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1.  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
2.  Performance of the Chronic Kidney Disease Epidemiology Collaboration Equation to Estimate Glomerular Filtration Rate in Diabetic Patients 
Diabetes Care  2011;34(6):1320-1322.
The best method to estimate glomerular filtration rate (GFR) in diabetic patients is still largely debated. We compared the performance of creatinine-based formulas in a European diabetic population.
We compared the performance of Cockcroft and Gault, simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equations in 246 diabetic patients by calculating the mean bias and the interquartile range (IQR) of the bias, 10% (P10) and 30% (P30) accuracies, and Bland-Altman plots. GFR was measured by inulin clearance.
For the whole population, the IQR was slightly lower for CKD-EPI, but the mean bias was lower and P10 and P30 were higher for MDRD. Similar results were observed in specific subgroups, including patients with mild renal insufficiency, obese patients, or type 2 diabetic patients.
In our population, the CKD-EPI formula does not exhibit better performance than the simplified MDRD formula for estimating GFR.
PMCID: PMC3114318  PMID: 21540431
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  Simple Cystatin C Formula for Estimation of Glomerular Filtration Rate in Overweight Patients with Diabetes Mellitus Type 2 and Chronic Kidney Disease 
Experimental Diabetes Research  2012;2012:179849.
In clinical practice the glomerular filtration rate (GFR) is estimated from serum creatinine-based equations like the Cockcroft-Gault formula (C&G) and Modification of Diet in Renal Disease formula (MDRD). Recently, serum cystatin C-based equations, the newer creatinine formula (The Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)), and equation that use both serum creatinine and cystatin C (CKD-EPI creatinine & cystatin formula) were proposed as new GFR markers. Present study compares serum creatinine-based equations, combined (including both serum creatinine and cystatin C) equation, and serum simple cystatin C formula (100/serum cystatin C) against 51CrEDTA clearance in 113 adult overweight Caucasians with diabetes mellitus type 2 (DM2) and chronic kidney disease (CKD). The results of present study demonstrated that the simple cystatin C formula could be a useful tool for the evaluation of renal function in overweight patients with DM2 and impaired kidney function in daily clinical practice in hospital and especially in outpatients. Despite the advantages of the simple cystatin C formula, cystatin C-based equations cannot completely replace the “gold standard” for estimation of the GFR in a population of DM2 patients with CKD, but may contribute to a more accurate selection of patients requiring such invasive and costly procedures.
PMCID: PMC3447360  PMID: 23008697
12.  Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation Pronouncedly Underestimates Glomerular Filtration Rate in Type 2 Diabetes 
Diabetes Care  2011;34(11):2353-2355.
To evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) in type 2 diabetic patients with GFR >60 mL/min/1.73 m2.
This was a cross-sectional study including 105 type 2 diabetic patients. GFR was measured by 51Cr-EDTA method and estimated by the MDRD and CKD-EPI equations. Serum creatinine was measured by the traceable Jaffe method. Bland-Altman plots were used. Bias, accuracy (P30), and precision were evaluated.
The mean age of patients was 57 ± 8 years; 53 (50%) were men and 90 (86%) were white. Forty-six (44%) patients had microalbuminuria, and 14 (13%) had macroalbuminuria. 51Cr-EDTA GFR was 103 ± 23, CKD-EPI GFR was 83 ± 15, and MDRD-GFR was 78 ± 17 mL/min/1.73 m2 (P < 0.001). Accuracy (95% CI) was 67% (58–74) for CKD-EPI and 64% (56–75) for MDRD. Precision was 21 and 22, respectively.
The CKD-EPI and MDRD equations pronouncedly underestimated GFR in type 2 diabetic patients.
PMCID: PMC3198274  PMID: 21926286
13.  Performance of Creatinine and Cystatin C GFR Estimating Equations in an HIV-positive population on Antiretrovirals 
To evaluate the performance of CKD-EPI creatinine, cystatin C and creatinine-cystatin C estimating equations in HIV-positive patients.
We evaluated the performance of the MDRD Study and CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012 and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate (GFR) estimating equations compared to GFR measured using plasma clearance of iohexol in 200 HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were standardized to certified reference materials.
Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an undetectable HIV-viral load. Mean (SD) measured GFR (mGFR) was 87 (26) ml/min/1.73m2. All CKD-EPI equations performed better than the MDRD Study equation. All three CKD-EPI equations had similar bias and precision. The cystatin C equation was not more accurate than the creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the cystatin C equation and there was a trend toward greater accuracy than the creatinine equation. Accuracy was equal or better in most subgroups with the combined equation compared to either alone.
The CKD-EPI cystatin C equation does not appear to be more accurate than the CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-EPI creatinine equation for routine clinical care for use in North American populations with HIV. The use of both filtration markers together as a confirmatory test for decreased estimated GFR based on creatinine in individuals who are HIV-positive requires further study.
PMCID: PMC3598619  PMID: 22842844
measured glomerular filtration rate; estimated glomerular filtration rate; Chronic Kidney Disease Epidemiology collaboration equation (CKD-EPI); Modification of Diet in Renal Disease Study equation (MDRD); creatinine; cystatin C
14.  Difference between CKD-EPI and MDRD equations in calculating glomerular filtration rate in patients with cirrhosis 
AIM: To evaluate the difference between the performance of the (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations in cirrhotic patients.
METHODS: From Jan 2004 to Oct 2008, 4127 cirrhotic patients were reviewed. Patients with incomplete data with respect to renal function were excluded; thus, a total of 3791 patients were included in the study. The glomerular filtration rate (GFR) was estimated by the 4-variable MDRD (MDRD-4), 6-variable MDRD (MDRD-6), and CKD-EPI equations.
RESULTS: When serum creatinine was 0.7-6.8 mg/dL and 0.6-5.3 mg/dL in men and women, respectively, a significantly lower GFR was estimated by the MDRD-6 than by the CKD-EPI. Similar GFRs were calculated by both equations when creatinine was > 6.9 mg/dL and > 5.4 mg/dL in men and women, respectively. In predicting in-hospital mortality, estimated GFR obtained by the MDRD-6 showed better accuracy [81.72%; 95% confidence interval (CI), 0.94-0.95] than that obtained by the MDRD-4 (80.22%; 95%CI, 0.96-0.97), CKD-EPI (79.93%; 95%CI, 0.96-0.96), and creatinine (77.50%; 95%CI, 2.27-2.63).
CONCLUSION: GFR calculated by the 6-variable MDRD equation may be closer to the true GFR than that calculated by the CKD-EPI equation.
PMCID: PMC3218145  PMID: 22110285
Chronic Kidney Disease Epidemiology Collaboration; Estimated glomerular filtration rate; Liver cirrhosis; Modification of Diet in Renal Disease; Renal function
15.  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
16.  Assessment of Glomerular Filtration Rates by Cockcroft-Gault and Modification of Diet in Renal Disease Equations in a Cohort of Omani Patients 
Glomerular filtration rate (GFR) is the best index of renal function and is frequently assessed by corrected creatinine clearance (CCLcr). The limitations of CCLcr have inspired researchers to derive easy formulas to estimate GFR, with Cockcroft-Gault (C-G) and the modification of diet in renal disease (MDRD) being the most widely used. This study aimed to evaluate the validity of these equations by finding the relation between CCLcr and estimated GFR (eGFR) by C-G, modified C-G and MDRD equations.
From 2007 to 2011, 158 subjects were analysed for serum creatinine and CCLcr at Bowsher Polyclinic, Muscat, Oman. The C-G equation was used to obtain eGFRC-G which was adjusted to body surface area (BSA) to obtain eGFRmC-G, and the MDRD equation was used to obtain eGFRMDRD. The eGFRMDRD, eGFRmC-G and eGFRC-G were then compared to CCLcr.
The eGFRMDRD, eGFRmC-G and eGFRC-G significantly correlated with CCLcr, with a slightly stronger correlation with eGFRMDRD (r = 0.701, 0.658 and 0.605, respectively). A receiver operating characteristic curve analysis showed that the diagnostic accuracy of eGFRMDRD for diagnosing chronic kidney disease (CKD) was higher than that of eGFRmC-G, which in turn was higher than that of eGFRC-G (area under the curve was 0.846, 0.831, and 0.791; cut-off limits were 61.9, 58.3 and 59.5, respectively).
C-G and MDRD equations can be an alternative to the CCLcr test for assessing GFR, thus avoiding the need for the cumbersome and expensive GFR test. The MDRD formula had greater validity than the C-G equation and the C-G equation validity was improved by an adjustment to BSA.
PMCID: PMC3916281  PMID: 24516758
Creatinine; Glomerular Filtration Rate; Diet Modification; Chronic Kidney Disease; Oman
17.  Estimating Renal Function for Drug Dosing Decisions 
In order to adjust the dose of renally excreted drugs in response to reduced renal function, it is necessary to make a quantitative estimate of the glomerular filtration rate (GFR) of the patient. Traditionally this has been done with the use of the Cockcroft and Gault equation or a measured creatinine clearance. More recently the MDRD (Modification of Diet in Renal Disease) formula has become available, providing an estimate of GFR readily available on routine pathology reports. The presence of these different methods of assessing renal function has created some confusion for healthcare workers as to the best approach. In this paper the two methods are compared, together with a newer formula CKD-EPI (named after the Chronic Kidney Disease Epidemiology Collaborative), and a proposal is made for future practice.
PMCID: PMC3100285  PMID: 21611081
18.  Risk Implications of the New CKD Epidemiology Collaboration (CKD-EPI) Equation as Compared With the MDRD Study Equation for Estimated GFR: The Atherosclerosis Risk in Communities (ARIC) Study 
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently published an equation for estimated glomerular filtration rate (eGFR) using the same variables (serum creatinine, age, gender and race) as the Modification of Diet in Renal Disease Study (MDRD) equation. Although the CKD-EPI equation estimates GFR more precisely as compared with the MDRD equation, whether this equation improves risk prediction is unknown.
Study Design
Prospective cohort study, the Atherosclerosis Risk in Communities (ARIC) Study.
Setting & Participants
13,905 middle-aged participants without a history of cardiovascular disease with median follow-up of 16.9 years.
Outcomes & Measurements
We compared the association of eGFR in categories (≥120, 90–119, 60–89, 30–59, <30 ml/min/1.73m2) by the CKD-EPI and MDRD equations with risk of incident end-stage renal disease (ESRD), all-cause mortality, coronary heart disease (CHD), and stroke.
Median of eGFRCKD-EPI was higher than that of eGFRMDRD (97.6 vs. 88.8 ml/min/1.73m2, P<0.001). The CKD-EPI equation reclassified 44.9% (n=3,079) and 43.5% (n=151) of participants with eGFRMDRD 60–89 and 30–59, respectively, upward to a higher eGFR category but no one with eGFRMDRD 90–119 or <30, lowering the prevalence of CKD stage 3–5 from 2.7% to 1.6%. Participants with eGFRMDRD 30–59 who were reclassified upward had lower risk as compared to those who were not reclassified (ESRD incidence rate ratio, 0.10 [95% CI, 0.03–0.33], all-cause mortality, 0.30 [0.19–0.48], CHD, 0.36 [0.21–0.61], stroke, 0.50 [0.24–1.01]). Similar results were observed for participants with eGFRMDRD 60–89. More frequent reclassification of younger, female, and white participants explained some of these trends. Net reclassification improvement among participants with eGFR <120 was positive for all outcomes (P<0.001).
Limited number of cases with eGFR <60 and no measurement of albuminuria.
The CKD-EPI equation more appropriately categorized individuals with respect to long-term clinical risk as compared to the MDRD equation, suggesting improved clinical usefulness in this middle-aged population.
PMCID: PMC2858455  PMID: 20189275
19.  Variability of glomerular filtration rate estimation equations in elderly Chinese patients with chronic kidney disease 
Chronic kidney disease (CKD) is recognized worldwide as a public health problem, and its prevalence increases as the population ages. However, the applicability of formulas for estimating the glomerular filtration rate (GFR) based on serum creatinine (SC) levels in elderly Chinese patients with CKD is limited.
Materials and methods
Based on values obtained with the technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) renal dynamic imaging method, 319 elderly Chinese patients with CKD were enrolled in this study. Serum creatinine was determined by the enzymatic method. The GFR was estimated using the Cockroft–Gault (CG) equation, the Modification of Diet in Renal Disease (MDRD) equations, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the Jelliffe-1973 equation, and the Hull equation.
The median of difference ranged from −0.3–4.3 mL/min/1.73 m2. The interquartile range (IQR) of differences ranged from 13.9–17.6 mL/min/1.73 m2. Accuracy with a deviation less than 15% ranged from 27.6%–32.9%. Accuracy with a deviation less than 30% ranged from 53.6%–57.7%. Accuracy with a deviation less than 50% ranged from 74.9%–81.5%. None of the equations had accuracy up to the 70% level with a deviation less than 30% from the standard glomerular filtration rate (sGFR). Bland–Altman analysis demonstrated that the mean difference ranged from −3.0–2.4 mL/min/1.73 m2. However, the agreement limits of all the equations, except the CG equation, exceeded the prior acceptable tolerances defined as 60 mL/min/1.73 m2. When the overall performance and accuracy were compared in different stages of CKD, GFR estimated using the CG equation showed promising results.
Our study indicated that none of these equations were suitable for estimating GFR in the elderly Chinese population investigated. At present, based on overall performance, as well as performance in different CKD stages, the CG equation may be the most accurate for estimating GFR in elderly Chinese patients with CKD.
PMCID: PMC3474145  PMID: 23091374
elderly; equation; glomerular filtration rate; serum creatinine; Chinese
20.  Assessment of accuracy of Cockcroft-Gault and MDRD formulae in critically ill Indian patients 
Cockroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae have not been validated in critically ill Indian patients. We sought to quantify the discrepancy, if any, in Glomerular Filteration Rate (GFR) estimated by CG and MDRD formulae with 24 hrs urine Creatinine Clearance (Cr Cl).
Materials and Methods:
Prospective cohort study in 50 adult patients in a mixed medical-surgical intensive care unit. Inclusion criteria: Intensive Therapy Unit (ITU) stay >48 hrs and indwelling urinary catheter. Exclusion criteria: Age <18 years, pregnancy, dialysis, urine output <400 ml/day and patients receiving ranitidine, cefoxitin, trimethoprim or diuretics. We estimated Creatinine Clearance by CG and MDRD formula and measured GFR by 24 hrs urine creatinine clearance. Bland Altman plot was used to find the difference between the paired observations. The association between the methods was measured by the product moment correlation coefficient.
The mean GFR as calculated by Creatinine Clearance was 79.76 ml/min/1.73 m2 [95% Confidence Interval (CI) 65.79 to 93.72], that by CG formula was 90.05 ml/min/1.73 m2 [95% CI: 74.50 to 105.60], by MDRD was 85.92 ml/min/1.73 m2 [95% CI: 71.25 to 100.59]. The Bias and Precision between CG and Cr Cl were −4.5 and 140.24 respectively, between MDRD and Cr Cl was −6.1 and 122.52. The Correlation coefficient of CG formula as a measure of GFR was 0.65 (P < 0.0001), that of MDRD was 0.70 (P < 0.0001).
We conclude that CG and MDRD formulae have a strong correlation with measured GFR but are not a reliable measure and overestimate GFR in critically ill Indian patients.
PMCID: PMC3752870  PMID: 23983410
Cockroft gault formula; glomerular filteration rate; modification of diet in renal disease; one hour urine creatinine clearance
21.  Relationship Between Serum Cystatin C and Creatinine or Dialysis Adequacy in Patients on Chronic Maintenance Hemodialysis 
Nephro-urology Monthly  2013;5(2):733-735.
Glomerular filtration rate (GFR) is widely estimated by serum creatinine based equations such as Cockcroft-Gault (CG) standardized for body surface, and an abbreviated formula derived from MDRD (modification of diet in renal disease) study. However, some studies suggested that creatinine based estimation of GFR formula can be replaced by cystatin C based formula.
The aim of this study was to determine whether cystatin C based equation could be used as an indicator for renal function in hemodialysis patients compared to MDRD equation; and whether cystatin C, a dialyzable molecule, was related to Kt/V, the marker for dialysis adequacy.
Patients and Methods
In this cross-sectional study, 98 patients on chronic hemodialysis were included. Plasma levels of urea and creatinine were measured before and after dialysis, and cystatin C was measured before dialysis. GFR was calculated and compared.
The mean age of patients was 55.50 ± 16.10 (24-86) years and 66 cases were male (67.3%). The GFR was estimated at 6.05 ± 2.36 and 5.83 ± 2.19 cc/min by MDRD and cystatin C based formulas, respectively, with a significant correlation (r = 0.51; P < 0.001). Serum cystatin C level was 9.74 ± 2.47 mg/L which showed significant reverse correlation with both MDRD (r = -0.46; P < 0.001) and cystatin C based formulas (r = -0.87; P < 0.001). Neither creatinine nor serum cystatin C showed correlation with Kt/V, as the marker of dialysis adequacy.
Serum cystatin C may be considered as an indicator of renal function in patients under maintenance hemodialysis.
PMCID: PMC3703130  PMID: 23841035
Cystatin C; Glomerular Filtration Rate; Creatinine; Renal Dialysis
22.  MDRD or CKD-EPI study equations for estimating prevalence of stage 3 CKD in epidemiological studies: which difference? Is this difference relevant? 
BMC Nephrology  2010;11:8.
Prevalence of stage 3 chronic kidney disease (CKD) is increasing according to the NHANES study. Prevalence has been calculated using the MDRD study equation for estimating glomerular filtration rate (GFR). Recently, a new estimator based on creatinine, the CKD-EPI equation, has been proposed which is presumed to better perform in normal GFR ranges. The aim of the study was to measure the difference in prevalence of stage 3 CKD in a population using either the MDRD or the CKD-EPI study equations.
CKD screening is organized in the Province of Liège, Belgium. On a voluntary basis, people aged between 45 and 75 years are invited to be screened. GFR is estimated by the MDRD study equation and by the "new" CKD-EPI equations.
The population screened consisted in 1992 people (47% of men). Mean serum creatinine was 0.86 ± 0.20 mg/dL. The prevalence of stage 3 CKD in this population using the MDRD or the CKD-EPI equations was 11.04 and 7.98%, respectively. The prevalence of stage 3 CKD is significantly higher with the MDRD study equation (p < 0,0012).
Prevalence of stage 3 CKD varies strongly following the method used for estimating GFR, MDRD or CKD-EPI study equations. Such discrepancies are of importance and must be confirmed and explained by additional studies using GFR measured with a reference method.
PMCID: PMC2891733  PMID: 20515483
23.  A Comparison of Serum Cystatin C and Creatinine with Glomerular Filtration Rate in Indian Patients with Chronic Kidney Disease 
Oman Medical Journal  2011;26(6):421-425.
There is no literature available on the performance of cystatin C in Chronic Kidney Disease (CKD) patients of Indian population based on age group. Hence, this study is aimed to compare the diagnostic performance of serum cystatin C and creatinine with measured glomerular filtration rate (GFR) and estimated GFR (eGFR) in subjects of Indian origin.
The study was carried out at Tiruchirappalli, South India during the period of September 2010 to march 2011. One hundred and six CKD patients (82 males, 24 females) were enrolled and categorized into three groups based on age. The eGFR was calculated using Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Serum cystatin C was measured with a particle-enhanced nephelometric immunoassay (PENIA) method. GFR was measured using 99mTC - diethylene triamine penta aceticacid (DTPA) renal scan method.
Serum cystatin C showed significant correlation with measured GFR in all the three groups (r=-0.9735, r=-0.8975 and r=-0.7994 respectively) than serum creatinine (r=-0.7380, r=-0.6852 and r=-0.5127 respectively).
Serum cystatin C showed a high correlation with measured GFR in young and older patients with CKD than creatinine. Thus, cystatin C is a good alternative marker to creatinine in CKD patients.
PMCID: PMC3251200  PMID: 22253951
GFR; eGFR; CKD; Cystatin C; Creatinine; 99mTC-DTPA
24.  Comparison of Two Creatinine-Based Equations for Predicting Decline in Renal Function in Type 2 Diabetic Patients with Nephropathy in a Korean Population 
Aim. To compare two creatinine-based estimated glomerular filtration rate (eGFR) equations, the chronic kidney disease epidemiology collaboration (CKD-EPI) and the modification of diet in renal disease (MDRD), for predicting the risk of CKD progression in type 2 diabetic patients with nephropathy. Methods. A total of 707 type 2 diabetic patients with 24 hr urinary albumin excretion of more than 30 mg/day were retrospectively recruited and traced until doubling of baseline serum creatinine (SCr) levels was noted. Results. During the follow-up period (median, 2.4 years), the CKD-EPI equation reclassified 10.9% of all MDRD-estimated subjects: 9.1% to an earlier stage of CKD and 1.8% to a later stage of CKD. Overall, the prevalence of CKD (eGFR < 60 mL/min/1.73 m2) was lowered from 54% to 51.6% by applying the CKD-EPI equation. On Cox-regression analysis, both equations exhibited significant associations with an increased risk for doubling of SCr. However, only the CKD-EPI equation maintained a significant hazard ratio for doubling of SCr in earlier-stage CKD (eGFR ≥ 45 mL/min/1.73 m2), when compared to stage 1 CKD (eGFR ≥ 90 mL/min/1.73 m2). Conclusion. In regard to CKD progression, these results suggest that the CKD-EPI equation might more accurately stratify earlier-stage CKD among type 2 diabetic patients with nephropathy than the MDRD study equation.
PMCID: PMC3884626  PMID: 24454370
25.  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

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