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Objective: To determine the incidence of abnormal renal function tests at presentation in patients from Karachi admitted with severe COVID-19 pneumonia and determine its effect on disease severity and clinical outcomes. Study type,settings& duration:This was a cross-sectional study conducted at the COVID Intensive care unit of a largetertiary care government hospital in Karachifrom February2021to June2021. Methodology:A totalof 190 patients admittedover five months were included in the study. Patient demographic characteristics, comorbidities, and clinical manifestations of COVID-19 infection were recorded. Laboratory values at the time of presentation, including hemoglobin,neutrophil lymphocyte ratio, platelets, blood urea nitrogen,estimated glomerular filtration rate (eGFR), inflammatory markers, liver function tests, and electrolytes were recorded. Patient outcomesand need for mechanical ventilation were assessed 28 days after admission and compared with the incidence of abnormal renal functions at presentation. Results:Mean eGFR and BUN at presentation were 69.7 and 28.4 respectively. Of the total,109 (57.4%)patients had abnormal renal function tests at the time of presentation. Among them,76 (40%)patients had low eGFR and 33 (17.4%)had only raised BUN with normal eGFR. Mean eGFR was lower in non-survivors vs survivors (p-value 0.000) and in patients who required mechanical ventilation (p-value 0.008). Patients whohad low eGFR showed greater mortality than those with normal eGFR (p-value 0.04) and were more likely to require mechanical ventilation (p-value 0.04). Conclusion:Low eGFR at presentation is common in patients with severe COVID-19 pneumonia and is associated with a higher in-hospital mortality rate and need for mechanical ventilation.

Objective: To determine the incidence of abnormal renal function tests at presentation in patients from Karachi admitted with severe COVID-19 pneumonia and determine its effect on disease severity and clinical outcomes. Study type, settings & duration: This was a cross-sectional study conducted at the COVID Intensive care unit of a large tertiary care government hospital in Karachi from February 2021 to June 2021. Methodology: One hundred ninety patients admitted over five months were included in the study. Patient demographic characteristics, comorbidities, and clinical manifestations of COVID-19 infection were recorded. Laboratory values at the time of presentation, including hemoglobin, neutrophil lymphocyte ratio, platelets, blood urea nitrogen, estimated glomerular filtration rate (eGFR), inflammatory markers, liver function tests, and electrolytes were recorded. Patient outcome and need for mechanical ventilation were assessed 28 days after admission and compared with the incidence of abnormal renal functions at presentation. Results: Mean eGFR and BUN at presentation were 69.7 and 28.4 respectively. Of the total 109 (57.4%) patients had abnormal renal function tests at the time of presentation. About 76 (40%) patients had low eGFR and 33 (17.4%) had only raised BUN with normal eGFR. Mean eGFR was lower in non-survivors vs survivors (p-value 0.000) and in patients who required mechanical ventilation (p-value 0.008). Patients who had low eGFR showed greater mortality than those with normal eGFR (p-value 0.04) and were more likely to require mechanical ventilation (p-value 0.04). Conclusion: Low eGFR at presentation is common in patients with severe COVID-19 pneumonia and is associated with a higher in-hospital mortality rate and need for mechanical ventilation. [ABSTRACT FROM AUTHOR]

Abstract Background Prior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR). A recent cross-sectional study suggested that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio is larger when GFR is lower among patients with chronic kidney disease (CKD); but there have been no validation of this in other cohorts. Methods To fill these gaps in knowledge regarding the relation between CrCl and GFR, we conducted cross-sectional and longitudinal analysis of the Modification of Diet in Renal Disease study (MDRD) and African American Study of Kidney Disease and Hypertension (AASK); and cross-sectional analysis of a clinical dataset from the Mayo Clinic of four different patient populations (CKD patients, kidney transplant recipients, post kidney donation subgroup and potential kidney donors). In the cross-sectional analyses (MDRD, AASK and Mayo Clinic cohort), we examined the relation between the CrCl/iothalamate GFR (iGFR) ratio at different categories of iGFR or different levels of CrCl. In the MDRD and AASK longitudinal analyses, we studied how the CrCl/iGFR ratio changed with those who had improvement in iGFR (CrCl) over time versus those who had worsening of iGFR (CrCl) over time. Results Observed CrCl/iGFR ratios were generally on the lower end of the range reported in the literature for CKD (median 1.24 in MDRD, 1.13 in AASK and 1.25 in Mayo Clinic cohort). Among CKD patients in whom CrCl and iGFR were measured using different timed urine collections, CrCl/iGFR ratio were higher with lower iGFR categories but lower with lower CrCl categories. However, among CKD patients in whom CrCl and iGFR were measured using the same timed urine collections (which reduces dis-concordant measurement error), CrCl/iGFR ratio were higher with both lower iGFR categories and lower CrCl categories. Conclusions These data refute the recent suggestion that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio increases as GFR decreases in CKD patients. They also highlight the lack of certainty in our knowledge with regard to how much CrCl actually overestimates GFR.

Background: Contrast induced nephropathy (CIN) is a potential stumbling block in administration of contrast media. CIN has been defined as an elevation of serum creatinine (sCr) of more than >0.5 mg/dl (44 ≥mol/l) or 25% from the baseline within 48-72 hours in the truancy of alternate tenets of acute kidney injury. Incidence of CI-AKI in patients undergoing coronary angiography with normal baseline renal function was reported to be <3%. However, the occurrence of CI-AKI was found to be as high as 50% in CKD patients undergoing Coronary Angiography. This high incidence reported by different studies is mainly because of the difference in definition, underlying renal failure, type and dose of contrast media used and frequency of other co-existing important causes of acute kidney injury (AKI). Recent studies have been published showing that risk of CIN is an overestimated and over-reckoned entity in literature. Objective: To determine the frequency of CIN in CKD patients with Creatinine clearance (Crcl) less than 60 ml/min undergoing contrast exposure. Methods: We conducted Prospective, controlled single center trial in 42 patients having the creatinine clearance of less than 60 ml/min, they were risk stratified according to Mehran scoring system and underwent coronary angiography or contrast enhanced CT scan with contrast and specific protocol for prevention of CIN including intra- venous (IV) hydration with 0.9% Normal Saline was given before the procedure and were followed up to initial 72 hours post procedure. Results: 33 out of 42 patients, i.e., got adequate hydration as per protocol however 11 patients underwent procedure as pre-existing condition did not allow so. Out of 42 patients, risk stratification according to Mehran Scoring system revealed that 15 patients out of 42 patients were included in very high risk group, 14 were in high risk group and 13 patients were in intermediate risk group. Our experience revealed that 5 out of 42 patients (11.3%) were those who experienced CI-AKI and interestingly none of them required haemodialysis. Conclusion: Our study has raised serious question on incidence of CIN in high risk patients as reported previously. However, more studies are needed over this issue till that time we might consider CIN A myth rather than a reality. [ABSTRACT FROM AUTHOR]

Background: Prior papers have been inconsistent regarding how much creatinine clearance (CrCl) overestimates glomerular filtration rate (GFR). A recent cross-sectional study suggested that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio is larger when GFR is lower among patients with chronic kidney disease (CKD); but there have been no validation of this in other cohorts.Methods: To fill these gaps in knowledge regarding the relation between CrCl and GFR, we conducted cross-sectional and longitudinal analysis of the Modification of Diet in Renal Disease study (MDRD) and African American Study of Kidney Disease and Hypertension (AASK); and cross-sectional analysis of a clinical dataset from the Mayo Clinic of four different patient populations (CKD patients, kidney transplant recipients, post kidney donation subgroup and potential kidney donors). In the cross-sectional analyses (MDRD, AASK and Mayo Clinic cohort), we examined the relation between the CrCl/iothalamate GFR (iGFR) ratio at different categories of iGFR or different levels of CrCl. In the MDRD and AASK longitudinal analyses, we studied how the CrCl/iGFR ratio changed with those who had improvement in iGFR (CrCl) over time versus those who had worsening of iGFR (CrCl) over time.Results: Observed CrCl/iGFR ratios were generally on the lower end of the range reported in the literature for CKD (median 1.24 in MDRD, 1.13 in AASK and 1.25 in Mayo Clinic cohort). Among CKD patients in whom CrCl and iGFR were measured using different timed urine collections, CrCl/iGFR ratio were higher with lower iGFR categories but lower with lower CrCl categories. However, among CKD patients in whom CrCl and iGFR were measured using the same timed urine collections (which reduces dis-concordant measurement error), CrCl/iGFR ratio were higher with both lower iGFR categories and lower CrCl categories.Conclusions: These data refute the recent suggestion that measurement error alone could entirely account for the longstanding observation that CrCl/GFR ratio increases as GFR decreases in CKD patients. They also highlight the lack of certainty in our knowledge with regard to how much CrCl actually overestimates GFR. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Nil, (© 2024 Biomedical Informatics.)

Introduction: Cardiovascular disease has emerged as a major health burden worldwide with coronary artery disease (CAD) causing highest mortality and morbidity. Coronary surgery has revolutionized CAD management and has been one of the most studied procedures worldwide. Based on the application of cardiopulmonary bypass (CPB), coronary artery bypass grafting (CABG) can be on-pump or off-pump. The CPB is known to have multifactorial effects on all end-organ functions due to nonpulsatile flow and inflammation response. Renal function alteration is one of the multiple deleterious effects. There have been reports on better renal function using off-pump CABG. The present study aimed to investigate and compare the prevalence of renal dysfunction in the two techniques (i.e., on-pump and off-pump CABG). Materials and Methods: This was a single-center retrospective study conducted with the data from 199 patients categorized into two groups of off-pump [n=106] and on-pump [n=93]. Renal parameters were monitored at days 0, 1, 3, and 5 after the operation using glomerular filtration rate and creatinine clearance of patients with diabetes, hypertension, as well as both diabetes and hypertension. In addition, normal patients were analyzed in the present study. Results: Among 199 subjects who underwent the surgery, renal functions were compared between the two groups. Accordingly, no significant difference was observed in renal function derangement between the off-pump and on-pump groups. Conclusion: It was concluded that CPB does not have any additional role as the culprit in renal dysfunction. Both groups shared an almost similar change of trends in renal functions. [ABSTRACT FROM AUTHOR]

Introduction: Chronic kidney disease (CKD) is a progressive health care issue that is increasing cost burden on patients and health care system. In different researches it was concluded that relatives of patients suffering from CKD are at more risk of development of kidney problems and diagnosed with CKD. Objectives: To evaluate the early diagnosis of CKD in at risk population by screening the close family relatives of CKD patients. Study Design: Cross-sectional screening study. Setting: Nephrology Department of Jinnah Postgraduate Medical Centre (JPMC), Karachi. Period: September 2015 to January 2017. Methods: Total 200 relatives (58% male and 42% female) of CKD patients close relatives were enrolled and screened for medical history, physical examination (weight, height and BMI) and clinical investigations such as urine analysis, serum Creatinine and Glomerular filtration rate (GFR) calculated by Cock Graft Gault equation for assessment of renal functions. Results: we observed53 abnormalities in relatives of CKD patients. Family history for Diabetes was present in 58(29%) relatives, Hypertension in 42(21%) relatives, 26 (13%) relatives with Glomerulonephritis (GN), and 74 patients (37%) with Tuberculosis (TB), Kidney damage and Stone diseases. Albuminuria was high in 33% relatives of CKD patients, mostly affecting first degree relatives 20.5% as compared to second degree relatives 2.5%. Relatives of CKD patients were diagnosed with high albuminuria in DM (36.2%) as compare to HTN (35.8%) and GN (27.0%). For final diagnosis, albuminuria and CrCl were monitored, that were found abnormalin 26.5% relatives of CKD patients. Conclusion: The screened relatives of CKD patients are at higher risk of kidney problems in the future, especially patients suffering from DM, HTN and GN. [ABSTRACT FROM AUTHOR]

Highlights: [•] SEM is a novel method to model multi-variable, biological issues. [•] The impact of cadmium on renal function was sigmoidal. [•] The impact of lead on renal function was linear. [ABSTRACT FROM AUTHOR]

Background: Information regarding dosing of low-molecular-weight heparins (LMWH) for therapeutic anticoagulation in hemodialysis (HD) patients is limited. The aim of this study was to retrospectively compare the safety and efficacy of enoxaparin versus unfractionated heparin (UFH) for therapeutic anticoagulation in HD patients. Materials and Methods: This retrospective chart review evaluated HD patients treated with subcutaneous enoxaparin that were matched based on the indication for anticoagulation with patients treated with intravenous UFH to achieve therapeutic anticoagulation. Primary outcome measures included 30-day incidence of thromboembolic events and major bleeding. Secondary outcomes included rehospitalization within 30days, length of stay, and mortality. Results: One hundred sixty-four patients were evaluated, 82 in each group. The average daily dose of enoxaparin used to target therapeutic levels was 0.7±0.2mg/kg/day (range=0.4-1). Comparing enoxaparin to UFH, there was no significant difference in major bleeding (6.1% vs 11%, p=0.4) or thromboembolism (0% vs 2.4%, p=0.5). Hospital length of stay was shorter in the enoxaparin group (20±53.8 vs 28.9±44.5days, p=0.02); there was no significant difference between groups in mortality or readmission. Adjusting for risk factors for bleeding there was a slight but statistically non-significant difference between enoxaparin versus UFH (OR=0.77, 95%CI: 0.2-3.5, p=0.73). Conclusions: These findings suggest that therapeutic dosing of enoxaparin, in doses that ranged from 0.4-1mg/kg/day, was as safe as intravenous UFH in providing therapeutic anticoagulation in stable patients requiring chronic hemodialysis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To examine whether factors in a child’s perinatal history influence renal function in adolescence, using a cross-sectional study, as during the past two decades researchers have tried to ascertain whether factors such as low birth weight might be related to a decline in kidney function in adolescence, although published data for children born with vesico-ureteric reflux (VUR) remain insufficient. Patients and methods: Sixty-one children (20 boys and 41 girls), born between 1985 and 1989 in Greece and diagnosed with VUR, were assessed. A detailed personal and family history was taken and basic anthropometric variables were measured. Kidney function was calculated from serum creatinine levels, and the glomerular filtration rate (GFR), fractional excretion of sodium, albumin levels in urine, creatinine clearance, cystatin C level and the dimensions of each kidney were measured. Results: The results showed a positive relationship of birth weight (P =0.01) with blood pressure in adolescence in children diagnosed with any degree of VUR. Renal function seemed to be intact whatever the cause of VUR, the volume of the kidneys in adolescence (P =0.386 and 0.483, respectively, for the right and left kidney) and the values of GFR (P =0.105), creatinine clearance (P =0.213) and cystatin C (P =0.055). Conclusions: These results showed that although there is a positive association between blood pressure in adolescence and birth weight, in children born with VUR there was no deterioration in renal function. Kidneys seem to function normally regardless of the gestational age at birth. [Copyright &y& Elsevier]

Objectives: The goal of this study was to analyze the impact of dabigatran plasma concentrations, patient demographics, and aspirin (ASA) use on frequencies of ischemic strokes/systemic emboli and major bleeds in atrial fibrillation patients. Background: The efficacy and safety of dabigatran etexilate were demonstrated in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, but a therapeutic concentration range has not been defined. Methods: In a pre-specified analysis of RE-LY, plasma concentrations of dabigatran were determined in patients treated with dabigatran etexilate 110 mg twice daily (bid) or 150 mg bid and correlated with the clinical outcomes of ischemic stroke/systemic embolism and major bleeding using univariate and multivariate logistic regression and Cox regression models. Patient demographics and ASA use were assessed descriptively and as covariates. Results: Plasma concentrations were obtained from 9,183 patients, with 112 ischemic strokes/systemic emboli (1.3%) and 323 major bleeds (3.8%) recorded. Dabigatran levels were dependent on renal function, age, weight, and female sex, but not ethnicity, geographic region, ASA use, or clopidogrel use. A multiple logistic regression model (c-statistic 0.657, 95% confidence interval [CI]: 0.61 to 0.71) showed that the risk of ischemic events was inversely related to trough dabigatran concentrations (p = 0.045), with age and previous stroke (both p < 0.0001) as significant covariates. Multiple logistic regression (c-statistic 0.715, 95% CI: 0.69 to 0.74) showed major bleeding risk increased with dabigatran exposure (p < 0.0001), age (p < 0.0001), ASA use (p < 0.0003), and diabetes (p = 0.018) as significant covariates. Conclusions: Ischemic stroke and bleeding outcomes were correlated with dabigatran plasma concentrations. Age was the most important covariate. Individual benefit–risk might be improved by tailoring dabigatran dose after considering selected patient characteristics. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600) [Copyright &y& Elsevier]

Abstract: Pulmonary embolism (PE) remains a major healthcare problem. PE presents with a variety of non-specific symptoms, and confirmation of diagnosis involves the use of clinical risk scores, scanning techniques and laboratory tests. Treatment choice is informed by the risk of sudden death, with high-risk patients recommended to receive thrombolytic therapy or thrombectomy. Patients with less severe presentations are given anticoagulant therapy, traditionally with parenteral heparins in the acute phase of treatment, transitioning to oral vitamin K antagonists (VKAs). The limitations of these agents and the introduction of non-VKA oral anticoagulants challenge this paradigm. To date, clinical studies of four non-VKA oral anticoagulants to treat acute thrombosis have been published, and rivaroxaban is now approved for treatment and prevention of PE (and deep vein thrombosis). Rivaroxaban and apixaban alone, and dabigatran and edoxaban after parenteral anticoagulant induction, were non-inferior to enoxaparin/VKA for the prevention of recurrent venous thromboembolism; the risk of major bleeding was similar with dabigatran and edoxaban and significantly reduced with rivaroxaban and apixaban. Patients with an initial PE are recommended to receive continued anticoagulation for 3months or longer, depending on individual risk factors, and studies of non-VKA oral anticoagulants have shown a continued benefit for up to 2years, without a significantly increased risk of major bleeding. Given that the non-VKA oral anticoagulants are given at fixed doses without the need for routine coagulation monitoring, their adoption is likely to ease the burden on both PE patients and healthcare practitioners when longer-term or extended anticoagulation is warranted. [Copyright &y& Elsevier]

A large number of patients worldwide receive anticoagulant and antiplatelet agents, collectively known as antithrombotic agents. Several new anticoagulants and antiplatelet agents recently were approved for use. Gastroenterologists may be unfamiliar with the mechanism of action, indications for use, and pharmacokinetics of these newer drugs. In patients undergoing elective and urgent endoscopic procedures, clinicians must be familiar with these medications to optimize outcomes. When the decision is made to continue the newer antithrombotic agents for elective procedures, the clinician must understand the risk that these agents may impart on procedural-induced bleeding. Finally, it is important to understand how to manage these agents in the presence of acute gastrointestinal bleeding. In this article the use of newer antithrombotic agents is reviewed. [Copyright &y& Elsevier]

Abstract: Contrast medium-induced acute kidney injury (CI-AKI) remains a leading cause of iatrogenic, drug-induced acute renal failure. This study aimed to investigate the protective effects of atorvastatin against renal tubular cell apoptosis in diabetic rats and the related mechanisms. CI-AKI was induced by intravenous administration of iopromide (12ml/kg) in streptozotocin-induced diabetic rats. Atorvastatin (ATO) was administered intragastrically at the dose of 5, 10 and 30mg/kg/d in different groups, respectively, for 5 days before iopromide injection. Renal function parameters, kidney histology, renal tubular cell apoptosis, the expression of apoptosis regulatory proteins, caspase-3 and Rho-associated protein kinase 1 (ROCK-1), and the phosphorylation of myosin phosphatase target subunit -1 (MYPT-1), were determined. Atorvastatin was shown to notably ameliorate contrast medium induced medullary damage, restore renal function, and suppress renal tubular apoptosis. Meanwhile, atorvastatin up-regulated the expression of Bcl-2, down-regulated the expression of Bax, caspase-3 and ROCK-1, restored the ratio of Bcl-2/Bax, and suppressed the phosphorylation of MYPT-1 in a dose-dependent manner. Thus, atorvastatin pretreatment could dose-dependently ameliorate the development of CI-AKI, which was partly attributed to its suppression of renal tubular cell apoptosis by inhibiting the Rho/ROCK pathway. [Copyright &y& Elsevier]

Purpose: Accurate assessment of kidney function is critical to evaluate living kidney donors. Direct glomerular filtration rate measurement using isotopes is currently the gold standard but it is complex and costly. We evaluated the performance of surrogate markers of the glomerular filtration rate in living kidney donors by comparing direct measurement of the rate to the creatinine based equation estimated rate, the kidney volume based estimated rate using a newly developed equation and creatinine clearance. Materials and Methods: We first statistically compared direct glomerular filtration rate measurement to the results of the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) creatinine based equations, and to creatinine clearance in 54 potential renal donors from 2006 to 2010. In 32 donors with cross-sectional computerized tomography available we used measured functional renal volume with age, gender, weight and serum creatinine to estimate the rate based on kidney volume according to a previously reported model. Kidney volume based measurement was compared to direct glomerular filtration rate measurement and assessed against the results of the best performing creatinine based equation. Results: In the first group of 54 donors the correlation index of the estimated glomerular filtration rate according to MDRD and CKD-EPI creatinine based equations, and to creatinine clearance was low compared to direct measurement. In the subset of 32 potential donors the kidney volume based estimated rate correlated better with direct measurement than MDRD equation results with higher accuracy (estimated 87.5% and 75.0% within 30% and 10% of direct rate measurement, respectively). Conclusions: To estimate the glomerular filtration rate in healthy individuals a volume based model correlated better than the MDRD equation, which is the best performing creatinine based equation used to estimate the rate. By providing a more robust estimation of the glomerular filtration rate in healthy potential kidney donors, the volume based model adds value to routine preoperative computerized tomography above that of anatomical evaluation. [Copyright &y& Elsevier]

Objectives: This study sought to validate the Logistic Clinical SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score in patients with non–ST-segment elevation acute coronary syndromes (ACS), in order to further legitimize its clinical application. Background: The Logistic Clinical SYNTAX score allows for an individualized prediction of 1-year mortality in patients undergoing contemporary percutaneous coronary intervention. It is composed of a “Core” Model (anatomical SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction), and “Extended” Model (composed of an additional 6 clinical variables), and has previously been cross validated in 7 contemporary stent trials (>6,000 patients). Methods: One-year all-cause death was analyzed in 2,627 patients undergoing percutaneous coronary intervention from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. Mortality predictions from the Core and Extended Models were studied with respect to discrimination, that is, separation of those with and without 1-year all-cause death (assessed by the concordance [C] statistic), and calibration, that is, agreement between observed and predicted outcomes (assessed with validation plots). Decision curve analyses, which weight the harms (false positives) against benefits (true positives) of using a risk score to make mortality predictions, were undertaken to assess clinical usefulness. Results: In the ACUITY trial, the median SYNTAX score was 9.0 (interquartile range 5.0 to 16.0); approximately 40% of patients had 3-vessel disease, 29% diabetes, and 85% underwent drug-eluting stent implantation. Validation plots confirmed agreement between observed and predicted mortality. The Core and Extended Models demonstrated substantial improvements in the discriminative ability for 1-year all-cause death compared with the anatomical SYNTAX score in isolation (C-statistics: SYNTAX score: 0.64, 95% confidence interval [CI]: 0.56 to 0.71; Core Model: 0.74, 95% CI: 0.66 to 0.79; Extended Model: 0.77, 95% CI: 0.70 to 0.83). Decision curve analyses confirmed the increasing ability to correctly identify patients who would die at 1 year with the Extended Model versus the Core Model versus the anatomical SYNTAX score, over a wide range of thresholds for mortality risk predictions. Conclusions: Compared to the anatomical SYNTAX score alone, the Core and Extended Models of the Logistic Clinical SYNTAX score more accurately predicted individual 1-year mortality in patients presenting with non–ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention. These findings support the clinical application of the Logistic Clinical SYNTAX score. [Copyright &y& Elsevier]

Permeability glycoprotein (P-gp) mediates the export of drugs from cells located in the small intestine, blood-brain barrier, hepatocytes, and kidney proximal tubule, serving a protective function for the body against foreign substances. Intestinal absorption, biliary excretion, and urinary excretion of P-gp substrates can therefore be altered by either the inhibition or induction of P-gp. A wide spectrum of drugs, such as anticancer agents and steroids, are known P-gp substrates and/or inhibitors, and many cardiovascular drugs have recently been observed to have clinically relevant interactions as well. We review the interactions among commonly prescribed cardiovascular drugs that are P-gp substrates and observe interactions involving P-gp that may be relevant to clinical practice. Cardiovascular drugs with narrow therapeutic indexes (e.g., antiarrhythmic agents, anticoagulant agents) have demonstrated large increases in concentrations when coadministered with potent P-gp inhibitors, thus increasing the risk for drug toxicity. Therefore, dose adjustment or use of alternative agents should be considered when strong P-gp-mediated drug-drug interactions are present. Finally, interactions between novel drugs and known P-gp inhibitors are now being systematically evaluated during drug development, and recommended guidelines for the administration of P-gp substrate drugs will be expanded. [Copyright &y& Elsevier]

Objectives: This study aimed to investigate the prevalence of a reduced glomerular filtration rate (GFR) with and without albuminuria and its ability to predict cardiac events in asymptomatic diabetic patients undergoing stress-rest thallium-201 myocardial perfusion single-photon emission computed tomography. Background: Diabetic patients have a higher prevalence of asymptomatic coronary heart disease. Therefore, identifying predictors of cardiac events in asymptomatic diabetic patients is needed. Methods: In 269 asymptomatic patients, baseline evaluation included diabetes-related complications, including creatinine clearance (CrCl) and albuminuria. During follow-up (mean 2.3 ± 1.0 years), all cardiac events were recorded. Results: Seventy-seven patients (29%) had a reduced GFR defined by CrCl <60 ml/min/1.73 m2. Compared with the 177 patients with CrCl ≥60 ml/min/1.73 m2, the reduced GFR group was older (p < 0.0001), had a longer duration of diabetes (p = 0.002), and had a higher prevalence of albuminuria (p = 0.04). Nevertheless, 35% of the reduced GFR group had normoalbuminuria. Patients with reduced GFR had a significant two-fold increase in total cardiac events (unstable angina, nonfatal myocardial infarction, and cardiac procedures) (25% vs. 13%, p = 0.019), and multivariate analysis found that reduced GFR was an independent predictor of cardiac events (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1 to 4.46). Other independent predictors of cardiac events included stress-induced abnormal myocardial perfusion imaging (OR 3.1, 95% CI 1.3 to 7.5), an electrocardiographic ischemic response (OR 2.7, 95% CI 1.01 to 7.14), and peripheral artery disease (OR 2.1, 95% CI 1.05 to 4.23); however, albuminuria was not. Conclusions: A reduced GFR was common in our group of asymptomatic diabetic patients and was associated with a two-fold increase in cardiac events. Multivariate analysis found that reduced GFR independent of albuminuria was a significant predictor of cardiac events. [Copyright &y& Elsevier]

Objectives: The aim of this study was to determine the reference intervals for serum creatinine, the renal creatinine output and the creatinine clearance (CrCl) with two new methods for accurate creatinine determination. Methods: The reference population consisted of 252 healthy subjects (127 males and 125 females) at the age between 18 and 74 years, median 27. Urine was collected for exactly 24 h. Creatinine in serum and urine was measured with an enzymatic assay (“Creatinine Plus”) and a modification of the kinetic Jaffé reaction, named “Jaffé compensated”. Results: Reference values for serum creatinine were almost identical to previously published ones obtained with the same methods: 0.73–1.18 and 0.55–1.02 mg/dl for males and females, respectively, with the enzymatic, 0.72–1.16 and 0.55–0.96 mg/dl with the compensated Jaffé method (Jcomp). CrCl values were normally distributed and showed no gender difference in contrast to some previous studies. The reference interval for the entire group was found to be 66–143 ml/min with the enzymatic assay and 71–151 ml/min with the chemical one. [Copyright &y& Elsevier]

: ObjectivesWe examined the prevalence and severity of renal artery stenosis (RAS) in patients undergoing cardiac catheterization who were deemed at risk for RAS based on clinical or laboratory criteria for study entry, but who had not previously been suspected of having RAS.: BackgroundThe diagnosis of atherosclerotic RAS remains problematic because its clinical manifestations are nonspecific.: MethodsConsecutive patients undergoing non-emergent cardiac catheterization at a single institution during a 12-month period were evaluated using standardized clinical, laboratory, and angiographic criteria. Patients exhibiting at least one of four predefined selection criteria (severe hypertension, unexplained renal dysfunction, acute pulmonary edema with hypertension, or severe atherosclerosis) were prospectively registered and underwent coincident diagnostic renal angiography.: ResultsRenal angiography was performed in 851 patients and was diagnostic in 837. Angiographically evident renal atherosclerosis was present in 39% of the population, with RAS ≥50% in 120 (14.3%) and severe stenosis (≥70%) in 61 (7.3%). Severe stenosis was present in 48 (7%) patients with severe atherosclerosis, 38 (16%) with renal dysfunction, 25 (9%) with hypertension, and 2 (22%) with acute pulmonary edema with hypertension. The prevalence was higher in those exhibiting multiple selection criteria. In a multivariate model, severe RAS was associated with age, female gender, reduced creatinine clearance, increased systolic blood pressure, and peripheral or carotid artery disease.: ConclusionsIn a population at risk of, but not previously suspected of having RAS, severe RAS is associated with simple and readily determined clinical and laboratory patient characteristics. These data facilitate focused application of diagnostic renal angiography. [Copyright &y& Elsevier]

Introduction: Ximelagatran is a novel, oral direct thrombin inhibitor that is currently being investigated for the prophylaxis and treatment of thromboembolic events. This study evaluated the pharmacokinetics, pharmacodynamics, and clinical effects of melagatran, the active form of ximelagatran, in patients with both deep vein thrombosis (DVT) and pulmonary embolism (PE). Materials and methods: In this open-label study, 12 patients received a fixed dose of 48 mg oral ximelagatran twice daily for 6–9 days. Plasma samples were collected for determination of melagatran concentrations and scintigraphic changes and adverse events were recorded. Results: Peak plasma concentrations of melagatran were attained approximately 2 h after administration of ximelagatran. Melagatran plasma concentration profiles were similar on Days 1, 2, and 6–9. Plasma activated partial thromboplastin time increased following administration of ximelagatran and reached a peak that was approximately twofold higher than the predose activated partial thromboplastin time and correlated with melagatran plasma concentrations (R2=0.69). All but one patient (with malignancy) showed regressed or unchanged lung scintigraphic findings, and six of these demonstrated no, or only minor, perfusion defects at central evaluation after 6–9 days of ximelagatran treatment. Clinical symptoms, including chest pain, dyspnoea, cough, and oedema, and pain in the affected leg, were improved. Ximelagatran was well tolerated with no deaths or severe bleeding events reported during treatment. Conclusion: Treatment with a fixed dose of oral ximelagatran, used without routine coagulation monitoring, showed reproducible pharmacokinetics and pharmacodynamics with a rapid onset of action and promising clinical results in patients with pulmonary embolism. [Copyright &y& Elsevier]

The pharmacokinetics of the low-molecular-weight heparin enoxaparin were evaluated in 12 healthy volunteers and 36 patients with mild, moderate or severe renal impairment. Enoxaparin was administered once daily by subcutaneous injections at a dose of 40 mg for 4 days and venous blood samples were taken over a 5-day period to determine antifactor Xa and antifactor IIa activity and the activated partial thromboplastin time. Adverse events were also recorded. The results for anti-Xa activity showed that the rate of absorption of enoxaparin was similar across the four groups of study participants. The elimination half-life increased with the degree of renal impairment, and this relationship was more evident after repeated dosing. Anti-Xa exposure was not significantly different between healthy volunteers and patients with mild or moderate renal impairment, but was significantly increased in patients with severe renal impairment (creatinine clearance ≤30 ml/min). Anti-Xa clearance decreased with the degree of renal impairment after repeated dosing, but only the difference between patients with severe renal impairment and healthy volunteers was statistically significant, the clearance on Day 4 being 39% lower in patients with severe renal impairment than in healthy volunteers (P=.0001). Anti-IIa activity was low in all study participants, and the activated partial thromboplastin time was not significantly different between the study groups. In conclusion, the clearance of enoxaparin is reduced in patients with severe renal impairment. Dose adjustment of enoxaparin may need to be recommended in these patients, but no recommendation can be made in patients with mild or moderate renal impairment. [Copyright &y& Elsevier]

Background: Polymyxin B (PMB) is a basic cyclic polypeptide antibiotic produced by Bacillus polymyxa , and is one of the last options for treating multi-drug-resistant negative bacterial infections in clinical practice. In recent years, many population pharmacokinetic studies of PMB have been conducted. This paper sought to comprehensively summarize the characteristics of population pharmacokinetic models of PMB and provide a theoretical basis for the individualized use of PMB., Methods: In this review, we systematically searched the PubMed and Embase databases to find articles on population pharmacokinetic models published from database establishment to August 2021., Results: A total of 10 studies were included in this review, including studies on various types of severe infections caused by multi-drug-resistant bacteria, hospital-acquired infections with fibrosis and other male and female populations, and a study of 2 continuous renal replacement therapy (CRRT) patients, aged 16-94 years, who received PMB doses of 10-360 mg/day (0.13-3.45 mg/kg/day), at an administration time of 0.5-6 hours. First-order linear elimination was used in all the studies; a 1-compartment model was used in 5 studies, and a 2-compartment model was used in 5 studies. The most common covariates were creatinine clearance (CrCL) and body weight., Discussion: Although these studies included several covariates and total clearance (CL) was close, but the external validation of some models was poorly correlated between the actual and predicted value. Novel or potential covariates represent important directions for further study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-236/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)