Estimated Creatinine Clearance Research Articles

The ETNA-AF Europe registry: 4-year data of edoxaban use in atrial fibrillation in the Italian real world compared to the European cohort

The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years. Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population. In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding. These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

Baseline shock index-creatinine clearance score and long-term mortality after ACS. Results from 24 years of follow-up of the ABC study on heart disease

Abstract Background Shock Index-Creatinine Clearance score (SI-C) is an updated version of the shock index that includes renal function. Recent studies reported its potential as a novel and simple risk stratification tool for predicting in-hospital mortality in acute coronary syndrome (ACS) patients. Purpose To assess the long-term predictive value of baseline SI-C score in patients after ACS. Methods This preliminary prospective analysis included 589 patients with ACS admitted to three Italian hospitals and discharged alive. Baseline clinical and laboratory data were collected within the first 7 hospitalization days and baseline SI-C score was calculated as [(SI×100)-estimated creatinine clearance]. Patients were prospectively followed for 24 years or until death. Results Virtually all patients completed the follow-up, representing 7066 person-years. Patients' mean age was 66±12 years, 70% were males, and 482(82%) had died during follow-up. Compared to those who survived, deceased patients were significantly different in many of the baseline clinical characteristics. They also showed a significantly higher SI-C values ( -11± 25 vs. -36±23, p&amp;lt;0.0001). The predictive value of SI-C for 24-year mortality was very good (area under the curve= 0.783, 95% CI: 0.738-0.827, p&amp;lt;0.001). The cumulative risk was significantly higher in the upper SI-C tertile (log-rank = 162.1, p &amp;lt; 0.001). Unadjusted Cox regression survival analysis showed that the SI-C score was significantly associated with long-term all-cause mortality (HR: 2.1, 95%CI 1.8-2.3, p&amp;lt;0.0001). Similar results were obtained with the fully adjusted model. Conclusion Baseline SI-C seems to be an effective and independent predictor of long-term all-cause mortality after ACS.

Evaluation of concordance and association with clinical outcomes across eGFR values calculated with eight different formulas in a large cohort of european patients with atrial fibrillation

Abstract Background In randomized clinical trials of Direct Oral Anticoagulants (DOACs), the assessment of renal function impairment glomerular filtration rate (eGFR) in patients with Atrial Fibrillation (AF) has predominantly utilized the Cockroft-Gault (CG) formula for estimating Creatinine clearance (CrCl). However, in clinical practice, several other formulas for estimating glomerular filtration rate (eGFR) are employed. Limited data exist regarding the evaluation and comparison of eGFR/CrCl in AF patients. Objectives This study aimed to assess the concordance in the categorisation of renal function in in 6 classes taking into account eight different formulas for eGFR/CrCl (CG, CKD-EPI, CG/body surface area [BSA], BIS1, LMK, EKFC, FAS, MDRD) and their associations with a composite outcome (Major Adverse Cardiovascular Events [MACE] and all-cause death) in AF patients. Methods A contemporary European AF patient registry was utilized, and eGFR/CrCl were calculated using CG, CKD-EPI, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. eGFR was categorized according to KDIGO classes, with CKD patients defined as having eGFR/CrCl &amp;lt;60 ml/min/m2. Concordance was estimated using weighted Cohen’s kappa. Associations were evaluated through adjusted Cox regression analyses for the composite outcome, and results were plotted as spline curves. Results: A total of 8516 patients were included in the analysis (Median [IQR] age: 70 [63-77] years; 3518 women, 41.3%). Among the formulas, EKFC exhibited the highest median values of eGFR and the lowest prevalence of CKD patients, while BIS1 had the lowest median eGFR values, and the FAS formula led to the highest prevalence of CKD patients [Figure 1]. In the concordance analysis, CKD-EPI demonstrated the highest concordance with all other formulas, even if Cohen’s kappa for measuring the degree of concordance ranged from 0.61 to 0.88 [Figure 1]. In adjusted Cox regression analyses, all formulas were associated with an increased risk for the composite outcome, progressively as eGFR decreased. When plotted as spline curves, the associations with the composite outcome visually showed a similar behaviour of risks across eGFR values in all formulas compared to the CG spline [Figure 2]. Conclusions Among AF patients, the CKD-EPI formula exhibited variable, but substantially good concordance with CG, CG/BSA, BIS1, LMK, EKFC, FAS, and MDRD formulas. All calculated eGFR values showed a strong association with the composite outcomes, similarly to the CG formula, with higher risk when renal function decreased.FIGURE 1FIGURE 2

Markers of Maternal Bone and Renal Toxicity Through 50 Weeks Postpartum: IMPAACT 2010 (VESTED) Trial.

Safety data from randomized trials of antiretrovirals in pregnancy are scarce. We evaluated maternal bone and renal data from the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 trial, which compared the safety and efficacy of 3 antiretroviral therapy regimens started in pregnancy: dolutegravir + emtricitabine/tenofovir alafenamide (DTG + FTC/TAF), dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG + FTC/TDF), and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). A subset of participants underwent dual-energy X-ray absorptiometry scans at postpartum week 50 only. Maternal bone mineral density (BMD) Z-scores were compared between arms. Maternal creatinine was measured at enrolment and periodically through week 50 postpartum, and by-arm differences in average weekly change in estimated creatinine clearance were compared. Six hundred forty-three participants were randomized to DTG + FTC/TAF (N = 217) or DTG + FTC/TDF (N = 215) or EFV/FTC/TDF (N = 211). Median age = 27 years (IQR 23, 32), median CD4 count = 466 cells/mm3 (IQR 308, 624); 564 (88%) women enrolled in Africa and 479 (74%) breastfed. Week 50 postpartum dual-energy X-ray absorptiometry results from 154 women were included in the analysis. Hip and spine BMD was on average higher in women in the DTG + FTC/TAF and lower in the DTG + FTC/TDF and EFV/FTC/TDF arms, but no significant differences in BMD Z-scores were observed between treatment groups. The weekly rate of change in estimated creatinine clearance differed among treatment groups during the antepartum period, but not over the full study follow-up. Markers of bone and renal toxicity did not differ significantly through week 50 postpartum among women randomized to start DTG + FTC/TAF or DTG + FTC/TDF or EFV/FTC/TDF in pregnancy.

A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.

Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre-clinical studies showed benefit with a histone-neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis. We studied 26 patients with sepsis divided into four cohorts of one, five, ten, and ten subjects, respectively. We conducted a dose-adjusted, open-label study to determine the safety, tolerability, and pharmacokinetics of STC3141 administered as an IV infusion for up to 72 h, with rate adjusted to estimated creatinine clearance. Four steady-state concentrations were targeted. Twenty of the 26 subjects (77%) in the study experienced at least one adverse event (AE). The most frequently reported study drug-related AE was a mildly prolonged aPTT (four events). Only one AE (pulmonary hemorrhage) led to discontinuation of the drug. After excluding patients receiving renal replacement therapy (RRT) patients, clearance ranged from 3.3 to 4.2 L/h across cohorts and was essentially completely renal in nature. Half-life values ranged from 5 to 7 h. The mean (±SD) terminal half-life for non-RRT subjects and for whom it was possible to calculate was approximately 9 (±4.77) h but increased to 19 (±7.94) h for subjects on RRT. Overall, 18 (69.2%) patients completed the study to day eight in the ICU, and 22 (84.6%) survived to 28 days. STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics. Cautious, larger randomized efficacy trials in sepsis appear justified.

Population Pharmacokinetic Modeling of Cefepime, Meropenem, and Piperacillin-Tazobactam in Patients with Cystic Fibrosis.

Patients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. Management of these infections is increasingly challenging due to decreased antimicrobial susceptibility to beta-lactam antibiotics. The pharmacokinetics of these agents are inadequately characterized in patients with CF. One hundred fifty-five pediatric and adult participants with CF receiving cefepime (n=82), meropenem (n=42), or piperacillin-tazobactam (n=31) were enrolled. Opportunistic blood samples were obtained during hospitalization. Population PK analysis was conducted using nonlinear mixed-effects modeling. Clinical and demographic characteristics were evaluated as potential covariates. Monte Carlo simulations were performed to evaluate probability of target attainment (PTA) for different dosing regimens. Estimated creatinine clearance, and total or lean body weight, affected the pharmacokinetics of cefepime and meropenem. No covariates were identified for piperacillin and tazobactam. In the cefepime group, a 3-h infusion achieved higher PTA than a 0.5-h infusion for all participants. Estimated breakpoints (the respective minimum inhibitory concentration (MIC) up to which ≥90% of patients are predicted to reach a PK/PD target) were two- to four-fold higher in pediatric participants receiving a 3-h vs. 0.5-h infusion. In the meropenem group, increased creatinine clearance led to reduced PTA. In the piperacillin-tazobactam group, total daily dose and mode of administration were principal drivers of PTA. Standard dosing regimens fail to achieve specific MIC targets in patients with CF. Therefore, clinicians should incorporate local antibiograms and PK models to determine optimal dosing. Further PK optimization to account for interindividual differences could be achieved by real-time beta-lactam therapeutic drug monitoring.

Early Diagnostic and Prognostic Value of the Urinary TIMP-2 and IGFBP-7 in Acute Kidney Injury in Critically Ill Children.

Acute kidney injury (AKI) is a hidden complication among children within pediatric intensive care units (PICU). To evaluate the early predictive and diagnostic value of Urinary [TIMP-2][IGFBP7] to detect AKI in PICU patients. A case-control study was conducted on 112 children (72 admitted to PICU and 40 healthy controls) Urinary [TIMP-2][IGFBP7] was measured within 24 hours of PICU admission. Acute kidney injury developed in 52 (72.2%) out of 72 critically ill patients. The AKI group had significantly higher serum creatinine, CRP, and pediatric sequential organ failure assessment score (pSOFA) score (p = 0.001, 0.01, and 0.001, respectively) and significantly lower estimated creatinine clearance (eCCl) (p = 0.001). Urinary [TIMP-2][IGFBP7] was significantly higher in the AKI group as compared with the non-AKI group (p = 0.007). The duration of the PICU stay was 1.8-fold higher in the AKI group (p = 0.004). At the time of study enrollment, 7 (13.5%) patients had normal initial eCCl. 26 patients (50.0%) fulfilled the "Risk," 18 patients (34.6%) the "Injury," 1 patient (1.9%) the "Failure" and 0 patient (0%) the "Loss" criteria. Nine (17%) patients progressed to the next higher pediatrics risk, injury, failure, loss, end-stage renal disease (pRIFLE) stage. Urinary [TIMP-2][IGFBP7] was significantly higher in the "Failure" stage followed by "Injury," stage then the "Risk," stage (p = 0.001). Hypovolemia/dehydration had the highest [TIMP-2][IGFBP7] values followed by sepsis. Urinary [TIMP-2][IGFBP7] was significantly increased in mechanically ventilated and patients who received inotropic medications. [TIMP-2]·[IGFBP7] was higher in AKI patients compared with non-AKI ones especially cases with hypovolemia and sepsis. It may predict severe morbidity and mortality because its higher levels in mechanically ventilated children and those on positive inotropic support. Ismail M, Abdelhamid N, Hasanin HM, Hamed HM, Motawie A, Kamel S, et al. Early Diagnostic and Prognostic Value of the Urinary TIMP-2 and IGFBP-7 in Acute Kidney Injury in Critically Ill Children. Indian J Crit Care Med 2024;28(10):970-976.

Target Attainment and Population Pharmacokinetics of Cefazolin in Patients with Invasive Staphylococcus aureus Infections: A Prospective Cohort Study.

This study aimed to determine cefazolin target attainment in patients with invasive Staphylococcus aureus (S. aureus) infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive S. aureus infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined. The primary outcome was the proportion of patients attaining 100% fT>MIC at all time points evaluated. A population PK model was developed, using non-linear mixed-effects modelling. Overall, 51 patients were included, with a total of 226 unbound and total cefazolin concentrations measured (mean: 4.4 per patient). The median daily dosage in patients with an estimated glomerular filtration rate of >60 mL/min/m2 was 8 g. The median age was 74 years (interquartile range (IQR) 57-82) and 26% were female. A history of chronic kidney disease and acute kidney injury were present in 10/51 (19.6%) and 6/51 (11.7%), respectively. Achievement of 100% fT>MIC occurred in 86% of the patients and decreased to 45% when a target of 100% fT>4xMIC was evaluated. The mean unbound cefazolin fraction was 27.0% (standard deviation (SD) 13.4). Measured and estimated mean cefazolin trough concentrations differed significantly [13.1 mg/L (SD 23.5) vs. 7.4 mg/L (SD 7.9), p < 0.001]. In the population PK model, elevated estimated creatinine clearance and bolus instead of continuous application were covariates for target non-attainment. In conclusion, cefazolin target achievement was high, and the measurement of the unbound cefazolin concentration may be favored. The Monte Carlo simulations indicated that target attainment was significantly improved with continuous infusion.

Prognostic Value of Shock Index Creatinine in Patients with Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Introduction: Shock index (SI) and its derivatives have been reported to have prognostic value in various cardiovascular diseases. This study aims to ascertain the utility of shock index creatinine (SIC) in predicting mid-term mortality among patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods: We conducted a retrospective analysis of 555 patients with severe AS who underwent TAVR from April 2016 to March 2023. SIC was calculated as (SI × 100) – estimated creatinine clearance (CCr). The primary endpoint was all-cause mortality during the follow-up period, and secondary endpoints included in-hospital complications as defined by the Valve Academic Research Consortium-3 (VARC-3) criteria. Patients were stratified into two groups based on the optimal cutoff value determined by the receiver-operating characteristic (ROC) curve. Cox regression analysis was employed to identify independent predictors of all-cause mortality. Additionally, restricted cubic spline (RCS) was deployed to illustrate the relationship between SIC and mortality risk. The predictive performance of risk scores was evaluated using the area under the ROC curve (AUC). Results: Over a mean follow-up period of 21.5 months, there were 51 cases of all-cause mortality. Patients with a high SIC, identified by a cutoff of 16.5, exhibited a significantly higher cumulative all-cause mortality compared to those with a low SIC (18.3% vs. 5.2%, p < 0.001; adjusted HR = 2.188; 95% CI 1.103–4.341, p = 0.025). Patients with a high SIC were older (p = 0.002) and exhibited a higher prevalence of frailty (p < 0.001). Furthermore, they exhibited a heightened probability of moderate or severe mitral regurgitation (p < 0.001), tricuspid regurgitation (p < 0.001), and pulmonary hypertension (p < 0.001) compared to those with a low SIC. In terms of perioperative complications, acute kidney injury (10.1% vs. 3.9%, p = 0.008) and bleeding (13.6% vs. 6.7%, p = 0.014) were more prevalent in patients with a high SIC. The RCS demonstrated a positive correlation between SIC and all-cause mortality rate. Furthermore, incorporating high SIC into the STS score improved its predictive value for 1-year all-cause mortality (AUC: 0.731 vs. 0.649, p = 0.01). Conclusion: Patients with a high SIC are more likely to experience frailty and cardiac damage and exhibit an increased in-hospital and mid-term mortality rate. SIC may provide additional information for risk stratification of patients undergoing TAVR.

Underrepresentation of black individuals in pivotal trials for novel anticancer drugs: Potential consequence of using estimated creatinine clearance to assess kidney function?

BackgroundBlack individuals are historically underrepresented in oncology clinical trials. One potential reason for this is the prevalence of kidney disease in Black individuals, utilization of estimated creatinine clearance as a surrogate for glomerular filtration rate (GFR) in oncology, and GFR-based trial eligibility criteria. We characterized the representation of racial minorities in anticancer agent pivotal trials and examined if GFR-based trial eligibility criteria impact the proportion of Black individuals in trial populations. MethodsWe constructed a data repository for anticancer drugs FDA-approved from 2015 to 2019 and associated pivotal trials, from which we extracted trial population racial compositions and GFR-based trial eligibility criteria. We calculated the participation-to-incidence ratio (PIR) and participation-to-mortality ratio (PMR) for a variety of cancer sites, where PIR or PMR >1.2 and <0.8 indicate overrepresentation and underrepresentation, respectively. We evaluated the relationship between GFR eligibility cutoffs and the proportion of Black enrollees with Spearman rank correlation coefficient. ResultsWe assessed 24,698 patients in 74 trials. Black individuals were underrepresented in all trials (PIR ≤0.48, PMR ≤0.50). For trials with GFR-based eligibility criteria (n = 49), a lower GFR cutoff was modestly associated with a higher proportion of Black enrollees (r = −0.29, p = 0.039). This relationship was strengthened for trials that only used estimated creatinine clearance to estimate GFR (r = −0.43, p = 0.004). ConclusionsGFR-related eligibility, and specifically the use of estimated creatinine clearance, may contribute to Black individuals being disproportionately excluded from cancer clinical trials. This highlights the need for implementation of contemporary GFR equations and other interventions to boost racial minority trial enrollment.

Inonotus obliquus (Chaga) against HFD/STZ-induced glucolipid metabolism disorders and abnormal renal functions by regulating NOS-cGMP-PDE5 signaling pathway

Our prior investigations have established that Inonotus obliquus (Chaga) possesses hypoglycemic effects. Persistent hyperglycemia is known to precipitate renal function abnormalities. The functionality of the kidneys is intricately linked to the levels of cyclic guanosine-3',5'-monophosphate (cGMP), which are influenced by the activities of nitric oxide synthase (NOS) and phosphodiesterase (PDE). Enhanced cGMP levels can be achieved either through the upregulation of NOS activity or the downregulation of PDE activity. The objective of the current study is to elucidate the effects of Chaga on disorders of glucolipid metabolism and renal abnormalities in rats with type 2 diabetes mellitus (T2DM), while concurrently examining the NOS-cGMP-PDE5 signaling pathway. A model of T2DM was developed in rats using a high-fat diet (HFD) combined with streptozotocin (STZ) administration, followed by treatment with Chaga extracts at doses of 50 and 100 mg·kg−1 for eight weeks. The findings revealed that Chaga not only mitigated metabolic dysfunctions, evidenced by improvements in fasting blood glucose, total cholesterol, triglycerides, and insulin resistance, but also ameliorated renal function markers, including serum creatinine, urine creatinine (UCr), blood urea nitrogen, 24-h urinary protein, and estimated creatinine clearance. Additionally, enhancements in glomerular volume, GBM thickness, podocyte foot process width (FPW), and the mRNA and protein expressions of podocyte markers, such as nephrin and wilms tumor-1, were observed. Chaga was found to elevate cGMP levels in both serum and kidney tissues by increasing mRNA and protein expressions of renal endothelial NOS and neural NOS, while simultaneously reducing the expressions of renal inducible NOS and PDE5. In summary, Chaga counteracts HFD/STZ-induced glucolipid metabolism and renal function disturbances by modulating the NOS-cGMP-PDE5 signaling pathway. This research supports the potential application of Chaga in the clinical prevention and treatment of T2DM and diabetic nephropathy (DN), with cGMP serving as a potential therapeutic target.

The Relationship Between Postoperative Drainage Volume and the Incidence of Postoperative Renal Injury in Infants Undergoing Cardiac Surgery

Cardiac surgery-related acute kidney injury (CS-AKI) is a serious and frequently encountered complication that occurs in children undergoing cardiac surgery. It is particularly prevalent among those who undergo complex and prolonged surgical procedures. CS-AKI is a complex condition that can lead to significant morbidity and even mortality, and thus, understanding its pathogenesis and identifying potential risk factors is crucial for improving patient outcomes. One of the most consistent contributing factors to the development of CS-AKI is intraoperative bleeding. Bleeding during surgery can lead to hemodynamic instability, which in turn can affect renal perfusion and oxygen supply, ultimately leading to kidney injury. Intraoperative renal hypoperfusion and oxygen supply and demand imbalances are recognized as important pathogenic mechanisms underlying CS-AKI. To further investigate the relationship between intraoperative bleeding and postoperative kidney damage, researchers have conducted prospective observational studies. These studies focus on infants and young children undergoing cardiac surgery, as they are particularly vulnerable to the complications of such surgeries. By carefully observing and documenting the postoperative drainage volume, researchers aim to evaluate the correlation between postoperative blood loss and the incidence of postoperative renal injury. The results of these studies have provided valuable insights into the pathophysiology of CS-AKI. However, it is important to note that the correlation between postoperative eCrCl (estimated creatinine clearance) and postoperative drainage volume has not been found to be significant. This suggests that while intraoperative bleeding may contribute to the development of kidney injury, it may not be the sole determinant of renal outcome.

Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation.

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15ml/min/1.73m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKAs) or direct anticoagulants (DOACs). Moreover, it remains unclear which is more effective and safer, because estimated creatinine clearance <25-30ml/min was an exclusion criterion in the randomized controlled trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint, as they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC versus OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in haemodialysis patients with AF and undergoing LAAC compared with patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient to consider individual risks and benefits of each treatment option is underlined.

Comparatively tested potential risk factors across survivors and non-survivors critically patients

Background: The risk factors associated with mortality in critically ill patients have been the subject of numerous studies. However, a considerable amount of variation is evident when one considers the dispersion of patients, the geographical spread, and the classification of healthcare establishments. Aim: The purpose of this study was to compare potential risk factors between Survivors and Non-Survivors, including demographics, anthropometrics, kidney and liver indices, complete blood counts, and biochemical assays. Patients whose condition is critical. Methods: An ICU retrospective investigation was conducted in Jordan, where critically ill patients with surgical and medical conditions were examined. Using the Electronic Medical Record System (Hakeem), the study analysed data and classified patients into two cohorts according to their survival status. Demographic information, clinical characteristics, insulin administration rate, blood glucose levels, dosing schedules for vasopressors, and the burden of comorbidities were all included in the data. The research was granted approval by the Institutional Review Board committee of the Royal Medical Services, Jordan. Results: The research examined the male-to-female ratios among COVID-19 patients and classified them into six distinct age groups. A significant proportion of critical patients, ranging in age from 50 to 60, exhibited elevated corrected sodium levels and a diminished normontraemia status. Higher albumin levels and mean arterial pressures were associated with survivors, whereas a greater proportion of non-survivors were underweight and had a low BMI. A normal temperature was observed in the majority of critically ill patients, whereas non-survivors exhibited elevated fractional blood glucose levels and estimated creatinine clearances. The research emphasises the significance of treatment outcomes and patient demographics. Conclusion: SI may be a more accurate prognostic indicator than non-septic patients due to the effect of norepinephrine, a vasopressor, on heart rate and systolic blood pressure, which may account for the difference in SI values between the two groups.

Diagnostic accuracy of estimated glomerular filtration rate in pediatric oncology patients.

Objective: To compare eGFR using different equations with 24-hour creatinine clearance Methodology: We collected data of standardized 24-hour creatinine clearance of pediatric oncology patients for a period of one year and compared the efficiency of various equations for estimation of creatinine clearance with it. For error estimation we used mean relative prediction error (MRPE) and root mean square error (RMSE) and for accuracy estimation we used Lin’s correlation. Results: Out of 100 study participants, 57 were males and 43 were females. Mean age of the population studied was 11.8 while mean BMI was 13.95. Most common tumor reported was osteosarcoma. Out of 18 equations evaluated only 5 showed an accuracy of 0.80 or more, while SEM of none of the equation is near to the desired value (zero). Minimum SEM was found to be for Schwartz (2012) equation. Conclusions: According to our study none of the equations in current clinical practices showed a good correlation with creatinine clearance adjusted according to body surface area. Keywords: eGFR, creatinine clarence, renal function, pediatric oncology.

Therapeutic effect of Corbrin (Bailing) capsule on patients with renal insufficiency: A meta-analysis

ObjectiveAt present, there remains controversy regarding the clinical efficacy of Corbrin (Bailing) capsules in the treatment of renal insufficiency (RI). A meta-analytic approach was adopted in this study to assess the clinical efficacy of Corbrin capsules for treating RI, aiming to provide a certain level of clinical evidence to guide the selection of RI therapeutic interventions. MethodsThe meta-analysis was conducted on databases containing PubMed, CNKI, Weipu Database, Cochrane Library and Wanfang until January 2023. The search for relevant studies was conducted without language restrictions. The study encompassed a randomized controlled trial that examined the efficacy of Corbrin capsules in treating RI. Blood urea nitrogen (BUN), serum creatinine (Scr), 24-h urine protein quantity (24 h UPQ), and estimated creatinine clearance (ECC) were amalgamated using standardized mean difference (SMD) and its corresponding 95 % confidence interval (CI). Meanwhile, the treatment effect (TE) outcome was aggregated using odds ratio (OR) and its corresponding 95 % CI. To evaluate heterogeneity, the Q test and I2 statistics were employed within a random-effects model framework. ResultsA total of 11 eligible articles were included, involving 1100 patients (594 in the Corbrin capsule group and 516 in the control group). Compared with control subjects, the SMD was-1.3532 for Ser (95 % CI: 2.0617 to −0.6448), −1.7868 for UPQ (95 % CI: 2.8901 to −0.6836), −1.3302 for BUN (95 % CI: 2.2428 to −0.4176), and 1.7842 for ECC (95 % CI: 0.6774–2.8910). TE had an OR of 1.9786 (95 % CI: 0.7153–5.4734), and publications were not found to be biased (t = 0.5627, P = 0.6738). ConclusionIn RI patients, Corbrin capsule has a relatively good therapeutic effect.

Serum Biochemical Evaluation of Patients with Chronic Renal Failure on Hemodialysis

Introduction: Chronic renal failure (CRF) is associated with aberrations in the metabolism of minerals, such as calcium, phosphates, sodium, and potassium and other biochemical parameters. Various studies have identified parathyroid hormone (PTH) as the main regulator of minerals and biochemical parameters homeostasis. This study was conducted to evaluate the biochemical profile in CRF patients on hemodialysis in Aden. Methods: This study is a descriptive, cross sectional study, conducted in Aden Hemodialysis Center for the period Jan.1st to June 30th, 2022. Included 82 patients with CRF on HD. The data collected included demographic with clinical data, and blood samples taken for complete blood count and serum creatinine; urea; sodium; potassium; total calcium, ionized calcium; phosphate; alkaline phosphatase, and parathyroid hormone. Results: More male were found than female patients with CRF (67.1% vs. 32.9% respectively), with a mean age of 48.8 ± 12.6 years. The mean body mass index was (23.3 ± 4.7 kg/m2) and the mean duration of CRF was (4.8 ± 2.9 years). For renal function, the mean serum creatinine, urea, and estimated creatinine clearance were (9.9 mg/dl, 128.6 mg/dl, and 7.1 mL/min per 1.73 m2 respectively). For minerals, the mean serum sodium, potassium, chloride, phosphorus, calcium and ionized calcium were (134.4 mmol/L, 5.04 mmol/L, 104.1 mmol/L, 4.37 mg/dl, 9.4 mg/dl, and 1.12 mmol/L, respectively). The mean Calcium x Phosphorus product was in the recommended range (40.7mg2/dl2). The mean alkaline phosphatase was (286.2 U/L), and the mean parathyroid hormone was (322.7 pg/ml). Secondary hyperparathyroidism (PTH level of ≥130 pg/ml) was detected in (58.5%) of them. Parathormone concentration showed significant positive correlation to alkaline phosphatase (r: 0.640, p:0.001) in patients with CRF on hemodialysis. Conclusion: This study concluded that in patients with CRF on HD, there is an increase level of alkaline phosphatase which is considered as an adjunct marker of high-turnover bone disease associated with disturbed level of calcium and phosphorus that increase serum PTH level.

Imipenem/relebactam pharmacokinetics in critically ill patients supported on extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a life-saving modality but has the potential to alter the pharmacokinetics (PK) of antimicrobials. Imipenem/cilastatin/relebactam is an antibiotic with utility in treating certain multi-drug resistant Gram-negative infections. Herein, we describe the population pharmacokinetics of imipenem and relebactam in critically ill patients supported on ECMO. Patients with infection supported on ECMO received 4-6 doses of imipenem/cilastatin/relebactam per current prescribing information based on estimated creatinine clearance. Blood samples were collected following the final dose of the antibiotic. Concentrations were determined via LC-MS/MS. Population PK models were fit with and without covariates using Pmetrics. Monte Carlo simulations of 1000 patients assessed joint PTA of fAUC0-24/MIC ≥ 8 for relebactam, and ≥40% fT > MIC for imipenem for each approved dosing regimen. Seven patients supported on ECMO were included in PK analyses. A two-compartment model with creatinine clearance as a covariate on clearance for both imipenem and relebactam fitted the data best. The mean ± standard deviation parameters were: CL0, 15.21 ± 6.52 L/h; Vc, 10.13 ± 2.26 L; K12, 2.45 ± 1.16 h-1 and K21, 1.76 ± 0.49 h-1 for imipenem, and 6.95 ± 1.34 L/h, 9.81 ± 2.69 L, 2.43 ± 1.13 h-1 and 1.52 ± 0.67 h-1 for relebactam. Simulating each approved dose of imipenem/cilastatin/relebactam according to creatinine clearance yielded PTAs of ≥90% up to an MIC of 2 mg/L. Imipenem/cilastatin/relebactam dosed according to package insert in patients supported on ECMO is predicted to achieve exposures sufficient to treat susceptible Gram-negative isolates, including Pseudomonas aeruginosa.

Evaluation of measured and estimated creatinine clearance in patients with septic shock admitted to the ICU: a prospective observational study

Evaluation of measured and estimated creatinine clearance in patients with septic shock admitted to the ICU: a prospective observational study

Expedited loading with intravenous sotalol is safe and feasible—primary results of the Prospective Evaluation Analysis and Kinetics of IV Sotalol (PEAKS) Registry

BackgroundLoading of oral sotalol for atrial fibrillation requires 3 days, frequently in the hospital, to achieve steady state. The Food and Drug Administration approved loading with intravenous (IV) sotalol through model-informed development, without patient data. ObjectiveWe present results of the first multicenter evaluation of this recent labeling for IV sotalol. MethodsThe Prospective Evaluation Analysis and Kinetics of IV Sotalol (PEAKS) Registry was a multicenter observational registry of patients undergoing elective IV sotalol load for atrial arrhythmias. Outcomes, measured from hospital admission until first outpatient follow-up, included adverse arrhythmia events, efficacy, and length of stay. ResultsOf 167 consecutively enrolled patients, 23% were female; the median age was 68 (interquartile range, 61–74) years, and the median CHA2DS2-VASc score was 3 (interquartile range, 2–4). Overall, 99% were admitted for sotalol initiation (1% for dose escalation), with a target oral sotalol dose of either 80 mg twice daily (85 [51%]) or 120 mg twice daily (78 [47%]); 62 patients (37%) had an estimated creatinine clearance ≤90 mL/min. On presentation, 40% of patients were in sinus rhythm, whereas 26% underwent cardioversion before sotalol infusion. In 2 patients, sotalol infusion was stopped for bradycardia or hypotension. In 6 patients, sotalol was discontinued before discharge because of QTc prolongation (3), bradycardia (1), or recurrent atrial arrhythmia (2). The mean length of stay was 1.1 days, and 95% (n = 159) were discharged within 1 night. ConclusionIV sotalol loading is safe and feasible for atrial arrhythmias, with low rates of adverse events, and yields shorter hospitalizations. More data are needed on the minimal duration required for monitoring in the hospital.