Chronic Kidney Disease Factors Research Articles

Comparative mathematical modeling of causal association between metal exposure and development of chronic kidney disease

BackgroundPrevious studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk.MethodsWe investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment.ResultsSerum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively.ConclusionsCumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.

Complete genome sequence of hepatitis B virus identified from a patient suffering from chronic kidney disease in Bangladesh.

Hepatitis B virus (HBV) infection is reported as a risk factor for chronic kidney disease (CKD). In this study, we sequenced the complete genome of an HBV strain identified in a CKD patient in Bangladesh, followed by genomic characterization and mutational analyses.

Elucidating ascorbate and aldarate metabolism pathway characteristics via integration of untargeted metabolomics and transcriptomics of the kidney of high-fat diet-fed obese mice.

Obesity is a major independent risk factor for chronic kidney disease and can activate renal oxidative stress injury. Ascorbate and aldarate metabolism is an important carbohydrate metabolic pathway that protects cells from oxidative damage. However the effect of oxidative stress on this pathway is still unclear. Therefore, the primary objective of this study was to investigate the ascorbate and aldarate metabolism pathway in the kidneys of high-fat diet-fed obese mice and determine the effects of oxidative stress. Male C57BL/6J mice were fed on a high-fat diet for 12 weeks to induce obesity. Subsequently, non-targeted metabolomics profiling was used to identify metabolites in the kidney tissues of the obese mice, followed by RNA sequencing using transcriptomic methods. The integrated analysis of metabolomics and transcriptomics revealed the alterations in the ascorbate and aldarate metabolic pathway in the kidneys of these high-fat diet-fed obese mice. The high-fat diet-induced obesity resulted in notable changes, including thinning of the glomerular basement membrane, alterations in podocyte morphology, and an increase in oxidative stress. Metabolomics analysis revealed 649 metabolites in the positive-ion mode, and 470 metabolites in the negative-ion mode. Additionally, 659 differentially expressed genes (DEGs) were identified in the obese mice, of which 34 were upregulated and 625 downregulated. Integrated metabolomics and transcriptomics analyses revealed two DEGs and 13 differential metabolites in the ascorbate and aldarate metabolic pathway. The expression levels of ugt1a9 and ugt2b1 were downregulated, and the ascorbate level in kidney tissue of obese mice was reduced. Thus, renal oxidative stress injury induced by high-fat diet affects metabolic regulation of ascorbate and aldarate metabolism in obese mice. Ascorbate emerged as a potential marker for predicting kidney damage due to high-fat diet-induced obesity.

Metabolic dysfunction, rather than obesity, is a risk factor for chronic kidney disease in Chinese population

Background Metabolic dysfunction and obesity are closely related to chronic kidney disease (CKD). However, studies on the relationship between various metabolic syndrome-body mass index (MetS-BMI) phenotypes and the risk of CKD in the Chinese population have not yet been explored. Materials and methods Data from the China Health and Retirement Longitudinal Study (CHARLS) 2015 were analyzed in this study. This study enrolled 12,054 participants. Participants were divided into six distinct groups according to their MetS-BMI status. Across the different MetS-BMI groups, the odd ratios (ORs) for CKD were determined using multivariable logistic regression models. Results The prevalence of CKD was higher in metabolically unhealthy groups than in the corresponding healthy groups. Moreover, the fully adjusted model showed that all metabolically unhealthy individuals had an increased risk of developing CKD compared to the metabolically healthy normal weight group (OR = 1.62, p = 0.002 for the metabolically unhealthy normal weight group; OR = 1.55, p < 0.001 for the metabolically unhealthy overweight group; and OR = 1.77, p < 0.001 for the metabolically unhealthy obesity group. Conclusions This study is the first to evaluate the relationship between the MetS-BMI phenotype and renal prognosis in the Chinese population. Individuals with normal weights are at different risk of developing CKD depending on their different metabolic phenotypes.

Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study.

Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). Multicenter prospective cohort study. 7 U.S. clinical centers. 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin-creatinine ratio (UACR) less than 30 mg/g. Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. UACR was measured once. Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. None.

THE RELATIONSHIP BETWEEN SOFT DRINK CONSUMPTION AND CHRONIC KIDNEY DISEASE IN MUHAMMADIYAH PALEMBANG HOSPITAL

Chronic kidney disease (CKD) has become one of the leading causes of death worldwide. It is one of several non-communicable diseases that have seen an associated increase in mortality over the past two decades. The causes of decreased kidney function are due to several factors, including a history of hypertension, cardiovascular history, family history of CKD, history of drinking preserved beverages, colored beverages, and other chemicals, and older age groups. Consuming soft drinks is associated with diabetes, hypertension, and kidney stones as risk factors for chronic kidney disease. This study aims to analyze the relationship between the frequency of soft drinks and chronic kidney disease at the Muhammadiyah Palembang Hospital. The sample of this study was 47 cases and 47 controls with an analytic observational research design with a case-control approach. This study used questionnaires and medical record data at the Palembang Muhammadiyah Hospital. Sampling used a consecutive sampling technique. The results showed that 61.7% of CKD patients and 55.3% of control subjects consumed soft drinks. The types of soft drinks consumed by CKD patients and control subjects were soft drinks with added sweeteners (100.0%). The results of the Pearson Chi-square test showed a value of p=0.644 (p&gt;0.05). This study concluded that there is no relationship between the frequency of soft drinks and chronic kidney disease.

Diabetes mellitus is a risk factor for incident chronic kidney disease: A nationwide cohort study

ObjectiveDiabetes mellitus and chronic kidney disease are multifactorial conditions with multiple etiologies that share similar pathophysiologies. This nationwide cohort study examined the impact of diabetes mellitus on the follow-up development of chronic kidney disease. MethodsBy retrieving the Longitudinal Health Insurance Database 2005, 5121 patients with diabetes mellitus were included in this study and 5121 patients without diabetes mellitus, who were matched according to sex, age, and Charlson comorbidity index made up the control group. The adjusted hazard ratios for chronic kidney disease were calculated using Cox proportional hazards regression analysis. Kaplan–Meier analysis was used to estimate the cumulative incidence of chronic kidney disease rate in the diabetes mellitus and control groups. ResultsAfter adjusting for sex, age, and Charlson comorbidity index score, the diabetes mellitus group had a 1.380 times higher (95% CI: 1.277–1.492) risk of developing chronic kidney disease than the control group. Further stratified analysis showed that patients with diabetes mellitus had a significantly higher risk of developing chronic kidney disease regardless of their sex, age, and Charlson comorbidity index score, compared to those without diabetes mellitus. ConclusionsThere is a possibility that diabetes mellitus serves as an independent risk factor for chronic kidney disease development. Early screening and monitoring of diabetes mellitus appear to be of great importance in the prevention of chronic kidney disease.

Risk factors for chronic kidney disease in middle eastern patients with type 2 diabetes mellitus: A cross-sectional study using the KDIGO classification

AimsChronic kidney disease (CKD) is prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate risk factors for CKD progression across the kidney disease-Improving Global Outcomes (KDIGO)categories in a Middle Eastern population beyond hyperglycemia as emphasized by KDIGO guidelines which classifying CKD by cause and severity. MethodsThis cross-sectional study targeted 1603 patients with T2DM. Risk factors for CKD progression were determined using odds ratios (ORs) and 95 % confidence intervals (CIs). ResultsOverall, 35.5 %, 31.7 %, and 32.8 % of patients were classified as low-risk, moderate-risk, and high-/very high-/highest-risk, respectively. Several factors were associated with high/very high/highest risk categorization, including being aged >45 years (OR: 1.85, 95 % CI: 1.36–2.49; P < 0.001), male gender (OR: 1.87, 95 % CI: 1.38–2.54; P < 0.001), hypertension (OR: 3.66, 95 % CI: 2.32–5.78; P < 0.001), and T2DM duration of ≥15 years (OR: 3.2, 95 % CI: 2.27–4.5; P < 0.001). Patients with more concurrent risk factors were notably represented in the high/very high/highest risk category. ConclusionsMale patients, older patients, and those with comorbid hypertension, longstanding T2DM, and additional concurrent risk factors have a significantly higher risk of advanced CKD. Such findings should be considered when planning management approaches for patients with CKD.

Serum Homocysteine and Folic Acid Levels as Risk Factors of Chronic Kidney Disease

Chronic kidney disease (CKD) is a worldwide health problem. Homocysteine (Hcy) and folic acid (FA) have been found to correlate with intra-renal atherosclerosis, which leads to decreased renal perfusion pressure and may impair the endothelial function of renal arterioles and glomerular capillaries, thus being considered as new risk factors for CKD. Objective: To investigate serum Hcy and FA as risk factors for CKD. Methods: A cross-sectional study was conducted on 80 patients who underwent creatinine examination. Hcy and FA levels were examined using enzyme-linked immunosorbent assay (ELISA) method. Bivariate analysis to calculate the prevalence ratio (PR) using a 2x2 table and using Receiver Operating Characteristic (ROC) curves to determine the cut off value of HCY and FA in CKD. Results: The mean Hcy level of CKD patients was 7.66±4.25 µmol/L and without CKD was 4.29 ± 2.71 µmol/L. The mean FA levels of CKD and non-CKD patients were 6.75±1.75 and 9.27±9.28 ng/mL, respectively. The prevalence ratio of Hcy to CKD was 2.17 (95%CI=1.35-3.45; p=0.001). The prevalence ratio of FA to CKD was 1.75 (95%CI=1.11-2.75; p 0.014). Conclusion: Increased Hcy levels and decreased serum FA levels are risk factors for CKD.

Investigating the use of finerenone in children with chronic kidney disease and proteinuria: design of the FIONA and open-label extension studies

IntroductionProteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria.ObjectiveFIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria.DesignFIONA (NCT05196035; Eudra-CT: 2021–002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months’ duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021–002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data.FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints.ConclusionFIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD.Trial registrationClinicalTrials.gov NCT05196035. Registered on 19 January 2022.

Pharmacological inhibition of Src family kinases attenuates hyperuricemic nephropathy.

Hyperuricemia is an independent risk factor for chronic kidney disease and contributes to renal fibrosis. This study aims to investigate the effect of Src family kinase (SFK) inhibition on the development of hyperuricemic nephropathy (HN) and the mechanisms involved. In a rat model of HN, feeding rats a mixture of adenine and potassium oxonate increased Src phosphorylation, severe glomerular sclerosis, and renal interstitial fibrosis, accompanied by renal dysfunction and increased urine microalbumin excretion. Administration of PP1, a highly selective SFK inhibitor, prevented renal dysfunction, reduced urine microalbumin, and inhibited activation of renal interstitial fibroblasts and expression of extracellular proteins. PP1 treatment also inhibited hyperuricemia-induced activation of the TGF-β1/Smad3, STAT3, ERK1/2, and NF-κB signaling pathways and expression of multiple profibrogenic cytokines/chemokines in the kidney. Furthermore, PP1 treatment significantly reduced serum uric acid levels and xanthine oxidase activity. Thus, blocking Src can attenuate development of HN via a mechanism associated with the suppression of TGF-β1 signaling, inflammation, and uric acid production. The results suggest that Src inhibition might be a promising therapeutic strategy for HN.

Kaempferitrin attenuates unilateral ureteral obstruction-induced renal inflammation and fibrosis in mice by inhibiting NOX4-mediated tubular ferroptosis.

Tubular ferroptosis significantly contributes to renal inflammation and fibrosis, critical factors in chronic kidney disease (CKD). This study aims to investigate Kaempferitrin, a potent flavonoid glycoside from Bauhinia forficata leaves, renowned for its anti-inflammatory and antitumor effects, and to elucidate its potential mechanisms in mitigating inflammation and fibrosis induced by tubular ferroptosis. The study investigated Kaempferitrin's impact on tubular ferroptosis using a unilateral ureteral obstruction (UUO) model-induced renal inflammation and fibrosis. In vitro, erastin-induced ferroptosis in primary tubular epithelial cells (TECs) was utilized to further explore Kaempferitrin's effects. Additionally, NADPH oxidase 4 (NOX4) transfection in TECs and cellular thermal shift assay (CETSA) were conducted to identify Kaempferitrin's target protein. Kaempferitrin effectively improved renal function, indicated by reduced serum creatinine and blood urea nitrogen levels. In the UUO model, it significantly reduced tubular necrosis, inflammation, and fibrosis. Its renoprotective effects were linked to ferroptosis inhibition, evidenced by decreased iron, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) levels, and increased glutathione (GSH). Kaempferitrin also normalized glutathione peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11(SLC7A11) expression, critical ferroptosis mediators. In vitro, it protected TECs from ferroptosis and consistently suppressed NOX4 expression. NOX4 transfection negated Kaempferitrin's antiferroptosis effects, while CETSA confirmed Kaempferitrin-NOX4 interaction. Kaempferitrin shows promise as a nephroprotective agent by inhibiting NOX4-mediated ferroptosis in tubular cells, offering potential therapeutic value for CKD.

EPIDEMIOLOGY OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN UKRAINE

The article reports on the prevalence of chronic kidney disease (CKD) in Ukrainian diabetic patients. A total of 194 patients who seeking an appointment with an endocrinologist underwent CKD screening. Materials and methods. The mean age of the patients was 64.82±0.88 years, and the duration of diabetes mellitus amounted to 9.29±0.60 years. Of these, 53.1% were female and 46.9% were male. Out of the screened patients, 79.4% had type 2 diabetes mellitus, 3.6% had type 1 diabetes mellitus, 9.3% had prediabetes, and 7.7% had other types of diabetes. We diagnosed CKD by calculating the estimated glomerular filtration rate (GFR) based on the creatinine level using the CKD-EPI Creatinine formula and determining albuminuria as the albumin-to-creatinine ratio. Results. Among diabetic patients, 26.8% had stage 1 CKD, 42.3% had stage 2, 21.6% had stage 3a, 8.2% had stage 3с, and 0.5% had each of stage 4 and 5. 70.6% of patients were found to have albumin-to-creatinine ratio (ACR) A1, 21.6% – A2, and 7.7% – A3. Of these, 30.0% were at high and very high risk of developing end-stage CKD. The regression analysis revealed a negative correlation between the duration of diabetes mellitus and the level of GFR, B (95% CI) = -0.102 (-0.179/-0.26), p = 0.009, and a positive correlation with ACR, B (95% CI) = 2.87 (0.089/5.605), p = 0.043. Conclusions. Among the examined patients with diabetes mellitus, 73.2% had stage 2-5 chronic kidney disease, and 29.3% had stage A2 and A3 albuminuria. Of these, 30% belong to the high- and very high-risk group for developing end-stage chronic kidney disease, requiring regular monitoring of glomerular filtration rate and albuminuria at least 3-4 times a year and conservative treatment. The duration of diabetes is a negative risk factor for chronic kidney disease. Hence, chronic kidney disease screening should be performed in all patients with diabetes with no exception.

Caspase-11/GSDMD contributes to the progression of hyperuricemic nephropathy by promoting NETs formation

Hyperuricemia is an independent risk factor for chronic kidney disease (CKD) and promotes renal fibrosis, but the underlying mechanism remains largely unknown. Unresolved inflammation is strongly associated with renal fibrosis and is a well-known significant contributor to the progression of CKD, including hyperuricemia nephropathy. In the current study, we elucidated the impact of Caspase-11/Gasdermin D (GSDMD)-dependent neutrophil extracellular traps (NETs) on progressive hyperuricemic nephropathy. We found that the Caspase-11/GSDMD signaling were markedly activated in the kidneys of hyperuricemic nephropathy. Deletion of Gsdmd or Caspase-11 protects against the progression of hyperuricemic nephropathy by reducing kidney inflammation, proinflammatory and profibrogenic factors expression, NETs generation, α-smooth muscle actin expression, and fibrosis. Furthermore, specific deletion of Gsdmd or Caspase-11 in hematopoietic cells showed a protective effect on renal fibrosis in hyperuricemic nephropathy. Additionally, in vitro studies unveiled the capability of uric acid in inducing Caspase-11/GSDMD-dependent NETs formation, consequently enhancing α-smooth muscle actin production in macrophages. In summary, this study demonstrated the contributory role of Caspase-11/GSDMD in the progression of hyperuricemic nephropathy by promoting NETs formation, which may shed new light on the therapeutic approach to treating and reversing hyperuricemic nephropathy.

Factors Associated with the Development of Chronic Kidney Disease in Patients with Arterial Hypertension.

Chronic kidney disease affects a large part of the population with hypertension, diabetes mellitus as well as those over 50 years of age. Research reported that male sex and other comorbidities such as obesity and anemia are more frequent in Chronic kidney disease, as well as uncontrolled diabetes mellitus or hypertension. To determine the risk factors associated with the development of chronic kidney disease in adults with arterial hypertension. Retrospective cohort study of 455 patients with hypertension treated in a primary health care hospital. Medical records and laboratory information were reviewed for the diagnosis of chronic kidney disease and its staging. Patients aged 40 years and older, of both sexes and evaluated between the years 2015 -2017 were included. Logistic regression analysis allowed the identification of risk factors associated with the development of chronic kidney disease. 63.7% were female and 36.3% male. The average age for 2015 was 69.79 ± 9.03, more than half of participants had diabetes mellitus and controlled hypertension and the predominant nephroprotection was with Losartan (53%) that year. Male sex (OR 1.68, CI 1.03-2,76), age: 60 years or older (OR 6.38, CI 2.65-15,37) and anemia (OR 1.71, CI 1.03-2,85), were risk factors for the development of chronic kidney disease (p < 0.05), whereas nephroprotection (OR 0.39, CI 0.18-0,88) and controlled diabetes mellitus (OR: 0.18, CI 0.07-0,47) were shown to be protective factors (p < 0.05). The prevalence of chronic kidney disease between 2015 and 2017 was 19% and 45%, respectively, with predominance of category G2. The comparison group is the same cohort analyzed in each year under study. Male sex, age over 60 years, and anemia are risk factors for chronic kidney disease. Nephroprotection, controlled diabetes mellitus, and patient follow-up are factors that prevent its development.

Serum PRO-C3 is useful for risk prediction and fibrosis assessment in MAFLD with chronic kidney disease in an Asian cohort.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an emerging risk factor for chronic kidney disease (CKD). N-terminal propeptide of collagen type 3 (PRO-C3) is a biomarker of advanced fibrosis in MAFLD and PRO-C3 may be involved in renal fibrosis. We aimed to use PRO-C3 measurements to generate a new algorithmic score to test the prediction of MAFLD with chronic kidney disease (MAFLD-CKD). A derivation and independent validation cohort of 750 and 129 Asian patients with biopsy-confirmed MAFLD were included. Serum PRO-C3 concentration was measured and regression analyses were performed to examine associations with MAFLD-CKD. A derivative algorithm for MAFLD-CKD risk prediction was evaluated with receiver operator characteristic (ROC) curve analysis. The study included two Asian cohorts (n = 180 with MAFLD-CKD; mean-eGFR: 94.93 mL/min/1.73 m2 ; median-urinary albumin-to-creatinine ratio: 6.58 mg/mmol). PRO-C3 was associated with the severity of MAFLD-CKD and independently associated with MAFLD-CKD (adjusted odds ratio = 1.16, 95% confidence interval [CI]: 1.08-1.23, p < .001). A new non-invasive score (termed PERIOD) including PRO-C3 efficiently predicted MAFLD-CKD (AUROC = .842, 95% CI: .805-.875). Accuracy, specificity and negative predictive values were 80.2%, 85.1% and 88.4%, respectively. In the validation cohort, the PERIOD score had good diagnostic performance (AUROC = .807, 95% CI: .691-.893) with similar results in all patient subgroups. In the MAFLD-CKD subgroup, the accuracy for identifying advanced fibrosis was further improved by combining the PRO-C3-based ADAPT with the Agile 3+ scores (AUROC = .90, 95% CI: .836-.964). The PERIOD score is helpful for accurately predicting the risk of MAFLD-CKD. PRO-C3 can also be used to assess liver fibrosis in people with MAFLD-CKD.

Renal sinus fat is associated with intrarenal hemodynamic abnormalities independent of visceral fat in patients with chronic kidney disease

ObjectiveObesity is a risk factor of chronic kidney disease (CKD), contributing to the rising incidence of cardiometabolic diseases. Renal sinus fat (RSF) is an ectopic fat depot located at the renal cavity that could impair renal function and hemodynamic through compression of renal structures. The major purpose of this study was to explore the relationship between RSF accumulation and renal dysfunction in CKD patients. MethodsWe evaluated the associations between computed tomography measured RSF volume and key clinical and histologic parameters involved in renal function and hemodynamics in 132 well-characterized CKD patients who underwent renal biopsy (median age: 62 years; 63.6% men). ResultsRSF volume normalized by renal volume (RSF%) positively correlated with obesity-related traits such body mass index and visceral fat volume (VFV) (all P < 0.001) whereas it negatively correlated with estimated glomerular filtration rate (eGFR) (ρ = −0.42, P < 0.001) and 24-h urinary creatinine clearance (CCr) (ρ = −0.34, P < 0.001). Notably, we found robust positive correlations between RSF% and renal resistive index (RRI) measured by the Doppler ultrasound (ρ = 0.40, P < 0.001), and the histological severity of global glomerular sclerosis (ρ = 0.48, P < 0.001) and interstitial fibrosis and tubular atrophy (IFTA) (ρ = 0.35, P < 0.001). In the multivariate linear regression models, after accounting for potential confounders including VFV, RSF% remained significantly associated with CCr (β = −0.26, P < 0.001), RRI (β = 0.17, P = 0.022), global glomerular sclerosis (β = 0.21, P = 0.002), and IFTA (β = 0.17, P = 0.012). ConclusionRSF accumulation is associated with renal dysfunction and hemodynamic abnormalities independent of visceral adiposity. Our results suggest that RSF may have a potential unique role in the pathogenesis of CKD.

Cardiovascular and Kidney Risks in Individuals With Type 2 Diabetes: Contemporary Understanding With Greater Emphasis on Excess Adiposity.

In high-income countries, rates of atherosclerotic complications in type 2 diabetes have declined markedly over time due to better management of traditional risk factors including lipids, blood pressure, and glycemia levels. Population-wide reductions in smoking have also helped lower atherosclerotic complications and so reduce premature mortality in type 2 diabetes. However, as excess adiposity is a stronger driver for heart failure (HF), and obesity levels have remained largely unchanged, HF risks have not declined as much and may even be rising in the increasing number of people developing type 2 diabetes at younger ages. Excess weight is also an underrecognized risk factor for chronic kidney disease (CKD). Based on evidence from a range of sources, we explain how excess adiposity must be influencing most risks well before diabetes develops, particularly in younger-onset diabetes, which is linked to greater excess adiposity. We also review potential mechanisms linking excess adiposity to HF and CKD and speculate on how some of the responsible pathways-e.g., hemodynamic, cellular overnutrition, and inflammatory-could be favorably influenced by intentional weight loss (via lifestyle or drugs). On the basis of available evidence, we suggest that the cardiorenal outcome benefits seen with sodium-glucose cotransporter 2 inhibitors may partially derive from their interference of some of these same pathways. We also note that many other complications common in diabetes (e.g., hepatic, joint disease, perhaps mental health) are also variably linked to excess adiposity, the aggregated exposure to which has now increased in type 2 diabetes. All such observations suggest a greater need to tackle excess adiposity earlier in type 2 diabetes.

ВРОЖДЕННЫЙ (АНТЕНАТАЛЬНЫЙ) ГИДРОНЕФРОЗ-МОДИФИЦИРУЕМЫЙ ФАКТОР РИСКА ХРОНИЧЕСКОЙ БОЛЕЗНИ ПОЧЕК У ДЕТЕЙ: МЕЖДИСЦИПЛИНАРНЫЙ ПОДХОД В КОНТЕКСТЕ ПРОФЛАКТИКИ ХРОНИЧЕСКОГО ЗАБОЛЕВАНИЯ (ОБЗОР ЛИТЕРАТУРЫ И СОБСТВЕННЫЕ ДАННЫЕ)

Congenital hydronephrosis (CHN) is the most common malformation of the kidney which leads to the development of chronic kidney disease (CKD) in children up to its terminal stage. Current clinical practices related to observation and analysis of long-term outcome of the disease and interdisciplinary collaboration are in the need for further improvement. The purpose of the research was to determine whether CHN is a modifiable risk factor for the onset and progression of CKD in children. Materials and methods used: a single-center cohort retrospective study of the results of antenatal screening of fetuses with congenital defects of organs and systems both with CAKUT syndrome and CHN was conducted at the Samara Oblast Regional Clinical Hospital named after V.D. Seredavin (Samara, Russia) in 2013-2022. Results: 13,484 fetuses were registered with congenital malformations of organs and systems, of which 2,818 (20.9% [20.2%; 21.6%]) with those of urinary organs. 390 were born alive with CHN (13.8% [12.6%; 15.2%]), of which 359 (92%) had surgical intervention using Heinz-Andersen method at the age of 37 [0.3-44.5] weeks: 208 (58%) boys/151 (42%), girls; unilateral CHN in 345 (96%) and bilateral in 14 (4%). Recovery occurred in 328 (91.4% [88.0%; 93 ,9%]) cases with CHN after the surgery. Based on the results of the research, an algorithm for interdisciplinary interaction of healthcare specialists was developed for routing of the pregnant women with fetal CAKUT syndrome. Conclusion: CHN is a modifiable risk factor for the development of CKD since 91.4% of children recovered in the long term.

Impact of obesity on renal function in elderly Korean adults: a national population-based cohort study.

Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001). In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.