.025 -
American Journal of Kidney Diseases :... Aug 2016
Topics: Adult; Aged; Chromatography, High Pressure Liquid; Chromatography, Liquid; Contrast Media; Creatinine; Female; Glomerular Filtration Rate; Humans; Iohexol; Iothalamic Acid; Male; Middle Aged; Renal Insufficiency, Chronic; Tandem Mass Spectrometry
PubMed: 26851202
DOI: 10.1053/j.ajkd.2016.01.007 -
World Journal of Nephrology Jul 2015Kidney transplantation is the treatment of choice for end-stage renal disease. The evaluation of graft function is mandatory in the management of renal transplant... (Review)
Review
Kidney transplantation is the treatment of choice for end-stage renal disease. The evaluation of graft function is mandatory in the management of renal transplant recipients. Glomerular filtration rate (GFR), is generally considered the best index of graft function and also a predictor of graft and patient survival. However GFR measurement using inulin clearance, the gold standard for its measurement and exogenous markers such as radiolabeled isotopes ((51)Cr EDTA, (99m)Tc DTPA or (125)I Iothalamate) and non-radioactive contrast agents (Iothalamate or Iohexol), is laborious as well as expensive, being rarely used in clinical practice. Therefore, endogenous markers, such as serum creatinine or cystatin C, are used to estimate kidney function, and equations using these markers adjusted to other variables, mainly demographic, are an attempt to improve accuracy in estimation of GFR (eGFR). Nevertheless, there is some concern about the inability of the available eGFR equations to accurately identify changes in GFR, in kidney transplant recipients. This article will review and discuss the performance and limitations of these endogenous markers and their equations as estimators of GFR in the kidney transplant recipients, and their ability in predicting significant clinical outcomes.
PubMed: 26167457
DOI: 10.5527/wjn.v4.i3.345 -
Advances in Chronic Kidney Disease Jan 2018Accurate determination of glomerular filtration rate (GFR) is crucial for the diagnosis of kidney disease. Estimated GFR (eGFR) calculated by serum creatinine and/or... (Review)
Review
Accurate determination of glomerular filtration rate (GFR) is crucial for the diagnosis of kidney disease. Estimated GFR (eGFR) calculated by serum creatinine and/or cystatin C is a mainstay in clinical practice and epidemiologic research but lacks precision and accuracy until GFR <60 mL/min/1.73 m. Furthermore, eGFR may not precisely and accurately represent changes in GFR longitudinally. The lack of precision and accuracy is of concern in populations at high risk for kidney disease, as the dissociation between changes in eGFR and GFR may lead to missed diagnoses of early kidney disease. Therefore, improved methods to quantify GFR are needed. Whereas direct measures of GFR have been too cumbersome for screening and ambulatory care, a practical method of measuring GFR by iohexol clearance using dried capillary blood spots exists. In this review, we examine the current literature and data addressing GFR measurements by dried capillary blood spots and its potential application in high-risk groups.
Topics: Biomarkers; Dried Blood Spot Testing; Glomerular Filtration Rate; Humans; Kidney Diseases
PubMed: 29499891
DOI: 10.1053/j.ackd.2017.09.003 -
Journal of Nuclear Medicine : Official... Apr 1990True glomerular filtration rate (GFR) was measured in normal volunteers and in patients with normal and impaired renal function by the iothalamate clearance (IC) method... (Comparative Study)
Comparative Study
Comparison of methods for calculating glomerular filtration rate: technetium-99m-DTPA scintigraphic analysis, protein-free and whole-plasma clearance of technetium-99m-DTPA and iodine-125-iothalamate clearance.
True glomerular filtration rate (GFR) was measured in normal volunteers and in patients with normal and impaired renal function by the iothalamate clearance (IC) method of Sigman. Within 24 hr, GFR was also determined by two other methods: technetium-99m- (99mTc) DTPA scintigraphic analysis (SA) utilizing a modification of the Gates computer program, and by measuring disappearance of 99mTc-DTPA from whole plasma (WPC) and from protein-free ultrafiltered plasma (PFPC). Determinations of GFR by IC and by PFPC methods were virtually identical (mean absolute error 5.36 ml/min, r = 0.99, p greater than 0.05). GFRs measured in protein-free, ultrafiltered plasma differed significantly from those obtained from whole plasma only in sicker patients and in those taking multiple medications (in whom alterations in protein-binding of DTPA may be seen). The SA method correlated less well with the iodine-125-(125I) IC method than did either the protein-free or whole-plasma clearance methods (mean absolute error 32.36 ml/min, r = 0.74, p less than 0.05). However, the SA method provided useful information with respect to differential (split) renal function.
Topics: Adult; Female; Glomerular Filtration Rate; Humans; Iodine Radioisotopes; Iothalamic Acid; Male; Organotechnetium Compounds; Pentetic Acid; Radioisotope Renography; Technetium Tc 99m Pentetate
PubMed: 2182797
DOI: No ID Found -
Nefrologia 2021Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and...
BACKGROUND
Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors.
MATERIALS AND METHODS
A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC.
RESULTS
Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m) and 38.6% (60ml/min/1.73m) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73m) and 13.8% (60ml/min/1.73m). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73m) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age.
CONCLUSIONS
Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.
PubMed: 36165380
DOI: 10.1016/j.nefroe.2020.07.002