Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation.

BACKGROUND: Based on the data derived from the Modification of Diet in Renal Disease (MDRD) study, a new equation was developed for the estimation of glomerular filtration rate (GFR). This equation, which takes into account body weight, age, sex, serum creatinine, race, serum urea, and serum albumin, provided a more accurate estimation of GFR in patients with renal insufficiency. However, this prediction equation has not been validated in subjects with normal or supra-normal GFR. METHODS: In a cross-sectional study, we measured GFR by inulin clearance in 46 healthy controls and 46 non-complicated type 1 diabetic patients. In this study population, GFR was predicted by measured creatinine clearance, the Cockcroft-Gault formula, and the MDRD equation. RESULTS: In the healthy subjects, mean GFR (+/-SD) was 107+/-11 as compared to 122+/-18 ml/min per 1.73 m(2) in the diabetic patients. This difference in GFR was reflected by a lower serum creatinine (76+/-8 vs 71+/-8 micro mol/l) in the diabetic patients. In the healthy controls, median absolute differences (and the 50th-75th-90th percentile of percentage absolute differences) between predicted and measured GFR were 5.2 ml/min per 1.73 m(2) (4.9-9.8-18.5%) for creatinine clearance, 9.0 ml/min per 1.73 m(2) (8.6-14.3-24.6%) for the Cockcroft-Gault formula, and 10.7 ml/min per 1.73 m(2) (10.9-16.3-25.5%) for the MDRD equation. In the diabetic patients, these differences were 8.3 ml/min per 1.73 m(2) (7.6-9.3-13.0%) for creatinine clearance; 11.8 ml/min per 1.73 m(2) (10.1-16.0-22.5%) for the Cockcroft-Gault formula, and 18.8 ml/min per 1.73 m(2) (16.0-24.2-31.9%) for the MDRD equation. CONCLUSIONS: In subjects with a normal or increased GFR, the new MDRD-prediction equation of GFR is less accurate than creatinine clearance or the Cockcroft-Gault formula, and offers no advantage.     

Influence of apolipoprotein E polymorphisms on serum creatinine levels and predicted glomerular filtration rate in healthy subjects.

BACKGROUND: There are conflicting results regarding the effect of apolipoprotein (ApoE) polymorphisms on the progression of a variety of renal diseases. However, there are no data on the possible effect of the ApoE alleles on serum creatinine levels and predicted glomerular filtration rate (GFR) in healthy subjects. METHODS: 290 apparently healthy individuals were studied. ApoE genotyping was performed by the polymerase chain reaction; the Modification of Diet in Renal Disease equation (MDRD) predicted the GFR. RESULTS: ApoE2 was associated with lower levels of total cholesterol, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol, as well as with higher levels of triglycerides in our population. Furthermore, the ApoE2 allele was associated with increased serum creatinine levels compared with both the E3 and E4 alleles (1.04+/-0.13 vs 0.92+/-0.13 vs 0.88+/- 0.11 mg/dl, respectively, P = 0.0077), while the MDRD-predicted GFR was decreased in ApoE2 carriers compared with both E3 and E4 carriers (80.3+/-10.2 vs 88.1+/-9.6 vs 89.3+/-9.7 ml/min/1.73 m(2), respectively, P = 0.031). These observations remained significant statistically even if the effect of ApoE polymorphisms on age- and body-mass index-adjusted serum creatinine and MDRD-predicted GFR was separately analysed in both men and women. Although, ApoE4 carriers tended to exhibit lower levels of serum creatinine and higher values of predicted GFR compared with the E3 carries, these differences did not reach statistical significance. CONCLUSIONS: ApoE2 allele seems to be associated with increased serum creatinine levels and decreased MDRD-predicted GFR in healthy subjects.     

Inaccuracy of estimated creatinine clearance for prediction of iothalamate glomerular filtration rate

The clinical practice of estimating creatinine clearance (Ccr) from a patient's serum creatinine value by use of various nomograms and prediction formulas is widespread. The predictive accuracy of such Ccr estimates as substitutes for measured values of glomerular filtration rate (GFR) has not been determined. In addition, the effect of patient physical parameters on GFR prediction accuracy has not been assessed. To investigate these issues, 500 predicted Ccr values from each of four versions of the formula of Cockcroft and Gault were statistically compared with GFR values measured by sodium iothalamate clearance (Cio) in 394 human subjects representing every level of renal function. We conclude that (1) the original formula of Cockcroft and Gault is an inaccurate predictor of GFR; (2) correction of the formula for patient physical parameters does improve its accuracy for GFR prediction; (3) the best formula is not accurate enough to replace laboratory measurement of GFR; and (4) GFR prediction inaccuracy is more often associated with extremes in patient age, weight, serum creatinine, body surface area, and measured GFR but may occur for any value of each of these parameters.     

Estimating glomerular filtration rate in the general population: the second Health Survey of Nord-Trondelag (HUNT II).

BACKGROUND: Guidelines recommend the modification of diet in the renal disease (MDRD) formula or the Cockcroft-Gault formula for estimating the glomerular filtration rate (GFR). However, there is an ongoing discussion whether the MDRD formula should be used in the general population as several studies have found a large underestimation of its GFR estimates. METHODS: In this study, 1,029 low-risk subjects, eligible for kidney donation according to internationally accepted criteria were selected from the population-based second Health Survey of Nord-Trondelag (HUNT II). Serum creatinine values traceable to isotope dilution mass spectrometry were used with the re-expressed MDRD formula recently published. The 2.5th, 50th and 97.5th percentiles of GFR by age were calculated and compared to reference values from the literature, which are based on GFR measured with gold standard methods in potential kidney donors. RESULTS: The difference between the 50th percentiles for MDRD estimates and measured GFR in the literature was small and constant over age: +0.5 ml/min/1.73 m(2) at age 20 and -2.0 ml/min/1.73 m(2) at age 80. Bias for Cockcroft-Gault estimates varied from 0.0 ml/min/1.73 m(2) to -21.4 ml/min/1.73 m(2). Other formulae also had a too steep age correction, and bias among the elderly varied from -10 to -30 ml/min/1.73 m(2). Hence, 30-80% of the general population above age 60 had GFR estimates below their age-specific 2.5th percentile of normal kidney function, while the MDRD formula was much more conservative (13.3%). CONCLUSION: The MDRD formula gave nearly unbiased estimates for normal GFR. All other formulae tested had, especially in the elderly, a much larger negative bias and cannot be recommended for use in the general population.     

Lean body mass-adjusted Cockcroft and Gault formula improves the estimation of glomerular filtration rate in subjects with normal-range serum creatinine

BACKGROUND: Assessment of glomerular filtration rate (GFR) in individuals with normal-range serum creatinine is important in certain clinical situations, such as in potential living kidney donors. Accurate measurements of GFR invariably involve using an invasive method (e.g. inulin clearances), but is inconvenient. The aim of the present study was to determine whether serum creatinine-based prediction formulae adjusted for lean body mass (LBM) could improve the accuracy of GFR estimation in these subjects. METHODS: Glomerular filtration rate was determined by the clearance of technetium-99m-labelled diethylenetriamine penta-acetic acid ((99m)Tc DTPA) from plasma in 56 subjects with normal serum creatinine. For each subject, GFR was estimated using prediction formulae +/- LBM adjustment and compared with measured GFR. Formulae analysed include Cockcroft-Gault, Levey, Gates, Mawer, Hull, Toto, Jellife and Bjornsson. RESULTS: All formulae +/- LBM adjustment underestimated measured GFR, with poor precision, poor agreement and correlation (r (2) 相似文献   

Comparison of methods for determination of glomerular filtration rate: low and high-dose Tc-99m-DTPA renography,predicted creatinine clearance method,and plasma sample method

The gamma camera uptake method with Tc-99m-DTPA (diethylenetriaminepentaacetic acid) is a simple method for determination of glomerular filtration rate (GFR), and is less time-consuming than other methods, but its diagnostic accuracy is debated. Gate’s method (low-dose; LD), the high-dose method (HD), the predicted-clearance method, and the plasma-clearance method with Tc-99m-DTPA are compared in this study. We also performed GFR measurement and diuretic renography simultaneously. Tc-99m DTPA renography was performed in 36 patients aged 18–72 years with a wide range of renal function (serum creatinine 1.37 ± 0.49 mg/dl). GFR was determined by four methods: the gamma camera uptake method with low-dose Tc-99m DTPA (Gates, LD); the gamma camera uptake method with high-dose Tc-99m DTPA (HD); the predicted creatinine clearance method (Cockcroft–Gualt, CG); and the plasma sample clearance (PSC) method using a mono-exponential curve. The PSC method was chosen as reference. The regression equations for the CG, Gates (low-dose), and HD methods against the PSC method were 28.68 + 0.80X (r = 0.72; P value < 0.0001, RMSE = 21.65 ml/min/1.73 m²), 6.19 + 0.79X (r = 0.90; P value < 0.0001, RMSE = 10.64 ml/min/1.73 m²), and 6.53 + 0.88X (r = 0.93; P value < 0.0001, RMSE = 9.35 ml/min/1.73 m²), respectively. In comparison with determination of GFR by the PSC method, the CG method tended to overestimate GFR while, perversely, the LD and HD methods tended to underestimate GFR. The three methods were in agreement with the PSC method but the high-dose GFR method resulted in less error in estimation of GFR. Furthermore, GFR measurement and diuretic renography could be performed at the same time when the high-dose method was used. Because of the low cost and negligible radiation burden, this method might be preferred for routine practice in nuclear medicine.     

Effect of alcohol consumption on estimated glomerular filtration rate and creatinine clearance rate.

BACKGROUND: Moderate alcohol consumption is widely recognized as beneficial in the prevention of cardiovascular disease, yet the renal effects of alcohol intake are still controversial. The present study is designed to investigate the influence of alcohol consumption on calculated creatinine clearance rate (CCr) and glomerular filtration rate (GFR) in a Southern Taiwan Pai-Wan aboriginal community with a high prevalence of alcohol consumption. METHODS: This is a cross-sectional community-based study. The 1466 aboriginal subjects, 40-95 years of age, are a stratified random subpopulation identified during an integrative health care programme. They were sampled for drinking patterns. The main outcome measurements were serum creatinine, estimated CCr and GFR. RESULTS: Subjects with alcohol consumption had significantly higher levels of serum triglycerides, high-density lipoprotein cholesterol, uric acid, estimated CCr and GFR values than non-drinkers. Their blood pressure was also significantly higher. They had lower total cholesterol and low-density lipoprotein cholesterol concentrations. Increasing alcohol consumption was independently and significantly associated with a higher level of estimated CCr and GFR when analysed as both a categorical and continuous variable. CONCLUSIONS: The present study shows that chronic alcohol consumption has a negative effect on blood pressure and lipid profile and stimulates the estimated GFR.     

Predicted creatinine clearance to assess glomerular filtration rate in chronic renal disease in humans

The work was designed to assess the suitability of both measured endogenous creatinine clearance (CCR) and predicted creatinine clearance (P-CCR) to evaluate GFR in chronic renal disease (CRD) by utilizing the renal clearance of inulin (CIN) as gold standard. A total of 124 subjects were studied (62 healthy, 62 with CRF). CCR significantly overestimated GFR in healthy subjects as well as in CRF, whereas P-CCR was identical to GFR. The CCR/CIN ratio which calculates the fractional creatinine clearance and provides a rough estimation of the contribution of creatinine secretion in explaining the differences between CCR and GFR was increased in CRD and especially in CRD of glomerular origin. The ration P-CCR/CIN was significantly lower than CCR/CIN in healthy subjects and in patients with CRD of glomerular origin. The data are against the use of CCR in assessing GFR in healthy subjects and in patients with CRD.     

Relationship of gender, age, and body mass index to errors in predicted kidney function.

BACKGROUND: Previous studies have shown conflicting data on accuracy of equations for kidney function prediction. The present work analysed the relationship of gender, age and body mass index (BMI) to error of predictions by the Cockcroft-Gault equation (CG(eq)), the simplified equation of the Modification of Renal Diseases Study (MDRD(eq)) and the Mayo Clinic equation (Mayo(eq)). METHODS: Inulin clearance (glomerular filtration rate; GFR) and other variables were measured in 380 subjects of both sexes, aged 18-88 years, with and without kidney disease. GFR was defined as low when <60 ml/min x 1.73 m2. BMI was used for definition of underweight/overweight. Relative error of predictions was used as an index of bias. It was calculated as prediction minus GFR (positive values =overestimates, negative values = underestimates) and expressed as a percentage of the GFR. Absolute error was used as an index of imprecision and was calculated as the absolute value of relative error. RESULTS: CG(eq) relative error was inversely associated with age and directly associated with BMI (P<0.001), but not with gender or GFR. MDRD(eq) relative error was inversely associated with female gender and GFR (P<0.001), but not with age or BMI. Mayo(eq) relative error was directly associated with male gender, BMI and GFR (P<0.01), but not with age. Absolute error was higher for CG(eq) than for MDRD(eq) but only at low GFR (P<0.001). Mayo(eq) had a higher absolute error than CG(eq) and MDRD(eq) (P<0.01). CONCLUSIONS: Errors of predictions varied not only with GFR but also with gender, age and BMI. Without using creatinine assay calibration, Mayo(eq) was less accurate than both MDRD(eq) and CG(eq), whereas MDRD(eq) was slightly more precise than CG(eq) but only at low GFR.     

Estimating glomerular filtration rate at the transition from pediatric to adult care

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Screening for renal disease using serum creatinine: who are we missing?

BACKGROUND: Appropriate management and timely referral of patients with early renal disease often depend on the identification of renal insufficiency by primary care physicians. Serum creatinine (SCr) levels are frequently used as a screening test for renal dysfunction; however, patients can have significantly decreased glomerular filtration rates (GFR) with normal range SCr values, making the recognition of renal dysfunction more difficult. This study was designed to estimate the prevalence of patients who have significantly reduced GFR as calculated by the Cockcroft-Gault (C-G) formula, but normal-range SCR: METHODS: The study included 2781 outpatients referred by community physicians to an urban laboratory network for SCr measurement. GFR was estimated using the C-G formula. Patients were grouped according to the concordance of SCr level abnormalities (abnormal >130 micromol/l) with significantly abnormal C-G values (abnormal or =70 years old, 12.6% 60-69 years old, and 1.2% 40-59 years old. Analysis of historical available laboratory data for patients with abnormal SCr and abnormal C-G values showed that 2 years prior to the study period, 72% of this group had abnormal SCr, while 18% had normal SCr with abnormal C-G values, and 10% had normal SCr with normal C-G values. CONCLUSIONS: This study documents the substantial prevalence of significantly abnormal renal function among patients identified by laboratories as having normal-range SCR: Including calculated estimates of GFR in routine laboratory reporting may help to facilitate the early identification of patients with renal impairment.     

Creatinine clearance estimation from serum creatinine values: an analysis of three mathematical models of glomerular function

The logarithmic relationship of serum creatinine and creatinine clearance was analyzed in 100 adult patient studies using a geometric regression technique. Each sex was independently analyzed, and the subsequently derived regression formulae were age corrected resulting in mathematical models useful in estimating creatinine clearance from serum creatinine concentrations. These formulae were tested prospectively in another group of 100 patient studies in which creatinine clearance had been determined, and the results compared to values derived by use of two other published formulae. This newer method resulted in a closer distribution of data around a line of identity compared to other formulae and allowed for a good "bedside" estimation of creatinine clearance from serum creatinine concentration.     

A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate.

BACKGROUND: In clinical practice, the glomerular filtration rate (GFR) is often estimated from plasma creatinine. Several studies have shown cystatin C (cys C) to be a better parameter for the diagnosis of impaired renal function. No data are available, however, on the performance of cys C in follow-up of patients, compared with creatinine. Also, comparisons of cys C with the Cockcroft and Gault (C&G) formula for estimation of GFR are few. METHODS: Plasma samples were obtained from 93 consecutive patients seen for GFR determination and from 30 patients with diabetes mellitus type 2, of whom 23 were investigated a second time after 2 years. GFR was determined with [125I]iothalamate. Plasma creatinine was determined enzymatically and the creatinine clearance calculated according to C&G. Cys C was measured with a particle-enhanced immunonephelometric method. RESULTS: GFR correlated with 1/cys C (r = 0.873) as well as with C&G (r = 0.876). The area under the curve (AUC) of the receiver operating curves (ROCs), a measure of diagnostic accuracy, for cys C (0.931) and C&G (0.938) were equal (P = 0.815) and both better than the creatinine AUC (0.848; P = 0.006). Bland and Altman analysis showed that the simple formula GFR = -4.32 + 80.35 x 1/cys C, derived from our data, gave more accurate (P < 0.0001) and more precise (P = 0.024) GFR estimates than obtained with the C&G formula. The day-to-day variation (biological +analytical) for cys C was small (3.1%, SD 2.51%) in diabetic patients. In the follow-up study in diabetic patients, cys C was the parameter which had the best correlation (r = 0.66) with changes in GFR. CONCLUSIONS: Cys C shows a high correlation with GFR. With a very simple formula, cys C gives a good estimate of GFR, more accurate and precise than C&G. Because biological variation is low, cys C gives also a good assessment of GFR changes during follow-up. Cys C is the preferred endogenous parameter for GFR.     

Estimation of the glomerular filtration rate in children and young adults by means of the CKD-EPI equation with age-adjusted creatinine values

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Comparison of serum cystatin C and creatinine levels in determining glomerular filtration rate in children with stage I to III chronic renal disease

Abstract

Background: Pediatric studies are relatively scarce on the superiority of cystatin C over creatinine in estimation of glomerular filtration rate (GFR). This study measured cystatin C and serum creatinine levels, and compared GFR estimated from these two parameters in patients with chronic renal disease. Methods: This prospective, observational, controlled study included 166 patients aged 1–18 years diagnosed with stage I to III chronic renal disease, and 29 age- and sex-matched control subjects. In all patients, GFR was estimated via creatinine clearance, Schwartz formula, Zappitelli 1 and Zappitelli 2 formula and the results were compared using Bland–Altman analysis. Results: Patients and controls did not differ with regard to height, body weight, BMI, serum creatinine and serum cystatin levels, and Schwartz formula-based GFR (p?>?0.05). There was a significant relationship between creatinine and cystatin C levels. However, although creatinine levels showed a significant association with age, height, and BMI, cystatin C levels showed no such association. ROC analysis showed that cystatin C performed better than creatinine in detecting low GFR. Conclusion: Cystatin C is a more sensitive and feasible indicator than creatinine for the diagnosis of stage I to III chronic renal disease.     

Limitations of glomerular filtration rate equations in the renal transplant patient

This study aims to compare the performance of endogenous creatinine clearance (CL(cr)) and a number of published mathematical equations to calculate glomerular filtration rate (GFR) in renal transplant patients considering (99m)Tc DTPA isotope scan as the reference method. A total of 152 GFR were performed on 81 renal transplant patients. Accuracy of each method was measured at different percentiles. The bias and precision of all the methods were then compared. A paired t-test was used to compare the performance of each calculation to the respective GFR measured by isotope study performed on the same day. In the total population, all calculated methods correlated significantly with the isotope results. Accuracies within specific ranges of the isotope GFR were limited in all equations (agreement with isotope result /= 50 mL/min and Gates in patients with GFR < 50 mL/min. Salazar (D.E. Salazar and G.B. Corcoran, Am J Med 1988; vol. 84: p. 1053) had the least bias in patients with BMI above 30 kg/m(2) and the Davis equation (G.A. Davis and M.H. Chandler, Am J Health Syst Pharm 1996; vol. 53: p. 1028) in patients with BMI <25 kg/m(2). In all analyses, Nankivell (B.J. Nankivell, S.M. Gruenwald, R.D.M. Allen and J.R. Chapman, Transplantation 1995; vol. 59: p. 1683) overestimated GFR by more than 80% and MDRD 1 and 2 in <10% of the time. The results demonstrate the inherited limitation in the currently available equations to calculate GFR in renal transplant patients.     

Correlation between serum creatinine, creatinine clearance, the calculated creatinine clearance and the glomerular filtration rate in heart transplant patients.

Assessment of glomerular filtration rate (GFR) in heart transplant (HTx) patients is based on serum creatinine (sCr), the endogenous creatinine clearance (C(Cr)) and radionuclide GFR (rGFR); however, the latter is expensive and time consuming. We reviewed the data of 32 adult HTx patients to determine the correlation between sCr, C(Cr), the calculated C(Cr) (Calc.C(Cr); based on gender, age, weight and sCr) and rGFR in long-term (>1 year) HTx patients receiving calcineurin inhibitors. The Calc.C(Cr) was found to have the best correlation with rGFR (r(2) = 0.65), followed by C(Cr) (r(2) = 0.53) and sCr (r(2) = 0.38). The use of Calc.C(Cr) to estimate GFR may be cost-effective in assessing renal function after HTx.     

Comparison between creatinine and cystatin C-based GFR equations in renal transplantation.

BACKGROUND: Estimation of glomerular filtration rate (GFR) from serum creatinine (Scr) or cystatin C (Cys C) exhibit variable performances. METHODS: We compared the performances of 14 Scr and 9 Cys C estimated GFR equations using inulin clearance (Clin) as the reference test in 103 stable renal transplant populations. Bias, precision, receiving operation characteristics (ROC), accuracy within 30% ranges from the reference method and agreements of each test were compared. RESULTS: Mean Clin was 46.4+/-20.9 ml/min/1.73 m2. Scr and Cys C levels correlated well with each other (r=0.83, P<0.0001) and with Clin (r=-0.57 and -0.53, P<0.001, respectively). ROC analysis demonstrated no superiority of Cys C over Scr. Gats equation achieved the highest accuracy of 70% in patients with GFR>or=60 ml/min/1.73 m2. In patients with GFR>or=60 ml/min/1.73 m2, the Nankivell equation demonstrated the highest accuracy of 73.91%. Cys C-based equations were not depicted to be thoroughly accurate. Bias, precision and agreement were otherwise similar in all GFR tests. CONCLUSION: Scr-based equations did not appear to be inferior to Cys C-based equations as a means to estimate GFR in renal transplant patients.     

Sequential analysis of variation in glomerular filtration rate to calculate the haemodynamic response to a meat meal

BACKGROUND: The renal haemodynamic response to a meat meal is usually measuredas either filtration capacity (maximal achieved GFR), or renalreserve (maximal GFR increase over baseline), or percent renalreserve (maximal GFR increase as a percentage of baseline).The time-course of GFR response to a meat meal varies in differentindividuals as the peak GFR tends to occur late in renal disease.This study proposes a new method to measure the GFR responseindependently of differences in peaking time. METHODS: The study is based on measurement of GFR (inulin clearance,ml/minx1.73 m² BSA) in three 30-min pre-meal clearance periods(baseline) followed by analysis of the GFR changes for up to180 min (four 30-min and one 60-min clearance periods) aftera meat meal (2 g of protein/kg of BW as red cooked meat). Datawere analysed from 85 healthy people (GFR100) and 273 individualswith renal disease (RD) who were divided into three groups basedon their baseline GFR (RD1, n=115, GFR 99–66; RD2, n=85,GFR 65–33; RD3, n=73, GFR<33). RESULTS: In healthy people after the meat meal GFR peaked between 30and 60 min and returned to baseline by 120 min. In the threeRD groups GFR peaked later than in healthy people (P<0.001)and remained higher than baseline for up to 180 min (P<0.001).Cumulative post-meal GFR changes, calculated as cumulative GFRincrease over baseline up to 120 min after meal (ml/120minx1.73m²BSA), were significantly different (P<0.01) in the four groups(healthy people, 937±141; RD1, 1222±141; RD2,587±104; RD3, 361±89). Interindividual variabilityin cumulative GFR increase was only partially explained by thevalue of nitration capacity (r²=0.285), renal reserve (r²=0.640),and percent renal reserve (r₂=0.175). CONCLUSIONS: The data indicate that commonly used parameters are poor indicesof the actual total time-course of the renal response to a proteinload.