Serum Creatinine Research Articles

Inhibition of complement system-related gene ITGB2 attenuates epithelial–mesenchymal transition and inflammation in diabetic nephropathy

PurposeEmerging evidences have indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN). Thus, this study was conducted to explore the complement system-related key biomarkers for patients with DN.MethodsDN microarray datasets were downloaded from the GEO database, followed by differentially expressed genes (DEGs) screening. Complement system-related genes (CSRGs) were searched from various databases. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to screen the DN-related genes, then the differential CSRGs (DCSRGs) were identified, followed by protein–protein interaction (PPI) network construction. In addition, key biomarkers were acquired by two machine learning algorithms, then immune infiltration analysis, Gene Set Enrichment Analysis (GSEA), and potential drugs screening were conducted. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were utilized to detect the ITGB2 expression. Then the cell viability, inflammatory factors, and the expression of epithelial–mesenchymal transition (EMT) and fibrosis markers were determined by using Cell Counting Kit-8 (CCK-8) assay, enzyme linked immunosorbent assay (ELISA), western blotting assays, respectively.ResultsIn total, 1012 DEGs and 974 DN-related genes were screened, and intersection analysis of the three (DN-related genes, DEGs and CSRGs) yielded 13 intersection genes, which were considered as the DCSRGs. Subsequently, 2 key biomarkers were identified by machine learning, namely VWF and ITGB2. The VWF and ITGB2 were both enriched in the pathways of chemokine signaling pathway, CAMs, focal adhesion and natural killer cell-mediated cytotoxicity, and significantly correlated with the activated mast cells, resting NK cells, and macrophages. Also, VWF and ITGB2 were significantly related to the clinical features, including age, serum creatinine level, and GFR (MDRD). Besides, mRNA and protein expression levels of ITGB2 in HG-treated HK-2 cells were remarkably elevated. Moreover, the viability of HK-2 cells, expression of TNF-α, IL-6, IL-12, α-SMA, E-cadherin and vimentin in HK-2 cells changed by HG administration were reversed by ITGB2-silence.ConclusionComplement system-related gene ITGB2 was overexpressed in DN, and inhibition of ITGB2 attenuated EMT and inflammation in DN.

T cell costimulatory blockade ameliorates induction of experimental membranous nephropathy potentially through T-helper 17 cell suppression in the kidney.

Recent advances in membranous nephropathy treatment have focused on B cell depletion, which is incompletely effective, potentially due to persistent autoantibody-producing plasma cells or alternative pathways of injury. T cell costimulatory blockade (cytotoxic-T-lymphocyte-associated antigen 4 (CTLA4)-Ig) to prevent T cell-dependent B cell activation and short-course proteasome inhibition (bortezomib) to deplete plasma cells may represent a complementary form of treatment. Lewis rats were immunized with Fx1A and complete Freund's adjuvant (CFA) to induce experimental membranous nephropathy (Heymann nephritis or HN) and treated with CTLA4-Ig alone or CTLA4-Ig plus a short-course of bortezomib. Serum creatinine, proteinuria, kidney histology, serum anti-Fx1A levels, kidney and spleen messenger RNA expression, and flow cytometry on splenocytes were evaluated at 12 weeks. CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats had significant and similar reductions in serum creatinine and proteinuria, with less histological kidney injury compared to untreated HN rats. Glomerular IgG deposition was reduced in CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats compared to untreated HN rats but there were no significant differences in serum anti-Fx1A levels. CTLA4-Ig-treated and CTLA4-Ig plus bortezomib-treated rats exhibited significantly reduced T helper (Th)-17 cell cytokines (interleukin (IL)-6, IL-17, IL-21) and regulatory T cell (Foxp3, TGF-β) expression in the kidney but not the spleen. Immunohistochemical staining of CD4+ and intracellular STAT3+ cells were reduced in CTLA4-Ig plus bortezomib-treated and CTLA4-Ig-treated compared to untreated HN rats. On flow cytometry, CTLA4-Ig reduced B cells and plasma cells but not T cell subsets. CTLA4-Ig ameliorated induction of experimental membranous nephropathy, potentially through suppression of Th17 cells in the kidney and may represent an effective adjunct treatment in membranous nephropathy.

Parathyroid Hormone Concentration in Dogs Affected by Acute Kidney Injury Compared with Healthy and Chronic Kidney Disease

Information about parathyroid hormone (PTH) status in the course of AKI is lacking. In contrast, renal secondary hyperparathyroidism (RSHPT) is a well-known consequence of canine chronic kidney disease (CKD). This study aimed to investigate PTH status in dogs affected by AKI, comparing PTH concentrations between healthy dogs, dogs affected by AKI and dogs affected by CKD. Three groups of dogs (35 affected by AKI, 35 affected by CKD and 41 healthy) were retrospectively included. PTH concentrations were significantly higher in both the AKI and CKD groups (p < 0.0001) compared to healthy ones but without significant differences between the AKI and CKD groups. In the AKI group, increased PTH was detected in 88.6% of dogs. Moreover, in AKI dogs, PTH increases with AKI grading and is correlated with serum creatinine (p < 0.0001; r = 0.67) and phosphate concentrations (p < 0.0001; r = 0.74). PTH in AKI dogs was not correlated with total calcium (tCa), while it was negatively correlated with ionized calcium (iCa) (p < 0.0037; r = −0.53). Higher PTH concentrations also occurred in canine AKI, as reported in canine CKD and human AKI, presumably as a rapid response to ionized hypocalcemia and hyperphosphatemia, frequently reported in our patients. PTH seems not to be a useful tool in distinguishing AKI and CKD.

Serum Dickkopf-3 as a biomarker for predicting acute kidney injury in postoperative intensive care patients.

Acute kidney injury (AKI) is a common and significant complication in the Intensive Care Unit (ICU), affecting more than half of all patients admitted. This condition is associated with increased morbidity and mortality, underscoring the urgent need for accurate and specific biomarkers to enable early diagnosis and intervention. Dickkopf-3 (DKK3) has emerged as a promising candidate biomarker for renal injury. We conducted a single-center, prospective cohort study from March 1 to July 1, 2023, enrolling 166 non-cardiac postoperative patients admitted to the ICU. Serum and urinary DKK3 levels were quantified using enzyme-linked immunosorbent assay (ELISA) kits. A multifactorial logistic regression model was constructed, incorporating changes in serum creatinine (ΔScr), cystatin C (CysC), serum DKK3 levels, and the serum DKK3 to urine DKK3 ratio. Elevated serum DKK3 levels were significantly associated with an increased incidence of AKI and a composite outcome of adverse events (AKI or death). The multifactorial logistic regression model exhibited excellent performance, with an area under the receiver operating characteristic curve (AUC) of 0.98. Decision curve analysis (DCA) demonstrated a net clinical benefit of utilizing serum DKK3 levels to guide treatment decisions, particularly at higher risk thresholds. Serum DKK3 is a robust diagnostic biomarker for AKI, effectively stratifying patients based on protein levels. The predictive model that incorporates DKK3 provides a valuable tool for clinical decision-making in the ICU setting. Further validation in larger and more diverse populations is warranted.

Clinical, immune and genetic risk factors of malaria-associated acute kidney injury in Zambian children: A study protocol.

Acute kidney injury (AKI) affects nearly half of children with severe malaria and increases the risk of adverse outcomes such as death and poor cognitive function. The pathogenesis and predictors of malaria-associated acute kidney injury (MAKI) are not fully described. This study aims to determine the clinical, immune, and genetic correlates of risk to AKI in Zambian children admitted with malaria. In addition, we intend to assess a modified renal angina index (mRAI), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and soluble urokinase receptor (suPAR), when done on the first day of admission, for the ability to predict AKI two days later (day 3) in children admitted with malaria. This is an unmatched case-control study with a nested prospective observational study. A case-to-control ratio of 1:1 is used and 380 children with malaria and aged less than 16 years are being recruited from two hospitals in Zambia. Eligible children are recruited after obtaining written informed consent. Recruitment occurs during the malaria season and began on 6th March 2024 and will continue until July 2025. AKI is defined using the 2012 KIDGO AKI creatinine criteria, and cases are defined as children admitted with malaria who develop AKI within 72 hours of admission, while controls are children admitted with malaria but with no AKI. Serum creatinine is collected on Day 1 within 24 hours of admission, on Day 3 and then again on discharge or day 7, whichever comes sooner. Baseline biomarker concentrations will be determined using the Luminex multiplex Elisa system or high-sensitivity ELISA. SPSS version 29 will be used for data analysis. Descriptive statistics and inferential statistical tests will be run as appropriate. A p ≤ 0.05 will be considered as significant. The sensitivity, specificity, and estimates of the area under the curve (AUC) for the renal angina score will be determined.

Role of shearing wave elastography in detecting early diabetic nephropathy.

Diabetes mellitus is one of the systemic diseases affecting the kidneys that eventually develop end-stage kidney disease. Shear wave elastography (SWE) is a reliable and non-invasive ultrasonography test used to determine tissue elasticity. The aim of this study is to detect early diabetic nephropathy by measuring renal stiffness using shear wave elastography (SWE), renal resistivity indices, and laboratory findings in DN patients. Shear wave elastography and color duplex sonography assessments were performed in 60 diabetic nephropathy patients (divided according to eGFR into 3 stages: stage I-II-III diabetic nephropathy with equal groups of 20 patients in each stage) and 20 healthy age-matched control subjects. The SWE-derived mean value of the tissue stiffness, given in kilopascals (kPa), was correlated to patients' clinico-laboratory data (serum creatinine and eGFR) and resistive index. There is a statistically significant increase in SWE and RI in the diabetic group than control group and a statistically significant increase in SWE (mean) in CKD stage II and III when compared with CKD stage I, SWE can be used to discriminate between diabetic groups and control group at a cutoff level of > 10.5 (kPa), and also, SWE (mean) can be used to discriminate between CKD stage II and III patients at a cutoff level of > 41 (kPa), with 66.7% sensitivity and 64.9% specificity. Shear wave elastography is a sensitive, non-invasive, and specific diagnostic tool for the detection of diabetic nephropathy and differentiation between different stages of DN.

Estimating measured creatinine clearance for critically ill trauma patients with presumed normal kidney function.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. The intent of this study was to evaluate the predictive performance of two common methods for estimating kidney function in critically ill trauma patients with presumed normal kidney function. A retrospective analysis of 2 common methods for estimating kidney function, the Cockcroft-Gault (CG) and Chronic Kidney Disease Epidemiology Collaboration (2021 CKD-EPI) equations, was undertaken for adult trauma patients. Patients with a 24-hour urine collection for determination of measured creatinine clearance (mCrCl) within 4 to 14 days after admission were included in the study. Patients with a serum creatinine concentration of >1.5mg/dL or who required dialysis were excluded. The 200 patients included in the study had a median (IQR) mCrCl of 184 (141-233) mL/min; both the CG and CKD-EPI equations were biased towards underpredicting mCrCl, with median (IQR) values of 135 (100-177) mL/min and 135 (113-155) mL/min, respectively (P < 0.001). One hundred twenty-two patients had augmented renal clearance (ARC), defined as an mCrCl of >129mL/min/1.73m2, and those patients had a median (IQR) mCrCl of 216 (188-265) mL/min; both the CG and CKD-EPI equations were biased towards underpredicting mCrCl in patients with ARC: the median (IQR) estimates were 160 (126-197) mL/min and 147 (129-164) mL/min, respectively (P < 0.001). For those without ARC (n = 78), the median (IQR) mCrCl was 125 (98-153) mL/min; both the CG and CKD-EPI equations underpredicted mCrCl, with median estimates of 98 (76-116) mL/min and 112 (92-132) mL/min, respectively (P < 0.001). The CKD-EPI equation outperformed the CG method for all markers of precision in patients without ARC (P < 0.003). Common predictive equations for assessing kidney function in critically ill patients with traumatic injuries underpredicted mCrCl, especially in those with ARC.

Identification of Fatty Acid-Binding Protein 4 as a Potential Biomarker and Therapeutic Target for ANCA-Associated Glomerulonephritis

Introduction: Fatty acid-binding protein 4 (FABP4) is a novel adipokine that is critically involved in many inflammatory and immune diseases. However, the role of FABP4 in anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) remains unclear. The current study aimed to investigate the role of FABP4 in patients with ANCA-GN. Methods: Plasma and urine samples from 37 patients with active ANCA-GN and kidney biopsy specimens from another group of 56 patients with ANCA-GN were collected. The plasma and urinary level of FABP4 were measured by enzyme-linked immunosorbent assay and the kidney FABP4 expression was determined by immunohistochemistry and immunofluorescence staining. Associations between FABP4 levels with clinical and pathologic parameters were analyzed. To further elucidate the role of FABP4 in ANCA-GN, a novel FABP4 inhibitor BMS309403 was employed in a recognized rat model of experimental autoimmune vasculitis (EAV). Results: Plasma and urinary levels of FABP4 in active ANCA-GN patients were significantly higher than those in normal controls (52.8 ± 23.6 ng/ml vs. 16.9 ± 8.8 ng/ml, P&lt;0.01; median 126.6 [interquartile range (IQR) 28.4-311.2] ng/g Cr vs. median 0.0 [IQR 0.0-0.0] ng/g Cr, P&lt;0.01, respectively). Immunohistochemical analysis revealed higher glomerular and tubular expression of FABP4 in the kidneys of ANCA-GN patients than those in normal controls (0.015 ± 0.012 vs. 0.004 ± 0.003, P&lt;0.001; 0.053 ± 0.026 vs. 0.011 ± 0.010, P&lt;0.001, respectively). Moreover, for ANCA-GN patients, urinary FABP4 levels were significantly higher in active ANCA than those in remission (184.3 ± 187.0 ng/g Cr vs. 9.4 ± 23.9 ng/g Cr, P&lt;0.01). Correlation analysis showed that urinary levels of FABP4 correlated with serum creatinine (r=0.596, P&lt;0.0001), urinary albumin/Cr (r=0.523, P=0.001), blood neutrophil ratio (r=0.386, P=0.018), PT (r=0.583, P=0.001), APTT (r=0.364, P=0.034), hemoglobin level (r=-0.398, P=0.015), eGFR (r=-0.680, P&lt;0.0001), crescent proportion (r=0.661, P=0.032) and all-cause death of ANCA-GN patients (HR 2.93, 95%CI (1.05-8.19)). Furthermore, FABP4 inhibition by BMS309403 ameliorated renal injury in a rat mole of ANCA-GN. Conclusions: Urinary FABP4 levels might reflect the disease activity and renal involvement of ANCA-associated vasculitis, and FABP4 might act as a promising therapeutic target against ANCA-GN.

Clinical Characteristics and Short-Term Outcomes of COVID-19 Positive Hospitalized Hemodialysis Patients

Presentation of Novel Corona virus disease (COVID-19) and its clinical features and outcomes were different in maintenance hemodialysis (MHD) patients than in general population due to relative immunosuppression and high prevalence of co-morbidities in MHD patients. The aim of this study is to identify the clinical characteristics and outcome of MHD patients requiring hospitalization for COVID 19. In this retrospective observational study, a total of 100 adult patients of both sex who were on maintenance hemodialysis therapy having A-V fistula or permanent venous catheter admitted in Nephrology department of Mugda Medical College Hospital due to COVID-19 from April 21, 2020 to April 30, 2021 were included. Demographic data (age, sex, comorbidities), initial clinical presentations (fever, cough, shortness of breath, fatigue), oxygen saturation, chest radiograph and laboratory tests CBC, RBS, Serum Creatinine, SGPT, CRP, LDH, D dimer, Ferritin, Albumin at admission and during hospital stay were retrieved from patient file. Treatment of these hemodialysis patients was given and modified according to the hospital treatment committee including Nephrologist and Medicine specialist. As the patients were followed up from admission in hospital until discharge or death, so they were divided in two groups- Survived and death. All data were compiled and edited meticulously using SPSS version 27 software. The mean age of the patients was 53.8±13.3 (Range 15-90). Male and female ratio was 1.7.1. No significant difference was observed regarding age and sex of the study subjects. Most patients had HTN (78%) followed by DM (52%), IHD (42%), CLD (24%), pulmonary disease (21%) and Stroke (6%). The most common symptoms during admission in hospital were fever 65%, cough 52%, fatigue 43%, SOB 35% and diarrhea 8% respectively. Fever, cough, fatigue and SOB and in case of co-morbidities only IHD were statistically significant. Mean Oxygen saturation during admission was statistically significantly lower in death group (96.0±1.32 vs 90.2±2.9; p&lt;0.001). Regarding biochemical parameters lymphocyte count (1058.4±289.3 vs 2575.9±536.6 p &lt;0.001), albumin (3.38±0.80 vs 3.89±0.57; p&lt;0.001) were statistically significantly low and N:L ratio (10.48±2.77 vs 3.24±0.40; p&lt;0.001), creatinine (9.75±2.28 vs 6.11±2.27; p&lt;0.001), CRP (33.09±12.99 vs 13.29±5.35; p&lt;0.001), LDH (367.09±78.25 vs 294.06±58.1; p&lt;0.001) were significantly high in death group. Lung abnormalities on CXR PA view showed normal CXR in 48.7% patients in survived group and bilateral GGO in 68.2% in death group which were also statistically significant. Outcome of these admitted patients revealed total death rate 22%, ICU admission rate 18% and discharge from hospital rate was 78%. Logistic regression of these risk factors regarding mortality in COVID19 showed oxygen saturation (p=0.00), N:L ratio (p=0.00), and CRP (p=0.035) were statistically significant. In this study, we found a high mortality rate in COVID 19 positive hospitalized maintenance hemodialysis patients. Markers of inflammation neutrophil-to-lymphocyte ratio (N:L ratio), CRP and oxygen status are significant predictors of COVID 19 patients’ morbidity, highlighting the importance of monitoring these parameters for clinical management and risk stratification. Mugda Med Coll J. 2024; 7(2): 58-65

Real-world interpatient variability in the pharmacokinetics of levetiracetam.

Levetiracetam (LEV) is an antiepileptic drug (AED) used to treat a variety of seizures in adult and pediatric populations. It is an ideal AED due to its favorable pharmacokinetic (PK) and pharmacodynamic profile and lack of interactions with other AEDs. This retrospective cohort study was designed to identify covariates that affect LEV clearance and volume of distribution and to generate a population PK model. Adults with a seizure history receiving LEV during hospital admission with a minimum of one serum LEV concentration available were included in the study. Population PK modeling and covariate testing was performed with MONOLIX Suite 2020R1 (Lixoft, France). A total of 162 serum concentrations were collected from 143 patients. Age, sex, body weight descriptors, serum creatinine, creatinine clearance (CrCL), serum albumin, liver enzymes, and total bilirubin were evaluated. Body surface area (BSA) was a significant covariate for the apparent volume of distribution (V/F). The exclusion of BSA as a covariate of V/F increased the objective function value (OFV) 5.6. CrCL was a significant covariate of apparent plasma clearance (CL/F). The exclusion of CrCL increased the OFV by 18.16 and significantly increased the root square error (RSE) % of the between-subject variabilities of the parameters. LEV clearance is an effective predictor of serum concentration. CrCL was a significant covariate influencing LEV clearance, and BSA was found to influence the volume of distribution. Further studies are needed to determine the effect of body weight descriptors on LEV clearance and, ultimately, outcomes.

Ionized and total magnesium levels and health outcomes in patients with type 2 diabetes mellitus

Magnesium (Mg) is a vital trace element in cellular processes, including glucose metabolism and insulin action. This study aimed to assess the prevalence of dysmagnesemia among patients with type 2 diabetes mellitus (T2DM) and its relationship with glycaemic control and diabetic complications. A cross-sectional study was conducted at Sultan Qaboos University Hospital (SQUH) from August 1, 2023, to April 30, 2024. The study included adult patients with T2DM treated with oral hypoglycemic agents (OHA), insulin, glucagon-like-peptide 1 (GLP-1) injections or their combinations. Both ionized (iMg) and total (tMg) concentrations were measured and the iMg/tMg ratio was calculated. A total of 329 patients with T2DM of which179 females (54.4%), were studied. Hypomagnesemia was observed in 10.0% based on iMg concentrations and 56.2% based on tMg concentrations, while hypermagnesemia was observed in 11.85% (iMg) and 1.82% (tMg). A positive correlation was found between iMg and tMg (r = 0.589, p < 0.01). Hypermagnesemia was associated with higher serum creatinine concentrations (p < 0.01) and lower estimated glomerular filtration rate (eGFR) (p = 0.026). An iMg/tMg ratio above 80% was associated with elevated HbA1c levels, while ratios below 60% were associated with diabetic retinopathy and hypertension. Dysmagnesemia was common among patients with T2DM. The iMg/tMg ratio was associated with diabetic control and presence of complications. The iMg/tMg ratio could be further studied as a potential marker for glycemic control.

Early Escalation to CentriMag for Acute Myocardial Infarction-Induced Out-of-Hospital Cardiac Arrest With Refractory to Extracorporeal Membrane Oxygen Support.

The mortality rate of acute myocardial infarction (AMI)-related refractory cardiogenic shock (rCS) remains high, particularly in patients experiencing cardiac arrest with extracorporeal cardiopulmonary resuscitation (ECPR). This study aimed to evaluate the outcomes of early escalation to CentriMag for AMI-induced out-of-hospital cardiac arrest (OHCA) with ECPR. Patients with AMI-induced OHCA with refractory to ECMO support after ECPR were enrolled. Clinical data were analyzed to identify predictive factors for mortality and survival benefits. Eighty-nine patients were enrolled, of whom 26 underwent CentriMag implantation. The 1-year survival rate for those with the implantation was 34.6%. In contrast, those without implantation showed a survival rate of 7.9%. The average time from the initiation of ECPR to CentriMag implantation was 22.5 ± 14.6 h. The surgical mortality group exhibited a larger body surface area, longer intervals from CPR to ECPR, shorter duration of CentriMag support, and higher preoperative serum creatinine and postoperative day 1 serum aspartate aminotransferase levels. A prolonged interval from CPR to ECPR was identified as an independent risk factor for mortality. Extended duration of CentriMag support was associated with improved survival outcomes. Early CentriMag implantation rescues patients experiencing AMI-related OHCA with rCS and refractory to ECMO support after ECPR. This intervention provides a critical time window, serving as a safe bridge to decision.

A U-shaped non-linear association between serum uric acid levels and the risk of Hashimoto’s thyroiditis: a cross-sectional study

ObjectivePrevious studies have found that the relationship between metabolic indicators and Hashimoto’s thyroiditis (HT) in non-diabetic adults remains unclear. This study aims to explore the association between metabolic indicators and HT, providing new theoretical insights for the clinical management of HT.MethodsClinical data were collected from 2,015 non-diabetic adults at Guangdong Provincial Hospital of Chinese Medicine. The relationship between metabolic indicators and HT was analyzed using SPSS 26.0, R (version 4.2.1), and Zstats.ResultsAmong the 2,015 non-diabetic adult participants included in the study, 1,877 were in the non-HT group, while 138 were in the HT group. Significant differences were observed in metabolic indicators, including serum uric acid (SUA), serum creatinine (SCr), albumin (ALB) and high-density lipoprotein cholesterol (HDL-C), between the two groups, with statistical significance. A binary logistic regression model was established, revealing that SCr had a significant impact in both univariate and multivariate analyses. To further investigate the relationship between metabolic indicators and HT, we conducted a restricted cubic spline (RCS) analysis. The results demonstrated a clear non-linear relationship between SUA and HT, both before and after adjustment (All P &amp;lt; 0.01). Therefore, based on the inflection points derived from the RCS analysis, a segmented logistic regression analysis was performed. The findings indicated a significant association between both low and high levels of SUA and HT (Lower OR: 2.043; 95% CI: 1.405-3.019; P &amp;lt; 0.001; Higher OR: 2.369; 95% CI: 0.998-4.999; P = 0.034).ConclusionThis study is the first to reveal a U-shaped association between SUA levels and the risk of HT, suggesting that maintaining SUA levels within the range of 359.0-540.0 μmol/L may help reduce the risk of HT occurrence. This finding provides a new perspective for early intervention and long-term management of HT, particularly in terms of SUA regulation in HT patients, which holds potential clinical value.

Non-Invasive Biomarkers for Early Diagnosis of Kidney Allograft Dysfunction: Current and Future Applications in the Era of Precision Medicine

Kidney transplantation stands as the preferred treatment for end-stage kidney disease, significantly improving both the quality and longevity of life compared to dialysis. In recent years, the survival rates for patients and grafts have markedly increased thanks to innovative strategies in desensitization protocols for incompatible transplants and advancements in immunosuppressive therapies. For kidney transplant recipients, preventing allograft rejection is of paramount importance, necessitating the use of immunosuppressive medications. Regular follow-up appointments are essential, as monitoring the function of the kidney allograft is critical. Currently, established biomarkers such as serum creatinine, estimated Glomerular Filtration Rate (eGFR), proteinuria, and albuminuria are commonly employed to assess allograft function. However, these biomarkers have limitations, as elevated levels often indicate significant allograft damage only after it has occurred, thereby constraining treatment options and the potential for restoring graft function. Additionally, kidney biopsies, while considered the gold standard for diagnosing rejection, are invasive and carry associated risks. Consequently, the identification and development of new, sensitive, and specific biomarkers like dd-cfDNA, microRNAs (e.g., miR-21, miR-155), and sCD30 for allograft rejection are crucial. To tackle this challenge, intensive ongoing research employing cutting-edge technologies, including “omics” approaches, like genomic techniques, proteomics, or metabolomics, is uncovering a variety of promising new biomarkers.

Serum uric acid/creatinine ratio and 1-year stroke recurrence in patient with acute ischemic stroke and abnormal renal function: results from the Xi'an stroke registry study of China

BackgroundThe relationship between abnormal renal function and serum uric acid levels in patients with acute ischemic stroke (AIS) remains insufficiently explored. Although uric acid is associated with cardiovascular and cerebrovascular risk, the specific link between normalized serum uric acid (SUA/SCr) and stroke recurrence in patients with impaired renal function has not been well studied. This study aims to fill this gap by investigating the association between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function.MethodsThis study utilized the ratio of serum uric acid (SUA) to serum creatinine (SCr) to represent SUA levels normalized for renal function. Abnormal Renal function was defined by the estimated glomerular filtration rate (eGFR) &amp;lt; 90 mL/min/1.73 m2. Multivariable Cox regression, curve fitting, and stratified analyses were employed to assess the relationship between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function, considering SUA/SCr as both a continuous variable and in quartiles (Q1–Q4).ResultsOf 1,932 enrolled patients (65.3% male; mean age 66.7 ± 11.3 years), each unit of increase in SUA/SCr was associated with a 17% decrease in 1-year stroke recurrence (HR = 0.83, 95% CI 0.73 to 0.96, P = 0.009). Compared to Q1, the Q2 and Q4 groups showed significantly reduced risk in 1-year stroke recurrence (Q2: HR = 0.46, 95% CI 0.27 to 0.79, P = 0.005; Q4: HR = 0.47, 95% CI 0.27 to 0.81, P = 0.007), with a significant trend across all quartiles (P = 0.01 for trend tests). Curve fitting revealed a negative but non-linear correlation. Subgroup analyses showed that in patients with eGFR &amp;lt; 60 ml/min/1.73 m2, Q4 had significantly lower 1-year stroke recurrence risk than Q1 (HR = 0.19, 95% CI 0.04 to 0.86, P = 0.031).ConclusionLow SUA/SCr independently predicts 1-year stroke recurrence in patients with AIS and abnormal renal function, particularly in those with eGFR &amp;lt; 60 mL/min/1.73 m2.

Analysis of outcomes in adult deceased donor dual kidney transplantation

Objective: To investigate the efficacy of dual kidney transplantation (DKT) from adult donors. Methods: Clinical data of adult DKT donors and recipients in the Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2015 to June 2024 were retrospectively analyzed. The patients were followed up until September 2024. The clinical data of donor and recipient, donor kidney, surgical techniques, complications, and follow-up were collected. Transplant renal function and recipient/graft survival rates within 5 years were analyzed. Results: A total of 102 pairs of DKT donors and recipients were included. Among the donors, 83 were male and 19 were female, with age of (57.8±11.1) years and body mass index (BMI) of (23.1±3.2) kg/m². Among the recipients, 95 were male and 7 were female, with age of (42.0±11.0) years and BMI of (22.1±3.1) kg/m². The postoperative hospitalization and follow-up duration [M (Q1, Q3)] for recipients were [20.0 (15.0, 27.0)] days and [30.0 (12.5, 49.0)] months, respectively. China Class Ⅱ donation accounted for 64.7% (66/102) of donor categories. The pre-procurement serum creatinine (Scr) level of donors was [97.0 (66.5, 144.5)] μmol/L, and the hypothermic machine perfusion utilization rate was 52% (53/102). The warm ischemia time was (5.5±1.7) minutes, and the mean cold ischemia time was (8.7±3.8) hours. The Remuzzi scores for the left and right kidneys before transplantation were (4.8±1.3) and (5.1±1.4) scores, respectively. The glomerulosclerosis rates for the left and right kidneys were 34.0%±16.2% and 35.3%±16.7%, respectively. The primary nephropathy was unknown in 80.3% (82/102) of recipients, and IgA nephropathy was diagnosed in 8.8% (9/102) of the recipients. Bilateral kidneys were implanted ipsilaterally in 94.1% (96/102) of recipients, with operative time of (5.3±1.4) hours. Lymphocyte-depleting induction therapy was administered to 74.5% (76/102) of recipients. One recipient experienced primary graft non-function after surgery. The incidences of delayed graft function and rejection were 30.4% (31/102) and 9.8% (10/102), respectively. The overall incidence of surgical complications was 10.8% (11/102). The 1, 3, and 5-year recipient survival rates were 100.0%, 98.3%, and 98.3%, respectively. The 1, 3, and 6-month and 1, 3, and 5-year graft survival rates were 97.1%, 96.1%, 95.0%, and 94.0%, 89.3%, 85.6%, respectively. The recipient's kidney function remains stable for 5 years after transplantation. At 5 years, the recipient median Scr level and mean estimated glomerular filtration rate (eGFR) were 153.0 (120.0, 232.0) μmol/L and (42.1±17.1) ml-1·min-1·(1.73 m²)-1, respectively. Conclusion: Adult donor DKT demonstrates favorable short-term and 5-year clinical efficacy.

Endovascular Aortic Aneurysm Repair for Abdominal Aortic Aneurysm With Type V Horseshoe Kidney.

Abdominal aortic aneurysm (AAA) with concomitant Horseshoe kidney (HSK) is rare. When open surgery is not feasible, preserving the renal isthmus artery (RIA) during endovascular treatment presents a challenge. A 70-year-old male presented with a 57.8 mm × 54.3 mm AAA and type V HSK perfused by a 4.4 mm RIA from the inferior mesenteric artery and a 4.6 mm RIA from the aortic bifurcation. This case report describes an endovascular aortic aneurysm repair (EVAR) performed on an AAA coexisting with a type V HSK. One-year follow-up: the AAA had regressed, and the HSK remained perfused without any endoleak or increase in serum creatinine levels. The utilization of EVAR offers a feasible option for AAA combined with type V HSK, particularly in cases of high surgical risk. In Abdominal aortic aneurysm (AAA) with type V horseshoe kidney (HSK), preserving renal isthmus arteries (RIAs) is critical when they provide a substantial portion of the HSK blood supply.When open surgery is not feasible, preserving the RIA during endovascular treatment presents a challenge.The use of EVAR, incorporating a periscope stent and embolization, provides a viable treatment option for patients with AAA and type V HSK, especially in high surgical risk cases.

ZBiotics ameliorates T2DM-induced histopathological damage in liver, kidney and adipose tissues by modulating the NOD-like receptor signaling in Wistar rats.

Probiotics serve as promising candidates in type 2 diabetes mellitus (T2DM) therapy. Not only they presumably reduce the T2DM prevalence, but also keep down its complications. In the present study, we explored the beneficial impact of ZBiotics, an engineered probiotic, on T2DM Wistar rats. In silico analysis was performed to construct a genetic-epigenetic network linked to STING-NOD pathway and autophagy signaling. Then, 30 Wistar rats were divided into 5 groups (each n = 6); normal group, diabetic model, B. subtilis, and ZBiotics treated rats at high and low doses. Experimental procedures were carried out including biochemical and histopathologic analyses. Samples were extracted from rats' blood, liver, kidney and adipose tissues. At the molecular aspect, the molecular players, chosen by the in silico analysis, were assessed using 2-ΔΔCt to estimate their relative quantification. With immunohistochemistry, TNF-alpha and LC3B were assessed as reflectors for inflammation and autophagy respectively. ZBiotics was reported to ameliorate the T2DM-induced histological damage. Besides, it downregulated TNF-alpha and upregulated LC3B expression levels. At the biochemical aspect, ZBiotics corrected LDL-c and improved serum creatinine and CK-MB levels. Inflammation relevant genes have been downregulated regarding CHUK, NFKB1 and miR-611. Therefore, ZBiotics is speculated to operate by modulating the genetic-epigenetic network linked to inflammatory cGAS-STING and autophagy signaling. ZBiotics is recommended for clinical trials as a separate candidate or as an adjuvant to the conventional T2DM therapy.

Enhanced therapeutic effects of hypoxia-preconditioned mesenchymal stromal cell-derived extracellular vesicles in renal ischemic injury

BackgroundExtracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been shown to provide significant protection against renal ischemia–reperfusion injury (IRI). Hypoxia has emerged as a promising strategy to enhance the tissue repair capabilities of MSCs. However, the specific effects of hypoxia on MSCs and MSC-EVs, as well as their therapeutic potential in renal IRI, remain unclear. In this study, we investigated the alterations occurring in MSCs and the production of MSC-EVs following hypoxia pre-treatment, and further explored the key intrinsic mechanisms underlying the therapeutic effects of hypoxic MSC-EVs in the treatment of renal IRI.MethodsHuman umbilical cord MSCs were cultured under normoxic and hypoxic conditions. Proliferation and related pathways were measured, and RNA sequencing was used to detect changes in the transcriptional profile. MSC-EVs from both normoxic and hypoxic conditions were isolated and characterized. In vivo, the localization and therapeutic effects of MSC-EVs were assessed in a rat renal IRI model. Histological examinations were conducted to evaluate the structure, proliferation, and apoptosis of IRI kidney tissue respectively. Renal function was assessed by measuring serum creatinine and blood urea nitrogen levels. In vitro, the therapeutic potential of MSC-EVs were measured in renal tubular epithelial cells injured by antimycin A. Protein sequencing analysis of hypoxic MSC-EVs was performed, and the depletion of Glutathione S-Transferase Omega 1 (GSTO1) in hypoxic MSC-EVs was carried out to verify its key role in alleviating renal injury.ResultsHypoxia alters MSCs transcriptional profile, promotes their proliferation, and increases the production of EVs. Hypoxia-pretreated MSC-EVs demonstrated a superior ability to mitigate renal IRI, enhancing proliferation and reducing apoptosis of renal tubular epithelial cells both in vivo and in vitro. Protein profiling of the EVs revealed an accumulation of numerous anti-oxidative stress proteins, with GSTO1 being particularly prominent. Knockdown of GSTO1 significantly reduced the antioxidant and therapeutic effects on renal IRI of hypoxic MSC-EVs.ConclusionsHypoxia significantly promotes the generation of MSC-EVs and enhances their therapeutic effects on renal IRI. The antioxidant stress effect induced by GSTO1 is identified as one of the most critical underlying mechanisms. Our findings highlight that hypoxia-pretreated MSC-EVs represent a novel and promising therapeutic strategy for renal IRI.Graphical

Yiqi Juanshen decoction alleviates renal interstitial fibrosis by targeting the LOXL2/PI3K/AKT pathway to suppress EMT and inflammation

Chronic kidney disease (CKD) is a major health concern, with renal interstitial fibrosis (RIF) as a key feature. Effective management of RIF is crucial for treating CKD. Yiqi Juanshen decoction (YQJSD), as traditional Chinese medicine, has shown promising results in CKD treatment. This study evaluates YQJSD’s effectiveness in ameliorating RIF and explores the underlying molecular mechanisms using the unilateral ureteral obstruction (UUO) model. YQJSD has been shown to effectively reduce serum creatinine and blood urea nitrogen levels, decrease extracellular matrix deposition, and down-regulate the expression of α-SMA, COL4α1, Fibronectin (FN). Mechanistically, YQJSD exerts its effects by modulating multiple pathways: it inhibits the NF-κB signaling pathway, inhibiting the expression of pro-inflammatory cytokines like NF-κB1, IL-1β, TNF-α, and CCR1. Simultaneously, YQJSD suppresses the epithelial-mesenchymal transition (EMT) by downregulating the expression of Snail1, Vimentin, Twist1, and FSP1, while increasing E-cadherin expression. Moreover, YQJSD can regulate the PI3K/AKT signaling pathway by decreasing the expression of LOXL2 and PIK3R1, along with p-AKT1/2/3. This modulation of the LOXL2/PI3K/AKT pathway contributes to the inhibition of both EMT and inflammation, highlighting a critical role in the therapeutic intervention against RIF. These findings suggest that YQJSD may serve as a promising therapeutic management of RIF in CKD patients.