Prognosis Of Chronic Kidney Disease Research Articles

Clinical and pathological significance of Orai1 channel expression in human diabetic nephropathy.

Targeted therapies for diabetic nephropathy (DN) are lacking, partly due to their irreversible nature. The role of Orai1, a store-operated Ca2+ channel, in DN remains debated, with conflicting evidence on its effect on proteinuria in animal models. We aimed to elucidate the functional relevance of Orai1 expression for clinicopathological parameters in patients with DN. In this study, we included 93 patients diagnosed with DN between 2009 and 2019. Immunohistochemical staining for Orai1 was performed on paraffin-embedded kidney sections. The significance of Orai1 expression in human DN was assessed by examining its correlation with DN's pathological and clinical parameters using Pearson's correlation coefficient and univariate logistic regression. Orai1 was significantly overexpressed in DN patients compared to control. A strong correlation was observed between increased Orai1 expression and higher Renal Pathology Society DN classification, enhanced interstitial fibrosis and tubular atrophy scores. Positive correlations with serum creatinine levels and prognosis of chronic kidney disease (CKD) by glomerular filtration rate (GFR) and albuminuria category were noted but the estimated GFR was inversely related to Orai1 expression. Orai1's association with advanced CKD stages persisted even after adjusting for confounding variables in multivariate logistic regression analysis. Orai1 expression is closely associated with histological and clinical severities of DN, suggesting its potential as a predictive biomarker for disease progression and prognosis. These findings provide new perspectives on therapeutic interventions targeting Orai1 in DN.

#1816 CA 125 as a surrogate marker for plasma volume in patients with cardiorenal syndrome

Abstract Background and Aims Assessing volume status in heart failure (HF) and end-stage chronic kidney disease (CKD) is challenging. Plasma volume expansion is an early step in the pathophysiology of decompensated HF and an independent risk factor for death and HF hospitalization, and should be addressed early. Evaluating plasma volume, especially its variation with diuretic therapy, can be a useful clinical tool for guiding decongestive therapy. There's a growing need for accurate and simple tools to guide clinician decisions on patient volume management. Cancer antigen 125 (CA125), a glycoprotein produced in mesothelial cells in the pericardium, pleura, or peritoneum, is primarily associated with ovarian and gynecological malignancies. Recent studies link CA125 to inflammation and congestion. In acute HF, elevated CA125 is associated with fluid overload indicators like increased central venous and pulmonary wedge pressure. Elevated CA125 in acute HF patients is linked to worse outcomes in death and hospital stay length. Evidence supports CA125-guided therapy in acute HF, but its role in managing chronic volume overload is still uncertain. We aim to assess the relationship between CA125 levels and estimated plasma volume (ePV). Method A retrospective unicentric observational study was conducted between June 2022, and April 17, 2023, at the Renocardiac clinic of a tertiary hospital. Clinical data were extracted from electronic patient records. CKD staging was determined following the Kidney Disease Improving Global Outcomes (KDIGO) classification. ePV was calculated using the Kaplan-Hakim formula. CA125 and ePV were assessed for the same patient in 2 different visits and their variation was calculated. The correlation between CA125 and ePV, as well as CA125 and ePV variation, was evaluated using Spearman's rank correlation coefficient for bivariate analysis, conducted with IBM SPSS®. Results This study comprised 65 patients, totaling 124 hospital visits. The patient demographic was 67.7% male, with a mean age of 76.4 (±12.47) years. In terms of CKD staging, 48.5% were classified as KDIGO 5, 40.6% as KDIGO 4, 9.4% as KDIGO 3, and 1.5% as KDIGO 2. HF etiology distribution included 59% ischemic, 9.8% hypertensive, 6.5% valvular, and 24.5% other causes. The mean ejection fraction was 37.35 (±12.36)% and 19% had preserved ejection fraction; 75% of them were treated with prognostic-modifying medication, including SGLT2 inhibitors. This proportion was lower (19%) in patients with reduced ejection fraction, receiving ACE/angiotensin ± neprilysin inhibitor + mineralocorticoid receptor inhibitor + beta-blocker + SGLT2 inhibitor. During the follow-up period, 13 hospitalizations, 1 major adverse cardiovascular event (MACE), and 5 deaths were recorded. The mean CA125 level was 193.98 (±154.55) U/mL, and patients had a mean ePV of 2.41 (±1.19) L. A significant positive correlation was found between CA125 levels and ePV (r = 0.355, p = 0.000). However, there was no significant correlation between the variation of CA125 and ePV levels between visits (p = 0.535). Conclusion This study focuses on a population with limited implementation of disease-modifying therapy due to advanced CKD, complicating the clinical management of volume status, kidney function, potassium levels, and long-term prognosis in both CKD and HF. CA125 shows potential clinical utility as a marker of congestion, aiding clinicians in assessing volume status by correlating with plasma volume. However, this study found no correlation between CA125 variation and changes in plasma volume. The outpatient nature of the studied population, typically euvolemic, may hinder assessing the relationship between CA125 and ePV changes. Future studies with larger sample sizes are essential to clarify this relationship and potentially identify volume-expanded patients early.

#493 CKDG4/5 with K-elevated metabolic acidosis under RAAS inhibitor use show a slow renal decline and preservation of response to alkalizing therapy

Abstract Background and Aims Renin-angiotensin-aldosterone system inhibitors (RAASi) are well-established renoprotective agents, but can induce serum potassium (K) elevation and metabolic acidosis (MA). MA contributes to the progression of chronic kidney disease (CKD), thus the renoprotective potential of RAASi is unknown in advanced CKD with MA due to the use of RAASi. MA with elevated serum K may discourage the use of RAASi. In highly advanced CKD, besides factors such as age, proteinuria, and diabetes, it is still debatable under what conditions the continued use of RAASi is favorable for renal prognosis. Furthermore, no studies have focused on the relationship between the response to alkalizing therapy for MA and renal prognosis in advanced CKD with MA and serum K elevation under RAASi use. Method In this single-center retrospective observational study, CKDG4 or G5 outpatients with MA ([HCO3−] < 22 mM) and elevated K (serum [K]≥5.0 mEq/L) at our center and who had started alkalinizing therapy (i.e., sodium bicarbonate and/or low-dose trichlormethiazide plus fludrocortisone) for MA were included. A total of 45 patients were selected, excluding those who had already been prepared for renal replacement therapy at the start of treatment. The RAASi group (Ri group, N = 39) and the non-RAASi group (non-Ri group, N = 16) were divided by the presence or absence of continued RAASi use prior to alkalizing therapy for MA, and the two groups were followed and compared up to 2 years after treatment. Background factors including age, sex, cause of CKD, estimated glomerular filtration rate (eGFR), CKD stage, diabetes, urinary protein (g/gCr), serum [K]/ [HCO3−]/[Na]/[CL]/albumin/phosphate, hemoglobin levels, and the use of K binders, diuretics were investigated. The endpoints were rapid response to alkalizing therapy (i.e., changes in serum [HCO3−], [K], [Na]-[CL] levels 2 months after the start of alkalinizing therapy, and percentage of patients achieving [HCO3−] ≥22 mM at 2 months after the start of alkalizing therapy) and incidence of renal events (>30% reduction in eGFR or renal replacement therapy). Results In all 45 subjects, the mean age was 71.3±11.8 years, 84% were male, mean eGFR was 18.3 ± 5.6 mL/min/1.73 m2, G4 67%/G5 33%, primary disease was diabetic nephropathy 31%, nephrosclerosis 40%, K binders and diuretics use was 25% and 24%, respectively. Mean serum [HCO3−] was 17.9 ± 2.3 mM and mean serum [K] was 5.5 ± 0.4 mEq/L. Comparison of background factors showed no significant difference between the two groups. The changes in serum [K], [HCO3−], [Na]-[CL] 2 months after the start of alkalinizing therapy and the percentage of patients achieving [HCO3−] ≥22 mM after 2 months of starting alkalizing therapy did not differ at all between the Ri and non-Ri groups (Table 1). Cumulative renal survival (non-renal events) was significantly higher in the Ri group than in the non-Ri group(p = 0.010) (Figure 1). None of the rapid responses to alkalizing therapy (i.e., changes in serum[HCO3−], [K], [Na]-[CL], and the percentage of patients achieving [HCO3−] ≥22 mM) were significantly associated with cumulative renal survival (p = 0.186, p = 0.266, p = 0.65, p = 0.114). In a Cox proportional hazards multivariate model adjusted for age, sex, eGFR, cause of CKD, diabetes, urinary protein(g/gCr), method of alkalizing therapy, and rapid response to alkalizing therapy, the risk of renal events without RAASi use was significantly higher (Table 2). Conclusion In CKDG4/5 with MA with elevated serum K under RAASi use, renal function declines more slowly than with non-RAASi use, ensuring a rapid response to alkalizing therapy for MA.

Associations between serum 25-hydroxyvitamin D and prognosis of chronic kidney disease: a prospective cohort study.

25-hydroxyvitamin D [25(OH)D] deficiency is prevalent in patients with chronic kidney disease (CKD), the associations between serum 25(OH)D levels and mortality in patients with CKD remain unclear, and this study aimed to explore these associations further. 4989 participants with CKD were enrolled in the study, and the Cox regression model was used to assess the effects of serum 25(OH)D concentrations on mortality risk. A restricted cubic spline model was used to explore the dose-response relationships, and threshold effect analysis was performed based on inflection points identified by a two-piecewise linear regression model. In addition, subgroup and sensitivity analyses were employed. 1255 participants died during a mean follow-up period of 70months. Compared with the 25(OH)D-deficient group, the fully adjusted hazard ratios and 95% confidence intervals for the 25(OH)D-adequate group were 0.631 (0.545, 0.730) for all-cause mortality, 0.569 (0.435, 0.743) for cardiovascular mortality, 0.637 (0.461, 0.878) for hypertension mortality, and cancer mortality was 0.596 (0.426, 0.834). The inflection points of serum 25(OH)D concentration affecting all-cause and cardiovascular mortality were 89nmol/L, and 107nmol/L, respectively. Subgroup analyses and interaction tests suggested that the effects varied across populations. The results of sensitivity analyses indicated a reliable correlation. We found an association between serum 25(OH)D concentrations and the prognosis of patients with CKD as a reliable predictor of early intervention and intensive care.

A Chinese patent medicine's long-term efficacy on non-dialysis patients with CKD stages 3-5: a retrospective cohort study.

Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

The role of mitophagy in the development of chronic kidney disease.

Chronic kidney disease (CKD) represents a significant global health concern, with renal fibrosis emerging as a prevalent and ultimate manifestation of this condition. The absence of targeted therapies presents an ongoing and substantial challenge. Accumulating evidence suggests that the integrity and functionality of mitochondria within renal tubular epithelial cells (RTECs) often become compromised during CKD development, playing a pivotal role in the progression of renal fibrosis. Mitophagy, a specific form of autophagy, assumes responsibility for eliminating damaged mitochondria to uphold mitochondrial equilibrium. Dysregulated mitophagy not only correlates with disrupted mitochondrial dynamics but also contributes to the advancement of renal fibrosis in CKD. While numerous studies have examined mitochondrial metabolism, ROS (reactive oxygen species) production, inflammation, and apoptosis in kidney diseases, the precise pathogenic mechanisms underlying mitophagy in CKD remain elusive. The exact mechanisms through which modulating mitophagy mitigates renal fibrosis, as well as its influence on CKD progression and prognosis, have not undergone systematic investigation. The role of mitophagy in AKI has been relatively clear, but the role of mitophagy in CKD is still rare. This article presents a comprehensive review of the current state of research on regulating mitophagy as a potential treatment for CKD. The objective is to provide fresh perspectives, viable strategies, and practical insights into CKD therapy, thereby contributing to the enhancement of human living conditions and patient well-being.

Determinant and Impact of Left Ventricular Hypertrophy (LVH) in Chronic Renal Failure (CRF) Patients

Left ventricular hypertrophy is the most common cardiovascular complication in chronic renal failure. It appears to be associated with excess mortality. Objective: To determine the factors associated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD), and to describe their influence on renal function. Patients and methods: This was a descriptive and analytical study conducted over 6 years (January 1, 2012 to December 31, 2017) on CKD patients who had an electrocardiogram or cardiac ultrasound. Results: A total of 329 patients were included. LVH was found in 223 patients, a prevalence of 68%. The sex ratio M/F was 2.1. Mean age was 51.05±14.17 years (range 11-95 years). Arterial hypertension predominated (97% of cases), followed by diabetes (26%).Univariate and multivariate analysis showed that LVH was associated with: age ≤51 years (p=0.0037) and with arterial hypertension (p=0.0018) and anemia (p=0.0018). Over a 5-year period, CKD patients with LVH experienced a more rapid decline in renal function than those without LVH (p&lt;0.0001). There was also a higher rate of death in patients with LVH (83%) than in those without (46%) during a 5-year follow-up. Conclusion: LVH is an important factor in the poor prognosis of CKD. This calls for systematic screening and early management by a multidisciplinary team.

Clinical significance of amphiregulin in patients with chronic kidney disease.

Amphiregulin (AREG) is a ligand of epidermal growth factor receptor (EGFR), which plays an important role in injury-induced kidney fibrosis. However, the clinical significance of serum soluble AREG in chronic kidney disease (CKD) is unclear. In this study, we elucidated the clinical significance of serum soluble AREG in CKD by analyzing the association of serum soluble AREG levels with renal function and other clinical parameters in patients with CKD. In total, 418 Japanese patients with CKD were enrolled, and serum samples were collected for the determination of soluble AREG and creatinine (Cr) levels, and other clinical parameters. Additionally, these parameters were evaluated after 2 and 3years. Moreover, immunohistochemical assay was performed ate AREG expression in the kidney tissues of patients with CKD. Soluble AREG levels were positively correlated with serum Cr (p < 0.0001). Notably, initial AREG levels were positively correlated with changes in renal function (ΔCr) after 2 (p < 0.0001) and 3years (P = 0.048). Additionally, soluble AREG levels were significantly higher (p < 0.05) in patients with diabetic nephropathy or primary hypertension. Moreover, AREG was highly expressed in renal tubular cells in patients with advanced CKD, but only weakly expressed in patients with preserved renal function. Serum soluble AREG levels were significantly correlated with renal function, and changes in renal function after 2 and 3years, indicating that serum soluble AREG levels might serve as a biomarker of renal function and renal prognosis in CKD.

Identification of risk factors and development of a predictive model for chronic kidney disease in patients with obesity: a four-year cohort study

ObjectiveThe sneaky onset and dismal prognosis of chronic kidney disease (CKD) make it an important public health issue. Obesity-related kidney illness has garnered more attention in recent times. Establishing and validating a risk prediction model for chronic renal illness in overweight or obese adults was the goal of this investigation.MethodsData from the China Health and Retirement Longitudinal Study were used for analysis. The definition of CKD was reduced renal function (eGFR < 60 mL/min/1.73 m²), while overweight and obesity were characterized through a body mass index exceeding 24 kg/m². The dataset was divided into derivation and validation cohorts using a 7:3 ratio. With respect to the derivation cohort, we constructed a prediction model using LASSO analysis and multivariate logistic regression. The model’s performance was evaluated using Hosmer-Lemeshow tests, calibration curves, decision curve analysis, and receiver operating characteristic (ROC) curves. The validation cohort’s model was subjected to additional assessment.ResultsThe study was based on survey data from 2011 to 2015 and comprised 3246 individuals who were overweight or obese, with 2274 being part of the derivation cohort and 972 being part of the validation cohort. The research constructed a prediction model that included age, sex, fasting blood glucose, glycated hemoglobin, triglyceride, hypertension, and BMI. The validation cohort’s area under the ROC curve was 0.812 (95% CI = 0.763, 0.859) while the derivation cohort’s was 0.789 (95% CI = 0.754, 0.831). Hosmer-Lemeshow tests were utilized to evaluate the model’s accuracy in the validation and derivation cohorts (P = 0.681 and 0.547, respectively). The calibration curve showed a high level of consistency between the actual observations and the projected outcomes. According to decision curve analysis, the model offered significant net advantages.ConclusionsThe forecasting model established in this research has predictive value for CKD in patients with overweight or obesity. These findings could help doctors conduct early detection and intervention in clinical practice and further improve patient prognosis.

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3–5

Background and aimsThe role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. Methods and resultsLeveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3–5. The study finally included 2644 patients with CKD stages 3–5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. ConclusionsBoth higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3–5.

Extracellular Histones Promote Calcium Phosphate-Dependent Calcification in Mouse Vascular Smooth Muscle Cells.

Vascular calcification, a major risk factor for cardiovascular events, is associated with a poor prognosis in chronic kidney disease (CKD) patients. This process is often associated with the transformation of vascular smooth muscle cells (VSMCs) into cells with osteoblast-like characteristics. Damage-associated molecular patterns (DAMPs), such as extracellular histones released from damaged or dying cells, are suspected to accumulate at calcification sites. To investigate the potential involvement of DAMPs in vascular calcification, we assessed the impact of externally added histones (extracellular histones) on calcium and inorganic phosphate-induced calcification in mouse VSMCs. Our study found that extracellular histones intensified calcification. We also observed that the histones decreased the expression of VSMC marker genes, while simultaneously increasing the expression of osteoblast marker genes. Additionally, histones treated with DNase I, which degrades dsDNA, attenuated this calcification, compared with the non-treated histones, suggesting a potential involvement of dsDNA in this process. Elevated levels of dsDNA were also detected in the serum of CKD model mice, underlining its potential role in vascular calcification in CKD. Our findings suggest that extracellular histones could play a pivotal role in the vascular calcification observed in CKD.

Lipid parameters, adipose tissue distribution and prognosis prediction in chronic kidney Disease patients

BackgroundLipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis.PurposeExplore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3–5.MethodsThis is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3–5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness..Results255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis..ConclusionComprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3–5.

The association between dietary antioxidant quality score and uric acid related mortality in patients with chronic kidney disease.

Antioxidants diet is beneficial for the prognosis of chronic kidney disease (CKD). However, the relationship between the Dietary Antioxidant Quality Score (DAQS), a measure of overall quality on antioxidant diet, and hyperuricemia related mortality is unclear. This study aimed to investigate the relationship between the DAQS and hyperuricemia mortality in CKD patients. In this cohort study, data were collected in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. The DAQS was calculated based on the six dietary antioxidants. Mortality status were determined by NHANES-linked National Death Index public access files through December 31, 2019. Weighted Cox proportional hazard models were used to investigate the association between the DAQS and hyperuricemia related mortality. A total of 3,684 participants were included. During the median follow-up of 63.83 months, 820 deaths were recorded. The results showed that higher dietary antioxidants intake associated with lower hyperuricemia related mortality risk among CKD patients (HR = 1.28, 95%CI: 1.07 to 1.54). In subgroup analyses, the association of antioxidants intake and hyperuricemia related mortality risk remained exist in groups of aged ≥65 years (HR = 1.23, 95%CI: 1.01 to 1.52), with hypertension (HR = 1.26, 95%CI: 1.02 to 1.55), with dyslipidemia (HR = 1.30, 95%CI: 1.07 to 1.58), with CVD (HR = 1.31, 95%CI: 1.03 to 1.67), and diabetes (HR = 1.62, 95%CI: 1.24 to 2.12). Higher antioxidants intake associated with lower odds of hyperuricemia related mortality in CKD patients. Future interventional studies are needed to elucidate the beneficial effect of antioxidants diets.

Implications of Untreated Hypertension on Chronic Kidney Disease: A Literature Review

The untreated progression of hypertension holds significant implications for the development and progression of chronic kidney disease (CKD). Therefore, necessitating the implementation of strategic hypertension management measures to mitigate its impact on CKD. This review highlights the necessity of precise diagnostic methodologies that employ oscillometric equipment and advocates for pharmacological interventions, the incorporation of combination therapies such as the "Polypill" to effectively control hypertension, and lifestyle adjustments. The pivotal role of the renin-angiotensin-aldosterone system (RAAS) in hypertension is acknowledged, noting the importance of stringent blood pressure regulation and the utilization of RAAS-blocking agents to attenuate its association with CKD. A comprehensive analysis is provided on the effects of various classes of antihypertensive medications on renal function, encompassing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and nonsteroidal mineralocorticoid receptor antagonists. Additionally, both non-invasive and invasive therapeutic modalities for managing resistant hypertension in CKD patients are examined, alongside discussions on prognostic indicators and outcomes across different stages of CKD. Lifestyle modifications such as sodium restriction, weight management, and moderation of alcohol intake are assessed for their influence on CKD prognosis. The review also extensively delves into the impact of ethnicity on the prevalence and outcomes of hypertension-induced CKD, highlighting disparities and distinctive trends among diverse ethnic cohorts including Indian, African American, Middle Eastern, Chinese, Pacific Islander, Native American, and Hispanic populations. Additionally, this study addresses the intricate relationship between cardiovascular abnormalities and CKD, the significance of gastrointestinal disorders, and the importance of multidisciplinary approaches in CKD management. Furthermore, insights are provided into the significance of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for identifying renal injury and CKD progression, alongside factors influencing adverse prognosis and life expectancy in CKD patients. This study accentuates the importance of tailored treatment assessments and interventions to address varied patterns and obstacles within ethnic groups, with the aim of optimizing CKD management strategies and reducing health disparitie

Determinant and Impact of Left Ventricular Hypertrophy (LVH) in Chronic Renal Failure (CRF) Patients

Left ventricular hypertrophy is the most common cardiovascular complication in chronic renal failure. It appears to be associated with excess mortality. Objective: To determine the factors associated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD), and to describe their influence on renal function. Patients and methods: This was a descriptive and analytical study conducted over 6 years (January 1, 2012 to December 31, 2017) on CKD patients who had an electrocardiogram or cardiac ultrasound. Results: A total of 329 patients were included. LVH was found in 223 patients, a prevalence of 68%. The sex ratio M/F was 2.1. Mean age was 51.05±14.17 years (range 11-95 years). Arterial hypertension predominated (97% of cases), followed by diabetes (26%).Univariate and multivariate analysis showed that LVH was associated with: age ≤51 years (p=0.0037) and with arterial hypertension (p=0.0018) and anemia (p=0.0018). Over a 5-year period, CKD patients with LVH experienced a more rapid decline in renal function than those without LVH (p&lt;0.0001). There was also a higher rate of death in patients with LVH (83%) than in those without (46%) during a 5-year follow-up. Conclusion: LVH is an important factor in the poor prognosis of CKD. This calls for systematic screening and early management by a multidisciplinary team.

Impact of hemoglobin adducts of ethylene oxide on the prevalence and prognosis of chronic kidney disease in US adults: an analysis from NHANES 2013-2016.

Animal experiments have shown that high exposure to ethylene oxide (EO) can cause multiple system damages including the renal system. Recent studies have reported associations between exposure to EO and cancer, dyslipidemia, diabetes, and cardiovascular disease. However, the impact of exposure to EO on the prevalence and prognosis of chronic kidney disease (CKD) in humans is scarcely investigated. The study was designed to investigate the associations between EO exposure and incidence and prognosis of CKD among 2900 US adults. Exposure to EO was measured by detecting the levels of hemoglobin adducts of EO (HbEO). The diagnosis of CKD was made according to an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) > 30 mg/g. Prognosis of CKD was assessed based on the evaluation system initiated by KDIGO that consists of eGFR and UACR. Survey-weighted generalized linear models and proportional odds models were constructed to assess the associations between HbEO and prevalence and prognosis of CKD, with odds ratios (ORs) and proportional odds ratios (PORs) and their 95% confidence intervals (CIs) reported, respectively. Restricted cubic spline (RCS) function was performed to depict the correlation between HbEO and CKD. The weighted median (interquartile range) of HbEO was 31.3 (23.1-60.3) pmol/g Hb. A total of 491 participants (16.9%) were diagnosed with CKD, and 153 participants (5.31%) were identified to be at high or very high risk. Referred to the first tertile of HbEO, the adjusted ORs (95% CIs) for CKD in the second and third tertile were 1.46 (0.85, 2.50) and 1.69 (1.00, 2.85), and the adjusted PORs (95% CIs) for prognosis of CKD in the second and third tertile were 1.37 (0.94, 1.99) and 1.58 (1.10, 2.26). When HbEO was analyzed as a continuous variable, the adjusted OR (95% CI) for CKD and POR (95% CI for prognosis of CKD were 1.24 (0.97, 1.58) and 1.22 (1.01, 1.47), respectively. RCS analysis revealed a non-linear positive correlation between HbEO and prevalence of CKD (P for nonlinearity < 0.05). Subgroup analysis indicated smoking status had a significant impact on this association, which remained significant among never smokers but lost significance among smokers. Among US adults, increased EO exposure was independently related to increased CKD prevalence and poor CKD outcomes, which was established in never smokers but not among ever smokers.

Carbon dot-copper nanocomposite-based fluorescent sensor for detection of creatinine in urine samples of CKD patients

Creatinine (CR) is accepted as a clinical biomarker of chronic kidney disease (CKD) such as renal injury and kidney failure. To help facilitate the prognosis of CKD, a highly luminescent carbon dot (CD)-based fluorescent (FL) sensor has been built and employed for CR detection in diverse media (e.g., artificial and human urine). CDs, synthesized from sucrose precursor by a rapid microwave-assisted method (average diameter 20 nm), exhibited highly luminescent green emission upon UV exposure (λexcitation = 390 nm, λemission = 453 nm) with excellent temporal stability over three months. The nanocomposites are formed between CDs and metal ions (e.g., Cu2+) to realize the optimum biosensing of CR. Although Cu2+ ions showcases a maximum quenching (73 %) of the CDs, Cu2+/CDs system restores 77 % of the original FL intensity upon the addition of CR. The linear detection range and limit of detection for CR are estimated as 10-5 to 0.1 mg·dL-1 (R2 = 0.936) and 5.1 × 10-16 mg·dL-1, respectively. Furthermore, our biosensor shows excellent reproducibility and selectivity for CR in urine samples of healthy subjects and CKD patients. The Bland-Altman analysis for urine samples (n = 30) showcased an excellent agreement (R2 = 0.95) between our method and the gold standard ‘Jaffe’ method. These observations supported the practical utility of our method proposed for detection of CR in clinical samples.

Trends in the epidemiology of chronic kidney disease in patients with diabetes in Russian Federation according to the Federal diabetes register (2010–2022)

BACKGROUND: Chronic kidney disease (CKD) in diabetes mellitus (DM) is a supranosological concept that characterizes multifactorial kidney damage associated with increased cardiovascular and mortality risk, which determines the high medical and social significance of this problem in diabetic patients.AIMS: To assess the clinical and epidemiological characteristics of CKD in adult DM patients with type 1(T1) and type 2 (T2) in Russian Federation (RF) in 2010–2022 according to the Federal Register of Diabetes Mellitus (FDR) and to present the capabilities of the register’s analytical tools for assessing organ-protective therapy and predicting the risk of pathology.MATERIALS AND METHODS: We have used the database of FRD (http://diaregistry.ru), 85 regions of the RF. The data are presented as of 01.01.2023 and in dynamics for the period 2010–2022.RESULTS: The CKD prevalence in adult DM patients in RF in dynamics 2010→2022 showed in an increase in the rate for T1 from 21.5 to 27.1% (1.3 times), for T2 from 5.2 to 19.1% (3.7 times). The incidence of new CKD cases was 153.3→106.3/10 000 adult patients in T1, and 64.3→212.8/10 000 adult patients in T2. The analysis of the distribution by CKD stage indicates improved diagnosis of the complication. In the structure of new cases of CKD in the dynamics of 2010→2022. The proportions of patients with low and moderate combined risk of cardiovascular events and end-stage renal failure according to KDIGO criteria increased for T1 63.7→82.4%, for T2 64.5→77.4%. The proportions of patients with very high risk progressively decreased for T1 12.3→4.0%, for T2 13.1→1.6%. The average age of onset of CKD increased by an average of 6 years in persons with type 1 and type 2 diabetes (35.6→42 years, 63.3→69.3 years, respectively), with the dynamics of the average DM duration at the time of CKD development: in T1 11.5→14.8 years, in T2 7.4→7.8 years. The cause of terminal CKD in the structure of mortality in DM patients took only in T1 patients 5.6% and in T2D — 2.0%. A retrospective analysis of factors influencing the fatal outcome of DM patients with COVID-19 showed the significance of a history of CKD in T2DM patients, which increases the risk of death by 1.49 times (95% CI 1.01–2.04). Analysis of the structure of glucose-lowering therapy in T2DM patients and CKD indicates a more frequent prescription of drugs from the group of SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor antagonists compared to the general cohort of T2DM. There is the CKD prognosis calculator in the FRD, which allows assessing the risk of developing of pathology within 5 years in a particular patient based on a set of the most significant predictors, which included 6 factors for T1 and 11 factors for T2. CONCLUSIONS: Epidemiological trends in the prevalence of CKD over a 13-year period indicate the growing importance of this problem in DM patients who are at risk. Along with the positive trends in the development of pathology with a longer duration of diabetes, in clinical practice the problem remains of untimely detection of CKD with impaired renal function at advanced stages. The progressive nature of the course and the negative impact of kidney damage on the risks of premature mortality in patients determine the priority of preventive diagnostic and therapeutic strategies aimed at compliance with the standard of examination, detection of pathology in the early stages and a multifactorial approach to nephroprotection, according to clinical recommendations.

Unlocking Precision Medicine for Prognosis of Chronic Kidney Disease Using Machine Learning.

Chronic kidney disease (CKD) is a significant global health challenge that requires timely detection and accurate prognosis for effective treatment and management. The application of machine learning (ML) algorithms for CKD detection and prediction holds promising potential for improving patient outcomes. By incorporating key features which contribute to CKD, these algorithms enhance our ability to identify high-risk individuals and initiate timely interventions. This research highlights the importance of leveraging machine learning techniques to augment existing medical knowledge and improve the identification and management of kidney disease. In this paper, we explore the utilization of diverse ML algorithms, including gradient boost (GB), decision tree (DT), K-nearest neighbor (KNN), random forest (RF), histogram boost (HB), and XGBoost (XGB) to detect and predict chronic kidney disease (CKD). The aim is to improve early detection and prognosis, enhancing patient outcomes and reducing the burden on healthcare systems. We evaluated the performance of the ML algorithms using key metrics like accuracy, precision, recall, and F1 score. Additionally, we conducted feature significance analysis to identify the most influential characteristics in the detection and prediction of kidney disease. The dataset used for training and evaluation contained various clinical and demographic attributes of patients, including serum creatinine level, blood pressure, and age, among others. The proficiency analysis of the ML algorithms revealed consistent predictors across all models, with serum creatinine level, blood pressure, and age emerging as particularly effective in identifying individuals at risk of kidney disease. These findings align with established medical knowledge and emphasize the pivotal role of these attributes in early detection and prognosis. In conclusion, our study demonstrates the effectiveness of diverse machine learning algorithms in detecting and predicting kidney disease. The identification of influential predictors, such as serum creatinine level, blood pressure, and age, underscores their significance in early detection and prognosis. By leveraging machine learning techniques, we can enhance the accuracy and efficiency of kidney disease diagnosis and treatment, ultimately improving patient outcomes and healthcare system effectiveness.

Gender and sex in the development and progression of renal diseases

Sex-based disparities in nephrology have been a historically understudied area. In nephrology, gender differences exist with regard to the epidemiology, evolution and prognosis of chronic kidney disease (CKD). In some cases, these differences run contrary to the general population trends. We discuss such gender and sex disparities, including differing impact of traditional and novel risk factors, as well as hormonal factors, all of them potentially influencing propensity, progression and biochemical and psychological aspects of CKD. The factors involved in this gender disparity may include diet, kidney and glomerular size, differences in glomerular hemodynamics, and the direct effects of sex hormones. The progression rate of many renal diseases is affected by sex. In polycystic kidney disease, membranous nephropathy, immunoglobulin A nephropathy, and “chronic renal disease of unknown etiology”, men progress at a faster rate to end-stage renal failure than women do. In many, but not all, animal models of renal disease, estrogens slow progression rate. Animal and experimental studies have tried to offer further mechanistic explanations for gender differences in disease progression. It has been suggested that the gender dimorphism of CKD progression may represent the effects of the interaction of circulating steroids with specific kidney receptors. Endogenous estrogens have in general been considered to have anti-fibrotic and anti-apoptotic effects on the kidney. On the other hand, the faster decline of kidney function in men has been attributed to the specific pro-apoptotic and pro-fibrotic properties of androgens.