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1.  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
2.  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
3.  Comparisons between validated estimated glomerular filtration rate (GFR) equations and isotopic GFR in HIV patients 
AIDS (London, England)  2012;26(14):1781-1788.
Understanding how best to measure renal function in HIV-infected patients is critical because estimated glomerular filtration rate (eGFR) in HIV-infected patients can be affected by ethnicity and body composition. We validated the available eGFR equations and compared them to the plasma 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance in HIV-infected patients.
Test of diagnostic accuracy.
196 HIV-infected patients underwent measuring 99mTc-DTPA plasma clearance, 5 creatinine-based eGFR equations, cystatin-C GFR and 24-hour urine creatinine clearance (CrCl).
Mean (SD) 99mTc-DTPA GFR was 117.7±29.2 mL/min per 1.73 m2. The re-expressed MDRD, CKD-EPI, re-expressed MDRD formula with Thai racial correction factor, Thai eGFR equation, Cockcroft & Gault, cystatin-C GFR, and 24 hr urine CrCl, underestimated the reference GFR. The bias estimated by the mean of differences the limits of agreement for the re-expressed MDRD equation, CKD-EPI, re-expressed MDRD formula with Thai racial correction factor, Thai eGFR, Cockcroft & Gault, cystatin C, and 24 hr urine CrCl can be expressed as 18.9±27.3, 11.1±25.5, 6.2±28.8, 13.5±27.0, 30.4±28.0, 3.2±36.1, and 5.0±12.1 mL/min per 1.73 m2 respectively.
The available eGFR equations underestimated GFR in HIV-infected adults. However, the eGFR by cystacin C GFR was the most precise and accurate. Among Cr-based eGFR equations, re-expressed MDRD formula with Thai racial correction factor was the most precise and accurate. The racial factor for each ethnicity is important and the existing eGFR equation should be validated before using it in the HIV population.
PMCID: PMC3782632  PMID: 22713478
99mTc-DTPA GFR; eGFR equation; glomerular filtration rate; HIV-infected patients; race
4.  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
5.  Comparison of renal function markers in Kuwaiti patients with sickle cell disease 
Journal of Clinical Pathology  2006;59(4):345-351.
Proteinuria is a common manifestation of renal disease which is a significant cause of morbidity in patients with sickle cell disease (SCD).
To evaluate and compare cystatin C, β2‐microglobulin, and creatinine as markers of renal disease in relation to the degree of proteinuria and other complications of SCD.
24 h urine collections were used for estimation of urine protein and creatinine clearance in 59 patients with SCD. Results were correlated with plasma cystatin C, β2‐microglobulin, creatinine, glomerular filtration rate (GFR; derived from plasma creatinine by Cockcroft‐Gault, MDRD formulae, and calculated cystatin C clearance), and clinical and haematological variables.
Comparing the different methods of GFR, the proportion of patients with hyperfiltration (GFR >140 ml/min) were 30.5% (MDRD), 44.1% (Cockcroft‐Gault), and 10.2 % (calculated cystatin C clearance). Cystatin C was the most consistent marker of hyperfiltration. The endogenous markers of GFR showed an increasing trend with increasing proteinuria, but haematological variables were not correlated with cystatin C, β2‐microglobulin, or plasma creatinine. Urine protein excretion was correlated with age (r = 0.33) and significant proteinuria was present in 13.6% of patients. Patients with proteinuria had lower haemoglobin concentration (p = 0.027) than those without proteinuria but HbF was not related to the degree of proteinuria or to markers of GFR.
Markers of GFR show variable ability to identify hyperfiltration in patients with SCD, but cystatin C is the best endogenous marker. Proteinuria is associated with age, haemoglobin, and abnormalities of GFR. Routine screening is recommended to allow for early detection and intervention.
PMCID: PMC1860381  PMID: 16567469
cystatin C; β2‐microglobulin; glomerular filtration rate; sickle cell disease
6.  Race Adjustment for Estimating Glomerular Filtration Rate Is Not Always Necessary 
Nephron Extra  2012;2(1):293-302.
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.
PMCID: PMC3521477  PMID: 23243414
Biomarkers; Creatinine clearance; Glomerular filtration rate; Glomerulonephritis
7.  Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury - true GFR versus urinary creatinine clearance and estimating equations 
Critical Care  2013;17(3):R108.
Estimation of kidney function in critically ill patients with acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but challenging due to fluctuations in kidney function, creatinine metabolism and fluid balance. Data on the agreement between estimating and gold standard methods to assess glomerular filtration rate (GFR) in early AKI are lacking. We evaluated the agreement of urinary creatinine clearance (CrCl) and three commonly used estimating equations, the Cockcroft Gault (CG), the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in comparison to GFR measured by the infusion clearance of chromium-ethylenediaminetetraacetic acid (51Cr-EDTA), in critically ill patients with early AKI after complicated cardiac surgery.
Thirty patients with early AKI were studied in the intensive care unit, 2 to 12 days after complicated cardiac surgery. The infusion clearance for 51Cr-EDTA obtained as a measure of GFR (GFR51Cr-EDTA) was calculated from the formula: GFR (mL/min/1.73m2) = (51Cr-EDTA infusion rate × 1.73)/(arterial 51Cr-EDTA × body surface area) and compared with the urinary CrCl and the estimated GFR (eGFR) from the three estimating equations. Urine was collected in two 30-minute periods to measure urine flow and urine creatinine. Urinary CrCl was calculated from the formula: CrCl (mL/min/1.73m2) = (urine volume × urine creatinine × 1.73)/(serum creatinine × 30 min × body surface area).
The within-group error was lower for GFR51Cr-EDTA than the urinary CrCl method, 7.2% versus 55.0%. The between-method bias was 2.6, 11.6, 11.1 and 7.39 ml/min for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA. The error was 103%, 68.7%, 67.7% and 68.0% for eGFRCrCl, eGFRMDRD, eGFRCKD-EPI and eGFRCG, respectively, when compared to GFR51Cr-EDTA.
The study demonstrated poor precision of the commonly utilized urinary CrCl method for assessment of GFR in critically ill patients with early AKI, suggesting that this should not be used as a reference method when validating new methods for assessing kidney function in this patient population. The commonly used estimating equations perform poorly when estimating GFR, with high biases and unacceptably high errors.
PMCID: PMC4056314  PMID: 23767877
8.  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
9.  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
10.  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
11.  GFR-estimating models in kidney transplant recipients on a steroid-free regimen 
Nephrology Dialysis Transplantation  2010;25(5):1653-1661.
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.
PMCID: PMC2910331  PMID: 20118486
glomerular filtration rate; kidney transplant; steroid free
12.  Serum creatinine in patients with advanced liver disease is of limited value for identification of moderate renal dysfunction: Are the equations for estimating renal function better? 
The Cockcroft-Gault formula (CGF) is used to estimate the glomerular filtration rate (GFR) based on serum creatinine (Cr) levels, age and sex. A new formula developed by the Modification of Diet in Renal Disease (MDRD) Study Group, based on the patient’s Cr levels, age, sex, race and serum urea nitrogen and serum albumin levels, has shown to be more accurate. However, the best formula to identify patients with advanced liver disease (ALD) and moderate renal dysfunction (GFR 60 mL/min/1.73 m2 or less) is not known. The aim of the present study was to compare calculations of GFR, using published formulas (excluding those requiring urine collections) with standard radionuclide measurement of GFR in patients with ALD.
Fifty-seven consecutive subjects (40% women) with a mean age of 50 years (range 16 to 67 years) underwent 99m-technetium-diethylenetriamine pentaacetic acid (99mTc-DTPA) (single injection) radionuclide measurement of GFR. To calculate GFR, three formulas were used: the reciprocal of Cr multiplied by 100 (100/Cr), the CGF and the MDRD formulas. Pearson’s correlation coefficient (r) and Bland-Altman analyses of agreement were used to analyze the association between 99mTc-DTPA clearance and the three equations for GFR.
The mean 99mTc-DTPA clearance was 83 mL/min/1.73 m2 (range 28 mL/min/1.73 m2 to 173 mL/min/1.73 m2). Mean calculated GFRs by 100/Cr, the CGF and the MDRD formula were 106 mL/min/1.73 m2, 98 mL/min/1.73 m2 and 86 mL/min/1.73 m2, respectively. Regression analysis showed good correlation between radionuclide GFR and calculated GFR with r(100/Cr)=0.74, r(CGF)=0.80, r(MDRD)=0.87, all at P≤0.0001. The MDRD formula provided the least bias. The Bland-Altman plot showed best agreement between GFR calculated by the MDRD formula and 99mTc-DTPA clearance, with only 3 mL/min/1.73 m2 overestimation. There was higher variability between radionuclide GFR and calculated GFR by the CGF and by 100/Cr. Although there was no difference in precision, GFR calculated by the MDRD formula had the best overall accuracy. The sensitivity and specificity for detection of moderate renal dysfunction by the MDRD formulas were 73% and 87%, respectively.
Among the Cr-based GFR formulas, the MDRD formula showed a larger proportion of agreement with radionuclide GFR in patients with ALD. In clinical practice, the MDRD is the best formula for detection of moderate renal dysfunction among those with ALD.
PMCID: PMC2659934  PMID: 16955148
Cirrhosis; Cockcroft-Gault formula; Creatinine; Glomerular filtration rate; Liver disease
13.  Chronic kidney diseases in mixed ancestry south African populations: prevalence, determinants and concordance between kidney function estimators 
BMC Nephrology  2013;14:75.
Population-based data on the burden of chronic kidney disease (CKD) in sub-Saharan Africa is still very limited. We assessed the prevalence and determinants of CKD, and evaluated the concordance of commonly advocated estimators of glomerular filtration rate (eGFR) in a mixed ancestry population from South Africa.
Participants were a population-based sample of adults selected from the Bellville-South community in the metropolitan city of Cape Town. eGFR was based on the Cockroft-Gault (CG), Modification of Diet in Kidney Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) equations (with and without adjustment for ethnicity). Kidney function staging used the Kidney Disease Outcome Quality Initiative (KDOQI) classification. Logistic regressions and kappa statistic were used to investigate determinants of CKD and assess the agreement between different estimators.
The crude prevalence of CKD stage 3–5 was 14.8% for Cockcroft-Gault, 7.6% and 23.9% respectively for the MDRD with and without ethnicity correction, and 7.4% and 17.3% for the CKD-EPI equations with and without ethnicity correction. The highest agreement between GFR estimators was between MDRD and CKD-EPI equations, both with ethnicity correction, Kappa 0.91 (95% CI: 0.86-0.95), correlation coefficient 0.95 (95% CI: 0.94-0.96). In multivariable logistic regression models, sex, age and known hypertension were consistently associated with CKD stage 3–5 across the 5 estimators.
The prevalence of CKD stages greater than 3 is the highest reported in Africa. This study provides evidence for support of the CKD-EPI equation for eGFR reporting and CKD classification.
PMCID: PMC3637389  PMID: 23547953
CKD-EPI eGFR; Cockroft-Gault eGFR; MDRD eGFR; Prevalence; South Africa
14.  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
15.  The prevalence of hypertension and abnormal kidney function in children with sickle cell disease –a cross sectional review 
BMC Nephrology  2013;14:237.
Renal disease is a known contributor to mortality in adults with sickle cell disease (SCD) and renal abnormalities are evident in childhood. Hyperfiltration (evidenced by elevated glomerular filtration rate, GFR) occurs in children with SCD early in disease. However, the incidence of low GFR (<90 ml/min/1.73 m2) suggestive of chronic kidney disease (CKD), is not well established. The prevalence of hypertension is also not well known. The goal of this study was to determine the prevalence of hypertension and CKD in a cohort of children with SCD.
We performed a retrospective chart review of patients followed at the Rainbow Babies and Children’s Sickle Cell Disease Clinic who were seen during routine follow up visits. Inclusion criteria were all patients ages 3–18. Exclusion criteria included recent (within 2 weeks) hospitalization and/or episode of acute chest, pain crises, febrile illness or red blood cell transfusion. Data collected included serum creatinine, blood pressure and history of sickle cell complications (acute chest syndrome, stroke or stroke risk). Estimated GFR (eGFR) was calculated using the updated Schwartz creatinine-based estimating formula. Analysis examined the associations among eGFR, blood pressure and sickle cell complications. The Institutional Review Board at University Hospitals Case Medical Center approved this study.
A total of 48 children had complete data available. Mean eGFR was 140 mL/min/1.73 m2 +/- 34.9 (range 71.9-404.2 mL/min/1.73 m2). Four patients (8.3%) had eGFRs < 90 mL/min/1.73 m2, 35 patients (72.9%) had eGFRs > 120 mL/min/1.73 m2 and 9 patients (18.8%) had eGFRs in the normal range. Eight patients (16.7%) had evidence of elevated blood pressures (pre-hypertension or hypertension). There was no correlation between eGFR and age, and no association of eGFR with acute chest or stroke risk.
In this SCD cohort, we identified abnormally low eGFR (suggestive of early CKD) in 8.3% of patients and elevated blood pressure in 16.7%. These findings are in contrast to other published studies that show primarily normal or elevated GFR and the absence of or minimal hypertension. These findings indicate that elevated blood pressure and decreased eGFR are not uncommon in children with SCD, and should be more rigorously studied.
PMCID: PMC4231610  PMID: 24168027
Sickle cell disease; Nephropathy; Chronic kidney disease; Hypertension
16.  Overestimation of carboplatin doses is avoided by radionuclide GFR measurement 
British Journal of Cancer  2012;107(8):1310-1316.
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.
PMCID: PMC3494427  PMID: 22935580
carboplatin; glomerular filtration rate; EDTA
17.  Use of glomerular filtration rate estimating equations for drug dosing in HIV-positive patients 
Antiviral therapy  2013;18(6):793-802.
Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population.
We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the Food and Drug Administration (FDA) Guidance for Industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations.
For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared to recommended dosages based on the level of estimated kidney function, 3% to 19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation.
The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function.
PMCID: PMC4018994  PMID: 23963249
18.  Is an estimated glomerular filtration rate better than creatinine to be incorporated into the end-stage liver disease score? 
World Journal of Hepatology  2012;4(11):291-298.
AIM: To incorporate estimated glomerular filtration rate (eGFR) into the model for end-stage liver disease (MELD) score to evaluate the predictive value.
METHODS: From January 2004 to October 2008, the records of 4127 admitted cirrhotic patients were reviewed. Patients who survived and were followed up as outpatients were defined as survivors and their most recent available laboratory data were collected. Patients whose records indicated death at any time during the hospital stay were defined as non-survivors (in-hospital mortality). Patients with incomplete data or with cirrhosis due to a congenital abnormality such as primary biliary cirrhosis were excluded; thus, a total of 3857 patients were enrolled in the present study. The eGFR, which was calculated by using either the modification of diet in renal disease (MDRD) equation or the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, was incorporated into the MELD score after adjustment with the original MELD equation by logistic regression analysis [bilirubin and international normalized ratio (INR) were set at 1.0 for values less than 1.0].
RESULTS: Patients defined as survivors were significantly younger, had a lower incidence of hepatoma, lower Child-Pugh and MELD scores, and better renal function. The underlying causes of cirrhosis were very different from those in Western countries. In Taiwan, most cirrhotic patients were associated with the hepatitis virus, especially hepatitis B. There were 16 parameters included in univariate logistic regression analysis to predict in-hospital mortality and those with significant predicting values were included in further multivariate analysis. Both 4-variable MDRD eGFR and 6-variable MDRD eGFR, rather than creatinine, were significant predictors of in-hospital mortality. Three new equations were constructed (MELD-MDRD-4, MELD-MDRD-6, MELD-CKD-EPI). As expected, original MELD score was a significant predictor of in-hospital mortality (odds ratio = 1.25, P < 0.001). MELD-MDRD-4 excluded serum creatinine, with the coefficients refit among the remaining 3 variables, i.e., total bilirubin, INR and 4-variable MDRD eGFR. This model represented an exacerbated outcome over MELD score, as suggested by a decrease in chi-square (2161.45 vs 2198.32) and an increase in -2 log (likelihood) (2810.77 vs 2773.90). MELD-MDRD-6 included 6-variable MDRD eGFR as one of the variables and showed an improvement over MELD score, as suggested by an increase in chi-square (2293.82 vs 2198.32) and a decrease in -2 log (likelihood) (2810.77 vs 2664.79). Finally, when serum creatinine was replaced by CKD-EPI eGFR, it showed a slight improvement compared to the original MELD score (chi-square: 2199.16, -2 log (likelihood): 2773.07). In the receiver-operating characteristic curve, the MELD-MDRD-6 score showed a marginal improvement in area under the curve (0.909 vs 0.902), sensitivity (0.854 vs 0.819) and specificity (0.818 vs 0.839) compared to the original MELD equation. In patients with a different eGFR, the MELD-MDRD-6 equation showed a better predictive value in patients with eGFR ≥ 90, 60-89, 30-59 and 15-29.
CONCLUSION: Incorporating eGFR obtained by the 6-variable MDRD equation into the MELD score showed an equal predictive performance in in-hospital mortality compared to a creatinine-based MELD score.
PMCID: PMC3536835  PMID: 23293714
Liver cirrhosis; Estimated glomerular filtration rate; End-stage liver disease; Modification of diet in renal disease; Renal function
19.  Imprecision of Urinary Iothalamate Clearance as a Gold Standard Measure of GFR Decreases the Diagnostic Accuracy of Kidney Function Estimating Equations 
Evaluating the accuracy of estimated glomerular filtration rate (eGFR) derived from serum creatinine (SCr) and serum cystatin C (SCysC) equations requires gold standard measures of GFR. However, the influence of imprecise measured GFRs (mGFRs) on estimates of equation error is unknown.
Study Design
Diagnostic test study
Setting & Participants
1995 participants from the Modification of Diet in Renal Disease (MDRD) Study and African American Study of Kidney Disease (AASK) with at least two baseline mGFRs from125I-iothalamate urinary clearances, one standardized Scr value, and one SCysC value.
Index Tests
eGFRs calculated from the 4-variable IDMS-traceable MDRD Study equation, the CKD-EPI SCysC equation, the CKD-EPI SCr-SCysC equation, and mGFRs collected from another pre-randomization visit
Reference Tests
A single reference mGFR, average of two, and average of three mGFRs; additional analysis limited to consistent mGFRs (difference fl 25% from the reference mGFR)
We found that mGFRs had stable means but substantial variability across visits. Of all the mGFRs collected a mean of 62 days apart from the reference visit, 8.0% fell outside 30% of the single reference mGFR (1-P30). The estimation equations were less accurate as 12.1%, 17.1% and 8.3% of the eGFR from MDRD Study, CKD-EPI SCysC, and CKD-EPI SCr-SCysC equations fell outside 30% of the same gold standard (1-P30). However, improving the precision of the reference test from a single mGFR to the average of three consistent mGFRs reduced these error estimates (1-P30) to 8.0%, 12.5% and 3.9% respectively.
Study population limited to those with CKD.
Imprecision in gold standard measures of GFR contribute to an appreciable proportion of the cases where estimated and measured GFR differs by more than 30%. Reducing and quantifying errors in gold standard measurements of GFR is critical to fully estimating the accuracy of GFR estimates.
PMCID: PMC3671926  PMID: 20537455
gold standard; measured glomerular filtration rate; kidney function estimation equations; cystatin C; creatinine
20.  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
21.  Comparison between Three Different Equations for the Estimation of Glomerular Filtration Rate in Omani Patients with Type 2 Diabetes Mellitus 
Estimated glomerular filtration rate (eGFR) is an important component of a patient’s renal function profile. The Modification of Diet in Renal Disease (MDRD) equation and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation are both commonly used. The aim of this study was to compare the performance of the original MDRD186, revised MDRD175 and CKD-EPI equations in calculating eGFR in type 2 diabetes mellitus (T2DM) patients in Oman.
The study included 607 T2DM patients (275 males and 332 females, mean age ± standard deviation 56 ± 12 years) who visited primary health centres in Muscat, Oman, during 2011 and whose renal function was assessed based on serum creatinine measurements. The eGFR was calculated using the three equations and the patients were classified based on chronic kidney disease (CKD) stages according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines. A performance comparison was undertaken using the weighted kappa test.
The median eGFR (mL/min/1.73 m2) was 92.9 for MDRD186, 87.4 for MDRD175 and 93.7 for CKD-EPI. The prevalence of CKD stage 1 was 55.4%, 44.7% and 57% while for stages 2 and 3 it was 43.2%, 54% and 41.8%, based on MDRD186, MDRD175 and CKD-EPI, respectively. The agreement between MDRD186 and CKD-EPI (к 0.868) was stronger than MDRD186 and MDRD175 (к 0.753) and MDRD175 and CKD-EPI (к 0.730).
The performances of MDRD186 and CKD-EPI were comparable. Considering that CKD-EPI-based eGFR is known to be close to isotopically measured GFR, the use of MDRD186 rather than MDRD175 may be recommended.
PMCID: PMC3997536  PMID: 24790742
Diet Modification; Chronic Renal Insufficiency; Epidemiology; Collaboration; Glomerular Filtration Rates; Type 2 Diabetes Mellitus; Oman
22.  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
23.  Appraisal of GFR Estimating Equations Following Kidney Donation 
It is not clear which serum creatinine-based glomerular filtration rate (GFR) estimating model performs best in kidney donors.
Study Design
Study of diagnostic accuracy.
Setting and Participants
From a population of 3,698 kidney donors, 255 donors underwent iohexol GFR measurement (mGFR).
Index Test (Intervention)
mGFR by the plasma disappearance of iohexol.
Reference Test or Outcome
eGFR was estimated using the Cockcroft-Gault equation, (eGFRCG), the Mayo Clinic equation (eGFRMC), and the MDRD Study equation (eGFRMDRD).
Mean mGFR was 71.8±11.8 mL/min/1.73m2 and 85.5% had mGFR > 60 mL/min/1.73m2. eGFRCG underestimated mGFR by 3.96±13.3 mL/min/1.73m2 and was within 30% of mGFR in 89.4% of the time. eGFRMC overestimated mGFR by 8.44±11.9 mL/min/1.73m2 and was within 30% of mGFR in 83.1% of cases. eGFRMDRD underestimated mGFR by only 0.43±11.7 mL/min/1.73m2 and the proportion within 30% of mGFR was the highest amongst the tested model; 94.1% of the time. The eGFRMC, however, was most accurate in classifying donors according to having eGFR < 60 mL/min/1.73m2.
Lack of ethnic diversity and response bias.
The MDRD Study equation is least biased and since it is routinely reported by most laboratories, is the best readily available model for estimating GFR in kidney donors.
PMCID: PMC2693296  PMID: 19394733
Glomerular filtration rate; kidney donor; Cockcroft-Gault; Modification of Diet in Renal Disease
24.  Chronic kidney disease: a large-scale population-based study of the effects of introducing the CKD-EPI formula for eGFR reporting 
BMJ Open  2011;1(2):e000308.
To evaluate the effects of introducing the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula for estimated glomerular filtration rate (eGFR) reporting in the adult population in routine clinical practice with clinician-directed testing.
Retrospective study of all creatinine measurements and calculation of eGFRs using Modification of Diet in Renal Disease (MDRD) and CKD-EPI formulae.
General population, Oxfordshire, UK.
An unselected population of around 660 000.
Reporting of eGFRs using MDRD or CKD-EPI formulae.
Primary and secondary outcome measures
Evaluation of the effects of the CKD-EPI formula on the prevalence of different stages of chronic kidney disease (CKD).
The CKD-EPI formula reduced the prevalence of CKD (stages 2–5) by 16.4% in patients tested in primary care. At the important stage 2–stage 3 cut-off, there was a relative reduction of 7.5% in the prevalence of CKD stages 3–5 from 15.7% to 14.5%. The CKD-EPI formula reduced the prevalence of CKD stages 3–5 in those aged <70 but increased it at ages >70. Above 70 years, the prevalence of stages 3–5 was similar with both equations for women (around 41.2%) but rose in men from 33.3% to 35.5%. CKD stages 4–5 rose by 15% due exclusively to increases in the over 70s, which could increase specialist referral rates. The CKD classification of 18.3% of all individuals who had a creatinine measurement was altered by a change from the MDRD to the CKD-EPI formula. In the UK population, the classification of up to 3 million patients could be altered, the prevalence of CKD could be reduced by up to 1.9 million and the prevalence of CKD stages 3–5 could fall by around 200 000.
Introduction of the CKD-EPI formula for eGFR reporting will reduce the prevalence of CKD in a primary care setting with current testing practice but will raise the prevalence in the over 70s age group. This has implications for clinical practice, healthcare policy and current prevalence-based funding arrangements.
Article summary
Article focus
Estimated glomerular filtration rates form the basis for clinical and health policy decisions in chronic kidney disease.
The new CKD-EPI formula for estimated glomerular filtration rates estimates renal function better than the Modification of Diet in Renal Disease formula in current use.
We have studied the effects of using the CKD-EPI formula in a UK population of over half a million.
Key messages
Overall, the CKD-EPI formula produces higher better estimated glomerular filtration rates, which reduces the diagnosis of chronic kidney disease. However, in men older than 70 years, it produces lower worse estimated glomerular filtration rates and increases the number with chronic kidney disease stages 3–5.
Our results predict a net reduction of around 200 000 in the numbers with chronic kidney disease stages 3–5 in the UK. This would reduce the primary care chronic kidney disease registers, inappropriate disease labelling and patient monitoring.
The chronic kidney disease classification of up to 3 million patients could be altered by the use of the CKD-EPI formula in the UK.
Strengths and limitations of this study
The study is large and unbiased. All primary care samples taken during the study period were analysed, so the results represent current clinical testing practice.
Estimated glomerular filtration rates are sufficient to diagnose chronic kidney disease stages 3–5, but stages 1–2 also require proteinuria or a structural abnormality, which cannot be assessed in this study. However, a change in estimated glomerular filtration rate can still alter the classification of stage 1 or 2.
PMCID: PMC3244664  PMID: 22184586
25.  Modification of Diet in Renal Disease (MDRD) Study and CKD Epidemiology Collaboration (CKD-EPI) Equations for Taiwanese Adults 
PLoS ONE  2014;9(6):e99645.
Estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) study or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations may not be accurate for Asians; thus, we developed modified eGFR equations for Taiwanese adults.
This cross-sectional study compared the Taiwanese eGFR equations, the MDRD study, and the CKD-EPI equations with inulin clearance (Cin). A total of 695 adults including 259 healthy volunteers and 436 CKD patients were recruited. Participants from the Kaohsiung Medical University Hospital were used as the development set (N = 556) to develop the Taiwanese eGFR equations, whereas participants from the National Taiwan University Hospital were used as the validation set (N = 139) for external validation.
The Taiwanese eGFR equations were developed by using the extended Bland-Altman plot in the development set. The Taiwanese MDRD equation was 1.309×MDRD0.912, Taiwanese CKD-EPI was 1.262×CKD-EPI0.914 and Taiwanese four-level CKD-EPI was 1.205×four-level CKD-EPI0.914. In the validation set, the Taiwanese equations had the lowest bias, the Taiwanese equations and the Japanese CKD-EPI equation had the lowest RMSE, whereas the Taiwanese and the Japanese equations had the best precision and the highest P30 among all equations. However, the Taiwanese MDRD equation had higher concordance correlation than did the Taiwanese CKD-EPI, the Taiwanese four-level CKD-EPI and the Japanese equations. Moreover, only the Taiwanese equations had no proportional bias among all of the equations. Finally, the Taiwanese MDRD equation had the best diagnostic performance in terms of ordinal logistic regression among all of the equations.
The Taiwanese MDRD equation is better than the MDRD, CKD-EPI, Japanese, Asian, Thai, Taiwanese CKD-EPI, and Taiwanese four-level CKD-EPI equations for Taiwanese adults.
PMCID: PMC4057229  PMID: 24927124

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