This study examines global trends in cardiovascular disease (CVD) associated with kidney dysfunction (KD) from 1990 to 2021 and projects future trends through 2050.

This study analyzed the 2021 Global Burden of Disease (GBD) database, focusing on age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years rate (ASDR), absolute numbers, estimated annual percentage change, and average annual percent change. A Bayesian age-period-cohort model was employed to project global trends from 2022 to 2050. Variables included age, gender, national levels, and Socio-demographic Index (SDI) regions.

From 1990 to 2021, the CVD burden from KD increased, with deaths rising from 1,312,393 to 2,095,800 and DALYs from 27,382,767 to 41,589,861. However, the ASMR decreased from 40.58 per 100,000 in 1990 to 25.55 in 2021, while ASDR fell from 742.17 to 489.81 during the same period. The burden was higher in men, peaking at ages 70-74 and in women at ages 85-89. Regions with lower-middle and low SDI recorded the highest CVD burden, inversely related to SDI levels. Geographically, Central Asia and Eastern Europe recorded the highest rates, while high-income Asia Pacific and Southern Latin America had the lowest. Projections suggest a sustained decline in global CVD burden due to KD from 2022 to 2050, although disparities between sexes are expected to persist, with men bearing a heavier burden.

CVD attributable to KD remains a major global public health challenge, especially for men, the elderly, and low SDI regions. These spatial and temporal variations highlight the need for region-specific healthcare strategies.

Chronic kidney disease (CKD) is characterized as a progressive dysfunction of the kidney. The estimated glucose disposal rate (eGDR) is widely recognized as a dependable marker of insulin resistance (IR). Nonetheless, the potential link between eGDR and CKD incidence remains insufficiently clarified. This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS). The outcome of this study was CKD events. We performed adjusted Cox proportional hazards regression, restricted cubic splines (RCS), and mediation analyses. Among the 6,737 participants followed for a median of 108 months, 1,356 (20.13%) developed CKD. Relative to the lowest quartile (Q1) of eGDR, the adjusted HR for the highest quartile (Q4) was 0.85 (95% CI: 0.72-0.99). Each standard deviation increase in eGDR was linked to a 7% reduction in CKD risk (HR: 0.93, 95% CI: 0.88-0.99). The RCS curve indicated a linear relationship between eGDR and CKD risk (threshold = 8.21). The cardiovascular disease (CVD) significantly mediated 27.0% of the association between eGDR and CKD risk. This study demonstrates a significant inverse correlation between eGDR levels and CKD risk in middle-aged and elderly individuals within the Chinese population. Moreover, CVD emerges as a key intermediary linking eGDR and the heightened risk of CKD.

HRS-1780 is a selective non-steroidal mineralocorticoid receptor antagonist developed for the treatment of chronic kidney disease. This study aimed to assess the pharmacokinetics (PK) and safety profiles of HRS-1780 in subjects with renal impairment.

Eligible participants were enrolled in the healthy (glomerular filtration rate [GFR] of ≥90 mL/min), mild (GFR of 60-89 mL/min), and moderate renal impairment (GFR of 30-59 mL/min) groups with 9 subjects each and orally received 20 mg HRS-1780. Concentrations of HRS-1780 and its main metabolites were measured in plasma and urine. PK profiles between healthy and renal impairment subjects were compared using analysis of variance.

A total of 27 subjects completed the study. HRS-1780 was rapidly absorbed and eliminated, with Tmax of 0.50-0.52 hour and t1/2 of 2.06-2.56 hours. Exposure (AUC0-inf) to HRS-1780 was comparable between mildly and moderately renal impaired subjects, while higher, but not significantly than that in healthy subjects. Similar plasma protein binding among different renal function groups suggested a consistent effect of renal function on total and unbound HRS-1780. Renal clearance of HRS-1780 decreased with severity of renal impairment, but renal elimination of HRS-1780 was minimal. Exposure to SX2183-M3 was significantly increased in the moderate renal impairment subjects. Renal impairment did not appear to be associated with an increased risk of adverse events.

HRS-1780 PK and safety profiles did not differ significantly between healthy and renal impairment subjects. This supports the drug dose regimen for renal impairment patients in clinical practice.

(1) Background: The SCORE2-Diabetes model has been developed as an effective tool to estimate the 10-year cardiovascular risk in patients with diabetes. Coronary computed tomography angiography (CCTA) and its derived Coronary Artery Calcium Score (CACS) are widely used non-invasive imaging tools for assessing coronary artery disease (CAD). This study aimed to evaluate the correlation between CACS and SCORE2-Diabetes in patients with T2DM. (2) Methods: A cross-sectional study was conducted from October 2023 to May 2024. We included patients aged 40 to 69 years with T2DM who underwent a coronary multislice CT scan due to atypical angina. The correlation between CACS and SCORE2-Diabetes was analyzed using Spearman's rank correlation coefficient. (3) Results: A total of 100 patients met the inclusion criteria, including 71 males and 29 females, with a mean age of 61.9 ± 5.4 years. The differences in CACS and SCORE2-Diabetes among different degrees of coronary artery stenosis were statistically significant (p < 0.05). A statistically significant but weak positive correlation was observed between CACS and SCORE2-Diabetes across all risk categories, with Spearman's rank correlation coefficients ranging from 0.27 to 0.28 (p < 0.01). (4) Conclusions: Despite the weak correlation between CACS and SCORE2-Diabetes, understanding their relationship and independent associations with disease severity is valuable. The combination of these two tools may warrant investigation in future studies to potentially enhance cardiovascular risk assessment in T2DM patients.

Kidney failure can be prevented or delayed if chronic kidney disease (CKD) is detected and treated early. Targeted screening has been shown effective in detecting CKD worldwide, but a recently updated summary of evidence is lacking. We synthesized up-to-date evidence of the effectiveness of risk factor-based screening for the early detection of CKD among adults in primary care.

We retrieved articles from Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Scopus. Relevant gray literature and hand-searching bibliographies of key articles were also performed.

Adult patients (age ≥ 18 years) with at least 1 known CKD risk factor in primary care.

Prospective studies applying CKD screening in adults based on at least 1 CKD risk factor.

Data were abstracted from full texts and the risk of bias was assessed using the Joanna Briggs Institute critical appraisal tools.

No meta-analysis was conducted.

In total, 24 studies from 11 countries fulfilled the inclusion criteria. Diverse screening tests, CKD definitions, formulas for estimating kidney function, and positive screening test cutoffs were used. Most studies (n = 22) employed estimated glomerular filtration rate (eGFR), albumin-creatinine ratio (ACR) (n = 14), and dipstick urinalysis (n = 9) for screening. The prevalence of reduced kidney function and/or kidney damage was between 2.9% and 56%, and confirmed CKD varied from 4.4% to 17.1%. Increased patient referrals and physician visits, higher patient satisfaction, and some form of patient willingness to pay for the services were reported because of screening.

Meta-analysis was not conducted, and the findings might not be generalized to resource-limited settings.

Risk factor-based screening effectively identifies a substantial proportion of people with undiagnosed CKD, but there is still scope for improvement. We recommend future studies have robust designs and multidimensional interventions to establish the effectiveness of targeted CKD screening in primary care.

Studies exploring the correlation between Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and the increased risk of chronic kidney disease (CKD) from a country-specific perspective have been limited. This study addresses regional variations and the role of the Socio-Demographic Index (SDI) in this relationship.

This analysis integrates MASLD and country-level CKD data from the Global Burden of Disease study 2021. To evaluate the relationships between MASLD and CKD incidence, mixed-effects linear regression models that account for country-level random effects were employed. This analysis was adjusted for median age, percentage of males, SDI, and metabolic risk factors.

The incidence of MASLD and CKD demonstrated a similar regional distribution, with the highest of MASLD and CKD occurring in North Africa and the Middle East. After adjusting for age, gender, systolic blood pressure, fasting plasma glucose, body mass index, and SDI, a higher incidence of MASLD was associated with an increased incidence of CKD (p < 0.001), with MASLD incidence accounting for 53.0% of the explained variance in CKD incidence. Additionally, SDI, demographic variables (median age, population of male) and metabolic risks (High SBP, FPG and BMI), were responsible for 10.4%, 6.3%, and 30.3% of the explained variance in CKD incidence, respectively. Different patterns emerged in this association according to SDI status. In low SDI countries, significant associations were observed between increasing MASLD incidence rates and higher CKD incidence (p = 0.007), whereas in high SDI countries, no significant associations were found between MASLD and CKD incidence (p = 0.106).

Our findings reveal a geographical correlation between MASLD and CKD incidence, contingent upon socioeconomic factors. To effectively mitigate the global burden of MASLD and CKD, it is imperative to design and implement targeted public health strategies that consider the unique socioeconomic contexts of each region, thus fostering equitable health outcomes.

Raising awareness of chronic kidney disease (CKD) is essential for early detection and prevention, since the condition remains largely underdiagnosed, particularly in primary care settings. The present study aimed to evaluate awareness levels regarding the causes and symptoms of CKD among individuals receiving primary care.

This cross-sectional study included 457 participants recruited from two primary care centers in Türkiye using systematic random sampling. The data were collected via face-to-face interviews using a pre-tested questionnaire between April and June 2023. Awareness levels were classified using Bloom's cutoff points-high awareness (≥ 80%), moderate awareness (60-79%), and low awareness (< 60%).

The mean age of the participants was 42.3 ± 14.9 years. The study population consisted of 55.4% women, 51.2% of the participants were aged 18-39, 74.6% were married, and 53.4% held at least a university bachelor's degree. As for CKD awareness, 64.1% were aware that CKD can be caused by pain medication, 56% that it can be caused by hypertension, and 48.8% that it can result from diabetes. Additionally, 58.6% were aware that swelling of the feet and ankles can represent a symptom of CKD. Awareness of the causes and symptoms of CKD was low in 78.6% of our participants (n = 359), moderate in 17.5% (n = 80) and high in 3.9% (n = 18). Individuals who recalled having been informed about these causes and symptoms by their primary care physicians exhibited higher awareness. No significant differences in awareness were observed across different sociodemographic groups. A positive correlation was observed between awareness of the causes of CKD and awareness of its symptoms.

Awareness of CKD causes and symptoms among the participants was limited, nearly half being unaware of key risk factors such as painkiller use, obesity, hypertension, smoking, diabetes, and herbal product use. Increased education, particularly by primary care physicians, may improve awareness and early detection rates.

The kidneys and retina are highly vascularized organs that frequently exhibit shared pathologies, with nephropathy often associated with retinopathy. Previous studies have successfully predicted estimated glomerular filtration rates (eGFRs) using fundus photographs. We evaluated the performance of the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas in eGFR prediction.

We enrolled patients with fundus photographs and corresponding creatinine measurements taken on the same date. One photograph per eye was randomly selected, resulting in a final dataset of 45,108 patients (88,260 photographs). Data including sex, age, and blood creatinine levels were collected for eGFR calculation using the MDRD and CKD-EPI formulas. EfficientNet B3 models were used to predict each parameter.

Deep neural network models accurately predicted age and sex using fundus photographs. Sex was identified as a confounding variable in creatinine prediction. The MDRD formula was more susceptible to this confounding effect than the CKD-EPI formula. Notably, the CKD-EPI formula demonstrated superior performance compared to the MDRD formula (area under the curve 0.864 vs. 0.802).

Fundus photographs are a valuable tool for screening renal function using deep neural network models, demonstrating the role of noninvasive imaging in medical diagnostics. However, these models are susceptible to the influence of sex, a potential confounding factor. The CKD-EPI formula, less susceptible to sex bias, is recommended to obtain more reliable results.

The rising incidences of chronic kidney disease (CKD) and renal failure are a major public health concern. Arsenic, a widespread water contaminant and environmental toxicant, is well-known to contribute to kidney disease in adults. However, its long-term effects on kidney health following early-life exposure remain poorly understood. Therefore, we investigated the impact of prenatal arsenic exposure on kidney health in offspring using a BALB/c mouse model. 0.4 ppm arsenic, an environmentally relevant dose, was orally administered to female mice from 15 days before mating until delivery. Structural and ultrastructural changes in the kidney were assessed using histopathology and transmission electron microscopy, while markers of inflammation, kidney injury, and function were evaluated through Luminex assays, FITC-sinistrin-based glomerular filtration rate (GFR), real-time PCR, immunohistochemistry, and immunoblotting. Notably, arsenic-exposed offspring showed reduced body weight, crown-to-rump length, inflammation, and early signs of kidney injury on postnatal day 2 (PND-2). By 6 weeks, examination showed tubular dilation, mitochondrial damage, vacuolated cytoplasm, and basement membrane disruption were more evident in the kidneys. Furthermore, elevated levels of kidney injury markers, including kidney injury molecule-1, beta-2 microglobulin, cystatin C, and tissue inhibitor of metalloproteinase 1, were detected in urine. These changes were accompanied by increased serum creatinine and a decline in kidney function, as evidenced by reduced GFR levels. Proinflammatory cytokines (TNF-α, IL-6) and NF-κB were significantly elevated along with an increased immune cell infiltration in the kidneys of arsenic-exposed offspring. Further analysis showed increased mesenchymal markers fibronectin and alpha-smooth muscle actin and reduced epithelial marker E-cadherin in the kidneys, indicating fibrosis and epithelial-to-mesenchymal transition. Mechanistic studies revealed that arsenic exposure leads to increased levels of epigenetic regulators enhancer of zeste homolog 2 (EZH2) and histone H3 lysine 27 trimethylation (H3K27me3), which were associated with the activation of inflammatory pathways, fibrosis, and impaired kidney function. Overall, our findings demonstrate that only developmental exposure to arsenic can cause dysregulation of EZH2 and H3K27me3, driving inflammation and renal fibrosis. These changes ultimately lead to chronic kidney disease in offspring, highlighting a critical window of vulnerability for arsenic toxicity with significant implications for long-term kidney health.

The aim of this study was to investigate the association of macular microcirculation with renal function and the feasibility of using macular microcirculatory parameters to monitor renal function in Chinese non-diabetic patients with hypertension.

This case-control study included 62 non-diabetic patients with hypertension, including 31 with renal dysfunction (estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2) and 31 with normal renal function (eGFR ≥90 mL/min/1.73 m2). Age, sex and clinic blood pressure were matched between groups. Macular microcirculatory parameters of 124 eyes of the 62 patients were evaluated by optical coherence tomography (OCT) and OCT angiography (OCTA).

In comparison with the patients with normal renal function, patients with renal dysfunction had lower macular superficial parafovea vessel density (18.6 vs. 19.4%, P = 0.029), macular cube average thickness (273.0 vs. 280.2 µm, P = 0.003), and average ganglion cell layer and inner plexiform layer (GCL-IPL) thickness (79.5 vs. 82.8 µm, P = 0.006), but similar macular central fovea vessel density and central fovea thickness (P ≥ 0.54). After adjustment for confounders, eGFR was significantly associated with macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness (P < 0.02). In detecting renal dysfunction, areas under the curve were 0.61, 0.66 and 0.65 for macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness.

In non-diabetic patients with hypertension, macular superficial parafovea vessel density, cube average thickness and GCL-IPL thickness were significantly worse in patients with renal dysfunction than those with normal renal function. Using macular parameters to monitor renal function is feasible.

Despite the majority of patients with chronic kidney disease (CKD) live in low- and middle-income countries, most evidence on screening strategies is derived from high-income countries, where the contexts differ significantly. This study aims to assess the cost-effectiveness of population-based CKD screening strategies in both the general population and adults with diabetes in China.

A validated microsimulation model of CKD was developed to evaluate the costs and health consequences of population-based CKD screening strategies from a societal perspective. A cohort of the population aged 45 years in China was simulated over their lifetime. Model parameters were estimated based on the existing literature and various data sources in China. Main outcomes included the averted number of cases with cardiovascular disease (CVD) and kidney failure with replacement therapy (KFRT) under the population-based screening strategy compared with usual care, and the incremental cost-effectiveness ratios (ICERs). CKD screening with different frequencies and for different age groups in both the general population and adults with diabetes were considered. One-way sensitivity analyses were performed to assess the robustness of the results.

The ICER of annual screening starting at 45 years of age was $10,588 per quality-adjusted life year (QALY) for the general population and $9184 per QALY for adults with diabetes. Other screening strategies were also cost-effective compared to usual care, with ICERs less than three times the per-capita gross domestic product of China ($35,501). The most prominent absolute decrease in lifetime incidence of KFRT and CVD were also observed with the annual screening strategy in both the general population and in adults with diabetes. Specifically, the decreases were 1.88 and 8.55 per 1000 individuals for KFRT, and 35.07 and 19.92 per 1000 individuals for CVD, respectively.

CKD screening in both the general population and adults with diabetes is cost-effective and could avert substantial numbers of KFRT and CVD cases in China.

This study was supported by grants from National Natural Science Foundation of China (72125009), National Key Research and Development Program of China (2022YFF1203001), National High Level Hospital Clinical Research Funding (State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, 24QZ007), Peking University Medicine Sailing Program for Young Scholars' Scientific & Technological Innovation (BMU2023YFJHMX014), Young Elite Scientists Sponsorship Program by CAST (2022QNRC001), and CAMS Innovation Fund for Medical Sciences (2019-I2M-5-046).

The prevalence of kidney-related diseases has been increasing and has emerged globally as a leading cause of mortality, especially in developing countries where they are considered a neglected public health problem. Renal diseases are commonly progressive and may cause irreversible loss of organ function, eventually necessitating renal replacement therapy. Although different pharmaceuticals are considered for the treatment of these pathologies, the uncertain effectiveness and presence of adverse effects have generated a growing need for the development of novel nephroprotective compounds. Because many medicinal herbs are typically used in Brazilian folk medicine to prevent and cure kidney ailments, ethnomedicine may play a promising and strategic role in identifying and adding new potential molecules to the pharmacological arsenal. This review focuses on the use of plants and secondary metabolites belonging to different classes to treat renal diseases, associating the screened plant extracts with the bioactive components present in each species. Flavonoids and triterpenes are notable metabolites that have therapeutic potential. The putative pharmacological mechanisms related to nephroprotective properties are also discussed in in vitro and in vivo models, when available.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Guideline for Identification and Management of Chronic Kidney Disease (CKD) is a welcome development, coming 12 years after the paradigm-changing 2012 guidelines. We are living in an unprecedented era in nephrology with novel therapies, including sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists, now being proven in multiple randomized controlled clinical trials to reduce both the progression of CKD and cardiovascular morbidity and mortality. The KDIGO 2024 CKD Guideline is aimed at a broad audience looking after children and adults with CKD and provide practical and actionable steps to improve care. This commentary reviews the guideline sections pertaining to the evaluation and risk assessment of individuals with CKD from a European perspective. We feel that despite the last guideline being published 12 years ago, and the fact that the assessment of CKD has been emphasized by many other national/international nephrology, cardiology and diabetology guidelines and societies, the diagnosis and treatment of CKD remains poor across Europe. As such, the KDIGO 2024 CKD Guideline should be seen as an urgent call to action to improve diagnosis and care of children and adults with CKD across Europe. We know what we need to do. We now need to get on and do it.

A slower adoption rate of fixed dose combinations (FDC) in diabetes management is partly due to insufficient data. This study evaluates the safety and efficacy of an FDC of dapagliflozin + sitagliptin + metformin hydrochloride extended release (XR), compared to a dual FDC of sitagliptin + metformin hydrochloride XR among patients with type 2 diabetes mellitus (T2DM) with poor glycemic control when treated with metformin monotherapy.

A total of 274 patients with T2DM were randomized (1:1) to either arm X, receiving FDC of dapagliflozin (10 mg) + sitagliptin (100 mg) + metformin hydrochloride XR (1000 mg) (Dapa + Sita + Met) tablets, or arm Y, receiving sitagliptin phosphate (100 mg) + metformin hydrochloride XR (1000 mg) (Sita + Met) tablets, and treated for 16 weeks. The outcome measures included changes in hemoglobin A1c (HbA1c)(%), fasting plasma glucose (FPG), 2-h post-prandial glucose (PPG), weight, and the proportion of patients achieving target HbA1c levels of < 7.0% by week 16 of the study period.

The reduction in HbA1c at week 16 was significantly higher in arm X than in arm Y [estimated treatment difference (ETD), - 0.65% (95% CI - 0.76 to - 0.53; P < 0.0001)]. Arm X showed a marked decrease in FPG [ETD - 15.42 mg/dl; 95% CI (17.63, 13.22; P < 0.0001)], PPG [ETD - 30.39 mg/dl; 95% CI (35.59, 25.19; P < 0.0001)], and weight [ETD - 1.47 kg; 95% CI (1.59, 1.28; P < 0.0001)] after 16 weeks. In arm X, 54% of patients reached HbA1c < 7.0% compared to 29.9% in arm Y. The incidence of adverse events was comparable [13.14% (arm X) vs 12.4% (arm Y)]. There was no severe hypoglycemia-led treatment discontinuation.

Among patients with T2DM who have poor glycemic control with metformin monotherapy, triple FDC (Dapa + Sita + Met) effectively helped achieve better glycemic response compared to dual FDC (Sita + Met), with a comparable safety and tolerability profile.

CTRI/2022/01/039857.

Malnutrition is a prevalent complication in patients undergoing peritoneal dialysis (PD). This study established a multidisciplinary team for medical nutrition therapy (MNT) to investigate the impact of this approach on enhancing the nutrition, anemic, and microinflammatory status of patients receiving PD.

This randomized controlled trial study involved 81 patients undergoing PD (n = 41 in the intervention group, n = 40 in the control group). The intervention group received comprehensive MNT management, whereas the control group received standard nutrition care. The intervention spanned a 6-month period. Various nutrition parameters, markers of anemia, and microinflammatory indexes were assessed before the intervention, at 3 months, and at 6 months postintervention. Repeated-measures analysis of variance and the nonparametric Scheirer-Ray-Hare test were used for within-group and between-group comparisons.

There were no statistically significant differences between the groups in terms of age, sex, duration of dialysis, primary disease, or baseline prenutrition inflammation data. At 6 months postintervention, the intervention group exhibited higher levels of serum albumin, blood calcium, serum iron, hemoglobin, total iron-binding capacity, body mass index, midarm circumference, triceps skinfold thickness, handgrip strength, and daily energy and protein intake compared with the control group (P < 0.05). Additionally, the intervention group demonstrated lower levels of subjective nutrition assessment value, C-reactive protein, and neutrophil-to-lymphocyte ratio than the control group (P < 0.05), with no statistically significant differences in other markers after interventions.

Multidisciplinary MNT can ameliorate the nutrition status of patients receiving PD, decrease the incidence of malnutrition, and improve anemia and microinflammatory outcomes.

Chronic kidney disease (CKD) is defined by persistent abnormalities of kidney function or structure that have consequences for the health. A progressive decline of excretory kidney function has effects on body homeostasis. CKD is tightly associated with accelerated cardiovascular disease and severe infections, and with premature death. Kidney failure without access to kidney replacement therapy is fatal - a reality in many regions of the world. CKD can be the consequence of a single cause, but CKD in adults frequently relates rather to sequential injuries accumulating over the life course or to the presence of concomitant risk factors. The shared pathomechanism of CKD progression is the irreversible loss of kidney cells or nephrons together with haemodynamic and metabolic overload of the remaining nephrons, leading to further loss of kidney cells or nephrons. The management of patients with CKD focuses on early detection and on controlling all modifiable risk factors. This approach includes reducing the overload of the remaining nephrons with inhibitors of the renin-angiotensin system and the sodium-glucose transporter 2, as well as disease-specific drug interventions, if available. Hypertension, anaemia, metabolic acidosis and secondary hyperparathyroidism contribute to cardiovascular morbidity and reduced quality of life, and require diagnosis and treatment.

Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic clinical condition characterized by pathological and physiological interactions among metabolic abnormalities, chronic kidney disease, and cardiovascular diseases, leading to multi-organ dysfunction and a higher incidence of cardiovascular endpoints. Traditional approaches to managing CKM syndrome risk are inadequate in these patients, necessitating strategies targeting specific CKM syndrome risk factors. Increasing evidence suggests that addressing uremic toxins and/or pathways induced by uremic toxins may reduce CKM syndrome risk and treat the disease. This review explores the interactions among heart, kidney, and metabolic pathways in the context of uremic toxins and underscores the significant role of uremic toxins as potential therapeutic targets in the pathophysiology of these diseases. Strategies aimed at regulating these uremic toxins offer potential avenues for reversing and managing CKM syndrome, providing new insights for its clinical diagnosis and treatment.

The C-reactive protein/Lymphocyte Ratio (CLR) is a novel biomarker whose role in the development of chronic kidney disease (CKD) is not well understood. This study aimed to investigate the correlation between CLR and the prevalence of CKD.

This cross-sectional study included participants from the US National Health and Nutrition Examination Survey conducted between 1999 and 2010. Multivariate regression analyses and subgroup analyses were performed, controlling for socio-demographic variables, lifestyle behaviors, chronic diseases associated with kidney disease, and biochemical markers of bone metabolism. The associations between CLR and CKD prevalence, as well as indicators of renal damage, were explored. Non-linear relationships were analyzed using weighted restricted cubic splines. The predictive ability of CLR for CKD was assessed by the receiver operating characteristic curve and the area under the curve was calculated. Subgroup and sensitivity analyses were conducted to validate the robustness of the model.

A total of 13,862 respondents were included, comprising 2,449 CKD patients and 11,413 non-CKD patients. Weighted logistic regression modeling revealed a positive correlation between CLR levels and CKD prevalence (Odds ratio [OR] = 1.54, 95% Confidence interval [CI] = 1.30 to 1.83, P < 0.001). Additionally, CLR levels were negatively correlated with the glomerular filtration rate, a marker of renal injury, and positively correlated with the urinary albumin/creatinine ratio. The receiver operating characteristic curve demonstrated that the area under the curve for CLR in predicting CKD was 0.653 (95% CI, 0.641-0.665). The optimal cutoff value was 0.856, with a sensitivity of 0.703, specificity of 0.526, positive predictive value of 0.874, and negative predictive value of 0.275. The robustness of the model was confirmed through subgroup and sensitivity analyses.

Analysis of a large cross-sectional dataset demonstrated a positive correlation between CLR levels and CKD prevalence, suggesting that CLR may serve as a novel marker for the development and treatment of CKD.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Chronic Kidney Disease (CKD) is recognized as a major global public health problem. Dialysis is the mainstay of treatment for patients with end-stage renal disease and can prolong survival in patients with CKD. As patient survival increases, the treatment of complications becomes more important. CKD-mineral and bone disorders (CKD-MBD) and renal anemia are common complications in patients with CKD. Cinacalcet is a calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in adult dialysis patients, which regulates the synthesis and secretion of parathyroid hormone by increasing the sensitivity of calcium-sensitive receptors. This retrospective study evaluated the efficacy of cinacalcet in dialysis patients.

Forty-six patients on dialysis with elevated parathyroid hormone were included. The selected patients have regular follow-up visits in our outpatient clinic and regular use of cinacalcet for no less than 6 months.

During the 6-month efficacy evaluation phase, cinacalcet not only reduced the levels of the intact parathyroid hormone (iPTH, P ≤ 0.05), serum calcium (P ≤ 0.01), and Ca×P (P ≤ 0.05) but also reduced weekly erythropoietin (EPO) dosage (P ≤ 0.01) and erythropoietin resistance index (ERI, P ≤ 0.05).

While controlling SHPT in patients with CKD, cinacalcet reduced EPO resistance and improved renal anemia. In conclusion, cinacalcet not only decreased the levels of the iPTH, serum calcium, and Ca×P but also reduced weekly EPO dosage and ERI levels. Controlling SHPT in patients with CKD, cinacalcet also reduced ERI and improved renal anemia.

Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.

Chronic Kidney Disease of Unknown Etiology (CKDu) is a worldwide hidden health threat that is associated with progressive loss of kidney functions without showing any initial symptoms until reaching end-stage renal failure, eventually leading to death. It is a growing health problem in Asia, Central America, Africa, and the Middle East, with identified hotspots. CKDu disease mainly affects young men in rural farming communities, while its etiology is not related to hypertension, kidney stones, diabetes, or other known causes. The main suspected causal factors are heat-stress, dehydration, exposure to agrochemicals, heavy metals and use of hard water, infections, mycotoxins, nephrotoxic agents, altitude, and genetic factors. This review gives an overview of CKDu and sheds light on its medical history, geographic distribution, and worldwide prevalence. It also summarizes the suspected causal factors, their proposed mechanisms of action, as well as the main methods used in the CKDu prior detection and surveillance. In addition, mitigation measures to reduce the burden of CKDu are also discussed. Further investigation utilizing more robust study designs would provide a better understanding of the risk factors linked to CKDu and their comparison between affected regions.

This research aims to enhance our comprehensive understanding of the influence of type-2 diabetes on the development of cardiovascular diseases (CVD) risk, its underlying determinants, and to construct precise predictive models capable of accurately assessing CVD risk within the context of Bangladesh. This study combined data from the 2011 and 2017 to 2018 Bangladesh Demographic and Health Surveys, focusing on individuals with hypertension. CVD development followed World Health Organization (WHO) guidelines. Eight machine learning algorithms (Support Vector Machine, Logistic Regression, Decision Tree, Random Forest, Naïve Bayes, K-Nearest Neighbor, Light GBM, and XGBoost) were analyzed and compared using 6 evaluation metrics to assess model performance. The study reveals that individuals aged 35 to 54 years, 55 to 69 years, and ≥ 70 years face higher CVD risk with adjusted odds ratios (AOR) of 2.140, 3.015, and 3.963, respectively, compared to those aged 18 to 34 years. "Rich" respondents show increased CVD risk (AOR = 1.370, P < .01) compared to "poor" individuals. Also, "normal weight" (AOR = 1.489, P < .01) and "overweight/obese" (AOR = 1.871, P < .01) individuals exhibit higher CVD risk than "underweight" individuals. The predictive models achieve impressive performance, with 75.21% accuracy and an 80.79% AUC, with Random Forest (RF) excelling in specificity at 76.96%. This research holds practical implications for targeted interventions based on identified significant factors, utilizing ML models for early detection and risk assessment, enhancing awareness and education, addressing urbanization-related lifestyle changes, improving healthcare infrastructure in rural areas, and implementing workplace interventions to mitigate stress and promote physical activity.

The purpose of the research was to investigate the effects of aerobic training on renal function, oxidative stress, intrarenal renin-angiotensin system, and mortality of hypertensive and diabetic (SHR-STZ) rats.

Blood pressure, creatinine, urea levels, urinary glucose, urine volume, and protein excretion were reduced in trained SHR-STZ rats.

Aerobic training not only attenuated oxidative stress but also elevated the activity of antioxidant enzymes in the kid'ney of SHR-STZ rats. Training increased intrarenal levels of angiotensin-converting enzymes (ACE and ACE2) as well as the neprilysin (NEP) activity, along with decreased intrarenal angiotensin II (Ang II) levels. Aerobic training significantly improved the survival of STZ-SHR rats.

The protective role of aerobic training was associated with improvements in the renal antioxidative capacity, reduced urinary protein excretion along with reduced intrarenal Ang II and increased NEP activity. These findings might reflect a better survival under the combined pathological conditions, hypertension, and diabetes.

To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators.

This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy.

A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients' protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = -2.880, p = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = -0.109, p = 0.001). Pearson correlation analysis revealed that dietary DPI (r = -0.109, p < 0.05), DEI (r = -0.226, p < 0.05) and phosphorus (r = -0.195, p < 0.001) intake were statistically correlated to Kt/V; dietary nDPI (r = 0.101, p < 0.05) and sodium (r = -0.144, p < 0.001) intake were statistically correlated to serum urea nitrogen; dietary DPI (r = 0.200, p < 0.001), DEI (r = 0.241, p < 0.001), potassium (r = 0.129, p < 0.05), phosphorus (r = 0.199, p < 0.001), and fiber (r = 0.157, p < 0.001) intake were statistically correlated to serum creatinine; dietary phosphorus (r = 0.117, p < 0.05) and fiber (r = 0.142, p < 0.001) intake were statistically correlated to serum phosphorus; dietary nDPI (r = 0.125, p < 0.05), DPI (r = 0.135, p < 0.05), nDEI (r = 0.116, p < 0.05), DEI (r = 0.125, p < 0.05), potassium (r = 0.148, p < 0.001), and phosphorus (r = 0.156, p < 0.001) intake were statistically correlated to subjective global assessment scores; dietary nDPI (r = 0.215, p < 0.001), DPI (r = 0.341, p < 0.001), nDEI (r = 0.142, p < 0.05), DEI (r = 0.241, p < 0.001), potassium (r = 0.166, p < 0.05), phosphorus (r = 0.258, p < 0.001), and fiber (r = 0.252, p < 0.001) intake were statistically correlated to handgrip strength in males; dietary fiber (r = 0.190, p < 0.05) intake was statistically correlated to handgrip strength in females.

The dietary nutrient intake of MHD patients need improvement. Inadequate dietary nutrient intake among MHD patients could have a detrimental effect on their blood test indexes and overall nutritional status. It is crucial to address and optimize the dietary intake of nutrients in this patient population to enhance their health outcomes and well-being.

Background. National surveys have reported variable prevalence of chronic kidney disease (CKD), due to differences in the characteristics of the population, study design, equations used for the estimated glomerular filtration rate (eGFR), and definitions. The EH-UH 2 survey is the first study evaluating CKD prevalence, characteristics, and awareness in Croatia. Methods. This was a cross-sectional nationwide observational study designed to assess the prevalence of CKD and cardio-kidney-metabolic risk factors in Croatia, which included 1765 randomly selected subjects. We estimated the prevalence of CKD by means of the albumin-to-creatinine ratio (ACR) and eGFR (CKD-EPI equation). Comorbidities and anthropometric and social factors related to the prevalence of CKD were analyzed, and the CV risk profile was evaluated. Results. The weighted prevalence of CKD (any stage), CKD stage ≥G3A A2, and CKD defined only as an eGFR <60 mL/min/1.73 m2 were estimated at 17.1%, 9.8%, and 7.9%, respectively. The prevalence was higher in men than in women (11.8% vs. 7.9%; p < 0.001). The weighted prevalence of an ACR >30 mg/g was 15.1%. Older age, male gender, diabetes, ePWV, and uric acid were independently associated with CKD prevalence. The awareness of CKD was 9.5%. Persons unaware of CKD were older with lower income, less education, more frequent diabetes, hypertension (less frequently controlled), and milder renal impairment. Conclusions. In Croatia, the estimated prevalence of CKD is high, being presented more frequently in men than in women. CKD patients have an unfavorable CV risk profile. The awareness of CKD is very low, reflecting poor health literacy in the general population but also in health-care workers.

This study aimed to explore the correlation between the extent of fundus damage and the severity of chronic kidney disease (CKD).

We collected data from 118 CKD patients, including general information, renal function indicators, and fundoscopic examination results. The stages of CKD and degrees of fundus lesions were graded. SPSS 25.0 software facilitated the analysis of correlations using Kendall's tau-b correlation analysis and ordinal regression analysis.

Statistically significant differences were observed among multiple CKD stages in the distribution of age, systolic blood pressure, diastolic blood pressure, hemoglobin, total cholesterol, homocysteine, cystatin C, serum creatinine, blood urea, eGFR, 24-h urine protein, urine microalbumin, urine microalbumin/urine creatinine, and blood β2-microglobulin, complement C3. Notably, the levels of cytokeratin 19 fragment and transforming growth factor β significantly increased in all CKD stages. Kendall's tau-b correlation analysis revealed a significant positive correlation between CKD stage and fundus lesion grade. Ordinal regression analysis indicated that sex differences, total cholesterol levels, and hemoglobin levels were significant predictors of fundus lesion risk. Compared with patients at stage 5 CKD, the risk of fundus damage is significantly lower in patients in stage 2 and stage 3, further demonstrating a positive correlation between renal function deterioration and increased risk of fundus damage.

Routine fundus screening and early intervention for fundus lesions are vital for assessing CKD deterioration, providing new directions for future related research.

The connection between peritoneal function and gut microbiota in peritoneal fibrosis (PF) patients remains uncertain.

Peritoneal equilibration test (PET) was employed to evaluate peritoneal function in patients with peritoneal fibrosis (PF). 16S rRNA sequencing was used to analyze the gut flora in incident peritoneal dialysis (PD) and PF groups, identifying differential microbial communities. Spearman's correlation analysis, conducted using SPSS 26.0, was employed to explore the microbial associations with PF.

In the PF group, the PET showed a 4-h dialysate-to-plasma creatinine ratio (D/PCr) ratio of 0.62 ± 1.01 and a 4-h ultrafiltration (UF) volume of 41.73 ± 76.71 mL with a 2.5% glucose dwell. The alpha diversity between the PD and PF groups did not exhibit a significant difference. The PD and PF groups were predominantly composed of Firmicutes, Tenericutes, and Ignavibacteriae. Linear discriminant analysis effect size (LEfse) analysis indicates that the Firmicutes, Lactobacillales, and Bacilli were significantly enriched in the PD group, whereas Lachnospiraceae, Phenylobacterium, and Caulobacteraceae were enriched among the PF group. The functional prediction of gut microbiota genes revealed variations in metabolic pathways related to lipid transport, energy metabolism, and post-translational protein modifications between the two cohorts. In the PF group, Ignavibacteriae and Bdellovibrio correlated positively with the 4-h D/PCr ratio (p <0.05), while Prevotella negatively correlated with the 4-h UF from 2.5% glucose dwell (p <0.05).

The intestinal microbiota of patients newly initiated on peritoneal dialysis significantly differs from that of those with long-term peritoneal dialysis complicated by peritoneal fibrosis, with the latter's peritoneal function potentially linked to Prevotella, Ignavibacteriae, and Bdellovibrio.

This was a retrospective study aimed at evaluating the efficacy of laparoscopic sleeve gastrectomy (LSG) as a strategy for weight loss in obese prospective voluntary kidney donors who were unable to achieve weight reduction through lifestyle changes.

This retrospective study included living kidney donors who underwent LSG as a strategy for weight loss in obese prospective voluntary kidney donors between 2012 and 2022. Prospective donors who were initially rejected due to obesity underwent LSG after pretransplantation evaluation. Changes in weight, body mass index (BMI), and laboratory parameters (hemogram, kidney function tests, liver function tests, fasting and postprandial glycemia, HbA1c, and lipid profile measurements) were recorded before bariatric surgery and before nephrectomy.

Of the 16 candidates who underwent LSG, one did not proceed with donor nephrectomy due to the intended recipient's death. Among the remaining 15 subjects, the average interval between bariatric surgery and donor nephrectomy was 165.95 ± 48.86 days. There was a significant decrease in BMI following bariatric surgery (P < .0001); the mean BMI before bariatric surgery was 40.94 ± 4.53 kg/m², and before nephrectomy, it was 30.91 ± 3.87 kg/m2. The mean weight loss was 22.64 ± 5.75 kg.

This study supports LSG as an effective approach for obese individuals who are potential kidney donors to achieve weight loss, mitigate obesity-associated risks, and become successful kidney donors.

The complexity of left ventricular (LV) trabeculae is related to the prognosis of several cardiovascular diseases.

To evaluate the prognostic value of LV trabecular complexity in patients with end-stage renal disease (ESRD).

Prospective outcome study.

207 participants on maintenance dialysis, divided into development (160 patients from 2 centers) and external validation (47 patients from a third center) cohorts, and 72 healthy controls.

3.0T, steady-state free precession (SSFP) and modified Look-Locker imaging sequences.

All participants had their trabecular complexity quantified by fractal analysis using cine SSFP images. Patients were followed up every 2 weeks until April 2023, or endpoint events happened. Random Forest (RF) and Cox regression models including age, diabetes, LV mass index, mean basal fractal dimension (FD), and left atrial volume index, were developed to predict major adverse cardiac events (MACE). Patients were divided into low- and high-risk groups based on scores derived from the RF model and survival compared.

Receiver operating characteristic curve analysis; Kaplan-Meier survival analysis with log rank tests; Harrel's C-index to assess model performance. A P value <0.05 was considered statistically significant.

Fifty-five patients (26.57%) experienced MACE during a median follow-up time of 21.83 months. An increased mean basal FD (≥1.324) was associated with a significantly higher risk of MACE. The RF model (C-index: 0.81) had significantly better discrimination than the Cox regression model (C-index: 0.74). Participants of the external validation dataset classified into the high-risk group had a hazard of experiencing MACE increased by 12.29 times compared to those in the low-risk group.

LV basal FD was an independent predictor for MACE in patients with ESRD. Reliable risk stratification models could be generated based on LV basal FD and other MRI variables using RF analysis.

2 TECHNICAL EFFICACY: Stage 2.

Oral corticosteroids (OCS) are effective anti-inflammatory agents used across a range of conditions. However, substantial evidence associates their use with increased risks for adverse events (AEs), causing high burden on healthcare resources. Emerging biologics present as alternative agents, enabling the reduction of OCS use. However, current modelling approaches may underestimate their effects by not capturing OCS-sparing effects. In this study, we present a modelling approach designed to capture the health economic benefits of OCS-sparing regimens and agents.

We developed a disease-agnostic model using a UK health technology assessment (HTA) perspective, with discounting of 3.5% for costs and outcomes, a lifetime horizon, and 4-week cycle length. The model structure included type 2 diabetes mellitus, established cardiovascular disease, and osteoporosis as key AEs and drivers of morbidity and mortality, as well as capturing transient events. Quality-adjusted life-years (QALYs), life-years, and costs were determined for OCS-only and OCS-sparing treatment arms. Outcomes were determined using baseline 50% OCS-sparing, considering several OCS average daily doses (5, 10, 15 mg).

A treatment regimen with 50% OCS dose-sparing led to lifetime incremental cost savings per patient of £1107 (95% confidence interval £1014-£1229) at 5 mg, £2403 (£2203-£2668) at 10 mg, and £19,501 (£748-£51,836) at 15 mg. Patients also gained 0.033 (0.030-0.036) to 0.356 (0.022-2.404) QALYs dependent on dose. The benefits of OCS sparing were long-term, plateauing after 35-40 years of treatment.

We present a modelling approach that captures additional long-term health economic benefits from OCS sparing that would otherwise be missed from current modelling approaches. These results may help inform future decision making for emerging OCS-sparing therapeutics by comparing them against the cost of such treatments.

Diabetic nephropathy (DN) is one of the leading clinical causes of end-stage renal failure. The classical aldose reductase (AR) inhibitor epalrestat shows beneficial effect on renal dysfunction induced by DN, with metabolic profile and molecular mechanisms remains to be investigated further. In the current study, integrated untargeted metabolomics, network pharmacology and molecular dynamics approaches were applied to explore the therapeutic mechanisms of epalrestat against DN. Firstly, untargeted serum and urine metabolomics analysis based on UPLC-Q-TOF-MS was performed, revealed that epalrestat could regulate the metabolic disorders of amino acids metabolism, arachidonic acid metabolism, pyrimidine metabolism and citrate cycle metabolism pathways after DN. Subsequently, metabolomics-based network analysis was carried out to predict potential active targets of epalrestat, mainly involving AGE-RAGE signaling pathway, TNF signaling pathway and HIF-1 signaling pathway. Moreover, a 100 ns molecular dynamics approach was employed to validate the interactions between epalrestat and the core targets, showing that epalrestat could form remarkable tight binding with GLUT1 and NFκB than it with AR. Surface-plasmon resonance assay further verified epalrestat could bind GLUT1 and NFκB proteins specifically. Overall, integrated system network analysis not only demonstrated that epalrestat could attenuate DN induced metabolic disorders and renal injuries, but also revealed that it could interact with multi-targets to play a synergistic regulatory role in the treatment of DN.

Since chronic kidney disease is highly insidious in the early stages, most diagnosed patients have already developed irreversible renal failure. There is a lack of effective implementation and standardization of health education management for patients with chronic kidney disease, and the impact of health education management on health information literacy is not yet known.

This randomized controlled clinical trial was conducted from March 2022 to March 2023. A total of 130 patients with chronic kidney disease stage 3-4 were selected from a tertiary hospital in Zhuhai via a convenience sampling method and were then randomly assigned to intervention and control groups. The Health Information Literacy Questionnaire for Chronic Kidney Disease was used to assess the health literacy of the patients at month 0 and month 12. In addition, the renal function-related indices of the patients were measured before and after the intervention. The study adhered to SPIRIT guidelines.

There was no significant difference between the two groups in health information literacy, platelet count, estimated glomerular filtration rate, or albumin level. However, the intervention group showed a significant improvement in health behavioral status such as information acquisition, checkups, and physical activity. Subgroup analysis revealed that hemoglobin was significantly higher in non-employed patients than in the intervention group. There was a significant improvement in hemoglobin level after receiving health guidance in patients with intermediate education, and acquisition capacity and estimated glomerular filtration rate in the intervention group were lower than in the control group for patients with elementary education.

Receiving health coaching helped to improve self-management behaviors and hemoglobin levels of patients with stage 3-4 chronic kidney disease. Education level is an important factor influencing the effectiveness of health coaching techniques.

This study was prospectively registered in the China Clinical Trial Registry on November 10, 2021, with registration number: ChiCTR2100053103.