INTRODUCTION:To explore the risk factors of in-hospital death in patients with severe acute kidney injury (AKI) after continuous renal replacement therapy (CRRT) and to build a prediction model. METHODS:In total, 378 patients with AKI were treated in the ICU of affiliated hospital of Fujian Medical University, Zhangzhou City, between June 2018 and August 2024. All patients received CRRT. According to prognosis, patients were divided into the survivor and mortality groups. The clinical data from both groups were compared. A nomogram prediction model was developed based on independent risk factors identified through multivariable logistic regression analysis. RESULTS:Overall, 195 patients (51.59%) died in the hospital. Compared with the Acute Physiology and Chronic Health Evaluation II (APACHE II), the mortality group had significantly higher Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, mechanical ventilation rates, lactic acid levels, SCr at baseline, the last recorded SCr before death or discharge, duration of anuria before CRRT, total duration of RRT, and ICU stay, while initial and final eGFR were significantly lower (all, P < .05). Multivariable logistic regression analysis showed that APACHE Ⅱ score, SOFA score, duration of anuria before CRRT, and total duration of RRT were independent risk factors for hospital death in AKI (P < .05), while initial higher eGFR was a protective factor (P < .05). The consistency index (C-index) of the nomogram model was 0.751 (95%CI: 0.683~0.819), and the AUC of the ROC curve was 0.738 (95%CI: 0.701~0.775), which had good discrimination. The evaluation results of the calibration curve and clinical decision curve suggested that the model was accurate and effective. CONCLUSION:The APACHE II score, SOFA score, anuria duration before CRRT, and total RRT time were independently associated with in-hospital mortality of AKI patients treated with CRRT. These findings demonstrate the severity markers of AKI; nevertheless, prospective validation will remain necessary.
INTRODUCTION:IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. The Oxford classification (MEST-C) a standardized histopathological scoring system evaluating mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), interstitial fibrosis/tubular atrophy (T), and cellular or fibrocellular crescents (C), provides a histopathological framework to predict disease progression. However, the role of immune cell infiltration-particularly CD68+ macrophages-in these pathological features remains underexplored. OBJECTIVE:To investigate the association between renal CD68+ macrophage infiltration and the Oxford classification parameters in patients with IgA nephropathy. METHODS:This study included 146 patients with biopsy-proven IgAN at Hasheminejad Kidney Center between 2013 and 2020. Immunohistochemical staining for CD68 was performed on paraffin-embedded kidney biopsy sections. CD68+ macrophages were quantified separately in the glomerular and interstitial compartments. Finally, the associations between macrophage counts and Oxford classification components (M, E, S, T, C) were analyzed. RESULTS:Glomerular CD68+ cell counts were significantly higher in samples with M1, E1, T1, and C1 lesions (P < .05). Interstitial CD68+ cells were significantly elevated in T1 lesions (mean: 10.6 vs. 4.7 in T0; P < .001). Receiver operating characteristic (ROC) analysis demonstrated high diagnostic accuracy for interstitial CD68+ cells in predicting T1 (AUC = 0.98) and for glomerular CD68⁺ macrophage in predicting E1 (AUC = 0.88). CONCLUSION:CD68+ macrophage infiltration is closely associated with active and chronic lesions in IgAN, particularly endocapillary hypercellularity and tubular atrophy. Quantification of CD68+ macrophage may serve as a valuable histological marker for assessing disease activity and guiding prognosis in IgAN.
Granulomatosis with polyangiitis (GPA) is an uncommon vasculitis affecting small- and medium-sized vessels, predominantly in adults (average age approximately 45 years) and infrequently in children. It can involve multiple organ systems. In patients with end-stage kidney disease (ESKD) due to GPA, disease activity is often tends to wane after the commencement of dialysis. We report a 12-year-old girl with ESKD due to GPA who presented with severe gastrointestinal (GI) bleeding and profound anemia, owing to diffuse microaneurysms in the small bowel (particularly the ileum) and colon-an exceedingly rare manifestation. She responded dramatically to induction therapy comprising methylprednisolone pulse, plasmapheresis, rituximab followed by maintenance therapy with prednisolone and mycophenolate mofetil. This case highlights that while the recurrence risk of ANCA-associated vasculitis in dialysis patients is low, the possibility remains and may present with atypical extrarenal involvement. Given the elevated risk of infection with immunosuppression in ESKD patients, maintenance immunosuppressive therapy may be discontinued in the absence of extrarenal disease-but this decision necessitates careful consideration.
INTRODUCTION:Melatonin plays a crucial role in regulating sleep and has potent antioxidant properties. However, the relationship between melatonin supplementation and metabolic factors related to diabetes and lipid profiles-which are associated with increased mortality in kidney transplant recipients has not yet been fully clarified. METHODS:This randomized, double-blind, placebo-controlled trial was conducted at Labbafinejad Hospital, Tehran, Iran. Adult kidney transplant recipients (≥6 months post-transplant) received either 6 mg/day melatonin or placebo for three months. A modified intention-to-treat analysis included 42 patients per group. The primary outcomes were changes in fasting blood sugar (FBS) and HbA1c levels, while secondary outcomes included blood pressure and lipid profile parameters. Between-group effects were estimated using linear regression adjusted for baseline values and confounders. RESULTS:In the melatonin group, FBS decreased by a median of 6.5 mg/dL (P < .001) and HbA1c by 0.25 units (P < .001), whereas both parameters increased in the placebo group. The adjusted between-group effect favored melatonin for HbA1c (β = -0.30%; 95% CI: -0.59 to -0.01; P < .001) but not for FBS (β = -2.61 mg/dL; 95% CI: -17.93 to 12.71; P = .283). Triglyceride levels decreased by 16 mg/dL in the melatonin group compared with an increase of 13.5 mg/dL in the placebo group (adjusted β = -23.77 mg/dL; 95% CI: -45.50 to -2.04; P = .032). No significant differences were observed in blood pressure and renal function. CONCLUSION:Melatonin supplementation for three months modestly improved glycemic control and lowered serum triglyceride levels in kidney transplant recipients, with no effects on blood pressure or kidney function. These results support melatonin's potential as an adjunct therapy for metabolic dysregulation in this population, warranting further investigation into its long-term benefits.
INTRODUCTION:This systematic review aimed to evaluate the impact of dapagliflozin therapy on the progression of chronic kidney disease (CKD) in individuals with CKD. METHODS:A comprehensive search for randomized controlled trials (RCTs) concerning dapagliflozin was conducted across multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov, and Google Scholar, from their inception until January 10, 2025. Of 2,806 identified studies, 15 trials met the inclusion criteria. Upon careful assessment to avoid overlapping populations, 11 publications derived from the Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) parent trial were excluded, leaving four unique independent trials for narrative synthesis. Due to substantial heterogeneity (I² > 90%) and the limited number of studies, meta-analysis was not performed and findings are presented narratively. RESULTS:A total of 15 articles were identified, 11 were secondary analyses of the DAPA-CKD trial (NCT03036150) reporting on the same 4,304 participants. Following exclusion of overlapping publications, four unique trials remained. The findings for eGFR decline were highly variable across studies, ranging from a mean difference of -6.60 mL/min/1.73m² (Cherney et al., 2020) to +0.93 mL/min/1.73m² (Heerspink et al., 2020). Substantial heterogeneity (I² = 93.7%) precluded meaningful meta-analysis. For composite renal outcomes, only one unique trial reported this outcome, preventing quantitative synthesis. CONCLUSION:While the effect of Dapagliflozin on eGFR decline was inconclusive due to substantial heterogeneity, the available evidence from the DAPA-CKD trial suggests a reduction in the risk of adverse clinical renal outcomes. However, the limited number of independent trials and considerable heterogeneity underscore the need for more standardized RCTs. Overall, dapagliflozin appears to confer renal protective benefits and is considered safe for patients with CKD.
INTRODUCTION:High-grade vesicoureteral reflux (VUR) in infants with febrile urinary tract infections is linked to a heightened risk of renal scarring. Identifying risk factors for high-grade vesicoureteral reflux could enable more selective use of voiding cystourethrography, thereby reducing unnecessary invasive procedures. This study aimed to determine the independent risk factors of high-grade vesicoureteral reflux in children ≤ two years with febrile urinary tract infections. METHODS:According to the defined sample size, a total of 223 children aged two years or younger were referred to the nephrology clinic of Dr.Sheikh children's hospital affiliated to Mashhad University of Medical Sciences from March 2006 to August 2023, meeting the inclusion criteria. Participants who underwent both kidney ultrasound and voiding cystourethrography (VCUG) were included in the analysis. Univariable and multivariable logistic regression tests were utilized to identify independent risk factors of high-grade VUR. RESULTS:Of 223 children included in the study, 180 were girls (80.7%). The median age at the presentation was 8.5 months. High-grade vesicoureteral reflux was identified in 23.8%. The univariable analysis revealed that male sex, abnormal renal ultrasound, hydronephrosis, prenatal hydronephrosis, and infections with non- E.coli as potential risk factors. In the multivariable analysis, male sex (OR = 4.41, P < .001), abnormal renal ultrasound (OR = 3.35, P < .001), hydronephrosis (OR = 5.69, P < .001), and prenatal hydronephrosis (OR = 6.31, P = .004) were confirmed independent risk factors . CONCLUSION:Male sex, abnormal kidney ultrasound, hydronephrosis, and prenatal hydronephrosis are independent risk factors of high-grade vesicoureteral reflux in children aged ≤2 years with febrile urinary tract infections.
INTRODUCTION:End-stage kidney disease (ESKD) is a growing global public health problem, and patients undergoing hemodialysis (HD) experience a high mortality rate despite advances in medical care. Identifying reliable prognostic biomarkers is therefore essential. Regression-based survival models are widely used in HD studies; however, while they estimate associations, they do not directly quantify the predictive accuracy of biomarkers. This study aimed to evaluate the predictive performance of selected baseline biomarkers for survival in HD patients using the time-dependent receiver operating characteristic (ROC) curve. METHODS:This retrospective cohort study included 2,192 ESKD patients undergoing maintenance HD in Fars province, Iran, between 2011 and 2020. Time-dependent area under the ROC curve (AUC) values were calculated to assess the prognostic performance of baseline biomarkers at 3, 12, 24, and 36 months after initiation of dialysis. RESULTS:Age, serum albumin, creatinine, and calcium showed relatively better predictive performance for survival. For age, the AUCs at 3, 12, 24, and 36 months were 64.2, 57.1, 57.1, and 58.8, respectively, while corresponding values for serum albumin were 67.5, 62.3, 61.4, and 59.8. Serum albumin and calcium demonstrated higher discrimination for early survival, whereas serum creatinine showed more stable predictive performance over the follow-up period. The combined risk score outperformed individual biomarkers, with AUCs of 71.2, 63.9, 63.5, and 64.1 at 3, 12, 24, and 36 months, respectively. CONCLUSION:Time-dependent ROC analysis revealed time-varying prognostic performance of baseline biomarkers in HD patients and demonstrated improved discrimination when biomarkers were combined into a composite risk score.
INTRODUCTION:Oxidative stress is a key contributor to acute kidney injury (AKI), a condition exacerbated by nephrotoxic agents like carbon tetrachloride (CCl₄). Humulus lupulus L. (hops), which is rich in polyphenols, exhibits potent antioxidant properties. This study evaluated the nephroprotective effects of Humulus lupulus L. extract on CCl₄-induced AKI in rats. METHODS:Twenty-four male Wistar rats were divided into four groups (n = 6): normal control, CCl₄ control, and two treatment groups receiving Humulus lupulus extract (100 or 200 mg/kg/day, intraperitoneally) for 14 days. On day 14, all groups except the normal control received CCl₄ (1 mL/kg, 1:1 v/v in olive oil, intraperitoneally). Forty-eight hours post-CCl₄ administration, serum and renal tissue samples were collected to assess biochemical markers (urea, creatinine, uric acid), oxidative stress parameters (malondialdehyde [MDA], total antioxidant capacity [TAC], catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx]), and histopathological changes. RESULTS:CCl₄ significantly increased serum urea, creatinine, uric acid, and renal MDA levels while decreasing TAC, CAT, SOD, and GPx activities. Pretreatment with Humulus lupulus extract significantly attenuated these alterations, with the 200 mg/kg dose demonstrating superior efficacy. Histopathological analysis revealed reduced tubular and glomerular damage in treated groups. CONCLUSION:Humulus lupulus extract attenuated CCl4-induced nephrotoxicity in rats by enhancing antioxidant defenses. These preclinical findings suggest that hops extract warrants further investigation as a potential candidate for mitigating oxidative stress in AKI.
Relapsing polychondritis (RP) is a rare autoimmune disorder with minimal reported renal involvement. We describe the first case of tip lesion variant of focal segmental glomerulosclerosis (FSGS) in a 60-year-old male with familial RP. The patient initially presented with nephrotic syndrome concomitant with RP, which was diagnosed 17 years ago; renal biopsy revealed minimal change disease at that time. Over the subsequent 17 years, he experienced four RP flares without nephrotic syndrome recurrence until his recent presentation with severe nephrotic syndrome. Repeated renal biopsy confirmed tip lesion variant of FSGS, demonstrating excellent response to corticosteroid therapy with prednisolone 1 mg/kg/day; proteinuria declined from 7g/24h to 0.98g/24h and serum albumin increased from 0.9g/dL to 2.2g/dL within three months. This case underscores the importance of considering FSGS in RP-associated nephrotic syndrome and suggests potential shared immune/genetic mechanisms. To our knowledge, this represents both the first report of tip lesion FSGS in RP and the first documented familial RP case with FSGS development.
INTRODUCTION:Coronavirus Disease 2019 (COVID-19) affected the entire world. While the effects on the lungs are more pronounced, the kidneys are also susceptible, and there is a potential risk of acute kidney injury (AKI) among COVID-19 patients. This study aimed to evaluate the incidence, clinical characteristics, and outcomes of AKI in patients hospitalized with COVID-19. METHODS:This study analyzed the incidence, characteristics, and outcomes of AKI in hospitalized patients with COVID-19. Medical records of 755 COVID-19 patients with AKI and 4647 patients without kidney injury admitted between March 2020 and July 2022 were analyzed at Karabuk Training and Research Hospital. We recorded patients' demographic information, length of stay, laboratory results, and the necessity for renal replacement therapy. AKI staging was based on initial and peak values of renal parameters such as serum. RESULTS:The results indicated a high incidence of AKI in COVID-19patients, particularly in those requiring intensive care units (ICU), where mortality rates were significantly high. The findings revealed that patients with AKI, especially those requiring hemodialysis (n = 110, 49.32%), had lower rates of recovery and discharge (n = 633, 83.84%), and significantly higher mortality rates compared to those without AKI (P = .032). The mortality rate in patients requiring hemodialysis was 33.64%, underscoring the severity of AKI and the high mortality risk associated with cases necessitating hemodialysis. CONCLUSION:The development of AKI in COVID-19 patients is associated with a significant increase in mortality risk, indicating the need for further detailed investigations to better understand this condition.
INTRODUCTION:Hemodialysis patients experience significantly lower quality of life compared to the healthy individuals, largely due to symptoms such as bone pain, fatigue, pruritus, anorexia, inflammation, malnutrition, and anemia. This study aimed to investigate the effects of sarcopenia and low muscle mass on quality of life, with a particular focus on physical health indices. METHODS:The study included 62 patients on maintenance hemodialysis. Sarcopenia was diagnosed using the fat-free mass index (FFMI), defined as skeletal muscle mass divided by height squared (kg/m²). Additionally, skeletal muscle mass was normalized to body surface area (BSA); values below the sample mean of 46.12 kg/m² were classified as low muscle mass. Quality of life was assessed with the Kidney Disease Quality of Life (KDQOL) Version 1.3 questionnaire and scored using the KDQOL-SF™ Version 1.3 Scoring Program. RESULTS:Sarcopenia was present in 18 patients (29%) according to FFMI. Patients scored lowest in general health (35.6), energy/fatigue (40.9), and both SF-12 physical (37.5) and mental health (37.2) domains. Sarcopenic patients reported significantly higher pain scores (60.97 ± 29.54 vs. 46.19 ± 27.37; P = .046), but other domains did not differ. Patients with low muscle mass/BSA (kg/m2) had lower sleep (51.5 ± 11.7 vs. 59.6 ± 13.0; P = .01), energy/fatigue (35.6 ± 20.1 vs. 52.8 ± 20.7; P = .005), and SF-12 physical health scores (35.7 ± 9.0 vs. 40.6 ± 8.3; P = .03). Muscle mass indexed to BSA was an independent predictor of the SF-12 physical health composite score. CONCLUSION:Low muscle mass, particularly when indexed to BSA, is associated with reduced physical health in hemodialysis patients and poorer quality of life across multiple domains. BSA-indexed muscle mass showed stronger and more consistent associations than FFMI-based definitions.
INTRODUCTION:Diazinon (DZN) is a widely used pesticide applied in agriculture to eliminate pests, but it can cause adverse effects on various organs. This study investigated the nephrotoxic changes and oxidative stress induced by diazinon, as well as the potential protective role of garlic in ameliorating kidney toxicity in male Wistar rats. METHODS:The animals were treated with diazinon (DZN; 70 mg/ kg/day, orally) with or without garlic extract (500 mg/kg, orally) for four consecutive weeks. Biomarkers including malondialdehyde (MDA), total antioxidant capacity (TAC), catalase (CAT), superoxide dismutase (SOD), and total thiol molecules were measured to evaluate oxidative stress. In addition, kidney histopathology was examined using the hematoxylin and eosin (H&E) staining. RESULTS AND CONCLUSION:As expected, DZN significantly increased MDA levels while decreased the levels of CAT, SOD, TAC, and total thiol molecules in kidney tissue. Co-treatment with garlic reversed the oxidative stress status. Moreover, garlic ameliorated the kidney histopathological injuries induced by DZN. Our findings suggest that garlic can be considered a safe and effective agent for mitigating DZN-induced nephrotoxicity.
INTRODUCTION:Occult kidney disease (OKD), a term that describes the initial phase of renal failure, is usually overlooked in routine clinical evaluations. Therefore, the goal of this study was to determine whether OKD is associated with the disease severity and mortality in COVID-19 patients. METHODS:A retrospective study was conducted in patients with COVID-19. COVID-19 was considered based on a positive reverse transcriptase-polymerase chain reaction test for SARS-CoV-2. OKD was defined with an estimated glomerular filtration rate < 60 ml/min/1.73 m2 and creatinine concentrations ≤1.3 mg/dl. RESULTS:A total of 809 patients with COVID-19 were selected for the study. The frequency of OKD, acute kidney injury, and chronic kidney disease was 7.7%, 15.0%, and 12.4%, respectively. The logistic regression analysis adjusted showed that OKD (OR = 1.86; CI 95%: 1.05-3.32), acute kidney injury (OR = 2.03; CI 95%: 1.42-2.89), and chronic kidney disease (OR = 3.07; CI 95%: 1.90-4.97) were associated with mortality by COVID-19. CONCLUSION:Our results indicate that OKD is associated with increased mortality in patients with COVID-19.
INTRODUCTION:Chronic Kidney Disease (CKD) is associated with high 30-day hospital readmission rates due to progressive renal dysfunction, multiple comorbidities, and complications related to dialysis and catheter use. Artificial Intelligence (AI) and Machine Learning (ML) offer promising tools for early identification of high-risk patients. To develop and evaluate ML models for predicting 30-day hospital readmission among CKD patients and identify key clinical and laboratory predictors related to readmission risk. METHODS:This retrospective study analyzed 277 hospitalized patients with CKD at Hasheminejad Kidney Center (2019-2022). Forty-four demographic, clinical, and laboratory features were included. Preprocessing included handling missing data, normalization, outlier removal, categorical encoding, and oversampling. Six ML models, including eXtreme Gradient Boosting (XGBoost), Random Forest, Decision Tree, AdaBoost, Multilayer Perceptron (MLP), and Logistic Regression, were trained using a 70/30 train-test split with cross-validation. Feature selection employed SHAP values, mutual information, F-values, SVM, and chi-squared tests. RESULTS:XGBoost outperformed other models (accuracy > 90%). The strongest predictors were estimated Glomerular Filtration Rate (eGFR), Blood Urea Nitrogen (BUN) and creatinine levels, age, presence of diabetes mellitus and hypertension, catheter-related infection, and triglycerides, intact Parathyroid hormone (iPTH), and albumin levels. Catheter infection emerged as a modifiable, high-impact predictor. The SHAP values analysis confirmed strong contributions of kidney function markers, inflammatory indicators, and metabolic variables to re-admission risk. CONCLUSION:ML-based prediction models, particularly XGBoost, demonstrated high accuracy in identifying CKD patients at risk of 30-day readmission. Integration of these models into clinical workflows may improve early intervention, reduce hospital readmissions, and support evidence-based nephrology care.
INTRODUCTION:In studies involving hemodialysis patients, repeated laboratory measurements (longitudinal data) and survival outcomes are often analyzed separately, which can lead to biased results due to ignoring measurement errors and the intrinsic dependency between the two analyses. Joint modeling has emerged as a powerful approach to handle such data. This study aims to investigate the impact of six time-varying biochemical markers, along with baseline covariates, on the survival of hemodialysis patients using a multivariate joint model. METHODS:A longitudinal cohort of 894 maintenance hemodialysis (MHD) patients, who had started dialysis between 2004 and 2023, were included. Baseline and follow-up clinical information and monthly laboratory measurements were analyzed. A multivariate linear mixed-effects model was jointly fitted with a Cox proportional hazards model to simultaneously assess the longitudinal biomarkers and time-to-event data. Analyses were performed using R software. RESULTS:The model indicated that older age (Hazard Ratio, HR = 1.02, P < .001), male gender (HR = 1.72, P < .001), diabetes mellitus (HR = 1.61, P < .001), walking disability at admission (HR = 1.78, P < .001), and catheter-based vascular access (HR = 1.71, P < .001) were significantly associated with an increased risk of mortality. Higher square root of phosphate levels (HR = 13.97, P < .001) were linked to increased, and higher square root of creatinine (HR = 0.32, P < .001), hemoglobin (HR = 0.75, P = .009) and albumin (HR = 0.31, P < .001) levels were associated with decreased mortality. CONCLUSION:Findings of the joint model confirm the importance of baseline clinical risk factors and modifiable biochemical markers on the survival outcomes of hemodialysis patients.
INTRODUCTION:Chronic kidney disease (CKD) is an important public health problem that is increasingly prevalent in Türkiye and the world. Patients with CKD should be informed about renal replacement therapy (RRT) before progression to end-stage kidney disease, and the most appropriate therapy should be selected for each patient. Although three different renal replacement therapy modalities exists, hemodialysis appears to be the most commonly chosen. In this study, we aimed to investigate why hemodialysis is often selected as the first-line therapy by patients. Methods. In this cross-sectional, survey study; patients aged 18-80, who had been receiving treatment for more than three months and had initiated hemodialysis as their first RRT between 2010 and 2020 in Kahramanmaras, Kocaeli, and Istanbul were included. Patients completed a self-administered multiple-choice questionnarire. RESULTS:A total of 1908 patients were included in the study. Before initiating hemodialysis, 61.1% of patients were under nephrology follow-up, whereas 38.3% had no prior follow-up. Alternative therapies to hemodialysis (peritoneal dialysis and kidney transplantation) were explained to 720 patients (37.7%), but not to 1,159 patients (60.7%). A total of 635 patients (33.3%) were asked about their treatment preferences, while 66% were not. After hemodialysis initiation, 937 patients (49.1%) were listed for cadaveric kidney transplantation, wheras 49.5% were not. CONCLUSION:Our study is a large, cross-sectional investigation of 1908 patients who selected hemodialysis as their initial RRT. The reasons patients choose hemodialysis over other modalities have long been debated, and substantial knowledge gaps among patients have been identified. We believe that nephrologist follow-up and patient information are important in choosing renal replacement therapy.
Introduction. Rapamycin, also referred to as Sirolimus, is an immunosuppressive medication used in kidney transplantation to prevent organ rejection. Sirolimus is metabolized predominantly by the enzymes CYP3A4 and CYP3A5. The objective of this study was to evaluate the distribution of CYP3A4*1/*1B (rs2740574, -392A > G) and CYP3A5*1/*3 (rs776746, 6986A > G) genetic variants in renal transplant recipients treated with Sirolimus in Urmia (Iran). Methods. This assessment involved thirty-nine renal transplant recipients in Urmia Imam Khomeini University Hospital, Urmia (Iran) who were treated with a daily dose of 1mg/day Sirolimus. The CYP3A4*1/*1B and CYP3A5*1/*3 allelic variants were identified using the Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR) technique. Results. The frequencies of CYP3A4 *1/*1 (-392AA), CYP3A4 *1/*1B (-392AG), and CYP3A4 *1B/*1B (-392GG) genotypes and CYP3A4 *1 (-392A) and CYP3A4 *1B (-392G) alleles were 37(94.87%), 2(5.13%), 0(0%), 76(97%), and 2(3%), respectively. The genotypic distribution for CYP3A5 was 0(0%) for CYP3A5*1/*1 (6986AA), 6(15.38%) for CYP3A5*1/*3 (6986AG), and 33(84.62%) for CYP3A5*3/*3 (6986GG). The allelic frequencies were 6(8%) for CYP3A5*1 (6986A) and 72(92%) for CYP3A5*3 (6986G). Only one patient with CYP3A4.
INTRODUCTION:Chronic kidney disease (CKD) is a progressive condition with complex genetic and environmental influences. This study aims to investigate the genetic causal relationships between gastrointestinal diseases and CKD using the Mendelian Randomization (MR) approach and bioinformatics analysis. METHODS:We analyzed genetic associations between nineteen gastrointestinal diseases including celiac disease (CeD), inflammatory bowel disease (IBD), intestinal malabsorption, and CKD. A two- sample MR analysis was performed using publicly available Genome-Wide Association Studies (GWAS) data with SingleNucleotide Polymorphisms (SNPs) as instrumental variables (IVs). The primary analysis employed the inverse variance weighted (IVW) method, with MR-Egger and weighted median as supplements. To explore potential biological mechanisms, Functional Mapping and Annotation (FUMA) analysis was used to map genes corresponding to IVs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS:Significant genetic causal effects were observed for CeD (OR = 1.021, 95% CI = 1.002-1.041, P = .032), IBD (OR = 1.051, 95% CI = 1.014-1.089, P = .006), and intestinal malabsorption (OR = 1.031, 95% CI = 1.006-1.056, P = .013) on the risk of developing CKD. Other gastrointestinal diseases did not demonstrate significant causal effects on CKD. Reverse MR analyses did not reveal significant causal effects of CKD on CeD, IBD, or intestinal malabsorption, respectively. FUMA analysis identified 93 genes associated with CeD, 143 genes with IBD, and 26 genes with intestinal malabsorption. GO and KEGG enrichment analyses highlighted key pathways, including T-cell receptor signaling, cytokine-cytokine receptor interaction, chromatin regulation, and immune-related pathways. CONCLUSIONS:This study provides genetic and bioinformatics evidence linking CeD, IBD, and intestinal malabsorption to an increased risk of CKD, highlighting the systemic impact of immune dysregulation and inflammation on kidney health.
INTRODUCTION:In this study, we compared the oxidative stress responses of patients with chronic kidney disease (CKD) and those with CKD-associated vascular calcification (CKD-VC), and established a risk predictive model for CKD-VC based on this comparison, providing a new approach for the clinical prevention and treatment of CKD-VC. METHODS:We conducted several cross-sectional surveys involving 173 patients with chronic kidney disease (CKD) who were admitted between September 2023 and October 2024 admitted to Affiliated Hospital of Hebei University. Sixty-two patients had VC (CKD-VC group), while the 111 patients did not have VC (CKD group). The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and catalase (CAT) of the two groups were measured. Additionally, factors influencing CKD-VC were analyzed using Logistic regression, and a risk predictive model was established accordingly. RESULTS:The levels of SOD and GSH-Px were lower in the CKD-VC group than the CKD group, whereas the CAT and MDA level was higher (P < .05). Logistic regression analysis indicated that SOD, GSH-Px, CAT, MDA, serum calcium, serum phosphorus, age, hypersensitive C-reactive protein (hs-CRP), albumin (ALB), and urine acid (UA) were all independent factors affecting CKD-VC (P < .05). The risk predictive model established based on these factors had high diagnostic sensitivity and specificity for CKD-VC, reaching 100.00% and 87.39%, respectively, with an area under the curve (AUC) of 0.980. CONCLUSION:This study established a risk predictive model for CKD-VC based on oxidative stress response, which has high diagnostic efficacy. This model provides a new approach for the clinical prevention and treatment of CKD-VC in the future, helping to more accurately identify high-risk patients and take corresponding intervention measures to effectively ensure patient safety.
