Measured Creatinine Clearance Research Articles

Multiparametric renal function assessment in cirrhotic patients shows high prevalence of medically actionable changes in multiple modules.

Renal dysfunction is a common complication of cirrhosis, occurring either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. To date, no study has comprehensively assessed multiple renal function parameters in hospitalized patients with cirrhosis through a multiparametric analysis of renal biochemistry markers. We conducted a retrospective, observational study including all consecutive patients hospitalized with cirrhosis who underwent a 43-multiparametric renal function assessment between January 1, 2021, and June 30, 2023. All patients showed at least one of the following renal abnormalities: Kidney Disease: Improving Global Outcomes stage G2 or higher, sodium and/or chloride excretion fraction <1%, electrolyte-free water clearance <0.4mL/min, or tubular maximum phosphate reabsorption capacity <0.8mmol/L. The estimated glomerular filtration rate equations significantly overestimated the measured creatinine clearance with median differences of +14mL/min/1.73m2 (95% CI 6-29) and +9mL/min/1.73m2 (95% CI 2-15) for European Kidney Function Consortium equations, respectively. Notably, 54% and 39% of patients demonstrated estimated glomerular filtration rates exceeding 30% of the measured creatinine clearance when the Chronic Kidney Disease - Epidemiology Collaboration and European Kidney Function Consortium formulas were employed, respectively. Substantial discrepancies in Kidney Disease: Improving Global Outcomes stage assignments were observed between the estimated glomerular filtration rate- and measured creatinine clearance-based assessments. This study underscores the value of a multiparametric renal function assessment as a routine tool for evaluating renal function in patients with cirrhosis. A high prevalence of medically actionable renal abnormalities spanning multiple renal function modules, including alterations in glomerular function, salt and solute-free water excretion, and proximal tubule phosphate reabsorption, has been demonstrated in hospitalized patients with cirrhosis.

Abbreviated Urine Collection Compared With 24-Hour Urine Collection for Measuring Creatinine Clearance in Adult Critically Ill Patients: A Systematic Review.

To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients. We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates. After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision. Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m2. Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established. Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients.

Evaluation of kidney disease using e-GFR compared to measured creatinine clearance.

Measurement of renal function is required for diagnosis and stratification of kidney disease. GFR is considered as the best overall measure of kidney function for diagnosis and treatment of patients with CKD. Measuring GFR is time consuming and hence eGFR is calculated using equations with endogenous markers like SCr. Therefore, it is of interest to examine the accuracy of creatinine based estimates (CrCl and CG formula) of GFR among patients. Thus, 60 in-patients (30 men and 30 women) at the GVP hospital and 40 controls were enrolled in the study. SCr and 24 hrs urine creatinine are estimated using blood sample and same day 24-hr urine collection. SCr is estimated using the Kinetic Jaffe's method in Auto analyzer for serum and urine. eGFR is calculated using the CG formula for the SCr value. We evaluated the correlation between measured CrCl derived from 24-hr urine collection and calculated/predicted CrCl using the CG equations. A positive correlation was observed between measured GFR and e-GFR in case and control groups.

Continuous passive paracentesis versus large-volume paracentesis in the prevention and treatment of intra-abdominal hypertension in the critically ill cirrhotic patient with ascites (COPPTRIAHL): study protocol for a randomized controlled trial

BackgroundCritically ill patients with cirrhosis and ascites are at high risk for intra-abdominal hypertension (IAH) which increases mortality. Clinical guidelines recommend maintaining intra-abdominal pressure (IAP) below 16 mmHg; nonetheless, more than three quarters of critically ill patients with cirrhosis develop IAH during their first week of ICU stay. Standard-of-care intermittent large-volume paracentesis (LVP) relieves abdominal wall tension, reduces IAP, optimizes abdominal perfusion pressure, and is associated with short-term improvement in renal and pulmonary dysfunction. However, there is no evidence of the superiority of different paracentesis strategies in the prevention and treatment of IAH in critically ill patients with cirrhosis.This trial aims to compare the outcomes of continuous passive paracentesis versus LVP in the prevention and treatment of IAH in patients with cirrhosis and ascites.MethodsAn investigator-initiated, open label, randomized controlled trial, set in a general ICU specialized in liver disease, was initiated in August 2022, with an expected duration of 36 months. Seventy patients with cirrhosis and ascites will be randomly assigned, in a 1:1 ratio, to receive one of two methods of therapeutic paracentesis. A stratified randomization method, with maximum creatinine and IAP values as strata, will homogenize patient baseline characteristics before trial group allocation, within 24 h of admission.In the control group, LVP will be performed intermittently according to clinical practice, with a maximum duration of 8 h, while, in the intervention group, continuous passive paracentesis will drain ascitic fluid for up to 7 days.The primary endpoint is serum creatinine concentration, and secondary endpoints include IAP, measured creatinine clearance, daily urine output, stage 3 acute kidney injury and multiorgan dysfunction assessed at day 7 after enrollment, as well as 28-day mortality rate and renal replacement therapy-free days, and length-of-stay. Prespecified values will be used in case of renal replacement therapy or, beforehand ICU discharge, liver transplant and death. Safety analysis will include paracentesis-related complication rate and harm. Data will be analyzed with an intention-to-treat approach.DiscussionThis is the first trial to compare the impact of different therapeutic paracentesis strategies on organ dysfunction and outcomes in the prevention and treatment of IAH in critically ill patients with cirrhosis and ascites.Trial registrationClinicalTrials.gov NCT04322201. Registered on 20 December 2019

Comparison of CKD-EPI, C-G and MDRD equations for estimating glomerular filtration rate in chronic kidney disease population in South-Western Nigeria

Background: Ethnic variabilities make reliability of formula equations for assessing glomerular filtration rate (GFR) doubtful in many populations. We compared Cockroft-Gault (CG), modification of diet in renal disease (MDRD), and chronic kidney diseases epidemiology collaboration (CKD-EPI) equations in adult Nigerian CKD subjects.&#x0D; Methodology: We measured 24-hour-urinary creatinine clearance of 311 adult CKD patients and compared with the three estimated equations. Bland-Altman plots were used to assess agreement between estimated equations and measured creatinine clearance (mGFR). Receiver-operating curve (ROC) analysis was used to assess the diagnostic power of the equations. Equation with accuracy within 30% of mGFR of ≥90% was considered acceptable for use.&#x0D; Results: Mean age was 41.9±12.7 years with 182(58.5%) females. The mean GFR using CKD-EPI, 2 MDRD and CG equations were 69.5±33.9, 65.9±33.0 and 66.2±30.9 mls/min/1.73m respectively 2 (mGFR 68.3±31.1mls/min /1.73m ). The 3 equations showed positive correlation to mGFR (r=0.95) but CKD-EPI had the least bias.&#x0D; Conclusion: All three equations can be used but CKD-EPI equation is preferable in Nigerian CKD patients, especially with GFR&gt; 60mls/min.

Development and validation of the creatinine clearance predictor machine learning models in critically ill adults

BackgroundIn critically ill patients, measured creatinine clearance (CrCl) is the most reliable method to evaluate glomerular filtration rate in routine clinical practice and may vary subsequently on a day-to-day basis. We developed and externally validated models to predict CrCl one day ahead and compared them with a reference reflecting current clinical practice.MethodsA gradient boosting method (GBM) machine-learning algorithm was used to develop the models on data from 2825 patients from the EPaNIC multicenter randomized controlled trial database. We externally validated the models on 9576 patients from the University Hospitals Leuven, included in the M@tric database. Three models were developed: a “Core” model based on demographic, admission diagnosis, and daily laboratory results; a “Core + BGA” model adding blood gas analysis results; and a “Core + BGA + Monitoring” model also including high-resolution monitoring data. Model performance was evaluated against the actual CrCl by mean absolute error (MAE) and root-mean-square error (RMSE).ResultsAll three developed models showed smaller prediction errors than the reference. Assuming the same CrCl of the day of prediction showed 20.6 (95% CI 20.3–20.9) ml/min MAE and 40.1 (95% CI 37.9–42.3) ml/min RMSE in the external validation cohort, while the developed model having the smallest RMSE (the Core + BGA + Monitoring model) had 18.1 (95% CI 17.9–18.3) ml/min MAE and 28.9 (95% CI 28–29.7) ml/min RMSE.ConclusionsPrediction models based on routinely collected clinical data in the ICU were able to accurately predict next-day CrCl. These models could be useful for hydrophilic drug dosage adjustment or stratification of patients at risk.Trial registration. Not applicable.

Comparison of Three Glomerular Filtration Rate Estimating Equations with 24-Hour Urine Creatinine Clearance Measurement in Potential Living Kidney Donors.

The accuracy of the measurement of renal function in potential living kidney donors (PLKD) is essential. The direct measurement of glomerular filtration rate (mGFR) has been considered the "gold standard." The estimated GFR (eGFR) with 24-hour urinary creatinine clearance (CrCl) is frequently used because of its availability. We aim to evaluate the correlation and agreement of eGFR using serum-based creatinine formulas (Cockcroft-Gault, MDRD, and CKD-EPI) and the eGFR based on 24-hour urinary CrCl to evaluate kidney function in PLKD. We evaluated the kidney function in 799 PLKD using 24-hour urinary CrCl method and compared the correlation and agreement with the eGFR based on creatinine formulas (Cockcroft-Gault, MDRD, and CKD-EPI). We calculated the mean bias (difference), precision (SD of this difference), accuracy, and performed Bland-Altman plots. A total of 799 PLKD were analyzed. The age of the PLKD ranged from 18 to 73 years. Weak to mild correlation was observed between 24-hour urinary CrCl and all formulas (ranged from 0.31 to 0.49). The three equations underestimated the GFR. Using the Bland-Altman graphic, we observed that the CKD-EPI was the least scattered and most precise; however, mean bias and the interval range (limits of agreement) of all formulas were too big to assume equivalence between 24-hour urinary CrCl method and eGFR based on creatinine. Results of mean bias were similar when comparing the three equations in patients with CrCl GFR <60. However, the accuracy of all formulas was better for the female group and the youngest individuals (≤40 years old). In this PLKD cohort, of all the three equations, the CKD-EPI was the least scattered and most precise. However, the correlation and the level of agreement between the three equations and 24-hour urinary CrCl were too low to assume the equivalence.

#4506 ACCURACY OF NOVEL GFR ESTIMATING EQUATIONS BASED ON CREATININE, CYSTATIN C OR BOTH IN ROUTINE CARE

Abstract Background and Aims New equations to estimate GFR (eGFR) based on creatinine, cystatin C or both have been developed in the last two years. A comprehensive comparison of their accuracy is currently lacking, particularly in cohorts not involved in their development or validation and among people with comorbid conditions. Method We included 6174 adults from the Stockholm Creatinine Measurements (SCREAM) project referred for plasma clearance of iohexol during 2011-2021, in whom we observed 9579 concurrent measurements of creatinine, cystatin C and iohexol clearance. We assessed the performance against measured GFR (mGFR) of eGFR equations proposed by the CKD-EPI collaboration (CKD-EPI 2009, 2012 and 2021), European Kidney Function Consortium (EKFC 2021 and 2023), and the revised Lund-Malmö (2011) and CAPA (2014) equations, which are used in Sweden. Bias was expressed as the median difference in eGFR minus mGFR, with negative biases indicating underestimation of mGFR. P30 described the percentage of individuals with eGFR within 30% of mGFR. Correct classification was defined as agreement of eGFR and mGFR categories using the KDIGO GFR categories. Subgroup analyses were conducted according to age, sex, BMI, eGFR, cancer, cardiovascular disease, diabetes, heart failure and liver disease. Results Mean age was 57 years, 46% of participants were female, mean mGFR was 62 mL/min/1.73 m2 and mean BMI was 26 kg/m2. Cardiovascular disease was the most common comorbid condition (30%), followed by liver disease (28%), diabetes (26%) and cancer (26%). Equations that used both creatinine and cystatin C had better performance than eGFR using each marker alone, regardless of the equation used; all such equations had small bias and P30 close to 90%. Among creatinine-based equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger overestimates of mGFR than EKFC 2021 and revised Lund-Malmö, with median biases of 5.6, 9.1, 2.7 and 0.2 mL/min/1.73 m2, respectively (Table 1). There were no meaningful differences in performance across eGFR equations based on cystatin C. Findings were consistent across subgroup analyses stratifying for comorbid conditions (Figure 1). Conclusion eGFR equations that combined information on creatinine and cystatin C performed better than equations based on creatinine or cystatin C alone in this Swedish cohort of routine referrals for plasma clearance of iohexol. There was larger variation in the performance of equations based on creatinine than cystatin C.

#3337 ACCURACY OF ESTIMATED GLOMERULAR FILTRATION RATE EQUATIONS IN PATIENTS WITH DISCORDANCES BETWEEN CREATININE AND CYSTATIN C-BASED ESTIMATIONS

Abstract Background and Aims Cystatin C is recommended for use along with creatinine in estimating glomerular filtration rate (eGFR) when precise estimates are needed for clinical decision-making. Although eGFR based on both creatinine and cystatin (eGFRcr-cys) is the most accurate in research studies, it is uncertain as to whether this remains true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFRcr) and that based on cystatin C (eGFRcys). Method We included 6185 adults from the Stockholm Creatinine Measurements (SCREAM) project referred for plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C and iohexol clearance. The performance of eGFRcr, eGFRcys and eGFRcr-cys was assessed against mGFR with bias, P30 and correct classification of GFR strata. We stratified analyses within three categories: eGFRcys at least 20% lower than eGFRcr (eGFRcys &amp;lt; eGFRcr), eGFRcys within 20% of eGFRcr (eGFRcys ≈ eGFRcr) and eGFRcys at least 20% higher than eGFRcr (eGFRcys &amp;gt; eGFRcr). Bias was expressed as the median difference in estimated GFR minus mGFR, with negative biases indicating underestimation of mGFR. P30 described the percentage of individuals with eGFR within 30% of mGFR. Correct classification of GFR categories was defined as agreement of eGFR and mGFR categories using the KDIGO GFR categories (&amp;lt;15, 15-29, 30-44, 45-59, 60-89 and ≥90 ml/min/1.73 m2). Results eGFRcr and eGFRcys were similar in 4226 (45%) of samples, and there all three estimating equations displayed similar performance (Table 1). In contrast, eGFRcr-cys was much more accurate in cases of discordance. For example, when eGFRcys &amp;lt; eGFRcr (47% of samples), median biases were 15.0 (overestimation), −8.5 (underestimation) and 0.8 ml/min/1.73 m2 for eGFRcr, eGFRcys and eGFRcr-cys, respectively; P30 was 50%/73%/84%, respectively; and correct classification was 38%/45%/62%, respectively. When eGFRcys &amp;gt; eGFRcr (8% of samples), median biases were −4.5, 8.4, and 1.4 ml/min/1.73 m2. Findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease and cancer (Figure 1). Conclusion When large discordances between eGFRcr and eGFRcys are found in clinical practice, eGFRcr-cys is more accurate than either eGFRcr or eGFRcys.

Obesity, Hyperfiltration, and Early Kidney Damage: A New Formula for the Estimation of Creatinine Clearance.

Glomerular hyperfiltration may represent a direct pathogenetic link between obesity and kidney disease. The most widely used methods to estimate creatine clearance such as Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) have not been validated in subjects with obesity. The performance of prediction formulas was compared with measured creatinine clearance (mCrCl) in subjects with obesity. The study population included 342 patients with obesity (mean BMI 47.6 kg/m2) without primary kidney disease. A urine collection was performed over 24 hours for measurement of CrCl. mCrCl increased with body weight. The CG formula showed an overestimation at high CrCl, whereas an underestimation resulted from CKD-EPI and MDRD. To improve the accuracy of estimated CrCl (eCrCl), a new CG-based formula was developed:53+0.7×(140-Age)×Weight/(96xSCr)×(0.85iffemale)A cut-off point for BMI of 32 kg/m2 was identified, at which the new formula may be applied to improve eCrCl. In patients with obesity the glomerular filtration rate increases with body weight, and it is associated with the presence of albuminuria, suggesting an early kidney injury. We propose a novel formula that improves the accuracy of eCrCl to avoid missed diagnoses of hyperfiltration in patients with obesity.

Prevalence of Augmented Renal Clearance (ARC), Utility of Augmented Renal Clearance Scoring System (ARC score) and Augmented Renal Clearance in Trauma Intensive Care Scoring System (ARCTIC score) in Predicting ARC in the Intensive Care Unit: Proactive Study.

We aimed to study the prevalence of augmented renal clearance (ARC) and validate the utility of ARC and ARCTIC scores. We also aimed to assess the correlation and agreement between estimated GFR (eGFR-EPI) and 8-hour measured creatinine clearance (8 hr-mCLcr). This was a prospective, observational study done in the mixed medical-surgical intensive care unit (ICU) and 90 patients were recruited. 8 hr-mCLcr, ARC, and ARCTIC scores and eGFR-EPI were calculated for all patients. ARC was said to be present if 8 hr-mCLcr was ≥ 130 mL/min. Four patients were excluded from the analysis. The prevalence of ARC was 31.4%. The sensitivity, specificity, and positive and negative predictive values of ARC and ARCTIC scores were found to be 55.6, 84.7, 62.5, 80.6, and 85.2, 67.8, 54.8, and 90.9 respectively. AUROC for ARC and ARCTIC scores were 0.802 and 0.765 respectively. A strong positive correlation and poor agreement were observed between eGFR-EPI and 8 hr-mCLcr. The prevalence of ARC was significant and the ARCTIC score showed good potential as a screening tool to predict ARC. Lowering the cut-off of ARC score to ≥5 improved its utility in predicting ARC. Despite its poor agreement with 8 hr-mCLcr, eGFR-EPI with a cut-off ≥114 mL/min showed utility in predicting ARC. Kanna G, Patodia S, Annigeri RA, Ramakrishnan N, Venkataraman R. Prevalence of Augmented Renal Clearance (ARC), Utility of Augmented Renal Clearance Scoring System (ARC score) and Augmented Renal Clearance in Trauma Intensive Care Scoring System (ARCTIC score) in Predicting ARC in the Intensive Care Unit: Proactive Study. Indian J Crit Care Med 2023;27(6):433-443.

Development of 8‐h urine collections and an augmented renal clearance dosing program at an academic medical center

AbstractEnsuring appropriate dosing of medications is an essential practice of clinical pharmacists. Dose adjustments in the setting of decreased renal function are common but may also be warranted for patients with supraphysiologic or augmented renal clearance (ARC). Conventional estimates of creatinine clearance using only serum creatinine may not be accurate in the setting of ARC, thus a measured creatinine clearance using serum and urine creatinine measurements are preferred. We describe the development of an 8‐h urine collection and ARC dosing program at a large academic medical center initiated by critical care and infectious disease pharmacists. Using a Plan–Do–Study–Act approach, we implemented and updated the 8‐h collection program with the guidance of our clinical laboratories. Eight‐hour urine collections are useful for patients with suspected ARC and for other scenarios where accurate dose adjustments are needed to minimize toxicity in the absence of therapeutic drug monitoring.

Effects of Dietary Sodium and Protein Intake on Glomerular Filtration Rate in Subjects with Type 2 Diabetes Treated with Sodium-Glucose Cotransporter 2 Inhibitors.

Approximately one-fourth of patients treated with sodium-glucose cotransporter 2 inhibitors (SGLT2i) experience an acute estimated glomerular filtration rate (eGFR) reduction of more than 10% ("dippers"). High sodium and protein intake can increase intraglomerular pressure and predispose to a decline in renal function. We investigated whether measured creatinine clearance (CrCl) is a sensitive enough method to detect the initial dip of GFR and if dietary sodium and protein intake might influence the extent of the early change in GFR. 28 subjects with type 2 diabetes (T2D) were enrolled. For sodium and urea determination, 24-h urinary samples were collected to estimate sodium and protein intake respectively before and 1, 3 and 6 months after SGLT2i initiation. Mean CrCl was 83.23±25.52 mL/min/1.73 m2 (eGFR 67.32±16.07) and dropped by 19% at month 1 (eGFR by 6%). Dippers were 64 and 40%, according to CrCl and eGFR, respectively. Exploring the potential correlation between changes in renal function and salt intake, ΔCrCl and baseline urinary sodium were inversely related at month 1 (r=-0,61; p<0.01), at month 3 (r=-0.51; p=0.01) and month 6 (r=-0,48; p<0.05). Likewise, an inverse correlation between ΔCrCl and baseline urinary urea was demonstrated at months 1 and 3 (r=-0.46; p<0.05 for both); at month 6, a similar trend was observed (r=-0.47; p=0.054). The present study suggests that a higher dietary sodium and protein intake may amplify the extent of the early dip in GFR, as detected with measured CrCl, in diabetic patients undergoing SGLT2i treatment.

Renal function estimating equations performance during pregnancy and postpartum.

The objectives of this study were to evaluate the performance of renal function estimating equations compared to measured creatinine clearance (CrCl) during pregnancy and postpartum and to evaluate which body weight (pre-pregnancy weight (PPW), actual body weight (ABW), and ideal body weight (IBW)) provides the best performance. A retrospective study. Collections tookplace in the University of Washington clinical research unit. Women (n = 166) who completed ≥1 pharmacokinetic (PK) study with a 6-24 h measured CrCl during pregnancy and/or ≥3 months postpartum were included. CrCl was estimated utilizing estimated glomerular filtration rate (eGFR) and CrCl equations with common weight descriptors. Analyses included Bland-Altman, relative accuracies within 10% and 25%, and root mean squared error (RMSE). Overall performance was determined by summation of rank for evaluation parameters. During pregnancy, correlations between measured CrCl and estimated CrCl were between 0.5-0.8; equations with slopes closest to one were Modification of Diet in Renal Disease (MDRD2; PPW and ABW) and Cockcroft-Gault (CG) (PPW); and y-intercept closest to zero was Preeclampsia Glomerular Filtration Rate (PGFR). The lowest bias was seen with CG (ABW), and the highest accuracy within 25% was CG (ABW). CG (PPW) had the lowest RMSE. Postpartum, the best correlation was found with MDRD2 (PPW), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI (ABW)), and CKD-EPI 2021 (PPW). For slopes closest to one, MDRD2 (ABW) was best, whereas the equation with y-intercept closest to zero was CKD-EPI (ABW). CG (PPW) had the highest accuracy within 25%, and 100/serum creatinine (SCr) had the lowest bias. Based on overall performance, CG (PPW) was the best followed by CG (ABW) and PGFR during pregnancy and 100/SCr followed by CG (PPW) and CG (ABW) postpartum. The new CKD-EPI 2021 equation did not perform well during pregnancy. When 24-h CrCls are not available during pregnancy, CG (PPW or ABW) performed the best overall, whereas at 3 months postpartum, 100/SCr performed the best overall.

Mild Chronic Kidney Disease Associated with Low Bone Formation and Decrease in Phosphate Transporters and Signaling Pathways Gene Expression.

The initial phases of molecular and cellular maladaptive bone responses in early chronic kidney disease (CKD) remain mostly unknown. We induced mild CKD in spontaneously hypertensive rats (SHR) by either causing arterial hypertension lasting six months (sham-operated rats, SO6) or in its' combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, respectively). Sham-operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with a two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. Upon follow-up completion in each animal, we measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho, Dickkopf-1, sclerostin, and assessed bone response by static histomorphometry and gene expression profiles. The mild CKD groups had no increase in renal Pi excretion, FGF23, or PTH levels. Serum Pi, Dickkopf-1, and sclerostin were higher in Nx6. A decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast numbers. The decline in eroded perimeter, a resorption index, was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. We found an association between mild CKD and histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.

External Validation of the Augmented Renal Clearance Predictor in Critically Ill COVID-19 Patients.

The ARC predictor is a prediction model for augmented renal clearance (ARC) on the next intensive care unit (ICU) day that showed good performance in a general ICU setting. In this study, we performed a retrospective external validation of the ARC predictor in critically ill coronavirus disease 19 (COVID-19) patients admitted to the ICU of the University Hospitals Leuven from February 2020 to January 2021. All patient-days that had serum creatinine levels available and measured creatinine clearance on the next ICU day were enrolled. The performance of the ARC predictor was evaluated using discrimination, calibration, and decision curves. A total of 120 patients (1064 patient-days) were included, and ARC was found in 57 (47.5%) patients, corresponding to 246 (23.1%) patient-days. The ARC predictor demonstrated good discrimination and calibration (AUROC of 0.86, calibration slope of 1.18, and calibration-in-the-large of 0.14) and a wide clinical-usefulness range. At the default classification threshold of 20% in the original study, the sensitivity and specificity were 72% and 81%, respectively. The ARC predictor is able to accurately predict ARC in critically ill COVID-19 patients. These results support the potential of the ARC predictor to optimize renally cleared drug dosages in this specific ICU population. Investigation of dosing regimen improvement was not included in this study and remains a challenge for future studies.

Accuracy of GFR Estimating Equations in Patients with Discordances between Creatinine and Cystatin C-Based Estimations.

Large discordances between eGFR on the basis of creatinine (eGFR cr ) or cystatin C (eGFR cys ) are common in clinical practice. However, which GFR estimating equation (eGFR cr , eGFR cys , or eGFR cr-cys ) is most accurate in these settings is not known. In this real-world study of 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance, all three equations performed similarly when eGFR cr and eGFR cys were similar (45% of cases). However, with large discordances (55% of cases), eGFR cr-cys was much more accurate than either alone. These findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer who have been underrepresented in research cohorts. Thus, when eGFR cr and eGFR cys are largely discordant in clinical practice, eGFR cr-cys is more accurate than eGFR cr or eGFR cys . Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin (eGFR cr-cys ) is the most accurate estimate in research studies, it is uncertain whether this is true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFR cr ) and that based on cystatin C (eGFR cys ). We included 6185 adults referred for measured GFR (mGFR) using plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance. The performance of eGFR cr , eGFR cys , and eGFR cr-cys was assessed against mGFR with median bias, P30 , and correct classification of GFR categories. We stratified analyses within three categories: eGFR cys at least 20% lower than eGFR cr (eGFR cys <eGFR cr ), eGFR cys within 20% of eGFR cr (eGFR cys ≈eGFR cr ), and eGFR cys at least 20% higher than eGFR cr (eGFR cys >eGFR cr ). eGFR cr and eGFR cys were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR cr-cys was much more accurate in cases of discordance. For example, when eGFR cys <eGFR cr (47% of samples), the median biases were 15.0 (overestimation), -8.5 (underestimation), and 0.8 ml/min per 1.73 m 2 for eGFR cr , eGFR cys , and eGFR cr-cys , respectively; P30 was 50%, 73%, and 84%, respectively; and correct classification was 38%, 45%, and 62%, respectively. When eGFR cys >eGFR cr (8% of samples), the median biases were -4.5, 8.4, and 1.4 ml/min per 1.73m 2 . The findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer. When eGFR cr and eGFR cys are highly discordant in clinical practice, eGFR cr-cys is more accurate than either eGFR cr or eGFR cys .

Measuring Creatinine Clearance Is the Most Accurate Way for Calculating the Proper Continuous Infusion Meropenem Dose for Empirical Treatment of Severe Gram-Negative Infections among Critically Ill Patients

Assessment of glomerular filtration rate (GFR) is necessary for dose adjustments of beta-lactam that are excreted by the kidneys, such as meropenem. The aim of this study was to compare the daily dose of 24 h-continuous infusion (CI) meropenem when GFR was calculated by means of measured creatinine clearance (mCLCR) or estimated by the CKDEPI (eGFRCKDEPI), Cockcroft-Gault (eGFRCG), and MDRD (eGFRMDRD) equations. Adult critically ill patients who underwent therapeutic drug monitoring (TDM) for the assessment of 24 h-CI meropenem steady state concentration (Css) and for whom a 24 h-urine collection was performed were retrospectively enrolled. Meropenem clearance (CLM) was regressed against mCLCR, and meropenem daily dose was calculated based on the equation infusion rate = daily dose/CLM. eGFRCKDEPI, eGFRCG, and eGFRCKDEPI were regressed against mCLCR in order to estimate CLM. Forty-six patients who provided 133 meropenem Css were included. eGFRCKDEPI overestimated mCLCR up to 90 mL/min, then mCLCR was underestimated. eGFRCG and eGFRMDRD overestimated mCLCR across the entire range of GFR. In critically ill patients, dose adjustments of 24 h-CI meropenem should be based on mCLCR. Equations for estimation of GFR may lead to gross under/overestimates of meropenem dosages. TDM may be highly beneficial, especially for critically ill patients with augmented renal clearance.

Which glomerular filtration rate estimation formula should be used for nephrological evaluation in patients with common variable immune deficiency

Background: Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults. In addition to renal complications of the disease, there may be an increased likelihood of renal dysfunction due to sucrose in immunoglobulin replacement therapies or other drugs used in treatment. In CVID patients, it is important to monitor patients for renal complications at routine intervals. We compared creatinine-based calculation methods for estimated glomerular filtration rate (eGFR) such as Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) with 24-hour urine creatinine clearance measurement. We aimed to investigate which calculation method was more reliable and consistent in this patient population. Methods: The records of 14 patients who had clinical follow-up at our hospital were retrospectively reviewed. Patients’ eGFR values were measured by three different methods (CKD-EPI, MDRD , and CG formulas). The 24-hour urinary creatinine clearance of all patients and e-GFR calculated by the formula were compared. Results: The eGFR calculated using the MDRD formula was 122.99±41.22 mL/min/1.73 m2, whereas the eGFR measured using the 24-hour urinary creatinine clearance was 99.64(83.35-156.58) mL/min/1.73 m2. Moreover, eGFR calculated by CKD-EPI formula was 113.83±26.46 mL/min/1.73 m2, while eGFR calculated by CG formula was 133.52±45.35 mL/min/1.73 m2. 24-hour urinary creatinine clearance was positively correlated with MDRD, CKD-EPI and CG formulas (r=0.726, p=0.003, r=0.634, p=0.015, r=0.806, p=0.001, respectively). Conclusions: We found that all creatinine-based formulas used in clinical practice for eGFR measurement correlate with 24-hour urine creatinine clearance in patients with CVID. In addition, we have shown that eGFR calculated with the formula CKD-EPI is more closely related to 24-hour urinary creatinine clearance. Therefore, we believe that the eGFR measurement calculated with CKD-EPI is more useful for nephrological follow-up of patients with CVID. It should be noted that our study has some limitations due to the small number of patients.

Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system for augmented renal clearance prediction in a trauma subgroup of a mixed ICU population

Augmented renal clearance is prevalent in trauma patients and leads to subtherapeutic levels of renally eliminated medications with potentially unfavourable clinical outcomes. The Augmented Renal Clearance of Trauma in Intensive Care (ARCTIC) score has been developed to predict augmented renal clearance in critically ill trauma patients. Our primary objective was to validate this score among the trauma subgroup of a mixed intensive care patient cohort. This single-centre, retrospective, observational cohort study assessed augmented renal clearance using a timed 24-h urine collection performed weekly. ARC was defined as a measured creatinine clearance of ≥130 ml/min/1.73 m2 . ARCTIC score performance was evaluated through a receiver operator characteristic curves and analysis of sensitivities and specificities for the trauma subgroup, the medical/surgical subgroup and the pooled cohort. Augmented renal clearance was observed in 33.9% (n=58) of trauma patients (n=171) and 15.7% (n=24) of medical/surgical patients (n=153). Examination of different cutoffs for the ARCTIC score in our trauma population confirmed that the optimal cutoff score was ≥6. Comparison between ROC curves for ARCTIC score and for regression model based upon our data in trauma patients indicated validation of the score in this subgroup. Comparison of sensitivities and specificities for ARCTIC score between trauma (93.1% and 41.6%, respectively) and medical/surgical subjects (87.5% and 49.6%, respectively) showed no clinical nor statistical difference, suggesting validation for the medical/surgical subgroup as well. In our mixed ICU population, the ARCTIC score was validated in the trauma subgroup. We also found that the score performed well in the medical/surgical population. Future studies should assess the performance of the ARCTIC score prospectively.