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Background: Testicular microlithiasis (TM) is thought to be associated with testicular tumors and impaired spermatogenesis; however, its etiology remains unclear. Objectives: To identify factors, other than testicular function, that are associated with testicular microlithiasis. Materials and methods: We enrolled males who underwent ultrasound examination of the scrotum at Tokyo Dental College Ichikawa General Hospital. The patients were categorized into two groups: those with or those without testicular microlithiasis. Background and blood test data were compared between the groups. Results: Testicular microlithiasis was observed in 72 of the 828 (8.7%) patients enrolled. Ages ranged from 15 to 87 years (mean age, 40.0 years). A history of germ cell tumor was significantly more prevalent in patients with testicular microlithiasis than in those without (1.3 vs. 16.7%; p < 0.001). Blood test data showed that, patients with testicular microlithiasis had significantly higher serum creatinine levels (0.91 vs. 1.04 mg/dL; p = 0.046) and lower calcium levels (9.4 vs. 9.3 mg/dL; p = 0.031) than those without. Serum creatinine levels (> 1.00 mg/dL) and germ cell tumors were significantly associated with testicular microlithiasis in both univariate and multivariate analyses. The prevalence of testicular microlithiasis increased in patients older than 50 years. Age (> 50 years) was associated with testicular microlithiasis in univariate analysis. The mean body weight tended to be heavier (70.7 vs. 72.2 kg; p = 0.051) and epididymitis was observed more frequently (3.2 vs. 8.3%; p = 0.056) in patients with testicular microlithiasis than in those without. Discussion and conclusion: A history of testicular tumors and elevated serum creatinine levels were associated with testicular microlithiasis. Testicular microlithiasis was observed across all age groups, with a tendency to increase in patients older than 50 years. Patients with testicular microlithiasis were slightly heavier and had a higher prevalence of epididymitis than those without. Our findings suggest that, in addition to testicular dysgenesis, other factors are involved in the development of testicular microlithiasis. [ABSTRACT FROM AUTHOR]

Background and purpose: The ratio of serum uric acid (SUA) to serum creatinine (SCr), representing normalized SUA for renal function, is associated with functional outcome in acute ischaemic stroke (AIS) patients. However, its effect on AIS patients undergoing mechanical thrombectomy (MT) remains unknown. This study aimed to investigate the influence of the SUA/SCr ratio on clinical outcome in MT‐treated AIS patients. Methods: Acute ischaemic stroke patients who underwent MT were continuously enrolled from January 2018 to June 2023. Upon admission, SUA and SCr levels were recorded within the initial 24 h. Stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS) score. Clinical outcome included poor functional outcome (modified Rankin Scale score >2) at 90 days, symptomatic intracranial haemorrhage and death. Results: Amongst 734 patients, 432 (58.8%) exhibited poor functional outcome at 90 days. The SUA/SCr ratio exhibited a negative correlation with NIHSS score (ρ = −0.095, p = 0.010). Univariate analysis revealed a significant association between SUA/SCr ratio and poor functional outcome. After adjusting for confounders, the SUA/SCr ratio remained an independent predictor of functional outcome (adjusted odds ratio 0.348, 95% confidence interval 0.282–0.428, p < 0.001). Receiver operating characteristic curve analysis highlighted the ability of the SUA/SCr ratio to predict functional outcome, with a cutoff value of 3.62 and an area under the curve of 0.757 (95% confidence interval 0.724–0.788, p < 0.001). Conclusion: The SUA/SCr ratio is correlated with stroke severity and may serve as a predictor of 90‐day functional outcome in AIS patients undergoing MT. [ABSTRACT FROM AUTHOR]

Aims: To explore the effect of renal function on the pharmacokinetic (PK) and pharmacodynamic (PD) profile and safety of enavogliflozin, a selective sodium‐glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). Methods: An open‐label, two‐part clinical trial was conducted in T2DM patients, stratified by renal function: Group 1, normal renal function; Group 2, mild renal impairment (RI); Group 3, moderate RI; and Group 4, severe RI. In Part A, Groups 2 and 4 received enavogliflozin 0.5 mg once. In Part B, Groups 1 and 3 received enavogliflozin 0.5 mg once daily for 7 days. Serial blood and timed urine samples were collected to analyse the PK and PD characteristics of enavogliflozin. Pearson's correlation coefficients were calculated to assess the correlations between PK or PD parameters and creatinine clearance (CrCL). Results: A total of 21 patients completed the study as planned. The area under the curve (AUC) for enavogliflozin was not significantly correlated with CrCL, although the maximum concentration slightly decreased as renal function decreased. By contrast, daily urinary glucose excretion (UGE) was positively correlated with CrCL after both single‐ (r = 0.7866, p < 0.0001) and multiple‐dose administration (r = 0.6606, p = 0.0438). Conclusions: Systemic exposure to oral enavogliflozin 0.5 mg was similar among the patients with T2DM regardless of their renal function levels. However, the glucosuric effect of enavogliflozin decreased with RI. Considering the UGE observed and approved therapeutic use of other SGLT2 inhibitors, the efficacy of enavogliflozin with regard to glycaemic control could be explored in patients with mild and moderate RI (estimated glomerular filtration rate ≥30 or ≥45 mL/min/1.73 m2) in a subsequent larger study. [ABSTRACT FROM AUTHOR]

Background: Prophylactic peritoneal dialysis (PD) in neonates undergoing cardiopulmonary bypass (CPB) is safe and improves outcomes. We sought to (1) derive the pre-operative characteristics of neonates who are most likely to benefit from PD after CPB and (2) validate a new prophylactic PD protocol based on our retrospective analysis. Methods: First, we retrospectively evaluated neonates requiring cardiac surgery with CPB from October 2012 to June 2016. We categorized neonates as those who "needed PD" and those who "did not need PD" based on prior experience with neonates requiring kidney support therapy. Pre-operative serum creatinine ≥ 0.8 mg/dL, pre-operative weight ≤ 2.5 kg, or having an open chest post-operatively were independently associated with "needed PD." Next, beginning in March 2019, we implemented a new prophylactic PD protocol in which only those who met at least one of the three criteria derived in the retrospective analysis had a PD catheter placed in the OR. Results: In Era 2, after the implementation of a new prophylactic PD protocol, 100% of neonates in the "needed PD" group had a PD catheter placed in the OR, which was more than in the prior era (Era 1 = 86.6%) (p = 0.05). Only 26.1% in the "did not need PD" group had a PD catheter placed in the OR which was less than in the prior era (Era 1 = 50.6%) (p < 0.01). Conclusions: We successfully developed and implemented an evidence-based prophylactic PD protocol that has improved our ability to provide prophylactic PD in neonates after CPB. [ABSTRACT FROM AUTHOR]

Background: Assessing bias (estimated – measured) is key to evaluating glomerular filtration rate (GFR). Stratification by subgroups can indicate where equations perform differently. However, there is a fallacy in the assessment of two instruments (e.g., eGFR and mGFR) when stratifying on the level of only one of those instruments. Here, we present statistical aspects of the problem and a solution for GFR stratification along with an empirical investigation using data from the CKiD study. Methods: Compared and contrasted biases (eGFR relative to mGFR) with 95% confidence intervals within strata of mGFR only, eGFR only, and the average of mGFR and eGFR using data from the Chronic Kidney Disease in Children (CKiD) study. Results: A total of 304 participants contributed 843 GFR studies with a mean mGFR of 48.46 (SD = 22.72) and mean eGFR of 48.67 (SD = 22.32) and correlation of 0.904. Despite strong agreement, eGFR significantly overestimated mGFR when mGFR < 30 (+ 6.2%; 95%CI + 2.9%, + 9.7%) and significantly underestimated when mGFR > 90 (–12.2%; 95%CI − 17.3%, − 7.0%). Significant biases in opposite direction were present when stratifying by eGFR only. In contrast, when stratifying by the average of eGFR and mGFR, biases were not significant (+ 1.3% and − 1.0%, respectively) congruent with strong agreement. Conclusions: Stratifying by either mGFR or eGFR only to assess eGFR biases is ubiquitous but can lead to inappropriate inference due to intrinsic statistical issues that we characterize and empirically illustrate using data from the CKiD study. Using the average of eGFR and mGFR is recommended for valid inferences in evaluations of eGFR biases. [ABSTRACT FROM AUTHOR]

Background: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. Methods: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1–18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland–Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. Results: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate—both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland–Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). Conclusions: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR. [ABSTRACT FROM AUTHOR]

Background: In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response. Methods: A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia. Results: Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time. Conclusions: Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment. [ABSTRACT FROM AUTHOR]

Background: On February 6th, 2023, two consecutive earthquakes struck southeastern Türkiye with magnitudes of 7.7 and 7.6, respectively. This study aimed to analyze the clinical and laboratory findings, as well as management of pediatric victims with Crush Syndrome (CS) and Acute Kidney Injury (AKI). Methods: The study included pediatric earthquake victims who were presented to Mersin University Hospital. Clinical and laboratory characteristics of the patients were collected retrospectively. Results: Among 649 patients, Crush injury (CI), CS and AKI was observed in 157, 59, and 17 patients, respectively. White blood cell count (12,870 [IQR: 9910–18700] vs. 10,545 [IQR: 8355–14057] /µL, P < 0.001), C-reactive protein (51.27 [IQR: 14.80–88.78] vs. 4.59 [1.04–18.25] mg/L, P < 0.001) and myoglobin levels (443.00 [IQR: 198.5–1759.35] vs. 17 [11.8–30.43] ng/ml) were higher in patients with CS, while their sodium (IQR: 134 [131–137] vs. 136 [134–138] mEq/L, P < 0.001) levels were lower compared to non-CS patients. An increase in myoglobin levels was identified as an independent risk factor for developing CS (OR = 1.017 [1.006–1.027]). Intravenous fluid replacement was administered to the patients with CS at a dose of 4000 cc/m2/day. Hypokalemia was observed in 51.9% of the CS patients on the third day. All patients with AKI showed improvement and no deaths were reported. Conclusions: Hyponatremia and increase in inflammation markers associated with CS may be observed. An increase in myoglobin levels was identified as a risk factor for CS. Hypokalemia may be seen as a complication of vigorous fluid therapy during hospitalization. [ABSTRACT FROM AUTHOR]

Over the past two decades, our understanding of the impact of acute kidney injury, disorders of fluid balance, and their interplay have increased significantly. In recent years, the epidemiology and impact of fluid balance, including the pathologic state of fluid overload on outcomes has been studied extensively across multiple pediatric and neonatal populations. A detailed understating of fluid balance has become increasingly important as it is recognized as a target for intervention to continue to work to improve outcomes in these populations. In this review, we provide an update on the epidemiology and outcomes associated with fluid balance disorders and the development of fluid overload in children with acute kidney injury (AKI). This will include a detailed review of consensus definitions of fluid balance, fluid overload, and the methodologies to define them, impact of fluid balance on the diagnosis of AKI and the concept of fluid corrected serum creatinine. This review will also provide detailed descriptions of future directions and the changing paradigms around fluid balance and AKI in critical care nephrology, including the incorporation of the sequential utilization of risk stratification, novel biomarkers, and functional kidney tests (furosemide stress test) into research and ultimately clinical care. Finally, the review will conclude with novel methods currently under study to assess fluid balance and distribution (point of care ultrasound and bioimpedance). [ABSTRACT FROM AUTHOR]

Objective(s): To investigate whether 3-methyladenine (3-MA) can protect the kidney of streptozotocin (STZ) - induced diabetes mice, and explore its possible mechanism. Materials and Methods: STZ was used to induce diabetes in C57BL/6J mice. The mice were divided into normal control group (NC), diabetes group (DM), and diabetes+3-MA intervention group (DM+3-MA). Blood glucose, water consumption, and body weight were recorded weekly. At the end of the 6th week of drug treatment, 24-hour urine was collected. Blood and kidneys were collected for PAS staining to evaluate the degree of renal injury. Sirius red staining was used to assess collagen deposition. Blood urea nitrogen (BUN), serum creatinine, and 24-hour urine albumin were used to evaluate renal function. Western blot was used to detect fibrosis-related protein, inflammatory mediators, high mobility group box 1 (HMGB1)/NF-κB signal pathway molecule, vascular endothelial growth factor (VEGF), and podocin, and immunohistochemistry (IHC) was used to detect the expression and localization of autophagy-related protein and fibronectin. Results: Compared with the kidney of normal control mice, the kidney of diabetes control mice was more pale and hypertrophic. Hyperglycemia induces renal autophagy and activates the HMGB1/ NF-κB signal pathway, leading to the increase of inflammatory mediators, extracellular matrix (ECM) deposition, and proteinuria in the kidney. In diabetic mice treated with 3-MA, blood glucose decreased, autophagy and HMGB1/NF-κB signaling pathways in the kidneys were inhibited, and proteinuria, renal hypertrophy, inflammation, and fibrosis were improved. Conclusion: 3-MA can attenuate renal injury in STZ-induced diabetic mice through inhibition of autophagy and HMGB1/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Increased body fluids during pregnancy complicates the application of estimated glomerular filtration rate (eGFR) formulas that are based on body surface area. Furthermore, gestational renal dysfunction cannot be identified if the serum creatinine (SCr) concentration is within the non-pregnant reference interval (RI) despite inadequate pregnancy-related renal hyperfiltration. 1484 SCr measurements from 957 healthy pregnant women were collected. The average SCr value of gestational week (GW) 0–3 was the representative SCr value of non-pregnant status. While the distribution of SCr measurements varied across GWs, it was transformed into a normal distribution using the bootstrap resampling method. A polynomial linear regression method was applied to achieve a continuous and smooth transformation of values. The normally distributed SCr values of each GW were compared to the non-pregnant status, leading to the calculation of SCr hyperfiltration. The final equation, (2 − SCr (μmol/L) / 55.25) × 103.1 × 55.25/(56.7 − 0.223 × GW − 0.113 × GW2 + 0.00545 × GW3 − 0.0000653 × GW4), and reference intervals for both SCr and eGFR for each GW were obtained. These RIs and novel equations can be effectively used to monitor renal dysfunction in pregnant women. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation. Methods: This is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators. Results: 28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected. Conclusions: No evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19. Trial registration: The trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21. [ABSTRACT FROM AUTHOR]

Iodine deficiency and excessive salt intake have adverse health effects. This study evaluated the iodine level and salt intake in Chinese adults aged 18–59 years after implementing the salt reduction program and compared with both the World Health Organization (WHO) and Chinese recommendations. Adults aged 18–59 years were randomly selected using multi-stage stratified random sampling in coastal urban area (CUA), non-coastal urban area (Non-CUA), coastal rural area (CRA), and non-coastal rural area (Non-CRA) of Fujian Province, China. Iodine, sodium, and creatinine concentrations in spot urine samples were measured. Knudsen equation was used to determine 24-h urinary iodine and sodium excretion. The median urinary iodine concentration (mUIC) and urinary sodium concentration (mUNaC) among adults (n = 3513) were 132.0 μg/L and 4.0 g/d, respectively. The mUIC and median daily iodine intake in CUA, Non-CUA, CRA and Non-CRA were 112.1, 127.5, 128.5, 167.5 μg/L and 189.6, 182.5, 199.4, 236.0 μg/d, respectively. The mUNaC and median daily salt intake (mDSI) in these four areas were 2.4, 2.8, 2.9, 2.9 g/L and 9.8, 10.4, 10.4, 10.6 g/d, respectively. The mUIC and DII of residents were higher in the Non-CRA than in the other three areas (P < 0.05). The UNaC and DSI of residents were lower in the CUA than in the other three areas (P < 0.05). The logistic regression demonstrated that the people living in CUA and Non-CUA consumed less salt compared with those in Non-CRA. Except for Non-CUA, the DII was lower (< 150 μg/d) among women of childbearing age in the low–salt intake group (< 5 g/d) compared with the high–salt intake group (≥ 5 g/d) (P < 0.05). Iodine nutrition in Chinese adults aged 18–59 years was sufficient, but the salt intake was substantially higher than the WHO and Chinese recommendations. Further policy implementation is needed to reduce salt intake and improve the monitoring of iodine levels in Chinese adults, especially in women of childbearing age. [ABSTRACT FROM AUTHOR]

COX-2 plays a key role in converting arachidonic acid into prostaglandins. This makes it a significant target for treating inflammation. Selective COX-2 inhibitors have marked a new phase in inflammatory treatment, providing significant effectiveness while reducing negative side effects. Herein, we aimed at the design and synthesis of new anti-inflammatory agents 5a–f, 7a–b, 10a–f, and 13a–b with expected selective inhibition for COX-2. Compounds 5d–f, 7b, and 10c–f showed significant COX-2 inhibition with IC50 in the range of 0.06–0.09 μM, indicating powerful pharmacological potential. In light of this, eight compounds were selected for further testing in vivo to assess their selectivity toward COX-1/COX-2 enzymes with the ability to reduce paw thickness. Compounds 5f and 7b showed significant anti-inflammatory effects without causing stomach ulcers, as they showed significant in vivo inhibition for paw thickness at 63.35% and 46.51%, as well as paw weight at 68.26% and 64.84%. Additionally, the tested compounds lowered TNF-α by 61.04% and 64.88%, as well as PGE-2 by 60.58% and 57.07%, respectively. Furthermore, these potent compounds were thoroughly analyzed for their pain-relieving effects, histological changes, and toxicological properties. Assessing renal and stomach function, as well as measuring liver enzymes AST and ALT, together with kidney indicators creatinine and urea, offered valuable information on their safety profiles. Molecular modeling studies explain the complex ways in which the strong interacts with the COX-2 enzyme. This comprehensive strategy emphasizes the therapeutic potential and safety profiling of these new analogues for managing inflammation. [ABSTRACT FROM AUTHOR]

Accurate assessment of kidney function in children requires age and gender-specific reference ranges for serum creatinine. Traditional reference values, often derived from adult populations and different ethnic backgrounds, may not be suitable for children. This study aims to establish specific reference ranges for serum creatinine in the Thai pediatric population, addressing the gap in localized and age-appropriate diagnostic criteria. This retrospective study analyzed serum creatinine levels from Thai children aged newborn to 18 years, collected from the Laboratory Information System of the Queen Sirikit National Institute of Child Health from January 2017 to December 2021. The Bhattacharya method was employed to establish reference ranges, considering different age groups and genders. The study compared these newly established reference values with international studies, including those of Schlebusch H., Pottel H., and Chuang GT., to validate their relevance and accuracy. A total of 27,642 data entries (15,396 males and 12,246 females) were analyzed. The study established distinct reference ranges for serum creatinine, which varied significantly across different age groups and between genders. These ranges were found to gradually increase with age from 2 months to 18 years. The study also highlighted notable differences in reference values when compared with other ethnic populations. The study successfully establishes tailored reference ranges for serum creatinine in Thai children, providing a valuable tool for more accurate diagnosis and monitoring of kidney health in this demographic. This initiative marks a significant advancement in pediatric nephrology in Thailand and suggests a need for continuous refinement of these ranges and further research in this area. [ABSTRACT FROM AUTHOR]

The error of estimated glomerular filtration rate (eGFR) and its consequences in predialysis are unknown. In this prospective multicentre study, 315 predialysis patients underwent measured GFR (mGFR) by the clearance of iohexol and eGFR by 52 formulas. Agreement between eGFR and mGFR was evaluated by concordance correlation coefficient (CCC), total deviation index (TDI) and coverage probability (CP). In a sub-analysis we assessed the impact of eGFR error on decision-making as (i) initiating dialysis, (ii) preparation for renal replacement therapy (RRT) and (iii) continuing clinical follow-up. For this sub-analysis, patients who started RRT due to clinical indications (uremia, fluid overload, etc.) were excluded. eGFR had scarce precision and accuracy in reflecting mGFR (average CCC 0.6, TDI 70% and cp 22%) both in creatinine- and cystatin-based formulas. Variations -larger than 10 ml/min- between mGFR and eGFR were frequent. The error of formulas would have suggested (a) premature preparation for RTT in 14% of stable patients evaluated by mGFR; (b) to continue clinical follow-up in 59% of subjects with indication for RTT preparation due to low GFRm and (c) to delay dialysis in all asymptomatic patients (n = 6) in whom RRT was indicated based on very low mGFR. The error of formulas in predialysis was frequent and large and may have consequences in clinical care. [ABSTRACT FROM AUTHOR]

Enterovirus is not a common cause of myositis and rhabdomyolysis in children. We report a case of a two-year-old boy with acute lymphoblastic leukemia with disseminated enterovirus infection complicated by hepatitis, myositis, and rhabdomyolysis. The case was managed successfully with supportive care and high-dose intravenous immunoglobulins. [ABSTRACT FROM AUTHOR]

Objectives: Extracorporeal circulation, while facilitating coronary artery bypass grafting (CABG) surgery, accelerates inflammatory processes and increases morbidity and mortality in elderly patients. The primary aim of this study was to evaluate the effect of aging on postoperative renal function after open heart surgery using an estimated glomerular filtration rate (eGFR) biomarker. The secondary aim was to evaluate the relationship between postoperative extubation times and other laboratory parameters and age and eGFR. Methods: The data of 90 patients in the American Society of Anesthesiologists score (ASA) I–II groups who underwent CABG with cardiopulmonary bypass under general anesthesia were retrospectively analyzed. Patients were divided into two groups according to age (Group 1 aged ≥65 years and Group 2 aged <65 years). Statistical differences between the groups were evaluated according to the eGFR of the patients (eGFR <60 and >60 mL/min). Results: The number and percentage of patients with preoperative eGFR <60 mL/min were similar in both groups (p=0.052). However, the number and percentage of patients with eGFR <60 mL/min postoperatively were higher in Group 1 than in Group 2 (p=0.024). Extubation times were found to be higher in Group 1, with 540 and 390 min in Groups 1 and 2, respectively (p=0.002). Conclusion: The results of this study show that the renal and pulmonary systems of patients aged ≥65 years will be more affected by cardiovascular surgery and anesthesia than those of patients aged <65 years. In CABG surgery, we can obtain an idea about the postoperative extubation time by monitoring preoperative and postoperative eGFR changes. [ABSTRACT FROM AUTHOR]

Purpose: The Swiss voluntary salt iodisation programme has successfully prevented iodine deficiency for 100 years, but dietary habits are changing and today only one-third of processed foods contain iodised salt. We aimed to monitor the current iodine status in children and pregnant women. Methods: We conducted a nationwide cross-sectional study in children (6–12 years) and pregnant women and measured the urinary iodine concentration (UIC) in spot urine samples. We estimated the iodine intake using UIC and urinary creatinine concentration (UCC) and determined the prevalence of intakes below the average requirement (AR) using the SPADE method. We measured dried blood spot (DBS) thyroglobulin (Tg), TSH and total T4 in pregnant women. Results: The median UIC was 127 μg/L (bootstrapped 95% CI 119, 140, n = 362) in children and 97 μg/L (bootstrapped 95% CI 90, 106, n = 473) in pregnant women. The estimated prevalence of inadequate iodine intake (< 65 μg/day) was 5.4% (bootstrapped 95% CI 0.0, 14.6) in children. Half (47%) of the women consumed iodine-containing multivitamin and mineral supplements (≥ 150 μg/day). Compared to non-users, users had higher median UIC (129 vs. 81 μg/L, P < 0.001), lower prevalence of inadequacy (< 160 μg/day; 0.2 vs. 31%) and lower DBS-Tg (23 vs. 29 μg/L, P < 0.001). All women were euthyroid. Conclusions: The Swiss diet and current salt fortification provides adequate iodine intake in children, but not in all pregnant women. Iodine supplements cover the dietary gap in pregnancy but are not universally consumed. Therefore, improved use of iodised salt in processed foods is desired to ensure adequate iodine intake in all population groups. This trial was registered at clinicaltrials.gov as NCT04524013. [ABSTRACT FROM AUTHOR]

Population pharmacokinetic (pop-PK) models constructed for model-informed precision dosing often have limited utility due to the low number of patients recruited. To augment such models, an approach is presented for generating fully artificial quasi-models which can be employed to make individual estimates of pharmacokinetic parameters. Based on 72 concentrations obtained in 12 patients, one- and two-compartment pop-PK models with or without creatinine clearance as a covariate were generated for piperacillin using the nonparametric adaptive grid algorithm. Thirty quasi-models were subsequently generated for each model type, and nonparametric maximum a posteriori probability Bayesian estimates were established for each patient. A significant difference in performance was found between one- and two-compartment models. Acceptable agreement was found between predicted and observed piperacillin concentrations, and between the estimates of the random-effect pharmacokinetic variables obtained using the so-called support points of the pop-PK models or the quasi-models as priors. The mean squared errors of the predictions made using the quasi-models were similar to, or even considerably lower than those obtained when employing the pop-PK models. Conclusion: fully artificial nonparametric quasi-models can efficiently augment pop-PK models containing few support points, to make individual pharmacokinetic estimates in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Myocardial protection during operations with cardiopulmonary bypass (CPB) and aortic cross clamping is vital. For this purpose, Del Nido (DN) and Custodiol cardioplegia (CC) solutions are used for single-dose cardioplegia in cardiac surgical procedures with CPB. Present study aimed to compare the effects of DN and CC on peri-operative clinical outcomes in pediatrics with Tetralogy of Fallot (TF) undergoing cardiopulmonary bypass. Methods: Present randomized clinical trial was performed in two trial groups with parallel design. One group received DN and another group received CC. We assessed circulatory Troponin-I (cTnI) and coronary sinus lactate level as primary outcomes. Secondary outcomes were ventilation time, electrolytes levels, pump time, cross-clamp time and other clinical parameters. Results: Duration of CPB and cross-clamp were the same in both groups. There were no significant differences in hemodynamic parameters, left ventricular ejection fraction after the surgery and discharge time between the two trial groups. Ventilation time (8.5 vs. 18; p = 0.001), ICU stay, Troponin-I in ICU admission and Coronary sinus lactate level (p = 0.001) were significantly higher among patients of Custodiol group compared to other trial group. Electrolytes Na, Cl and K levels, during CPB, were significantly less in Custodiol group. Conclusion: When used for inducing cardiac arrest during CPB, DN solution offers better maintenance of the electrolyte balance during CPB, and is associated with less circulatory cTnI and coronary sinus lactate level compared with the CC. [ABSTRACT FROM AUTHOR]

Lamotrigine, widely used for managing epilepsy and bipolar disorder, carries potential side effects, including severe anticonvulsant hypersensitivity syndrome (AHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which may lead to hepatotoxicity. Patients with Type 2 Diabetes (TD2) and Non-Alcoholic Fatty Liver Disease (NAFLD) are identified as more susceptible to these adverse reactions. This exploratory analysis aims to identify clinical parameters influencing lamotrigine pharmacokinetics across diverse populations, shedding light on toxicity and therapeutic drug monitoring (TDM) considerations. Starting with a retrospective analysis of 41 lamotrigine-treated patients at Hospital Santo António reveals changes or deviations from normal levels in various blood parameters and significant correlations between these parameters. Serum level changes, including creatinine, albumin, gamma-glutamyl transferase, total bilirubin, and Vitamin B12, are observed, with strong negative correlations between Vitamin B12 and creatinine. Then, we used GastroPlus and DILIsym to explore the impact of clinical parameters on lamotrigine for different patient populations. We constructed a Physiologically Based Pharmacokinetic (PBPK) model for lamotrigine in GastroPlus, based on ADMET predictions and data from the literature, to simulate the pharmacokinetic variability of lamotrigine in different populations, and we visualized the impact of increasing lamotrigine dose on its plasma concentration–time profiles (200 mg, 400 mg, 600 mg, 1200 mg) and reduced bioavailability. At higher doses, it is possible that the saturation of metabolic pathways leads to the formation of toxic metabolites or intermediates. These metabolites may exert inhibitory effects on drug-metabolizing enzymes or disrupt normal physiological processes, thereby impeding the drug's clearance and potentially lowering its bioavailability. In DILIsym, we investigated lamotrigine's DILI potential for individuals with diabetes and NAFLD. The results demonstrated an increased risk, emphasizing the need for careful monitoring. This study underscores the importance of understanding lamotrigine's pharmacokinetics for tailored treatment decisions, improved outcomes, and minimized adverse reactions. [ABSTRACT FROM AUTHOR]

Objective: Methyl alcohol, which is quite cheap compared to ethyl alcohol, can be used to produce imitated alcohol. For this reason, cases of methyl alcohol intoxication can be observed from time to time. Although it is rare, it is an emergency that needs to be diagnosed and treated early because of its high mortality. Methods: In this study, 22 patients aged ≥18 years who were admitted to the intensive care unit (ICU) due to methyl alcohol intoxication between 2015 and 2022 were included. The patients were divided into 2 groups, survivor and non-survivor, and compared retrospectively in terms of factors predicting mortality. Results: Except for one of the 22 patients included in the study, all patients developed methyl alcohol intoxication because of the use of imitated alcohol. Only one patient had a history of using perfume for suicidal purposes. Of the patients who developed methyl alcohol intoxication, 13 (59%) were in the non-survivor group and 9 (41%) were in the survivor group. While the rate of invasive mechanical ventilation needed before the ICU was 55.6% in the survivor group, it was 100% in the non-survivor group, and there was a statistically significant difference between them (p<0.017). In the non-survivor patient group, blood HCO3 and pH levels were found to be significantly lower after ICU admission (p=0.002, p=0.008). At the same time, blood creatinine, potassium, and total bilirubin levels were significantly higher (p=0.002, p=0.007, p<0.035). Acute physiology and chronic health evaluation-II and sequential organ failure assessment scores after ICU admission were also significantly higher in the non-survivor group than in the survivor group (p=0.005, p=0.035). Conclusion: It was determined that in patients who died due to methyl alcohol intoxication, deeper metabolic acidosis and irreversible multiorgan failure developed during the period until ICU admission. The acute physiology and chronic health evaluation-II and sequential organ failure assessment scores were both effective in predicting mortality. [ABSTRACT FROM AUTHOR]

Objective: The Kahramanmaraş earthquake resulted in great destruction and death. We presented the characteristics of patients with crush syndrome (CS) and acute kidney injury (AKI) brought to our hospital from this region. Methods: Data of all earthquake victims admitted to our hospital between February 7th, 2023 and February 15th, 2023 were reviewed in this retrospective study. Data of 51 victims over 17 years who were rescued from the rubble were reviewed and the demographic, laboratory, and clinical findings of these patients were investigated. They were evaluated for mortality, AKI, renal replacement therapy (RRT) requirement, and complications, including fasciotomy, amputation, intensive care unit (ICU) hospitalization requirement, microbial growth, antibiotic requirement, and duration of antibiotic treatment days. Results: Twenty patients (39.22%) required ICU hospitalization, 21 patients (41.18%) had AKI, but 10 of the total patients (19.61%) required RRT, 1 patient (1.9%) died. There was a positive correlation between the time of the patients under the dent and the maximum creatine kinase (CK) level, severity of renal failure, number of hemodialysis sessions, number of albumin and erythrocyte replacements, and length of stay in the ICU. A positive correlation was found between CK and creatinine level, as well as between creatinine level and number of complications. Conclusion: Patients with CS should be closely followed in terms of their renal survival, and early treatment should be started. Follow-up of these patients requires a multidisciplinary approach with the contribution of surgeons and nephrologists. [ABSTRACT FROM AUTHOR]

Background. Diabetes self-management education (DSME) provides diabetic patients with knowledge of diabetes, requires attention and recording of dietary habits, and increases the frequency and accuracy of blood glucose monitoring. DSME also achieves better blood glucose control, thus benefiting diabetic patients and reducing the risk of diabetes complications. However, few studies have systematically examined whether DSME follows AADE 7 Self-Care Behaviors (AADE7™). Therefore, this study aimed to investigate the control effect of AADE7™-based management on laboratory test indicators of diabetic patients. Methods. The patients with diabetes who received shared care management in our hospital between June 2014 and April 2022 were analyzed retrospectively. According to the process of outpatient consultation, each patient received health education provided by diabetes education nurses and dietitians after consultation. Health education was a process from assessment to health guidance. The basic information of all patients was recorded, and AADE7™ behavior assessment and health education session were conducted through interviews. A total of 13,650 were given shared care management, requiring more than 6 follow-up visits per year, as well as health education. It was reassessed annually according to AADE standards. The impact of the patients' behavior change after the AADE7™-based management on the relevant test indicators was observed. Results. After eight years of intervention, a total of 8319 samples were obtained after excluding the outliers. Stepwise regression analysis was performed, and the results showed that, with other conditions held constant, a greater number of days per week to follow a healthy diet, to take hypoglycemic medication as prescribed, to monitor blood glucose, and to exercise and higher education level were associated with lower levels of glycosylated hemoglobin. The change from drinking to nondrinking was associated with lower triglycerides. If low blood glucose was monitored, patients who reviewed and took immediate action showed lower levels of low-density lipoprotein, urine microalbumin, and urine microalbumin/creatinine ratio compared with those without review and immediate action. Significance tests for each term showed P value <0.05. Conclusions. The AADE7™ framework is a tool supporting patient-centered self-management and education. In the AADE7™ standards, successful self-management is considered as a key outcome in the care of patients with diabetes and related diseases. This tool can effectively improve patient compliance and increase the rate of blood glucose compliance rates in patients with diabetes and therefore is worthy of clinical promotion. [ABSTRACT FROM AUTHOR]

Aim: In Japan, Niraparib maintenance therapy for primary and recurrent ovarian cancer was approved in September 2020 and is expected to improve the prognosis of ovarian cancer. However, the safety of niraparib maintenance therapy in Japanese patients has not been fully evaluated. Methods: Patients with ovarian cancer (including fallopian tube and peritoneal cancer) treated with niraparib at Jichi Medical University Hospital from September 2020 to August 2022 were enrolled in this study. Patient background, starting dose, rates of interruption, reduction, or discontinuation, adverse events (AEs) during treatment, and estimated glomerular filtration rate (eGFR) trends were retrospectively analyzed. Results: Twenty‐nine patients received niraparib maintenance therapy during the study period, including 21 with primary cancer and 8 patients with recurrent cancer. Seventeen patients (58.6%) required dose interruptions and 16 patients (55.2%) required dose reductions. Only two patients (6.9%) discontinued treatment due to fatigue and nausea. The most frequent AE was creatinine increases in 18 patients (62.1%, all grades). Although eGFR levels decreased significantly after niraparib therapy compared to before niraparib therapy (59.3 vs. 50.3 mL/min/1.73 m2, p < 0.001), the levels returned to pre‐niraparib initiation levels after discontinuation of niraparib (64.6 vs. 64.6 mL/min/1.73 m2, p = 0.96). Multivariate regression analysis showed that diabetes was independently associated with decreased eGFR (p = 0.013). Conclusions: Niraparib maintenance therapy frequently increased serum creatinine, but the change was reversible. Further studies are needed to determine the effects of niraparib on renal function in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a recognized comorbidity in pediatric diabetic ketoacidosis (DKA), although the exact etiology is unclear. The unique physiology of DKA makes dehydration assessments challenging, and these patients potentially receive excessive amounts of intravenous fluids (IVF). We hypothesized that dehydration is over-estimated in pediatric DKA, leading to over-administration of IVF and hyperchloremia that worsens AKI. Methods: Retrospective cohort of all DKA inpatients at a tertiary pediatric hospital from 2014 to 2019. A total of 145 children were included; reasons for exclusion were pre-existing kidney disease or incomplete medical records. AKI was determined by change in creatinine during admission, and comparison to a calculated baseline value. Linear regression multivariable analysis was used to identify factors associated with AKI. True dehydration was calculated from patients' change in weight, as previously validated. Fluid over-resuscitation was defined as total fluids given above the true dehydration. Results: A total of 19% of patients met KDIGO serum creatinine criteria for AKI on admission. Only 2% had AKI on hospital discharge. True dehydration and high serum urea levels were associated with high serum creatinine levels on admission (p = 0.042; p < 0.001, respectively). Fluid over-resuscitation and hyperchloremia were associated with delayed kidney recovery (p < 0.001). Severity of initial AKI was associated with cerebral edema (p = 0.018). Conclusions: Dehydration was associated with initial AKI in children with DKA. Persistent AKI and delay to recovery was associated with hyperchloremia and over-resuscitation with IVF, potentially modifiable clinical variables for earlier AKI recovery and reduction in long-term morbidity. This highlights the need to re-address fluid protocols in pediatric DKA. [ABSTRACT FROM AUTHOR]

Background: Reference values for urinary calcium (Ca) and other solutes/creatinine (Cr) ratios in infants and young children are scarce. Its variation with type of lactation administered, breastfed (BF) or formula (F), is incompletely known. Methods: A total of 511 spot urine samples from 136 children, aged 6 days to < 5 years, was collected. Urine was collected no fasting in infants < 18 months and first morning fasting in children aged 2.5–4 years. Urinary osmolality, Cr, urea, Ca, phosphate (P), magnesium (Mg), and uric acid (UA) were determined. Values are expressed as solute-to-Cr ratio. Results: Urinary values were grouped according to the child's age: 6–17 days (G1), 1–5 months (G2), 6–12 months (G3), 13–18 months (G4), and 2.5–4 years (G5). G1 was excluded; Ca/Cr and UA/Cr (95th percentile) decreased with age (G2 vs. G5) from 1.64 to 0.39 and 2.33 to 0.83 mg/mg, respectively. The P/Cr median rises significantly with age from 0.31 (G2) to 1.66 mg/mg (G5). Mg/Cr was similar in all groups (median 0.20, 95th percentile 0.37 mg/mg). Ca/Cr (95th percentile) of BF infants was 1.80 mg/mg (< 3 months) and 1.63 mg/mg (3–5 months), much higher than F infants (0.93 and 0.90 mg/mg, respectively). P/Cr and P/Ca were lower in BF infants. Conclusions: Values for urinary Ca/Cr, P/Cr, Mg/Cr, and UA/Cr in infants and children < 5 years were updated. BF infants < 6 months showed higher Ca/Cr and lower P/Cr than F infants. New cutoff values to diagnose hypercalciuria in infants < 6 months, according to the type of lactation, are proposed. [ABSTRACT FROM AUTHOR]

Background: Individual variation in kidney function can be affected by both congenital and acquired factors, and kidney function in children is possibly correlated with that in their mothers. However, the mother–child correlation in kidney function remains directly unconfirmed. Methods: We conducted a cross-sectional study of 655 healthy pairs of 7- or 8-year-old children and their mothers as an adjunct study of a nationwide epidemiological study (Japan Environment and Children's Study). Results: Both serum creatinine level (all children, r = 0.324, p < 0.001; girls, r = 0.365, p < 0.001; boys, r = 0.278, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = 0.274, p < 0.001; r = 0.352, p < 0.001; r = 0.195, p < 0.001, respectively) in children were weakly associated with their maternal values. In the single linear regression analyses, maternal values of serum creatinine and eGFR were significantly associated with the children's values. Moreover, several body composition values in children, such as weight-SDS, fat (%), and predicted muscle weight, were also significantly associated with kidney function values in children. In the multiple linear regression analysis for serum creatinine levels in children, in which weight-SDS and predicted muscle weight in children were selected as adjustment factors, maternal serum creatinine level showed a significant positive association (B = 0.214, p < 0.001 in the adjusted model). Moreover, in the multiple linear regression analysis for eGFR value in children, in which fat (%) and predicted muscle weight in children were selected as adjustment factors, maternal eGFR values showed a significant positive association (B = 0.319, p < 0.001). Conclusions: We directly confirmed mother–child correlations in both serum creatinine levels and eGFR values, particularly in girls. [ABSTRACT FROM AUTHOR]

Background: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. Methods: We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20 ml/min/1.73 m2 after 1 year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1 year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. Results: Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. Conclusion: PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies. [ABSTRACT FROM AUTHOR]

Background: Tubulointerstitial lesions and glomerular inflammation severity have been shown to correlate with proteinuria in children with IgA nephropathy (cIgAN). However, there is a lack of data regarding severity of histopathologic findings in cIgAN in patients with minimal to absent proteinuria since kidney biopsy indications are not well defined in these cases. Methods: Twenty-eight cIgAN patients with kidney biopsy from 4 different centers in Paris (France) and Montreal (Canada) with a urine protein/creatinine ratio (UPCr) ≤ 0.03 g/mmol and a normal estimated glomerular filtration rate (eGFR > 90 ml/min/1.73 m2) on the day of kidney biopsy prior to treatment were included. Results: Median age was 11.82 (9.32–13.45) years, and median follow-up was 4 years (2.87–6.53). At time of biopsy, median eGFR was 116 (102.3–139.7) ml/min/1.73 m2, and median UPCr was 0.02 (0.011–0.03) g/mmol. Microscopic or macroscopic hematuria was present in 35.7% and 64.3% of cases, respectively. Kidney biopsy microscopy analysis showed mesangial (M1), endocapillary (E1), or extracapillary (C1) hypercellularity in 53.5%, 32.1%, and 7.1% of patients, respectively. Chronic histological lesions were also present: glomerulosclerosis (S1) in 42.8% and tubular atrophy/interstitial fibrosis in 7.1%. Podocytopathic features were detected in 21.4%. An ACE inhibitor or immunosuppressive therapy (IS) was prescribed in 42.8% and 21.4% of these patients respectively. One-third (35.7%) received no treatment. At last follow-up, median eGFR was 111.9 (90.47–136.1) ml/min/1.73 m2, and median UPCr was 0.028 (0.01–0.03) g/mmol. Conclusion: cIgAN with minimal proteinuria at time of biopsy might be linked with acute and chronic glomerular lesions. [ABSTRACT FROM AUTHOR]

Context.--Monoclonal gammopathy of renal significance (MGRS) is a relatively new concept for patients with renal monoclonal protein deposition (RMPD) (except monoclonal cast nephropathy) and has been used as a reason for nephrologists to obtain a bone marrow biopsy (BMB). It takes a team of pathologists and clinicians to determine when RMPD at our institution can be defined as MGRS. Objective.--To identify the proportion of various subtypes of tentative MGRS diagnosed by renal biopsy that can be confirmed as final MGRS after BMB. Design.--One hundred thirty kidney biopsies with variants of RMPD were identified during the past 10 years. Biopsy cases with known myeloma, B-cell lymphoma, or monoclonal cast nephropathy were separated as a heavy-burden group. The remaining biopsies with RMPD were considered tentative MGRS. Their BMB and clinical indices were further analyzed to determine the final percentage of MGRS diagnoses. Results.--Among the 130 renal paraprotein deposition cases, 44 (33.8%) were categorized as the heavy-burden group. In the remaining 86 cases, 33 (38.4%) with subsequent identification of myeloma (.10% of monoclonal plasma cells) or lymphoma in BMB were further considered as heavy-burden cases. Eighteen cases (18 of 86; 20.9%) did not receive follow-up BMB; thus, no further analysis was performed. BMBs diagnosed as either nonmalignant (no plasma cells; 8 of 86 cases; 9.3%) or premalignant (,10% plasma cells; 27 of 86 cases; 31.4%) were confirmed to be final MGRS (35 of 86; 40.7%). Conclusions.--The data indicate that BMB is an important element in the confirmation of MGRS. [ABSTRACT FROM AUTHOR]

Aim: Cerium oxide, particularly in nanoparticle form (nanoceria), has been investigated for biomedical applications as a promising new agent for treating several pathologies. The aim of the present study was to characterize the pharmacologic effects of nanoceria in an animal model of chronic kidney disease. Methods: We created the chronic kidney disease animal model by feeding rats a 0.25% adenine diet. Male Wistar rats were divided into five groups: normal diet, 0.25% adenine diet, or adenine diet containing three different doses or durations of nanoceria treatment. Blood was collected weekly from the tail veins of each rat and analyzed for renal function markers. After 5 weeks, various biochemical markers in serum, plasma, and urine were also analyzed. Results: In the adenine‐treated group, body weight was significantly decreased, and the kidneys lost much of their healthy reddish color and became lumpy and white in appearance. In addition, levels of serum creatinine, blood urea nitrogen, and plasma uremic toxins were significantly increased in adenine‐treated rats compared with controls. Renal functional and structural damage in adenine diet model rats tended to be ameliorated by nanoceria ingestion. The high‐dose cerium‐treated group maintained reddish areas in the kidneys, and the increases in biomarker levels of creatinine, blood urea nitrogen, and inorganic phosphorus were markedly reduced, regardless of treatment duration. Conclusions: Ingestion of nanoceria may be effective for improving or preventing renal damage caused by adenine. Geriatr Gerontol Int 2024; 24: 88–95. [ABSTRACT FROM AUTHOR]

Introduction: Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a quality improvement program that assesses for AKI in those exposed to NTM with daily serum creatinine (SCr) levels. However, blood draws for SCr are invasive and have clinical disadvantages. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a promising indicator of AKI. We tested the hypothesis that uNGAL could reliably screen for NTM-AKI in the Baby NINJA program. Methods: This two-center prospective study screened 174 NICU subjects, of whom 148 met screening criteria from January 29, 2019, to September 18, 2020. Daily SCr and urine samples were obtained for up to 7 days of NTM exposure plus 2 days after exposure ended or end of AKI. AKI was defined by a SCr rise of 50% from baseline. The highest uNGAL obtained was evaluated to determine its relationship to the diagnosis of AKI. Logistic regression models were used to determine optimal uNGAL cutoffs. Results: The negative predictive value of a uNGAL value ≥250 ng/mL was 96.8% (95% CI = 93.3–100%). Urine NGAL ≥400 ng/mL demonstrated the highest ROC-AUC value of 0.72 with a positive likelihood risk for AKI of 2.76 (1.39–4.13). Discussion/Conclusion: We propose that uNGAL could be used to screen for NTM-AKI and thus replace many blood draws needed in those exposed to NTM. The ideal uNGAL threshold requires further investigation in infants. [ABSTRACT FROM AUTHOR]

Background: The incidence of type 1 diabetes (T1D) is showing a rising trend all over the world, and these patients are living longer than before. With increasing longevity, they are at increased risk of chronic complications including fractures. However, the bone mineral density (BMD) data in T1D patients are conflicting and variable across the studies. Here, we aimed to study the BMD in adult patients with T1D and delineate its predictors. Material and methods: We recruited 40 T1D patients and equal number of age- and sex-matched control subjects. Clinical, biochemical, hormonal, and densitometric assessments were performed for each of the participants and compared between the two groups. Results: The median age of T1D and control subjects was 23.5 (21–27.75) years and 24 (22–26) years, respectively. The median duration of diabetes in T1D patients was 12.5 (9–15.75) years with a mean HbA1C of 8.7 ± 1.9%. The serum corrected calcium, phosphorous, alkaline phosphatase, creatinine, and plasma 25-hydroxyvitamin D and iPTH levels were comparable between the groups. In T1D subjects, the mean lumbar spine and left hip BMD were 0.876 ± 0.154 gm/cm2 and 0.780 ± 0.112 gm/cm2, respectively, which corresponded to mean Z-scores of -1.5 ± 1.4 and -1.4 ± 0.9, respectively, which were significantly lower compared to control group. Multiple linear regression analyses showed that BMI and serum albumin were significant determinant of lumbar spine and hip BMD, respectively, in patients with T1D. Conclusion: Patients of T1D have apparently reduced BMD, which is being influenced by BMI and serum albumin level. [ABSTRACT FROM AUTHOR]

Irisin is a myokine with potential effects on glucose metabolism and the development of diabetes in humans. We analysed irisin serum levels (ISL) in 47 patients without diabetes before and 1, 2, 3, 4 and 5 weeks after kidney transplantation (KTx). All measurements of irisin before KTx levels were lower than 25 ng/mL (median 8.4 ng/mL). We found an outstanding increase in ISL measured after KTx, reaching more than 1000 times in 44% of patients (HIL—high irisin level group). The increase appeared at the first measurement (one week after KTx). Factors connected to the large growth of ISL were, i.e., BMI > 30 (p = 0.04) and subsequent KTx—second and third (p < 0.001). The global mean blood glucose level during the first two weeks after KTx was significantly lower in the HIL group (p = 0.002), the same as the day-by-day analysed mean fasting and postprandial serum glucose in the first days after KTx. In 12 months of observation, diabetes requiring insulin therapy occurred in the HIL group at a rate of 19%, while in the rest of the patients, the rate was 27%, p = 0.526. Irisin levels increase significantly in some patients after kidney transplantation, accompanied by lower blood glucose levels in the early post-transplant period. Whether an increase in irisin levels results in better glycaemic control remains questionable and requires further research, as well as the relationship between irisin levels and the occurrence of PTDM. [ABSTRACT FROM AUTHOR]

Polyoxotungstate nanoclusters have recently emerged as promising contrast agents for computed tomography (CT). In order to evaluate their clinical potential, in this study, we evaluated the in vitro CT imaging properties, potential toxic effects in vivo, and tissue distribution of monolacunary Wells–Dawson polyoxometalate, α2-K10P2W17O61.20H2O (mono-WD POM). Mono-WD POM showed superior X-ray attenuation compared to other tungsten-containing nanoclusters (its parent WD-POM and Keggin POM) and the standard iodine-based contrast agent (iohexol). The calculated X-ray attenuation linear slope for mono-WD POM was significantly higher compared to parent WD-POM, Keggin POM, and iohexol (5.97 ± 0.14 vs. 4.84 ± 0.05, 4.55 ± 0.16, and 4.30 ± 0.09, respectively). Acute oral (maximum-administered dose (MAD) = 960 mg/kg) and intravenous administration (1/10, 1/5, and 1/3 MAD) of mono-WD POM did not induce unexpected changes in rats' general habits or mortality. Results of blood gas analysis, CO-oximetry status, and the levels of electrolytes, glucose, lactate, creatinine, and BUN demonstrated a dose-dependent tendency 14 days after intravenous administration of mono-WD POM. The most significant differences compared to the control were observed for 1/3 MAD, being approximately seventy times higher than the typically used dose (0.015 mmol W/kg) of tungsten-based contrast agents. The highest tungsten deposition was found in the kidney (1/3 MAD—0.67 ± 0.12; 1/5 MAD—0.59 ± 0.07; 1/10 MAD—0.54 ± 0.05), which corresponded to detected morphological irregularities, electrolyte imbalance, and increased BUN levels. [ABSTRACT FROM AUTHOR]

Cardiac contractility modulation (CCM) is a novel device‐based therapy used to treat patients with heart failure with reduced ejection fraction (HFrEF). In both randomized clinical trials and real‐life studies, CCM has been shown to improve exercise tolerance and quality of life, reverse left ventricular remodeling, and reduce hospitalization in patients with HFrEF. In this case report, we describe for the first time the use of CCM combined with left bundle branch pacing (LBBP) cardiac resynchronization therapy pacemaker (CRT‐P) implantation therapy in a female with a 22‐year history of non‐ischemic dilated cardiomyopathy. With the optimal medical therapy and cardiac resynchronization therapy (CRT) strategies, the patient's quality of life initially recovered to some extent, but began to deteriorate in the past year. Additionally, heart transplantation was not considered due to economic reasons and late stage systolic heart failure. This is the first case of CCM implantation in Fujian Province and the first report of a combined CCM and left bundle branch pacing CRT‐P implantation strategy in a patient with non‐ischemic etiology dilated cardiomyopathy in China. [ABSTRACT FROM AUTHOR]

A chronic microvascular consequence of diabetes mellitus (DM), diabetic nephropathy (DN) can affect the kidneys. Micro albuminuria and impaired renal function, as shown by a reduction in glomerular filtration and rise in serum urea and creatinine levels, are hallmarks of Diabetic Nephropathy (DN), which is a subtype of nephropathy caused by Diabetes. One of the initial markers of DN is called microalbuminuria. In order to stop the progression of Diabetic Nephropathy, effective screening procedures are essential for early identification and care. Aim & Objectives: The purpose of this research was to investigate the correlation between diabetic and nondiabetic participants' blood levels of urea and creatinine, as well as their blood glucose levels, in order to determine the diagnostic value of these parameters in the context of diabetic nephropathy and to compare these parameters to glycaemic status. Material and Methods: This is a cross sectional study conducted among 100 patients of type- 2 DM admitted in the medical ward GGH Hospital Kurnool, who fulfilled the inclusion and exclusion criteria. RFT, FBS, PPBS, HbA1c. Urine analysis for ACR from random urine sample and 24-hours urine protein from 24-hour urine sample were done. Results; 100 people who were diagnosed with diabetes mellitus; of them, 67 were males and 33 were females. The mean age was 52.67 ±11.5 years old, and the duration of diabetes mellitus was10.02±3.20 years. The average glycosylated haemoglobin was 8.78 ±1.54 percent, and the fasting blood glucose was 193.25± 82.23mg/dl. Post prandial blood sugar was 220.56±12.76. Mean eGFR (ml/min/1.73 m²) was 65.39±4.09. Mean Urinary protein (mg/dl) was 385.23±65.23. Mean Urine creatinine (mg/dl) was 125.23±25.29. Mean Urine protein creatinine ratio was 3.35±1.56. Among 100 patients 14 patients had minimal proteinuria of (<1 g/day), 38 patients had moderate proteinuria (1- 3g/day), 48 patients had heavy proteinuria (>3g/day) Conclusions: The P C ratio of a random urine sample can give a very helpful, simple, and convenient approach for the quantitative assessment of proteinuria, for judging the level of kidney damage, and for avoiding the problems of the 24 - hr urine collections. Hence urine protein creatinine ratio as an earlier predictor in diabetic nephropathy. [ABSTRACT FROM AUTHOR]

A paper-based analytical device (PAD) with an integrated composite electrode has been designed and fabricated for non-enzymatic creatinine sensing. Reduced graphene oxide (rGO) was employed to modify the PAD so that it could function as a solid-contact transducer. A new macrocyclic pyrido-hexapeptide derivative was made and used as a special ionophore in the creatinine membrane sensor. The synthesized PAD showed a detection limit of 1.0 µM (S/N = 3) and a potentiometric response towards creatinine throughout a log-linear range of 2.0 µM–10 mM (R2 = 0.9998). The sensor shows significant selectivity for a few related substances, including ephedrine, codeine, ketamine, caffeine, urea, urate, carbinoxamine, and dextromethorphan. It has been established that the testing method is appropriate for the direct potentiometric detection of creatinine in a variety of human urine sample types. When an indicating electrode and a reference electrode are put on the same flexible disposable, this lets applications with a small sample volume be done. For point-of-care creatinine measurement, the developed paper-based analytical equipment is a good choice because it is affordable, easily accessible, and self-pumping (especially when combined with potentiometric detection). [ABSTRACT FROM AUTHOR]

Background: The objective is to evaluate the prevalence of acute kidney injury (AKI) as an early complication of the percutaneous nephrolithotomy (PCNL) procedure. Materials and Methods: From May 2022 to October 2022, we conducted a retrospective study on patients undergoing PCNL procedures in two of the tertiary medical centers affiliated with Isfahan University of Medical Sciences. Patients' baseline characteristics, laboratory values, perioperative data, and stone features were documented. AKI was defined either as a ≥0.3 mg/dL increase in the serum creatinine level within 2 days, or a ≥1.5-fold increase in baseline serum creatinine level within 7 days after the operation. Laboratory values were measured 1 day before PCNL and daily thereafter until discharge. Patients were followed 1 week later to detect all of the possible cases of AKI. Results: The final analysis was performed on 347 individuals. AKI developed in 16 (4.61%) cases. The two groups were comparable regarding age (P = 0.887), gender (P = 0.566), and underlying comorbidities including diabetes mellitus (P = 0.577) and hypertension (P = 0.383). The mean body mass index (BMI) (P < 0.001) and both frequency and severity of hydronephrosis (P < 0.001) were significantly different. A higher mean PCNL duration (P < 0.001), period of hospitalization (P < 0.001), and blood loss volume (P < 0.001) were observed in those who developed AKI. Overall, 56.3% (9) of patients in the AKI group and 2.7% (9) in the non-AKI group required the establishment of more than one access tract, during the procedure (P < 0.001). A lower preoperative hemoglobin level was observed in the AKI group (P < 0.001). Those with AKI had significantly larger stones (3.08 ± 0.46 vs. 2.41 ± 0.23 cm, P < 0.001) and higher Hounsfield units (P < 0.001). In addition, in the AKI group, most of the calculi (81.3%, 13) were of staghorn type, whereas in the non-AKI group, calculi were most frequently located in the middle calyx (30.2%, 100), (P < 0.001). Conclusion: The prevalence of post-PCNL AKI is approximately 4.61%. The mean BMI, preoperative hemoglobin level, PCNL duration, intraoperative blood loss volume, and hospitalization period were significantly higher among patients who developed AKI. Those with AKI had significantly larger stones with higher Hounsfield units and more frequently of staghorn type. The two groups were not statistically different regarding age, gender, and presence of comorbidities (hypertension and diabetes mellitus). [ABSTRACT FROM AUTHOR]

Obesity combined with critical illness might increase the risk of acquiring infections and hence mortality. In this patient population the pharmacokinetics of antimicrobials vary significantly, making antimicrobial dosing challenging. The objective of this study was to assess the predictive performance of published population pharmacokinetic models of vancomycin in patients who are critically ill or obese for a cohort of critically ill patients who are obese. This was a multi‐center retrospective study conducted at 2 hospitals. Adult patients with a body mass index of ≥30 kg/m2 were included. PubMed was searched for published population pharmacokinetic studies in patients who were critically ill or obese. External validation was performed using Monolix software. A total of 4 models were identified in patients who were obese and 5 models were identified in patients who were critically ill. In total, 138 patients who were critically ill and obese were included, and the most accurate models for these patients were the Goti and Roberts models. In our analysis, models in patients who were critically ill outperformed models in patients who were obese. When looking at the most accurate models, both the Goti and the Roberts models had patient characteristics similar to ours in terms of age and creatinine clearance. This indicates that when selecting the proper model to apply in practice, it is important to account for all relevant variables, besides obesity. [ABSTRACT FROM AUTHOR]

Sparsentan (FILSPARI®), an oral, dual endothelin and angiotensin receptor antagonist, is an emerging new treatment option for patients with immunoglobulin A (IgA) nephropathy. Sparsentan received accelerated approval in the USA for the treatment of adults with IgA nephropathy who are at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UP/C) ≥ 1.5 g/g, as well as a positive opinion recommending approval in the EU. In the ongoing phase 3 PROTECT trial in adults with IgA nephropathy, sparsentan was associated with favourable antiproteinuric effects, which were maintained over 110 weeks of treatment. The change in UP/C from baseline at week 36 was significantly greater with sparsentan than with irbesartan, an angiotensin receptor blocker. Early results from the 110-week final analysis of PROTECT also suggested that sparsentan may provide long-term benefits in preserving kidney function in patients with IgA nephropathy. Final analyses from the PROTECT trial, including its open-label extension period, are awaited with interest. Sparsentan was generally well tolerated, with its tolerability profile being similar to that of irbesartan. The most common treatment-emergent adverse events with sparsentan included peripheral oedema, hypotension, dizziness and hyperkalaemia. Longer-term data revealed no new safety signals. Plain Language Summary: Immunoglobulin A (IgA) nephropathy is a serious immune complex-mediated glomerulonephritis, and a leading cause of kidney failure. It is suggested that reducing proteinuria (elevated protein in the urine) is key to slowing kidney disease progression in patients with IgA nephropathy. Sparsentan (FILSPARI®), an oral, dual endothelin and angiotensin receptor antagonist, is the first non-immunosuppressive therapy approved in the USA for IgA nephropathy in adults who are at risk of rapid disease progression, generally a urine protein-to-creatinine ratio ≥ 1.5 g/g, and has been recommended for approval in the EU. In an ongoing phase 3 clinical trial, sparsentan provided greater and durable (up to 110 weeks) antiproteinuric effects than irbesartan, an angiotensin-receptor blocker, in patients with IgA nephropathy. Sparsentan also demonstrated long-term benefits in kidney function preservation. Sparsentan was generally well tolerated, with its tolerability profile being similar to that of irbesartan. Current evidence indicates that sparsentan is an effective emerging treatment option for adults with IgA nephropathy. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic values of estimated glomerular filtration rate (eGFR) calculated by different formulas have not been adequately compared in patients with heart failure with preserved ejection fraction (HFpEF). Aim: We compared the predictive values of serum creatinine-based eGFRs calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, Modification of Diet in Renal Disease Study (MDRD) formula, and full-age-spectrum creatinine (FAS Cr) equation in 1751 HFpEF patients. Methods: The area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were employed. Results: eGFR values were lowest calculated with FAS Cr equation (p < 0.001). When patients were classified into 4 subgroups (eGFR ≥ 90, 89–60, 59–30, and < 30 ml/min/1.73 m2) or only 2 subgroups (≥ 60 or < 60 ml/min/1.73 m2), the 3 formulas correlated significantly, with the best correlation found between the MDRD and CKD-EPI formulas (kappa = 0.871 and 0.963, respectively). The 3 formulas conveyed independent prognostic information. After adjusting for potential cofounders, risk prediction for all-cause mortality was more accurate (p = 0.001) using the CKD-EPI equation than MDRD formula as assessed by AUC. Compared with MDRD formula, CKD-EPI equation exhibited superior predictive ability assessed by IDI and NRI of 0.32% (p < 0.001)/10.4% (p = 0.010) for primary endpoint and 0.37% (p = 0.010)/10.8% (p = 0.010) for HF hospitalization. The risk prediction for deterioration of renal function was more accurate (p ≤ 0.040) using the CKD-EPI equation than FAS Cr equation as assessed by AUC, IDI, and NRI. Conclusion: The CKD-EPI formula might be the preferred creatinine-based equation in clinical risk stratification in HFpEF patients. [ABSTRACT FROM AUTHOR]

Background: Patients on hemodialysis are particularly vulnerable to COVID-19 and may have a reduced response to vaccination because of a decreased immune response. The nutritional status before or during the infection could also impact on the clinical effectiveness of vaccination. Objectives: We aim to describe the evolution of clinical and nutritional biomarkers of hemodialysis patients infected with SARS-CoV-2 and to assess their association with vaccination status. Methods: An observational, analytic, longitudinal, retrospective multicenter study was carried out in 82 patients on hemodialysis with SARS-CoV-2 infection. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), anthropometry, and biochemical parameters. The association of the vaccine doses with clinical- and nutritional-related variables was also evaluated. Results: The percentage of vaccinated patients was similar to that of nonvaccinated patients. Before infection, most of the patients were malnourished. They presented lower albumin, creatinine, and urea levels than the well-nourished patients. Significant deterioration of nutritional status after infection was evidenced considering GNRI score, dry weight, and body mass index. Albumin and creatinine also decreased significantly after infection, whereas C-reactive protein increased in the acute phase. Significant inverse correlation was found between the variation of post–pre GNRI scores and basal albumin and C-reactive protein at 7 days. In addition, we observed the opposite trend between albumin at 30 days and basal cholesterol. A negative value in the GNRI variation was associated with bilateral pneumonia, need for hospitalization, and nutritional support. Vaccinated patients presented substantially less bilateral pneumonia and hospitalization. No significant effects were observed between vaccine doses and the variation in nutritional status, although a positive correlation was detected with the albumin at 7 days and C-reactive protein before infection and the number of vaccine doses received. Discussion: COVID-19 is associated with affectations in the nutritional status and biomarkers in hemodialysis patients. In this study, vaccines have shown a protective effect against the clinical consequences of COVID. However, they have shown limitations in preventing the deterioration of nutritional status after infection. The results highlight the importance of promoting the vaccination in these patients as well as incorporating nutritional assessment before, during, and after the infection. [ABSTRACT FROM AUTHOR]

Simple Summary: CPX-351 has been approved for the treatment of acute myeloid leukemia. Previous studies have indicated that dose adjustment is not warranted for patients with mild to moderate renal impairment. However, the effect of severe renal impairment on the use of CPX-351 has not been established. In this study, we evaluated CPX-351 in patients with normal renal function and in patients with moderate and severe renal impairment. We compared how CPX-351 moves through the body, as well as the safety of the drug, in these different patient groups. The results suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment. This open-label phase 1 study (clinicaltrials.gov, NCT03555955) assessed CPX-351 pharmacokinetics (PK) and safety in patients with hematologic malignancies with normal or impaired renal function. Patients were enrolled into three cohorts based on their creatinine clearance (CrCl): ≥90 mL/min (Cohort 1, normal renal function, n = 7), 30 to <59 mL/min (Cohort 2, moderate renal impairment, n = 8), or <30 mL/min (Cohort 3, severe renal impairment, n = 6). Patients received intravenous CPX-351 for initial induction; blood and urine samples were collected for PK analysis. The primary objective was to assess the PK parameters for cytarabine, daunorubicin, and their respective metabolites, arabinosyluracil (Ara-U) and daunorubicinol. Renal impairment did not significantly impact the cytarabine, daunorubicin, or daunorubicinol exposure, but it caused a slight increase in the Ara-U exposure. The CPX-351 side effect profile was similar in patients with impaired renal function compared to those with normal renal function. All the patients reported ≥1 treatment-emergent adverse event (TEAE), most commonly febrile neutropenia and nausea (57% each) and hyperglycemia (43%); no patients discontinued treatment due to TEAEs. These data suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment. [ABSTRACT FROM AUTHOR]

Large biological variation hinders application of patient-based real-time quality control (PBRTQC). The effect of analyte ratios on the ability of PBRTQC to improve error detection was investigated. Four single analyte-ratio pairs (alanine aminotransferase [ALT] vs. ALT to aspartate aminotransferase ratio [RALT]; creatinine [Cr] vs. Cr to cystatin C ratio [RCr]; lactate dehydrogenase [LDH] vs. LDH to hydroxybutyrate dehydrogenase ratio [RLDH]; total bilirubin [TB] vs. TB to direct bilirubin ratio [RTB]) were chosen for comparison. Various procedures, including four conventional algorithms (moving average [MA], moving median [MM], exponentially weighted moving average [EWMA] and moving standard deviation [MSD]) were assessed. A new algorithm that monitors the number of defect reports per analytical run (NDR) was also evaluated. When a single analyte and calculated ratio used the same PBRTQC parameters, fewer samples were needed to detect systematic errors (SE) by taking ratios (p<0.05). Application of ratios in MA, MM and EWMA significantly enhanced their ability to detect SE. The influence of ratio on random error (RE) detection depended upon the analytes and PBRTQC parameters, as consistent advantage was not demonstrated. The NDR method performed well when appropriate parameters were used, but was only effective for unilateral SE. Rearrangement of sample order led to a significant deterioration of conventional algorithms' performance, while NDR remained almost unaffected. For analytes with large variation and poor PBRTQC performance, using ratios as PBRTQC indexes may significantly improve performance and achieve better anti-interference ability, providing a new class of monitoring indicators for PBRTQC. [ABSTRACT FROM AUTHOR]

Background and Design: Isotretinoin, a vitamin A derivative, is widely used to treat moderate and severe acne. Although the effect of systemic isotretinoin treatment on hemogram parameters has been demonstrated, the results are still controversial. In the present study, we investigated the effect of isotretinoin on biochemical parameters, hemogram, and inflammatory markers in the Black Sea Region. Materials and Methods: Medical data of 300 patients with moderate and severe acne vulgaris who received systemic isotretinoin treatment for at least three months were analyzed retrospectively. Hemogram parameters, serum creatinine levels, liver transaminase levels, serum lipid levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and monocyte/high-density lipoprotein (HDL) ratios were evaluated before and three months after the treatment. Results: A significant decrease was found in leukocyte count, red blood cell count, neutrophil count, monocyte count, HDL levels, and NLR after three months of treatment compared to the baseline. A significant increase was found in platelet count, plateletcrit (PCT), platelet distribution width (PDW), red cell distribution width, hematocrit, mean erythrocyte hemoglobin, total cholesterol, low-density lipoprotein, triglyceride, and aspartate aminotransferase levels. Conclusion: According to our results, isotretinoin can affect several hemogram and biochemical parameters. In addition, this article is the only article demonstrating a decrease in monocyte count and an increase in PDW and PCT levels after the treatment of isotretinoin in the literature. [ABSTRACT FROM AUTHOR]

Background: Digoxin is primarily metabolized by the kidney, and its toxicity is strongly associated with high concentrations, particularly in elderly patients. The purpose of this study was to evaluate the predictive performance of renal function biomarkers for supratherapeutic digoxin concentrations in elderly patients with heart failure (HF) and chronic kidney disease (CKD). Methods: Data were retrospectively obtained from elderly patient with HF and CKD who received digoxin treatment from January 2022 and December 2022. Logistic regression was used to assess independent risk factors for supratherapeutic concentrations. The predictive performance of serum creatinine, serum cystatin C, and blood urea nitrogen on supratherapeutic concentrations was compared by receiver operating characteristic analysis. Results: A total of 115 elderly patients with HF and CKD were enrolled in our study. Supratherapeutic concentrations were detected in 49 patients. Logistic regression analysis showed that estimated glomerular filtration rate calculated by serum cystatin C [eGFRCysC, odds ratio (OR): 0.962, P = 0.006], heart rate (OR: 1.024, P = 0.040), and NYHA class (OR: 3.099, P = 0.010) were independent risk factors for supratherapeutic concentration. Cutoff value for eGFRCysC between the two groups was 41 ml/min/1.73m2. Predictive performance of serum cystatin C was further improved in patients with obesity, CKD stage 4–5, and older than 75 years compared with normal weight, CKD stage 3, and aged 60–75-year-old patients. Conclusions: Serum cystatin C is a sensitive renal function biomarker to predict supratherapeutic digoxin concentration in elderly patients with HF and CKD. [ABSTRACT FROM AUTHOR]

Introduction: Serum cystatin C has been proposed as a sensitive marker for detecting renal impairment. Renal impairment can often co-exist with liver cirrhosis, as decreased blood flow through the cirrhotic liver can lead to kidney dysfunction. However, its role in patients with liver cirrhosis has not been extensively studied, especially in the detection of early renal impairment. Aim: To investigate whether serum cystatin C could serve as a potential marker for detecting early renal dysfunction in patients with liver cirrhosis. Materials and Methods: This hospital-based cross-sectional study was conducted on 60 patients with liver cirrhosis at Assam Medical College and Hospital, Dibrugarh, Assam, India, from June 2019 to May 2020. All patients were assessed for clinical symptoms and laboratory parameters, focusing on renal function tests, measurement of serum cystatin C levels, and Glomerular Filtration Rate (GFR). A two-tailed p-value <0.05 was considered statistically significant in all calculations. Results: In total, 60 consecutive patients with liver cirrhosis were evaluated during the study period, 85% of whom were males. The mean age was 47.4±9.3 years. The mean values of GFR calculated from the mean values of serum creatinine and serum cystatin C were 59.57±31.48 and 31.25±18.32, respectively, both showing a negative correlation (r=-0.802 and r=-0.817, respectively), indicating that cystatin C has a superior correlation with GFR when compared to serum creatinine. Regression analysis showed a tighter distribution of results around the regression line for cystatin C, as indicated by an R2 value of 0.67, compared to 0.64 for creatinine. It was also observed that for every unit rise in serum creatinine and cystatin C value, GFR decreased by 29.89 and 14.67, respectively. Conclusion: Serum cystatin C is a better predictor of GFR than serum creatinine and can therefore be used as an early marker of renal dysfunction in the course of liver cirrhosis. [ABSTRACT FROM AUTHOR]