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1.  Comparisons between the 2012 New CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Equations and Other Four Approved Equations 
PLoS ONE  2014;9(1):e84688.
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) reported two equations in 2012: one based on cystatin C concentration (CKD-EPI2012cys) and the other using both serum creatinine and cystatin C concentrations (CKD-EPI2012Scr-cys). We compared the adaptability of new formulae with other four equations.
Participants (n = 788; median age, 54 [range, 19–94] years) were recruited from the First Affiliated Hospital of Nanjing Medical University. The reference glomerular filtration rate (rGFR) was measured by a 99mTc-DTPA renal dynamic imaging method, and the estimated glomerular filtration rate (eGFR) was calculated separately by the Chinese adapted Modification of Diet in Renal Disease equation (C-MDRD), MacIsaac, Ma, serum creatinine-based CKD-EPI equation (CKD-EPI2009Scr), CKD-EPI2012cys and CKD-EPI2012Scr-cys equations. We compared the performance of six equations with rGFR.
Median rGFR was 76.35 (interquartile range, 59.03–92.50) mL/min/1.73 m2. Compared with CKD-EPI2009Scr, CKD-EPI2012Scr-cys formula had better diagnostic value with larger area under the receiver operating characteristic curve (ROCAUC, 0.879, p = 0.006), especially in young participants (ROCAUC, 0.883, p = 0.005). CKD-EPI2012cys equation did not perform better than other available equations. Accuracy (the proportion of eGFR within 30% of rGFR [P30]) of the CKD-EPI2012Scr-cys equation (77.03%) was inferior only to MacIsaac equation (80.2%) in the entire participants, but performed best in young participants with normal or mildly-injured GFR. Neither of the two new CKD-EPI equations achieved any ideal P30 in the elderly participants with moderately-severely injured GFR. Linear regression analysis demonstrated a consistent result. In this study, CKD-EPI2012Scr-cys had a relatively better diagnosis consistency of GFR stage between the eGFR and rGFR in the whole cohort.
CKD-EPI2012Scr-cys appeared less biased and more accurate in overall participants. Neither of the new CKD-EPI equations achieved ideal accuracy in senior participants with moderately-severely injured GFR. A large-scale study with more subjects and cooperating centers to develop new formulae for the elderly is assumed to be necessary.
PMCID: PMC3890277  PMID: 24454737
2.  Is the Chronic Kidney Disease Epidemiology Collaboration creatinine–cystatin C equation useful for glomerular filtration rate estimation in the elderly? 
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.
PMCID: PMC3797613  PMID: 24143084
elderly; equation; glomerular filtration rate; serum creatinine; cystatin C
3.  Multicenter Study of Creatinine- and/or Cystatin C-Based Equations for Estimation of Glomerular Filtration Rates in Chinese Patients with Chronic Kidney Disease 
PLoS ONE  2013;8(3):e57240.
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.
PMCID: PMC3602457  PMID: 23526939
4.  Estimating glomerular filtration rate in a population-based study 
Glomerular filtration rate (GFR)-estimating equations are used to determine the prevalence of chronic kidney disease (CKD) in population-based studies. However, it has been suggested that since the commonly used GFR equations were originally developed from samples of patients with CKD, they underestimate GFR in healthy populations. Few studies have made side-by-side comparisons of the effect of various estimating equations on the prevalence estimates of CKD in a general population sample.
Patients and methods:
We examined a population-based sample comprising adults from Wisconsin (age, 43–86 years; 56% women). We compared the prevalence of CKD, defined as a GFR of <60 mL/min per 1.73 m2 estimated from serum creatinine, by applying various commonly used equations including the modification of diet in renal disease (MDRD) equation, Cockcroft–Gault (CG) equation, and the Mayo equation. We compared the performance of these equations against the CKD definition of cystatin C >1.23 mg/L.
We found that the prevalence of CKD varied widely among different GFR equations. Although the prevalence of CKD was 17.2% with the MDRD equation and 16.5% with the CG equation, it was only 4.8% with the Mayo equation. Only 24% of those identified to have GFR in the range of 50–59 mL/min per 1.73 m2 by the MDRD equation had cystatin C levels >1.23 mg/L; their mean cystatin C level was only 1 mg/L (interquartile range, 0.9–1.2 mg/L). This finding was similar for the CG equation. For the Mayo equation, 62.8% of those patients with GFR in the range of 50–59 mL/min per 1.73 m2 had cystatin C levels >1.23 mg/L; their mean cystatin C level was 1.3 mg/L (interquartile range, 1.2–1.5 mg/L). The MDRD and CG equations showed a false-positive rate of >10%.
We found that the MDRD and CG equations, the current standard to estimate GFR, appeared to overestimate the prevalence of CKD in a general population sample.
PMCID: PMC2922323  PMID: 20730018
chronic kidney disease; glomerular filtration rate; MDRD equation; Cockcroft–Gault equation; Mayo equation
5.  Estimation of glomerular filtration rate from serum creatinine and cystatin C in octogenarians and nonagenarians 
BMC Nephrology  2013;14:265.
Equations to estimate GFR have not been well validated in the elderly and may misclassify persons with chronic kidney disease (CKD). We measured GFR and compared the performance of the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease-Epidemiology Collaboration (CKD-Epi) and the Berlin Initiative Study (BIS) equations based on creatinine and/or cystatin C in octogenarians and nonagenarians.
Using cross-sectional analysis we assessed 95 very elderly persons (mean 85 years) living in the community. GFR was measured by iohexol (mGFR) and compared with estimates using six equations: MDRD, CKD-Epi_creatinine, CKD-Epi_cystatin, CKD-Epi_creatinine-cystatin, BIS_creatinine and BIS_creatinine-cystatin.
Mean mGFR was 55 (range,19–86) ml/min/1.73 m2. Bias was smaller with the CKD-Epi_creatinine-cystatin and the CKD-Epi_creatinine equations (-4.0 and 1.7 ml/min/1.73 m2). Accuracy (percentage of estimates within 30% of mGFR) was greater with the CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and BIS_creatinine equations (85%, 83% and 80%, respectively). Among the creatinine-based equations, the BIS_creatinine had the greatest accuracy at mGFR < 60 ml/min/1.73 m2 and the CKD-Epi_creatinine was superior at higher GFRs (79% and 90%, respectively). The CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and CKD-Epi_cystatin equations yielded the greatest areas under the receiver operating characteristic curve at GFR threshold = 60 ml/min/1.73 m2 (0.88, 0.88 and 0.87, respectively). In participants classified based on the BIS_creatinine, CKD-Epi_cystatin, or BIS_creatinine-cystatin equations, the CKD-Epi_creatinine-cystatin equation tended to improve CKD classification (net reclassification index: 12.7%, p = 0.18; 6.7%, p = 0.38; and 15.9%; p = 0.08, respectively).
GFR-estimating equations CKD-Epi_creatinine-cystatin and BIS_creatinine-cystatin showed better accuracy than other equations using creatinine or cystatin C alone in very elderly persons. The CKD-Epi_creatinine-cystatin equation appears to be advantageous in CKD classification. If cystatin C is not available, both the BIS_cr equation and the CKD-Epi_cr equation could be used, although at mGFR < 60 ml/min/1.73 m2, the BIS_cr equation seems to be the best alternative.
PMCID: PMC4219437  PMID: 24295505
Chronic kidney disease; Creatinine; Cystatin C; Elderly; Glomerular filtration rate; Iohexol
6.  Chronic kidney disease and underdiagnosis of renal insufficiency among diabetic patients attending a hospital in Southern Ethiopia 
BMC Nephrology  2014;15(1):198.
Diabetic patients with chronic kidney disease (CKD), as defined by a reduced glomerular filtration rate (GFR), are at greater risk for cardiovascular and renal events and mortality. The aim of this study was to determine the prevalence of CKD among diabetic patients attending a hospital in southern Ethiopia, and to assess underdiagnosis of renal insufficiency among those with normal serum creatinine.
A total of 214 randomly selected diabetics attending the follow-up clinic at Butajira hospital of southern Ethiopia participated in this study during the period from September 1 to October 31, 2013. All patients completed an interviewer-administered questionnaire and underwent clinical assessment. The simplified Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault (C-G) equations were used to estimate GFR (eGFR) from serum creatinine.
CKD, defined as eGFR < 60 ml/min/1.73 m2, was present in 18.2% and 23.8% of the study participants according to the MDRD and Cockcroft-Gault (C-G) equations, respectively. Only 9.8% of the total participants, and 48.7% (for the MDRD) and 37.3% (for C-G) of those with eGFR <60 ml/min/1.73 m2 had abnormal serum creatinine values, i.e. > 1.5 mg/dl. Normal serum creatinine was observed in 90.2% of participants attending the hospital. A large proportion of participants ranging from 38.9-56.5% have shown to have mild to moderate renal insufficiency (stage 2–3 CKD) despite normal creatinine levels. CKD, eGFR < 60 ml/min/1.73 m2, was found in 10.4 and 16.9% of participants with normal serum creatinine using the MDRD and C-G equations, respectively.
CKD is present in no less than 18% of diabetics attending the hospital, but it is usually undiagnosed. A significant number of diabetics have renal insufficiency corresponding to stages 2–3 CKD despite normal creatinine levels. Therefore, GFR should be considered as an estimate of renal insufficiency, regardless of serum creatinine levels being in normal range.
PMCID: PMC4277829  PMID: 25511372
Chronic kidney disease; Diabetes; Estimated glomerular filtration rate; Serum creatinine; Renal insufficiency
7.  Assessment of GFR by four methods in adults in Ashanti, Ghana: the need for an eGFR equation for lean African populations 
Nephrology Dialysis Transplantation  2010;25(7):2178-2187.
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.
PMCID: PMC2891745  PMID: 20100724
CKD-EPI eGFR; Cockcroft–Gault eGFR; creatinine clearance measurement; Ghana; MDRD-4 eGFR
8.  Modified Glomerular Filtration Rate-Estimating Equations Developed in Asiatic Population for Chinese Patients with Type 2 Diabetes 
Objectives. To evaluate eight modified equations developed in Asiatic populations in type 2 diabetic patients in China. Methods. A total of 209 Chinese patients with type 2 diabetes were recruited. Using the technetium—99m diethylenetriaminepentaacetic acid—glomerular filtration rate (GFR) to act as the reference, comparisons of their efficiency to estimate GFR in the subjects were made between various equations. Results. Median of difference of the Chinese equation 1 was the lowest (median of difference, 0.51 mL/min/1.73 m2). Median percent of absolute difference of the Chinese equation 2 was less than those of the other equations (26.97 versus ranged from 32.54 to 37.61 mL/min/1.73 m2, [P < 0.001 for all]). Precision of the simplified reexpressed MDRD equation was the best (92.9 mL/min/1.73 m2). Accuracies of the Chinese equation 2 were greater (P < 0.05 for all). There was also an improvement in chronic kidney disease (CKD) stage misclassification of the Chinese equation 2 (55.0 versus ranged from 61.2 to 64.6%, [P < 0.001 for all]). However, the 30% accuracies of all the equations were less than 70%. Conclusions. Our study highlighted a limitation in the use of the above equations in the majority of Chinese diabetic subjects. A better equation is needed in order to give an accurate estimation of GFR in type 2 diabetic patients in China.
PMCID: PMC3966408  PMID: 24734043
9.  Renal Function and Risk of Coronary Heart Disease in General Populations: New Prospective Study and Systematic Review 
PLoS Medicine  2007;4(9):e270.
End-stage chronic kidney disease is associated with striking excesses of cardiovascular mortality, but it is uncertain to what extent renal function is related to risk of subsequent coronary heart disease (CHD) in apparently healthy adults. This study aims to quantify the association of markers of renal function with CHD risk in essentially general populations.
Methods and Findings
Estimated glomerular filtration rate (eGFR) was calculated using standard prediction equations based on serum creatinine measurements made in 2,007 patients diagnosed with nonfatal myocardial infarction or coronary death during follow-up and in 3,869 people without CHD in the Reykjavik population-based cohort of 18,569 individuals. There were small and nonsignificant odds ratios (ORs) for CHD risk over most of the range in eGFR, except in the lowest category of the lowest fifth (corresponding to values of <60 ml/min/1.73m2), in which the OR was 1.33 (95% confidence interval 1.01–1.75) after adjustment for several established cardiovascular risk factors. Findings from the Reykjavik study were reinforced by a meta-analysis of six previous reports (identified in electronic and other databases) involving a total of 4,720 incident CHD cases (including Reykjavik), which yielded a combined risk ratio of 1.41 (95% confidence interval 1.19–1.68) in individuals with baseline eGFR less than 60 ml/min/1.73m2 compared with those with higher values.
Although there are no strong associations between lower-than-average eGFR and CHD risk in apparently healthy adults over most of the range in renal function, there may be a moderate increase in CHD risk associated with very low eGFR (i.e., renal dysfunction) in the general population. These findings could have implications for the further understanding of CHD and targeting cardioprotective interventions.
John Danesh and colleagues conclude there may be a moderate increase in risk of coronary heart disease associated with very low estimated glomerular filtration rate.
Editors' Summary
Coronary heart disease (CHD), the leading cause of death in most Western countries, is a “cardiovascular” disease—literally a disorder affecting the heart and/or blood vessels. In CHD, the blood vessels that supply the heart become increasingly narrow. Eventually, the flow of blood to the heart slows or stops, causing chest pains (angina), breathlessness, and heart attacks. Many factors increase the risk of developing CHD and other cardiovascular diseases, including high blood pressure, high blood levels of cholesterol (a type of fat), or being overweight. Individuals can reduce their chances of developing cardiovascular disease by taking drugs to reduce their blood pressure or cholesterol levels or by making lifestyle changes (so-called cardioprotective interventions). Another important risk factor for cardiovascular disease is end-stage chronic kidney disease (CKD), a condition in which the kidneys stop working. (In healthy people, the kidneys remove waste products and excess fluid from the body.) People with end-stage CKD (which is treated by dialysis) have about a five times higher risk of dying from cardiovascular disease compared with healthy people.
Why Was This Study Done?
End-stage CKD is preceded by a gradual loss of kidney function. There is a clear association between non-dialysis–dependent CKD and the incidence of cardiovascular events (such as heart attacks) in people who already have signs of cardiovascular disease. But are people with slightly dysfunctional kidneys (often because of increasing age) but without any obvious cardiovascular disease at greater risk of developing cardiovascular diseases than people with fully functional kidneys? If the answer is yes, it might be possible to reduce CHD deaths by minimizing the exposure of people with CKD to other risk factors for cardiovascular disease. In this study, the researchers have taken two approaches to answer this question. In a population-based study, they have examined whether there is any association in healthy adults between kidney function measured at the start of the study and incident CHD (the first occurrence of CHD) over subsequent years. In addition, they have systematically searched the published literature for similar studies and combined the results of these studies using statistical methods, a so-called “meta-analysis.”
What Did the Researchers Do and Find?
Between 1967 and 1991, nearly 19,000 middle-aged men and women without a history of heart attacks living in Reykjavik, Iceland, enrolled in a prospective study of cardiovascular disease. Baseline blood samples were taken at enrollment and the participants' health monitored for 20 years on average. The researchers identified 2,007 participants who suffered a nonfatal heart attack or died of CHD during follow-up and 3,869 who remained disease free. They then calculated the estimated glomerular filtration rate (eGFR; a measure of kidney function) for each participant from baseline creatinine measurements (creatinine is a muscle waste product). There was no association between lower-than-average eGFRs and the risk of developing CHD over most of the range of eGFR values. However, people whose eGFR was below approximately 60 units had about a 40% higher risk of developing CHD after allowing for established cardiovascular risk factors than individuals with higher eGFRs. This finding was confirmed by the meta-analysis of six previous studies, which included a further 2,700 incident CHD cases.
What Do These Findings Mean?
These findings indicate that people with an eGFR below about 60 units (the cut-off used to define CKD) may have an increased risk of developing CHD. They also indicate a nonliner association between kidney function and CHD risk. That is, any association with CHD became evident only when the eGFR dropped below about 60 units. These findings need confirming in different ethnic groups and by using more accurate methods to measure eGFRs. Nevertheless, they suggest that improving kidney function across the board is unlikely to have much effect on the overall incidence of CHD. Instead, they suggest that targeting cardioprotective interventions at the one in ten adults in Western countries whose eGFR is below 60 units might be a good way to reduce the burden of CHD.
Additional Information.
Please access these Web sites via the online version of this summary at
MedlinePlus encyclopedia pages on coronary heart disease, chronic kidney failure, and end-stage kidney disease (in English and Spanish).
Information for patients and carers from the American Heart Association on all aspects of heart disease, including prevention of CHD
Information from the British Heart Foundation on heart disease and on keeping the heart healthy
Information on chronic kidney disease from the US National Kidney Foundation, and the US National Kidney and Urologic Diseases Information Clearing House (in English and Spanish)
Information on chronic kidney disease from the UK National Kidney Foundation
PMCID: PMC1961630  PMID: 17803353
10.  A New Equation to Estimate Glomerular Filtration Rate 
Annals of internal medicine  2009;150(9):604-612.
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 levels.
To develop a new estimating equation (CKD-EPI creatinine equation).
Cross-sectional analysis. Separate pooled databases for equation development and validation. Representative U.S. population for prevalence estimates.
Research studies and clinical populations (“studies”) with measured GFR. National Health and Nutrition Examination Survey (NHANES) 1999-2006.
Equation development in 10 studies (8254 people) and validation in 16 studies (3896 people). Prevalence estimates based on 16,032 people.
GFR measured as the clearance of exogenous filtration markers (iothalamate in the development dataset; iothalamate and other markers in the validation dataset). Linear regression to estimate the logarithm of measured GFR from standardized creatinine, sex, race and age.
In the validation dataset, the CKD-EPI performed better than the MDRD Study equation (p<0.001 for all subsequent comparisons), especially at higher GFR: lesser bias (median difference between measured and estimated GFR of 2.5 vs. 5.5 mL/min/1.73 m2, respectively); improved precision (interquartile range of the differences of 16.6 vs. 18.3 mL/min/1.73 m2, respectively); and greater accuracy (percent of estimated GFR within 30% of measured GFR of 84.1 vs. 80.6%, respectively. In NHANES, median (interquartile range) estimated GFR was 94.5 (79.7 – 108.1) vs. 85.0 (72.9 – 98.5) mL/min/1.73 m2, and the prevalence (95% confidence interval) of CKD was 11.5 (10.6, 12.4) % vs. 13.1 (12.1, 14.0) %, respectively.
Limited number of elderly people and racial and ethnic minorities with measured GFR.
The CKD-EPI creatinine equation is more accurate than the MDRD Study equation and could replace it for routine clinical use.
PMCID: PMC2763564  PMID: 19414839
11.  Prevalence of low glomerular filtration rate, proteinuria and associated risk factors in North India using Cockcroft-Gault and Modification of Diet in Renal Disease equation: an observational, cross-sectional study 
BMC Nephrology  2009;10:4.
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.
PMCID: PMC2663556  PMID: 19220921
12.  The glomerular filtration rate estimated by new and old equations as a predictor of important outcomes in elderly patients 
BMC Medicine  2014;12:27.
The prevalence of chronic kidney disease (CKD) increases with age, and new glomerular filtration rate-estimating equations have recently been validated. The epidemiology of CKD in older individuals and the relationship between a low estimated glomerular filtration rate as calculated by these equations and adverse outcomes remains unknown.
Data from the BELFRAIL study, a prospective, population-based cohort study of 539 individuals aged 80 years and older, were used. For every participant, five equations were used to calculate estimated glomerular filtration rate based on serum creatinine and/or cystatin C values: MDRD, CKD-EPIcreat, CKD-EPIcyst, CKD-EPIcreatcyst, and BIS equations. The outcomes analyzed included mortality combined with the necessity of new renal replacement therapy, severe cardiovascular events, and hospitalization.
During the follow-up period, which was an average of 2.9 years, 124 participants died, 7 required renal replacement therapy, 271 were hospitalized, and 73 had a severe cardiovascular event. The prevalence of estimated glomerular filtration rate values <60 mL/min/1.73 m2 differed depending on the equation used as follows: 44% (MDRD), 45% (CKD-EPIcreat), 75% (CKD-EPIcyst), 65% (CKD-EPIcreatcyst), and 80% (BIS). All of the glomerular filtration rate-estimating equations revealed that higher cardiovascular mortality was associated with lower estimated glomerular filtration rates and that higher probabilities of hospitalization were associated with estimated glomerular filtration rates <30 mL/min/1.73 m2. A lower estimated glomerular filtration rate did not predict a higher probability of severe cardiovascular events, except when using the CKD-EPIcyst equation. By calculating the net reclassification improvement, CKD-EPIcyst and CKD-EPIcreatcyst were shown to predict mortality (+25% and +18%) and severe cardiovascular events (+7% and +9%) with the highest accuracy. The BIS equation was less accurate in predicting mortality (-12%).
Higher prevalence of CKD were found using the CKD-EPIcyst, CKD-EPIcreatcyst, and BIS equations compared with the MDRD and CKD-EPIcreat equations. The new CKD-EPIcreatcyst and CKD-EPIcyst equations appear to be better predictors of mortality and severe cardiovascular events.
PMCID: PMC3974109  PMID: 24517214
Cardiovascular events; eGFR; Hospitalizations; Mortality; Renal function
13.  Predictivity of survival according to different equations for estimating renal function in community-dwelling elderly subjects 
Nephrology Dialysis Transplantation  2008;24(4):1197-1205.
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.
PMCID: PMC2721425  PMID: 18988669
Cockcroft–Gault formula; elderly; MDRD equations; mortality; population-based study
14.  Comparative Performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study Equations for Estimating GFR Levels Above 60 mL/min/1.73 m2 
The MDRD Study equation underestimates measured GFR at levels greater than 60 ml/min per 1.73 m2, with variable accuracy among subgroups; consequently estimated GFR (eGFR) ≥ 60 ml/min/1.73 m2 is not reported by clinical laboratories. Here, the performance of a more accurate GFR estimating equation, the CKD-EPI equation, is reported by level of GFR and clinical characteristics.
Study Design
Test of diagnostic accuracy
Setting and Participants
Pooled dataset of 3896 people from 16 studies with measured GFR (not used for development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid organ transplant, and body mass index.
Index Tests
eGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine
Reference Test
Measured GFR using urinary or plasma clearance of exogenous filtration markers
Mean (SD) measured GFR was 68 (36) ml/min/1.73 m2. For eGFR less than 30 ml/min/1.73 m2, both equations have similar bias (median difference compared to measured GFR). For eGFR between 30-59 ml/min/1.73 m2, bias was reduced from 4.9 to 2.1 ml/min/1.73 m2 (57% improvement). For eGFR between 60-89 ml/min/1.73 m2, bias was reduced from 11.9 to 4.2 ml/min/1.73 m2 (61 % improvement). For eGFR between 90-119 ml/min/1.73 m2, bias was reduced from 10.0 to 1.9 ml/min/1.73 m2 (75% improvement). Similar or improved performance was noted for most subgroups with eGFR < 90 ml/min/1.73 m2, other than BMI less than 20 kg/m2, with greater variation noted for some subgroups with eGFR ≥ 90 ml/min/1.73 m2.
Limited number of elderly people and racial and ethnic minorities with measured GFR.
The CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR ≥ 60 ml/min/1.73 m2 can be reported using the CKD-EPI equation.
PMCID: PMC2926290  PMID: 20557989
Estimating equations; glomerular filtration rate; performance
15.  Creatinine-or cystatin C-based equations to estimate glomerular filtration in the general population: impact on the epidemiology of chronic kidney disease 
BMC Nephrology  2013;14:57.
Chronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study. Recently, new equations based either on cystatin C (CKD-EPI Cys) or both cystatin and creatinine (CKD-EPI mix) have been proposed by the CKD-EPI consortium. The aim of this study was to measure the difference in the prevalence of stage 3 CKD, defined as an estimated GFR less than 60 mL/min/1.73 m2, in a population using these four equations.
CKD screening was performed in the Province of Liège, Belgium. On a voluntary basis, people aged over 50 years have been screened. GFR was estimated by the four equations. Stage 3 CKD was defined as a GFR less than 60 mL/min/1.73 m2.
The population screened consisted of 4189 people (47% were men, mean age 63 ± 7y). Their mean serum creatinine and plasma cystatin C levels were 0.88 ± 0.21 mg/dL and 0.85 ± 0.17 mg/L, respectively. The prevalence of CKD in this population using the MDRD, the CKD-EPI, the CKD-EPI Cys and the CKD-EPI mix equations was 13%, 9.8%, 4.7% and 5%, respectively. The prevalence of CKD was significantly higher with the creatinine-based (MDRD and the CKD-EPI) equations compared to the new cystatin C-based equations.
Prevalence of CKD varies strongly depending on the method used to estimate GFR. Such discrepancies are of importance and must be confirmed and explained by additional studies, notably by studies using GFR measured with a reference method.
Trial registration
PMCID: PMC3637126  PMID: 23496839
Creatinine; Cystatin C; Chronic kidney disease; Glomerular filtration rate
16.  A New Modified CKD-EPI Equation for Chinese Patients with Type 2 Diabetes 
PLoS ONE  2014;9(10):e109743.
To improve the performance of glomerular filtration rate (GFR) estimating equation in Chinese type 2 diabetic patients by modification of the CKD-EPI equation.
Design and patients
A total of 1196 subjects were enrolled. Measured GFR was calibrated to the dual plasma sample 99mTc-DTPA-GFR. GFRs estimated by the re-expressed 4-variable MDRD equation, the CKD-EPI equation and the Asian modified CKD-EPI equation were compared in 351 diabetic/non-diabetic pairs. And a new modified CKD-EPI equation was reconstructed in a total of 589 type 2 diabetic patients.
In terms of both precision and accuracy, GFR estimating equations all achieved better results in the non-diabetic cohort comparing with those in the type 2 diabetic cohort (30% accuracy, P≤0.01 for all comparisons). In the validation data set, the new modified equation showed less bias (median difference, 2.3 ml/min/1.73 m2 for the new modified equation vs. ranged from −3.8 to −7.9 ml/min/1.73 m2 for the other 3 equations [P<0.001 for all comparisons]), as was precision (IQR of the difference, 24.5 ml/min/1.73 m2 vs. ranged from 27.3 to 30.7 ml/min/1.73 m2), leading to a greater accuracy (30% accuracy, 71.4% vs. 55.2% for the re-expressed 4 variable MDRD equation and 61.0% for the Asian modified CKD-EPI equation [P = 0.001 and P = 0.02]).
A new modified CKD-EPI equation for type 2 diabetic patients was developed and validated. The new modified equation improves the performance of GFR estimation.
PMCID: PMC4196932  PMID: 25313918
17.  Application of creatinine- and/or cystatin C-based glomerular filtration rate estimation equations in elderly Chinese 
No conventional creatinine- or cystatin C-based glomerular filtration rate (GFR) estimation equation performed consistently outstandingly in elderly Chinese in our previous studies. This research aimed to further evaluate the performance of some recently proposed estimation equations based on creatinine and cystatin C, alone or combined, in this specific population.
Materials and methods
The equations were validated in a population totaling 419 participants (median age 68 [range 60–94] years). The estimated GFR (eGFR) calculated separately by ten equations was compared with the reference GFR (rGFR) measured by the 99mTc-DTPA renal dynamic imaging method.
Median serum creatinine, cystatin C, and rGFR levels were 0.93 mg/L, 1.13 mg/L, and 74.20 mL/min/1.73 m2, respectively. The Chinese population-developed creatinine- and cystatin C-based (Cscr-cys) equation yielded the least median absolute difference (8.81 vs range 9.53–16.32, P<0.05, vs the Chronic Kidney Disease Epidemiology Collaboration serum creatinine equation), the highest proportion of eGFR within 15% and 30% of rGFR (P15 and P30, 55.13 and 85.44, P<0.05 and P<0.01, vs the Chronic Kidney Disease Epidemiology Collaboration serum creatinine equation), and the lowest root mean square error (14.87 vs range 15.30–22.45) in the whole cohort. A substantial agreement of diagnostic consistency between eGFR and rGFR (with a kappa 0.61–0.80) was also observed with the Cscr-cys equation. Moreover, measures of performance in the Cscr-cys equation were consistent across normal to mildly injured GFR strata and individuals aged ≤80 years. Among all the Cscr-cys equations, the elderly Chinese-developed creatinine-based (CEscr) equation performed best in this specific population. Nevertheless, none of the equations achieved ideal manifestation in the moderately to severely GFR-injured group or in individuals aged ≥80 years.
The Cscr-cys equation appeared to be optimal in elderly Chinese among the investigated equations. If cystatin C is not available, the CEscr equation is an acceptable alternative. A multicenter study with abundant subjects to develop an apposite formula for elderly Chinese is assumed to be essential.
PMCID: PMC4166349  PMID: 25246780
elderly Chinese; creatinine; cystatin C; glomerular filtration rate; equation
18.  Cystatin C enhances GFR estimating Equations in Kidney Transplant Recipients 
American journal of nephrology  2014;39(1):59-65.
The glomerular filtration rate (GFR) estimating equation incorporating both cystatin C and creatinine perform better than those using creatinine or cystatin C alone in patients with reduced GFR. Whether this equation performs well in kidney transplant recipients cross-sectionally, and more importantly, over time has not been addressed.
We analyzed four GFR estimating equations in participants of the Angiotensin II Blockade for Chronic Allograft Nephropathy Trial (NCT 00067990): Chronic Kidney Disease Epidemiology Collaboration equations based on serum cystatin C and creatinine (eGFR (CKD-EPI-Creat+CysC)), cystatin C alone (eGFR (CKD-EPI-CysC)), creatinine alone (eGFR (CKD-EPI-Creat)) and the Modification of Diet in Renal Disease study equation (eGFR(MDRD)). Iothalamate GFR served as a standard (mGFR).
mGFR, serum creatinine, and cystatin C shortly after transplant were 56.1 ± 17.0 mL/min/1.73 m2, 1.2 ± 0.4 mg/dL, and 1.2 ± 0.3 mg/L respectively. eGFR (CKD-EPI-Creat+CysC) was most precise (R2=0.50) but slightly more biased than eGFR (MDRD); 9.0 ± 12.7 ml/min/1.73m2 vs. 6.4 ± 15.8 ml/min/1.73m2, respectively. This improved precision was most evident in recipients with mGFR >60 ml/min/1.73m2. For relative accuracy, eGFR (MDRD) and eGFR (CKD-EPI-Creat+CysC) had the highest percentage of estimates falling within 30% of mGFR; 75.8% and 68.9%, respectively. Longitudinally, equations incorporating cystatin C most closely paralleled the change in mGFR.
eGFR (CKD-EPI-Creat+CysC) is more precise and reflects GFR change over time reasonably well. eGFR (MDRD) had superior performance in recipients with mGFR between 30–60 ml/min/1.73m2.
PMCID: PMC4026030  PMID: 24457184
Glomerular filtration rate; Chronic Kidney Disease Epidemiology Collaboration; Modification of Diet in Renal Disease; cystatin C; kidney transplantation
19.  A New Equation to Estimate Glomerular Filtration Rate in Chinese Elderly Population 
PLoS ONE  2013;8(11):e79675.
We sought to develop a new equation to estimate glomerular filtration rate (GFR) in Chinese elderly population.
A total of 668 Chinese elderly participants, including the development cohort (n = 433), the validation cohort (n = 235) were enrolled. The new equation using the generalized additive model, and age, gender, serum creatinine as predictor variables was developed and the performances was compared with the CKD-EPI equation.
In the validation data set, both bias and precision were improved with the new equation, as compared with the CKD-EPI equation (median difference, −1.5 ml/min/1.73 m2 vs. 7.4 ml/min/1.73 m2 for the new equation and the CKD-EPI equation, [P<0.001]; interquartile range [IQR] for the difference, 16.2 ml/min/1.73 m2 vs. 19.0 ml/min/1.73 m2 [P<0.001]), as were accuracies (15% accuracy, 40.4% vs. 30.6% [P = 0.02]; 30% accuracy, 71.1% vs. 47.2%, [P<0.001]; 50% accuracy, 90.2% vs. 75.7%, [P<0.001]), allowing improvement in GFR categorization (GFR category misclassification rate, 37.4% vs. 53.2% [P = <0.001]).
A new equation was developed in Chinese elderly population. In the validation data set, the new equation performed better than the original CKD-EPI equation. The new equation needs further external validations. Calibration of the GFR referent standard to a more accurate one should be an useful way to improve the performance of GFR estimating equations.
PMCID: PMC3823564  PMID: 24244543
20.  Comparison of Estimated Glomerular Filtration Rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equations with and without Cystatin C for Predicting Clinical Outcomes in Elderly Women 
PLoS ONE  2014;9(9):e106734.
Reduced estimated glomerular filtration rate (eGFR) using the cystatin-C derived equations might be a better predictor of cardiovascular disease (CVD) mortality compared with the creatinine-derived equations, but this association remains unclear in elderly individuals.
The aims of this study were to compare the predictive values of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-creatinine, CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C eGFR equations for all-cause mortality and CVD events (hospitalizations±mortality).
Prospective cohort study of 1165 elderly women aged>70 years. Associations between eGFR and outcomes were examined using Cox regression analysis. Test accuracy of eGFR equations for predicting outcomes was examined using Receiver Operating Characteristic (ROC) analysis and net reclassification improvement (NRI).
Risk of all-cause mortality for every incremental reduction in eGFR determined using CKD-EPI-creatinine, CKD-EPI-cystatin C and the CKD-EPI-creatinine-cystatic C equations was similar. Areas under the ROC curves of CKD-EPI-creatinine, CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C equations for all-cause mortality were 0.604 (95%CI 0.561–0.647), 0.606 (95%CI 0.563–0.649; p = 0.963) and 0.606 (95%CI 0.563–0.649; p = 0.894) respectively. For all-cause mortality, there was no improvement in the reclassification of eGFR categories using the CKD-EPI-cystatin C (NRI -4.1%; p = 0.401) and CKD-EPI-creatinine-cystatin C (NRI -1.2%; p = 0.748) compared with CKD-EPI-creatinine equation. Similar findings were observed for CVD events.
eGFR derived from CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C equations did not improve the accuracy or predictive ability for clinical events compared to CKD-EPI-creatinine equation in this cohort of elderly women.
PMCID: PMC4180254  PMID: 25265151
21.  Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study 
BMC Nephrology  2012;13:83.
Sickle cell disease (SCD) leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR) in SCD adult patients.
We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method.
Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]). Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations.
We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular hyperfiltration, and thus should be recommended to screen SCD adult patients at high risk for SCD nephropathy.
PMCID: PMC3465224  PMID: 22866669
Sickle cell disease; Glomerular hyperfiltration; Albuminuria; Glomerular filtration rate; CKD-EPI equation; Iohexol plasma clearance; Ethnicity
22.  Estimating Kidney Function in HIV-Infected Adults in Kenya: Comparison to a Direct Measure of Glomerular Filtration Rate by Iohexol Clearance 
PLoS ONE  2013;8(8):e69601.
More than two-thirds of the world's HIV-positive individuals live in sub-Saharan Africa, where genetic susceptibility to kidney disease is high and resources for kidney disease screening and antiretroviral therapy (ART) toxicity monitoring are limited. Equations to estimate glomerular filtration rate (GFR) from serum creatinine were derived in Western populations and may be less accurate in this population.
We compared results from published GFR estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV-infected, ART-naïve Kenyan adults. Iohexol concentration was measured from dried blood spots on filter paper. The bias ratio (mean of the ratio of estimated to measured GFR) and accuracy (percentage of estimates within 30% of the measured GFR) were calculated.
The median age was 35 years, and 60% were women. The majority had asymptomatic HIV, with median CD4+ cell count of 355 cells/mm3. Median measured GFR was 115 mL/min/1.73 m2. Overall accuracy was highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI) equation. Consistent with a prior report, bias and accuracy were improved by eliminating the coefficient for black race (85% of estimates within 30% of measured GFR). Accuracy of all equations was poor in participants with GFR 60–90 mL/min/1.73 m2 (<65% of estimates within 30% of measured GFR), although this subgroup was too small to reach definitive conclusions.
Overall accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for race further improved performance. Future studies are needed to determine the most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m2, in whom accurate estimation of kidney function is important to guide drug dosing. Direct measurement of GFR by iohexol clearance using a filter paper based assay is feasible for research purposes in resource-limited settings, and could be used to develop more accurate GFR estimates in African populations.
PMCID: PMC3738577  PMID: 23950899
23.  Improved Glomerular Filtration Rate Estimation by an Artificial Neural Network 
PLoS ONE  2013;8(3):e58242.
Accurate evaluation of glomerular filtration rates (GFRs) is of critical importance in clinical practice. A previous study showed that models based on artificial neural networks (ANNs) could achieve a better performance than traditional equations. However, large-sample cross-sectional surveys have not resolved questions about ANN performance.
A total of 1,180 patients that had chronic kidney disease (CKD) were enrolled in the development data set, the internal validation data set and the external validation data set. Additional 222 patients that were admitted to two independent institutions were externally validated. Several ANNs were constructed and finally a Back Propagation network optimized by a genetic algorithm (GABP network) was chosen as a superior model, which included six input variables; i.e., serum creatinine, serum urea nitrogen, age, height, weight and gender, and estimated GFR as the one output variable. Performance was then compared with the Cockcroft-Gault equation, the MDRD equations and the CKD-EPI equation.
In the external validation data set, Bland-Altman analysis demonstrated that the precision of the six-variable GABP network was the highest among all of the estimation models; i.e., 46.7 ml/min/1.73 m2 vs. a range from 71.3 to 101.7 ml/min/1.73 m2, allowing improvement in accuracy (15% accuracy, 49.0%; 30% accuracy, 75.1%; 50% accuracy, 90.5% [P<0.001 for all]) and CKD stage classification (misclassification rate of CKD stage, 32.4% vs. a range from 47.3% to 53.3% [P<0.001 for all]). Furthermore, in the additional external validation data set, precision and accuracy were improved by the six-variable GABP network.
A new ANN model (the six-variable GABP network) for CKD patients was developed that could provide a simple, more accurate and reliable means for the estimation of GFR and stage of CKD than traditional equations. Further validations are needed to assess the ability of the ANN model in diverse populations.
PMCID: PMC3596400  PMID: 23516450
24.  Determining Glomerular Filtration Rate in Homozygous Sickle Cell Disease: Utility of Serum Creatinine Based Estimating Equations 
PLoS ONE  2013;8(7):e69922.
Various estimating equations have been developed to estimate glomerular filtration rate (GFR) for use in clinical practice. However, the unique renal physiological and pathological processes that occur in sickle cell disease (SCD) may invalidate these estimates in this patient population. This study aims to compare GFR estimated using common existing GFR predictive equations to actual measured GFR in persons with homozygous SCD. If the existing equations perform poorly, we propose to develop a new estimating equation for use in persons with SCD.
98 patients with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had serum measurements of creatinine, as well as had GFR measured using 99mTc-DTPA nuclear renal scan. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and the serum creatinine based CKD-EPI equations. The Bland-Altman limit of agreement method was used to determine agreement between measured and estimated GFR values. A SCD-specific estimating equation for GFR (JSCCS-GFR equation) was generated by means of multiple regression via backward elimination.
The mean measured GFR±SD was 94.9±27.4 mls/min/1.73 m2 BSA, with a range of 6.4–159.0 mls/min/1.73 m2. The MDRD and CG equations both overestimated GFR, with the agreement worsening with higher GFR values. The serum creatinine based CKD-EPI equation performed relatively well, but with a systematic bias of about 45 mls/min. The new equation developed resulted in a better fit to our sickle cell disease data than the MDRD equation.
Current estimating equations, other than the CKD-EPI equation, do not perform very accurately in persons with homozygous SS disease. A fairly accurate estimating equation, suitable for persons with GFR >60 mls/min/1.73 m2 has been developed from our dataset and validated within a simulated dataset.
PMCID: PMC3716730  PMID: 23894560
25.  Epidemiology and prognostic significance of chronic kidney disease in the elderly--the Three-City prospective cohort study 
Nephrology Dialysis Transplantation  2011;26(10):3286-3295.
Little is known about normal kidney function level and the prognosis significance of low estimated glomerular filtration rate(eGFR) in the elderly.
We determined age and sex distribution of eGFR with both the Modification of Diet in Renal Disease (MDRD) study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 8705 community-dwelling elderly aged ≥ 65 years and studied its relation to 6-year mortality. In a subsample of 1298 examined at 4 yrs, we assessed annual eGFR decline and clinically relevant markers including microalbuminuria (3–30 mg/mmol creatinine) with diabetes, proteinuria ≥ 50 mg/mmol, haemoglobin<11 g/L, or resistant hypertension despite 3 drugs.
Median (interquartile range) MDRD eGFR was 78 (68–89)mL/min/1.73m2 in men and 74 (65–83)in women; there were 79 (68–87) and 77 (67–85) for CKD-EPI eGFR, respectively. Prevalence of MDRD eGFR< 60mL/min/1.73m2 was13.7%, and of CKD-EPI eGFR, 12.9%. After adjustment for several confounders, only those with an eGFR<45 mL/min/1.73 m2 had significantly higher all-cause and cardiovascular mortality than those with an eGFR of 75 to 89 mL/min/1.73 m2 whatever the equation. In subsample men and women with MDRD eGFR of 45–59 mL/min/1.73m2, 15% and 13% had at least one clinical marker, and 15% and 3% had microalbuminuria without diabetes, respectively; these percentages were 41% and 21%, and 23% and 10%, in men and women with eGFR<45, respectively. Mean MDRD eGFR decline rate was steeper in men than women, 1.75 vs 1.41 mL/min/1.73m2 per year.
Moderately decreased eGFR is more often associated with clinical markers in men than women. In both sexes, eGFR< 45 mL/min/1.73m2 is related to poor outcomes. The CKD-EPI and the MDRD equations provide very similar prevalence and long-term risk estimates in this elderly population.
PMCID: PMC3925095  PMID: 21677301
Aged; Cardiovascular Diseases; epidemiology; etiology; mortality; Creatinine; blood; urine; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; complications; epidemiology; mortality; Male; Prevalence; Prognosis; Prospective Studies; Proteinuria; diagnosis; etiology; mortality; Risk Factors; Survival Rate; chronic kidney disease; elderly; glomerular filtration rate; mortality; proteinuriaanaemia

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