Serum Creatinine Concentration Research Articles

Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex)

Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR.

Pseudo-Worsening of Kidney Function Due to Inhibition of Renal Creatinine Secretion: Quality of Information Provided in Prescribing Information/SmPC.

Determination of serum creatinine concentrations and subsequent calculation of estimated glomerular filtration rates (eGFR) is a cornerstone of clinical medicine. Crucial clinical decisions such as drug treatment discontinuations are based on eGFR calculated from serum creatinine measurements. However, creatinine is not only filtered in the kidneys, but also actively secreted into urine. Creatinine transporters such as OCT2, OCT3, MATE1, MATE2-K, and OAT2 expressed in proximal tubular cells are responsible for active renal secretion of creatinine. Multiple drugs (e.g., oral antitumor drugs) inhibit these transporters thereby causing a pseudo-worsening of kidney function with an increase in serum creatinine concentrations and a decrease in eGFR while other methods for eGFR determination (e.g., by cystatin C) reveal normal kidney function. Since US Prescribing Information (PI) and European Summaries of Product Characteristics (SmPCs) are the most relevant source of information for physicians, we investigated the quality of information in US PI/German SmPCs of drugs with clear evidence for pseudo-worsening of kidney function. 514 drugs putatively interacting with creatinine transporters were identified. For 149 of those drugs, an increase in serum creatinine concentrations has been described. Available data confirmed the existence of pseudo-worsening of kidney function for 30 of those drugs, for the remaining 119 drugs existing data are insufficient. Only 23.5% (12/51) of the 30 drugs' PI/SmPCs contained unambiguous statements on this proven pseudo-worsening of kidney function and gave clear recommendations for clinical management. Taken together, inadequate information provided in PI or SmPCs on the pseudo-worsening of kidney function poses patients at unnecessary risks.

Research on Predicting Survival in Heart Failure Patients of Logistic Regression Models

Abstract. The purpose of this paper is to study a logistic regression model for predicting the survival of patients with heart failure. Heart failure is a serious clinical syndrome that usually develops from multiple heart diseases, and its inadequate pumping function of the heart poses a significant threat to the life and health of the patient and a significant economic burden on the healthcare system. Using medical record data from 299 patients with heart failure in the UCI database, this research utilized logistic regression models to identify the critical factors influencing the survival of heart failure patients and to forecast their survival outcomes. This paper found that age, ejection fraction, serum creatinine concentration and follow-up period are significant factors affecting survival in patients with heart failure. By adopting backward elimination method to optimize the model, the accuracy of prediction is further improved. The optimized logistic regression model yields an area under the Receiver Operating Characteristic (ROC) curve of 0.845, showing high prediction accuracy. The conclusions of this study provide a new perspective for the early diagnosis, risk assessment and personalized treatment of heart failure.

Clinical findings, prognostic factors, and outcome of protein-losing nephropathy in cats: A retrospective study.

Primary glomerular disease resulting in protein-losing nephropathy (PLN) is an uncommon cause of chronic kidney disease in cats, yet is important to recognize because it warrants specific treatment that impacts outcome. Characterize clinicopathologic findings, prognostic indicators, and short- (≤30 days) and long-term survival of cats with PLN. Thirty-seven cats with naturally occurring PLN. Medical records of cats with PLN admitted to a veterinary teaching hospital were retrospectively reviewed. Median age was 3 years (range, 1.5-11.5 years) and 17/37 (46%) were males. Short-term survival was 57%. The estimated median survival time of all cats was 424 days (95% confidence interval [CI], 0-1098 days). Common clinical signs included lethargy (57%), edema (46%) and weight loss (35%). Edema was more common in short-term survivors compared with nonsurvivors (odds ratio [OR], 0.21; 95% CI, 0.05-0.86-20.4; P = .04). Serum creatinine concentration at presentation was negatively associated with long-term survival (OR, 1.3; 95% CI, 1.03-1.52; P = .01). Administration of immunosuppressive and antiproteinuric medications was more common among short-term survivors compared with nonsurvivors (18/20 [90%] vs 9/16 [56%]; OR, 7.0; 95% CI, 1.2-40.8; P = .05 and 17/20 [85%] vs 7/16 [44%]; OR, 7.3; 95% CI, 1.5-35.2; P = .01, respectively). Partial or complete remission was documented in 11/31 (36%) cats and was associated with both short (OR, 3.3; 95% CI, 1.7-6.5; P < .001) and long-term survival (P = .003). Cats with PLN have a guarded prognosis, but achieving remission improves outcome. Cats presented with edema rather than azotemia are more likely to respond to treatment.

Determinants of the serum potassium concentration in chronic kidney disease.

If Ccr is creatinine clearance, a surrogate for glomerular filtration rate (GFR), the serum potassium concentration (Ks) is the sum of EK/Ccr and TRK/Ccr, which are amounts of potassium excreted and (net) reabsorbed per volume of filtrate (Ks = EK/Ccr + TRK/Ccr). We investigated changes in EK/Ccr, TRK/Ccr, and Ks through the stages of chronic kidney disease (CKD). We performed a retrospective study of 452 patients with CKD stages G1 - 5. Simultaneous measurements of serum and urine potassium and creatinine concentrations (Ks, Ku, crs, and cru) were used to calculate 1,007 individual values of EK/Ccr and TRK/Ccr as Ku×crs/cru and Ks - EK/Ccr, respectively. Mean values of EK/Ccr and TRK/Ccr were determined in CKD stages G1 - 5. Within each stage, means of the ratios were also ascertained in subsets with hyperkalemia (Ks > 5.1 mmol/L), normokalemia (Ks 3.8 - 5.1 mmol/L), and hypokalemia (Ks < 3.8 mmol/L). In comparison to values in CKD stages G1 - 2, EK/Ccr rose and TRK/Ccr fell in each higher stage. Decrements in TRK/Ccr equaled increments in EK/Ccr in G3a and G3b, and Ks remained stable. In G4 - 5, the ascent of EK/Ccr exceeded the decline in TRK/Ccr, and Ks rose accordingly. Within each CKD stage, EK/Ccr was remarkably similar in the three kalemic subsets; consequently, differences in TRK/Ccr were the sole source of differences in Ks. EK/Ccr rises and TRK/Ccr falls through the stages of CKD. Ks remains stable in stages G3a - 3b in association with equal and opposite changes in EK/Ccr and TRK/Ccr. In stages G4 - 5, Ks increases progressively because EK/Ccr rises more than TRK/Ccr falls. Within each CKD stage, differences in TRK/Ccr account entirely for differences in Ks among hyper-, normo-, and hypokalemic subsets. Causes of variability of TRK/Ccr require additional investigation.

Acute kidney injury in relation to high-sensitivity cardiac troponin T levels in the emergency department

Abstract Background The clinical implications of high-sensitivity cardiac troponin T (hs-cTnT) measurements in all-comers with AKI in the emergency department (ED) is largely unknown. Purpose To investigate the prevalence of myocardial injury, associations between serum-creatinine concentrations (SCC) and hs-cTnT kinetics, and the accuracy of established hs-cTnT-based myocardial infarction (MI) risk stratification algorithm criteria in patients with AKI. Methods This observational cohort study was based on patient visits to 7 EDs in Sweden from December 9, 2010 to August 31, 2017. All visits by patients ≥18 years fulfilling criteria for AKI with ≥1 hs-cTnT measurement and the exposure was dynamic change in SCC (ΔSCC) during the visits. Linear mixed models were used to estimate linear predictors of kinetic change in hs-cTnT (Δhs-cTnT). Logistic regression models were applied to calculate odds ratios (ORs) for Δhs-cTnT indicative of acute myocardial injury (Δhs-cTnT &amp;gt;20% and elevated hs-cTnT) in relation to ΔSCC among patients without MI, and to assess the diagnostic performance of hs-cTnT for MI in a subgroup of patients presenting with chest pain. Results A total of 15,211 visits by patients with AKI were included, of whom 1174 (8%) had an MI. Four of five (81%) patients without MI had myocardial injury (hs-cTnT &amp;gt;14 ng/l), and almost one of three (31%) had acute myocardial injury. These entities were common in both cardiac and non-cardiac conditions. The Δhs-cTnT in non-MI patients was 1.8-fold (β: 1.78, 95% CI: 1.62-1.96) in the highest quartile of ΔSCC and was paralleled by a 2-fold risk of acute myocardial injury (OR: 2.32, 95% CI: 2.08-2.59), compared with the lowest ΔSCC quartile. Using a 0 h hs-cTnT cut-off ≥52 ng/l assigned 627 (26%) patients to a high-risk group in whom the specificity and positive predictive value (PPV) for MI was low (78.5% (95% CI: 76.7-80.2) and 27.6% (95% CI: 24.1-31.3), respectively). Conclusions Hs-cTnT concentrations indicative of acute myocardial injury are frequently observed among all-comers with AKI in the ED and are associated with dynamic changes in SCC. These observations are accompanied by poor performance of recommended hs-cTnT-based algorithms for MI risk stratification in patients with chest pain.

Gender-related differences in clinical characteristics of patients with hypertrophic cardiomyopathy in our city

Abstract Background Female patients with hypertrophic cardiomyopathy (HCM) tend to display a higher rate of heart failure as well as lower survival compared to male patients. Despite this, gender-related differences in the clinical characteristics of HCM patients remain unclear. Methods and Aim Consecutive HCM patients were prospectively enrolled at a tertiary referral center. The primary objective of this study was to investigate and emphasize gender differences in clinical characteristics including imaging and laboratory parameters. Results Between May 2018 and January 2024, a total of 301 HCM patients were included, of which 41.9% were female (n=125). Female patients were significantly older and more symptomatic than male counterparts (59 years [IQR 47-67] vs. 53 years [IQR 39-61], p=0.001; New York Heart Association functional class ³III: 28.8% vs. 17.6%, p=0.002, respectively). No significant differences in body mass index were found (28.4 kg/m² [IQR 24.9-31.6] vs. 28.4 kg/m² [IQR 25.9-31.8], p=0.8). With respect to echocardiographic parameters, although interventricular septal thickness was comparable (19.0 mm [IQR 16.0-22.0] vs. 19.5 mm [IQR 17.0-22.0], p=0.4) left atrial as well as right atrial volume index were higher in women (30.0 cm³/m² [IQR 27.0-35.0] vs. 27.0 cm³/m² [IQR 24.0-30.0], p&amp;lt;0.001; 27.1 cm³/m² [IQR 25.4-29.3] vs. 24.7 cm³/m² [IQR 22.5-28.2], p&amp;lt;0.001). These findings were further supported by elevated filling pressures in female patients reflected by E/e’ ratio (16 [IQR 14-22] vs. 10 [IQR 9-12], p&amp;lt;0.001). Moreover, these patients showed more frequent left ventricular (LV) outflow tract obstruction (50% vs. 33%, p=0.029) which is accompanied by a slightly higher LV ejection fraction compared to men (69% [IQR 62-74] vs. 62% [IQR 55-67], p=0.004). In terms of cardiac biomarkers, female HCM patients presented with higher levels of serum N-terminal pro brain natriuretic peptide (671 pg/ml [IQR 333-1613] vs. 357 pg/ml [IQR 115-959], p&amp;lt;0,001) as well as lower concentrations of serum creatinine (0.84 mg/dl [IQR 0.75-0.95] vs. 0.98 mg/dl [IQR 0.87-1.15], p&amp;lt;0.001) whereas no differences regarding high-sensitive troponin-T levels were observed. Conclusion This single-center analysis illustrates profound gender-related differences among HCM patients in Vienna. Female patients tend to present in a more advanced clinical status, rather reflecting the phenotype of heart failure with preserved ejection fraction. Whether these findings should prompt an early HCM diagnosis in female patients with unspecific symptoms, or may result in early treatment initiation of e.g. sodium-glucose-transporter 2 inhibitors, should be part of future research.

Growth Performance, Dietary Energetics, Blood Metabolites, Carcass Traits, Meat Quality, and Gene Expression of Lambs Supplemented with a Polyherbal Phytogenic Additive

This study aimed to evaluate the effects of supplementation with a polyherbal phytogenic additive (PPA) on the productive performance, dietary energetics, blood metabolites, carcass traits, meat quality, and gene expression of finishing lambs. Thirty-six male Pelibuey lambs (23.61 ± 0.57 kg body weight (BW)) were housed in individual pens and assigned to four treatments (n = 9) with different doses of PPA: 0 (CON), 2.5 (PPAL), 5 (PPAM), and 7.5 (PPAH) g of PPA/kg of DM for 56 days. Average daily gain, dry matter intake, and observed dietary net energy for maintenance and weight gain increased linearly (p &lt; 0.05) in lambs supplemented with PPAH. A linear reduction (p = 0.02) in FCR was detected in lambs fed PPAM and PPAH. The PPAH supplementation linearly increased (p &lt; 0.001) Longissimus dorsi muscle area, but other carcass traits were not affected (p &gt; 0.05) by PPA doses. The physicochemical characteristics of the meat and the hematological parameters of the lambs were not affected (p &gt; 0.05) by the PPA doses. The glucose, uric acid, creatinine, and bilirubin serum concentrations decreased linearly (p &lt; 0.05) in lambs supplemented with PPAM and PPAH. Gene ontology analyses showed that nine biological processes were modified (p &lt; 0.05), including DNA replication, drug metabolism–cytochrome P450, oxidative phosphorylation, and chemical carcinogenesis–reactive oxygen species. In conclusion, high doses (7.5 g/kg DM) of PPA can improve growth performance and dietary energy utilization efficiency in finishing lambs. Likewise, gene expression analysis indicates that supplementation with high doses of PPA could improve energy production and antioxidant status in finishing lambs.

Accuracy of estimating equations for the assessment of glomerular filtration rate in critically ill patients versus outpatients.

Estimating equations for the assessment of glomerular filtration rate (GFR) have been poorly investigated in the critical care setting. We evaluated the agreement between the GFR measured with 51CrEDTA/iohexol (mGFR) and four estimating equations based on serum concentrations of creatine and/or cystatin C (eGFR) in two cohorts: critically ill patients and outpatients with normal-to-moderately reduced GFR. Forty-three patients in the critical care group and 48 patients in the outpatient group were included. GFR was measured (mGFR) by plasma infusion clearance of 51Cr-EDTA/iohexol (critical care group) and the single injection, one-sample plasma 51Cr-EDTA clearance technique (outpatients). The following estimating equations (eGFR) were used: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for creatinine (CKD-EPICr), cystatin C (CKD-EPICys C), creatinine+cystatin C (CKD-EPICr + Cys C) and the Lund-Malmö creatinine+cystatin C equation (LMCr + Cys C). Agreement between mGFR and eGFR was assessed by the Bland-Altman method and accuracy by calculating P30 and P10. In the critically ill group, the bias between the estimating equations and mGFR was -3.6 to 2.8 mL/min/1.73 m2, while the error was 121%-127% and the accuracy (P30) 33%-40%. In the outpatients, the bias between the estimating equations and mGFR was -13.0 to 7.6 mL/min/1.73 m2, while the error was 31%-41% and the accuracy (P30), 67%-96%. All four equations performed poorly in assessing GFR in the critically ill cohort with an unacceptably high error and low accuracy in contrast to the outpatient group. To accurately assess GFR in critically ill patients, GFR must be measured not estimated. For the assessment of glomerular filtration rate (GFR), it can be measured directly, but is frequently estimated using a point measure of serum creatinine concentration. In this study, ICU case GFR estimations, by different adjusted equations, done also for a cohort of outpatients, showed that these serum creatinine-based estimations for ICU cases are not highly precise or reliable.

Effect of Dapagliflozin on Measured vs. Panel-Estimated Glomerular Filtration Rate.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors can cause a reversible decline in glomerular filtration rate (GFR), which may influence dosing recommendations for renally excreted medications. In practice, GFR is typically estimated by serum creatinine concentration, but creatinine may not be a reliable indicator of GFR decline in the setting of SGLT2 inhibitor use. Alternative filtration markers such as cystatin C, β-trace protein (BTP), and β2-microglobulin (B2M) may be more appropriate, but little is known about how these markers are affected by SGLT2 inhibitor use. Therefore, we determined creatinine, cystatin C, BTP, and B2M concentration in a crossover study of 35 people with type 2 diabetes receiving 12 weeks of dapagliflozin treatment or placebo. Estimated GFR (eGFR) based on creatinine (eGFRcre), cystatin C (eGFRcys), their combination (eGFRcomb), or a panel of all four markers (eGFRpanel) was compared with measured GFR (mGFR) based on plasma clearance of chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA). Dapagliflozin treatment was associated with a significant decrease in mGFR (-9 mL/min/1.73 m2, P < 0.001) but not a corresponding increase in concentration of any filtration marker. No eGFR equation accurately predicted change in mGFR between treatment periods, but eGFRcomb and eGFRpanel yielded the highest overall accuracy relative to mGFR across both treatment periods. These findings highlight the stability in performance gained by combining multiple filtration markers but suggest that eGFR in general is not an ideal metric for assessing short-term GFR decline in people initiating SGLT2 inhibitor therapy.

Higher dose antiviral therapy for herpes infections is associated with a risk of serious adverse events in older adults with chronic kidney disease.

Antiviral use has been linked to encephalopathy and elevated serum creatinine concentrations in individuals with chronic kidney disease (CKD) in case reports. Using linked healthcare data in Ontario, we conducted a population-based cohort study on adults aged ≥66 years not receiving dialysis and newly prescribed oral acyclovir, valacyclovir, or famciclovir in the outpatient setting (2008-2022) at higher versus lower doses. The primary composite outcome, a hospital visit with encephalopathy or acute kidney injury (AKI) within 14 days of initiating antiviral treatment, was examined in a primary cohort. AKI was assessed in a secondary cohort of older adults with CKD with available linked hospital-based laboratory (lab) data. We used inverse probability of treatment weighting on the propensity score to balance comparison groups on baseline health. Weighted risk ratios (RR) and risk differences (RD) were obtained using modified Poisson and binomial regression. In the primary cohort, higher- versus lower-dose antiviral was not associated with an increased 14-day risk of hospital visit with encephalopathy or AKI. However, Higher- versus lower-dose antiviral was associated with a higher risk of a hospital visit with AKI when assessed using lab values (weighted number of events, 70 of 8407 [0.83%] versus 18 of 8230 [0.22%], respectively; weighted RR, 3.83 [95% CI, 1.87-7.87]; weighted RD, 0.62% [95% CI, 0.37%-0.86%]). In older adults with CKD, starting an antiviral at a higher versus lower dose was associated with a higher risk of AKI, although the absolute risk of this event was <1%.

CircTMCO3 alleviates sepsis-induced acute kidney injury via regulating miR-218-5p/ZEB2 axis.

Growing evidence has found the critical role of circular RNAs (circRNAs) in sepsis-induced acute kidney injury (S-AKI). CircTMCO3 has been found to be involved in tumor microenvironment changes of ovarian cancer. This study aimed to explore whether circTMCO3 functions in S-AKI, and if so, to elucidate the molecular mechanism. CircTMCO3 expression was analyzed in lipopolysaccharide (LPS)-induced HK-2 cells and in the kidney tissues of mice treated with cecal ligation and puncture (CLP), respectively. Furthermore, the effects of circTMCO3 on S-AKI and the related mechanisms were evaluated in both models through gain- and/or loss-of-function strategies. CircTMCO3 expression was suppressed in both S-AKI models. Upregulation of circTMCO3 mitigated LPS-induced apoptosis, oxidative stress and inflammation in HK-2 cells. In contrast, circTMCO3 downregulation exacerbated LPS-induced injuries in HK-2 cells. Intravenous injection of circTMCO3 lentivirus to increase circTMCO3 expression improved renal function and attenuated kidney injury in S-AKI mice, as evidenced by the decrease in serum creatinine and blood urea nitrogen concentrations, amelioration of tubular pathological injury, reduction of renal cell apoptosis, and mitigation of oxidative stress and proinflammatory cytokines (TNF-α, IL-1β, and IL-6). Moreover, circTMCO3 directly targeted miR-218-5p, and the mimic of which abolished the protective effect of circTMCO3 in cell models. ZEB2 was identified to be a target of miR-218-5p; its downregulation not only reversed the impacts of miR-218-5p inhibitor on S-AKI, but also mitigated the effects mediated by circTMCO3 upregulation in vitro. CircTMCO3 protects against S-AKI by regulating miR-218-5p/ZEB2 axis, thereby mediating anti-apoptotic, antioxidant and anti-inflammatory activities. This indicates that increasing circTMCO3 expression might be a future therapeutic method for S-AKI.

Predictive performance of urinalysis for urine culture results according to causative microorganisms: an integrated analysis with artificial intelligence.

Urinary tract infections (UTIs) are pervasive and prevalent in both community and hospital settings. Recent trends in the changes of the causative microorganisms in these infections could affect the effectiveness of urinalysis (UA). We aimed to evaluate the predictive performance of UA for urinary culture test results according to the causative microorganisms. In addition, UA results were integrated with artificial intelligence (AI) methods to improve the predictive power. A total of 360,376 suspected UTI patients were enrolled from two university hospitals and one commercial laboratory. To ensure broad model applicability, only a limited range of clinical data available from commercial laboratories was used in the analyses. Overall, 53,408 (14.8%) patients were identified as having a positive urine culture. Among the UA tests, the combination of leukocyte esterase and nitrite tests showed the highest area under the curve (AUROC, 0.766; 95% CI, 0.764-0.768) for predicting urine culture positivity but performed poorly for Gram-positive bacteriuria (0.642; 0.637-0.647). The application of an AI model improved the predictive power of the model for urine culture results to an AUROC of 0.872 (0.870-0.875), and the model showed superior performance metrics not only for Gram-negative bacteriuria (0.901; 0.899-0.902) but also for Gram-positive bacteriuria (0.745; 0.740-0.749) and funguria (0.872; 0.865-0.879). As the prevalence of non-Escherichia coli-caused UTIs increases, the performance of UA in predicting UTIs could be compromised. The addition of AI technologies has shown potential for improving the predictive performance of UA for urine culture results.IMPORTANCEUA had good performance in predicting urine culture results caused by Gram-negative bacteria, especially for Escherichia coli and Pseudomonas aeruginosa bacteriuria, but had limitations in predicting urine culture results caused by Gram-positive bacteria, including Streptococcus agalactiae and Enterococcus faecalis. We developed and externally validated an AI model incorporating minimal demographic information of patients (age and sex) and laboratory data for UA, complete blood count, and serum creatinine concentrations. The AI model exhibited improved performance in predicting urine culture results across all the causative microorganisms, including Gram-positive bacteria, Gram-negative bacteria, and fungi.

Clinical characteristics of snake envenomation-related acute kidney injury in South Korea.

Acute kidney injury (AKI) is a common complication of bites by Viperidae snakes. The main venomous snakes in South Korea are members of the Viperidae family, but there is limited information on snake-bite induced AKI in South Korea. Therefore, we investigated snake envenomation-related AKI and the performance of surrogate baseline creatinine to diagnose true AKI. This retrospective, case-control study divided 71 patients with baseline serum creatinine into two groups according to the development of envenomation-related AKI determined based on Kidney Disease Improving Global Outcome Classification. The incidence of AKI was 14.1% with 10% having stage-3 AKI. During hospitalization, the AKI group did not develop venom-induced consumption coagulopathy more frequently than did the non-AKI group. Only one patient needed renal replacement therapy, and no patients died. The serum creatinine concentration at presentation underestimated the incidence of AKI, while the lowest creatinine concentration during hospitalization overestimated the incidence of AKI. After discharge, the incidence of chronic kidney disease did not increase in the AKI group. Snake envenomation-related AKI is characterized by a relatively lower incidence and severity, has no correlation with coagulation disturbance, and has favorable short- and long-term outcomes in South Korea. Based on this study, it is recommended that future envenomation-related AKI studies would utilize the baseline creatinine for diagnosing AKI. If not, envenomation-related AKI studies should include the definition of baseline creatinine used to diagnose AKI and report bias if a baseline creatinine surrogate is used.

Characterisation of older patients that require, but do not undergo, emergency laparotomy: a multicentre cohort study

BackgroundOlder adults (≥65 yr) account for the majority of emergency laparotomies in the UK and are well characterised with reported outcomes. In contrast, there is limited knowledge on those patients that require emergency laparotomy but do not undergo surgery (NoLaps). MethodsA multicentre cohort study (n=64 UK surgical centres) recruited 750 consecutive NoLap patients (February 15th - November 15th 2021, inclusive of a 90-day follow up period). Each patient was admitted to hospital with a surgical condition treatable by an emergency laparotomy (defined by The National Emergency Laparotomy Audit (NELA) criteria), but a decision was made not to undergo surgery (NoLap). ResultsNoLap patients were predominately female (452 patients, 60%), of advanced age (median age 83.0 yr, interquartile range 77.0–88.8), frail (523 patients, 70%), and had severe comorbidity (750 patients, 100%); 99% underwent CT scanning. The commonest diagnoses were perforation (26%), small bowel obstruction (17%), and ischaemic bowel (13%). The 90-day mortality was 79% and influencing factors were >80 yr, underweight BMI, elevated serum lactate or creatinine concentration. The majority of patients died in hospital (77%), with those with ischaemic bowel dying early. For the 21% of NoLap patients that survived to 90 days, 77% returned home with increased care requirements. ConclusionsThis study reports that the NoLap patient population present significant medical challenges because of their extreme levels of comorbidity, frailty, and physiology. Despite these complexities a fifth remained alive at 90 days. Further work is underway to explore this high-risk decision-making process. Clinical trial registrationISRCTN14556210.

AcFibroMASH Index for the Diagnosis of Fibrotic MASH and Prediction of Liver-related Events: An International Multicenter Study

Background & AimsMetabolic dysfunction-associated steatohepatitis (MASH) and fibrotic MASH are significant health challenges. This multi-national study aimed to validate the acMASH index (including serum creatinine and aspartate aminotransferase concentrations) for MASH diagnosis and develop a new index (acFibroMASH) for non-invasively identifying fibrotic MASH and exploring its predictive value for liver-related events (LREs). MethodsWe analyzed data from 3,004 individuals with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) across 29 Chinese and nine international cohorts to validate the acMASH index and develop the acFibroMASH index. Additionally, we utilized the independent external data from a multi-national cohort of 9,034 patients with MAFLD to examine associations between the acFibroMASH index and the risk of LREs. ResultsIn the pooled global cohort, the acMASH index identified MASH with an AUROC of 0.802 (95%CI 0.786-0.818). The acFibroMASH index (including the acMASH index plus liver stiffness measurement) accurately identified fibrotic MASH with an AUROC of 0.808 in the derivation cohort and 0.800 in the validation cohort. Notably, the AUROC for the acFibroMASH index was 0.835 (95% CI 0.786-0.882), superior to that of the FAST score at 0.750 (95% CI 0.693-0.800, P<0.01) in predicting the 5-year risk of LREs. Patients with acFibroMASH >0.39 had a higher risk of LREs than those with acFibroMASH <0.15 (adjusted-hazard ratio: 11.23 95%CI 3.98-31.66). ConclusionsThis multi-ethnic study validates the acMASH index as a reliable, non-invasive test for identifying MASH. The newly proposed acFibroMASH index is a reliable test for identifying fibrotic MASH and predicting the risk of LREs.

A sub-study of the POISE-3 randomized trial examined effects of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of acute kidney injury

In this pre-specified sub-study of the POISE-3 trial, we examined the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of postoperative acute kidney injury (AKI). Altogether, 7307 patients were included from 110 hospitals in 22 countries. Patients were 45 years and older, had or were at risk of atherosclerotic disease, took at least one antihypertensive medication, and were scheduled for noncardiac surgery. Hypotension-avoidance strategy: (i) target intraoperative mean arterial pressure (MAP) 80 mmHg or over, (ii) on day of surgery and for two days after, hold renin-angiotensin-aldosterone system inhibitors and use other antihypertensives in stepwise fashion if systolic blood pressure (SBP) 130 mmHg or more. Hypertension-avoidance strategy: (i) target intraoperative MAP 60 mmHg or more, (ii) continue all antihypertensives before and after surgery. Primary outcome: postoperative AKI, an increase in serum creatinine concentration of either 26.5 μmol/L or more (0.3 mg/dL or more) within 48 hours of randomization or 50% or more within seven days of randomization. The hypotension-avoidance group (3654 patients) used fewer antihypertensive medications than the hypertension-avoidance group (3653 patients); specifically, 6% vs. 38% used an ACEI or ARB on the day of surgery, and 6% vs. 47% and 7% vs. 50% one and two days after surgery, respectively. Patients also spent about half as much intraoperative time with a MAP under 80 mmHg (27 vs. 60 minutes, respectively), but had little difference in average BP before or after surgery. There was no significant difference in AKI risk (15.1% vs. 14.4%). Results were consistent with other definitions of AKI and in patients with preexisting chronic kidney disease. Thus, a hypotension-avoidance strategy targeting a MAP greater than 80 mmHg in the operating room and discontinued blood pressure medication during the perioperative period did not confer a lower risk of AKI compared to a hypertension avoidance strategy. Clinical trial registration number: NCT03505723.

Assessment of B2-Microglobulin Analysis for Renal Insufficiency in Iraqi β-Thalassemia Major Patients

Background: Beta-thalassemia is the most prevalent genetic hemoglobin apathy in the world. It is caused by a reduction or absence of beta-globin chain production, which is typically a portion of adult hemoglobin (HbA, which is α2β2). This genetic anomaly will lead to a rapid erythrocyte turnover, severe anemia, and compensatory ineffective erythropoiesis. The purpose of the current research is to reveal diagnostic, and predictive biomarkers that can be performed to detect the decline in renal function in β-thalassemia major patients with early stage renal impairment with high sensitivity and specificity, ascertain changes in B2-microglobulin as a biomarker in β-thalassemia patient. Objective: The samples were collected from Karama Hospital-Genetic Hematology Center/Baghdad during the period from the 1st of September 2022 until the 1st of January 2023. Methods: The patient group consisted of 45 patients with β-thalassemia major with repeated blood transfusion and the control group consisted of 45 individuals who seemed to be healthy. Age ranged between (18-35) years (for patients and control). The serum samples were used to measure biochemical parameters, S.Creatinine, blood urea, and Urine B2-microglobulin were measured from urine samples. B2-microglobulin level in Urine was estimated by Sandwich enzyme-linked immunosorbent assay (ELISA) technique, while serum Blood Urea and Serum Creatinine concentration were calculated by Colorimetric Kit by Spectrophotometer method, and Ferritin level in blood was estimated by BioMrieux Mini Vidas. Results: The statistical examination was carried out using SPSS software. B2-microglobulin biomarkers in the thalassemia Patient group were significantly higher than those in the control group (p&lt;0.001). While serum ferritin, B.Urea and S.Cr increased in patient groups compared to the control group (p&lt;0. 005). Conclusions: All parameters included in this study are significantly higher in β-thalassemia patients than in healthy subjects. Renal hemosiderosis and asymptomatic renal dysfunction are prevalent among β-thalassemia major patients with repeated blood transfusions, which are not found in routine renal investigations.

Comparative Analysis of The Effectiveness of Antihypertensive Therapy Including Spironolactone and Eplerenone in Patients With Essential Hypertension and Atrial Fibrillation.

To perform a comparative analysis of the efficacy of antihypertensive therapy (AHT) containing spironolactone or eplerenone in patients with essential arterial hypertension (AH) and atrial fibrillation (AF). The study included 99 male and female patients with essential AH complicated by permanent AF, who were receiving the outpatient treatment at the National Specialized Scientific and Practical Medical Center of Cardiology (Tashkent). The patients aged 61.3±9.5 years, the mean duration of AH was 12.9±8.3 years. All patients were divided into two groups: Group 1, patients who completed a 6-month combination AHT containing spironolactone (n=51); Group 2, patients who completed a 6-month combination AHT containing eplerenone (n=48). AF was diagnosed by electrocardiogram (ECG) and/or 24-hour ECG monitoring according to standard diagnostic criteria. The ECG study was performed in compliance with the American Society of Echocardiography Guidelines in M- and B-modes. The degree of structural vascular alterations was determined by the intima-media thickness of the common carotid artery by duplex scanning and microalbuminuria in morning urine. The concentrations of sex hormones were measured by the enzyme immunoassay. The serum concentrations of lipids, glucose, creatinine, and uric acid were measured by the enzymatic method. The glomerular filtration rate (GFR) was calculated with the EPI formula. Results of all studies were considered statistically significant at p&lt;0.05. The proportion of patients who achieved the target diastolic blood pressure (BP) values was significantly greater in the eplerenone-containing treatment group than in the spironolactone-containing treatment group: 87.8% vs. 67.5% (p=0.043). The proportion of patients who simultaneously achieved the target systolic and diastolic BP values was slightly greater in the eplerenone-containing treatment group than in the spironolactone-containing group (100% vs. 92.1%, p=0.060). The best cardioprotective efficacy was observed in the group of combination AHT containing eplerenone. Specifically, in Group 2, the left ventricular ejection fraction (LVEF) was significantly improved compared to Group 1: from 55.4±10.6% at baseline to 52.6±9.1% in Group 1 (p&gt;0.05) and from 54.8±8.8% at baseline to 58.2±6.4% in Group 2 (p&lt;0.02). Only in Group 2, the left atrial volume index (LAVI) was significantly decreased compared to Group 1. Thus, in Group 1, the LAVI changed from 42.2±15.1 ml/m2 at baseline to 40.4±12.2 ml/m2 (p&gt;0.05) and in Group 2, from 41.2±15.3 ml/m2 at baseline to 37.3±13.5 ml/m2 after the treatment (p&lt;0.05); the ∆% LAVI in the eplerenone group was -5.9% vs. -0.36% in the spironolactone group. In men of Group 1, estradiol significantly increased from 13.9±12.6 pmol/l at baseline to 22.7±12.4 pmol/l (p&lt;0.001). The good antihypertensive efficacy of the 6-month combination therapy containing eplerenone was significantly superior to spironolactone in achieving the target BP values. The eplerenone-containing treatment significantly improved LVEF and decreased LAVI compared to the spironolactone-containing treatment. A trend towards a beneficial effect of the AHT containing eplerenone on concentrations of sex hormones was noted in both women and men.

Contrast-Enhanced Ultrasound (CEUS) and Ultra-Microangiography (UMA) in Critically Ill Children with Acute Kidney Injury.

Acute kidney injury (AKI) is an acute condition of impaired kidney function with decreased glomerular filtration rate, which results in dysregulation in volume, electrolyte, and acid-base equilibrium. AKI can be a life-threatening condition and can also lead to chronic kidney disease. It is important to diagnose AKI early in the course of the disease or to predict its development, as this can influence therapeutic decisions, outcome, and, consequently, the prognosis. In clinical practice, an elevated serum creatinine concentration remains the most common laboratory indicator for diagnosing AKI. However, due to the delay in its rise, creatinine levels are often insensitive and inaccurate for early diagnosis. Novel biomarkers of kidney tubular injury and the renal angina index have shown promise in predicting AKI earlier and more accurately. Contrast-enhanced ultrasonography (CEUS) and ultra-microangiography (UMA) are radiological methods that can quantify renal microperfusion and may be able to predict the development of AKI. They have not yet been used for quantifying renal perfusion in children with risk factors for developing AKI. Further research is needed to compare these sonographic techniques with the renal angina index and emerging kidney injury biomarkers for predicting acute kidney injury (AKI) in both children and adults.