Creatinine clearance versus serum creatinine as a risk factor in cardiac surgery

Background  

Renal impairment is one of the predictors of mortality in cardiac surgery. Usually a binarized value of serum creatinine is used to assess the renal function in risk models. Creatinine clearance can be easily estimated by the Cockcroft and Gault equation from serum creatinine, gender, age and body weight. In this work we examine whether this estimation of the glomerular filtration rate can advantageously replace the serum creatinine in the EuroSCORE preoperative risk assessment.     

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.     

Prediction of creatinine clearance from serum creatinine.

A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18-92. Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccr's measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr's of 0.83; on average, the difference predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.     

Spreadsheet use to calculate creatinine clearance from serum creatinine

Spreadsheets may be created to include the Cockcroft-Gault Formula (CGF) for creatinine-based estimation of glomerular filtration rate. Creatinine clearance (CrCl) provides a more accurate method for perioperative risk assessment of renal function than serum creatinine. CrCl may be used to develop guidelines for renal protective management strategies during cardiopulmonary bypass. CGF uses serum creatinine, age, kilogram weight, sex, and "logical test" functions within the spreadsheet to calculate the CrCl. Implementation of spreadsheets has the potential for numerous other calculations and may provide an accurate and consistent method of clinical perfusion management.     

Formula and nomogram for predicting creatinine clearance from serum creatinine concentration

Background Quick estimation of creatinine clearance from serum without calculation or urine measurements may be useful in many bedside clinical circumstances. A novel formula and a nomogram for predicting creatinine clearance are presented here. Methods We determined 24-hour creatinine clearance in 155 men and 143 women. A formula for creatinine clearance prediction from serum creatinine (Scr), age, body weight (BW), and body mass index (BMI) was developed [men: creatinine clearance=(−0.065 Age−0.493BMI+33)BW/Scr/14.4; women: creatinine clearance=(−0.052 Age−0.202BMI+21)BW/Scr/14.4]. Variables in this formula were evaluated for suitability by multiple regression analysis. The correlation between creatinine clearance measured and creatinine clearance predicted using serum creatinine from the same subject group was high (r=0.882). A nomogram for creatinine clearance prediction was derived from an equation that included the logarithmic transformation of age, body weight, height, and creatinine excretion instead of the original, nonlogarithmic values. Results Correlation between measured and estimated creatinine clearance values for the nomogram was slightly lower (r=0.879) than ther value (0.882) obtained using the original formula. However, the nomogram still has considerable reliability in creatinine clearance prediction compared several other methods previously reported. Conclusion The improved formula and nomogram for creatinine clearance presented here show high correlation with measured creatinine clearance. However, almost all the subjects in this study were nondiabetic patients. Therefore, the formula and the nomogram should be applied in treating nondiabetic patients; a separate formula may be needed for patients with diabetic nephropathy.     

Preoperative prediction of creatinine clearance by using serum creatinine

BACKGROUND: Creatinine clearance (Ccr) is an efficient index of renal function. However, measurement of Ccr is not routinely performed for preoperative patients. To predict preoperative renal impairment, we estimated the preoperative Ccr by using serum creatinine (sCr) and other laboratory findings. METHODS: 702 patients served as the training samples and other 128 patients as the validation samples. (1) Values of sCr and BUN to predict lower Ccr levels were developed from the training samples. In the combination of sCr and BUN, we selected the optimal combination in receiver operating characteristics curve. This value was applied to the validation samples. (2) The predictive equation was derived from the training samples by multiple regression analysis, and it was compared with the equations previously reported. RESULTS: (1) The optimal sensitivity and specificity for predicting Ccr less than 30 ml x min(-1) x 1.48 m(-2) were 60% and 84%, respectively. (2) Among the equations to predict Ccr, our equation showed the highest correlation coefficient (r), and the smallest differences between predicted and measured Ccr. CONCLUSIONS: We determined the values of sCr and BUN to predict renal impairment and derived predictive equation. Our equation was the best to assess the preoperative renal function.     

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.     

Estimation of glomerular filtration rate by inulin clearance: comparison with creatinine clearance

Inulin clearance (Cin) is widely believed to be the gold standard of the glomerular filtration rate (GFR). However, in Japan, Cin has not been officially recognized by the Ministry of Health, Labour and Welfare of Japan for clinical use. Creatinine clearance (Ccr) has been used to estimate the renal function of patients, but there have been many studies in which Ccr estimates were GFR falsely high because the metabolism and tubular excretion of creatinine widely varied according to the pathophysiological state of the patient. In the present study, we determined Cin and Ccr simultaneously in 116 adult patients with renal diseases and diabetic mellitus. The clearance study was performed by the modified Wesson's method. The inulin preparation was FFI-1010 (Fuji Yakuhin Co. Ltd.). Inulin in serum and urine was determined by the newly devised enzymatic assay (Toyobo Co. Ltd.), which is specific for inulin. The mean Cin was 35.0 +/- 14.4 ml/min/1.73 m2. The mean Ccr(the enzyme assay) was 63.6 +/- 24.1 ml/min/1.73 m2 and that of the kinetic Jaffe assay was 55.3 +/- 19.3 ml/min/1.73 m2. Mean Ccr/Cin was 1.93 +/- 0.73, 1.69 +/- 0.62, respectively. This ratio was significantly different(p < 0.05) in the degree of reduction of Cin, with values of 2.07 +/- 0.82 (Cin < 40 ml/min/1.73 m2) and 1.64 +/- 0.32(40 < Cin < 80 ml/min/1.73 m2), respectively. Only 8 patients were classified into the same degree of reduced renal function (the Guideline of Japanese Society of Nephrology). The findings of this study suggest that the GFR determined by Ccr could misjudge the renal function of patient and delay the administration of proper treatment of the patient. Introduction of Cin into the clinical field is necessary to avoid this delay.     

Genomewide linkage analysis to serum creatinine, GFR, and creatinine clearance in a community-based population: the Framingham Heart Study

Kidney disease is a risk factor for the development of cardiovascular disease, all-cause mortality, and ESRD. It is not known to what extent genetic factors play a role in the development of kidney disease in the general population. Multipoint variance components linkage analysis was performed using Genehunter on 330 families from the Framingham Heart Study offspring cohort, using a 10-cM genomewide scan for serum creatinine, GFR, and creatinine clearance (CRCL) measured from 1998 to 2001. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation, and CRCL was estimated using the Cockcroft-Gault equation. Covariates in the adjustment included age, gender, body mass index, diabetes, systolic BP, hypertension treatment, tobacco use, and HDL cholesterol. Overall, 1224 subjects (52% women), mean age 59, were available for analysis. Mean creatinine was 0.87 mg/dl, mean GFR was 87 ml/min per 1.73 m(2), and mean creatinine clearance was 100 ml/min. The multivariable-adjusted heritability estimates for creatinine, GFR, and CRCL were 0.29, 0.33, and 0.46, respectively. The peak log of the odds ratio (LOD) scores for serum creatinine, GFR, and CRCL were 2.28 at 176 cM on chromosome 4, 2.19 at 78 cM on chromosome 4, and 1.91 at 103 cM on chromosome 3, respectively. In a community-based sample, measures of serum creatinine, GFR, and CRCL are heritable, suggesting an underlying genetic component. These results also provide suggestive evidence for linkage to measures of kidney function. Further research is necessary to identify the genes involved in the development of kidney disease and to understand their roles in this complex process.     

Renal function in the elderly (>70 years old) measured by means of iohexol clearance, serum creatinine, serum urea and estimated clearance

OBJECTIVE: A survey revealed that kidney donors live longer than non-donors. When measured using an injection technique in elderly former kidney donors, the glomerular filtration rate (GFR) was found to be markedly decreased. The aim of this study was to determine the relationship between GFR and age in a cohort of elderly controls with two kidneys. We were also interested to find out whether GFR estimated using different equations correlated with the exact measurements. MATERIAL AND METHODS: Renal function was determined using the iohexol technique in 52 elderly "healthy" persons aged 70-110 years. Blood tests were done at the same time. Estimated clearance was determined using the equations of Cockroft-Gault, Walser and Levey. RESULTS: GFR showed a strong correlation with age (p = 0.0002), with an annual decline of 1.05 ml/min. Using formulas for estimation of clearance, the best correlation was found with that of Levey. Probably the most widely-used formula, that of Cockroft-Gault, underestimated the clearance, the mean value being 46.2 +/- 11.3 ml/min/1.73 m2, compared to the measured mean value of 67.7 +/- 10.8 ml/min/1.73 m2. Serum (s)-creatinine did not correlate with age (p = 0.3997). However, s-urea increased with age (p = 0.0019), while s-albumin (p = 0.0018), blood haemoglobin (p = 0.0060) and s-ferritin (p = 0.0243) decreased with age. A total of 21/52 (30%) of the elderly subjects had a GFR >70 ml/min/1.73 m2, but none of these persons was aged >90 years. Of the 21 subjects with good function, eight seemed to be quite healthy, with normal test values. CONCLUSION: GFR decreases by approximately 1.05 ml/min per year in very old persons. S-urea seems to be more sensitive than s-creatinine for indicating renal function in the elderly. The best formula for estimation of clearance is that of Levey. The Cockroft-Gault formula seems to underestimate GFR.     

Creatinine clearance prediction in spinal cord injury patients: comparison of 6 prediction equations

The renal function of spinal cord injury patients frequently is overestimated by 3 commonly used equations to predict creatinine clearance. Overestimation of creatinine clearance may result in aminoglycoside overdosage and resultant nephrotoxicity. Three newer prediction equations have been developed from creatinine clearances measured in neurologically abnormal patients. These 6 equations were tested in 77 male and 9 female spinal cord injury patients (48 quadriplegics and 38 paraplegics, including 38 with acute and 48 with chronic injuries). The equation developed by Sawyer and Hutchins was superior to 2 other equations developed in spinal cord injury patients and 3 equations developed in neurologically normal patients. However, creatinine clearances predicted by this equation were within 30 ml. per minute of measured creatinine clearances in only two-thirds of the spinal cord injury patients. Errors ranged from overestimation by 95 ml. per minute (151 per cent) to underestimation by 106 ml. per minute (45 per cent). The potential for large errors in creatinine clearance prediction necessitates measurement of creatinine clearance as soon as possible when renal excreted and toxic pharmaceuticals are administered to spinal cord injury patients.     

Comparison between serum creatinine and creatinine clearance for the prediction of postoperative mortality in patients undergoing major vascular surgery

BACKGROUND: Poor renal function prior to surgery is associated with increased risk for mortality in patients undergoing major vascular surgery. Traditionally, this function is assessed by serum creatinine concentration (SeCreat). However, SeCreat is also influenced by age, gender and body weight. Hence, creatinine clearance (C(Cr)) is considered to be a better reflection of renal function. This study was undertaken to explore the prognostic value of preoperative calculated Cc, compared to SeCreat for the prediction of postoperative mortality. PATIENTS AND METHODS: The study group comprised 852 consecutive patients who underwent elective major vascular surgery at the Erasmus Medical Center, Rotterdam. Preoperative C(Cr) was calculated based on the Cockroft-Gault equation using preoperative SeCreat, age, body weight and gender. Univariable logistic regression analyses were used to study the relation between preoperative SeCreat, C(Cr) and postoperative mortality. Furthermore, multivariable logistic regression analysis was applied to evaluate the additional predictive value of age, body weight and gender additional to SeCreat. The receiver operating characteristic (ROC) curve was determined to evaluate the predictive power of several regression models for perioperative mortality. RESULTS: Postoperative mortality was 5.9% (50/852) within 30 days of surgery. In a univariable analysis, 10 micromol/l increment of SeCreat were associated with a 20% increased risk of postoperative mortality (OR = 1.2, 95% CI, 1.1-1.3) with an area under the ROC curve of 0.64 (95% CI, 0.56-0.71). If age, gender and body weight were added, the area under the ROC curve increased to 0.70 (95% CI, 0.63-0.77; p < 0.001), indicating that these risk factors had additional prognostic value. Indeed, in a separate regression analysis 10 ml/min decrease in C(Cr) was associated with a 40% increased risk of postoperative mortality (OR = 1.4,95% CI, 1.2-1.5; ROC area: 0.70, 95% CI, 0.63-0.76). ROC curve analysis showed that the cut-off value of 64 ml/min for C(Cr) yielded the highest sensitivity/specificity to predict postoperative mortality. CONCLUSION: Preoperative SeCreat was strongly associated with postoperative mortality, and adding age, gender, and body weight to the model showed improved predictive power indicating that preoperative C(Cr) calculated with these data has additional prognostic value.     

Bone mass is related to creatinine clearance in normal elderly women.

We determined the relationship between bone mass and age, anthropometric variables, creatinine clearance (Ccr), and serum and urine biochemical variables in 77 normal white women (aged 41-86, mean = 67) living in their own homes. A total of 74 women were postmenopausal. Skeletal status was assessed in all subjects by x-rays of the hand with measurement of the mean combined cortical thickness (CCT) of the second metacarpal bones. In 53 women, bone mineral content of the radial shaft (RMBC) was also measured by single-photon absorptiometry (SPA) and lumbar bone mineral density (LBMD) was measured by dual-photon absorptiometry (DPA). Serum and urine biochemical variables were measured under standardized conditions on the sixth and seventh days of a controlled diet. There was a strong positive correlation between Ccr and bone mass. Although our subjects showed the expected linear decline in Ccr with age, we found that the relationship between Ccr and bone mass in the radius and lumbar spine was independent of age. On the other hand, the relationship between Ccr and CCT was not independent of age. We concluded that the relationship between Ccr and lumbar and radial bone mass is probably indicative of a relationship between glomerular filtration rate and bone mass, although this requires validation with a noncreatinine method for measurement of glomerular filtration rate. Age per se does not appear to be a cause of declining lumbar bone mass after the menopause.