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?

BACKGROUND: 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. METHODS: 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. RESULTS: 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 > or = 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. CONCLUSIONS: 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.     

Accuracy of indirect estimates of renal function in advanced chronic renal failure patients

Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formula are indirect estimates of renal function which have been widely accepted, though their accuracies have been scarcely validated in advanced chronic renal failure. The purpose of this study was to determine the accuracy (bias and precision) of these formulas in advanced CRF patients. The study group consisted of 99 unselected patients (62 +/- 15 years, 59 females) with advanced CRF. The glomerular filtration rate (GFR) was measured by Tc(99m) DTPA. Simultaneously, estimates of GFR by CG corrected for 1.73 m2 and MDRD (formula 7) were calculated. Agreement was evaluated graphically, bias was assessed by mean and median difference, and precision by median absolute differences and Bland-Altman plots. Mean GFR by DTPA, CG and MDRD were: 16.24 +/- 4.38 and 16.77 +/- 4.65 and 13.58 +/- 4.27 ml/min/1.73 m2, respectively. MDRD equation significantly underestimated GFR-DTPA (p = 0.0001). Both CG and MDRD correlated significantly with GFR-DTPA (R = 0.53 and R = 0.62, respectively). CG formula performed better than the MDRD equation with respect to bias (0.30 vs -3.24 ml/min/1.73 m2, p = 0.0001), and precision (0.58 vs. -3.11 ml/min/1.73 m2, p = 0.0001). By multiple linear regression, the best determinants of the error of the estimation by CC formula were: serum creatinine (beta = -0.58; p < 0.0001), age (beta = -0.62; p < 0.0001), and body mass index (beta = 0.26, p = 0.004), and by MDRD formula were: serum creatinine (beta = -0.38; p < 0.0001), and body mass index (beta = -0.20, p = 0.03). In conclusion, in unselected patients with advanced chronic renal failure, estimates by CC formula were more accurate than those obtained by MDRD formula. Serum creatinine was the main source of error of the estimation of GFR by both formulas, though demographic and anthropometric characteristics influenced as well on their accuracies.     

A simplified Cockcroft-Gault formula to improve the prediction of the glomerular filtration rate in diabetic patients

AIM: The National Kidney Foundation recommends stratification of renal failure into moderate (Glomerular Filtration Rate: GFR = 30-60 mL/min/1.73 m2), severe (15-30) or terminal (<15) using the Cockcroft-Gault (CG) or the Modification of Diet in Renal Disease (MDRD) equations. We studied the biases in these methods in an attempt to improve the standard CG (MCG) and devise a strategy for stratification. METHODS: GFR was measured by 51Cr-EDTA clearance in 200 diabetic patients: 100 (Group 1: study of concordance) before 2003 and 100 thereafter (Group 2: validation of MCG). The CG was modified by replacing body weight by its mean value: 76. RESULTS: In group 1, the recommended equations only correctly stratified 50 patients. The CG, not the MDRD, underestimated GFR if BMI was normal, and overestimated it in obese patients. In group 2, the MCG was well correlated with GFR and not biased by weight. Over the whole population, the MCG and MDRD were more accurate for the diagnosis of moderate and severe renal failure. The MDRD showed the lowest differences with GFR, except if GFR > 60, where the MCG performed better. All formulae overestimated low GFR, the MDRD also underestimated high GFR. The best stratification (147/200) was obtained using the MCG if creatininemia < 120 micromol/l and the MDRD if creatininemia > or =120 micromol/l. CONCLUSION: The CG is biased by weight, the MCG corrects this. The more accurate MDRD cannot be used in all patients as it underestimates high GFR. The best stratification was obtained using the MCG at low and the MDRD at high creatininemia.     

Performance of the revised ‘175’ Modification of Diet in Renal Disease equation in patients with type 2 diabetes

AIMS/HYPOTHESIS: Estimation of GFR (eGFR) is recommended for the assessment of kidney function in all patients with diabetes. We studied performance of the traditional '186' Modification of Diet in Renal Disease (MDRD) equation, and the 2005 revised '175' MDRD equation in patients with type 2 diabetes. METHODS: Two hundred and ninety-three mainly normoalbuminuric (267/293) patients were recruited. Patients were classified as having mild renal impairment (group 1, GFR <90 ml min(-1) 1.73 m(-2)) or normal renal function (group 2, GFR >or=90 ml min(-1) 1.73 m(-2)). eGFR was calculated by the traditional 186 MDRD equation using traditional creatinine values and the revised 175 MDRD equation using isotope dilution mass spectrometry-standardised creatinine values. Isotopic GFR was measured by the four-sample plasma clearance of (51)Cr-EDTA. RESULTS: For patients in group 1, mean +/- SD isotopic (51)Cr-EDTA GFR (iGFR) was 83.8 +/- 4.3 ml min(-1) 1.73 m(-2), and eGFR was 73.2 +/- 11.9 and 75.8 +/- 13.7 ml min(-1) 1.73 m(-2) using the 186 and 175 MDRD equations, respectively. Method bias was -10.6 with the 186 MDRD and -7.9 ml min(-1) 1.73 m(-2) (p < 0.05) with the 175 MDRD equation. In group 2, iGFR was 119.4 +/- 20.2 ml min(-1) 1.73 m(-2), and eGFR was 92.3 +/- 18.6 and 97.5 +/- 21.6 ml min(-1) 1.73 m(-2) using the 186 and 175 MDRD equations, respectively. Method bias was -27.1 with the 186 MDRD equation and -21.9 ml min(-1) 1.73 m(-2) (p < 0.05) with the 175 MDRD equation. CONCLUSIONS/INTERPRETATION: In patients newly diagnosed with type 2 diabetes, the revised 175 MDRD equation was less biased than the traditional 186 MDRD equation. Despite a continued tendency to underestimate isotopically measured GFR, use of standardised creatinine values is a positive step towards improved estimation of GFR.     

Plasma cystatin C determinations in a healthy elderly population

Plasma cystatin C measurement has been previously shown to be a better indicator of changes in glomerular filtration rate (GFR) than plasma creatinine. The available literature on reference intervals for cystatin C concentration encompasses only paediatric and adult populations up to 60 years of age, therefore we set out to determine an elderly reference range. Blood was taken from 401 subjects (65-101 years) and cystatin C and creatinine concentrations measured using commercially available methodologies. The availability of height and weight measurements allowed the additional calculation of predicted creatinine clearances using the Cockcroft and Gault formulae. Whilst no notable gender difference in cystatin C values was observed (female, 1.48 mg/l; male, 1.53 mg/l), concentrations rose with increasing age (60-79 years, 1.39 mg/l; >80 years, 1.70 mg/l). Conversely, there was a significant (P<0.0001) gender difference in creatinine values (female, 99 micromol/l; male, 120 micromol/l) but none between age groups (60-79 years, 105 micromol/l; >80 years, 113 micromol/l). Calculated GFR determinations resulted in a predicted creatinine clearance range of 21-81 ml/min per 1.73 m2 (n=361). There was no significant difference between gender (male, 18-88 ml/min per 1.73 m2; female, 24-69 ml/min per 1.73 m2), but a very significant 20% decrease in predicted GFR per decade. Sex-related reference intervals for creatinine were established (female, 66-149 micromol/l; male, 71-204 micromol/l); whilst age-related reference intervals were established for both cystatin C (60-79 years, 0.93-2.68 mg/l; >80 years, 1.07-3.35 mg/l) and predicted creatinine clearance (60-79 years, 27-89 ml/min per 1.73 m2; >80 years=18-55 ml/min per 1.73 m2). Plasma cystatin C measurement offers a simple, more sensitive screening assay for early changes in GFR and reflects the decreasing GFR that occurs with increasing age.     

Effect of oral cyclosporin on renal function in Crohn's disease

Twenty-one patients with Crohn's disease were followed prospectively for 24 weeks to examine the effect of a low-dose cyclosporin regime on renal function (initial dose 5 mg/kg reduced by 1 mg/kg every two months to a maintenance of 2 mg/kg). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by radioisotope clearance at 0,6 and 24 weeks. GFR and ERPF fell significantly (mean GFR at baseline: 120.9 ml/min/1.73 m²; at six weeks: 100.9 ml/min/1.73 m²; mean ERPF at baseline: 497.3 ml/min/1.73 m²; at six weeks: 398.5 ml/min/1.73 m²). Following dose reduction, the ERPF remained lower than baseline (mean 408.6 ml/min/1.73 m²), and there was a trend towards the GFR remaining low (mean 111.8 ml/min/1.73 m²). Serum creatinine rose significantly (median pretreatment 72 mol/liter; median at four weeks 86 mol/liter) but returned to baseline after dose reduction. Plasma cyclosporin levels and serum creatinine did not help predict the extent of changes in renal function. At low doses, cyclosporin causes changes in renal hemodynamics that may not be reversed by dose reduction.     

A new method to estimate glomerular filtration rate based on serum concentration of creatinine, urea and albumin (MDRD, Modification of Diet in Renal Disease)

The equation developed from the MDRD (Modification of Diet in Renal Disease) study provides more accurate estimate of GFR than other commonly used equations. The aim of this study was to compare prediction of GFR based on MDRD and Cockcrof-Gault (CG) method. The study was performed in 111 patients (mean age 42 +/- 5 years) with chronic renal impairment (Scr = 281 +/- 83 micromol/l). The mean of MDRD was 0.480 +/- 0.345 ml/s/1.73 m2 and that of CG 0.608 +/- 0.336 ml/s/1.73 m2. The difference is highly significant (p < 0.0001). The mean of CG/MDRD ratio was 1.24 +/- 0.17. This ratio was significantly higher (p < 0.01) in obese patients (1.59 +/- 0.14 vs 1.22 +/- 0.09). The CG/MDRD ratio did not show relation to Scr. The results are in keeping with the assumption that the difference between MDRD and CG method cannot be explained by increased tubular secretion of creatinine in residual nephrons. Obesity seems to be on of the factors responsible for the difference between CG and MDRD values.     

Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy

OBJECTIVE: To determine whether serum cystatin C is more accurate than serum creatinine in the detection of diabetic nephropathy, also after adjustment for age. METHODS: Forty-one patients with type 1 and 82 patients with type 2 diabetes were evaluated with serum creatinine, serum cystatin C, and (51)Cr-EDTA clearance (reference method). Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Statistical estimations were performed both without and with age adjustment created by z-scores for (51)Cr-EDTA clearance, creatinine, and cystatin C. The cut-off levels for glomerular filtration rate (GFR) ((51)Cr-EDTA clearance) were 60 and 80 mL min(-1) 1.73 m(-2), respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age-adjusted values (z-scores). RESULTS: Estimations without age adjustment showed significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus (51)Cr-EDTA clearance as compared with creatinine (r = 0.678). However, when using age-adjusted values, the correlation for cystatin C and creatinine, respectively, versus (51)Cr-EDTA clearance did not differ. When comparing the diagnostic utilities for serum cystatin C versus serum creatinine in manifest renal impairment (GFR < 60 mL min(-1) 1.73 m(-2) or z-scores <-1.28 SD), there were no significant differences between the two markers whether age adjusted or not. However, for diagnosing mild nephropathy (GFR < 80 mL min(-1) 1.73 m(-2) or z-score -0.84 SD), serum cystatin C is significantly more useful. CONCLUSIONS: Serum cystatin C performed better compared with serum creatinine even when measured enzymatically, to detect mild diabetic nephropathy. However, serum creatinine was as efficient as serum cystatin C to detect advanced diabetic nephropathy.     

The Modification of Diet in Renal Disease (MDRD) equations provide valid estimations of glomerular filtration rates in patients with advanced heart failure

BACKGROUND: Glomerular filtration rate (GFR) has major prognostic implications in heart failure. Our objective was to validate the MDRD prediction equations for GFR in patients with advanced heart failure, and to compare their predictive performance to that of the Cockcroft-Gault (CG) equation. METHODS: We analysed GFR in 45 patients referred for heart transplantation evaluation. 51Cr-EDTA-measured GFR was compared to GFR estimates obtained by MDRD1 and MDRD2 equations, CG equation using actual body weight, and ideal body weight. Regression analyses and Pearson correlations were performed, and Bland and Altman plots were drawn. ROC curves were obtained to illustrate each equation's ability to predict a GFR less than 60 ml/min/1.73 m2 (moderate renal impairment). RESULTS: Patients had a mean age of 52 years, and 69% were in NYHA class III. The mean EDTA-measured GFR was 46.9+/-17.2 ml/min/1.73 m2. The MDRD1 equation provided the best predictive model (narrowest limits of agreement; r = 0.766, p < 0.001), and the highest performance in predicting a GFR less than 60 ml/min/1.73 m2 (area under curve: 0.901). CONCLUSIONS: MDRD equations, especially MDRD1, adequately predict GFR in advanced heart failure, with higher accuracy than the CG equation. MDRD1 also has higher performance in predicting a GFR less than 60 ml/min/1.73 m2.     

Decreased insulin requirement in relation to GFR in nephropathic Type 1 and insulin-treated Type 2 diabetic patients.

AIMS: In the presence of impaired renal function, patients require less insulin mainly because insulin clearance is prolonged. The aim of this study was to evaluate the insulin requirement related to glomerular filtration rate (GFR) in nephropathic Type 1 and Type 2 diabetic patients. METHODS: In a retrospective study we compared insulin requirement in 20 nephropathic Type 1 diabetic patients and 20 insulin-treated Type 2 diabetic patients from the onset of overt nephropathy until the final stage of renal disease. All patients had proteinuria > 0.5 g/24 h and creatinine clearance >/= 80 ml/min per 1.73 m2 at baseline. Creatinine clearance, urinary protein excretion, glycated haemoglobin and the required insulin doses were determined 3- to 6-monthly, basal C-peptide was measured at the beginning and the end of the observation period. The required insulin doses were evaluated at creatinine clearance rates of 80, 60, 40, 20 and 10 ml/min per 1.73 m2 (or at the initiation of dialysis treatment). RESULTS: The insulin requirement of patients with Type 1 diabetes was reduced from 0.72 +/- 0.16 IU/kg per day at a creatinine clearance rate of 80 ml/min, to 0.45 +/- 0.13 IU/kg per day at a creatinine clearance rate of 10 ml/min (decrement of 38%, P < 0.001). The insulin dose required by Type 2 diabetic patients was reduced from 0.68 +/- 0.28 IU/kg per day at a creatinine clearance rate of 80 ml/min to 0.33 +/- 0.19 IU/kg per day at a clearance rate of 10 ml/min (decrement 51%, P < 0.001). The fall in GFR, urinary protein excretion and glycated haemoglobin levels was similar in the two groups. In patients with Type 2 diabetes, C-peptide levels at the beginning and the end of renal function impairment were 2.2 (0.4-7.3) vs. 2.7 (0.1-4.9) ng/ml (NS). The reduction in insulin requirement was approximately the same in patients with an initial C-peptide level < 1.0 and in those >/= 1.0 ng/ml (decrement 57% vs. 46%). CONCLUSIONS: The reduction in insulin requirement in renal insufficiency is similar in Type 1 and insulin-treated Type 2 diabetic patients. In subjects with Type 2 diabetes, the residual insulin secretion has no impact on the reduction in insulin requirement dependent on the GFR.     

Renal clearance of pancreatic and salivary amylase relative to creatinine in patients with chronic renal insufficiency.

Pancreatic and salivary amylase/creatinine clearance ratios in patients with various degrees of renal impairment were compared with those obtained for control subjects. In chronic renal insufficiency (mean GFR 30 ml/min +/- 15 SD; n = 13) the clearance ratios for pancreatic (mean 3.5 +/- 1.85 SD) and salivary (mean 2.3 +/- 1.3 SD) amylase were significantly higher (P less than 0.05) than those in controls. Corresponding control values (n = 26) were 2.64 +/- 0.86 (pancreatic) and 1.64 +/- 0.95 (salivary). Three patients showed values above the normal limit. In the diabetic group (mean GFR 41 ml/min +/- 22 SD; n = 10) salivary amylase/creatinine clearance ratios (mean 2.36 +/- 1.55 SD) were significantly higher than in controls (P less than 0.05). Three patients showed raised values. Pancreatic amylase clearance was raised in only one of these patients. Three patients with terminal disease (mean GFR 10 ml/min) showed markedly raised (two- to threefold) clearance ratios for both salivary and pancreatic amylase. Of a total of 26 patients, eight had increased total amylase/creatinine clearance ratios. Pancreatic amylase/creatinine clearance was increased in seven patients, while nine patients showed raised salivary amylase/creatinine ratios. Patients with raised clearance ratios did not have clinical evidence of pancreatitis. We suggest that, in the presence of impaired renal function, a high amylase/creatinine clearance ratio need not be indicative of pancreatic disease.     

Is Modification of Diet in Renal Disease formula similar to Cockcroft-Gault formula to assess renal function in elderly hospitalized patients treated with low-molecular-weight heparin?

BACKGROUND: Repeated administration of low-molecular-weight heparin (LMWH) to elderly patients with an impaired renal function may lead to an accumulation effect with an increased risk of bleeding. In this setting, Cockcroft-Gault (CG) is the most widely used formula for glomerular filtration rate (GFR) estimation. In hospitalized patients over the age of 70, the six-variable Modification of Diet in Renal Disease (MDRD) formula was compared with the CG formula to detect patients with renal impairment who are at higher risk of bleeding when treated with LMWH. METHODS: We combined retrospective data from 366 patients aged 86.2 +/- 6.6 years, treated with LMWHs. CG and MDRD GFR estimates were compared using the Bland-Altman method and the agreement between the two formulae by the kappa coefficient. RESULTS: The mean CG and MDRD estimated GFR were 45.9 +/- 21.9 mL/min and 75.6 +/- 32.6 mL/min/1.73 m(2), respectively, with a mean bias of 29.6 mL/min. The concordance between the formulae to classify patients into stages of kidney disease was very poor (weighted kappa = 0.17): 21.8% patients had severe renal function impairment with the CG formula versus 1.3% with the MDRD formula. In our population, the MDRD thresholds that would correspond to CG estimates of 30 mL/min and 60 mL/min were found at 63 mL/min/1.73 m(2) and 80 mL/min/1.73 m(2), respectively. CONCLUSIONS: In elderly patients, GFR estimates using MDRD and CG formulae differ widely and identify different numbers of individuals with kidney disease. Prospective comparative studies are needed to validate these formulae and their different thresholds to better detect elderly patients at higher risk of bleeding when treated with LMWH.     

Renal functions in obstructive sleep apnea patients

Purpose

The aim of this study is to investigate possible factors influencing glomerular filtration rate (GFR) in obstructive sleep apnea (OSA).

Methods

Data of OSA patients admitted to Gaziantep University sleep clinic from January 2005 to January 2010 were retrospectively evaluated. GFR is calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Patients younger than 18 years old were excluded.

Results

The mean age of OSA (n?=?634) and control group (n?=?62) were 51.13?±?11.61 and 50.69?±?13.88 years, respectively (p?=?0.81). The mean estimated GFR (eGFR) was 90.73?±?19.59 ml/min/1.73 m² in OSA patients and 94.14?±?18.81 ml/min/1.73 m² in control subjects (p?=?0.19). GFR was 84.25?±?20.87 ml/min/1.73 m² in patients with left ventricular hypertrophy (LVH) while it was 93.94?±?18.44 ml/min/1.73 m² in patients without LVH (p?=?0.00). GFR of male subjects was 92.1?±?19.23 in OSA and 95.84?±?20.08 ml/min/1.73 m² in controls (p?=?0.33). GFR of female and male patients in the OSA were 87.45?±?20.10 and 92.91?±?18.02 ml/min/1.73 m², respectively (p?=?0.13). Serum creatinine was higher in OSA patients compared to controls (p?=?0.01). GFR was 92.30?±?19.27 in male and 88.33?±?19.84 ml/min/1.73 m² in female subjects (p?=?0.01). GFR was 84.86?±?19.95 in hypertensive patients while it was 95.11?±?18.20 ml/min/1.73 m² in normotensive subjects (p?=?0.00). GFR was 89.30?±?19.96 in patients with metabolic syndrome (MetS) and it was 93.46?±?18.68 ml/min/1.73 m² in patients without MetS (p?=?0.00).

Conclusions

GFR values were lower in sleep apneic patients with MetS as well as in patients with hypertension and LVH.

     

Study of renal function by creatinine clearance

This paper was designed to investigate the correlation between the renal clearance and the plasma concentration of creatinine. Of the curve obtained, three segments were studied: 1 - When the glomerular filtration rate (GFR) was greater than 60 ml per min. the plasma concentration fluctuated between 0.44 and 1.59 mg/dl. 2 - When GFR was between 30 and 60 ml per min. the plasma concentration reached 2.4 mg/dl, and 3 - When GFR was less than 30 ml per min. the plasma level increased to values as high as 28 ml/min. The urinary concentration of creatinine can be divided into two broad groups depending on the GFR. The boundary of this division is around 60 ml per min. This suggests that when GFR is depressed there would exist a limitation of the tubular secretion of creatinine or urinary dilution problems. It is demonstrated that there is a poor correlation between creatinine clearance and its plasma concentration, and hence the repeated measurement of creatinine clearance becomes imperative in the follow-up of patients.     

Fenofibrate increases blood creatinine, but does not change the glomerular filtration rate in patients with mild renal insufficiency

Fenofibrate is a potent hypolipemic agent, widely used in patients with mild to severe renal failure in whom hyperlipoproteinemia is frequent. A moderate reversible increase in creatinine plasma levels has been reported with fenofibrate therapy; however, it is not known whether this increased creatininemia reflects a fenofibrate induced alteration of renal function or if fenofibrate interferes with creatinine tubular handling. We prospectively examined the effect of 2 weeks fenofibrate treatment (200 mg daily) on renal function in thirteen hyperlipidemic patients with normal renal function or mild to moderate renal failure (Creat Cl: 110 to 30 ml/min). This study confirms that fenofibrate therapy significantly increases creatininemia in patients with mild to moderate renal failure (147 +/- 12 versus 170 +/- 15 mmol/l; p = 0.014), but does not alter renal hemodynamic nor glomerular filtration rate as assessed by the stability of PAH (304 +/- 56 versus 311 +/- 49 ml/min; p = NS) and inulin clearances (51.7 +/- 6 versus 52.3 +/- 7 ml/min; p = NS). The increase in creatininemia is neither due to an inhibition of creatinine tubular excretion, since no change in creatinine clearance was observed (69 +/- 8 versus 68 +/- 8 ml/min; p = NS), but appears to be associated to a parallel increase in creatinine daily urinary excretion (13.7 +/- 5 versus 15.4 +/- 4 mmol; p = 0.03). In conclusion, fenofibrate therapy in renal patients does not worsen renal function, nor diminish the reliability of creatinine clearance for its follow-up in spite of a significant rise in creatininemia. The mechanism of the fenofibrate-induced increase in urinary creatinine excretion remains to be determined.     

Creatinine clearance, Cockcroft-Gault formula and cystatin C: estimators of true glomerular filtration rate in the elderly?

BACKGROUND: The aim of this study was to assess the accuracy and precision of estimators of true glomerular filtration rate (GFR) (Cockcroft formula, measured creatinine clearance (CCR) and a cystatin-C-based estimation) in elderly patients attending a geriatric department. Additionally, parameters influencing GFR in the elderly were evaluated. METHODS: 30 patients aged 57-90 years treated in the Geriatric Department for pulmonary or cerebral diseases were included in the study. Nine patients were diabetic and 16 hypertensive. Exclusion criteria were advanced dementia, acute heart failure and primary renal disease. Inulin clearance (CINU), CCR and estimation by Cockcroft-Gault equation (CG) were performed on the same day. For comparison of the methods an analysis according to Bland and Altman was used, depicting the mean difference between the methods and the limits of agreement of the differences, representing their 95% interval of confidence. Furthermore, the influence of confounding variables on GFR estimation was analyzed by multiple regression. RESULTS: Baseline characteristics showed a median age of 74.5 years and a median body weight of 66.7 kg. Median values for serum creatinine 88.4 micromol/l, 5.74 mmol/l for urea and 1.57 mg/l for cystatin C. CCR (median: 51.6 ml/min) and CG (median: 63.0 ml/min) underestimated CINU (median: 83.3 ml/min). Both methods showed poor precision compared with CINU. The upper limit of agreement of the difference was 101.3 ml/min for CCR and 81.4 ml/min for CG, the lower limit was -33.8 ml/min for CCR and -24.6 ml/min for CG. Among frequently used variables to predict GFR, the reciprocal of serum creatinine and body weight revealed a significant influence but not age or gender. A cystatin-C-based estimation of GFR, derived from regression analysis, did not improve the precision of the estimation of GFR compared to CG. Additionally, the occurrence of diabetes mellitus disclosed a borderline influence on the estimation of GFR. CONCLUSION: CCR is not only inconvenient and time consuming, but also imprecise and inaccurate in the elderly, mainly due to reduced muscle mass and erroneous urine sampling. CG and a cystatin-C-based estimation are slightly more adequate, but overall there is no sufficiently precise formula for GFR estimation in the elderly.     

Cystatin C as estimator of glomerular filtration rate in patients with advanced chronic renal disease

Serum cystatin C (CysC) has been shown to be more accurate than serum creatinine (Cr) in estimating renal function, especially in patients with mildmoderate chronic renal failure. However, it is unknown whether CysC provides or not any advantage over Cr in severe chronic renal failure. The aim of this study was to establish the accuracy of CysC in estimating the glomerular filtration rate (GFR) in advanced chronic renal failure patients. The study group consisted of 94 patients (57 females, mean age 61 +/- 16 years) with advanced chronic renal failure. None of them had thyroid dysfunction or was on corticoid treatment. CFR was measured by TC99mDTPA, and simultaneously, serum CysC (particle enhanced immunonephelometry) and Cr (modified Jaffe's kinetic reaction) were also determined. Serum Cr and CysC levels were correlated with GFR, and the influences of age, sex and diabetes on these correlations were analyzed. The predictive value of CysC and Cr to estimate a GFR less than 15 ml/min/1.73 m2 was analyzed by measuring the crea-under-the-curve (AUC) with Receiver-Operating Characteristics (ROC) plots. The mean CFR was 16.49 +/- 4.65 ml/min/1.73 m2. The mean concentrations of Cr and CysC were 4.19 +/- 1.19 mg/L and 3.44 +/- 0.73 mg/L, respectively. Both Cr and CysC correlated significantly with GFR (R = 0.49, p < 0.0001 and R = 0.52, p < 0.0001, respectively). Age and sex influenced on the correlation between Cr and GFR, but these demographic characteristics did not influence on the correlation between CysC and GFR. The AUC for the prediction of a GFR less than 15 ml/min/1.73 m2 with serum Cr was 0.675 (p = 0.004), while with CysC was 0.633 (p = 0.030). In conclusion, both serum Cr and CysC are highly inaccurate markers of renal function in advanced chronic renal failure patients.     

Differences between the glomerular filtration rate estimated by the MDRD equation and the measurement of creatinine and urea clearance in unselected patients with terminal renal insufficiency

From the results of the Modification of Diet in Renal Disease (MDRD) study, a prediction equation for a more accurate estimate of glomerular filtration rate (GFR), was developed. The present study ais to compare the GFR estimated by MDRD formula and that calculated by the average of creatinine and urea clearances in unselected patients with advanced renal failure. The study group consisted of 320 (163 males) with advanced renal failure not yet on dialysis. Their mean age was 63 +/- 14 years. Diabetic nephropathy was the most common etiology of renal failure (25%). Significant comorbidity was observed in 115 patients. Serum creatinine (Cr), urea and albumin were determined in all patients. Creatinine (Ccr) and urea clearance (Cu) were calculated on a 24-hour urine collection. The GFR was estimated by summing Ccr and Cu, and dividing by two (Ccr-Cu). THe clearances were corrected for a body surface area of 1.73 m2. The MDRD formula for the estimation of GFR included the following parameters: serum Cr, BUN, age, gender and serum albumin. Linear regression analysis and Bland-Altmann plot were utilized to establish the degree of correlation and agreement between both estimations of GFR. The percent differences between the two estimations of GFR was especially analyzed in those subgroups of patients which were not included in the MDRD study (patients older than 70 years, diabetics and those with comorbid conditions). The mean GFR estimated by Ccr-Cu and by MDRD formula were 10.04 +/- 3.10 ml/min and 10.55 +/- 3.60 ml/min, respectively (p < 0.0001). The two parameters correlated significantly (R = 0.76, p < 0.0001). GFR by the MDRD formula tended to overestimate the highest values of Ccr-Cu. The mean percent difference between both methods was 6.5 +/- 23.6. MDRD predictive equation overestimated significantly Ccr-Cu in patients older than 70 years (mean overestimation of 15%), males (10%), diabetics (10%), and mainly in patients with comorbidity (17%). In conclusion, the GFR estimated by MDRD formula is very similar to Ccr-Cu in young uremic patients without comorbidity. However, major discrepancies between these two methods could be observed in older patients, and mainly in those with comorbidity.     

Serum cystatin C versus serum creatinine in the estimation of glomerular filtration rate in rhabdomyolysis

Cystatin C has emerged as a possible, usable surrogate marker of renal function. We present a case that illustrates the clinical utility of cystatin C in the setting of acute kidney injury secondary to rhabdomyolysis. An African American male whose baseline cystatin C and serum creatinine levels taken a month prior to admission were compared against their daily values during his admission and at follow up. On admission, the patient's reduction in glomerular filtration rate (GFR) from baseline was much less when calculated with cystatin C than with serum creatinine. His clinical recovery was more reflective of the higher GFR with cystatin C than what would be assumed with his serum creatinine, which at its worst was 5 ml/min/1.73 m(2). The patient was eventually discharged from the hospital with a GFR of 40 ml/min by cystatin C despite his GFR by the MDRD equation being 12. Cystatin C may be a more accurate marker of the both the amount of injury and the rate of resolution of acute kidney injury than serum creatinine in rhabdomyolysis.     

Pitfalls of using estimations of glomerular filtration rate in an intensive care population

Background: Accurate knowledge of the glomerular filtration rate (GFR) is imperative in the intensive care unit (ICU) as renal status is important for medical decisions, including drug dosing. Aims: Recently, an estimation of GFR (eGFR) was suggested as a method of estimating GFR. How well this formula predicts GFR in unwell patients with normal initial serum creatinine concentrations has not been examined. Methods: The accuracy of the eGFR (before and after adjustment for actual body surface area (BSA)) was compared with measured and with estimated creatinine clearance using the Cockcroft Gault (CG) formula adjusted for total and lean body weight. Results: A total of 237 observations was recorded in 47 subjects. These were initially analysed independently, and then using the first observation only. Overall the mean difference between measured creatinine clearance and eGFR was ?12 mL/min (95% confidence interval (CI) ?20 to ?3), between measured creatinine clearance and CG +17 mL/min (95% CI 9–24), between measured creatinine clearance and CG adjusted for ideal body weight +12 mL/min (95% CI 4–21) and between measured creatinine clearance and eGFR ‘unadjusted’ for BSA 5 mL/min (95% CI ?2–13). Conclusions: Using either eGFR or CG formulae to estimate renal function in ICU subjects with normal serum creatinine concentrations is inaccurate. Although correcting for BSA improves the eGFR, this requirement to measure height and weight removes a major attraction for its use. We suggest that eGFR should not be automatically calculated in the ICU setting.