We aimed to evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine–cystatin C equation in a cohort of elderly Chinese participants.
Materials and methods
Glomerular filtration rate (GFR) was measured in 431 elderly Chinese participants by the technetium-99m diethylene-triamine-penta-acetic acid (99mTc-DTPA) renal dynamic imaging method, and was calibrated equally to the dual plasma sample 99mTc-DTPA-GFR. Performance of the CKD-EPI creatinine–cystatin C equation was compared with the Cockcroft–Gault equation, the re-expressed 4-variable Modification of Diet in Renal Disease (MDRD) equation, and the CKD-EPI creatinine equation.
Although the bias of the CKD-EPI creatinine–cystatin C equation was greater than with the other equations (median difference, 5.7 mL/minute/1.73 m2 versus a range from 0.4–2.5 mL/minute/1.73 m2; P<0.001 for all), the precision was improved with the CKD-EPI creatinine–cystatin C equation (interquartile range for the difference, 19.5 mL/minute/1.73 m2 versus a range from 23.0–23.6 mL/minute/1.73 m2; P<0.001 for all comparisons), leading to slight improvement in accuracy (median absolute difference, 10.5 mL/minute/1.73 m2 versus 12.2 and 11.4 mL/minute/1.73 m2 for the Cockcroft–Gault equation and the re-expressed 4-variable MDRD equation, P=0.04 for both; 11.6 mL/minute/1.73 m2 for the CKD-EPI creatinine equation, P=0.11), as the optimal scores of performance (6.0 versus a range from 1.0–2.0 for the other equations). Higher GFR category and diabetes were independent factors that negatively correlated with the accuracy of the CKD-EPI creatinine–cystatin C equation (β=−0.184 and −0.113, P<0.001 and P=0.02, respectively).
Compared with the creatinine-based equations, the CKD-EPI creatinine–cystatin C equation is more suitable for the elderly Chinese population. However, the cost-effectiveness of the CKD-EPI creatinine–cystatin C equation for clinical use should be considered.
elderly; equation; glomerular filtration rate; serum creatinine; cystatin C
To establish equations for the estimation of glomerular filtration rates (eGFRs) based on serum creatinine (SCr) and/or serum cystatin C (SCysC) in Chinese patients with chronic kidney disease (CKD), and to compare the new equations with both the reference GFR (rGFR) and the literature equations to evaluate their applicability.
The 788 Chinese CKD patients were randomly divided into two groups, the training group and the testing group, to establish new eGFR-formulas based on serum CysC and to validate the established formulas, respectively. 99mTc-DTPA clearance (as the rGFR), serum Cr, and serum CysC were determined for all patients, and GFR was calculated using the Cockcroft-Gault equation (eGFR1), the MDRD formula (eGFR2), the CKD-EPI formulas (eGFR3, eGFR4), and the Chinese eGFR Investigation Collaboration formulas (eGFR5, eGFR6). The accuracy of each eGFR was compared with the rGFR.
The training and testing groups' mean GFRs were 50.84±31.36 mL/min/1.73 m2 and 54.16±29.45 mL/min/1.73 m2, respectively. The two newly developed eGFR formulas were fitted using iterative computation: and . Significant correlation was observed between each eGFR and the rGFR. However, proportional errors and constant errors were observed between rGFR and eGFR1, eGFR2, eGFR4, eGFR5 or eGFR6, and constant errors were observed between eGFR3 and rGFR, as revealed by the Passing & Bablok plot analysis. The Bland-Altman analysis illustrated that the 95% limits of agreement of all equations exceeded the previously accepted limits of <60 mL/min •1.73 m2, except the equations of eGFR7 and eGFR8.
The newly developed formulas, eGFR7 and eGFR8, provide precise and accurate GFR estimation using serum CysC detection alone or in combination with serum Cr detection. Differences in detection methods should be carefully considered when choosing literature eGFR equations to avoid misdiagnosis and mistreatment.
In clinical practice the glomerular filtration rate (GFR) is estimated from serum creatinine-based equations like the Cockcroft-Gault formula (C&G) and Modification of Diet in Renal Disease formula (MDRD). Recently, serum cystatin C-based equations, the newer creatinine formula (The Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)), and equation that use both serum creatinine and cystatin C (CKD-EPI creatinine & cystatin formula) were proposed as new GFR markers. Present study compares serum creatinine-based equations, combined (including both serum creatinine and cystatin C) equation, and serum simple cystatin C formula (100/serum cystatin C) against 51CrEDTA clearance in 113 adult overweight Caucasians with diabetes mellitus type 2 (DM2) and chronic kidney disease (CKD). The results of present study demonstrated that the simple cystatin C formula could be a useful tool for the evaluation of renal function in overweight patients with DM2 and impaired kidney function in daily clinical practice in hospital and especially in outpatients. Despite the advantages of the simple cystatin C formula, cystatin C-based equations cannot completely replace the “gold standard” for estimation of the GFR in a population of DM2 patients with CKD, but may contribute to a more accurate selection of patients requiring such invasive and costly procedures.
Background. How to best estimate glomerular filtration rate (GFR) in kidney transplant recipients on steroid-free immunosuppression has not been established.
Methods. Within 3 months of transplantation, iothalamate GFR (iGFR) was measured in 107 recipients on steroid-free and 27 on steroid-maintenance immunosuppression. A year later, a second GFR was performed. Serum creatinine was calibrated against a reference laboratory, and GFR was estimated (eGFR) using the re-expressed Cockcroft–Gault equation, eGFRCG; the Mayo Clinic equation, eGFRMC; the Modification of Diet in Renal Disease (MDRD) study equation, eGFRMDRD; and the newly introduced Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Results. All models overestimated GFR regardless of steroid use or timing of GFR. In those not receiving steroids, eGFRCG was least biased: 1.85 ± 15.2 ml/min at the first GFR and 0.23 ± 15.2 ml/min at the second. eGFRMC and eGFRCKD-EPI were most biased and were within 30% of iGFR less than 60% of the time in contrast to eGFRCG which was within 30% of iGFR 80.2% of the time. eGFRMDRD was intermediate in its performance at the first GFR but was comparable to eGFRCG at the second measurement. Importantly, the four models had comparable but poor precision. Exposure to steroids for a whole year did not appreciably alter the models’ bias or relative accuracy but resulted in a dramatic fall in their precision, R2 = 0.05–0.12.
Conclusions. GFR prediction equations overestimate measured GFR in recipients on and off steroid regimens. Long-term exposure to steroids results in a marked reduction in the precision of all models. In all, eGFRCG and eGFRMDRD are the two best available models.
glomerular filtration rate; kidney transplant; steroid free
The equations provide a rapid and low-cost method of evaluating glomerular filtration rate (GFR). Previous studies indicated that the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease-Epidemiology (CKD-EPI) and MacIsaac equations need further modification for application in Chinese population. Thus, this study was designed to modify the three equations, and compare the diagnostic accuracy of the equations modified before and after.
With the use of 99 mTc-DTPA renal dynamic imaging as the reference GFR (rGFR), the MDRD, CKD-EPI and MacIsaac equations were modified by two mathematical algorithms: the hill-climbing and the simulated-annealing algorithms.
A total of 703 Chinese subjects were recruited, with the average rGFR 77.14±25.93 ml/min. The entire modification process was based on a random sample of 80% of subjects in each GFR level as a training sample set, the rest of 20% of subjects as a validation sample set. After modification, the three equations performed significant improvement in slop, intercept, correlated coefficient, root mean square error (RMSE), total deviation index (TDI), and the proportion of estimated GFR (eGFR) within 10% and 30% deviation of rGFR (P10 and P30). Of the three modified equations, the modified CKD-EPI equation showed the best accuracy.
Mathematical algorithms could be a considerable tool to modify the GFR equations. Accuracy of all the three modified equations was significantly improved in which the modified CKD-EPI equation could be the optimal one.
Prevalence of stage 3 chronic kidney disease (CKD) is increasing according to the NHANES study. Prevalence has been calculated using the MDRD study equation for estimating glomerular filtration rate (GFR). Recently, a new estimator based on creatinine, the CKD-EPI equation, has been proposed which is presumed to better perform in normal GFR ranges. The aim of the study was to measure the difference in prevalence of stage 3 CKD in a population using either the MDRD or the CKD-EPI study equations.
CKD screening is organized in the Province of Liège, Belgium. On a voluntary basis, people aged between 45 and 75 years are invited to be screened. GFR is estimated by the MDRD study equation and by the "new" CKD-EPI equations.
The population screened consisted in 1992 people (47% of men). Mean serum creatinine was 0.86 ± 0.20 mg/dL. The prevalence of stage 3 CKD in this population using the MDRD or the CKD-EPI equations was 11.04 and 7.98%, respectively. The prevalence of stage 3 CKD is significantly higher with the MDRD study equation (p < 0,0012).
Prevalence of stage 3 CKD varies strongly following the method used for estimating GFR, MDRD or CKD-EPI study equations. Such discrepancies are of importance and must be confirmed and explained by additional studies using GFR measured with a reference method.
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently published an equation for estimated glomerular filtration rate (eGFR) using the same variables (serum creatinine, age, gender and race) as the Modification of Diet in Renal Disease Study (MDRD) equation. Although the CKD-EPI equation estimates GFR more precisely as compared with the MDRD equation, whether this equation improves risk prediction is unknown.
Prospective cohort study, the Atherosclerosis Risk in Communities (ARIC) Study.
Setting & Participants
13,905 middle-aged participants without a history of cardiovascular disease with median follow-up of 16.9 years.
Outcomes & Measurements
We compared the association of eGFR in categories (≥120, 90–119, 60–89, 30–59, <30 ml/min/1.73m2) by the CKD-EPI and MDRD equations with risk of incident end-stage renal disease (ESRD), all-cause mortality, coronary heart disease (CHD), and stroke.
Median of eGFRCKD-EPI was higher than that of eGFRMDRD (97.6 vs. 88.8 ml/min/1.73m2, P<0.001). The CKD-EPI equation reclassified 44.9% (n=3,079) and 43.5% (n=151) of participants with eGFRMDRD 60–89 and 30–59, respectively, upward to a higher eGFR category but no one with eGFRMDRD 90–119 or <30, lowering the prevalence of CKD stage 3–5 from 2.7% to 1.6%. Participants with eGFRMDRD 30–59 who were reclassified upward had lower risk as compared to those who were not reclassified (ESRD incidence rate ratio, 0.10 [95% CI, 0.03–0.33], all-cause mortality, 0.30 [0.19–0.48], CHD, 0.36 [0.21–0.61], stroke, 0.50 [0.24–1.01]). Similar results were observed for participants with eGFRMDRD 60–89. More frequent reclassification of younger, female, and white participants explained some of these trends. Net reclassification improvement among participants with eGFR <120 was positive for all outcomes (P<0.001).
Limited number of cases with eGFR <60 and no measurement of albuminuria.
The CKD-EPI equation more appropriately categorized individuals with respect to long-term clinical risk as compared to the MDRD equation, suggesting improved clinical usefulness in this middle-aged population.
Background. Equations for estimating glomerular filtration rate (GFR) have not been validated in Sub-Saharan African populations, and data on GFR are few.
Methods. GFR by creatinine clearance (Ccr) using 24-hour urine collections and estimated GFR (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD-4)[creatinine calibrated to isotope dilution mass spectrometry (IDMS) standard], Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft–Gault equations were obtained in Ghanaians aged 40–75. The population comprised 1013 inhabitants in 12 villages; 944 provided a serum creatinine and two 24-hour urines. The mean weight was 54.4 kg; mean body mass index was 21.1 kg/m2.
Results. Mean GFR by Ccr was 84.1 ml/min/1.73 m2; 86.8% of participants had a GFR of ≥60 ml/min/1.73 m2. Mean MDRD-4 eGFR was 102.3 ml/min/1.73 m2 (difference vs. Ccr, 18.2: 95% CI: 16.8–19.5); when the factor for black race was omitted, the value (mean 84.6 ml/min/1.73 m2) was close to Ccr. Mean CKD-EPI eGFR was 103.1 ml/min/1.73 m2, and 89.4 ml/min/1.73 m2 when the factor for race was omitted. The Cockcroft–Gault equation underestimated GFR compared with Ccr by 9.4 ml/min/1.73 m2 (CI: 8.3–10.6); particularly in older age groups. GFR by Ccr, and eGFR by MDRD-4, CKD-EPI and Cockcroft–Gault showed falls with age: MDRD-4 5.5, Ccr 7.7, CKD-EPI 8.8 and Cockcroft–Gault 11.0 ml/min/1.73 m2/10 years. The percentage of individuals identified with CKD stages 3–5 depended on the method used: MDRD-4 1.6% (7.2 % without factor for black race; CKD-EPI 1.7% (4.7% without factor for black race), Ccr 13.2% and Cockcroft–Gault 21.0%.
Conclusions. Mean eGFR by both MDRD-4 and CKD-EPI was considerably higher than GFR by Ccr and Cockcroft–Gault, a difference that may be attributable to leanness. MDRD-4 appeared to underestimate the fall in GFR with age compared with the three other measurements; the fall with CKD-EPI without the adjustment for race was the closest to that of Ccr. An equation tailored specifically to the needs of the lean populations of Africa is urgently needed. For the present, the CKD-EPI equation without the adjustment for black race appears to be the most useful.
CKD-EPI eGFR; Cockcroft–Gault eGFR; creatinine clearance measurement; Ghana; MDRD-4 eGFR
As a standard indicator of renal function, the glomerular filtration rate (GFR) is vital for the prognostic analysis of elderly patients with coronary artery disease (CAD). Thus, the search for the calculation equation of GFR with the best prognostic ability is an important task. The most commonly used Modification of Diet in Renal Disease (MDRD) equation and the Chinese version (CMDRD) of the MDRD equation has many shortcomings. The newly developed Mayo Clinic quadratic (Mayo) and Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) equations may overcome these shortcomings. Because the populations involved in these equation-related studies are almost completely devoid of subjects > 70 years of age, there are more debates on the performance of these equations in the elderly. This study was designed to compare the prognostic abilities of different calculation formulas for the GFR in elderly Chinese patients with CAD.
This study included 1050 patients (≥60 years of age) with CAD. The endpoint was all-cause mortality over a mean follow-up period of 417 days.
The median age was 86 years (60–104 years). The median values for the MDRD-GFR, CMDRD-GFR, CKD-EPI-GFR, and Mayo-GFR were 66.0, 69.2, 65.6, and 75.8 mL/minute/1.73 m2, respectively. The prevalence of GFR < 60 mL/minute/1.73 m2 based on these measures was 39.3%, 35.4%, 43.0%, and 28.7%, respectively. Their area under the curve values for predicting death were 0.611, 0.610, 0.625, and 0.632, respectively. Their cut-off points for predicting death were 54.1, 53.5, 48.0, and 57.4 mL/minute/1.73 m2, respectively. Compared with the MDRD-GFR, the net reclassification improvement values of the CMDRD-GFR, CKD-EPI-GFR, and Mayo-GFR were 0.02, 0.10, and 0.14, respectively.
The prognostic abilities of the CKD-EPI and Mayo equations were significantly superior to the MDRD and CMDRD equations; the Mayo equation had a mild, but not statistically significant superiority compared with the CKD-EPI equation in elderly Chinese patients with CAD.
chronic kidney disease; coronary artery disease; glomerular filtration rate; equation; elderly
Chronic kidney disease (CKD) is increasingly being recognized as an emerging public health problem in India. However, community based estimates of low glomerular filtration rate (GFR) and proteinuria are few. Validity of traditional serum creatinine based GFR estimating equations in South Asian subjects is also debatable. We intended to estimate and compare the prevalence of low GFR, proteinuria and associated risk factors in North India using Cockcroft-Gault (CG) and Modification of Diet In Renal Disease (MDRD) equation.
A community based, cross-sectional study involving multistage random cluster sampling was done in Delhi and its surrounding regions. Adults ≥ 20 years were surveyed. CG and MDRD equations were used to estimate GFR (eGFR). Low GFR was defined as eGFR < 60 ml/min/1.73 m2. Proteinuria (≥ 1+) was assessed using visually read dipsticks. Odds ratios, crude and adjusted, were calculated to ascertain associations between renal impairment, proteinuria and risk factors.
The study population had 3,155 males and 2,097 females. The mean age for low eGFR subjects was 54 years. The unstandardized prevalence of low eGFR was 13.3% by CG equation and 4.2% by MDRD equation. The prevalence estimates of MDRD equation were lower across gender and age groups when compared with CG equation estimates. There was a strong correlation but poor agreement between GFR estimates of two equations. The survey population had a 2.25% prevalence of proteinuria. In a multivariate logistic regression analysis; age above 60 years, female gender, low educational status, increased waist circumference, hypertension and diabetes were associated with low eGFR. Similar factors were also associated with proteinuria. Only 3.3% of subjects with renal impairment were aware of their disease.
The prevalence of low eGFR in North India is probably higher than previous estimates. There is a significant difference between GFR estimates derived from CG and MDRD equations. These equations may not be useful in epidemiological research. GFR estimating equations validated for South Asian populations are needed before reliable estimates of CKD prevalence can be obtained. Till then, primary prevention and management targeted at CKD risk factors must play a critical role in controlling rising CKD magnitude. Cost-benefit analysis of targeted screening programs is needed.
Background. Despite a higher incidence of end-stage renal disease (stage 5), blacks have been shown to have the same or lower prevalence of chronic kidney disease (CKD stages 3 and 4). Current creatinine-based glomerular filtration rate (GFR)-estimating equations may misclassify young, healthy blacks.
Methods. Among 3501 young adults (mean age 45), we compared the prevalence of CKD in blacks and whites using the Modification of Diet in Renal Disease (MDRD) and the CKD Epidemiology Collaboration (CKD-EPI) equations. In addition, we used measured creatinine excretion rates to determine the actual excretion ratio for CARDIA (race coefficient 12%) and applied this to the CKD-EPI equation. We also studied the prevalence of CKD risk factors among black and white participants near the CKD threshold cut-off (eGFR CKD-EPI 60–80 mL/min/1.73 m2) to estimate the relative likelihood of misclassification in blacks and whites.
Results. Using the MDRD equation, prevalence of CKD stages 4 and 5 was higher for blacks compared with whites (0.6% vs. 0.1%, P-value 0.05). In contrast, prevalence of eGFR <60 mL/min/1.73 m2 was significantly higher for whites (3.6%) compared with blacks (1.9%), due to higher prevalence of stage 3 among whites. Prevalence of CKD was similar for blacks and whites using CKD-EPI equation (1.2%), but was higher among blacks when using the CARDIA-derived race coefficient (1.6% vs.1.2%, P-value = 0.03). Among persons with eGFR by CKD-EPI of 60–80 mL/min/1.73 m2, blacks had higher levels of albuminuria, uric acid, systolic blood pressure and higher diabetes prevalence.
Conclusions. CKD classification among young blacks is very sensitive to the race coefficients. Despite whites having higher rates of CKD stage 3, blacks with eGFRs just above the CKD threshold had higher rates of CKD risk factors. Current equations used to define CKD may systematically miss a high-risk group of blacks at a time in the disease course when interventions are crucial.
chronic kidney disease; glomerular filtration rate; race
To assess the cardiovascular risk of diabetic subjects with chronic kidney disease (CKD) based on different estimated glomerular filtration rate (eGFR) equations and to evaluate which definition of CKD best improves cardiovascular risk prediction of the Framingham Cardiovascular Risk Score (Framingham-CV-RS).
RESEARCH DESIGN AND METHODS
CKD was defined as eGFR <60 mL/min/1.73 m2, estimated by the creatinine-based Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and a cystatin C–based equation (CKD-CysC). Cox regression was used to estimate hazard ratios (HRs) of subjects with CKD for incident cardiovascular events in a cohort of 1,153 individuals with diabetes (baseline age 50–74 years). Furthermore, the CKD definitions were added individually to a reference model comprising the Framingham-CV-RS variables and HbA1c, and measures of model discrimination and reclassification were assessed.
During 5 years of follow-up, 95 individuals had a primary cardiovascular event. Crude HRs were increased for all CKD definitions. However, after adjusting for established cardiovascular risk factors, HRs for both creatinine-based CKD definitions were attenuated to point estimates of 1.03, whereas the HRs for the cystatin C–based CKD definition remained significantly increased (HR 1.75 [95% CI 1.07–2.87]). Extension of the reference model by the different CKD definitions resulted in an increase in the c statistic only when adding CKD-CysC (from 0.638 to 0.644) along with a net reclassification improvement of 8.9%.
Only the cystatin C–based CKD definition was an independent risk predictor for cardiovascular events in our diabetic study cohort and indicated a potentially better clinical utility for cardiovascular risk prediction than creatinine-based equations.
Low awareness of chronic kidney disease (CKD) may reflect uncertainty about the accuracy or significance of a CKD diagnosis in individuals otherwise perceived to be low-risk. Whether reclassification of CKD severity using the CKD Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) modifies estimates of CKD awareness is unknown.
In this cross-sectional study, we used data collected from 2000 to 2009 for 26,213 participants in the Kidney Early Evaluation Program (KEEP), a community-based screening program, with CKD based on GFR estimated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation and measurement of albuminuria. We assessed CKD awareness after CKD stage was reclassified using the CKD-EPI equation.
Of 26,213 participants with CKD based on eGFRMDRD, 23,572 (90%) were also classified with CKD based on eGFRCKD-EPI. Based on eGFRMDRD, 9.5% of participants overall were aware of CKD, as were 4.9%, 6.3%, 9.2%, 41.9%, and 59.2% with Stages 1-5, respectively. Based on eGFRCKD-EPI, 10.0% of participants overall were aware of CKD, as were 5.1%, 6.6%, 10.0%, 39.3%, and 59.4% with Stages 1-5, respectively. Reclassification to a less advanced CKD stage with eGFRCKD-EPI was associated with lower odds for awareness (OR, 0.58; 95% CI, 0.50-0.67); reclassification to a more advanced stage was associated with higher odds for awareness (OR, 1.50; 95% CI, 1.05-2.13) after adjustment for confounding factors. Of participants unaware of CKD, 10.6% were reclassified as not having CKD using eGFRCKD-EPI.
Using eGFRCKD-EPI led to a modest increase in overall awareness rates, primarily due to reclassification of low-risk unaware participants.
awareness; chronic kidney disease; CKD-EPI; estimated glomerular filtration rate
The National Kidney Foundation has recommended that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation replace the Modification of Diet in Renal Disease (MDRD) Study equation. Before implementing this change in the Kidney Early Evaluation Program (KEEP), we compared characteristics of reclassified individuals and mortality risk predictions using the new equation.
Of 123,704 eligible KEEP participants, 116,321 with data available for this analysis were included. Glomerular filtration rate (GFR) was estimated using the MDRD Study (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI) equations with creatinine level calibrated to standardized methods. Participants were characterized by eGFR category: >120, 90-119, 60-89, 45-59, 30-44, and <30 mL/min/1.73 m2. Clinical characteristics ascertained included age, race, sex, diabetes, hypertension, coronary artery disease, congestive heart failure, cerebrovascular disease, peripheral vascular disease, and anemia. Mortality was determined over a median of 3.7 years of follow-up.
The prevalence of eGFRCKD-EPI <60 mL/min/1.73 m2 was 14.3% compared with 16.8% using eGFRMDRD. Using eGFRCKD-EPI, 20,355 participants (17.5%) were reclassified to higher eGFR categories, and 3,107 (2.7%), to lower categories. Participants reclassified upward were younger and less likely to have chronic conditions, with a lower risk of mortality. A total of 3,601 deaths (3.1%) were reported. Compared with participants classified to eGFR of 45-59 mL/min/1.73 m2 using both equations, those with eGFRCKD-EPI of 60-89 mL/min/1.73 m2 had a lower mortality incidence rate (6.4 [95% CI, 5.1-7.7] vs 18.5 [95% CI, 17.1-19.9]). Results were similar for all eGFR categories. Net reclassification improvement was 0.159 (P < 0.001).
The CKD-EPI equation reclassifies people at lower risk of CKD and death into higher eGFR categories, suggesting more accurate categorization. The CKD-EPI equation will be used to report eGFR in KEEP.
Chronic kidney disease; glomerular filtration rate estimation; mortality; risk factors
Glomerular filtration rate (GFR) is used in the calculation of carboplatin dose. Glomerular filtration rate is measured using a radioisotope method (radionuclide GFR (rGFR)), however, estimation equations are available (estimated GFR (eGFR)). Our aim was to assess the accuracy of three eGFR equations and the subsequent carboplatin dose in an oncology population.
Patients and methods:
Patients referred for an rGFR over a 3-year period were selected; eGFR was calculated using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations. Carboplatin doses were calculated for those patients who had received carboplatin chemotherapy. Bias, precision and accuracy were examined.
Two hundred and eighty-eight studies met the inclusion/exclusion criteria. Paired t-tests showed significant differences for all three equations between rGFR and eGFR with biases of 12.3 (MDRD), 13.6 (CKD-EPI) and 7.7 ml min−1 per 1.73 m2 (CG). An overestimation in carboplatin dose was seen in 81%, 87% and 66% of studies using the MDRD, CKD-EPI and CG equations, respectively.
The MDRD and CKD-EPI equations performed poorly compared with the reference standard rGFR; the CG equation showed smaller bias and higher accuracy in our oncology population. On the basis of our results we recommend that the rGFR should be used for accurate carboplatin chemotherapy dosing and where unavailable the use of the CG equation is preferred.
carboplatin; glomerular filtration rate; EDTA
The aim of this study was to assess the kidney function of an older community-dwelling population at baseline and appraise its evolution after 3 years of follow-up in terms of chronic kidney disease (CKD) stage progression, magnitude of glomerular filtration rate (GFR) changes, and value of serum creatinine. This was a prospective population-based study of 676 Italian participants, aged 65 years and older. GFR was estimated using the Cockcroft–Gault equation and the Modification of Diet in Renal Disease Study equation. Using the Cockcroft–Gault equation. A total of 33% of participants had criteria of CKD (GFR < 60 mL/min) at baseline; among them, the majority remained stable, 10% improved, and 7% progressed to more severe CKD stages at follow-up. Loss of GFR in participants with GFR < 60 mL/min was significantly lower (1.4 mL/min per year) than in participants with GFR ≥ 60 mL/min (3.3 mL/min per year) at baseline. Most participants classified with CKD stage 2 (GFR 60–89 mL/min) or stage 3 (GFR 30–59 mL/min) at baseline did not change stage, whereas 55% of people with CKD stage 1 (GFR > 90 mL/min) at baseline worsened to stage 2 and 10% worsened to stage 3. An abnormal high level of serum creatinine at baseline did not help to predict who might worsen at follow-up. Older people with CKD displayed a low progression of renal disease and therefore are at higher risk for co-morbidities related to CKD than for progression to end-stage renal disease.
The best method to estimate glomerular filtration rate (GFR) in diabetic patients is still largely debated. We compared the performance of creatinine-based formulas in a European diabetic population.
RESEARCH DESIGN AND METHODS
We compared the performance of Cockcroft and Gault, simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equations in 246 diabetic patients by calculating the mean bias and the interquartile range (IQR) of the bias, 10% (P10) and 30% (P30) accuracies, and Bland-Altman plots. GFR was measured by inulin clearance.
For the whole population, the IQR was slightly lower for CKD-EPI, but the mean bias was lower and P10 and P30 were higher for MDRD. Similar results were observed in specific subgroups, including patients with mild renal insufficiency, obese patients, or type 2 diabetic patients.
In our population, the CKD-EPI formula does not exhibit better performance than the simplified MDRD formula for estimating GFR.
Background. Detection of subjects with early chronic kidney disease (CKD) is important because some will progress up to stage 5 CKD, and most are at high risk of cardiovascular morbidity and mortality. While validity and precision of estimated glomerular filtration rate (eGFR) equations in tracking true GFR have been repeatedly investigated, their prognostic performance for mortality has not been hitherto compared. This is especially relevant in an elderly population in whom the risk of death is far more common than progression.
Methods. We analysed data of participants in the InCHIANTI study, a community-based cohort study of older adults. Twenty-four-hour creatinine clearance (Ccr), Cockcroft–Gault (C-G) and Modification of Diet in Renal Disease (MDRD)-derived equations (six and four input variables) were calculated at enrolment (1998–2000), and all-cause mortality and cardiovascular mortality were prospectively ascertained by Cox regression over a 6-year follow-up.
Results. Of the 1270 participants, 942 (mean age 75 years) had complete data for this study. The mean renal function ranged from 77 ml/min/1.73 m2 by Ccr to 64 ml/min/1.73 m2 by C-G. Comparisons among equations using K/DOQI staging highlight relevant mismatches, with a prevalence of CKD ranging from 22% (MDRD-4) to 40% (C-G). Reduced renal function was a strong independent predictor of death. In a Cox model–-adjusted for demographics, physical activity, comorbidities, proteinuria and inflammatory parameters—participants with Ccr 60–90 ml/min/1.73 m2 and Ccr <60 ml/min/1.73 m2 were, respectively, 1.70 (95% CI: 1.02–2.83) and 1.91 (95% CI: 1.11–3.29) times more likely to die over the follow-up compared to those with Ccr >90 ml/min/1.73 m2. For the C-G, the group with values <60 ml/min/1.73 m2 had a significant higher all-cause mortality compared to those with values >90 ml/min/1.73 m2 (HR 2.59, 95% CI: 1.13–5.91). The classification based on the MDRD formulae did not provide any significant prognostic information. The adjusted risk of all-cause mortality followed a similar pattern when Ccr and estimating equations were introduced as continuous variables or dichotomized as higher or lower than 60 ml/min. C-G was the best prognostic indicator of cardiovascular mortality. Possibly, Ccr and C-G are better prognostic indicators than MDRD-derived equations because they incorporate a stronger effect of age.
Conclusions. In a South-European elderly population, the prevalence of CKD is high and varies widely according to the method adopted to estimate GFR. Researchers and clinicians who want to capture the prognostic information on mortality related to kidney function should use the Ccr or C-G formula and not MDRD equations. These results highlight the importance of strategies for early detection and clinical management of CKD in elderly subjects.
Cockcroft–Gault formula; elderly; MDRD equations; mortality; population-based study
Estimated glomerular filtration rate (eGFR) is very important in clinical practice, although it is not adequately tested in different populations. We aimed at establishing the best eGFR formulas for a Brazilian population with emphasis on the need for race correction.
We evaluated 202 individuals with chronic kidney disease (CKD) and 42 without previously known renal lesions that were additionally screened by urinalysis. Serum creatinine and plasma clearance of iohexol were measured in all cases. GFR was estimated by the Mayo Clinic, abbreviated Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas, and creatinine clearance was estimated by the Cockcroft-Gault (CG) formula. Plasma clearance of iohexol was used as the gold standard for GFR determination and for the development of a Brazilian formula (BreGFR).
Measured and estimated GFR were compared in 244 individuals, 57% female, with a mean age of 41 years (range 18–82). Estimates of intraclass correlation coefficients among the plasma clearance of iohexol and eGFR formulas were all significant (p < 0.001) and corresponded to the following scores: CG 0.730; obesity-adjusted CG 0.789; Mayo Clinic 0.804; MDRD 0.848; MDRD1 (without race adjustment) 0.846; CKD-EPI 0.869; CKD-EPI1 (without race adjustment) 0.876, and BreGFR 0.844.
All cited eGFR formulas showed a good correlation with the plasma clearance of iohexol in the healthy and diseased conditions. The formulas that best detected reduced eGFR were the BreGFR, CKD-EPI, and CKD-EPI1 formulas. Notably, the race correction included in the MDRD and CKD-EPI formulas was not necessary for this population, as it did not contribute to more accurate results.
Biomarkers; Creatinine clearance; Glomerular filtration rate; Glomerulonephritis
The aim of this study is to investigate the usefulness of the GFR-estimating equations to predict renal function in kidney donors before and after transplantation. We compared the performance of 24-hour-urine–based creatinine clearance (24 hr urine-CrCl), the Cockcroft-Gault formula (eGFRCG), the Modification of Diet in Renal Disease equation (eGFRMDRD), and the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) with technetium-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance (mGFR) in 207 potential kidney donors and 108 uninephric donors. Before donation, eGFRCKD-EPI showed minimal bias and did not show a significant difference from mGFR (P = 0.65, respectively) while 24 hr urine-CrCl and eGFRMDRD significantly underestimated mGFR (P<0.001 for each). Precision and accuracy was highest in eGFRCKD-EPI and this better performance was more dominant when renal function is higher than 90 mL·min−1·1.73 m−2. After kidney donation, eGFRMDRD was superior to other equations in precision and accuracy in contrast to before donation. Within individual analysis, eGFRMDRD showed better performance at post-donation compared to pre-donation, but eGFRCKD-EPI and eGFRCG showed inferior performance at post-donation. In conclusion, eGFRCKD-EPI showed better performance compared to other equations before donation. In a uninephric donor, however, eGFRMDRD is more appropriate for the estimation of renal function than eGFRCKD-EPI.
The number of adults with diabetes mellitus is increasing worldwide, particularly in Asia and Africa. In sub-Saharan Africa, renal complications of diabetes may go unrecognized due to limited diagnostic resources. The prevalence of chronic kidney disease (CKD) among adult diabetics in sub-Saharan Africa has not been well described.
This study was conducted at the diabetes mellitus clinic of Bugando Medical Centre in Mwanza, Tanzania. A total 369 consecutive adult diabetic patients were enrolled and interviewed. Each patient provided a urine sample for microalbuminuria and proteinuria and a blood sample for serum creatinine level. Estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. CKD was staged according to the Kidney Disease Improving Global Outcomes system.
A total of 309 (83.7%) study participants had CKD; 295 (80.0%) had significant albuminuria and 91 (24.7%) had eGFR < 60 ml/min. None of these patients were aware of their renal disease, and only 5 (1.3%) had a diagnosis of diabetic nephropathy recorded in their file. Older age was significantly associated with CKD in this population [OR 1.03, p = 0.03, 95%CI (1.00-1.05)].
Chronic kidney disease is highly prevalent among adult diabetic outpatients attending our clinic in Tanzania, but is usually undiagnosed. Nearly ¼ of patients had an eGFR low enough to require dose adjustment of diabetic medications. More diagnostic resources are needed for CKD screening among adults in Tanzania in order to slow progression and prevent complications.
Diabetes mellitus; Microalbuminuria; Proteinuria; CKD; Chronic kidney disease; Sub-Saharan Africa
Chronic kidney disease (CKD) represents a global public health problem. Few data exist in the elderly. The objective of the current study is to estimate the prevalence of CKD by means of various established and new equations and to identify the main determinants of CKD in elderly.
The ActiFE Ulm (Activity and Function in the Elderly in Ulm) study is a population-based cohort study in people of 65 years and older. Kidney function was assessed by means of estimated glomerular filtration rate (eGFR) based on two creatinine- (Cr-; MDRD, CKD-EPI) and one cystatin C - (CysC-) based method. The relationship between various potential risk factors and CKD was quantified using unconditional logistic regression.
A total of 1471 subjects were in the final analysis (mean age 75.6 years, SD 6.56). Overall, prevalence of CKD (eGFR < 60 mL/min/1.73 m2) was 34.3% by MDRD, 33.0% by CKD-EPI, and 14.6% by the CysC-based eGFR. All eGFRs showed statistically significant correlations with C-reactive protein, uric acid, as well as with lipid values. In multivariable analysis age was clearly related to prevalence of CKD and the risks were highest with the CysC-based equation. Females had a higher risk for CKD stages 3–5 with MDRD (OR 1.63; 95% CI: 1.23–2.16) whereas the OR was 1.23 (95% CI 0.92–1.65) with the CKD-Epi and OR = 0.89 (95% CI 0.58–1.34) with the CysC-based equation after multivariable adjustment. Although the cystatin C based definition of CKD resulted in a lower prevalence compared to the creatinine based ones, other measures of renal damage such as albuminuria were more prevalent in those defined by CysC-eGFR.
Prevalence of CKD is very variable based on the used estimating equation. More work is needed to evaluate the various estimating equations especially in elderly before we are able to assess the practical consequences of the observed differences.
Elderly; Chronic kidney disease; Population-based study; Estimating equations; Risk factors
Chronic kidney disease (CKD) is associated with increased vascular risk. Some studies suggested that considering markers of CKD might improve the predictive accuracy of the Framingham risk equation.
To evaluate the links between kidney function and risk stratification in patients with primary dyslipidemia.
Dyslipidemic patients (n = 156; 83 men) who were non-smokers, did not have diabetes mellitus or evident vascular disease and were not on lipid-lowering or antihypertensive agents were recruited. Creatinine clearance (CrCl) was estimated using the Cockcroft-Gault equation. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation. We estimated vascular risk using the Framingham equation.
In both men and women, there was a significant negative correlation between estimated Framingham risk and both eGFR and CrCl (p < 0.001 for all correlations). When men were divided according to creatinine tertiles, there were no significant differences in any parameter between groups. When men were divided according to either eGFR or CrCl tertiles, all estimated Framingham risks significantly increased as renal function declined (p<0.001 for all trends). When women were divided according to creatinine tertiles, all estimated Framingham risks except for stroke significantly increased as creatinine levels increased. When women were divided according to either eGFR or CrCl tertiles, all estimated Framingham risks significantly increased as renal function declined.
Estimated vascular risk increases as renal function declines. The possibility that incorporating kidney function in the Framingham equation will improve risk stratification requires further evaluation.
Creatinine; estimated glomerular filtration rate; chronic kidney disease; vascular risk; Framingham risk score.
Soluble endoglin, a TGF-β receptor, plays a key role in cardiovascular physiology. Whether circulating concentrations of soluble endoglin are elevated in CKD or underlie the high risk of cardiovascular death associated with chronic kidney disease (CKD) is unknown.
Individuals with and without CKD were recruited at a single center. Estimated glomerular filtration rate (eGFR) was estimated using the modified MDRD study equation and the serum creatinine at the time of recruitment, and patients were assigned to specific CKD stage according to usual guidelines. Serum endoglin concentration was measured by ELISA and univariate and multivariable regression was used to analyze the association between eGFR or CKD stage and the concentration of soluble endoglin.
Serum endoglin was measured in 216 patients including 118 with stage 3 or higher CKD and 9 individuals with end stage renal disease (ESRD). Serum endoglin concentration did not vary significantly with CKD stage (increase of 0.16 ng/mL per 1 stage increase in CKD, P = 0.09) or eGFR (decrease -0.06 ng/mL per 10 mL/min/1.73 m2 increase in GFR, P = 0.12), and was not higher in individuals with ESRD than in individuals with preserved renal function (4.2±1.1 and 4.3±1.2 ng/mL, respectively). Endoglin concentration was also not significantly associated with urinary albumin excretion.
Renal function is not associated with the circulating concentration of soluble endoglin. Elevations in soluble endoglin concentration are unlikely to contribute to the progression of CKD or the predisposition of individuals with CKD to develop cardiovascular disease.
Cardiorenal syndrome (CRS) is a disorder of the heart and kidney whereby interactions between the 2 organs can occur. We recorded the clinical features of CRS in patients consecutively admitted to an Internal Medicine ward.
Patients and Methods:
We retrospectively analyzed the anthropometric, history, clinical, biochemical and treatment characteristics in 438 out of 2,998 subjects (14.6%) admitted to our unit (from June 2007 to December 2009), diagnosed with CRS, according to Acute Dialysis Quality Initiative (ADQI) recommendations. Estimated glomerular filtration (eGFR) was calculated using several equations: MDRD (Modification of Diet in Renal Disease; 2 variations GFRMDRD186, GFRMDRD175), Mayo, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockroft-Gault.
Mean age was 80±8 years, 222 (50.6%) were males, 321 (73.2%) were smokers, 229 (52.2%) were diabetic, 207 (47.2%) had a history of acute myocardial infarction, 167 (38.1%) had angina, 135 (30.8%) were affected by cerebrovascular disease, 339 (77.3%) had peripheral arterial disease. CRS was type 1 in 211 cases (48.2%), type 2 in 96 (21.9%), type 3 in 88 (20.1%), type 4 in 29 (6.6%) and type 5 in 14 (3.2%). eGFR, calculated by different formulae, ranged between 31 and 36 ml/min/1.73 m2. GFR was lower in CRS type 3 than in the other types, and the values ranged between 24 and 27 ml/min/1.73 m2. Mean hospital length-of-stay (LOS) was 9.8±6.3 days. Diuretics were the most prescribed medication (78.7%); only 5 patients underwent haemodialysis.
CRS is common, especially in the elderly. CRS Type 1 was the prevalent subset and patients had stage 3-4 renal insufficiency. Results obtained from the GFR equations were similar although the Mayo equation tended to overestimate the eGFR.
Cardio-renal syndrome; heart failure; chronic kidney disease; renal function; heart disease.