Assessment of GFR in Patients with Cancer: A Statement from the American Society of Onco-Nephrology.

Accurate assessment of GFR is crucial to guiding drug eligibility, dosing of systemic therapy, and minimizing the risks of both undertreatment and toxicity in patients with cancer. Up to 32% of patients with cancer have baseline CKD, and both malignancy and treatment may cause kidney injury and subsequent CKD. To date, there has been lack of guidance to standardize approaches to GFR estimation in the cancer population. In this two-part statement from the American Society of Onco-Nephrology, we present key messages for estimation of GFR in patients with cancer, including the choice of GFR estimating equation, use of race and body surface area adjustment, and anticancer drug dose-adjustment in the setting of CKD. These key messages are based on a systematic review of studies assessing GFR estimating equations using serum creatinine and cystatin C in patients with cancer, against a measured GFR comparator. The preponderance of current data involving validated GFR estimating equations involves the CKD Epidemiology Collaboration (CKD-EPI) equations, with 2508 patients in whom CKD-EPI using serum creatinine and cystatin C was assessed (eight studies) and 15,349 in whom CKD-EPI with serum creatinine was assessed (22 studies). The former may have improved performance metrics and be less susceptible to shortfalls of eGFR using serum creatinine alone. Since included studies were moderate quality or lower, the American Society of Onco-Nephrology Position Committee rated the certainty of evidence as low. Additional studies are needed to assess the accuracy of other validated eGFR equations in patients with cancer. Given the importance of accurate and timely eGFR assessment, we advocate for the use of validated GFR estimating equations incorporating both serum creatinine and cystatin C in patients with cancer. Measurement of GFR via exogenous filtration markers should be considered in patients with cancer for whom eGFR results in borderline eligibility for therapies or clinical trials.

Assessment of renal function in persons with motor complete spinal cord injury-cystatin C as an accurate single marker.

STUDY DESIGN: Observational cohort. AIM: To show that Cystatin C is an accurate single marker to estimate GFR in motor complete persons with SCI. OBJECTIVES: To assess if Cystatin C is an accurate for estimating GFR in persons with SCI with no preserved motor power. To study if use of Serum creatinine for estimation of GFR in this population significantly overestimates GFR, thereby inaccurate. SETTING: Tertiary care hospital and Medical College, Vellore, South India. METHODS: 30 persons with SCI (ASIA A and B) fulfilling the inclusion criteria were recruited. Serum Creatinine and Serum Cystatin C values were obtained, and eGFR was calculated based on available formulae. 24-h urine for urine creatinine clearance-based eGFR was used as a reference value. RESULTS: Analysis with a Bland-Atman plot showed that eGFR estimated with Serum Cystatin C was more accurate than Serum Creatinine, using 24-h urine creatinine as a reference value. eGFR using Serum Creatinine significantly overestimated GFR by over 50.6%. Estimated GFR using Serum Cystatin C showed a meager mean difference of 0.5% from the reference 24-h urine creatinine clearance (mean difference of -2.56%). CONCLUSION: Serum Cystatin C is a much more accurate marker for estimating GFR in SCI, compared to serum Creatinine which overestimates GFR.

Assessment of the 2023 European Kidney Function Consortium (EKFC) equations in a Chinese adult population.

OBJECTIVES: The European Kidney Function Consortium (EKFC) developed two novel equations in 2023 for estimating glomerular filtration rate (GFR): one sex-free cystatin C-based equation (EKFCCys) and one creatinine-cystatin C combined equation (EKFCCr-Cys). This study compared their performance with the previous creatinine-based EKFC equation (EKFCCr) and commonly used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study (BIS) equations in Chinese adults. METHODS: A total of 2,438 Chinese adults (mean age=53.04 years) who underwent the 99mTc-DTPA renal dynamic imaging for reference GFR (rGFR) were included. Diagnostic value was evaluated using correlation coefficients, sensitivity, specificity, and area under the receiver operating characteristic curve (ROCAUC). Performance was assessed in terms of bias, precision (interquartile range of the median difference [IQR]), accuracy (percentage of estimates ±30 % of rGFR [P30], and root-mean-square error [RMSE]) across age, sex, and rGFR subgroups. Gender differences in bias and P30 were also analyzed. RESULTS: Average rGFR was 73.37 mL/min/1.73 m2. EKFC equations showed stronger correlations and larger AUCs compared to the parallel CKD-EPI equations, with EKFCCr-Cys demonstrating the greatest improvement (R=0.771, ROCAUC=0.913). Concerning bias, precision, and accuracy, EKFC equations consistently outperformed CKD-EPI equations. EKFCCr-Cys and EKFCCr performed acceptably well in the entire population and were equivalent to BIS equations in the elderly. All equations, including EKFCCys, showed similar P30 accuracy across sexes. CONCLUSIONS: EKFC equations provided a reasonable alternative for estimating GFR in the Chinese adult population. While EKFCCys did not outperform EKFCCr, EKFCCr-Cys improved the accuracy of single-marker equations.

Toward Equitable Kidney Function Estimation in Critical Care Practice: Guidance From the Society of Critical Care Medicine's Diversity, Equity, and Inclusion in Renal Clinical Practice Task Force.

OBJECTIVES: Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. DATA SOURCES: Literature review and expert consensus. STUDY SELECTION: English language publications evaluating GFR assessment and racial disparities. DATA EXTRACTION: We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. DATA SYNTHESIS: Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. CONCLUSIONS: The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.

Association between socioeconomic position and cystatin C in the Heinz Nixdorf Recall Study.

Social inequalities in health and disease are well studied. Less information is available on inequalities in biomarker levels indicating subclinical stages of disease such as cystatin C, an early diagnostic marker of renal dysfunction and predictor for cardiovascular disease. We evaluated the relationship between cystatin C, socioeconomic position (SEP) and established cardiovascular risk factors in a population-based study. In 4475 men and women aged 45-75 years participating in the baseline examination of the Heinz Nixdorf Recall Study cystatin C was measured from serum samples with a nephelometric assay. SEP was assessed by education and household income. Linear regression models were used to analyse the association between SEP and cystatin C as well as the impact of cardiovascular risk factors (i.e., body mass index, blood pressure, blood glucose, diabetes mellitus, blood lipids, C-reactive protein, smoking) on this association. After adjustment for age and sex cystatin C decreased by 0.019 mg/l (95% confidence interval (CI) - 0.030 to - 0.008) per five years of education. While using a categorical education variable cystatin C presented 0.039 mg/l (95% CI 0.017-0.061) higher in men and women in the lowest educational category (≤ 10 years of education) compared to the highest category (≥ 18 years). Concerning income, cystatin C decreased by 0.014 mg/l (95% CI - 0.021 to - 0.006) per 1000 € after adjustment for age and sex. For men and women in the lowest income quartile cystatin C was 0.024 mg/l (95% CI 0.009-0.038) higher compared to the highest income quartile. After adjusting for established cardiovascular risk factors the observed associations were substantially diminished. Social inequalities seem to play a role in subclinical stages of renal dysfunction, which are also related to development of cardiovascular disease. Adjustment for traditional cardiovascular risk factors showed that these risk factors largely explain the association between SEP and cystatin C.

Assessment of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker on the split renal function in the patients with primary hypertension.

ABSTRACT: Bilateral kidney damage in hypertensive patients is not parallel. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), as a commonly used antihypertensive drug, could protect kidney function and delay its deterioration. Most studies focused on overall renal function, but the researches on split renal function (SRF) are rare. We investigated the effects of ACEI/ARB on the SRF in patients with primary hypertension.Patients with primary hypertension (n = 429; male: 213; female: 216) admitted to our department between January 2014 and December 2016 were included in this study. The glomerular filtration rate (GFR) of split and total renal function were determined using diethylenetriaminepentaacetic acid tagged with 99mTc renal dynamic imaging method. For the same patient, the side with high GFR was considered as higher GFR kidney, whereas that with a low GFR was considered as lower GFR kidney. The split function score (Q value) was utilized to evaluate the differences of bilateral renal function. The patients were divided into 3 groups based on the Q values (Group 1, Q value <5%; Group 2, Q value of 5%-10%; Group 3, Q value ≥10%). All the patients received antihypertensive therapy based on ACEI/ARB. The renal dynamic imaging was performed in the 1-year follow-up to investigate the changes of the SRF.Compared with the baseline level, significant decline was noticed in the serum creatinine (Scr) in Group 2 and Group 3 (P < .05). The cystatin C in Group 3 showed significant decline (P < .05). Compared with the baseline, there was significant decline in the Q value in Group 2, whereas the GFR of lower GFR kidney showed significant increase (P < .05). No statistical differences were noticed in the Q value and split GFR in Group 1 and Group 3 (P > .05).In primary hypertension patients, ACEI/ARB therapy could improve the SRF of lower GFR kidney in the presence of certain differences between the SRF. As a result, the SRF difference was reduced. In case of Q value in a range of 5% to 10%, ACEI/ARB could improve the renal function effectively. It may be significant for the design of antihypertensive drugs.

Population Pharmacokinetic Analysis and Dosing Optimization Based on Unbound Daptomycin Concentration and Cystatin C in Nonobese Elderly Patients with Hypoalbuminemia and Chronic Kidney Disease.

PURPOSE: This study evaluated the population pharmacokinetics of daptomycin in nonobese elderly patients with hypoalbuminemia and chronic kidney disease (CKD) using the glomerular filtration rate estimated from cystatin C (eGFRcys) and estimated its optimal dose. METHODS: We performed population pharmacokinetic analysis of the unbound concentrations of daptomycin. The probability of target attainment of 90% for achieving an area under the concentration-time curve of unbound daptomycin at steady state/ minimum inhibitory concentration ratio of ≥66.6 was stochastically simulated. RESULTS: In the population pharmacokinetic analysis of 25 patients aged ≥65 years, the two-compartment model using eGFRcys and age as covariates of clearance in central compartment of unbound daptomycin were optimal. The unbound fraction rate (fu) was 0.05-0.14. According to the Monte Carlo simulation, the optimal doses for patients with eGFRcys of 20-60 mL/min and aged 65-95 years were calculated as 200-500 mg q24h. CONCLUSION: These results suggest that establishing the dose using total concentrations may result in under- or overestimation caused by alterations in fu. The optimal dose for nonobese elderly patients with hypoalbuminemia and CKD depends on eGFRcys and age, and a standard dose may be insufficient for some patients.

[Assessment of Renal Function and Simulation Using Serum Cystatin-C in an Elderly Patient with Uncontrollable Plasma Vancomycin Levels Due to Muscular Dystrophy: A Case Report].

Herein, we describe a case of an elderly patient with muscular dystrophy for whom control of the plasma vancomycin (VCM) concentration proved difficult when he developed a catheter-related bloodstream infection. The pharmacist initially carried out therapeutic drug monitoring using an estimate of the creatinine clearance (CLcr) level, which was based on the serum creatinine (SCr) and serum cystatin-C (CysC) levels, but was ultimately unable to control the plasma VCM concentration. Therefore, the plasma VCM concentration was predicted ex post facto using population pharmacokinetic parameters as a covariate; that is, directly including the glomerular filtration rate (GFRCysC) estimated from the CysC level, which is not affected by the muscle mass. As a result, the estimated VCM concentration was closer to the actual concentration than that predicted using CLcr. Furthermore, the results of examining the predictive accuracy according to the assessment of renal function at the time of initial VCM administration suggested that estimation of the trough concentration using GFRCysC might be useful in elderly patients with muscular dystrophy.

Assessment of cystatin C in pediatric sickle cell disease and ß-thalassemia as a marker of subclinical cardiovascular dysfunction: a case-control study.

Cardiovascular complications represent the main determinant of survival in patients with hemoglobinopathies. Serum cystatin C is a well-known marker of nephropathy in sickle cell disease (SCD) and ß-thalassemia patients that has recently emerged as a strong predictor of cardiovascular dysfunction in patients with and without kidney disease. We performed a case control study to determine the role of cystatin C as a predictor of subclinical cardiovascular dysfunction in SCD and ß-thalassemia patients. We enrolled 40 SCD patients with a mean age of 12.4 years, 40 ß-thalassemia patients with a mean age of 11.4 years and 40 age and sex-matched controls. We assessed hematological profile, serum ferritin, urinary albumin-creatinine ratio (UACR), serum cystatin C, echocardiography and carotid intima media thickness (CIMT). UACR, cystatin C and CIMT were higher in SCD and ß-thalassemia patients compared to controls (p < .001). Significantly higher cystatin C levels were observed in SCD and ß-thalassemia patients with nephropathy or left ventricular systolic dysfunction (shortening fraction <30%, or ejection fraction <55%; p < .001). Moreover, SCD patients with pulmonary hypertension had significantly higher cystatin C levels. Cystatin C levels were positively correlated with CIMT in SCD (p = .02) and ß-thalassemia patients (p < .001) while negatively correlated with ejection fraction and shortening fraction (p < .001). The cutoff values of cystatin C ≥ 16.03 and ≥ 13.2 (ng/mL) could detect subclinical cardiac dysfunction risk among SCD and ß-thalassemia patients respectively. Cystatin C appears to be a promising marker for subclinical cardiovascular dysfunction in SCD and ß-thalassemia patients.

Assessment of renal function using cystatin C and creatinine in Saudi patients after transplantation.

Background: Rapid and accurate assessment of kidney function in patients after transplantation is of utmost importance. The aim of this study was to compare the relationships of serum creatinine and serum cystatin C with an estimated glomerular filtration rate (eGFR) in kidney transplants Saudi patients after a certain period of transplantation. Materials and Methods: In this prospective study, 127 patients were categorized into three groups based on their length of survival after kidney transplantation; <1 year, from 1 to 5 years, and above 5 years after transplantation. Results of cystatin C and creatinine levels were compared by eGFR derived from estimation equation chronic kidney disease epidemiology collaboration. Results: In the three assessed periods, the mean (standard deviation) cystatin C level was 1.72 (0.57), 1.59 (0.64), and 1.82 (0.82), respectively, being highest after 5 years of transplantation, normal in 9.40%, and elevated in 90.60% of the participants, while creatinine level, decreased from 1.57 (0.53) to 1.52 (0.64) in 1-5 years, then it became the highest at 1.75 (0.69) in more than 5 years. The mean was normal in 21.30% and elevated in 78.70% of the patients. Both serum creatinine and cystatin C levels were negatively correlated with posttransplantation time in kidney transplant patients. Conclusion: The cystatin C level was statistically significantly higher after 5 years of transplantation. It is a better parameter to rule out renal dysfunction after transplantation.

Résumé Une évaluation rapide et précise de la fonction rénale chez les patients après une transplantation est de la plus importance. Le but de cette étude était de comparer les relations de la créatinine et de la cystatine C sérique avec un taux de filtration glomérulaire estimé (DFG) chez des patients saoudiens transplantés rénaux après une certaine période de transplantation. Matériel et méthodes: Dans cette étude prospective, 127 patients ont été classés en trois groupes en fonction de leur durée de survie après une transplantation rénale; <1 an, de 1 à 5 ans et plus de 5 ans après la transplantation. Les résultats des taux de cystatine C et de créatinine ont été comparés par le DFG dérivé de l'équation d'estimation de la collaboration épidémiologique sur les maladies rénales chroniques. Résultats: Au cours des trois périodes évaluées, le taux moyen (écart-type) de cystatine C était de 1,72 (0,57), 1,59 (0,64) et 1,82 (0,82), respectivement, étant le plus élevé après 5 ans de transplantation, normal dans 9,40% et élevé chez 90,60% des participants, tandis que le niveau de créatinine est passé de 1,57 (0,53) à 1,52 (0,64) en 1 à 5 ans, puis il est devenu le plus élevé à 1,75 (0,69) en plus de 5 ans. La moyenne était normale chez 21,30% et élevée chez 78,70% des patients. Les taux sériques de créatinine et de cystatine C étaient corrélés négativement avec le temps post-transplantation chez les patients transplantés rénaux. Discussion: Le taux de cystatine C était significativement plus élevé après 5 ans de transplantation. C'est un meilleur paramètre pour exclure un dysfonctionnement rénal après une transplantation.

Assessment of kidney function using inulin-based and estimated glomerular filtration rates before and after allogeneic hematopoietic stem cell transplantation in pediatric patients.

BACKGROUND: Accurate evaluation of kidney function before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for both informed decision making and detection of chronic kidney disease. However, to the best of our knowledge, no report has evaluated the glomerular filtration rate (GFR) in pediatric patients who underwent HSCT using the gold standard GFR measurement, as well as inulin-based GFR (iGFR). METHODS: We assessed iGFR before and after allo-HSCT to evaluate the impact of allo-HSCT on GFR in a prospective cohort study of 17 pediatric patients. We also assessed the accuracy and bias of the values of estimated GFR (eGFR) calculated using serum creatinine (Cr), cystatin C (CysC), beta-2 microglobulin (ß2 MG), 24-h creatinine clearance (24hCcr), and the full chronic kidney disease in children (CKiD) index that combines Cr, CysC, and blood urea nitrogen-based equations with iGFR as a reference to identify the most reliable equation for GFR. RESULTS: There was no significant difference between the values before and after allo-HSCT. CKiD CysC-, 24hCcr-, and full CKiD-based values showed good within 30% (P30) accuracy (80.6%, 79.3%, and 80.6%, respectively), but only 24hCcr and full CKiD had good mean bias (8.5% and 8.9%, respectively) and narrow 95% limits of agreement (-32.2 to 52.7 mL/min/1.73 m2 and -29.3 to 47.4 mL/min/1.73 m2 , respectively) compared with the corresponding iGFR. CONCLUSION: There was no significant impact of allo-HSCT on GFR in our cohort. The most reliable equations for pediatric patients with allo-HSCT were eGFR-24hCcr and eGFR-full CKiD.

Cystatin C- Versus Creatinine-Based Assessment of Renal Function and Prediction of Early Outcomes Among Patients With a Left Ventricular Assist Device.

BACKGROUND: Estimated glomerular filtration rate (eGFR) based on serum creatinine (sCr) improves early after left ventricular assist device (LVAD) implantation but subsequently declines. Although sCr is a commonly accepted clinical standard, cystatin C (CysC) has shown superiority in assessment of renal function in disease states characterized by muscle wasting. Among patients with an LVAD, we aimed to (1) longitudinally compare CysC-eGFR and sCr-eGFR, (2) assess their predictive value for early postoperative outcomes, and (3) investigate mechanisms which might explain potential discrepancies. METHODS: A prospective cohort (n=116) with CysC and sCr concurrently measured at serial time points, and a retrospective cohort (n=91) with chest computed tomography performed within 40 days post-LVAD were studied. In the prospective cohort, the primary end point was a composite of in-hospital mortality, renal replacement therapy, or severe right ventricular failure. In the retrospective cohort, muscle mass was estimated using pectoralis muscle area indexed to body surface area (pectoralis muscle index). RESULTS: In the prospective cohort, sCr-eGFR significantly improved early post-LVAD and subsequently declined, whereas CysC-eGFR remained stable. CysC-eGFR but not sCr-eGFR predicted the primary end point: odds ratio per 5 mL/(min·1.73 m2) decrease 1.16 (1.02-1.31) versus 0.99 (0.94-1.05). In retrospective cohort, for every 5 days post-LVAD, a 6% decrease in pectoralis muscle index was observed (95% CI, 2%-9%, P=0.003). After adjusting for time on LVAD, for every 1 cm2/m2 decrease in pectoralis muscle index, there was a 4% decrease in 30-day post-LVAD sCr (95% CI, 1%-6%, P=0.004). CONCLUSIONS: Initial improvement in sCr-eGFR is likely due to muscle wasting following LVAD surgery. CysC may improve assessment of renal function and prediction of early postoperative outcomes in patients with an LVAD.

The Value of a Cystatin C-based Estimated Glomerular Filtration Rate for Cardiovascular Assessment in a General Japanese Population: Results From the Iwate Tohoku Medical Megabank Project.

BACKGROUND: Epidemiological studies have shown that high circulating cystatin C is associated with a risk of cardiovascular disease (CVD) independent of creatinine-based renal function measurements. The present study investigated the comparison between the cystatin C-based estimated glomerular filtration rate (GFRcys) and creatinine-based GFR (GFRcr) to determine whether these measurements are associated with CV biomarkers and elevated CVD risk in a general Japanese population. METHODS: The Iwate Tohoku Medical Megabank Organization pooled individual participant data from a general population-based cohort study in Iwate prefecture (n = 29,375). Chronic kidney disease (CKD) was estimated using the GFRcys, GFRcr and the urine albumin-to-creatinine ratio (UACR). RESULTS: The prevalence of CKD in the participants was found to be higher based on the GFRcr than the GFRcys. Multiple variable analyses after adjusting for baseline characteristics showed that high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with the GFRcys. The area under the receiver operating characteristic (AUROC) curve for identifying individuals with a high Suita score was higher for the GFRcys (AUROC = 0.68) than it was for the GFRcr (AUROC = 0.64, P < 0.001). The GFRcys provided reclassification improvement for the CVD risk prediction model by the GFRcr (net reclassification improvement = 0.341; integrated discrimination improvement = 0.018, respectively, P < 0.001). CONCLUSIONS: The GFRcys is more closely associated with CV biomarkers, including hs-cTnT and NT-proBNP levels, and a high Suita score than the GFRcr, and it provides additional value in the assessment of CVD risk using GFRcr.

Geriatric assessment of estimated glomerular filtration rate: a cross-sectional study.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is routinely calculated based on the serum creatinine level. However, the validity of such calculation in the geriatric population has not been sufficiently assessed. To examine whether the discrepancies between the eGFR determined based on the serum creatinine (eGFRcr) and that based on the serum cystatin C (eGFRcys) may be influenced to a lesser degree, by factors such as aging and muscle mass. METHODS: We measured the cystatin C and creatinine levels in 19,764 subjects (mean 77.0 years) and the eGFRcys and eGFRcr using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Japanese, and Berlin Invitation Study (BIS) equations were calculated. RESULTS: The mean measured eGFRcys and eGFRcr values by the CKD-EPI equation were 48.2 and 66.6 ml/min/1.73 m2 body surface area, respectively. The correlation between the eGFRcr (x) and eGFRcys (y) was y = 0.728x (r = 0.867; p < 0.001). Analysis of the slope among all ages could be shown by the relation, eGFRcys = (0.43 + 0.33/(1 + 10^((82-age)* - 0.046)))*eGFRcr. The correlation between the eGFRcr and eGFRcys by the Japanese equation were also similar. However, when it was calculated by the BIS equation, no drop of the slope of the linear regression line was observed with age. CONCLUSIONS: The eGFRcr was overestimated irrespective of whether the CKD-EPI or the Japanese equation was used. We could convert eGFRcr into eGFRcys by an equation using age. Estimation of eGFR including serum cystatin C was more accurate in elderly people.

Assessment of renal function in living kidney donors before and after nephrectomy: A Japanese prospective, observational cohort study.

OBJECTIVE: To investigate the utility of estimated glomerular filtration rate for assessing kidney function in living kidney donors before and after nephrectomy. METHODS: A total of 101 donors underwent inulin clearance measurements before and 1 year after nephrectomy. The mean of three inulin clearance values was used as the measured glomerular filtration rate. Estimated glomerular filtration rate based on serum creatinine and cystatin C levels was calculated using the Japanese estimated glomerular filtration rate equation, Chronic Kidney Disease Epidemiology Collaboration formula and new full age spectrum equation. Age-adjusted chronic kidney disease was defined as glomerular filtration rate <75 mL/min/1.73m2 for donors aged <40 years, <60 mL/min/1.73m2 for donors aged 40-65 years and <45 mL/min/1.73m2 for donors aged >65 years. RESULTS: The postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rate were 36.0% and 27.0%, respectively. In younger donors (aged <50 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rates were 5.3% and 26.3%, respectively. In older donors (aged >70 years), postoperative measured glomerular filtration rate <60 mL/min/1.73m2 and age-adjusted chronic kidney disease rates were 75.0% and 33.3%, respectively. Donor age and measured glomerular filtration rate were significant predictors of postoperative measured glomerular filtration rate. The Japanese estimated glomerular filtration rate equation based on creatinine and cystatin C showed the strongest correlation with measured glomerular filtration rate. However, the Japanese estimated glomerular filtration rate equation based on creatinine overestimated the prevalence of measured glomerular filtration rate <60 mL/min/1.73m2 , whereas the Japanese estimated glomerular filtration rate based on cystatin C underestimated it. CONCLUSIONS: Aged donors might have an increased risk of lower glomerular filtration rate after donor nephrectomy; post-surgery, long-term monitoring of renal function is recommended. Measurement of glomerular filtration rate should be carried out for donors, especially pre-surgery. A more precise glomerular filtration rate equation is required in the future.

A population pharmacokinetic model of vancomycin for dose individualization based on serum cystatin C as a marker of renal function.

OBJECTIVES: This study aimed to establish a vancomycin population pharmacokinetics (PPK) model based on serum cystatin C and to optimize dosing for achieving targeted steady-state trough concentrations (Css ) of 10-15 and 15-20 mg/l. METHODS: Patients aged ≥18 years were prospectively enrolled. A vancomycin PPK model was built with glomerular filtration rate (GFR) as a renal covariate estimated by cystatin C. A new group of patients were used for external evaluation. PPK analysis and Monte Carlo simulations were performed using nonlinear mixed effect modelling programme. KEY FINDINGS: Two hundreds of patients with 514 samples were included. The final model was CL (L/h) = (5.07 × (GFR/105.5)0.524 × (AGE/48.5)-0.309 × (WT/60)0.491 ); V (l) = 46.3. Internal and external evaluations demonstrated good stability and predictability. The average probability of target attainment (PTA) of optimal dosing regimens for targeted Css achieving 10-15 and 15-20 mg/l were 51.2% and 40.6%, respectively. An average PTA ≥71% for targeted concentration of 10-20 mg/l was obtained. CONCLUSIONS: A vancomycin PPK model with cystatin C as the renal marker has good stability and predictability. The new proposed dosing regimens were predicted to achieve a good PTA.

Multivariable models using administrative data and biomarkers to adjust for case mix in the ICU.

BACKGROUND: Routinely collected laboratory biomarkers could improve control of confounding from disease severity in non-interventional studies of general intensive care unit (ICU) patients. Their ability to predict both short- and long-term mortality was evaluated. METHODS: The performance of age, sex, Charlson co-morbidity index, and baseline values of ten predefined blood biomarkers as predictors of 30-day and 1-year mortality was evaluated in 5505 general ICU stays. RESULTS: Regression models based on age, sex, Charlson index, and biomarkers were somewhat less accurate in predicting 30-day mortality (c-index 0.83, Brier score 0.27) compared to the SAPS II score (c-index = 0.88, Brier score = 0.09) and in predicting 1-year mortality (c-index = 0.82, Brier score = 0.31) compared to the SAPS II score (c-index = 0.85, Brier score = 0.13). Cystatin C improved predictive ability slightly compared to creatinine, but age and Charlson comorbidity index were more important predictors. Using multiple imputation to replace missing biomarker values notably improved predictive ability of the models. CONCLUSIONS: Automatically collected baseline variables are almost as predictive of both short- and long-term mortality in general ICU patients, as the SAPS II score. This can facilitate internal control of confounding in non-interventional studies of mortality using administrative data.

A new diagnostic index for sarcopenia and its association with short-term postoperative complications in patients undergoing surgery for colorectal cancer.

AIM: Sarcopenia is a robust prognostic indicator of outcomes after surgery for colorectal cancer (CRC). However, there are no serum markers routinely available for estimating skeletal muscle mass (SMM). The present study aimed to describe a new sarcopenia index (SI), serum creatinine (Scr) × cystatin C-based glomerular filtration rate, and investigate its association with short-term complications after curative resection of CRC. METHOD: Consecutive patients who underwent curative resection of CRC from December 2011 to January 2017 were retrospectively identified. Skeletal muscle cross-sectional area was analysed on L3 computed tomographic images. Receiver operating characteristic curve analysis showed that the cutoff points of SI for sarcopenia were below 56.1 in men and below 43.7 in women. Patients were classified into low and high SI groups in accordance with these cutoff values. The association between SI and body composition and the impact of preoperative SI on postoperative outcomes were analysed. RESULTS: Among 417 patients, SI showed a stronger correlation with skeletal muscle area (SMA) (r = 0.537, P < 0.001) than with the Scr/cystatin C ratio (r = 0.469, P < 0.001) and Scr (r = 0.447, P < 0.001). The low SI group had a lower SMA, lower preoperative haemoglobin, a higher prevalence of sarcopenia and experienced more postoperative complications compared with the high SI group (all P < 0.001). Multivariate logistic regression analysis showed that the independent risk factors for overall complications were low preoperative haemoglobin, low SI, sarcopenia and American Society of Anesthesiologists grade ≥ 3. CONCLUSION: This new SI is a simple and useful surrogate marker for estimating SMM, and is associated with outcomes after CRC surgery.