Creatinine Production Rate Research Articles

Factors associated with 10-m walking speed in outpatients undergoing hemodialysis: a multicenter cross-sectional study

IntroductionWalking ability is an important prognostic factor for patients undergoing maintenance hemodialysis (HD). Since complications such as poor nutrition, anemia, malnutrition, and inflammation in patients undergoing HD may affect walking ability, the factors affected by 10-m walking speed must be investigated. This cross-sectional study enrolled 1205 outpatients undergoing HD and measured their 10-m walking speed.MethodsLower extremity muscle strength (LES), grip strength, one-leg standing time (OLST), and short physical performance battery (SPPB) score were measured as physical functions. Age, sex, body mass index, dialysis history, comorbidities, and hematological data were collected.ResultsA multiple regression analysis revealed that the 10-m walking speed was significantly associated with LES, grip strength, OLST, SPPB, and % creatinine production rate, even after adjusting for corresponding variables (R2 = 0.69, p < 0.05).ConclusionMuscle strength and muscle mass may be essential factors for the 10-m walking speed in patients undergoing HD.

Consistent methods for fat-free mass, creatinine clearance, and glomerular filtration rate to describe renal function from neonates to adults.

Quantifying the effect of kidney disease on glomerular filtration rate (GFR) is important when describing variability in the clearance of drugs eliminated by the kidney. We aimed to develop a continuous model for renal function (RF) from prematurity to adulthood based on consistent models for fat-free mass (FFM), creatinine production rate (CPR), and GFR. A model for fractional FFM in premature neonates to adults was developed using pooled data from 4462 subjects and 2847 FFM observations. It was found that girls have an FFM higher than that predicted from adult women based on height, total body mass, and sex, and boys have an FFM lower than adult men until around the onset of puberty, when it approaches adult male values. Data from 108 subjects with measurements of serum creatinine (Scr) and GFR were used to construct a model for CPR. Creatinine clearance was predicted using a model for CPR (based on FFM, postmenstrual age, and sex) and Scr that avoids discontinuous predictions between neonates, children, and adults. Individual CPR may then be used with individual Scr to predict the estimated GFR (eGFR; eGFR=CPR/Scr). A previously published model for human GFR based on 1153 GFR observations in 923 subjects without known kidney disease was updated using the model for fractional FFM to predict individual size and age-consistent values for the expected normal GFR (nGFR). Individual renal function was then calculated using RF=eGFR/nGFR.

Is an Acute Perioperative Increase in Creatinine Production Rate a Potential Mechanism for an Early Creatinine-Based Signal of Renal Injury After Cardiac Surgery?

Previous studies report a creatinine-based signal of injury within hours after cardiac surgery, which is sooner than expected based on creatinine kinetic modelling. A plausible mechanism for such an early signal has not been established, but might be explained by an acute perioperative increase in creatinine production rate (Crprod-rate). The authors sought to test the hypothesis that perioperative Crprod-rate increases from baseline in patients undergoing cardiac surgery. Prospective cohort study. Academic medical center. Fifty adult male patients undergoing cardiac surgery. None. Based on the principle of conservation of mass, precisely timed serial measurements of patient weight, plasma and urine creatinine concentration, and urine volume were used to calculate Crprod-rate over 3 consecutive periods: a baseline period immediately before surgery (period 0), the 24-hour period starting from induction of anesthesia (period 1), and again from 24 to 48 hours after induction of anesthesia (period 2). The primary outcome was change in Crprod-rate from period 0 to period 1 (∆Crprod-rate0-1). Median Crprod-rate0 was 5.4 (interquartile range [IQR], 4.7-5.7) μmol/kg/h at baseline and increased to 6.1 (IQR, 5.6-6.5) μmol/kg/h during period 1, a median increase of 14% (95% CI, 8%-27%; p=0.002). ∆Crprod-rate0-1 ranged from -58% to +129%, with an increase above baseline in 25 patients (76%) and an increase by ≥30% above baseline in 10 patients (30%). Perioperative Crprod-rate increased from baseline in patients undergoing cardiac surgery. This may represent a mechanism for an earlier creatinine-based signal of renal injury than previously thought possible.

Estimates Of Glomerular Filtration Rate in Critically Ill Patients With Sepsis: Comparisons of Different Equations

Introduction: Accurate assessment of glomerular filtration rate (GFR) is important in the critically ill. Kinetic estimate of GFR (keGFR) considers the changes of creatinine, creatinine production rate, and volume of distribution, hence postulated to be a more accurate estimate of GFR, where there are rapidly changing kidney functions. We evaluated the association of the estimated GFR by established equations and keGFR with creatinine clearance (CrCl) measurement. Materials and Methods: This is a prospective observational study of critically ill patients. Inclusion criteria were patients older than 18 years old with sepsis (clinical infection and increase in SOFA score&gt;2), and plasma procalcitonin&gt;0.5ng/ml. Plasma creatinine and Cystatin C (CysC) were measured on admission and 4 hours later, and the eGFR were calculated by the Cockcroft Gault (CG), MDRD, CKD-EPI and keGFR equations, and compared to the CrCl measurement. Results: A total of 70 patients were recruited. eGFR by all 4 equations strongly correlates with CrCl. keGFR had the least bias depicted by the mean differences nearest to zero (-18ml/min). Similarly, keGFRCysC had less bias than eGFRCysC, with mean difference of -21ml/min. eGFRCG had the greatest precision depicted by the narrower SD lines, however the precision of both keGFR were not much difference compared to those of eGFRCG. Conclusions: In critically ill patients with sepsis, keGFRCr and keGFRCysC had the least bias and fair precision when compared to creatinine clearance measurement. In the absence of creatinine clearance measurement, keGFR calculations is useful as surrogate for kidney function.

P1500SEASONAL VARIATIONS AND VARIATIONS DUE TO OTHER CAUSES IN CLINICAL AND LABORATORY PARAMETERS IN HEMODIALYSIS PATIENTS

Abstract Background and Aims In hemodialysis patients, seasonal variations and changes in dialysis prescription affect laboratory data, blood pressure, and body weight. We examined whether these fluctuations were due to seasonal variations or other causes. Although there are some reports on seasonal changes in hemodialysis patients, there are few reports on observations over multiple years in the same stable patients. Method We studied 65 patients on hemodialysis (36 males and 29 females; average age, 67.7 years; average duration of HD therapy, 13.8 years). The observation period was three years from January 2016 to December 2018; laboratory data and dialysis-related indicators, blood pressure, dry weight, and interdialysis weight gain were examined retrospectively. We excluded cases with dialysis time less than 4 h and patients who were hospitalized during the observation period. Differences in statistical analysis were tested with repeated-measures ANOVA or Friedman test. Results Factors that showed an influence on the laboratory parameters in hemodialysis patients more than twice in the same season in the three-year observation period were serum urea nitrogen (UN), serum creatinine (Cr), serum potassium (K), serum inorganic phosphorus (IP), and serum total bilirubin (T-Bil), serum creatine kinase (CPK), serum glycoalbumin (GA), normalized protein catabolic rate (nPCR), % creatinine production rate (% CGR), systolic blood pressure (sBP), diastolic blood pressure (dBP), and inter-dialytic weight gain (p&amp;lt;0.05). In contrast, the serum albumin concentration (Alb), serum magnesium (Mg), serum parathyroid hormone-INTACT (iPTH), and standardized dialysis amount of urea (KT/Vurea) exhibited gradual changes during the observation period (p&amp;lt;0.05). Conclusion There were indeed seasonal variations with UN, Cr, K, IP, T-Bil, CPK, GA, nPCR, %CGR, sBP, dBP, and inter-dialytic weight gain. However, Alb, Mg, iPTH, KT/Vurea changed owing to dialysis prescription and medicines.

Estimates of Glomerular Filtration Rate by the Chronic Kidney Disease Epidemiology Collaboration Equations Best Correlates with Kinetic Estimates of Glomerular Filtration Rates in the Critically Ill

Introduction: Kinetic estimate of GFR (keGFR) is a more accurate estimate of GFR in the acute settings with rapidly changing kidney functions. It takes into account the changes of creatinine over time, creatinine production rate, and the volume of distribution, however needs serial measurement of creatinine. We evaluated which methods of the conventional eGFR measurement best correlates with keGFR. This could assist clinicians in using a simpler method of calculation and is useful in the absence of serial plasma creatinine. Materials and method: This is a secondary analysis of prospective observational study. Inclusion criteria includes age more than 18 years old, and exclusion criteria includes ICU admission of less than 48 hours, post elective surgery, and ICU readmission. Plasma creatinine were measured daily for five days, and eGFR were calculated using the Cockcroft-Gault, MDRD, CKD-EPI and keGFR equations. Results: One hundred and forty three patients were analysed, of which 78(54.5%) had AKI. keGFR strongly correlated with eGFRCKD-EPI at all time points (all r≥0.90, p&lt;0.0001). The correlation persisted in both AKI and No AKI patients. keGFR only correlated well with eGFRMDRD and eGFRCG in AKI patients but less in patients without AKI. Bland Altman analysis showed that eGFRMDRD had the least bias, but eGFRCKD-EPI had the greatest precision. Conclusion: The new equation, keGFR strongly correlated with the eGFR by the CKD-EPI equation regardless of the time points and AKI status, and had the greatest precision. In the absence of serial plasma creatinine measurement, eGFR can accurately be estimated by the CKD-EPI equation compared to others.

025 ESTIMATES OF GLOMERULAR FILTRATION RATE IN THE CRITICALLY ILL WITH SEPSIS

Category: Research in AKI (Basic, translational, clinical including clinical trials) Presenter: Assoc. Prof Azrina Md Ralib Keywords: Glomerular Filtration Rate, Cystatin C, Creatinine Accurate assessment of glomerular filtration rate (GFR) in ICU patients is very important for institution of supportive therapy, preventive therapy, early renal support, drug dosing modification or avoidance of nephrotoxic drugs. Kinetic estimate of GFR (keGFR) takes into account the changes of creatinine over time, creatinine production rate, and the volume of distribution, hence postulated to be a more accurate estimate of GFR in the acute setting, where there are rapidly changing kidney functions as in the critically ill. We evaluated the association of the keGFR with estimated GFR (eGFR) by conventional method. This is an interim analysis of a single centre, prospective observational study of critically ill patients. The study has been registered with the National Medical Research Register (NMRR-14-1897-21447) and has obtained ethics approval. Inclusion criteria were patients older than 18 years old with sepsis, defined as clinical infection and acute increase in SOFA score>2, and plasma procalcitonin>0.5ng/ml. Plasma creatinine and Cystatin C were measured at seven time points, and eGFR were calculated by the Cockcroft-Gault, MDRD, CKD-EPI, and eGFRCysC and they were compared to their keGFR equations. Twenty four patients were recruited so far, of which 10 (41.7%) had AKI. Two patients needed dialysis, and one died. keGFRCr strongly correlated with eGFRCKD-EPI equation in all patients at all time points (all r≥0.76, p<0.0001). On the other hand, keGFRCr only correlated well with eGFRMDRD and eGFRCG in AKI patients but less in patients without AKI. keGFRCysC strongly correlated with eGFRCysC in all patients at all time points (all r≥0.89, p<0.0001) keGFRCr and keGFRCysC were not strongly correlated (min r=0.29) eGFRCKD-EPI distribution had the greatest precision depicted by the narrower SD lines. Similarly, keGFRCysC had higher precision when compared to eGFRCysC. eGFRMDRD and eGFRCG had the least bias depicted by the mean difference nearest to zero. Both eGFRCKD-EPI and eGFRCysC distribution differed significantly from the keGFRCr and keGFRCysC, respectively (Wilcoxon sign rank test, p<0.0001). The new equation, keGFR strongly correlated with the eGFR by the CKD-EPI equation with the highest precision. In the absence of serial plasma creatinine measurement, eGFR is best estimated by the CKD-EPI equation. eGFR of Cystatin C also correlated well with its keGFR. Further study would involve analysis of their association with urinary creatinine clearance.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Kinetic Estimation of GFR Improves Prediction of Dialysis and Recovery after Kidney Transplantation.

BackgroundThe early prediction of delayed graft function (DGF) would facilitate patient management after kidney transplantation.MethodsIn a single-centre retrospective analysis, we investigated kinetic estimated GFR under non-steady-state conditions, KeGFR, in prediction of DGF. KeGFRsCr was calculated at 4h, 8h and 12h in 56 recipients of deceased donor kidneys from initial serum creatinine (sCr) concentrations, estimated creatinine production rate, volume of distribution, and the difference between consecutive sCr values. The utility of KeGFRsCr for DGF prediction was compared with, sCr, plasma cystatin C (pCysC), and KeGFRpCysC similarly derived from pCysC concentrations.ResultsAt 4h, the KeGFRsCr area under the receiver operator characteristic curve (AUC) for DGF prediction was 0.69 (95% CI: 0.56–0.83), while sCr was not useful (AUC 0.56, (CI: 0.41–0.72). Integrated discrimination improvement analysis showed that the KeGFRsCr improved a validated clinical prediction model at 4h, 8h, and 12h, increasing the AUC from 0.68 (0.52–0.83) to 0.88 (0.78–0.99) at 12h (p = 0.01). KeGFRpCysC also improved DGF prediction. In contrast, sCr provided no improvement at any time point.ConclusionsCalculation of KeGFR from sCr facilitates early prediction of DGF within 4 hours of renal transplantation.

Estimation of renal function in the intensive care unit: the covert concepts brought to light.

Frantic efforts have been made up to this date to derive consensus for estimating renal function in critically ill patients, only to open the Pandora's box. This article tries to explore the various methods available to date, the newer concepts, and the uncared issues that may still prove to be useful in estimating renal function in intensive care unit patients. The concept of augmented renal clearance, which is frequently encountered in critically ill patients, should always be taken into account, as correct therapeutic dosage of drugs sounds vital which in turn depends on correctly calculated glomerular filtration rate. Serum creatinine and creatinine-based formulae have their own demerits that are well known and established. While Cockcroft-Gault and 4-variable modification of diet in renal diseases formulae are highly inadequate in the intensive care setup for estimating glomerular filtration rate, employing isotopic methods is impractical and cumbersome. The 6-variable modification of diet in renal diseases formula fairs better as it takes into account the serum albumin and blood urea nitrogen, too. Jelliffe's and modified Jelliffe's equations take into account the rate of creatinine production and volume of distribution which in turn fluctuates heavily in a critically ill patient. Twenty-four-hour and timed creatinine clearances offer values close to reality although not accurate and cannot provide immediate results. Cystatin C is a novel agent that offers a sure promise as it is least influenced by factors that affect serum creatinine to a major extent. Aminoglycoside clearance, although still in the dark area, may prove a simple yet precise way of estimating glomerular filtration rate in those patients in whom these drugs are therapeutically employed. Optic ratiometric method has emerged as the most sophisticated one in glomerular filtration rate estimation in critically ill patients.

Retooling the Creatinine Clearance Equation to Estimate Kinetic GFR when the Plasma Creatinine Is Changing Acutely

It is often desirable to estimate the GFR (eGFR) at the bedside to assess AKI or renal recovery. Current eGFR equations estimate kidney function when the plasma creatinine is stable, but do not work if the plasma creatinine is changing rapidly. To analyze kidney function in the acute setting, a simple formula is proposed that requires only a modest number of inputs that are readily obtainable from clinical laboratory data. The so-called kinetic eGFR (KeGFR) formula is derived from the initial creatinine content, volume of distribution, creatinine production rate, and the quantitative difference between consecutive plasma creatinines over a given time. For that period, the deciphered creatinine excretion then yields the creatinine clearance rate. The additional formula variables needed are any steady-state plasma creatinine, the corresponding eGFR by an empirical formula, and the maximum increase in creatinine per day if anuric. The kinetic formula complements clinical intuition but also adds a quantitative and visual dimension to the assessment of kidney function, demonstrated by its analysis of GFRs underlying the plasma creatinine fluctuations in several scenarios of AKI or renal recovery. Deduced from first principles regarding the physiology of creatinine balance, the KeGFR formula enhances the fundamental clearance equation with the power and versatility to estimate the kidney function when the plasma creatinine is varying acutely.

Impact of creatinine production on the agreement between glomerular filtration rate estimates using cystatin C-derived, and 4- and 6-variable Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations

Background. It has recently been reported that patient selection has a strong impact on the agreement between glomerular filtration rate (GFR) estimates from serum cystatin C and creatinine. The aim of our study was to evaluate the effect of creatinine production rate (CPR) on this subject. Material and methods. GFR was estimated from serum cystatin C and from creatinine using the 4- and 6-variable Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in 50 healthy subjects, 43 patients with renal failure, 794 kidney and 104 liver transplant recipients, 61 patients with heart failure, 59 patients with biliary obstruction, and 113 critically ill patients.Results. In the 295 patients with impaired CPR (< 900 mg/24 h/1.73 m2), discordances of more than 40% between GFRMDRD4 and GFRcystatinC were observed in 38% of cases, between GFRMDRD6 and GFRcystatinC in 22%, and between GFRCKD-EPI and GFRcystatinC in 27% (in all cases due to GFR overestimation from creatinine). In the 929 patients with maintained CPR (> 900 mg/24 h/1.73 m2), greater discordances than 40% between GFRMDRD4 and GFRcystatinC were observed in 8% of cases, between GFRMDRD6 and GFRcystatinC in 9%, and between GFRCKD-EPI and GFRcystatinC in 7% (in the major part of cases due to GFR overestimation from cystatin C). Conclusion. The main source of differences of more than 40% between GFR estimates from serum creatinine and cystatin C is a GFR overestimation in patients with low CPR and GFR underestimation in patients with high CPR by the creatinine-derived equations.

Assessing renal function - searching for the perfect marker continues!

Assessing renal function - searching for the perfect marker continues!

Serum Cystatin C for the Prediction of Glomerular Filtration Rate With Regard to the Dose Adjustment of Amikacin, Gentamicin, Tobramycin, and Vancomycin

Dosage regimes of aminoglycosides and vancomycin are modified according to the glomerular filtration rate (GFR). In 130 hospitalized patients who were administered amikacin, gentamicin, tobramycin, and vancomycin by intermittent intravenous infusion, we compared the predicted GFR values from the serum concentrations of creatinine (Cockcroft and Gault. Nephron. 1976;16:31-41) and cystatin C (Larsson et al. Scand J Clin Lab Invest. 2004;64:25-30) with respect to their relevance for proper dosage. In 83% and 67% of the cases, respectively, the serum levels of albumin and cholinesterase were below the corresponding lower limit of the reference range. The ratio of creatinine/cystatin C concentrations presented significant correlations with the predicted rate of creatinine production (r=0.762, P<0.001), serum albumin concentration (r=0.205, P<0.05), and catalytic serum concentrations of cholinesterase (r=0.207, P<0.05), gamma glutamyltransferase (r=-0.273, P<0.01), and alkaline phosphatase (r=-0.289, P<0.01). The GFR (mean+/-SD; median) predicted by the serum creatinine (84.0+/-35.1 mL/min/1.73 m; 82.6 mL/min/1.73 m) was significantly higher (P<0.001) than that predicted by the serum cystatin C (53.1+/-30.2 mL/min/1.73 m; 44.9 mL/min/1.73 m). The ratio between the GFR values predicted by creatinine and cystatin C had a highly significant negative correlation with the rate of creatinine production (r=-0.912, P<0.001). Furthermore, significant differences were found for the peak concentrations and clearances of amikacin and vancomycin estimated by means of the Abbottbase Pharmacokinetic Systems program, and using the GFR values predicted by the serum creatinine and cystatin C (P<0.005). In patients with hepatic dysfunction, the clearance of creatinine predicted by the Cockcroft-Gault formula leads to a significant overestimation of the GFR. Cystatin C seems to be a valid alternative as a GFR marker with regard to drug dose adjustment in these cases.

POSTOPERATIVE RENAL INSUFFICIENCY

The poor clinical outcomes associated with postoperative HARI necessitate increased vigilance for HARI detection and intervention to minimize the progression to dialysis dependency. Patient survival significantly worsens if HARI requires the initiation of dialysis. Postoperative changes, including intravascular volume expansion, SIRS, and reduced lean body mass, frequently confound the detection of HARI. Serum creatinine levels frequently do not reflect the decreased renal function because creatinine production rate is decreased with reduced lean body mass, and the serum creatinine concentration is reduced by increased intravascular volume expansion and increased volume of distribution associated with anasarca. Additional indices of renal function must be used postoperatively, including urine output, net volume status, urinalysis with microscopic examination of the spun pellet, and corrected estimations of creatinine clearance. Few therapeutic interventions currently exist to reverse HARI other than optimization of renal perfusion and limitation of nephrotoxin exposure. Dialysis remains a cornerstone of maintenance therapy for refractory and severe HARI. Selection of dialysis modality continues to be based on modality availability and patient stability.

Catabolism in critical illness: Estimation from urea nitrogen appearance and creatinine production during continuous renal replacement therapy

Thirty-eight intensive care unit (ICU) patients (26 men and 12 women with a mean age of 57.0 +/- 16.6 years) with acute renal failure (ARF) treated by venovenous continuous renal replacement therapy (CRRT) were evaluated while in relatively steady metabolic control. Twenty-seven were undergoing continuous venovenous hemodialysis, nine were undergoing continuous venovenous hemodiafiltration, and two were undergoing continuous venovenous hemofiltration. Periods of analysis varied between 24 and 408 hours (mean duration, 82.7 +/- 70.6 hours; median, 72 hours). Their mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score within 24 hours of admission to the ICU was 21.3 +/- 6.3 and survival rate was 31.6%. Urea nitrogen and creatinine concentrations were determined every 6 to 12 hours in both serum (Cun and Cc, respectively) and effluent (spent dialysate and/or ultrafiltrate). The mean effluent rate was 1,472 +/- 580 mL/h and blood flow rate, 166 +/- 32 mL/min. Urine was collected daily for urea nitrogen and creatinine measurement. Urea nitrogen appearance rate (UnA) and creatinine production rate (Pc), calculated from urea nitrogen (UnMR) and creatinine mass removal (CMR) from both the effluent and the urine, using Garred mass balance equations and the Forbes-Bruining formula, allowed normalized protein catabolic rate (nPCR) and estimates of lean body mass (LBM) to be derived. Creatinine metabolic degradation rate (Dc), estimated by the Mitch formula, was included in the calculation. The lowest body weight recorded during the study period was considered as dry weight (BW). The creatinine index (CI) was also obtained. For each parameter, the results are presented as mean, median, and range values: UnMRe (from effluent), 13.6 +/- 7.2, 12.5, 1.6 to 32.6 mg/min; UnMRu (from urine), 0.13 +/- 0.40, 0, 0 to 2.30 mg/min; UnA, 13.6 +/- 7.0, 12.5, 3.8 to 32.1 mg/min; nPCR, 1.75 +/- 0.82, 1.60, 0.61 to 4.23 g/kg/d; CMRe (from effluent), 942.0 +/- 362.3, 918.0, 211.2 to 1,641.6 mg/d; CMRu (from urine), 44.4 +/- 138.8, 0, 0 to 698.5 mg/d; Dc, 94.6 +/- 49.9, 81.9, 31.0 to 294.1 mg/d; Pc total, 1,067.1 +/- 409.7, 1,053.7, 261.5 to 1,988.2 mg/d; LBM, 38.3 +/- 11.9, 37.9, 15.0 to 65.0 kg; LBM/BW ratio, 49.5% +/- 14.0%, 50.3%, 22.5% to 86.0%; and CI, 13.7 +/- 4.7, 14.2, 4.1 to 25.8 mg/kg/d. When Pc was estimated from the Cockcroft-Gault equations (as Pc'), the mean value for Pc and Pc' was similar (1,067.1 +/- 409.7 v 1,284.9 +/- 484.1 mg/d), but there were relatively large differences for the majority of cases. A positive correlation was observed between UnA and Pc (R = 0.42). Serum albumin and LBM/BW correlated poorly (R = 0.20). Outcome was weakly related to UnA and to nPCR (R = 0.29 and R = 0.31, respectively). Urea nitrogen appearance appears widely variable in critically ill ARF patients. This simple approach can provide useful information for an easy estimate of net protein catabolism in critically ill patients with ARF undergoing CRRT. (Am J Kidney Dis 1998 Sep;32(3):444-53)

Analytical reviews in clinical biochemistry: the estimation of creatinine.

PHYSIOLOGY Creatine is synthesised by the body in a two-step process (Fig. 1) involving the initial synthesis of guanidinoacetate, which takes place in the kidneys, small intestinal mucosa, pancreas, and probably the liver. The reaction between glycine and arginine is catalysed by a transamidase, which is subject to feedback inhibition by increased creatine levels. Guanidinoacetate is transported to the liver where it is methylated to creatine, which then enters the blood to be widely distributed, chiefly to muscle cells, in which it is converted to creatine phosphate-a source of high energy phosphate bonds for the immediate reformation of ATP during muscular contraction. Creatinine is formed by a spontaneous and irreversible conversion from creatine and creatine phosphate. Formation of creatinine is reasonably constant, and about 2% of whole body creatine is so transformed every 24 h. Consequently, creatinine formation also has a direct relationship to total muscle mass and roughly to the body weight. Creatinine production rate therefore remains approximately the same from day to day unless the muscle mass changes. It is not altered significantly by illness, sepsis, trauma or fever, nor by the state of hydration; however, increased protein intake can result in increases in creatinine production of the order of 10%.

A method for determining the pharmacokinetics of endogenous creatinine without exogenous creatinine administration.

A method for determining the individual pharmacokinetics of endogenous creatinine is derived and applied in 10 post-renal transplant patients. All patients had rapidly decreasing serum creatinine concentrations (C), but relatively constant creatinine clearance (Clcr) during the study period. Based on the multiple consecutive Clcr and the corresponding C, the elimination rate constant (K), volume of distribution (V), and daily creatinine production rate (R) for each patient were derived. The creatinine 'normal' t1/2 (corresponding to a Clcr of 120 ml min-1) was also calculated. In the 10 patients studied, the observed Clcr ranged from 29.5 to 72.7 ml min-1. The corresponding calculated mean K was 0.076 +/- 0.028 h-1; R was 20.0 +/- 5.7 mg kg-1 day-1, and V was 0.60 +/- 0.1 1 kg-1. The 'normal' t1/2 was 4.0 +/- 0.93 h. These pharmacokinetic parameters are consistent with those derived from radiotracer studies and other methods reported in the literature. The present study shows that the individual endogenous creatinine pharmacokinetics can be determined by a relatively simple and noninvasive method in certain selected patients if the appropriate serum and urinary creatinine concentrations are obtained.

Overestimation of renal function in glucocorticosteroid treated patients

Creatinine clearance is commonly used as a parameter for individualization of dosages of drugs primarily excreted by the kidney. Nomograms and equations have been developed for estimating creatinine clearance from serum creatinine concentration, body weight, age and sex. Glucocorticosteroids are said to cause proximal muscle wasting and therefore may be expected to cause a decrease in the creatinine production rate. The purposes of the present investigation were first to evaluate by a computed tomography the effect of long term treatment with prednisone on the mid-thigh muscle area, and second, to establish whether the presumed supposed decrease in muscle mass was associated with a decrease in the urinary creatinine excretion rate, and hence in a systematic error whenever a nomogram is used to predict creatinine clearance in such subjects. Patients taking prednisone had smaller mid-thigh muscle areas than controls. A linear relationship between the mid-thigh muscle area and the observed urinary excretion of creatinine was found, suggesting that the muscle loss could account for the decrease in the urinary excretion rate of creatinine. The ratio of observed to predicted (by nomogram) urinary creatinine excretion was lower in patients than controls, resulting in a corresponding underprediction of creatinine clearance by nomograms in the patients taking prednisone.

Decreased rate of creatinine production in patients with hepatic disease: implications for estimation of creatinine clearance.

Serum creatinine concentration is commonly used in conjunction with individual patient characteristics (e.g., age, sex, and body weight) in order to estimate creatinine clearance. Such estimates of creatinine clearance are widely used as a parameter for individualization of dosages of drugs excreted primarily via the kidneys in patients with diminished renal function. However, estimation of creatinine clearance in patients with concurrent hepatic disease tends to result in substantial overprediction of observed creatinine clearance in this patient population. This report suggests that a diminished rate of creatinine production in patients with hepatic disease is a likely explanation for this anomaly. This postulated mechanism is based on a presentation of the biology of creatinine formation.

Nomogram for estimating creatinine clearance.

Several methods have been published for estimating creatinine clearance from serum creatinine concentrations. Such estimates of creatinine clearance are widely used for dosage adjustments of drugs which are primarily eliminated through the kidneys in patients with reduced renal function. Most of these methods involve the use of equations, requiring a few steps of calculations. A simple and easy-to-use nomogram is presented for estimating creatinine clearance from serum creatinine concentration, plus the age, sex, and bodyweight of the individual patient. This nomogram is based on the linear relationship between creatinine clearance and the reciprocal value of the serum creatinine concentration, where the slope of this relationship is determined by the rate of creatinine production. The rate of creatinine production, however, is related to age, sex, and bodyweight. These physical characteristics are therefore used to scale the slopes of the relationships between creatinine clearance and serum creatinine concentration. The validity of the nomogram was tested in 50 consecutive hospitalised patients for which creatinine clearance was measured. There was an excellent correlation (r = 0.903) between predicted and observed creatinine clearance values.