Cardiovascular Risk in Pediatric Renal Transplant Recipients.

BACKGROUND: The survival of pediatric chronic kidney disease (CKD) patients has improved in recent decades due to advances in dialysis and transplantation. However, cardiovascular disease (CVD) emerges as the main cause of mortality in patients with CKD. OBJECTIVES: To estimate cardiovascular risk in children with CKD at least 1 year after kidney transplantation. In addition, the possible association of cardiovascular risk with classic biochemical markers and potential new markers of this outcome was investigated. METHODS: An observational ambidirectional (retrospective capture of risk factors and prospective study of outcomes) research including 75 patients who underwent renal transplant between 2003 and 2013 with postoperative follow-up of at least 1 year was conducted. The outcome variables adopted were the LV mass Z-score and the presence of coronary calcification on computed tomography using calcium Agatston score. RESULT: Only one patient had an elevated calcium score, and three children (4%) had an LV mass Z-score ≥ 2.0. After multivariable analysis, only gender, serum triglyceride, and serum renalase concentration remained significantly associated with LV mass. CONCLUSION: The low incidence of cardiovascular changes in the population studied confirms the benefit of transplantation for the cardiovascular health of children. Nevertheless, long-term follow-up of these patients is recommended, given the limited duration of kidney function provided by transplantation and the high likelihood of further dialysis and kidney transplants being required in these children.

Epigenetic Mechanisms in Sepsis-Associated Acute Kidney Injury.

Sepsis, the dysregulated immune response of the host to infections, leads to numerous complications, including multiple organ dysfunction with sepsis-associated acute kidney injury (SA-AKI) being a frequent complication associated with increased risk of mortality and the progression toward chronic kidney disease (CKD). Several mechanisms have been widely investigated in understanding the complex pathophysiology of SA-AKI, including hemodynamic alterations, inflammation, oxidative stress, and direct cellular injury driven by pathogens or cell-derived products (pathogen-associated molecular patterns and damage-associated molecular patterns). Despite advancements in the management of septic patients, the prognosis of SA-AKI patients remains significantly poor and is associated with high in-hospital mortality and adverse long-term outcomes. Therefore, recent research has focused on the early identification of specific SA-AKI endotypes and subphenotypes through epigenetic analysis and the use of potential biomarkers, either alone or in combination with clinical data, to improve prognosis. Epigenetic regulation, such as DNA methylation, histone modifications, and noncoding RNA modulation, is crucial in modulating gene expression in response to stress and renal injury in SA-AKI. At the same time, these modifications are dynamic and reversible processes that can alter gene expression in several pathways implicated in the context of SA-AKI, including inflammation, immune response, and tolerance status. In addition, specific epigenetic modifications may exacerbate renal damage by causing persistent inflammation or cellular metabolic reprogramming, leading to progression toward CKD. This review aims to provide a comprehensive understanding of the epigenetic characteristics that define SA-AKI, also exploring targeted therapies that can improve patient outcomes and limit the chronic progression of this syndrome.

Hallmarks for Thrombotic and Hemorrhagic Risks in Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) is a global health issue causing a significant health burden. CKD patients develop thrombotic and hemorrhagic complications, and cardiovascular diseases are associated with increased hospitalization and mortality in this population. The hemostatic alterations are multifactorial in these patients; therefore, the results of different studies are varying and controversial. Endothelial and platelet dysfunction, coagulation abnormalities, comorbidities, and hemoincompatibility of the dialysis membranes are major contributors of hypo- and hypercoagulability in CKD patients. Due to the tendency of CKD patients to exhibit a prothrombotic state and bleeding risk, they require personalized clinical assessment to understand the impact of antithrombotic therapy. The evidence of efficacy and safety of antiplatelet and anticoagulant treatments is limited for end-stage renal disease patients due to their exclusion from major randomized clinical trials. Moreover, designing hemocompatible dialyzer membranes could be a suitable approach to reduce platelet activation, coagulopathy, and thrombus formation. This review discusses the molecular mechanisms underlying thrombotic and hemorrhagic risk in patients with CKD, leading to cardiovascular complications in these patients, as well as the evidence and guidance for promising approaches to optimal therapeutic management.

Frailty Is Associated with Malnutrition-Inflammation Syndrome in Older CKD Patients.

Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition-inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried's frailty phenotype (FP), while malnutrition-inflammation syndrome was assessed using the Malnutrition-Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1). A total of 48 patients were frail, and mean eGFR was comparable in both frail and non-frail patients (24 ± 10 vs. 25 ± 11 mL/min/1.73 m2; p = 0.63). Frail patients had higher MIS (6 [4-11] vs. 4 [3-5]; p < 0.0001) but cytokine concentrations were comparable in both groups. At multivariate regression, FP was independently associated with MIS, age, gender and pre-albumin but not with cytokines. However, we found some associations between inflammatory cytokines and some specific frailty criteria: weight loss and slowness were associated with MCP-1 (respectively p = 0.049 and p < 0.0001) and weakness with IL-6 (p = 0.005); in conclusion, in older patients with advanced CKD, frailty is strictly associated with malnutrition-inflammation syndrome but not with circulating inflammatory cytokines.

Clinical Utility of LC-MS/MS for Blood Myo-Inositol in Patients with Acute Kidney Injury and Chronic Kidney Disease.

BACKGROUND: Diagnosing acute kidney injury (AKI) and chronic kidney disease (CKD) relies on creatinine, which lacks optimal diagnostic sensitivity. The kidney-specific proximal tubular enzyme myo-inositol oxygenase (MIOX) catalyzes the conversion of myo-inositol (MI) to D-glucuronic acid. We hypothesized that proximal tubular damage, which occurs in AKI and CKD, will decrease MIOX activity, causing MI accumulation. To explore this, we developed an LC-MS/MS assay to quantify plasma MI and assessed its potential in identifying AKI and CKD patients. METHODS: MI was quantified in plasma from 3 patient cohorts [normal kidney function (n = 105), CKD (n = 94), and AKI (n = 54)]. The correlations between MI and creatinine were determined using Deming regression and Pearson correlation and the impact of age, sex, and ethnicity on MI concentrations was assessed. Receiver operating characteristic curve analysis was employed to evaluate MI diagnostic performance. RESULTS: In volunteers with normal kidney function, the central 95th percentile range of plasma MI concentrations was 16.6 to 44.2 µM. Age, ethnicity, and sex showed minimal influence on MI. Patients with AKI and CKD exhibited higher median MI concentrations [71.1 (25th percentile: 38.2, 75th percentile: 115.4) and 102.4 (77, 139.5) µM], respectively. MI exhibited excellent sensitivity (98.9%) and specificity (100%) for diagnosing CKD. In patients with AKI, MI increased 32.9 (SD 16.8) h before creatinine. CONCLUSIONS: This study unveils MI as a potential renal biomarker, notably elevated in plasma during AKI and CKD. Plasma MI rises 33 h prior to serum creatinine, enabling early AKI detection. Further validation and exploration of MI quantitation in kidney disease diagnosis is warranted.

Prevalence and Risk Factors of Chronic Kidney Disease in Patients With Type 2 Diabetes in China: Cross-Sectional Study.

BACKGROUND: Chronic kidney disease (CKD) is a significant long-term complication of diabetes and is a primary contributor to end-stage kidney disease. OBJECTIVE: This study aimed to report comprehensive nationwide data on the prevalence, screening, and awareness rates of CKD in Chinese patients with type 2 diabetes, along with associated risk factors. METHODS: Baseline data analysis of the ongoing prospective, observational IMPROVE study was conducted. The study cohort comprised patients who had been diagnosed with type 2 diabetes more than 12 months prior, received at least 1 hypoglycemic medication, and were aged ≥18 years. The participants completed questionnaires and underwent laboratory assessments, including blood and urine samples. The data encompassed patient demographics, medical history, concurrent medications, and comorbidities. Comprehensive evaluations involved physical examinations, urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c), fasting blood glucose, 2-hour postprandial blood glucose, fasting blood lipid profile, and urinalysis. Descriptive statistics were applied for data interpretation, and logistic regression analyses were used to identify the CKD-associated risk factors in patients with type 2 diabetes. RESULTS: A national study from December 2021 to September 2022 enlisted 9672 participants with type 2 diabetes from 45 hospitals that had endocrinology departments. The enrollees were from diverse regions in China, as follows: central (n=1221), east (n=3269), south (n=1474), north (n=2219), and west (n=1489). The prevalence, screening, and awareness rates of CKD among patients with type 2 diabetes were 31% (2997/9672), 27% (810/2997), and 54.8% (5295/9672), respectively. Multivariate binary regression analysis revealed that the CKD risk factors were screening, awareness, smoking, age, diabetes duration, concurrent antihypertensive and microcirculation medications, diabetic complications (foot, retinopathy, and neuropathy), hypertension, elevated low-density lipoprotein (LDL) cholesterol, and suboptimal glycemic control. Subgroup analysis highlighted an increased CKD prevalence among older individuals, those with prolonged diabetes durations, and residents of fourth-tier cities. Residents of urban areas that had robust educational and economic development exhibited relatively high awareness and screening rates. Notably, 24.2% (1717/7107) of patients with an eGFR ≥90 mL/min/1.73 m2 had proteinuria, whereas 3.4% (234/6909) who had a UACR <30 mg/g presented with an eGFR <60 mL/min/1.73 m2. Compared with patients who were cognizant of CKD, those who were unaware of CKD had increased rates of HbA1c ≥7%, total cholesterol >5.18 µmol/L, LDL cholesterol >3.37 µmol/L, BMI ≥30 kg/m2, and hypertension. CONCLUSIONS: In a Chinese population of adults with type 2 diabetes, the CKD prevalence was notable, at 31%, coupled with low screening and awareness rates. Multiple risk factors for CKD have been identified. TRIAL REGISTRATION: ClinicalTrials.gov NCT05047471; https://clinicaltrials.gov/study/NCT05047471.

High ferritin is associated with liver and bone marrow iron accumulation: Effects of 1-year deferoxamine treatment in hemodialysis-associated iron overload.

BACKGROUND: Iron (Fe) supplementation is a critical component of anemia therapy for patients with chronic kidney disease (CKD). However, serum Fe, ferritin, and transferrin saturation, used to guide Fe replacement, are far from optimal, as they can be influenced by malnutrition and inflammation. Currently, there is a trend of increasing Fe supplementation to target high ferritin levels, although the long-term risk has been overlooked. METHODS: We prospectively enrolled 28 patients with CKD on hemodialysis with high serum ferritin (> 1000 ng/ml) and tested the effects of 1-year deferoxamine treatment, accompanied by withdrawal of Fe administration, on laboratory parameters (Fe status, inflammatory and CKD-MBD markers), heart, liver, and iliac crest Fe deposition (quantitative magnetic resonance imaging [MRI]), and bone biopsy (histomorphometry and counting of the number of Fe positive cells in the bone marrow). RESULTS: MRI parameters showed that none of the patients had heart iron overload, but they all presented iron overload in the liver and bone marrow, which was confirmed by bone histology. After therapy, ferritin levels decreased, although neither hemoglobin levels nor erythropoietin dose was changed. A significant decrease in hepcidin and FGF-23 levels was observed. Fe accumulation was improved in the liver and bone marrow, reaching normal values only in the bone marrow. No significant changes in turnover, mineralization or volume were observed. CONCLUSIONS: Our data suggest that treatment with deferoxamine was safe and could improve Fe accumulation, as measured by MRI and histomorphometry. Whether MRI is considered a standard tool for investigating bone marrow Fe accumulation requires further investigation. Registry and the registration number of clinical trial: ReBEC (Registro Brasileiro de Ensaios Clinicos) under the identification RBR-3rnskcj available at: https://ensaiosclinicos.gov.br/pesquisador.

Association between estimated pulse wave velocity and in-hospital and one-year mortality of patients with chronic kidney disease and atherosclerotic heart disease: a retrospective cohort analysis of the MIMIC-IV database.

BACKGROUND: Carotid-femoral pulse wave velocity has been identified as an autonomous predictor of cardiovascular mortality and kidney injury. This important clinical parameter can be non-invasively estimated using the calculated pulse wave velocity (ePWV). The objective of this study was to examine the correlation between ePWV and in-hospital as well as one-year mortality among critically ill patients with chronic kidney disease (CKD) and atherosclerotic heart disease (ASHD). METHODS: This study included a cohort of 1173 patients diagnosed with both CKD and ASHD, sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The four groups divided into quartiles according to ePWV were compared using a Kaplan-Meier survival curve to assess variations in survival rates. Cox proportional hazards models were employed to analyze the correlation between ePWV and in-hospital as well as one-year mortality among critically ill patients with both CKD and ASHD. To further investigate the dose-response relationship, a restricted cubic splines (RCS) model was utilized. Additionally, stratification analyses were performed to examine the impact of ePWV on hospital and one-year mortality across different subgroups. RESULTS: The survival analysis results revealed a negative correlation between higher ePWV and survival rate. After adjusting for confounding factors, higher ePWV level (ePWV > 11.90 m/s) exhibited a statistically significant association with an increased risk of both in-hospital and one-year mortality among patients diagnosed with both CKD and ASHD (HR = 4.72, 95% CI = 3.01-7.39, p < 0.001; HR = 2.04, 95% CI = 1.31-3.19, p = 0.002). The analysis incorporating an RCS model confirmed a linear escalation in the risk of both in-hospital and one-year mortality with rising ePWV values (P for nonlinearity = 0.619; P for nonlinearity = 0.267). CONCLUSIONS: The ePWV may be a potential marker for the in-hospital and one-year mortality assessment of CKD with ASHD, and elevated ePWV was strongly correlated with an elevated mortality risk in patients diagnosed with both CKD and ASHD.

Prediction of metabolic syndrome and its associated risk factors in patients with chronic kidney disease using machine learning techniques.

INTRODUCTION: Chronic kidney disease (CKD) and metabolic syndrome (MS) are recognized as public health problems which are related to overweight and cardiometabolic factors. The aim of this study was to develop a model to predict MS in people with CKD. METHODS: This was a prospective cross-sectional study of patients from a reference center in São Luís, MA, Brazil. The sample included adult volunteers classified according to the presence of mild or severe CKD. For MS tracking, the k-nearest neighbors (KNN) classifier algorithm was used with the following inputs: gender, smoking, neck circumference, and waist-to-hip ratio. Results were considered significant at p < 0.05. RESULTS: A total of 196 adult patients were evaluated with a mean age of 44.73 years, 71.9% female, 69.4% overweight, and 12.24% with CKD. Of the latter, 45.8% had MS, the majority had up to 3 altered metabolic components, and the group with CKD showed statistical significance in: waist circumference, systolic blood pressure, diastolic blood pressure, and fasting blood glucose. The KNN algorithm proved to be a good predictor for MS screening with 79% accuracy and sensitivity and 80% specificity (area under the ROC curve - AUC = 0.79). CONCLUSION: The KNN algorithm can be used as a low-cost screening method to evaluate the presence of MS in people with CKD.

The effect of hyperuricemia and its interaction with hypertension towards chronic kidney disease in patients with type 2 diabetes: evidence from a cross- sectional study in Eastern China.

Objectives: This study aimed to explore the synergistic interaction effect between hyperuricemia and hypertension towards chronic kidney disease in patients with type 2 diabetes. Methods: This research originates from a cross-sectional study performed in Zhejiang Province, Eastern China, between March and November 2018. The correlation between serum uric acid levels and the risk of chronic kidney disease was assessed using a restricted cubic spline model. An unconditional multivariable logistic regression model, along with an interaction table, was utilized to explore the potential interaction effect of hyperuricemia and hypertension towards chronic kidney disease. Results: 1,756 patients with type 2 diabetes were included in this study, the prevalence of chronic kidney disease (CKD) was 27.62% in this population. A U-shaped non-linear pattern emerged correlating serum uric acid (SUA) levels and CKD risk, indicating that both low and high SUA levels were linked to an increased CKD risk. This risk achieved its lowest point (nadir) at SUA approximately equals to 285µmol/L (p for trend <0.05). Once adjustments for age, gender, education level, abnormal fasting plasma glucose (FPG), abnormal hemoglobin A1c (HbA1c), abnormal total cholesterol (TC), abnormal high-density lipoprotein cholesterol (HDL-C), alcohol consumption and duration of diabetes were factored in, it was found that patients with both hyperuricemia and hypertension demonstrated a 5.42-fold (95% CI: 3.72-7.90) increased CKD risk compared to the reference group. The additive interaction between hyperuricemia and hypertension was statistically significant, as manifested by the following values: a relative excess risk due to interaction (RERI) of 2.57 (95% CI: 0.71-4.71), an attributable proportion due to interaction (AP) of 0.47 (95% CI: 0.14-0.64), and a synergy index (SI) of 2.39 (95% CI: 1.24-4.58). In contrast, there was no significant interaction effect in multiplicative scale. Conclusion: Hyperuricemia and hypertension may contribute additively to CKD, beyond their isolated impacts. Evaluating the risk of CKD in type 2 diabetes patients necessitates considering this potential interaction.

Urinary tract infections in chronic kidney disease in Nephrology unit, University Hospital Center of Befelatanana, Antananarivo.

INTRODUCTION: Urinary tract infection is the leading cause of nosocomial infection worldwide. It is a factor in the progression of chronic kidney disease. AIM: To determine the epidemiological, clinical, microbiological, therapeutic and evolving profile of patients with chronic kidney disease and urinary tract infection. METHODS: This was a retrospective, descriptive study lasting 5 years, from January 2014 to december 2018 in chronic kidney disease with urinary tract infection. RESULTS: Fifty-one patients (7.15%) were retained with a mean age of 53.03 years and a sex ratio of 0.55. Chronic kidney disease was in end-stage in 45.1% (n=23). Cystitis was found in 49.02% (n=25) and gram-negative bacilli were found in 74.50% (n=38), predominantly Escherichia coli (54.90%). Third generation of cephalosporins and fluoroquinolones were frequently prescribed as probabilistic antibiotics. Resistance to beta-lactam antibiotics was 50% for Escherichia coli. Factors influencing severe infection were: advanced age, male gender, urinary lithiasis, multiple antibiotic resistance and non-enterobacterial germs. CONCLUSION: Urinary tract infection in chronic kidney disease were frequent and particularly severe.

UK survey of patient and caregiver perspectives on the impact of chronic kidney disease-associated anaemia.

OBJECTIVE: Chronic kidney disease (CKD)-associated anaemia has substantial biopsychosocial impacts. This study explores the impact of CKD-associated anaemia and treatment preferences from the patient perspective. DESIGN: Cross-sectional survey. SETTING: Anonymised online survey implemented by Ipsos UK on behalf of the National Kidney Federation and GSK from October 2022 to January 2023. PARTICIPANTS: Data were collected from UK adults living with CKD (self-reported). PRIMARY AND SECONDARY OUTCOME MEASURES: Outcome measures were exploratory and not predefined. The cross-sectional survey was designed to explore the biopsychosocial impact of living with anaemia on individuals with CKD; their unmet needs; the treatment strategies typically implemented and the associated barriers/facilitators to adherence; the healthcare professional-patient relationship with regard to anaemia diagnosis and management. RESULTS: Of 101 participants, 90 (89%) were patients with CKD and 11 (11%) were informal carers. 96 (95%) participants reported symptom(s) relevant to their experience of CKD. 88 (87%) participants reported symptom(s) associated with anaemia and 61 (64%) expressed an impact on daily life including 18 (19%) unable to perform daily activities, 13 (14%) unable to go to work and 9 (9%) reporting poor social life/interactions. 85 (84%) participants reported they have received treatment for anaemia: intravenous iron (n=55, 54%), iron tablets (n=29, 29%), erythropoietin-stimulating agents (ESAs) via an autoinjector (n=28, 28%), ESA injections via a syringe (n=24, 24%), ESA injections via a dialysis machine (n=17, 17%), folic acid (n=22, 22%) and blood transfusion (n=17, 17%). Six of seven (86%) participants who received their ESA from a healthcare professional at home preferred injections whereas 13/27 (48%) participants who injected themselves at home preferred oral tablets. CONCLUSIONS: There is not a 'one-size-fits-all' approach to the management of CKD-associated anaemia. A personalised approach incorporating the treatment preferences of the individual should be explored when discussing treatment options.

New triple therapy for the diagnosis of CKD-MBD: a cross-sectional study in Shanxi province.

OBJECTIVES: To seek a triple combination of biomarkers for early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and to explore the diagnostic efficacy of ß2-microglobulin, parathyroid hormone and blood urea nitrogen in chronic kidney disease-mineral and bone metabolic disorder. PARTICIPANTS: We collected medical records of 864 patients with chronic kidney disease (without direct contact with patients) and divided them into two groups based on the renal bone disease manifestations of all patients. PRIMARY AND SECONDARY OUTCOME MEASURES: There were 148 and 716 subjects in the Chronic kidney disease-mineral and bone metabolic disorder and the control groups, respectively. The aggregated data included basic information and various clinical laboratory indicators, such as blood lipid profile, antibody and electrolyte levels, along with renal function-related indicators. RESULTS: It was observed that most renal osteopathy occurs in the later stages of chronic kidney disease. In the comparison of two clinical laboratory indicators, 16 factors were selected for curve analysis and compared. We discovered that factors with high diagnostic values were ß2-microglobulin, parathyroid hormone and blood urea nitrogen. CONCLUSIONS: The triple combination of ß2-microglobulin+parathyroid hormone+blood urea nitrogen indicators can play the crucial role of a sensitive indicator for the early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and in preventing or delaying the progress of chronic kidney disease-mineral and bone metabolic disorder.

Effect of chronic kidney disease on adverse drug reactions to anti-tubercular treatment: a retrospective cohort study.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse. We studied the incidence and profile of ATT-associated ADRs in patients with CKD and compared them with those with normal kidney function. METHODOLOGY: This retrospective study analyzed all patients initiated on ATT from January 2016 to August 2019. Patients were grouped into CKD and normal kidney function based on their eGFR. Data on ATT-associated ADRs were collected from medical records. Predictors of ADRs were assessed using univariable and multivariable logistic regression. Additionally, Propensity score matching and analysis were done for CKD and normal kidney function in 1:3 ratio. RESULTS: Of 1815 patients on ATT, 75 (4.1%) had CKD. ADRs were more frequent [36/75 (48.0%) vs. 239/1740 (13.7%), p ≤ 0.0001] and more severe [15/46 (32.6%) vs. 43/283 (15.1%), p = 0.010] in CKD than those with normal kidney function. The most common ADRs were hepatobiliary [23/75 (30.6%) vs. 156/1740 (8.9%), p ≤ 0.0001], neuropsychiatric [8/75(10.6%) vs. 21/1740(1.2%), p ≤ 0.0001], renal [4/75(5.3%) vs. 8/1740(0.4%), p = 0.001], and gastrointestinal [5/75(6.6%) vs. 34/1740 (1.9%), p = 0.020]. CKD was an independent predictor for ADRs (OR -4.96, 95% CI: 2.79-8.82; p ≤ 0.0001). The matched cohort showed similar results. CONCLUSION: ATT-associated ADRs were more common and severe in patients with CKD, despite drug dose modifications. Optimal dosing of ATT in CKD needs to be further evaluated.

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Uremic pruritus, a severe complication in patients with chronic kidney disease, is associated with a high prevalence. It can cause depression and sleep disorders, and seriously affect the quality of life and the social relations of patients. Recently, there is growing evidence showing that κ-opioid receptor agonists, including nalfurafine, difelikefalin, and nalbuphine, can effectively and safely reduce itching symptoms in patients with refractory uremic pruritus. Herein, we reviewed the epidemiology, pathogenesis, clinical symptoms, and treatment strategies of uremic pruritus, and summarized in detail the progress in clinical research on the use of κ-opioid receptor agonists, including nalfurafine, difelikefalin, and nalbuphine, in the management of patients with uremic pruritus.

Examining the impact of renal dysfunction and diabetes on post-myocardial infarction mortality: insights from a comprehensive retrospective cohort study across different age groups.

Aim. Chronic kidney disease (CKD) and diabetes mellitus (DM) contribute significantly to cardiovascular disease (CVD) and mortality, with prevalence increasing. The evolving demographic of myocardial infarction (MI) patients, influenced by sedentary lifestyles and advanced medical care, lacks understanding regarding the interplay of CKD, DM, age, and post-MI mortality. This study aims to address this gap by evaluating the long-term impact of CKD and DM on post-MI mortality across age groups. Methods. A retrospective cohort study utilized data from the Estonian Myocardial Infarction Registry (EMIR), Estonian Population Register (EPR), and six major hospitals in Estonia, covering AMI hospitalizations from 2012 to 2019. Statistical analyses included Cox proportional hazards regression models and Kaplan-Meier's curves. Results. Analysis of 17,085 MI patients revealed age-dependent associations between renal function and mortality. In patients <65 years, even minor decreases in renal function increased both short-term (HR 2.79, 95% CI 1.71-4.55) and long-term (HR 1.24, 95% CI 1.05-1.47) mortality. Mortality significantly increased in patients >80 years only below an estimated glomerular filtration rate (eGFR) of 44 ml/min/1.73 m2. Newly diagnosed DM patients exhibited higher mortality rates (average HR 1.53, 95% CI 1.45-1.62), while pre-DM did not significantly differ from non-DM patients across all age groups. The DM-renal failure interaction did not significantly influence mortality. Conclusions. An age-dependent association between eGFR and post-MI outcomes emphasizes the need for personalized therapeutic approaches considering age-specific eGFR thresholds and comorbidities to optimize patient management.

Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic and Non-Diabetic Patients with Advanced Chronic Kidney Disease in Peritoneal Dialysis on Residual Kidney Function: In Real-World Data.

Background and Objectives: Peritoneal dialysis (PD) is a renal replacement therapy modality in which the dialysis dose can be individually adapted according to the patients' residual kidney function (RKF). RKF is a crucial factor for technique and patient survival. Pharmacological strategies aimed at slowing the loss of RKF in patients on PD are limited. Therefore, we aimed to assess the potential effects and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on the preservation of RKF in patients with and without type 2 diabetes mellitus (T2DM) on PD during an average follow-up of 6 months. Materials and Methods: In this retrospective observational, single-center study on real-world data, we included patients from the Peritoneal Dialysis Unit of the Hospital General Universitario de Ciudad Real, who started treatment with SGLT-2 inhibitors during the period from December 2022 to December 2023. Data on analytical and clinical parameters, RKF, and peritoneal membrane transport function were retrospectively collected at months 0, 3, and 6. Results: Out of 31 patients in our unit, 16 prevalent patients initiated treatment with SGLT-2 inhibitors (13 empagliflozin and 3 dapagliflozin). A total of 62.5% were male and the mean age was 67.3 years. The baseline peritoneal ultrafiltration was higher in the non-diabetic patient (NDMP) group than in the diabetic patient (DMP) group. However, the residual diuresis volume, 24 h residual renal clearance rate of urea in urine, and 24 h proteinuria were higher in the DMP group than in the NDMP group. At the sixth month, patients in both groups preserved RKF and diuresis, with a trend towards a non-significant reduction in proteinuria and blood pressure. Only two patients of the DMP group presented adverse effects. Conclusions: The use of SGLT-2 inhibitors in our sample of patients with and without T2DM on PD appears to be safe and effective to preserve RKF.

Anticoagulant therapy in renal insufficiency theme: Anticoagulation in complex situations.

Many patients with impaired renal function have concurrent indications for anticoagulant therapy, including atrial fibrillation and venous thromboembolism. For mild chronic kidney disease, data from clinical trials and existing guidelines can be applied to clinical management. The benefits and harms of anticoagulation therapy in patients with more advanced renal impairment are nuanced, as both thrombotic and bleeding risk are increased. Until recently, data regarding anticoagulants in severe renal impairment were primarily observational, but emerging evidence includes a few small clinical trials and the emergence of novel agents hypothesized to have improved efficacy and safety in this population. In this review, we summarize existing data on anticoagulation in patients with chronic kidney disease. We suggest a framework for anticoagulation decision-making in the burgeoning worldwide population of patients with chronic kidney disease.

Apixaban Use in Patients with Kidney Impairment: A Review of Pharmacokinetic, Interventional, and Observational Study Data.

Chronic kidney disease (CKD) remains a significant global health issue and is a leading cause of mortality worldwide. Patients with CKD have an increased risk of developing atrial fibrillation (AF) and venous thromboembolism (VTE). While direct oral anticoagulants (DOACs) have become a standard of care for anticoagulation (AC) in patients with AF and VTE, the appropriate use of these agents in comorbid kidney impairment warrants detailed discussion. This scientific narrative review summarizes the effectiveness and safety of apixaban use in patients with renal dysfunction by assessing the current published pharmacokinetic, interventional, observational, and guideline data. Apixaban is a highly selective, orally active, direct inhibitor of factor Xa, with well-established pharmacokinetics and consistent clinical outcomes across a broad range of patient populations, including those with kidney impairment. Overall, the scientific literature has shown that apixaban has a favorable clinical efficacy and safety profile compared with vitamin K antagonists for patients with AF or VTE and comorbid kidney impairment. These data support the approved label dosing strategy of apixaban in reducing the risk of stroke/systemic embolism in patients with nonvalvular AF and in treating VTE across all ranges of kidney function. Both clinician experience and knowledge of patient-specific factors may be required in the management of comorbid patients with advanced CKD or those requiring dialysis, as data on these patients are limited.