Overestimation Of Renal Function Research Articles

Factors influencing glomerular filtration rate as estimated using preoperative creatinine and cystatin C levels.

Estimated glomerular filtration rate (eGFR) using serum creatinine (Cr) is commonly used to evaluate renal function. However, it can be influenced by other factors, which can risk the overestimation of the true GFR. Impaired renal function prior to cardiovascular surgery reportedly increases mortality and the incidence of postoperative complications. Thus, overestimation of renal function may affect the assessment of postoperative complication risks. Therefore, we aimed to compare the eGFR calculated from serum Cr and cystatin C (Cys-C) levels to assess preoperative renal function and to investigate factors affecting renal function overestimation. 88 patients admitted for cardiovascular surgery who had preoperative serum Cr and Cys-C measurements were included in the study. Correlations between factors associated with eGFR calculated from serum Cr (eGFRcre) and Cys-C (eGFRcys) and their ratio (eGFRcre/eGFRcys) were examined using multiple regression analysis. Multiple regression analysis revealed that eGFRcre/eGFRcys was significantly negatively correlated with the Short Physical Performance Battery score (SPPB). A clinically significant difference in renal function overestimation was defined as GFRcre/eGFRcys > 1.2, with a cutoff value of 9 points for the SPPB score. The chair stand test, a component of the SPPB, had the same discriminative power as the SPPB for identification of renal function overestimation. The SPPB can be used to identify likely GFR overestimation in patients. Additionally, the chair stand test may be used as an alternative to the SPPB for the identification of renal function overestimation when the SPPB is difficult to perform.

Carboplatin dose calculations for patients with lung cancer: significant dose differences found depending on dosing equation choice

BackgroundCarboplatin is the backbone cytotoxic agent for many chemotherapy regimens for lung cancer. Dosing of carboplatin is complicated due to its relationship to renal function and narrow therapeutic index. Overestimation of renal function may lead to supratherapeutic dosing and toxicity, while underestimation may lead to underdosing and therapeutic failure. Although the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have higher accuracy in estimating glomerular filtration rate (eGFR), the Cockcroft Gault (CG) formula has been historically used for carboplatin dosing internationally.MethodsWe compared these formulae to identify patient profiles that were associated with significant carboplatin dose variation by retrospectively analysing the carboplatin dosing of 96 patients with lung cancer. Carboplatin doses were calculated using eGFR generated by MDRD, CKD-EPI 2009 and CKD-EPI 2021 equations. These three hypothetical doses were compared to actual CG-based doses prescribed.ResultsMDRD and CKD-EPI equations resulted in comparable carboplatin doses; however, CG doses diverged markedly with up to 17% of the patients receiving a carboplatin dose that was at least 20% higher than a non-CG formula would have predicted, and 20% received a dose that was at least 20% lower than a non-CG formula would have predicted. Our data suggest CG use overestimates kidney function in patients with a higher bodyweight and body surface area (BSA) while underestimating it in patients with a lower bodyweight and BSA. Importantly, we demonstrate potential real-world benefit as CKD-EPI predicted lower doses for patients whose (CG-derived) carboplatin dose was later reduced following clinical assessment prior to infusion.ConclusionsWe have therefore confirmed significant differences in carboplatin dosing depending on the equation used in our modern patient population and suggest that use of CKD-EPI provides the most clinically appropriate carboplatin dosing and should be implemented as the new standard of care internationally.

Changes in the estimated renal function after hepatitis C virus eradication with direct-acting antiviral agents: Impact of changes in skeletal muscle mass.

Hepatitis C virus (HCV) infection can cause renal dysfunction, expected to improve upon HCV eradication. However, adverse effects of HCV eradication using direct-acting antiviral agents (DAAs) on renal function have been recently reported. This retrospective study aimed to evaluate renal function with glomerular filtration rate (eGFR) estimated using creatinine (eGFRcre) and cystatin C (eGFRcys). Complete clinical information and preserved serum samples were collected from 207 patients with HCV infection treated with interferon-free DAA at baseline and SVR48 (SVR48). Patients who underwent paired computed tomography (CT) at baseline and ≥12months after DAA were evaluated for changes in skeletal muscle mass using the psoas muscle mass index (PMI). eGFRcre significantly worsened at SVR48, while eGFRcys was similar at baseline and SVR48. At baseline, eGFRcre was significantly higher than eGFRcys; eGFRcre and eGFRcys were similar at SVR48. Multivariate analysis revealed that the presence of liver cirrhosis and low-albumin level, as well as cirrhosis and age, was significantly associated with the overestimation of renal function by eGFRcre at baseline and SVR48, respectively. In the 57 patients who underwent paired CT at baseline and≥12months after DAA, relative values of PMI significantly increased after DAA. After DAA, in patients with increased PMI (65% 37/57), eGFRcre significantly worsened but did not change in patients without increased PMI. eGFRcre significantly worsened after DAAs; however, this might not reflect accurate changes in renal function, partially because of changes in skeletal muscle mass. eGFRcys did not change after DAAs, and it is a potential alternative to eGFRcre.

Overestimation of Renal Function by Creatinine-derived Estimated Glomerular Filtration Rate Correlates with the Loss of Appendicular Skeletal Muscle Index in Amyotrophic Lateral Sclerosis Patients (P4.446)

Overestimation of Renal Function by Creatinine-derived Estimated Glomerular Filtration Rate Correlates with the Loss of Appendicular Skeletal Muscle Index in Amyotrophic Lateral Sclerosis Patients (P4.446)

Are the equations for the creatinine-based estimated glomerular filtration rate applicable to the evaluation of renal function in Japanese children and adult patients receiving chemotherapy?

Equations for the creatinine-based estimated glomerular filtration rate (eGFR) were recently established for Japanese adults (>18 years old) and children (2-11 years old), respectively, but it is unclear whether eGFR can be as useful as 24-h creatinine clearance (CCr) for assessing renal function in patients receiving chemotherapy. This study examined the degree of concordance between eGFR and CCr and the risk factors leading to the overestimation of renal function by eGFR. A total of 53 data points of 19 children and 56 data points of 16 adults who received chemotherapy were analyzed retrospectively. Body mass index, serum creatinine concentration, 24-h urinary creatinine excretion (UCr), and nephrectomy were considered as risk factors for overestimation by eGFR. In the pediatric part of the study, 7 data points from 3 patients who underwent nephrectomy were included. The eGFR in patients with bilateral kidneys overestimated renal function to a greater degree than in patients with a unilateral kidney. In 45.7 % of pediatric patients with bilateral kidneys and in 19.6 % of adult patients, eGFR overestimated renal function. The risk factor for overestimation was lower UCr in pediatric patients with bilateral kidneys and adult patients. Concordance between eGFR and CCr in pediatric patients with a unilateral kidney should be assessed separately from that in patients with bilateral kidneys. In restricting calculation of eGFR to pediatric patients with bilateral kidneys and adult patients without little muscle mass, eGFR may be useful regardless of whether patients are receiving chemotherapy.

More Evidence that Cystatin C Predicts Mortality Better than Creatinine

The main clinical benefit of estimating renal function in the general population is to identify and treat patients at risk for developing ESRD, cardiovascular events, and death.1 Unfortunately, the most widely used equations to estimate GFR are limited, in part, by their reliance on serum creatinine as the filtration marker (estimated GFR [eGFR]). The Modification of Diet in Renal Disease (MDRD) equation, for example, overestimates renal function among individuals with low muscle mass and underestimates it among those with GFR >60 ml/min per 1.73 m2.2–4 The use of serum cystatin C, a cysteine protease inhibitor that is freely filtered by the glomerulus, has potential advantages over creatinine as a filtration marker in that its production is not dependent on muscle mass.2 As a result, cystatin C offers opportunities to estimate GFR more accurately than creatinine-based equations and additionally may predict worsening kidney function even when the GFR is actually near the normal range.5 Beyond the relationship to measured GFR, cystatin-C–derived eGFR (ecGFR) was a better predictor of mortality than creatinine-based estimates in a study of elderly individuals6; however, the ability to generalize these findings to a younger and broader set of individuals is unknown. In this issue of JASN , Astor et al. 7 extend previous observations and demonstrate convincingly that ecGFR predicts mortality more accurately than the MDRD equation in a sample from the general population in the United States. If replicated, then these findings should spur trials to determine whether the use of cystatin C improves patient outcomes by identifying those with an elevated risk for death, both within and outside the setting of diagnosed chronic kidney disease (CKD). Astor et al. 7 focus on the relationship of ecGFR to mortality, but it is instructive to examine the …

Use of aminoglycosides in elderly patients. Pharmacokinetic and clinical considerations.

Aminoglycosides still represent a mainstay in the treatment of serious infections caused by Gram-negative bacilli in elderly patients. The aging process is accompanied by various physiological changes (e.g. alterations in body composition, impairments in certain organ functions), which may affect drug disposition and, subsequently, drug action. For aminoglycosides that are eliminated by the renal route, kidney function is the key parameter that should be taken into account when dosage regimens are calculated. Because there is a progressive decline in renal function with aging, the glomerular filtration rate should be estimated for each patient. Any change in creatinine clearance (CLCR) should result in a proportional correction of the dosage regimen. Such individualised dosage of aminoglycosides is particularly important because of their narrow therapeutic indices. There are no conclusive data which indicate that age per se affects the elimination of aminoglycoside antibiotics. Overdosage may result from overestimation of renal function if crude serum creatinine (SCr) levels are used as a guide. Nomograms for the relationship between SCr and CLCR have been developed. However, nomograms should be used with caution because substantial interindividual variability in the plasma concentration-clearance relationship is still observed. Therefore, the choice of a maintenance dose based on an assessment of renal function, which change rapidly, should always be considered as preliminary, and verification by serum concentration measurements is necessary. As a result, the use of aminoglycoside serum concentration monitoring during therapy as the most important guide for dosage adjustment is particularly important in the elderly, and is indispensable in conjunction with frequent assessment of renal function. Although a matter of debate, the value of serum concentration monitoring has been demonstrated. With traditional multiple daily dosage, monitoring peak and trough concentrations has been recommended. For once daily dosage, however, no guidelines relating to therapeutic and/or toxic concentrations are available yet. In the meantime, we recommend monitoring at least trough concentrations. Once daily administration of aminoglycosides has emerged as a new mode of treatment. Compared with multiple daily administration, once daily dosage may have a number of advantages, and many clinical trials comparing the efficacy or safety of both modes have shown either superiority or equivalence of the new mode in most indications. At present, however, no data from studies of once daily administration in young compared with elderly adults are available.

Extended Measurement of Glomerular Filtration Rate and Effective Renal Plasma Flow in Ambulatory Patients

We describe a standardized clearance method over 5 h (one hour equilibration followed by eight consecutive 30 min clearance periods [period 2-9]) for the estimation of GFR (iothalamate I125) and ERPF (hippuran I131) during water diuresis in ambulatory and exercising patients. Four groups were examined. In group I (normal controls, n = 15) there were no significant changes in GFR, ERPF and FF (P > 0.10) during repeated clearance periods (mean of period 2-5 versus period 6-9). The reproducibility of the method was studied at a mean interval of 3.7 weeks in a group of patients with stable reduction of GFR (group II, n = 7). The values for GFR, ERPF, FF and RVR did not change significantly in this group, and correlated significantly between repeated studies (r = 0.81 to r = 0.99). In group III (untreated hypertensive patients with reduced GFR, n = 13) there was a time dependent 7.2% decrease in GFR (P < 0.05), significantly different from group I (P < 0.02), a 10.0% decrease in ERPF (P < 0.01) and no significant change in FF (P = 0.08) when the mean of period 2-5 was compared with the mean of period 6-9. In healthy controls (group IV, n = 8) light sustained bicycle exercise (25 W) induced a 7.1% decline in GFR (P < 0.01), 17.4% decline in ERPF (P < 0.001) and a 13.6% increase in FF (P < 0.001). We conclude that ambulatory measurements of GFR and RPF can be carried out over a period of 5 h with satisfactory precision and repeatability. Ambulatory hypertensive patients with moderately reduced GFR showed the same degree of time dependent downward drift of GFR and ERPF without exercise as was seen in healthy individuals during light exercise. Accordingly, in these groups single clearance periods imply a risk for under or overestimation of renal function, and time controls are necessary during clearance studies.

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.

Nephrotoxic antibiotics in patients with renal failures: guidelines for debilitated patients.

Fifty-seven cancer patients, who had had an 8--15% loss of body weight in the previous 6 months, were studied to establish the reliabity in wasted individuals of presently available nomograms correlating serum creatinine with creatinine clearance. Other predictors of renal function, such as osmolar clearance, free water clearance, and excreted fraction of filtered sodium, were also considered. In all patients, and especially in those with a measured creatinine clearance 10--50 ml/min, the use of standard nomograms based on serum creatinine resulted in gross overestimation of renal function. None of the other tests of renal function proved reliable for clinical purposes. It is concluded that in wasted patients administration of nephrotoxic drugs that are renally excreted should be adjusted to measured creatine clearance. Using other common predictors of renal function may result in overdosage.