Elevated Serum Creatinine Levels Research Articles

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study

BackgroundRhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group.ResultsBlood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment.ConclusionsTreatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.

Nephrotic syndrome due to focal segmental glomerulosclerosis complicating scleroderma: a case report

BackgroundSystemic scleroderma (SSc) is an insidious autoimmune connective tissue disorder with multiorgan involvement. Renal involvement is one of the important causes of morbidity and mortality in scleroderma; however, nephrotic syndrome is reported rarely in association with SSc. We present a patient with SSc who developed focal segmental glomerulosclerosis (FSGS) as a complication of scleroderma.Case presentationA 59 year old Caucasian female patient, with a known history of diffuse systemic sclerosis from 8 years, presented to our clinic with symptoms of anasarca and weight gain. Her physical examination was unremarkable except for periorbital and extremity edema. Her biochemistry assessment revealed decreased serum albumin levels and elevated serum creatinine levels. A renal biopsy was performed, which showed histopathological patterns of FSGS type of nephrotic syndrome. After administration of high doses of steroid and rituximab in the course of her treatment for 6 months, her symptoms and proteinuria were improved without the occurrence of scleroderma renal crises.ConclusionSSc is a complex multisystemic autoimmune disorder. SRC is the most prominent renal involvement in SSc, but other renal pathologies may also occur. Each patient should be precisely investigated since managing these renal conditions can differ significantly. Nephrotic syndrome is a rare complication of SSc, which could be managed with prompt diagnosis and steroid administration.

Therapeutic and toxicological assessment of hydroethanolic leaf extracts of Jatropha carcus and Justicia carnea in apparently healthy Sprague Dawley rats.

The study aimed at evaluating the effects of hydroethanolic leaf extracts of Justicia carnea and Jatropha carcus on the biochemical, hematological, and histological parameters of apparently healthy rats. Thirty adult rats (n = 30) with an average weight of 153 g were randomly divided into six groups (A-F). Group A: negative control; Group B: positive control; Group C: Jatropha curcas (low dose); Group D: Jatropha curcas (high dose); Group E: Justicia carnea (low dose); and Group F: Justicia carnea (high dose). Standard and scientifically approved methods were used for sacrifice and laboratory diagnosis. The study shows a significant increase in body weight across groups administered with the leaf extracts. Elevated levels of serum creatinine were recorded in rats administered with both extracts, indicating nephrotoxicity. The study also observed an increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase across groups, indicating hepatotoxicity. Both extracts caused an increase in white blood cell count and hemoglobin concentration, a significant reduction in bleeding time, increased prothrombin time, and partial thromboplastin time at high dosages. Total iron binding capacity and serum ferritin values were increased in high doses and were statistically significant at P<0.05. Histomorphology of both extracts shows hepatorenal toxicity at high concentrations and none in the lungs or heart. Oral administration of Justicia carnea and Jatropha carcus extracts at high concentrations is not safe for the liver and kidneys. Biochemical parameters should be monitored regularly in humans exposed to both plants. Therefore, this study scientifically confirms and supports the traditional use of the leaves of Jatropha carcus and Justicia carnea to enhance hematological parameters.

Novel anti-inflammatory effects of the IL-1 receptor in kidney myeloid cells following ischemic AKI.

Introduction: Acute kidney injury (AKI) is one of the most common causes of organ failure in critically ill patients. Following AKI, the canonical pro-inflammatory cytokine interleukin-1β (IL-1β) is released predominantly from activated myeloid cells and binds to the interleukin-1 receptor R1 (IL-1R1) on leukocytes and kidney parenchymal cells. IL-1R1 on kidney tubular cells is known to amplify the immune response and exacerbate AKI. However, the specific role of IL-1R1 on myeloid cells during AKI is poorly understood. The objective of the present study was to elucidate the function of myeloid cell IL-1R1 during AKI. As IL-1R1 is known to signal through the pro-inflammatory Toll-like receptor (TLR)/MyD88 pathway, we hypothesized that myeloid cells expressing IL-1R1 would exacerbate AKI. Methods: IL-1R1 was selectively depleted in CD11c+-expressing myeloid cells with CD11cCre + /IL-1R1 fl/fl (Myel KO) mice. Myel KO and littermate controls (CD11cCre - /IL-1R1 fl/fl-Myel WT) were subjected to kidney ischemia/reperfusion (I/R) injury. Kidney injury was assessed by blood urea nitrogen (BUN), serum creatinine and injury marker neutrophil gelatinase-associated lipocalin (NGAL) protein expression. Renal tubular cells (RTC) were co-cultured with CD11c+ bone marrow-derived dendritic cells (BMDC) from Myel KO and Myel WT mice. Results: Surprisingly, compared to Myel WT mice, Myel KO mice displayed exaggerated I/R-induced kidney injury, as measured by elevated levels of serum creatinine and BUN, and kidney NGAL protein expression. In support of these findings, in vitro co-culture studies showed that RTC co-cultured with Myel KO BMDC (in the presence of IL-1β) exhibited higher mRNA levels of the kidney injury marker NGAL than those co-cultured with Myel WT BMDC. In addition, we observed that IL-1R1 on Myel WT BMDC preferentially augmented the expression of anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra/Il1rn), effects that were largely abrogated in Myel KO BMDC. Furthermore, recombinant IL-1Ra could rescue IL-1β-induced tubular cell injury. Discussion: Our findings suggest a novel function of IL-1R1 is to serve as a critical negative feedback regulator of IL-1 signaling in CD11c+ myeloid cells to dampen inflammation to limit AKI. Our results lend further support for cell-specific, as opposed to global, targeting of immunomodulatory agents.

Fractional excretion of total protein in patients with nephrotic syndrome.

The urine protein to creatinine ratio (UPCR) correlates well with the 24-h urine protein test (24-h UPT) and is a reliable indicator of proteinuria. However, in nephrotic syndrome, the correlation between the UPCR and the 24-h UPT tends to decrease. To address this, we introduced the fractional excretion of total protein (FETP), which reflects serum total protein and creatinine levels because severe hypoproteinemia and/or elevated serum creatinine levels tend to occur under these conditions. The 24-h UPT corrected for body surface area (BSA) (24-h UPT/BSA) was used to take body size into consideration. The correlation coefficients for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR were calculated. The statistical significance of the differences between these coefficients was also calculated. Thirty-six pediatric patients with nephrotic syndrome were included in this study. The FETP was calculated as total protein clearance/creatinine clearance (%). Correlation coefficients were calculated for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR. The statistical significance of the differences between these coefficients was also calculated. The mean ± standard error of FETP was 0.11% ± 0.013%. The correlation coefficients of FETP and UPCR with 24-h UPT/BSA were 0.91 and 0.81, respectively. The FETP demonstrated a significantly stronger correlation with 24-h UPT/BSA than with UPCR (p = 0.01). The FETP correlated more strongly with 24-h UPT/BSA than with UPCR in patients with nephrotic syndrome. The FETP is a reliable indicator of proteinuria in nephrotic syndrome, especially in patients with severe hypoproteinemia or elevated serum creatinine levels.

Proteinuria is a clinical characteristic of intrahepatic cholestasis of pregnancy but it is not a marker of severity: A retrospective cohort study.

To determine the prevalence of proteinuria in patients diagnosed with intrahepatic cholestasis of pregnancy (IHCP), and the association between the presence of proteinuria and adverse pregnancy outcomes. This was a retrospective cohort study. The study included all pregnant patients between July 2014 and January 2022, at gestational age > 24weeks who had been diagnosed with IHCP and had completed a 24-hour protein collection. High order multifetal gestations were excluded. Patients were divided into 3 groups:1. IHCP without proteinuria (Non-proteinuric group);2. IHCP with proteinuria and normal blood pressure (Isolated proteinuria group), and 3. IHCP with proteinuria and elevated blood pressure (IHCP with preeclampsia (PET)). Primary outcome was defined as a composite maternal-fetal outcome including: preterm labor <34 weeks, arterial cord blood ph<7.1, rate of Cesarean delivery due to non-reassuring fetal monitoring. Parametric and non-parametric statistical methods were used for analysis. A total of 272 met all inclusion criteria and were included, 94 patients (34.5%) had proteinuria; of them, 67 (24.6%) had isolated proteinuria and 27 (9.9%) had PET. Demographic parameters were comparable among the groups. Patients with PET had higher rates of in-vitro fertilization (IVF) treatments, twin gestation and elevated serum creatinine and urea levels. The rate of composite adverse pregnancy outcome was higher in patients with PET compared with patients with and without proteinuria (14/27 (51.9%) vs. 18/67 (26.9%) vs. 49/178 (27.5%), respectively, p = 0.03). Approximately 35% of patients with IHCP have proteinuria. The presence of PET, rather than isolated proteinuria, is associated with adverse pregnancy outcome.

Pathological Characteristics of Ferroptosis in Kidney Tissues in Type 2 Diabetic Patients with Diabetic Kidney Disease.

Diabetes kidney disease (DKD) is a common complication of diabetes and is currently considered the primary cause of end-stage renal disease. Ferroptosis has been found to participate in the development of DKD. However, no ferroptosis-related markers have been evaluated in human DKD samples. This study aimed to examine the ferroptosis-related pathological alterations in DKD samples. This study enrolled patients with DKD at the Third Hospital of Hebei Medical University between January 2018 and December 2022, of whom 30 were diagnosed with DKD and 10 with non-DKD (CON). Clinical data of patients were collected, and hematoxylin-eosinstaining (H&E), PASM, and immunohistochemical staining were performed to evaluate pathological changes and the expression of ferroptosis-related proteins, including GPX4, ACSL4, Nrf2, TfR1, FTH, and FTL. Compared with the CON group, patients with DKD exhibited significantly elevated serum creatinine levels and reduced eGFR (P < 0.05). Iron content and the expression of the ferroptosis-related protein ACSL4 were significantly increased, while the expression of Nrf2 was significantly decreased in the renal tissues of patients with DKD (P all < 0.05). There were no differences in the expression of GPX4, TfR1, FTH, or FTL between the two groups. Nrf2 and ACSL4 expression were influential factors in the occurrence of DKD and both exhibited diagnostic value for DKD. Nrf2 was a protective factor (OR, < 1), whereas ACSL4 was a risk factor (OR, > 1). Ferroptosis-promoting gene profile was identified in DKD renal samples, indicating that ferroptosis may participate in the pathogenesis of DKD. The expression levels of Nrf2 and ASCL4 in the kidneys are related to the severity and progression of DKD.

Association between fasting stress hyperglycemia ratio and contrast-induced acute kidney injury in coronary angiography patients: a cross-sectional study.

Stress hyperglycemia ratio (SHR), an emerging indicator of critical illness, exhibits a significant association with adverse cardiovascular outcomes. The primary aim of this research endeavor is to evaluate the association between fasting SHR and contrast-induced acute kidney injury (CI-AKI). This cross-sectional study comprised 3,137 patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI). The calculation of fasting SHR involved dividing the admission fasting blood glucose by the estimated mean glucose obtained from glycosylated hemoglobin. CI-AKI was assessed based on elevated serum creatinine (Scr) levels. To investigate the relationship between fasting SHR and the proportion of SCr elevation, piecewise linear regression analysis was conducted. Modified Poisson's regression analysis was implemented to evaluate the correlation between fasting SHR and CI-AKI. Subgroup analysis and sensitivity analysis were conducted to explore result stability. Among the total population, 482 (15.4%) patients experienced CI-AKI. Piecewise linear regression analysis revealed significant associations between the proportion of SCr elevation and fasting SHR on both sides (≤ 0.8 and > 0.8) [β = -12.651, 95% CI (-23.281 to -2.022), P = 0.020; β = 8.274, 95% CI (4.176 to 12.372), P < 0.001]. The Modified Poisson's regression analysis demonstrated a statistically significant correlation between both the lowest and highest levels of fasting SHR and an increased incidence of CI-AKI [(SHR < 0.7 vs. 0.7 ≤ SHR < 0.9) β = 1.828, 95% CI (1.345 to 2.486), P < 0.001; (SHR ≥ 1.3 vs. 0.7 ≤ SHR < 0.9) β = 2.896, 95% CI (2.087 to 4.019), P < 0.001], which was further validated through subgroup and sensitivity analyses. In populations undergoing CAG or PCI, both lowest and highest levels of fasting SHR were significantly associated with an increased occurrence of CI-AKI.

A spurious elevation of serum creatinine level in a patient with Crohn’s disease without histologic kidney damage: a case report and review of the literature

RESUMO Pacientes com doença inflamatória intestinal (DII) são propensos a desenvolver lesão renal. O envolvimento renal em pacientes com DII é geralmente diagnosticado pela medição da creatinina sérica e pela estimativa da taxa de filtração glomerular. Descrevemos um paciente com DII que apresentou grandes flutuações em seu nível de creatinina sérica (~3,0 vezes) sem anormalidades histológicas significativas e com nível normal de cistatina C. Isso parece estar relacionado a uma dieta rica em proteínas e jejum intermitente. Ainda que o impacto de uma dieta rica em proteínas em elevações leves do nível de creatinina sérica tenha sido descrito, nunca foram relatadas grandes flutuações na creatinina sérica apenas devido à dieta, como observado neste caso, o que levanta a questão sobre a possível contribuição do intestino inflamado na absorção intestinal ou no metabolismo da creatinina. Esse caso destaca a importância de um histórico detalhado, incluindo os hábitos alimentares, ao se deparar com um paciente com nível de creatinina sérica aumentado, e a interpretação cuidadosa da creatinina sérica em um paciente com dieta rica em proteínas ou DII subjacente.

Brentuximab Vedotin in Combination with Methotrexate, L-Asparaginase, and Dexamethasone (B-MAD) As Frontline Treatment for Patients with Extranodal NK/T-Cell Lymphoma

Introduction Extranodal natural killer/T-cell lymphoma (ENKTL) is a unique lymphoma associated with Epstein-Barr virus infection. It is more common in Asia than in the Western. The prognosis is usually poor, especially in advanced disease, and no standard treatment exists. Brentuximab vedotin (BV) is a drug-conjugated monoclonal antibody which targets the cell-membrane protein CD30 linked to the potent anti-tubulin agent. Due to frequent expression of CD30 in ENKTL, we investigated the safety and efficacy of BV in combination with methotrexate, L-asparaginase, and dexamethasone (B-MAD) as frontline treatment in Thai patients with ENKTL. Methods The Thai Lymphoma Study Group conducted a prospective, multicenter phase I/II study and enrolled patients aged 18-60 years with newly diagnosed ENKTL between December 2018 and December 2021 from 9 hospitals in Thailand. Patients with localized ENKTL (stage I/II) received concurrent weekly cisplatin and involved-field radiation (IFRT) 40-50 Gy, followed by 3 cycles of B-MAD. Patients with advanced ENKTL (stage III/IV) received only B-MAD for 6 cycles. BV in combination with standard dose MAD chemotherapy was given every 21 days. The primary objective was to determine the safety and optimal dose of BV in B-MAD regimen using a 3+3 dose escalation design. The secondary objective was to evaluate the overall response rate (ORR) at the end of B-MAD treatment, safety, progression-free survival and overall survival. An analysis was performed at the data cutoff date of June 30, 2023. Results Thirty-four patients (pts.) were enrolled; 23 had localized and 11 had advanced diseases. The median age was 42 years (range, 18-59). Four pts. in the localized group did not receive B-MAD due to disease progression during concurrent cisplatin and IFRT (n=3) and consent withdrawal (n=1). Six pts. received B-MAD in phase I study (3 pts. at 1.2 mg/kg and 3 pts. at 1.8 mg/kg of BV). No dose-limiting toxicity was observed among six patients, therefore the recommended dose of BV in phase II study was 1.8 mg/kg. Of 30 evaluable pts., 20 (66.7%) achieved complete response (CR), 5 (16.7%) had partial response, and 5 (16.7%) progressed after treatment. The response rates (ORR/CR rate) in localized and advanced diseases were 89.5%/78.9% and 72.7%/45.5%, respectively. A total of 190 adverse events (AEs) were reported. The most common AEs were anemia 19/190 (10%), leukopenia 9/190 (4.7%), neutropenia 9/190 (4.7%), hypoalbuminemia 9/190 (4.7%), peripheral neuropathy 7/190 (3.7%), elevated ALT 7/190 (3.7%), and elevated serum creatinine level 5/190 (2.6%), respectively. Twenty-four events were classified as grade ≥ 3 including anemia (4/24), leukopenia (7/24), neutropenia (7/24), and elevated ALT (1/24), respectively. A total of 21 serious adverse events (SAEs) were reported. The causes of SAE were varied as follows: acute kidney injury 2/21, pneumonia 2/21, leukopenia 1/21, neutropenia 1/21, and thrombocytopenia 1/21. Most of the SAEs were suspected to be related to the treatment. Two cases of acute kidney injury related to methotrexate and one case of hypersensitivity reactions to L-asparaginase were reported as SAEs. They were manageable and completely resolved upon follow-up. There were no treatment-related deaths. At the data cutoff date, after the median follow up of 11.6 months, 25 pts. were alive, 7 experienced progressions, and 5 had died. Two pts. had progression in the central nervous system. Conclusion Treatment with standard-dose of BV in combination with MAD chemotherapy was well tolerated and showed encouraging efficacy in patients with newly diagnosed ENKTL. Evaluation of long-term survival data is ongoing. (ClinicalTrials.gov identifier: NCT03246750)

Valproic acid monitoring: Serum prediction using a machine learning framework from multicenter real-world data

BackgroundOur study employs machine learning to predict serum valproic acid (VPA) concentrations, aiming to contribute to the development of non-invasive assays for therapeutic drug monitoring. MethodsMedical records from 2002 to 2019 were obtained from the Taiwan Chang Gung Research Database. Using various machine learning algorithms, we developed predictive models to classify serum VPA concentrations into two categories (1–50 μg/ml or 51–100 μg/ml) and predicted the exact concentration value. The models were trained on 5142 samples and tested on 644 independent samples. Accuracy was the main metric used to evaluate model performance, with a tolerance of 20 μg/ml for continuous variables. Furthermore, we identified important features and developed simplified models with fewer features. ResultsThe models achieved an average accuracy of 0.80–0.86 for binary outcomes and 0.72–0.88 for continuous outcome. Ten top features associated with higher serum VPA levels included higher VPA last and daily doses, bipolar disorder or schizophrenia spectrum disorder diagnoses, elevated levels of serum albumin, calcium, and creatinine, low platelet count, low percentage of segmented white blood cells, and low red cell distribution width-coefficient of variation. The simplified models had an average accuracy of 0.82–0.86 for binary outcome and 0.70–0.86 for continuous outcome. LimitationsThe study's predictive model lacked external test data from outside the hospital for validation. ConclusionsMachine learning models have the potential to integrate real-world data and predict VPA concentrations, providing a promising tool for reducing the need for frequent monitoring of serum levels in clinical practice.

Intoxicación por vancomicina en un paciente con síndrome de secreción inadecuada de hormona antidiurética y diarrea

Vancomycin is an antibiotic used for infections by gram-positive bacteria with a two-compartment pharmacokinetic model. Its monitoring has an established therapeutic range (10-20 mg/L) to prevent nephrotoxicity and ototoxicity due to supra-therapeutic levels, and inefficiency and development of resistance by subtherapeutic levels.Nephrotoxicity for vancomycin monotherapy at standard doses according to pathogen and typical regimens (usual dose: 15-20 mg/kg/12 h) is rare and usually reversible. Moreover, monitoring plasma concentrations allows to achieve concentrations within therapeutic range to allow safe and effective drug use. The renal hypoperfusion can cause pre-renal damage, resulting in elevated levels of serum creatinine, resulting in decreased antibiotic elimination and nephrotoxicity.We report a case of unexpected vancomycin nephrotoxicity in a patient with syndrome Inappropriate antidiuretic hormone secretion associated paraneoplastic.

Study on Risk Factors Associated with Severity of Diabetic Retinopathy in Type-2 Diabetic Patients, Attending a Tertiary Care Centre in Kerala

Introduction: Diabetic retinopathy (DR) is a significant public health concern affecting individuals with diabetes mellitus (DM). Despite treatment advances, a substantial proportion of patients do not respond adequately. This study investigates risk factors associated with the progression of non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) in type-2 diabetes patients. Methods: A retrospective case-control study was conducted on diabetic patients older than 40 years with at least 5 years of Type-2 Diabetes Mellitus history, attending ophthalmology clinic in Government Medical College, Thrissur, a tertiary care hospital. Data from patients with retinal examination showing diabetic retinopathy were analyzed. Records with missing data were excluded. Patients with Proliferative Diabetic Retinopathy (n=153) were compared with those having Non- Proliferative Diabetic Retinopathy (n=230). Various risk factors were assessed using statistical analysis. Results: Among the studied variables, sex, duration of diabetes, serum urea, serum creatinine, serum triglycerides, and chronic kidney disease were significantly different between Proliferative Diabetic Retinopathy and Non-Proliferative Diabetic Retinopathy patients. Binary logistic regression revealed that duration of diabetes (OR = 1.8, 95% CI = 1.1 - 2.39) and serum creatinine (OR =1.8, 95% CI = 1.1 - 2.39) independently influenced Proliferative Diabetic Retinopathy development. Conclusion: This study highlights that longer diabetes duration and elevated serum creatinine levels independently increase the risk of Non- Proliferative Diabetic Retinopathy progressing to Proliferative Diabetic Retinopathy in type-2 diabetic patients. Other factors such as age, gender, hyperlipidemia, systemic hypertension, type of diabetic treatment, and history of ischemic heart disease did not show significant associations with disease progression. These findings emphasize the importance of close monitoring, early detection, and intervention in patients with Non- Proliferative Diabetic Retinopathy, particularly those with a longer diabetic history, to prevent Proliferative Diabetic Retinopathy development. Further research should explore the causal relationship between serum creatinine and diabetic retinopathy progression and evaluate the impact of renal disease management on disease outcomes. Keywords: Diabetic Retinopathy, diabetes mellitus (DM), Type-2 Diabetes Mellitus (T2DM).

Elevated serum creatinine levels and risk of cognitive impairment in older adults with diabetes: a NHANES study from 2011-2014.

The brain and kidney have similar microvascular structure, which makes them susceptible to certain common pathophysiological processes. In this study, we examined several indicators of kidney injury/function associated with cognitive function in older diabetic patients in the hope of finding effective markers for detecting cognitive impairment (CI). A total of 2209 older participants (aged ≥60 years) from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed for the association between diabetes and CI using a multiple linear regression analysis model. Using the same approach, we also analyzed the relationship between indicators of kidney injury/function and cognitive function (Animal Fluency Test, Digit Symbol Substitution Test) in the diabetic population. Diabetes was associated with CI. In age-adjusted model, older diabetics performed significantly poorer on tests of cognitive function compared to normoglycaemic individuals (1.145 points lower on the Animal Fluency Test (P = 0.005) and 7.868 points reduced on the Digit Symbol Substitution Test (P < 0.001)). In diabetics, we found elevated serum creatinine (SCr) (especially at SCr≥300uM) was associated with lower scores on cognitive function tests after strict adjustment for potential influences on cognitive function. While, albumin/creatinine ratio (ACR) was only associated with Digit Symbol Substitution score (DSS) not Animal Fluency score (AFS), and estimated glomerular filtration rate (eGFR) was only associated with CI (AFS and DSS) at the end-stage renal disease. SCr, as a sensitive indicator of kidney injury, was significantly associated with CI and can potentially be used as an effective marker for screening CI in older diabetics.

B-289 Acute Kidney Injury Urinary Biomarker, Neutrophil Gelatinase-Associated Lipocalin (NGAL) Analytical Performance Evaluation on Roche Cobas c502 Chemistry Platform

Abstract Background Acute kidney injury (AKI) is a sudden and serious kidney damage condition that affects more than 1.2 million people every year. KDIGO guidelines suggest serum creatinine increase as a diagnostic marker for AKI but elevation of serum creatinine levels can take up to seven days. Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early tubular injury biomarker for AKI that is detected within three hours of AKI patients’ urine. In this study, we evaluated technical performance of BioPorto NGAL assay on Roche cobas c502 chemistry analyzer. Methods BioPorto’s (Hellerup, Denmark) particle enhanced turbidimetry immunoassay (PETIA) NGAL assay was installed on cobas c502 chemistry analyzer (Roche, Indianapolis, U.S.A) following vendor-specific application parameters with few modifications. Linearity was determined with BioPorto’s linearity material and verified by serial dilutions of a high NGAL patient urine sample. Limit of quantitation was determined in urine samples with values 20, 25 and 35 ng/mL, run in duplicate for 10 days. Precisions were determined by running urine samples containing 100 ng/mL and 400 ng/ml NGAL 20 times for within-run precision and twice a day × 10 days for between-run precision, respectively. To determine the accuracy of the NGAL method on cobas 502, 40 sample results (provided by the vendor) were compared with those measured on Siemens Atellica using BioPorto’s NGAL assay. Reference interval verification was carried out in 40 urine samples collected from healthy adult volunteer-donors. Results The linearity was found to be excellent from 0–3000 ng/mL. Limit of quantification was found at 26 ng/mL. Precision results are in the table below. Method comparison showed a slope of 0.90 and intercept of 32.9. The reference interval was verified to be &amp;lt;50 ng/mL (in accordance with current NGAL reference cut­off for AKI diagnosis). Conclusion Performance of BioPorto’s NGAL PETIA assay was validated in urine on cobas c502 chemistry analyzer.

Clinical manifestations and outcomes in tubulointerstitial nephritis and uveitis syndrome: a case report and a systematic review in China

PurposeTubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon disease. We present a confirmed case of TINU syndrome, and a systematic review of epidemiological characteristics, clinical manifestations, management, and outcomes in Chinese patients.MethodsA systematic search was carried out using defined terms and updated up to September 2022, in PubMed, Web of Science, Wanfang, CNKI, and VIP, to identify reported cases of TINU in China, according to PRISMA guidelines.ResultsAn 18-year-old boy presented with elevated serum creatinine and 24-h urine protein level of > 2 g. Inspection result revealed acute tubulointerstitial nephritis, and bilateral uveitis. The patient was diagnosed with TINU syndrome and received treatment with methylprednisolone sodium succinate, which resulted in a significant decrease in creatinine and urinary protein levels. Systematic review identified 35 publications that met the inclusion criteria. A total of 71 cases were included in this article, of which 70 were from publications and 1 was from our hospital. The median age at onset was 42 years and was significantly lower in males than females (P < 0.05). The symptoms of uveitis often occurred after kidney injury (54%) and most uveitis was anterior (55%) and bilateral (75%). Among the 51 patients who were followed up for more than 6 months, 24 had recurrent ocular symptoms or progression to chronic uveitis. Twenty patients experienced chronic or progressive kidney disease.ConclusionTINU syndrome is prone to misdiagnosis because kidney damage may not occur simultaneously with uveitis. The incidence of kidney sequelae in children is lower than that in adults, and glucocorticoids are the preferred treatment.INPLASY registration number INPLASY202350050.

Daily dose of metformin caused acute kidney injury with lactic acidosis: a case report

BackgroundMetformin-induced lactic acidosis with acute kidney injury is rare but well known. Here we report a case of a Japanese patient taking metformin who experienced severe acute renal failure accompanied with significantly elevated metformin plasma concentrations and signs of lactic acidosis.Case presentationA 60-year-old Japanese man with type II diabetes, who was taking metformin (500 mg three times a day) along with several other medications, visited the emergency department with dizziness, malaise, and oliguria. The initial laboratory test results showed elevated levels of serum creatinine and blood urea nitrogen, although his renal function was normal approximately 2 weeks earlier. His lactate level was raised (4.27 mmol/L), and he was diagnosed with lactic acidosis. Considering the low creatinine clearance and elevated urinary albumin/serum creatinine ratio, urinary N-acetyl-β-d-glucosaminidase level, and β2-microglobulin level, the patient was further diagnosed with AKI (in other words, acute tubular necrosis). A renal biopsy performed on day 3 after admission revealed renal tubular epithelium necrosis, supporting this diagnosis. The patient underwent intermittent hemodialysis until he was discharged on day 13. The metformin concentrations on days 3, 5, and 7 were 8.95, 2.58, and 0.16 μg/mL, respectively, which is significantly higher than the maximal steady-state concentration of metformin at the recommended dosage (approximately 1 μg/mL). The calculated pharmacokinetic parameters of metformin suggested poor renal excretion and a low distribution volume at higher metformin levels. Other possible acute kidney injury-causing factors included dehydration, alcohol consumption, and the use of an angiotensin receptor blocker or SGLT2 inhibitor.ConclusionsThis is the first reported case of acute kidney injury possibly caused by high levels of metformin with lactic acidosis in a patient treated with the recommended metformin dose. Thus, the development of metformin-induced acute kidney injury should be considered for patients with several acute kidney injury risk factors who are taking metformin.

Anti-Nephrotoxic effect of green synthesized Actiniopteris radiata silver nanoparticles (AR-AgNPs) against gentamicin induced nephrotoxicity

A study on green synthesized silver nanoparticles (AgNPs) using aqueous extract of Actiniopteris radiata and investigated the effect of A. radiata biosynthesized silver nanoparticles (AR-AgNPs) against gentamicin induced nephrotoxicity. The surface plasmon resonance (SPR) peak at 440 nm in UV–visible absorbance spectrum reveals the presence of AgNPs. DLS analysis shows that the distribution of size is normal and the average size of AgNPs converges about 100 nm. SEM revealed the consistent shape, uniform distribution, and closely packed characteristics of NPs whereas EDX confirms the presence of metallic silver with a strong peak at 3 keV. The N–H and O–H stretching vibrations are observed in the FTIR spectrum around 3450 and 3423 cm−1. Gentamicin induced changes in serum parameters resulted in a significant increase in the level of serum urea, creatinine, bilurubin and uric acids. AgNPs even at modest doses (250 mg/kg), significantly reverted the level of serum markers. The gentamicin-induced AR-AgNP in mice with the levels of CAT, GPx, SOD and TBARS ensured the protection against the oxidative damage in mice which clearly implies that enhancing the antioxidant defense mechanism. Nephrotoxicity of gentamicin induced mice were demonstrated by significantly elevated levels of blood urea, serum creatinine, bilirubin, and uric acids. The exposure of AR-Ag nanoparticles leads to a substantial decrease in blood urea and serum creatinine levels and enhanced the antioxidant and anti-nephrotoxic activity.

Multiorgan failure caused by Chinese herbal medicine Xanthii Fructus poisoning: a case report

BackgroundXanthii Fructus was used in the treatment of rhinitis and related nasal disease. It is the most commonly used chemically active component in compounds formulated for the treatment of rhinitis. However, poisoning, resulting in serious consequences, can easily occur owing to cocklebur overdose, improper processing, or usage without processing.Case presentationWe reported on a 55-year-old man who experienced allergic rhinitis for 2.5 years. He ingested unprocessed Xanthii Fructus for 2 months as treatment. However, he developed anorexia; nausea; abdominal pain; general weakness; hiccups; oliguria and anuria; significantly elevated serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels; and abnormalities in blood coagulation series. Nutritional support; daily drugs for liver protection, gastric protection, inflammation reduction; fresh plasma; and cryoprecipitate infusion were administered. Continuous venovenous hemodialysis (Prismaflex ST100) was also administered. However, the patient’s multiple organ failure gradually worsened, ultimately leading to death.ConclusionXanthii Fructus poisoning affects multiple systems, and its clinical manifestations are complex. Therefore, it is easily misdiagnosed and missed. Along with careful inquiry of medical and medication history, early diagnosis and intervention are vital for a successful treatment. It is also important to educate people and create awareness about this poisoning. Therefore, this intractable case has great clinical significance.

Admission serum creatinine in non-hemodialysis-dependent patients with spontaneous supratentorial intracerebral hemorrhage: Is it a prognosticator?

IntroductionSpontaneous intracerebral hemorrhage (ICH) carries a high mortality rate, with end-stage renal disease (ESRD) and hemodialysis being risk factors for early mortality. However, the role of admission serum creatinine in ICH prognosis remains unclear. This study aimed to analyze the correlation between admission serum creatinine levels and short-term ICH prognosis in non-hemodialysis-dependent patients. MethodsThis retrospective study analyzed 296 adult patients admitted with spontaneous supratentorial ICH. Demographic, clinical, and radiographic data were collected, including admission serum creatinine levels. The primary outcomes were mortality and unfavorable outcomes, defined as Modified Rankin Scale scores of 4–6. Univariate or multivariate analysis was performed to examine the association between admission serum creatinine levels and ICH prognosis, with and without the inclusion of maintenance hemodialysis patients. ResultsAmong all patients, elevated admission serum creatinine levels were significantly associated with increased mortality (OR = 1.39, 95% CI: 1.21–1.59, P < 0.01). However, this association disappeared when excluding patients undergoing maintenance hemodialysis (OR = 0.95, 95% CI: 0.53–1.69, P = 0.86). No significant association was found between admission serum creatinine levels and unfavorable outcomes. Other well-established prognostic factors, such as age and admission GCS, demonstrated significant associations with both mortality and unfavorable outcomes in multivariate analysis. ConclusionAdmission serum creatinine appears to have limited prognostic value in non-hemodialysis-dependent patients with spontaneous supratentorial ICH. Our findings suggest that the relationship between renal function and ICH prognosis is complex and may be influenced by factors such as comorbidities and maintenance hemodialysis.