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Due to a plethora of risk factors, including prematurity, neonates are at risk for acute kidney injury (AKI) and, once established, AKI is associated with poor outcomes. The most widely used AKI biomarker is creatinine, despite research demonstrating creatinine to be a suboptimal tool for diagnosing neonatal AKI. This article uses an amalgamated case study to illustrate the inadequacies of creatinine for detection of preterm AKI and to present a range of novel AKI biomarkers relevant to the neonatal population. Clinical evaluation of novel AKI biomarkers is needed to improve precision and rapidity of AKI management in neonates.

Background: With increasing incidence and treatment costs, chronic kidney disease (CKD) has become an important public health problem in China, especially in females. However, the genetic determinants are very limited. The estimated glomerular filtration rate (eGFR) based on creatinine is commonly used as a measure of renal function but can be easily affected by other factors. In contrast, eGFR based on both creatinine and cystatin C (eGFRcr-cys) improved the diagnostic accuracy of CKD. To our knowledge, no genome-wide association analysis of eGFRcr-cys has been conducted in the Chinese population., Methods: By conducting a Genome-Wide association study(GWAS), a method used to identify associations between genetic regions (genomes) and traits/diseases, we examined the relationship between genetic factors and eGFRcr-cys in Chinese women, with 1983 participants and 3,838,121 variants included in the final analysis., Result: One significant locus (20p11.21) was identified in the Chinese female population, which has been reported to be associated with eGFR based on cystatin C (eGFRcys) in the European population. More importantly, we found two new suggestive loci (1p31.1 and 11q24.2), which have not yet been reported. A total of three single nucleotide polymorphisms were identified as the most important variants in these regions, including rs2405367 (CST3), rs66588571(KRT8P21), and rs626995 (OR8B2)., Conclusion: We identified 3 loci 20p11.21, 1p31.1, and 11q24.2 to be significantly associated with eGFRcr-cys. These findings and subsequent functional analysis describe new biological clues related to renal function in Chinese women and provide new ideas for the diagnosis and treatment development of CKD., Competing Interests: Declarations Ethics approval and consent to participate This study has been approved by the Institutional Review Board of Nanjing Medical University (2015077). All participants have provided written informed consent at enrollment into the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Microcirculatory dysfunction, hypoxia, and inflammation are considered to be central in the pathogenesis of sepsis-induced acute kidney injury (AKI). In this experimental study, we hypothesized that extracorporeal removal of inflammatory cytokines by hemoadsorption (HA) therapy may mitigate renal injury associated with sepsis-induced AKI. To this end, we investigated renal microcirculatory oxygenation and perfusion, oxygen consumption, lactate, systemic hemodynamic variables, tubular cell integrity, inflammatory mediators, and kidney function in a rat model of septic AKI elicited by endotoxin infusion. Three groups of rats were investigated on extracorporeal circulation: HA only, LPS, and LPS + HA. Endotoxin infusion reduced cortex microcirculatory oxygenation and raised creatinine and lactate levels. Renal microcirculatory oxygenation, measured by two independent techniques (phosphorescence (µPO 2 ) and spectrophotometry/Doppler (µHbO 2sat and [Formula: see text])), was ameliorated by HA therapy. The renal oxygen consumption, lactate and creatinine levels were restored in the LPS + HA group. A reduced amount of injured tubular cells was found in histological analysis of the kidneys. This experimental study demonstrated an improvement in multiple determinants of kidney oxygenation, damage, and systemic blood perfusion by HA in a clinically relevant rat model of septic AKI. Further studies are needed to optimize and support the clinical use of HA as a renal protective strategy., Competing Interests: Declarations Competing interests Dr. Ince is the CSO of Active Medical BV, Leiden, The Netherlands, a company that provides devices (OxyCam), software (MicroTools), education (Microcirculation Academy), and services related to clinical microcirculation. All other authors declare that they have no conflict of interest., (© 2024. The Author(s).)

Reduced muscle mass has been associated with the progression and prognosis of amyotrophic lateral sclerosis (ALS). However, it remains unclear whether decreased muscle mass is a risk factor for ALS or a consequence of motor neuron degeneration. Recently, serum creatinine-to-cystatin C ratio (CCR) have emerged as promising biomarkers for assessing muscle mass. We aimed to explore the association between CCR and the incidence of ALS using data from the UK Biobank. Between 2006 and 2010, 446,945 participants were included in the baseline. CCR was calculated as the ratio of serum creatinine to cystatin C. Cox regression models were used to analyze the relationship between CCR and ALS incidence. Furthermore, subgroup analyses were conducted to investigate potential covariates in these relationships. After adjusting for all covariates, the multivariate Cox regression analysis revealed a significant association between decreased CCR and an increased risk of ALS (hazard ratio (HR) = 0.990, 95% confidence interval (CI): 0.982-0.999, P = 0.026). Participants were stratified into groups based on CCR tertiles. Compared with participants in the highest tertiles of CCR, those in the lowest (HR = 1.388, 95% CI: 1.032-1.866, P = 0.030) and medium tertiles (HR = 1.348, 95% CI: 1.045-1.739, P = 0.021) had an increased risk of ALS incidence. Subgroup analysis showed that the relationship between CCR and ALS incidence was particularly significant among participants aged < 65 years (CCR tertile 1: HR = 1.916, 95% CI: 1.366-2.688, P < 0.001; CCR tertile 2: HR = 1.699, 95% CI: 1.267-2.278, P < 0.001). The present results demonstrate that lower CCR is significantly associated with a higher risk of ALS., Competing Interests: Competing interests The authors declare no competing interests. Ethical declarations All participants have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted., (© 2024. The Author(s).)

Backgrounds: Baricitinib, an oral selective inhibitor of Janus kinase 1 and 2, is approved for moderate and severe rheumatoid arthritis (RA) with insufficient response to conventional synthetic disease-modifying antirheumatic drugs. The study evaluated the safety of baricitinib 24 weeks 4 mg or 2 mg for the treatment of RA., Methods: The net change (least squares mean [LSM]) of alanine aminotransferase (ALT), creatinine, low-density lipoprotein cholesterol (LDL-C) levels from baseline with the comparison of baricitinib versus placebo was pooled, respectively. The risk ratios (RR) of serious advanced events (SAEs), major cardiovascular events (MACEs), infection, serious infection, and advanced events (AEs) at the end of treatment across groups were compared., Results: Five randomized controlled trials with 2901 patients were included in the summary analysis. Results showed that baricitinib 4 mg significantly increased ALT and creatinine levels, the net LSM change was respectively 3.59 U/L with 95% confidence interval (CI) (1.75-5.43), 4.25 µmol/L with 95% CI (3.38-5.12), however, baricitinib 2 mg of ALT and creatinine levels were not significantly different. Baricitinib 4 mg and 2 mg significantly increased LDL-C levels, the net LSM change was respectively 11.44 mg/dL with 95% CI (6.08-16.80), 8.70 mg/dL with 95% CI (4.19-13.20). Baricitinib 4 mg significantly increased the incidence of infection, the pooled RR (95% CI) was 1.29 (1.13-1.47), and baricitinib 2 mg was not significantly different. However, the pooled RRs of SAEs, MACEs, and serious infection were not statistically significant across groups. The pooled RRs of AEs were not statistically significant between baricitinib 4 mg and 2 mg., Conclusions: This study confirmed that patients with RA taking 4 mg baricitinib increased levels of ALT, creatinine, as well as an increased risk of infections, compared with those taking 2 mg baricitinib. Both 2 mg and 4 mg also increased the level of LDL-C, but it increased the most severely at 4 mg baricitinib. However, the incidence of SAEs, MACEs, and serious infection was not significantly different in patients treated with baricitinib 4 mg and 2 mg compared with placebo, the incidence of AEs was not significantly different between baricitinib 4 mg and 2 mg., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To explore the association between hyperuricemia and having periodontitis., Materials and Methods: A representative cross-sectional dataset of 10,158 adults was extracted from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. The association between hyperuricemia (the primary exposure) and having periodontitis (outcome) were evaluated using weighted logistic regression models. Serum uric acid (UA) levels and the UA to creatinine (UA/Cr) ratio were used as secondary exposures. Their associations with the diagnosis periodontitis were analyzed using weighted logistic regression or restricted cubic spline regression., Results: The prevalence of Stages III/IV periodontitis was 47.7% among individuals with hyperuricemia and 37.4% among those without. After adjustment, individuals with hyperuricemia had 0.281 times higher odds of developing Stages III/IV periodontitis compared to those without hyperuricemia (adjusted OR = 1.286, 95% CI = 1.040 to 1.591, P = 0.024). The increased odds could be explained by a linear relationship with the serum UA/Cr ratio and a U-shaped relationship with serum UA levels. Each unit increase in the serum UA/Cr ratio was associated with 0.048 times higher odds of developing Stages III/IV periodontitis (adjusted OR = 1.048, 95% CI = 1.008 to 1.088, P = 0.021). Additionally, each 1 mg/dL increase in serum UA was associated with 0.156 times higher odds (adjusted OR = 1.156, 95% CI = 1.009 to 1.323, P = 0.038) of developing Stages III/IV periodontitis when UA levels were greater than 5.9 mg/dL, but 0.118 times lower odds when UA levels were 5.9 mg/dL or lower (adjusted OR = 0.882, 95% CI = 0.790 to 0.984, P = 0.027). Sensitivity analyses validated the robustness of the findings., Conclusions: This study provides the first direct evidence that hyperuricemia is associated with Stages III/IV periodontitis., Clinical Relevance: Hyperuricemia may represent a new potential comorbidity of periodontitis, possibly contributing directly or indirectly to the disease burden in patients with periodontitis., Clinical Trial Number: Not applicable., Competing Interests: Declarations Ethics approval and consent to participate The NHANES project was approved by the Ethics Review Committee of the National Center for Health Statistics of the US. All participants provided their informed consent. Consent for publication No applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Sickle cell disease (SCD) is the most common monogenic disorder in Saudi Arabia, which associates with an increased risk of organs damage, including the kidney. The aim of this study is to investigate the prevalence and predictors of sickle cell nephropathy (SCN) in the Saudi population. A retrospective study was conducted from April to October 2023, and included 343 adult patients with SCD who were recruited from the hereditary blood diseases center (HBDC), Al-Ahsa, Saudi Arabia. Spot protein-to-creatinine ratio was measured and glomerular filtration rate (GFR) was estimated from serum creatinine using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. As per KIDGO guidelines, CKD was diagnosed in 93 (27.1%) patients. Based on the CKD-EPI equation, 2% of patients had low GFR (eGFR < 60mL/min), 28.3% had high GFR (eGFR > 140 mL/min), and 69.7% had normal GFR. Among SCD patients, proteinuria was observed in 26.5% of the patients. SCD patients with CKD were significantly older than non-CKD patients (p < 0.001) and had higher prevalence of diabetes mellitus (DM) and hypertension (HTN) (p = 0.045 and 0.001 respectively). The multivariate analysis showed that age (P = 0.001; OR 1.035; 95% CI 1.014-1.056) and low hemoglobin level (p = 0.034; OR -0.851; 95% CI 0.721-0.980) were independent risk factors for the development of SCN. Nephropathy is a common complication among patients with SCD as early as the third decade of life, although they remain asymptomatic. Advances in age and low hemoglobin levels are the main predictors of nephropathy. In addition, SCD patients with coexistent comorbidities, particularly DM and HTN, were at increased risk of developing kidney disease., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aims: Acute kidney injury (AKI) is a life-threatening condition marked by sudden kidney function loss and azotemia. While its management is limited to supportive care, the effects of hyperbaric oxygen therapy (HBO) on AKI remain a subject of conflicting animal research. This study aimed to systematically review and meta-analyze HBO's effects on renal function biomarkers serum creatinine (SCr) and blood urea nitrogen (BUN) in murine AKI models, also exploring tissue-level nephroprotection., Main Methods: The PUBMED, SciELO, and LILACS databases were searched until September 5, 2024. Effect sizes of HBO on SCr and BUN levels were expressed as standardized mean difference (SMD) alongside 95 % confidence interval (CI), calculated by random-effects model. Extracted data also included murine specie/strain, HBO parameters, AKI induction method (toxic, ischemic, others), and histological findings. Study quality and publication bias were respectively assessed using the CAMARADES checklist and Egger's test. This review adhered to PRISMA guidelines and was registered in PROSPERO (CRD42022369804)., Key Findings: Data synthesis from 21 studies demonstrates that HBO effectively reduces azotemia in AKI-affected animals (SCr's SMD = -1.69, 95 % CI = -2.38 to -0.99, P < 0.001; BUN's SMD = -1.51, 95 % CI = -2.32 to -0.71, P < 0.001) while mitigating histological damage. Subgroup analyses indicate that HBO particularly benefits ischemic and other AKI types (P < 0.05). In contrast, data from toxic AKI models were inconclusive due to insufficient statistical power (P > 0.05, 1-β < 30 %)., Significance: This meta-analysis provides compelling evidence supporting the adjunctive use of HBO in AKI management., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Creatinine, an important biomarker for renal functions, is often conventionally estimated using the gold standard Jaffe reaction from blood, which involves the usage of a spectrophotometric measurement, thus restricting its utilization scope in point-of-care settings. Here, we report the development of a method for the single-step quantification of creatinine from whole blood using a paper-based microfluidic device. Our platform uses Whatman filter paper integrated with an LF1 membrane. The on-chip separation of blood plasma is achieved through the LF1 membrane, while the Whatman component of the device contains the embedded reagents for the Jaffe reaction. The combination of two different grades of paper enables a single-step quantification of creatinine as the separated blood plasma traverses to the reaction zone through capillary imbibition. Colorimetric readouts were quantified using an RGB sensor instead of a smartphone, which is highly platform dependent and incurs a relatively higher cost compared to the other components in typical point-of care (POC) devices. Our sensor was integrated within a 3D box, thereby making the detection virtually instrument free and perfectly suited for POC settings. The limit of detection (LOD) of our device was 0.219 mg dL -1 , which falls within the lower range of physiological values. The coefficient of determination ( R 2 ) for the linearity and median accuracy were 0.978 and 94.047%, respectively. The relative standard deviation (RSD) for precision measurements remained below 5% for the developed protocol. Furthermore, we validated the performance of our device with 35 clinical samples in laboratory settings against the gold standard measurements. Our Bland-Altman plot as well as t -test and chi-square test results clearly confirmed the validity of our device within a 95% confidence interval.

Background: Chronic kidney disease (CKD) is a global health problem affected by under-recognition and under-treatment in primary care settings. Electronic clinical decision support (CDS) triggering systems have the potential to improve detection and management of people with CKD by assisting clinicians in adhering to guideline recommendations. We aimed to test whether an electronic CDS triggering system would improve the detection, recognition, and management of patients with CKD in primary care., Method/design: This is a pragmatic cluster-randomized controlled trial where 66 primary healthcare centers from the Stockholm Region, Sweden were randomized 1:1 to receive either a new expanded CDS-triggering system offering kidney-specific advice or to continue with their current CDS-triggering system. The expanded CDS system reminds and provides practical facilitators of the processes of CKD screening, recognition with a diagnosis, management and referral to specialist care. The trial duration is 24 months and it is embedded into the Stockholm CREAtinine measurements (SCREAM) project, a repository of healthcare data from the region, which minimizes disturbances with healthcare praxis due to the trial and makes it fully pragmatic. The primary outcomes are the number of eligible patients screened for creatinine and albuminuria once annually and the re-testing of these labs within 6 months in patients with abnormal eGFR or albuminuria. Secondary outcomes are the proportions of issued clinical diagnoses among those fulfilling criteria, proportions of patients with significant albuminuria receiving prescribed nephroprotective medications, proportions of accepted referrals to nephrologist care among those fulfilling criteria and proportion of referrals for ultrasound of the kidneys., Discussion: Prior pragmatic trials of CDS-systems in CKD has shown an improvement in quality indicators primarily in patients already diagnosed with CKD. This study expands this evidence by focusing on the process of screening, identification, monitoring and diagnostic work-up., Conclusion: This pragmatic trial will assess the value of CDS for improved adherence to CKD guidelines in primary care., Clinicaltrials: gov registration: NCT06386172, submitted 2024-04-23., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The serum albumin-to-serum creatinine ratio (sACR) is independently associated with the prognosis of multiple diseases. However, its relationship with in-hospital mortality of patients with severe acute pancreatitis (SAP) remains unclear., Methods: Patients diagnosed with SAP between April 2016 and December 2023 were collected. These patients were categorized into low and high sACR groups based on an optimal cut-off value calculated using Youden's index. Multivariate logistic regression analysis was utilized to examine the relationship between sACR levels and the in-hospital mortality. Additionally, a limited restricted cubic spline (RCS) method was employed to evaluate the nonlinear relationship between sACR values and the risk of in-hospital mortality. The potential for unmeasured confounders between sACR levels and in-hospital mortality was also explored through the calculation of the E value., Results: A total of 114 eligible patients were included in this sutdy. The multivariate logistic regression analysis indicated an independent association between sACR levels and in-hospital mortality (p < 0.001). The RCS analysis demonstrated a linear correlation between sACR values and the risk of in-hospital mortality (P for non-linearity > 0.05), where the risk increased as the sACR value decreased., Conclusions: The research findings suggest that sACR levels are independently associated with in-hospital mortality of patients with SAP, providing a means for early identification of those at high risk of in-hospital mortality. This early identification may facilitate the optimizing and strengthening of treatments, ultimately leading to improved outcomes., Competing Interests: Declarations Ethics approval and consent to participate Due to retrospective nature of the study, ethics approval and informed consent from patients were waived by the Division of Science and Technology of Yijishan hospital of Wannan Medical college in accordance with national legislation and institutional requirements. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aims: Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) both have microcirculation dysfunction. Urinary albumin-to-creatinine ratio (UACR) is a biomarker for DN. We aimed to explore the links between DPN and UACR in patients with type 2 diabetes mellitus (T2DM)., Methods: A total of 195 T2DM patients were defined as Control or DPN group. Clinical parameters were compared, and the association between HbA1c (or UACR) and DPN was analyzed. Risk factors for DPN were observed, and the diagnostic values of HbA1c and UACR were assessed., Results: Compared with 104 participants without DPN, 91 individuals with DPN exhibited higher HbA1c and UACR levels. In all patients, increased HbA1c and UACR were identified as risk factors for DPN in individuals with T2DM. Moreover, increased HbA1c was a risk factor for DPN in volunteers without DN, whereas elevated UACR was determined as a risk factor for DPN in participants with DN. The cut-off point for HbA1c (7.65%) in patients without DN had a sensitivity of 86.0% and specificity of 44.6%, while the cut-off point for UACR (196.081 mg/g) in patients with DN had a sensitivity of 52.9% and specificity of 76.2%., Conclusion: Elevated HbA1c and UACR levels are risk factors for DPN and may serve as potential biomarkers for DPN in T2DM patients., (© 2024. The Author(s).)

Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction., (© 2024. The Author(s).)

Background: Genetic epidemiological evidence for the kidney function traits in East Asian populations, including Japanese, remain still relatively unclarified. Especially, the number of genome-wide association studies (GWASs) for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful., Methods: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr])., Results: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; P < 5 × 10 -8 ), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; P < 5 × 10 -8 ), of which one locus (more than 1 Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding., Conclusion: The present GWAS meta-analysis of the largest genome cohort studies in Japanese subjects provided some original genomic loci associated with kidney function, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

Background: Plasma cell dyscrasias encompass a diverse set of disorders, where early and precise diagnosis is essential for optimizing patient outcomes. Despite advancements, current diagnostic methodologies remain underutilized in applying artificial intelligence (AI) to routine laboratory data. This study seeks to construct an AI-driven model leveraging standard laboratory parameters to enhance diagnostic accuracy and classification efficiency in plasma cell dyscrasias., Methods: Data from 1,188 participants (609 with plasma cell dyscrasias and 579 controls) collected between 2018 and 2023 were analyzed. Initial variable selection employed Kruskal-Wallis and Wilcoxon tests, followed by dimensionality reduction and variable prioritization using the Shapley Additive Explanations (SHAP) approach. Nine pivotal variables were identified, including hemoglobin (HGB), serum creatinine, and β 2 -microglobulin. Utilizing these, four machine learning models (gradient boosting decision tree (GBDT), support vector machine (SVM), deep neural network (DNN), and decision tree (DT) were developed and evaluated, with performance metrics such as accuracy, recall, and area under the curve (AUC) assessed through 5-fold cross-validation. A subtype classification model was also developed, analyzing data from 380 cases to classify disorders such as multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS)., Results: 1. Variable selection: The SHAP method pinpointed nine critical variables, including hemoglobin (HGB), serum creatinine, erythrocyte sedimentation rate (ESR), and β 2 -microglobulin. 2. Diagnostic model performance: The GBDT model exhibited superior diagnostic performance for plasma cell dyscrasias, achieving 93.5% accuracy, 98.1% recall, and an AUC of 0.987. External validation reinforced its robustness, with 100% accuracy and an F1 score of 98.5%. 3. Subtype Classification: The DNN model excelled in classifying multiple myeloma, MGUS, and light-chain myeloma, demonstrating sensitivity and specificity above 90% across all subtypes., Conclusions: AI models based on routine laboratory results significantly enhance the precision of diagnosing and classifying plasma cell dyscrasias, presenting a promising avenue for early detection and individualized treatment strategies., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yao et al.)

Background: Appropriate clinical decision-making relies on the interpretation of equivalent measurement results in the context of valid clinical decision limits. Besides guideline-based decision limits, reference intervals (RIs) are commonly used to discriminate between abnormal results and results from "healthy" individuals. This study evaluated the suitability of RIs in light of the analytical bias for laboratories in the Netherlands using one standardized, one harmonized, and one unharmonized measurand (creatinine, hemoglobin, and ferritin, respectively)., Methods: Three types of data were collected: (a) external quality assessment (EQA) performance data from the Dutch Foundation for Quality Assurance in Laboratory Medicine (SKML); (b) the RIs reported by laboratories for a 55-year-old female; and (c) harmonized RIs established by using unique routine patient results using RefineR. Routinely used RIs (b) were compared to the harmonized RIs (c) and evaluated in combination with the analytical bias at the lower and upper reference limits., Results: Laboratories reported a variety of routinely used RIs that were inconsistent with the analytical bias, with differences between measurement procedures. The use of assays that perform within allowable bias limits does not automatically guarantee that the appropriate RI is used, allowing potential for structural misinterpretation of important diagnoses in patients., Conclusions: The use of RIs that are inconsistent with the analytical bias causes unnecessary between-laboratory differences in clinical decision-making. Adopting harmonized RIs facilitates similar interpretation of results across facilities. Harmonized RIs can be adopted immediately if the observed bias is acceptable or eliminated, or after standardization/harmonization of measurands without complete metrological traceability., (© Association for Diagnostics & Laboratory Medicine 2024.)

In clinical practice, the glomerular filtration rate (GFR), a measurement of kidney functioning, is normally calculated using equations, such as the European Kidney Function Consortium (EKFC) equation. Despite being the most general equation, EKFC, just like previously proposed approaches, can still struggle to achieve satisfactory performance, limiting its clinical applicability. As a possible solution, recently machine learning (ML) has been investigated to improve GFR prediction, nonetheless the literature still lacks a general and multi-center study. Using a dataset with 19,629 patients from 13 cohorts, we investigate if ML can improve GFR prediction in comparison to EKFC. More specifically, we compare diverse ML methods, which were allowed to use age, sex, serum creatinine, cystatin C, height, weight and BMI as features, in internal and external cohorts against EKFC. The results show that the most performing ML method, random forest (RF), and EKFC are very competitive where RF and EKFC achieved respectively P10 and P30 values of 0.45 (95% CI 0.44;0.46) and 0.89 (95% CI 0.88;0.90), whereas EKFC yielded 0.44 (95% CI 0.43; 0.44) and 0.89 (95% CI 0.88; 0.90), considering the entire cohort. Small differences were, however, observed in patients younger than 12 years where RF slightly outperformed EKFC., (© 2024. The Author(s).)

Objectives: This study aimed to examine the relationship between measures of kidney function and impaired lung function in individuals with diabetes and to assess all-cause mortality risk associated with having chronic kidney disease (CKD) and or impaired lung function., Design: Cross-sectional and retrospective cohort study., Setting: The National Health and Nutrition Examination Survey 2007-2012., Participants: A total of 10 809 participants aged over 20 years were included in this study: 9503 with normal spirometry, 951 with preserved ratio impaired spirometry (PRISm) and 355 with variable obstruction (VO)., Exposure and Outcome Measures: Kidney function measures, including estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), were considered exposure variables. PRISm and VO were outcome variables. PRISm was defined as a forced expiratory volume in 1 s (FEV1)<80% predicted and an FEV1/forced vital capacity (FVC) ratio≥0.7, while VO was defined as an FEV1/FVC ratio <0.7 prebronchodilator and ≥0.7 postbronchodilator. In the cross-sectional analysis, multivariate logistic regression models were used to assess the relationship between kidney function measures and spirometry findings. In the retrospective cohort analysis, Cox proportional hazards models were employed to evaluate the impact of having PRISm or VO, combined with CKD, on all-cause mortality., Results: An increase in UACR was significantly associated with higher odds of PRISm (OR (95% CI)=1.10 (1.01, 1.21), p=0.03). Additionally, eGFR <60 was associated with the odds of variable obstructive lung function (OR (95% CI)=1.72 (1.07, 2.74), p=0.03) compared with eGFR >60. After adjustments, an increase in UACR was associated with higher odds of PRISm in individuals with diabetes (OR (95% CI)=1.21 (1.08, 1.36), p=0.002), and UACR ≥300 mg/g significantly increased odds of having PRISm in idividuals with diabetes (OR (95% CI)=2.34 (1.23, 4.47), p=0.01). During a mean follow-up of 12.3 years, 10 500 deaths occurred. In the diabetic group, compared with normal spirometry without CKD, those with both PRISm and CKD had a significantly increased risk of all-cause mortality (HR (95% CI)=3.46 (1.94, 6.16), p<0.0001)., Conclusion: An elevated UACR and albuminuria were linked to a higher risk of PRISm. Our study emphasises that kidney and lung function are correlated. Further research is necessary to confirm our findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chihuahua represents an increasingly widespread breed predisposed to cardiac disease. N-terminal pro-B-type natriuretic peptide (NT-proBNP) might be a useful point-of-care biomarker for dogs suspected of having heart disease, but breed differences have been reported. The urinary aldosterone-to-creatinine ratio (UAldo: C) appears to be a good indicator of renin-angiotensin-aldosterone system activity in dogs, but Chihuahuas showed significantly higher UAldo: C than other breeds. The objective of this study was to assess preliminary breed-specific reference intervals for NT-proBNP and UAldo: C in healthy Chihuahuas and evaluate sex differences in these parameters., Results: Forty-three healthy Chihuahuas dogs were enrolled. The median NT-proBNP was 347 (125-515) pmol/L, and the median UAldo: C was 2.59 (1.57-4.61) µg/g. The NT-proBNP reference interval was 125 (90% CI 125-125) - 2121.4 (90% CI 941.6-2248) pmol/L. 91% of the Chihuahuas were below the nonbreed-specific cut-off (900 pmol/L). The UAldo: C reference interval was 0.6 (90% CI 0.5-0.9) - 16.8 (90% CI 10.9-27.4) µg/g. No significant sex differences in NT-proBNP or UAldo: C were found., Conclusions: The median value, interindividual coefficient of variation and reference interval of NT-proBNP were in line with those reported for other small breeds. In contrast to previous studies, no sex differences in NT-proBNP were detected. As previously suggested, Chihuahuas seem to be characterized by higher values of UAldo: C than other breeds., (© 2024. The Author(s).)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous adverse drug eruption characterized by rash, fever, lymphadenopathy, hematologic abnormalities, and organ dysfunction. Identifying causative agents and monitoring disease course in DRESS syndrome is crucial to prevent end-organ damage. The temporal relationship between causative medications including vancomycin and laboratory abnormalities in DRESS has not been studied, limiting the utility of laboratory data in monitoring disease course. Our study aims to investigate associations between medication class and peak serum laboratory values using simple linear regression (absolute eosinophils, creatinine, alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). We found a significant difference between timing of peak AST values among vancomycin-triggered DRESS compared to other trigger groups. These findings draw attention to the increased role of AST as a diagnostic and monitoring tool in DRESS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To construct a prediction model for renal involvement in patients with hyperuricemia (HUA) based on logistic regression analysis, to achieve early risk stratification., Method: In this cross-sectional study, we collected data from the National Health and Nutrition Examination Survey (NHANES), and constructed a predicted model for renal involvement in HUA patients. The discriminative ability of the model was assessed using the receiver operating characteristic (ROC) curve. Model accuracy was evaluated using the Hosmer-Lemeshow test and calibration curve, while clinical utility was assessed using decision curve analysis (DCA). Furthermore, internal and external validation cohorts were also applied to validate the model., Results: A total of 1669 patients from NHANES between 2007 and 2010 were included in the final analysis for modeling and validation. Six predictive factors including age, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Cr, Uric Acid (UA), and sex were identified by binary logistic regression analysis for renal involvement in HUA patients and used to construct a nomogram with good consistency and accuracy. The AUC values for the predictive model, internal validation, and external validation were 0.881 (95% CI: 0.836-0.926), 0.908 (95% CI: 0.871-0.944), and 0.927 (95% CI: 0.897-0.957), respectively. The calibration curves demonstrated consistency between the nomogram and observed values. The DCA curves of the model and validation cohort indicated good clinical utility., Conclusion: This study developed a predictive model for renal involvement in hyperuricemia patients with strong predictive performance and validated by internal and external cohorts, aiding in the early detection of high-risk populations for renal involvement., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Exposure to brominated flame retardants (BFRs) may contribute the advancement of chronic kidney disease (CKD). The objective is to evaluate the renal effects of BFRs in patients with CKD., Methods: Totally 7235 US participants of whom 1187 (16.41 %) were diagnosed with CKD were screened for this investigation from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2005 to 2016. The isotope dilution gas chromatography high-resolution mass spectrometry (GC/IDHRMS) was employed for identification of 11 polybrominated diphenyl ethers (PBDEs) and PBB153 serving as the exposure factor. A set of covariates concerning basic characteristics, renal function indicators and suffering from diseases of these participants was considered as potential confounding factors. Subgroup analyses to examine the impact of age and gender on the relationship between serum BFRs and CKD, estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN). Weighted Quantile Sum (WQS) regression and Quantile G-computation (QGC) analyses were applied to identify relationship of individual BFRs and other anthropometric indicators in CKD., Results: After adjusting for available confounding factors, PBDE100, PBDE28, PBDE85, PBDE47, PBDE99, and PBDE154 were positively correlated with CKD. PBDE28, PBDE66, PBDE47, PBDE183, PBDE100, PBDE99, PBDE85, PBDE154, and PBB153 were significantly negatively correlated with eGFR. PBDE66 and PBDE183 were positively correlated with UACR. PBDE28, PBDE17, PBDE66, PBDE100, PBDE47, PBDE85, PBDE154, PBDE99, PBDE183 and PBB153 were positively correlated with Scr. PBDE17, PBDE28, PBDE154, PBDE66, PBDE47, PBDE99, and PBDE209 were negatively associated with BUN. PBB153 was positively correlated with BUN. The subgroup results gender and age are key factors affecting the relationship of PBDEs and renal function indicators. Both WQS and QGS analyses revealed that exposure to mixed BFR was negatively correlated with eGFR and BUN, of which PBB153 and PBDE66 contributed the most, respectively, as well as positively correlated with Scr, in which PBDE66 contributed the most., Conclusion: Specific BFRs exposure was significantly correlated with renal function indicators, enhancing the potential risk of CKD. This pioneer investigation shed light on an overlooked impact of BFR exposure on CKD in US., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Biomarkers of kidney function, including glomerular, tubular, and fibrotic markers, have been associated with blood pressure in elderly populations and individuals with kidney and cardiovascular diseases. However, limited information is available in young adults. In this study, we compared levels of several kidney function biomarkers between normotensive and hypertensive young adults and explored the associations of these biomarkers with blood pressure within these groups. In this cross-sectional assessment, twenty-four-hour (24-h) blood pressure measurements of 1055 participants (mean age = 24.6 years) were used to classify hypertension as per the 2018 ESC/ESH guidelines. Biomarkers of kidney function included estimated glomerular filtration rate, urinary albumin, alpha-1 microglobulin (uA1M), neutrophil gelatinase-associated lipocalin (uNGAL), uromodulin (uUMOD), and the CKD273 classifier. All urinary biomarkers, except for the CKD273 classifier, were standardized for urinary creatinine (Cr). In the hypertensive group (61.0% White; 73.2% men), urinary albumin-to-creatinine ratio (uACR), uNGAL/Cr and uUMOD/Cr were lower than the normotensive group. In multiple regression analyses, 24-h systolic blood pressure (SBP) (β = 0.14; p = 0.042), 24-h diastolic blood pressure (DBP) (β = 0.14; p = 0.040), and 24-h mean arterial pressure (MAP) (β = 0.16; p = 0.020) associated positively with uA1M/Cr in the hypertensive group, while 24-h MAP positively associated with uACR (β = 0.17; p = 0.017). In exploratory factor analysis, positive associations of 24-h DBP and 24-h MAP with a factor pattern including tubular biomarkers were observed in the hypertensive group (24-h DBP: β = 0.18; p = 0.026, 24-h MAP: β = 0.17; p = 0.032). In the setting of hypertension, high perfusion pressure in the kidneys may play a role in the development of proximal tubule damage and promote early deterioration in kidney function in young adults. Trial Registration: ClinicalTrials.gov identifier: NCT03292094., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

A 23-day-old Japanese Black female calf presented with distension of the lower abdomen. Abdominal ultrasonography revealed a cystic structure with fluid accumulation and moderate echoluminance in the right abdominal cavity. Ultrasonography and contrast-enhanced computed tomography revealed congenital hydronephrosis due to narrowing of the intrarenal ureter, and right kidney resection was performed. Blood urea nitrogen and serum creatinine levels, which were within reference values preoperatively, peaked on the third postoperative day and gradually decreased afterward until reaching preoperative values on the tenth day. In bovine hydronephrosis, nephrectomy may provide a favorable prognosis if one kidney is intact. Moreover, this case suggests that blood tests immediately after surgery are not suitable for evaluating residual kidneys.

We explored the potential value of the alcohol dehydrogenase (ADH) inhibitor isovaleramide (ISO) in the treatment of acute ethylene glycol (EG) poisoning-induced acute kidney injury. Sprague-Dawley rats were divided into the control, EG, EG + ISO (10 mg/kg) and EG + ISO (20 mg/kg) groups. It is found that ISO intervention significantly reduced the ADH activity in liver tissue by using visible spectrophotometry, inhibited the in vivo metabolism of EG by using gas chromatography, lowered the levels of toxic metabolites glycolic acid and oxalic acid by using high-performance liquid chromatography and decreased the expression of kidney injury markers serum creatinine (sCr), KIM-1, neutrophil gelatinase-associated lipocalin (NGAL) and liver fatty acid-binding protein (L-FABP) by ELISA. Additionally, Western blotting results showed that ISO down-regulated the expression of apoptotic factors Bax and cleaved caspase-3 in the kidneys and upregulated the expression of antiapoptotic factor Bcl-2. Pizzolato staining and polarized light microscopy results revealed the reduced deposition of calcium oxalate crystals in the kidney tubules. Using haematoxylin and eosin (H&E), periodic acid-Schiff (PAS) and Masson staining, we found attenuated kidney tissue pathological injury. Finally, ISO significantly reduced the mortality rate. In conclusion, ISO has the potential to be a valuable drug for the treatment of EG poisoning-induced acute kidney injury., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Women are participating in military and athletic activities in the heat in increasing numbers, but potential sex differences in sequelae from exertional heat illness remain poorly understood. We tested the hypothesis that women suffering from exertional heat stroke (EHS) would have similar severity of organ damage biomarkers compared with men, as measured in a hospital setting. We studied women and men presenting with EHS to the emergency department at Fort Moore, GA. We measured creatinine (CR), creatine kinase (CK), alanine-transaminase (ALT), aspartate aminotransferase (AST), and estimated glomerular filtration rate (eGFR). Core temperature was also assessed by medical personnel. Biomarker data were obtained for 62 EHS cases (11 women). Men were significantly taller, and heavier, and had larger body mass index (BMI) and body surface area ( P < 0.05 for all). The highest recorded body core temperature was not different between groups [women: 41.11°C (40.06, 41.67); men: 41.11°C (40.28, 41.72), P = 0.57]. Women had significantly lower peak CR [women: 1.39 (1.2, 1.48) m·dL -1 ; men: 1.75 (1.53, 2.16) mg·dL -1 , P < 0.01] and peak CK [women: 584 (268, 2,412) U·L -1 ; men: 2,183 (724, 5,856) U·L -1 , P = 0.02]. Peak ALT and AST were not different between groups; during recovery time points, ALT and AST were either similar or lower in women. Women spent approximately half as much time in the hospital following admittance compared with men. Our findings suggest that women may be less susceptible to organ injury resulting from EHS. Further research is necessary to understand the pathophysiology underlying these differences and how biomarkers of end-organ damage severity can differ between women and men following EHS. NEW & NOTEWORTHY We studied otherwise healthy women and men after exertional heat stroke in a military training environment. Peak values for biomarkers of kidney and muscle damage were lower in women compared with men despite similar (highest recorded) body core temperatures. During recovery, organ damage markers were similar or lower in women. These sex differences may indicate differences in the pathophysiology of responses, but more work is needed to clarify specific mechanisms.

Background and Aims: Contrast-associated acute kidney injury (CA-AKI) is a major complication following coronary procedures. We aimed to evaluate the effectiveness of a combination of urine flow rate-(UFR) guided hydration (RenalGuard TM ) and device-based contrast media (CM) reduction (DyeVert TM ) in CA-AKI prevention., Methods: Stable high-risk patients undergoing coronary procedures with the use of DyeVert TM and RenalGuard TM were prospectively included (Combined group) and matched with a similar cohort of patients treated only with RenalGuard TM in whom CM volume was controlled by operator-dependent strategies (Control group). CA-AKI was defined as a serum creatinine increase ≥0.3 mg/dL at 48 h., Results: Overall, 55 patients were enrolled and matched with comparable controls. Patients in the Combined group were exposed to a lower CM dose (Control: 55 [30-90] mL vs. Combined: 42.1 [24.9-59.4] mL; p = 0.024). A significant interaction was found between treatment allocation and serum creatinine changes (p = 0.048). CA-AKI occurred in five (9.1%) patients in the Combined group and in 14 (25.4%) patients in the Control group (OR 0.29, 95% CI [0.09-0.88])., Conclusions: A combined strategy of device-based CM reduction plus UFR-guided hydration is superior to operator-dependent CM sparing strategies plus UFR-guided hydration in preventing CA-AKI in high-risk patient., (© 2024 Wiley Periodicals LLC.)

Objective: To actively monitor and analyze the factors that affect the advancement of diabetic retinopathy (DR)., Method: In this study, we prospectively recruited patients diagnosed with non-proliferative diabetic retinopathy (NPDR) for concurrent monitoring. A total of 75 patients who transitioned from NPDR to proliferative diabetic retinopathy (PDR) comprised the progression group, while 112 NPDR patients who did not develop PDR formed the stable group in a prospective cohort study. Follow-up assessments occurred every six months, and patients were observed continuously over an eight-year period. Clinical parameters from both NPDR and PDR groups were collected to assess the stability of these indicators (with a coefficient of variation [CV] > 5 % indicating instability and CV < 5 % indicating stability)., Results: In the NPDR cohort, 80.4 % Control the stability ratio regulation of glycosylated hemoglobin (HbA1c), whereas in the PDR cohort, 80.0 % Control the proportion of instability (P = 0.001); for blood creatinine (Cr), 64.3 % of NPDR patients maintained stable levels, contrasting with 77.3 % of PDR patients with fluctuating levels (P = 0.001). Blood urea nitrogen (BUN) and homocysteine (HCY) control demonstrated instability in both NPDR and PDR groups. Instability in regulating HbA1c, Cr, BUN, and HCY served as independent risk factors for DR progression, with significant associations found between HbA1c CV (HR: 15.586; 95 % CI: 14.205-15.988; p = 0.001), Cr CV (HR: 9.231; 95 % CI: 9.088-10.235; p = 0.005), BUN CV (HR: 3.568; 95 % CI: 3.183-4.367; p = 0.01), and HCY CV (HR: 8.678; 95 % CI: 7.754-8.998；p = 0.003)., Conclusion: Inadequate regulation of HbA1c, Cr, BUN, and HCY independently impact the advancement of DR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Question: Is there an association between male creatinine levels and time to pregnancy (TTP) in couples planning pregnancy?, Summary Answer: Low and high male creatinine concentrations were associated with reduced couple fecundity., What Is Known Already: Abundant evidence suggests male creatinine dysfunction is associated with infertility in males with kidney diseases. However, the association of preconception creatinine levels with reduced fecundity among general reproductive-aged couples lacks evidence from an in-depth population study., Study Design, Size, Duration: Based on the population-based cohort study from the National Free Preconception Check-up Projects, 4 023 204 couples were recruited and met the inclusion criteria from 1 January 2015 to 31 December 2017. They were planning pregnancy and were followed up every 3 months until achieving pregnancy as detected by gynaecological ultrasonography or were followed up for 1 year for the analysis of TTP., Participants/materials, Setting, Methods: Cox regression models were used to estimate hazard ratios (HRs) and 95% CI for creatinine deciles. Restricted cubic spline regression was adopted for the dose-response relationship of creatinine with HRs. R statistical software was used for data analysis., Main Results and the Role of Chance: Of the included participants, 2 756 538 (68.52%) couples successfully conceived. The median male serum creatinine was 81.50 μmol/l. Compared with the reference group (78.00-81.49 μmol/l) including the median creatinine, fecundity in the first (≤64.89 μmol/l), second (64.90-69.99 μmol/l), third (70.00-73.99 μmol/l), and tenth (≥101.00 μmol/l) deciles decreased by 8%, 5%, 2%, and 1%, respectively (Decile 1 Adjusted HR 0.92, 95% CI 0.91-0.92; Decile 2 Adjusted HR 0.95, 95% CI 0.95-0.96; Decile 3 Adjusted HR 0.98, 95% CI 0.97-0.99; Decile 10 Adjusted HR 0.99, 95% CI 0.98-0.99). An inverse-U-shaped association was consistently presented among males such that non-inferiority for fecundity was shown when creatinine was in the 81.66-104.90 μmol/l range (P for non-linearity < 0.001). For males over 40 years old, the risk of fecundity impairment was more obvious and the recommended range of creatinine levels for TTP was reduced and more narrow, compared with that for younger males., Limitations, Reasons for Caution: Not including the time couples spend preparing for pregnancy before enrolment would lead to an overestimation of fecundity; additionally some couples place pregnancy plans on hold due to special emergencies, which would not have been recognized. Due to the lack of information regarding semen quality, psychological factors, sexual intercourse frequencies, and hazardous environmental factors, we could not adjust for these factors. Some variates were self-reported and dichotomized, which were prone to bias. Direct variables reflecting muscle mass and impaired kidney function were lacking. Thus, extrapolation should be done with caution., Wider Implications of the Findings: Male creatinine is associated with couples' fecundity and the relationship varied by age. This study provides a better understanding of the potential implications and significance of different creatinine levels and their association with the clinical significance regarding couples' fecundity., Study Funding/competing Interest(s): This research has received funding from the National Natural Science Foundation of China (Grant No. 81872634), the Basic Research Funds of Central Public Welfare Research Institutes of China (Grant No. 2023GJZ03), the National Key Research and Development Program of China (Grant No. 2016YFC1000307), and the Project of National Research Institute for Family Planning (Grant No. 2018NRIFPJ03), People's Republic of China. The authors have no conflicts of interest to declare., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Pregnant IgAN patients are more susceptible to adverse pregnancy outcomes (APO). However, the risk factor for APO and its effects on the long-term renal outcome of pregnant IgAN patients remained unclear., Methods: We performed a retrospective observational study covering 2003-2019 that included 44 female IgAN patients with pregnancy history to investigate the risk factor for APO and its impact on clinical outcome in IgAN. Renal function outcome and proteinuria remission were evaluated in pregnant IgAN women with and without APO., Results: In this retrospective and observational study, we found that patients with APO exhibited higher levels of serum creatinine and IgM, and lower haemoglobin levels while other clinical characteristics, pathological characteristics and therapy protocol had no significant difference. We found that anaemia and a higher level of serum IgM were independent risk factors for APO. IgAN pregnant women without APO experienced a higher proportion of proteinuria remission than those with APO, but there is no difference in the renal function outcome., Conclusion: Pregnant IgAN patients with higher risks, including lower haemoglobin levels and higher IgM levels deserve intensive monitoring, and aggressive therapy to reduce proteinuria should be carried out in pregnant IgAN patients with APO., (© 2024 Asian Pacific Society of Nephrology.)

Routinely used kidney biomarkers of injury and function such as serum creatinine and urine albumin to creatinine ratio, are neither sensitive nor specific. Future biomarkers are being developed for clinical use and have already been included in guidance from groups such as the U.S. Food and Drug Administration and the Predictive Safety Testing Consortium. These biomarkers have important implications for early identification of kidney injury and more accurate measurement of kidney function. Many antibiotics are either eliminated by the kidney or can cause clinically significant nephrotoxicity. As a result, clinicians should be familiar with new biomarkers of kidney function and injury, their place in clinical practice, and applications for antibiotic dosing., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The accumulation of uremic toxins in the human body poses a deadly risk because it causes chronic kidney disease. To increase the effectiveness of hemodialysis and raise the survival rate, these toxins must be effectively removed from the bloodstream. Developing effective materials for removing these dangerous substances requires a thorough understanding of the interactions between an adsorbent and the uremic toxins. Thankfully, metal-organic frameworks (MOFs) have shown considerable promise for the identification and treatment of kidney disorders. Herein, cotton gauze fabrics (CGF) were carboxylated using monochloroacetic acid to produce carboxymethylated cotton gauze fabrics (CM-CGF). CM-CGF was subsequently decorated in situ with zeolitic imidazolate framework-67, resulting in carboxymethylated cotton gauze fabrics-zeolitic imidazolate framework-67 (CM-CGF-ZIF). The CGF, CM-CGF, and CM-CGF-ZIF were evaluated for potential kidney applications by removing uric acid and creatinine from mimic blood. The results showed that CM-CGF-ZIF had the highest adsorption of uric acid and creatinine. The maximum adsorption capacity of uric acid and creatinine was 164 and 222 mg/g for CM-CGF-ZIF, respectively, compared to 45 and 67 mg/g for CGF. CM-CGF-ZIF showed excellent antibacterial activity, good antifungal activity, low cytotoxicity, and a satisfactory level of blood compatibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Children with overweight and obesity are at risk for developing chronic kidney disease (CKD). During lifestyle adjustment, the first step in the treatment of childhood obesity, body proportions are likely to change. The aim of this study was to examine how lifestyle intervention affects creatinine-based kidney function estimation in children with overweight and obesity., Methods: This longitudinal lifestyle intervention study included 614 children with overweight and obesity (mean age 12.17 ± 3.28 years, 53.6% female, mean BMI z-score 3.32 ± 0.75). Loss to follow-up was present: 305, 146, 70, 26, and 10 children were included after 1, 2, 3, 4, and 5 (about yearly) follow-up visits, respectively. Serum creatinine (SCr) was rescaled using Q-age and Q-height polynomials., Results: At baseline, 95-97% of the children had a SCr/Q-height and SCr/Q-age in the normal reference range [0.67-1.33]. SCr/Q significantly increased each (about yearly) follow-up visit, and linear mixed regression analyses demonstrated slopes between 0.01 and 0.04 (corresponding with eGFR FAS reduction of 1.1-4.1 mL/min/1.73 m 2 ) per visit. BMI z-score reduced in both sexes and this reduction was significantly higher in males. No correlation between change in rescaled SCr and BMI z-score reduction could be demonstrated., Conclusions: Rescaled serum creatinine (SCr/Q) slightly increases during multidiscipline lifestyle intervention in this cohort of children with overweight and obesity. This effect seems to be independent from change in BMI z-score. Whether this minor decrease in estimated kidney function has clinical consequences in the long term remains to be seen in trials with a longer follow-up period., Clinical Trial Registration: ClinicalTrial.gov; Registration Number: NCT02091544., (© 2024. The Author(s).)

Background: Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain., Methods: We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m 2 (milliliter per minute per 1.73 m 2 , as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status., Results: Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m 2 ). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology Collaboration Cr/CysC equation., Conclusions: Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs., Competing Interests: A.A. received speaker fees from AstraZeneca and holds research grants from Otsuka, all outside of the submitted work. M.M.S. received speaker fees from AstraZeneca, Otsuka, Bayer, and GlaxoSmithKline, all outside of the submitted work. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study addresses the critical need for differentiating between upper and lower gastrointestinal bleeding by focusing on blood routine parameters to enhance diagnostic precision., Objective: This study aims to identify and compare specific blood routine parameters to determine their efficacy in distinguishing between upper and lower gastrointestinal bleeding for improved clinical decision-making., Methods: This retrospective study analyzed 119 patients with gastrointestinal bleeding (GIB) admitted to our hospital between January 2017 and June 2020. Among them, 86 were diagnosed with upper GIB (UGIB) and 33 with lower GIB (LGIB). After admission, peripheral blood samples were collected for a comprehensive blood routine examination, including white blood cell count (WBC), red blood cell count (RBC), hemoglobin (Hb), platelet count (PLT), blood urea nitrogen (BUN), creatinine (Cr), and BUN to Cr ratio (BUN/Cr ratio). Differences in blood routine parameters were compared between the UGIB and LGIB groups. Receiver Operating Characteristic (ROC) curve analysis was conducted to assess the efficacy of blood routine examinations in differentiating between UGIB and LGIB., Results: The study revealed no significant differences in WBC and Cr levels between LGIB and UGIB patients (P > .05). However, UGIB patients exhibited statistically lower levels of RBC, Hb, and PLT, along with higher BUN and BUN/Cr ratio levels compared to LGIB patients (P < .05). Pearson correlation coefficient analysis indicated an inverse correlation of BUN/Cr with RBC, Hb, and PLT in GIB patients and a positive association between BUN/Cr and BUN (P < .05). ROC analysis demonstrated that RBC, Hb, PLT, BUN, and BUN/Cr ratios were effective in distinguishing UGIB from LGIB (P < .05)., Conclusions: Blood routine parameters, including RBC, Hb, PLT, BUN, and BUN/Cr ratio, are valuable in differentiating between UGIB and LGIB. These parameters can serve as early evaluation indexes for GIB, facilitating timely intervention and treatment to enhance therapeutic outcomes.

Background: Few studies have observed the direct effect of obesity on renal prognoses in immunoglobulin A nephropathy (IgAN) or separately evaluated its effects according to sex. We aimed to evaluate the direct and indirect effects of obesity on the renal outcomes of IgAN and observe these effects separately according to renal function and sex., Methods: We extracted patients with body mass index (BMI) descriptions from a multicenter retrospective cohort analysis in Japan, and excluded those with < 30 days of follow-up, diabetes mellitus, and steroid treatment. Patients were divided into normal (n = 720; 18.5 ≤ BMI < 25) and obese (n = 212; BMI ≥ 25) groups, which were then compared. The endpoints were a 1.5-fold increase in serum creatinine levels and the initiation of renal replacement therapy., Results: The obese group was older, included more males, and was more likely have hypertension, dyslipidemia, proteinuria, tubular atrophy, and lower renal function than the normal group. Patients with an eGFR < 60 mL/min/1.73 m 2 had well-matched characteristics between the groups; however, hypertension, low high-density lipoprotein cholesterol, and hypertriglyceridemia were more common in the obese group. Obesity contributed to tubular atrophy, even when adjusted for renal function. In addition, it contributed to proteinuria only in females. However, obesity itself was not a significant prognostic factor., Conclusions: Although no independent effect on renal prognosis was observed during the study period, the obese group had more risk factors for IgAN progression and obesity contributed to tubular atrophy and female proteinuria. Our results suggest that separately analyzing the prognostic effect of obesity according to sex is important., Competing Interests: Declarations Conflict of interest All authors have declared no competing interests regarding this study. Ethical approval All procedures were performed in accordance with the ethical standards of the responsible committee on human experimentation (Kitano Hospital Institutional Ethics Committee, approval number: 2106007) and the Helsinki Declaration of 1964 and later versions. Informed consent The data for this survey obtained from the patients’ medical records were anonymized for personal information so that the patients could not be identified. Anonymized data sets from each participating facility were used. Therefore, the requirement for written informed consent was waived., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: In recent decades, the analytical quality of clinical laboratory results has substantially increased because of collaborative efforts. To effectively utilize laboratory results in applications, such as machine learning through big data, understanding the level of harmonization for each test would be beneficial. We aimed to develop a quantitative harmonization index that reflects the harmonization status of real-world laboratory tests., Methods: We collected 2021-2022 external quality assessment (EQA) results for eight tests (HbA1c, creatinine, total cholesterol, HDL-cholesterol, triglyceride, alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and prostate-specific antigen [PSA]). This EQA was conducted by the Korean Association of External Quality Assessment Service, using commutable materials. The total analytical error of each test was determined according to the bias% and CV% within peer groups. The values were divided by the total allowable error from biological variation (minimum, desirable, and optimal) to establish a real-world harmonization index (RWHI) at each level (minimum, desirable, and optimal). Good harmonization was arbitrarily defined as an RWHI value ≤ 1 for the three levels., Results: Total cholesterol, triglyceride, and CEA had an optimal RWHI of ≤ 1, indicating an optimal harmonization level. Tests with a desirable harmonization level included HDL-cholesterol, AFP, and PSA. Creatinine had a minimum harmonization level, and HbA1c did not reach the minimum harmonization level., Conclusions: We developed a quantitative RWHI using regional EQA data. This index may help reflect the actual harmonization level of laboratory tests in the field.

Background: Acute kidney injury (AKI) diagnosis often lacks a baseline serum creatinine (Cr) value. Our study aimed to create a regression equation linking kidney morphology to function in kidney donors and chronic kidney disease patients. We also sought to estimate baseline Cr in minimal change disease (MCD) patients, a common AKI-predisposing condition., Methods: We analyzed 119 participants (mean age 60 years, 50% male, 40% donors) with CT scans, dividing them into derivation and validation groups. An equation based on kidney parenchymal volume (PV) was developed in the derivation group and validated in the validation group. We estimated baseline Cr in 43 MCD patients (mean age 45 years, 61% male) using the PV-based equation and compared with their 6 month post-MCD onset Cr values., Results: In the derivation group, the equation for the estimated glomerular filtration rate (eGFR) was: eGFR (mL/min/1.73m 2 ) = 0.375 × PV (cm 3 ) + (- 0.395) × age (years) + (- 2.93) × male sex + (- 13.3) × hypertension + (- 14.0) × diabetes + (- 0.210) × height (cm) + 82.0 (intercept). In the validation group, the eGFR and estimated Cr values correlated well with the measured values (r = 0.46, p = 0.01; r = 0.51, p = 0.004, respectively). In the MCD group, the baseline Cr values were significantly correlated with the estimated baseline Cr values (r = 0.52, p < 0.001), effectively diagnosing AKI (kappa = 0.76, p < 0.001)., Conclusions: The PV-based regression equation established in this study holds promise for estimating baseline Cr values and diagnosing AKI in patients with MCD. Further validation in diverse AKI populations is warranted., Competing Interests: Declarations Conflict of interest The are no conflicts of interests to be disclosed.Ethical approval.This study was approved by the Institutional Review Board of the Jikei University School of Medicine (IRB nos. 35–159 [11788] and 35–165 [11794]) and was conducted in accord with the Declaration of Helsinki. Informed consent Because this was a retrospective cohort study, information on the research plan was posted; an opportunity to refuse participation was provided, and individual informed consent was not required., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

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., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Intrauterine fetal growth restriction (IUGR) affects up to 10% of all pregnancies. Severe IUGR is associated with impaired kidney development, reduced nephron endowment, and chronic kidney disease later in life. Currently, no early predictive biomarker exists for detecting altered kidney function in neonates with IUGR. Because nephrons produce key enzymes for the metabolism of arginine and methylarginine components, we quantified and compared the concentrations of arginine and methylarginine metabolites between IUGR and non-IUGR neonates to identify potential biomarkers for the early detection of altered kidney function in IUGR neonates., Methods: Seventy-one IUGR and 123 non IUGR neonates were examined. Serum and Urine samples were obtained between 30 h and 5 days of life and between 5 and 70 days of life. Serum concentrations of creatinine, urea, symmetric and asymmetric-dimethylarginine metabolites (SDGV, SDMA, ADGV, and ADMA), guanidino-2-oxo-caproic acid (GOCA), citrulline, homocitrulline, arginine, and homoarginine were quantified using LC-MS/MS and standard clinical laboratory methods. Datasets were compared by Mann-Whitney--Wilcoxon or Chi-square tests for continuous and discrete parameters. P values were corrected for multiple comparisons using the Bonferroni method., Results: After Bonferroni correction, we found that serum creatinine, urea, SDGV, ADGV, and GOCA levels were significantly lower in neonates with IUGR. Consequently, the ratios of SDGV/SDMA, ADGV/ADMA, and GOCA/homoarginine were significantly lower in IUGR neonates., Conclusion: Our study suggests that arginine and methylarginine are possible early biomarkers for detecting altered kidney function in IUGR neonates., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Coronary heart disease (CHD) patients with changed serum soluble receptor for advanced glycation end products (sRAGE) will experience microalbuminuria and even kidney dysfunction. However, the role of sRAGE for microalbuminuria in CHD is still not established. This study aimed to evaluate the association between sRAGE and early kidney dysfunction in CHD patients., Materials and Methods: In this cross-sectional study, sRAGE and urinary albumin-to-creatinine ratio (uACR) were measured in hospitalized CHD patients who have undergone coronary arteriography to evaluate the distinction and correlation between sRAGE and uACR., Results: There were 127 CHD patients (mean age: 63.06 ± 10.93 years, 93 males) in the study, whose sRAGE were 1.83 ± 0.64 μg/L. The sRAGE level was higher in kidney injury group (uACR ≥ 30 mg/g) compared with no kidney injury group (uACR < 30 mg/g) [(2.08 ± 0.70 vs. 1.75 ± 0.61) μg/L, P < 0.05]. Moreover, the positive correlation between serum sRAGE and uACR was significant in CHD patients (r = 0.196, P < 0.05). Binary logistic regression suggests sRAGE as a predictor for microalbuminuria in CHD patients [Odd Ratio = 2.62 (1.12-6.15), P < 0.05)]. The area under the receiver operating characteristic curve (AUC) of sRAGE is higher than that of the traditional indicators of renal function such as creatinine and estimated glomerular filtration rate, indicating sRAGE might have a good performance in evaluating early kidney injury in CHD patients [AUC is 0.660 (0.543-0.778), P < 0.01)]., Conclusions: Serum sRAGE was positively correlated to uACR and might serve as a potential marker to predict early kidney injury in CHD patients., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Purpose of Review: Serum creatinine reflects both muscle mass and kidney function. Serum cystatin C has recently been recommended as an additional marker for estimating kidney function, and use of both markers together may provide an index of muscle mass. This review aims to describe the biological basis for and recent research examining the relationship of these markers to muscle mass in a range of adult populations and settings., Recent Findings: This review identified 67 studies, 50 of which had direct measures of muscle mass, and almost all found relationships between serum creatinine and cystatin C and muscle mass and related outcomes. Most studies have been performed in older adults, but similar associations were found in general populations as well as in subgroups with cancer, chronic kidney disease (CKD), and other morbid conditions. Creatinine to cystatin C ratio was the measure examined the most often, but other measures showed similar associations across studies., Summary: Measures of serum creatinine and cystatin C together can be an index of muscle mass. They are simple and reliable measures that can be used in clinical practice and research. Further study is needed to determine actionable threshold values for each measure and clinical utility of testing and intervention., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic kidney disease (CKD) is a major healthcare challenge, affecting >800 million people worldwide. Implications for population health result from the strong associations of CKD with increased rates of cardiovascular disease, heart failure, progressive CKD leading to kidney failure, acute kidney injury (AKI), and mortality. In addition to a single disease perspective, CKD commonly coexists alongside other long-term conditions, in particular type 2 diabetes and cardiovascular disease. CKD is therefore an important component of multimorbidity that influences individual management and impacts prognosis. CKD is defined by abnormalities of kidney structure or function of any cause with implications for health that are present for longer than 3 months. The diagnosis is usually made on the basis of an abnormal glomerular filtration rate (GFR < 60 mL/min/1.73 m 2 ) and/or the presence of proteinuria (urine albumin to creatinine ratio > 30 mg/g or >3 mg/mmol). GFR is usually estimated from serum creatinine concentration using a variety of validated equations. However, serum creatinine is closely related to muscle mass and may therefore not be an accurate marker of GFR in people with high or low muscle mass (sarcopaenia). Cystatin C is an alternative endogenous marker of GFR that is increasingly being used but also has limitations. An estimate of GFR based on both creatinine and cystatin C is the most accurate. Diagnosis should be followed by classification and risk stratification to guide the development of a risk-based, personalized care plan. Improved detection and widespread implementation of optimal CKD management has the potential to bring major benefits to population health., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: This study had two main goals: to determine which rhabdomyolysis patients need haemodialysis; and to highlight the significance of blood gas parameters, particularly base excess, as predictors of the need for haemodialysis., Method: A total of 270 patients were included in this multicentre, retrospective study. Among the patients who were transferred in from the earthquake region and developed rhabdomyolysis, those with creatine kinase (CK) values >1000 U/L were included in our study. The need for renal replacement in these patients was determined via laboratory tests, urine output monitoring and clinical follow-up., Findings: A total of 270 patients were included in our study. Univariate and multivariate regression analyses of laboratory parameters were performed to identify predictors of HD treatment. According to the univariate regression analysis, BE, HCO3, creatinine, CK, lactate, alanine transaminase (ALT) and aspartate transaminase (AST) levels were found to be significantly associated with receiving HD treatment. According to multivariate regression analysis, only BE (p = 0.003) was found to be a significant predictor of HD treatment. ROC analysis revealed that the optimal cutoff value for BE was -2.6; at this value, the sensitivity and specificity of BE for predicting HD treatment were 89% and 77.1%, respectively (AUC: 0.912; 95% CI: 0.872-0.943; p < 0.001)., Conclusion: Base excess is an effective predictor of the need for haemodialysis in patients with crush-related injuries that cause rhabdomyolysis and in patients who develop acute renal failure due to elevated CK., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children., Methods: A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed., Results: A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury., Conclusions: Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Serum creatinine (Scr) may be not suited to timely and accurately reflect kidney injury related to chronic liver disease. Currently, the ability of arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) sequences to evaluate renal blood flow (RBF) and blood oxygen in chronic liver disease remains to be verified., Purpose: To investigate the value of ASL and BOLD imaging in evaluating hemodynamics and oxygenation changes during kidney injury in an animal model of chronic liver disease., Study Type: Prospective., Animal Model: Chronic liver disease model was established by subcutaneous injection of carbon tetrachloride. Forty-three male Sprague-Dawley rats (8 weeks) were divided into a pathological group (0, 2, 4, 6, 8, 12 weeks, each group: N = 6) and a continuous-scanning group (N = 7)., Field Strength/sequence: 3-T, ASL, BOLD, and T2W., Assessment: Regions of interest in the cortex (CO), outer stripe of the outer medulla (OSOM), and inner stripe of the outer medulla (ISOM) are manually delineated. The RBF and T2* values at each time point (0, 2, 4, 6, 8, 12 weeks) are measured and compared. Hematoxylin-eosin score (HE Score, damage area scoring method), alpha-smooth muscle actin (α-SMA), hypoxia-inducible factor-1alpha (HIF-1α), peritubular capillar (PTC) density, Scr, and neutrophil gelatinase-associated lipocalin were harvested., Statistical Tests: Analysis of variance, Spearman correlation analysis, Kruskal-Wallis tests, and receiver operating characteristic analysis with the area under the curve (AUC). A P-value <0.05 was considered statistically significant., Results: Renal RBF and T2* values of CO, OSOM, and ISOM were significantly different from baseline. Both RBF and T2* were significantly correlated with HE Score, α-SMA, HIF-1α, and PTC density (|r| = 0.406-0.853). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in this model of chronic liver disease (AUC = 0.964)., Data Conclusion: Imaging by ASL and BOLD may detect renal hemodynamics and oxygenation changes related to chronic liver disease early., Evidence Level: 5 TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Introduction. Rituximab (RTX) holds promise as a treatment for idiopathic membranous nephropathy (IMN). While effective in standard regimens, the application of RTX is hampered by cost burdens and severe side effects. To address these issues, low-dose RTX has been proposed as an intervention strategy. Yet, the efficacy of this approach in treating IMN remain subject of debate. This systematic review and meta-analysis seek to examine the effectiveness of low-dose RTX in adult patients with IMN. Methodology. A literature search was conducted using PubMed, Wiley Online Library, ScienceDirect, Cochrane Library, Springer and other sources, published between 2004 and 2024. Specifically, articles reporting the intravenous application of RTX at doses lower than four weekly infusions of 375 mg/m² or two infusions of 1 gram each on day 0 and day 15 were considered for inclusion. The primary outcomes were complete response (CR) and partial response (PR) rates at last follow-up. Secondary endpoints included serum creatinine levels, serum albumin levels, 24-hour proteinuria levels, protein-creatinine ratio (PCR), estimated glomerular filtration rate (eGFR) and anti-PLA2R antibody levels. Results. Sixteen articles were included in this meta-analysis. The pooled analysis of odds ratios (OR) revealed that both main-line (OR = 0.48, 95% CI = 0.30-0.75, p = 0.001) and second-line (OR = 0.27, 95% CI = 0.11-0.67, p = 0.005) RTX treatments induced complete remission (CR) in IMN patients. At the last follow-up, patients treated with both main-line (mean difference [MD] = 1.45, 95% CI = 1.00-1.91, p < 0.00001) and second-line (MD = 0.88, 95% CI = 0.23-1.53, p < 0.00001) RTX treatments showed a significant increase in serum albumin levels. Conversely, in the analysed second line RTX therapy patients, low eGFR trend was noted in the post treatment arm compared to baseline levels (MD = 10.57, 95% CI = 0.30-20.83, p = 0.04). Moreover, RTX was found to be effective in reducing PCR (MD = 24.10, 95% CI= 1.07 to 47.13, p = 0.04) and depleting PLA2R antibody levels (MD = 127.36, 95% CI = 14.90-239.81, P = 0.03). However, RTX might be less effective in lowering proteinuria and serum creatinine levels in patients with nephrotic syndrome. Conclusion. Rituximab in a low-dose regimen is quite effective in treating adult patients with IMN. Therefore, it can be considered a promising treatment for both main-line and rescue therapy. More randomized controlled trials and research on optimizing the low-dose regimen, based on various health factors, are warranted., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Fall is common in the elderly, and chronic kidney disease is considered a major risk factor. Serum creatinine (Cre) and cystatin C (Cys C) are commonly used biomarkers for renal function, while the ratio of Cre to Cys C, known as the sarcopenia index (SI), provides insights into muscle health. This study investigates the relationships between Cre, Cys C, estimated glomerular filtration rates (eGFR), SI, and self-reported falls using National Health and Nutrition Examination Survey (NHANES) data. We included 4,272 older adults with eGFR > 30mL/min/1.73m 2 from NHANES (1999 to 2004) and divided them into the fall and non-fall groups based on the questionnaires. Correlations were assessed using restricted cubic spline, weighted generalized linear regression models. Multi-factor logistic regression analysis identified serum Cys C as significantly associated with falls (all participants: OR 1.16, 95% CI: 1.09 to 1.23, p < 0.001; participants with eGFR > 75 mL/min/1.73m 2 : OR 1.17, 95% CI: 1.05 to 1.30, p < 0.001,). In contrast, Cre and eGFR were not significant after adjustments; SI showed marginal significance (p = 0.045). Cys C is significantly associated with fall risk in older adults, demonstrating a positive linear relationship with self-reported falls., (© 2024. The Author(s).)

Background: Accurate estimation of glomerular filtration rate (GFR) is crucial in living kidney donation. While most estimated GFR (eGFR) equations are based on plasma creatinine, its levels are strongly influenced by muscle mass. Application of cystatin C (cysC)-based estimates before donation may improve both estimation of current GFR and prediction of post-donation GFR., Methods: We assessed the performance of Chronic Kidney Disease Epidemiology Collaboration equations based on creatinine (eGFRcreat-2009, eGFRcreat-2021), cysC (eGFRCysC-2012) or both (eGFRcombined-2012, eGFRcombined-2021) for estimating pre- and post-donation (mGFR) GFR in 486 living kidney donors. We subsequently focused on a subgroup of individuals with high/low muscle mass (25% highest/lowest 24-hour urinary creatinine excretion, sex stratified and height indexed)., Results: Pre-donation eGFRcombined-2012 and eGFRcombined-2021 showed the strongest associations with pre- and post-donation mGFR. Pre-donation eGFRcombined-2021 was most accurate for estimating both pre-donation (bias 0.01 ± 11.9 ml/min/1.73 m2) and post-donation mGFR (bias 1.3 ± 8.5 ml/min/1.73 m2). In donors with high/low muscle mass, cysC-based equations (with or without creatinine) performed better compared with equations based on only creatinine., Conclusions: Combined eGFR equations yielded a better estimate of pre- and post-donation mGFR compared with estimates based on creatinine or cysC only. The added value of cysC seems particularly pronounced in donors with high or low muscle mass., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Acute kidney injury (AKI) and multiple organ failure (MOF) are leading causes of mortality in trauma injuries. Early diagnosis of AKI and MOF is vital to improve outcomes, but current diagnostic criteria rely on laboratory markers that are delayed or unreliable. In this study, we investigated whether damage associated molecular patterns such as high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1) and C3a correlate with the development of trauma-induced AKI and MOF., Methods: Thirty-nine swine underwent smoke inhalation and severe burns, then received critical care for 72 hours or until death. AKI was defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria, which labels AKI when a 1.5-fold increase in blood creatinine levels from baseline or a urine output < 0.5 mL/kg/h for 6 hours or more occurs. MOF was defined by the presence of both AKI and acute respiratory distress syndrome (PaO 2 /FiO 2 <300 for 4 hours)., Results: Eight of 39 pigs developed AKI and seven of those developed MOF. Pathological analysis revealed that polytrauma induces significantly higher kidney injury scores compared to sham controls. The average time from injury to KDIGO AKI was 24 hours (interquartile range: 22.50-32.25). Twelve hours after injury, HMGB1 levels were significantly increased in animals that went on to develop AKI compared to those that did not (73.07 ± 18.66 ng/mL vs. 31.64 ± 4.15 ng/mL, p <0.01), as well as in animals that developed MOF compared to those that did not (81.52±19.68 ng/mL vs. 31.19 ± 3.972 ng/mL, p <0.05). SDC-1 and C3a levels were not significantly different at any time point between groups. ROC analysis revealed that HMGB1 levels at 12 hours post-injury were predictive of both AKI and MOF development (AKI: AUROC=0.81, cut-off value=36.41 ng/mL; MOF: AUROC=0.89, cut-off value=36.41 ng/mL). Spearman's correlation revealed that HMGB1 levels at 12 hours correlated with multiple parameters of AKI, including blood urea nitrogen, blood creatinine, and blood myoglobin., Conclusion: Twelve-hour post-injury HMGB1 levels predict AKI and MOF in a smoke inhalation and burn swine model. Further research is needed to validate this result in other polytrauma models and in critical combat causalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GZ declared a shared affiliation with the author AM to the handling editor at the time of review., (Copyright © 2024 Yang, Cancio, Willis, Young, Kneifel, Salinas and Meyer.)