Hemogram inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red-cell distribution width (RDW), and mean platelet volume (MPV) have been associated with type 2 diabetes mellitus (T2DM) and its complications, namely diabetic kidney diseases (DKD). We aimed to develop and validate logistic regression (LR) and CatBoost diagnostic models and study the role of adding these markers to the models.

All individuals who were managed in our secondary care center from March 2020 to December 2023 were identified. After excluding the ineligible patients, train-test splitting, and data preprocessing, two baseline LR and CatBoost-based models were developed using demographic, clinical, and laboratory features. The AUC-ROC of the models with biomarkers (NLR, PLR, RDW, and MPV) was compared to the baseline models. We calculated net reclassification improvement (NRI) and integrated discrimination index (IDI).

One thousand and eleven T2DM patients were eligible. The AUC-ROC of both LR (0.738) and CatBoost (0.715) models was comparable. Adding target inflammatory markers did not significantly change the AUC-ROC in both LR and CatBoost models. Adding RDW to the baseline LR model reclassified 41.7% of patients without DKD, in the cost of misclassification of 38.4% of DKD cases. This change was absent in CatBoost models, and other markers did not achieve improved NRI or IDI.

The basic models with demographical and clinical features had acceptable performance. Adding RDW to the basic LR model improved the reclassification of the non-DKD participants. However, adding other hematological indices did not significantly improve the LR and CatBoost models' performance.

The online version contains supplementary material available at 10.1007/s40200-024-01523-2.

With the advent of antiretroviral therapy, people with HIV (PWH) are living longer and are at risk of developing age-related comorbid illnesses, such as chronic kidney disease (CKD). The purpose of this review article is to summarize recent advances in the diagnosis and management of kidney disease in PWH, and ultimately inform clinical practice.

Individuals of West African descent are often genetically predisposed to develop CKD. Among carriers of the APOL-1 risk variant, Na+/K+ transport has been identified as the proximal driver in APOL-1-mediated pathogenesis. The use of urine biomarkers in CKD diagnosis among PWH has been supported and is comparable to the general population. Additionally, novel CKD therapies, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists can potentially offer significant clinical benefit to PWH with CKD.

Despite being an underrepresented group in clinical trials, recent research findings have broadened our understanding of kidney disease in PWH. Given that PWH experience an increased risk of developing CKD, early detection and management is vital in improving quality of life and overall healthcare outcomes.

Heart rate-corrected (QTc) interval prolongation is frequently linked to fatal arrhythmias and sudden cardiac death in chronic kidney disease (CKD) patients. In this cross-sectional study, we assessed the prevalence of prolonged QTc intervals and identified clinical factors associated with them across different stages of kidney failure.

723 patients with CKD stages 2-5 who had electrocardiogram records available were analyzed retrospectively. QTc intervals were calculated by correcting the QT intervals for all patients included in the study. QTc interval prolongation defined as a QTc interval ˃ 440 ms was assessed for its prevalence and its association with various clinical factors.

A total of 723 patients with CKD stages 2-5 were finally included in this study, among which 420 (58.1%) were male. The average age of the participants was 48.2 ± 14.6 years old. In patients with CKD stages 2-4, the prevalence of QTc interval prolongation was 26%, 24.1%, and 37.8%, respectively. Among patients with CKD stage 5, those not on dialysis had a prevalence of 63%, while those undergoing dialysis had a prevalence of 74.3%. Multivariate logistic regression analysis revealed that elevated levels of parathyroid hormone (PTH) were significantly associated with an increased risk of QTc intervals prolongation in CKD patients (aOR = 1.384, 95% CI 1.173-1.632; P < 0.001). This suggests that higher PTH levels may contribute to QTc interval prolongation in this population. The patients were then grouped by CKD stages. Elevated PTH levels were independently associated with an increased risk of QTc interval prolongation specifically in CKD stages 4 and 5 patients who were not on dialysis. After adjusting for potential confounders, this association remained significant (CKD stage 4: aOR = 2.571, 95% CI 1.030-6.416; P < 0.001; CKD stage 5, non-dialysis: aOR = 1.333, 95% CI 1.063-1.671; P < 0.001).

In patients with CKD, the prevalence of QTc prolongation increases with advancing CKD stages. Specially, among patients with CKD stage 4 and stage 5 who were not on dialysis, elevated PTH levels were independently associated with an increased risk of QTc interval prolongation.

Obesity is known to influence the circulating 25(OH)D level but less is known about whether it influences the time required to reach a stable 25(OH)D level after initiating vitamin D supplementation. This observational study was done to investigate whether BMI modified the time required to reach a steady-state 25(OH)D level in response to vitamin D supplementation. Participants in the Boston STOP IT study who were treated for 12 mo with 700 IU of vitamin D3 and 500 mg of calcium daily and had 25(OH)D measures at 0, 6, and 12 mo, were included. We assessed the trajectory of 25(OH)D levels by baseline BMI category (normal weight, BMI 18.5-24.9 kg/m2, n = 62; overweight and obese, BMI ≥ 25 kg/m2, n = 105). Baseline 25(OH)D levels were 78 ± 31.3 nmol/L (normal weight) and 74.7 ± 36.5 nmol/L (overweight and obese). In a linear mixed model examining the influence of time and baseline BMI category on change in the mean 25(OH)D level, there was a significant time x BMI group interaction (p = .024. The normal weight participants had reached steady-state 25(OH)D levels by 6 mo whereas 25(OH)D levels continued to rise between 6 and 12 mo in the overweight and obese participants. This analysis suggests that the time required to reach a steady-state 25(OH)D level after initiating vitamin D supplementation in overweight and obese adults is greater than the usual 3-mo time point commonly used in clinical practice. A more refined definition of the time course of circulating 25(OH)D response to supplementation is needed in overweight and obese individuals in order to optimize clinical monitoring of vitamin D status.

Among health care researchers, there is increasing debate over how best to assess and ensure the fairness of algorithms used for clinical decision support and population health, particularly concerning potential racial bias. Here we first distill concerns over the fairness of health care algorithms into four broad categories: (a) the explicit inclusion (or, conversely, the exclusion) of race and ethnicity in algorithms, (b) unequal algorithm decision rates across groups, (c) unequal error rates across groups, and (d) potential bias in the target variable used in prediction. With this taxonomy, we critically examine seven prominent and controversial health care algorithms. We show that popular approaches that aim to improve the fairness of health care algorithms can in fact worsen outcomes for individuals across all racial and ethnic groups. We conclude by offering an alternative, consequentialist framework for algorithm design that mitigates these harms by instead foregrounding outcomes and clarifying trade-offs in the pursuit of equitable decision-making.

Chronic kidney disease (CKD) is a complex health condition characterized by the gradual loss of renal function, often leading to end-stage renal disease (ESRD). It results from a combination of medical, environmental, and genetic factors. Predicting the rate of renal function decline and effectively managing the progression to ESRD is challenging in clinical practice. CKD assessment involves various indicators, including estimated glomerular filtration rate (eGFR), albuminuria levels, serum creatinine, and others. This study aimed to explore the predictive potential of specific blood cell indexes in forecasting further renal function decline and the transition from CKD stage 3-4 to ESRD. We assessed the following blood cell indexes in 377 CKD stage 3-4 patients: absolute neutrophil count (ANC), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), derived NLR (dNLR), mean platelet volume (MPV), aggregate index of systemic inflammation (AISI), and systemic inflammation index (SII). ANC, MPV, NLR, PLR, dNLR, and SII were found to independently predict a rapid decline in eGFR. Notably, NLR and dNLR demonstrated the highest sensitivity and specificity with cut-off values of 3.36 and 2.45, respectively (NLR: 88.6 and 81.7%; dNLR: 85.2 and 75.8%). The corresponding area under the ROC curve values were 0.877 (95% CI 0.837-0.918, p < 0.001) for NLR and 0.849 (95% CI 0.805-0.892, p < 0.001) for dNLR. However, none of the blood cell indexes independently predicted the transition to ESRD. The NLR and the dNLR exhibited the highest predictive capacity towards a rapid decline in renal function in CKD. No blood cell index, however, independently predicted the transition into ERSD.

Elevated total IgE levels are traditionally associated with allergic conditions; however, their potential role as biomarker for mortality risk beyond allergic diseases has not been extensively explored. Recent studies have suggested that IgE is associated with cardiovascular (CV) disease. We aimed to investigate the association between total IgE levels and the risk of all-cause and cause-specific mortality, as well as to explore the potential mediating role of vitamin status in these associations.

The association between IgE and mortality risk was examined in the National Health and Examination Survey 2005-2006. Weighted multivariable Cox proportional hazards model was employed. We further performed restricted cubic spline analysis to assess dose-response relationships and conducted mediation analysis to explore the influence of vitamins on IgE-related mortality risk. Individuals in the highest total IgE quantile (>107.0 kU/L) exhibited a 32 % increased risk of all-cause mortality (95 % CI: 1.07-1.64) and a 98 % elevated risk of CV mortality (95 % CI: 1.28-3.07) compared to the lowest quantile (<14.5 kU/L). Heterogeneity exists in the dose-response relationship and threshold effects among individuals with and without allergic diseases. Vitamin deficiency is associated with elevated total IgE levels, and vitamins mediated the relationship of the IgE-related all-cause mortality with the proportion of mediation ranging from 4.68 to 12.71 %.

Our findings introduce a novel dimension to the understanding of IgE as a biomarker for mortality beyond its traditional role in allergic diseases, challenging the current paradigm that elevated IgE levels without overt allergic symptoms are benign.

Co-existing primary aldosteronism (PA) and autonomous cortisol secretion (ACS) has been recently recognized as a distinct entity. This study aimed to assess the incidence of ACS in patients with PA, and its impact on clinical and laboratory parameters.

Ninety-two patients diagnosed with PA were included. Demographic data, comorbidities, laboratory and imaging results were retrospectively analyzed. Patients with overnight 1mg dexamethasone suppression test>1.8μg/dL were classified as PA with ACS.

Twenty-four patients (26.1%) were in the PA-with-ACS group, and 68 (73.9%) in the PA-without-ACS group. Mean age (P=0.034), body mass index (P=0.034), number of female patients (P=0.012) and maximum adenoma diameter (P<0.001) were higher in the PA-with-ACS group than in the PA-without-ACS group. Basal (P=0.001) and post-saline infusion plasma aldosterone concentrations (PAC) (P=0.009) were higher in the PA-without-ACS group than in the PA-with-ACS group. No significant differences between groups were found in intensity of antihypertensive treatment, presence of type 2 diabetes, coronary artery disease, proteinuria or glomerular filtration rate (P>0.05). Left ventricular hypertrophy (LVH) was detected in 49.4% of patients. Logistic regression demonstrated that PAC and gender were associated factors for LVH.

Cortisol co-secretion was identified in approximately one-quarter of patients diagnosed with PA. PA patients without ACS had higher PAC than those with co-existing ACS. According to our results, the co-existing ACS may not seem to have a significant negative impact on clinical parameters in patients with PA.

Objective: To identify factors associated with preserved split renal function (SRF) after robot-assisted partial nephrectomy (RAPN). Patients and Methods: The study included patients who underwent RAPN at Nagasaki University Hospital between November 2016 and December 2023. SRF was determined by 99mTc-dimercaptosuccinic acid renal imaging and the estimated glomerular filtration rate, with measurements obtained before and 6 months after surgery. The ipsilateral parenchymal volume (IPV) was measured at the same time. More than 90% SRF after surgery was considered to indicate successful preservation of renal function (the successful group), and ≤90% SRF was considered failure to preserve renal function (the unsuccessful group). The factors most relevant to SRF were sought in univariate and multivariate analyses. Results: Data for a total of 169 patients were analyzed. The median SRF was 32.04 mL/min/1.73 m2 (interquartile range [IQR] 25.95, 38.06) before surgery and 27.33 mL/min/1.73 m2 (IQR 21.64, 34.32) after surgery. The median SRF preservation rate was 88% (IQR 78.4, 97.0), with 94 cases (55.6%) having SRF >90% and 75 cases (44%) having SRF ≤90%. The median IPV on the surgical side was calculated by the software to be 152.2 cm3 (IQR 126.9, 186.6) preoperatively and 127.3 cm3 (IQR 102.9, 161.3) postoperatively, with a median preservation rate of 84.6% (IQR 72.2, 89.7). Univariate analysis showed significant between-group differences in diabetes status, RENAL Nephrometry score, operation time, warm ischemia time, whether or not parenchymal sutures were needed, and the amount of IPV preserved. Only percentage of IPV preserved remained significant in multivariate analysis. Conclusion: The findings of this study suggest that the residual IPV is an important determinant of SRF after RAPN.

Long-term complications such as renal diseases are well known in patients with chronic hypoparathyroidism (hypoPT), but risk of cardiovascular comorbidity remains less clear. This study comprehensively assessed cardiovascular parameters in hypoPT compared to matched controls.

Cross-sectional cohort study involving 168 patients with chronic hypoPT.

Patients underwent electrocardiograms, blood pressure measurements, and echocardiography. A 1:3 propensity score matching was performed with individuals from the German population-based Study of Health in Pomerania (SHIP-TREND) and the "Characteristics and Course of Heart Failure Stages A-B" (STAAB) cohort.

HypoPT showed significantly higher systolic (128 vs 125 mm Hg, P = .02) and diastolic blood pressures (83 vs 77 mm Hg, P < .01). Intake of antihypertensives was similar between groups. The QTc interval was markedly prolonged (438 vs 420 ms, P < .01) with QTc interval prolongation occurring significantly more frequently in hypoPT (24% vs 6%, P < .01). Interestingly, echocardiography revealed significantly lower left ventricular mass index (28 vs 43 g/m2.7, P < .01) and less frequent left ventricular hypertrophy (7%% vs 41%, P < .01) in hypoPT but comparable left ventricular ejection fraction (P = .48). HypoPT patients had higher prevalence of mitral (20 vs 0%, P < .01) and aortic valve stenoses (7 vs 2%, P < .01). Comparison with STAAB confirmed the increased prevalence of arterial hypertension and reduced myocardial mass indices.

Patients with hypoPT exhibit a higher prevalence of QTc interval prolongation despite established therapy and an increased incidence of hypertension. Conversely, echocardiography revealed lower left ventricular mass and less frequent left ventricular hypertrophy in hypoPT, but higher prevalence of valve stenosis. Regular monitoring of hypertension, QTc interval prolongation, and valve stenosis is recommended to reduce the risk of cardiovascular diseases.

NCT05585593.

With an increase in the elderly population, the frequency of hospitalizations in recent years has also risen at a rapid pace. This, in turn, has resulted in poor outcomes and costly treatments. Hospitalization rates increase in elderly patients due to a decline in glomerular filtration rate (GFR).

To investigate the connection between GFR and comorbidity and reasons for hospitalization in elderly patients.

We analyzed patients aged 75 years and over who were admitted to the internal medicine clinic of a tertiary hospital in Eskisehir. At admission, we calculated GFR values using the Modification of Diet in Renal Disease study formula and classified them into six categories: G1, G2, G3a, G3b, G4, and G5. We analyzed associations with hospitalization diagnoses and comorbidity factors.

The average age of the patients was 80.8 years (± 4.5 years). GFR was 57.287 ± 29.5 mL/kg/1.73 m2 in women and 61.3 ± 31.5 mL/kg/1.73 m2 in men (P = 0.106). Most patients were admitted to the hospital at G2 stage (32.8%). The main reasons for hospitalization were anemia (34.4% and 28.6%) and malnutrition (20.9% and 20.8%) in women and men, respectively (P = 0.078). The most frequent comorbidity leading to hospitalization was arterial hypertension (n = 168, 28%), followed by diabetes (n = 166, 27.7%) (P = 0.001).

When evaluating geriatric patients, low GFR alone does not provide sufficient information. Patients' comorbid factors should also be taken into account. There is no association between low GFR during hospitalization and hospitalization-related diagnoses. Knowing the GFR value before hospitalization will be more informative in such studies.

Accurate assessment of kidney function is essential for post-kidney transplant management. This study aims to develop a new equation tailored to Vietnamese kidney transplant recipients and validate its performance against established equations.

A total of 299 kidney transplant recipients underwent glomerular filtration rate (GFR) measurement using technetium-99m-diethylenetriaminepentaacetate renal dynamic scintigraphy, along with demographic, clinical, and laboratory assessments. Participants were divided into a development cohort (n = 150) to generate a new GFR-estimating equation and a validation cohort (n = 149) for internal validation against six equations.

The new equation, G F R = 100.430 × 1 . 080 sex × a g e - 0.097 × S c r - 0.524 × S c y s - 0.435 (sex: 0 = female; 1 = male), showed the smallest median bias (-0.11 [-1.40; 1.11]), highest P30 accuracy (94.0% [88.6; 96.6]), highest precision (interquartile range = 9.82 [7.63; 12.37]), and strongest correlation with measured GFR (r = 0.824 [0.752; 0.880]) among tested equations in the validation cohort. Among creatinine-based equations, the Modification of Diet in Renal Disease equation was the most accurate.

The new equation outperformed established equations and is recommended for Vietnamese kidney transplant recipients. The Modification of Diet in Renal Disease equation may serve as an alternative in centers lacking access to serum cystatin C. Further studies with larger cohorts, external validation, and comparisons with gold-standard GFR measurement methods are needed to confirm these results.

Remnant cholesterol (RC) has emerged as a novel therapeutic target beyond low-destiny-lipoproteins cholesterol (LDL-c). While elevated RC levels are strongly associated with cardiovascular disease risk in the general population, their specific role in young-onset acute myocardial infarction (AMI) among patients with type 2 diabetes mellitus (T2DM) remains insufficiently explored and warrants further investigation.

This retrospective study included AMI patients with T2DM admitted to the First Affiliated Hospital of Xi'an Jiaotong University from 2018 to 2022. Patients were stratified into tertiles according to RC levels and compared using thresholds derived the commanded values from the PREDIMED cohort study. The primary outcome was young-onset AMI. Group differences were analyzed using the chi-square test and the Kruskal-Wallis H test, while Spearman correlation analyses assessed relationships between variables. Univariate and multivariate logistic regression analyses were employed to evaluate the association between RC and young-onset AMI.

Among the 2,514 participants (mean age 61.58 ± 11.15 years), 802 (31.9%) had young-onset AMI. The increase of young-onset AMI increased significantly with rising RC levels (27.0% vs 29.7% vs 39.1%, P < 0.001). RC showed significant positive correlation with total cholesterol (TC, r = 0.497, P < 0.001), triglycerides (TG, r = 0.411, P < 0.001), and LDL-c (r = 0.166, P < 0.001). RC was independently associated with a higher risk of young-onset AMI (OR: 1.579; 95% CI: 1.354-1.842; P < 0.001), even after adjusting for other traditional risk factors of cardiovascular disease (OR: 1.415; 95% CI 1.189-1.684; P < 0.001). Notably, RC levels remained strongly linked to young-onset AMI regardless of whether LDL-c levels were within the desired range.

RC is a significant and independent risk factor for young-onset AMI in T2DM patients, irrespective of LDL-c level. These findings underscore the importance of monitoring and managing RC levels in clinical practice to mitigate cardiovascular risk in this population.

Prognostic prediction in heart failure (HF) is challenging and no single marker has proven effective. We propose an index based on B-type natriuretic peptide (BNP) and four widely available parameters.

We retrospectively analyzed adult outpatients with chronic HF with systolic dysfunction followed from January 2012 to December 2020. The new proposed index was calculated based on 5 parameters measured at the index visit. BASIC index = (BNP*(age)2) / (serum sodium*hemoglobin*estimated glomerular filtration rate). Patients were followed-up until January 2023; the primary endpoint was all-cause mortality. A receiver operator curve was used to assess the association of the index with outcome; a cut-off was chosen based on the curve. We used a Cox-regression analysis to determine the prognostic value of the index. Adjustments were made considering established prognostic predictors.

We studied 1065 patients. Mean age was 71 years, 65.8 % were male, 45.3 % had ischemic HF and 47.2 % had severe systolic dysfunction. During a 47-months median follow-up, 545 patients died (51.2 %). Median BASIC index: 11.7 (3.5-33.7). The area under the curve was 0.73 (0.70-0.76) vs 0.69 (0.66-0.72) for BNP, p < 0.001. The best cut-off value was 9.3; sensitivity = 71.4 %, specificity = 62.3 %, positive predictive value = 66.5 and negative predictive value = 67.5 %. Patients with a BASIC index above 9.3 had a multivariate-adjusted HR of all-cause mortality = 2.70 (2.20-3.22).

The incorporation of age, hemoglobin, serum sodium, glomerular filtration rate and BNP in an index significantly improves prognostic prediction when compared to BNP alone. Patients with a BASIC index above 9.3 have an almost 3-fold higher death-risk.

Renal aging is a physiological process characterized by structural and functional changes in the kidneys. The presence of disorders or pathologies can exacerbate these age-related changes, potentially leading to organ dysfunction. Chronic kidney disease (CKD), a significant global public health issue, is particularly prevalent in the elderly and is often associated with the age-related decline in kidney function. Anemia is one of the most frequent complications of CKD and is also highly prevalent in the elderly. Mild anemia, often multifactorial, is the most common presentation. Understanding the mechanisms driving anemia in this population is crucial to ensure appropriate treatment. The primary etiologies include nutritional deficiency, anemia of unknown cause, and anemia of chronic diseases, including CKD. This review provides an in-depth exploration of the complex pathophysiological mechanisms underlying anemia in elderly patients with CKD.

Population pharmacokinetic (PPK) models of vancomycin (VCM) commonly use creatinine clearance (CLcr) as a covariate for clearance (CL). However, relying on CLcr in patients of advanced age may lead to inaccuracies in estimating VCM clearance. Therefore, this study aimed to develop and validate a new PPK model specifically for patients aged 75 years and older.

PPK analysis was performed based on the blood concentrations of VCM (n = 159 patients). The predictive performance of the developed model was compared with that of previous models using mean absolute error (MAE) and mean squared error (MSE) for another dataset.

The PPK analysis optimized a two-compartment model using CLcr and the Alb levels as covariates at the central compartment of VCM clearance. The final model was as follows: CL (L/h) = 1.96 × (CLcr/3.09) 0.63 × (Serum albumin (Alb) /2.3) 0.22 × exponential (0.11). Clearance between the central and peripheral compartments (L/h) = 4.86. Central compartment volume of distribution (L) = 31.78. Peripheral compartment volume of distribution (L) = 53.64. The validation study revealed that compared with those of previous models (ranging from 0.67 to 0.79 L/h and from 0.81 to 1.11 (L/h)2, respectively), the final model demonstrated the smallest MAE of 0.60 L/h and MSE of 0.65 (L/h)2 for patients of advanced age with serum creatinine levels of < 0.6 mg/dL.

The PPK model of VCM for patients of advanced age was optimized by adding the Alb levels and CLcr as covariates for CL. The predictive accuracy of the PPK model for patients with an SCr of < 0.6 mg/dL tended to be higher than those of previous models based just on CLcr. Thus, dosage is suggested to be adjusted based on CLcr and Alb levels for patients with an SCr of < 0.6 mg/dL.

Contrast-induced acute kidney injury (CI-AKI) is a common complication of lower limb percutaneous transluminal angioplasty (PTA). Common risk models are based on cardiology cohorts for percutaneous coronary intervention. They include a mix of preoperative and perioperative variables, but do not include important information such as inflammatory parameters and preoperative medications. None make use of machine learning. We aimed to develop an accurate preoperative risk model for CI-AKI in lower limb PTA using machine learning methods and comparing these with conventional logistic regression.

A retrospective cohort of 456 patients who underwent lower limb PTA as an isolated procedure from 2015 to 2019 was identified. Patients <21 years old, patients with a preoperative estimated glomerular filtration rate of <15 mL/min/1.73 m2 as defined by the modification of diet in renal disease, and patients with no valid preoperative or postoperative serum creatinine were excluded. Conventional logistic regression and a range of machine learning models were fitted (logistic regression with elastic-net penalty, random forests, gradient boosting machines, k-nearest neighbors, Support vector machines, and multilayer perceptron), using 5-fold cross-validation and grid search for hyperparameter selection. Area under receiver operating curve, area under precision-recall curve, F1 score, and the sensitivity and specificity were determined on the test set. Variable importance was examined using SHapley Additive exPlanation plots.

Machine learning models performed well, with the best performance by the k-nearest neighbors algorithm (area under receiver operating curve = 0.914, area under precision-recall curve = 0.809). Important variables identified by SHapley Additive exPlanation plot analysis included modification of diet in renal disease estimated glomerular filtration rate, haemoglobin, and inflammatory indices (neutrophil: lymphocyte ratio, red cell distribution width).

We developed machine learning models to accurately predict CI-AKI in patients undergoing elective lower limb PTA, using preoperative variables only. This model may be used for preoperative patient risk counseling by surgeons and anesthetists and may assist in identifying high-risk patients for further monitoring.

Heart failure (HF) is known to reduce glomerular filtration rate (GFR), while chronic kidney disease (CKD) significantly increases the risk of left ventricular hypertrophy (LVH) and HF. Although these connections have been explored in separate studies, comprehensive research examining the mutual links between CKD and LVH progression is lacking.

Our study investigates the longitudinal relationship between estimated GFR (eGFR) and left ventricular mass index (LVMI) in a cohort of 106 CKD patients across stages G1-5. Using a cross-lagged model, we paired each predictor (eGFR or LVMI) with subsequent outcome measurements, adjusting for previous values to ensure accuracy. Over a three-year follow-up period, we analyzed 257 paired LVMI and eGFR measurements.

At baseline, the median eGFR was 54 ml/min/1.73 m2, and the LVMI was 134 ± 48 g/m2, with a 62% prevalence of LVH. Our adjusted models revealed that a decrease in eGFR by 1 ml/min/1.73 m2 predicted an increase in LVMI of 1.12 g/m2 (95% CI: 0.71-1.54, P < 0.001). In contrast, high LVMI did not predict a reduction in eGFR over time. This analysis highlights a significant risk of LVH worsening due to GFR loss, while the reverse risk does not achieve statistical significance.

Although these observational analyses cannot establish causality, they suggest that the risk of cardiomyopathy driven by kidney disease in stable CKD patients may be more substantial than the risk of CKD progression driven by heart disease. This insight underscores the importance of monitoring kidney function to manage cardiovascular risk in CKD patients.

Renal impairment (RI) is a common complication in newly diagnosed multiple myeloma (NDMM), with 1-5% of patients presenting with severe RI requiring dialysis, which is associated with significant morbidity and early mortality. Limited real-world data exist on outcomes for these patients.

We assessed renal response patterns and outcome determinants in 73 consecutive NDMM patients requiring dialysis, treated in a single centre (2010 to 2023).

Median age was 69 years; 52% had high-risk cytogenetics. All patients received bortezomib-based induction therapy (19% doublets, 71% triplets, 10% quadruplets; 12% anti-CD38 antibodies). Median follow-up was 37.2 months. Dialysis independence was achieved by 31 patients (42.5%) after a median of 52 days (range 3-247). Dialysis independence was associated with improved survival (median 36 vs. 13.3 months, P = .085) and lower early mortality (3.2% vs. 14.3%, P = .15). Factors associated with independence from dialysis were younger age) OR 0.92, P = .003), hypercalcemia (OR 1.43, P = .013) and hematologic response (≥ PR) at 1 month (OR 3.7, P = .015). In multivariate analysis, younger age (P = .012, OR 0.93) and hematologic response (≥ PR) at 1 month (P = .014, OR 4.94) were independent predictors of dialysis independence. Depth of hematologic response (≥ VGPR) significantly impacted renal recovery (OR 4.0, P = .020). High-risk cytogenetics independently predicted poor outcomes (HR 3.67, P = .003).

Dialysis independence is achievable in 42.5% of NDMM patients without special filters in the era of bortezomib-based regimens, with significant impact on outcome. Outcomes remain poor overall for patients who are dialysis-dependent at diagnosis and further evaluation of quadruplet regimens with anti-CD38 antibodies is needed.

We aimed to assess the decline in renal function in patients with chronic postoperative hypoparathyroidism.

We performed a multicenter, retrospective cohort study including patients with chronic hypoparathyroidism lasting ≥ 3 years. We evaluated the changes in serum creatinine and estimated glomerular filtration rate (eGFR) before surgery and at the last visit. Changes were evaluated in absolute value (ΔeGFR = eGFR at last visit - eGFR before thyroidectomy) and corrected for time (ΔeGFR/yr = ΔeGFR / time in years).

We included 236 patients with hypoparathyroidism (85.6% women, median age 47 [37-58] years, median time of follow-up 7.3 [5.0-11.0] years), and 458 control subjects with similar age, gender, and time of follow-up. Before thyroidectomy we found no significant differences in serum creatinine levels or eGFR between patients and controls. At the end of follow-up, ΔeGFR and ΔeGFR/yr in the patients with hypoparathyroidism were -4.87 (-17.0-0.00) ml/min/1.73 m2 and -0.68 (-2.31-0.00) ml/min/1.73 m2 per year, respectively, whereas in the control subjects these changes were 0.00 (-10.10-4.00) ml/min/1.73 m2 (P < 0.001), and 0.00 (-1.34-0.54) ml/min/1.73 m2 per year (P < 0.001). In multivariable regression analysis the annual eGFR decline in patients with hypoparathyroidism was related to age (P < 0.001), eGFR before thyroidectomy (P < 0.001), and incident nephrolithiasis (P = 0.028).

The decline in renal function over time is significantly higher in patients with chronic hypoparathyroidism after thyroidectomy compared to thyroidectomized patients without hypoparathyroidism. Age, preoperative eGFR and nephrolithiasis are the main determinants of renal function loss in these patients.

Little information exists about diabetic foot infections (DFIs) in older patients. We hypothesize that older patients with DFIs have different clinical features and worse outcomes than younger patients. We conducted a prospective observational study consisting of a cohort of patients with diabetes and moderate to severe DFIs. Patients included in the cohort were dichotomized into two groups using percentile 75 (P75) of age as the cut-off value. Patients aged > P75 presented with more comorbidities and foot-related complications, a higher rate of peripheral arterial disease (PAD), worse renal function (higher values of blood urea nitrogen and creatinine, and lower values of estimated glomerular filtration rate), and lower values of HbA1c compared with younger patients. Infection severity, microbiological features, and inflammatory markers were similar in both groups. In the multivariate analysis, minor amputations were associated with age > P75 (OR = 2.8, 95% CI 1.3-5.9, p <0.01), necrosis (OR = 4.2, 95% CI 1.8-10.1, p < 0.01), and CRP values (OR = 1.045, 95% CI 1.018-1.073, p < 0.01). Major amputations were associated with a history of amputation (OR = 4.7, 95% CI 1.3-16.7, p = 0.01), PAD (OR = 4.3, 95% CI 1.2-14.6, p = 0.01), and albumin values (OR = 0.344, 95% CI 0.130-0.913, p = 0.03). In conclusion, limb salvage can be achieved in older patients with diabetes-related foot infections at the same rate as in younger patients, despite the fact that they have more comorbidities and foot-related complications, a higher rate of PAD, and worse renal function.

Background: Our aim was to evaluate the prognostic value of detectable high-sensitivity cardiac troponin I (hs-cTnI) and ischaemia-modified albumin (IMA) in predicting all-cause death or non-fatal ischaemic events in patients with PAD after endovascular revascularisation of the lower limbs. Patients and methods: Patients who underwent successful endovascular revascularisation for chronic limb-threatening ischaemia (CLTI) or disabling intermittent claudication (IC) were prospectively included. Pre-procedural levels of hs-cTnI and IMA were measured, and patients were followed for one year for the occurrence of the composite outcome of all-cause death, non-fatal myocardial infarction, new-onset angina, non-fatal ischaemic stroke, transient ischaemic attack, or progression of PAD. Outcomes were evaluated using survival analyses. Results: A total of 487 patients concluded the study, of whom 175 (35.9%) experienced the composite outcome. When considering only the clinical presentation of PAD and biomarker values, in patients with CLTI, hs-cTnI above the limit of detection (LoD) conferred an increased risk of the composite outcome compared to hs-cTnI below the LoD (p=0.004), while for IMA we found no significant difference. Outcomes of patients with CLTI and hs-cTnI or IMA below the LoD did not differ from those of patients with IC (p=0.07 and p=0.462, respectively). When adjusting for clinical characteristics and common cardiovascular risk factors in multivariate Cox survival analysis, neither biomarker improved prognostic performance, however IMA emerged as an independent predictor of the composite outcome in patients with CLTI. Conclusions: In patients with PAD who underwent successful endovascular procedure, neither IMA nor hs-cTnI improved risk stratification beyond clinical determinants. However, detection of IMA was an independent predictor of major cardiovascular events or death in patients with CLTI.

Studying the mechanisms involved in the transition from prediabetes to diabetes and its associated complications, such as kidney disease, is a growing challenge. This study focuses on identifying valuable biomarkers for the early detection of kidney damage, evaluating molecules associated with oxidative stress and inflammation in prediabetic individuals across Europe.

In plasma samples from individuals with prediabetes included in the ePREDICE study, we determined molecules related to oxidative stress (advance oxidative protein products-AOPP) and inflammatory biomarkers (C-reactive protein - CRP; Interleukin 6 - IL-6), and correlated them with anthropometric and biochemical data, assessing their potential for the early diagnosis of renal involvement.

Among the 967 people with prediabetes, 94 presented some sign of renal impairment such as albuminuria, hyperfiltration or hypofiltration. Significant variations were identified between oxidative stress and inflammatory biomarkers (upper and lower quartiles of AOPP, CRP and IL6), and parameters associated with blood pressure, glucose metabolism, lipid profile, and fatty liver index. In particular, both types of biomarkers were associated with components of the metabolic syndrome. There were significant associations between AOPP and CRP, and the presence of albuminuria, but not with renal function. Overall, CRP was a better biomarker than IL-6 for most of the parameters studied.

These results highlight the important associations of oxidative stress and inflammation with metabolic abnormalities linked to the prediabetic state and its complications such as fatty liver and renal involvement. Although these results need to be confirmed, our study suggests that AOPP and CRP could be simple biomarkers of interest in predicting the risk of loss of renal function in people with prediabetes.

Chronic kidney disease affects around 10% of the global population and is associated with significant risk of progression to end-stage renal disease and vascular events. Aldosterone receptor antagonists such as spironolactone have shown prognostic benefits in patients with heart failure, but effects on patients with chronic kidney disease are uncertain.

To determine the effect of low-dose spironolactone on mortality and cardiovascular outcomes in people with chronic kidney disease stage 3b.

Prospective randomised open blinded end-point trial.

Three hundred and twenty-nine general practitioner practices throughout the United Kingdom.

Patients meeting the criteria for chronic kidney disease stage 3b (estimated glomerular filtration rate 30-44 ml/minute/1.73 m2) according to National Institute for Health and Care Excellence guidelines were recruited. Due to the higher than anticipated measurement error/fluctuations, the eligible range was extended to 30-50 ml/minute/1.73 m2 following the initial recruitment period.

Participants were randomised 1 : 1 to receive either spironolactone 25 mg once daily in addition to standard care, or standard care only.

Primary outcome was the first occurring of all-cause mortality, first hospitalisation for heart disease (coronary heart disease, arrhythmia, atrial fibrillation, sudden death, failed sudden death), stroke, heart failure, transient ischaemic attack or peripheral arterial disease, or first occurrence of any condition not listed at baseline. Secondary outcome measures included changes in blood pressure, renal function, B-type natriuretic peptide, incidence of hyperkalaemia and treatment costs and benefits.

One thousand four hundred and thirty-four participants were randomised of the 3022 planned. We found no evidence of differences between the intervention and control groups in terms of effectiveness with the primary combined vascular end points, nor with the secondary clinical outcomes, including progression in renal decline. These results were similar for the total treatment periods or a 3-year follow-up period as originally planned. More adverse events were experienced and more participants discontinued treatment in the intervention group. Two-thirds of participants randomised to spironolactone stopped treatment within six months because they met pre-specified safety stop criteria. The addition of low-dose spironolactone was estimated to have a cost per quality-adjusted life-year gained value above the National Institute for Health and Care Excellence's threshold of £30,000.

Main limitations were difficulties in recruiting eligible participants resulting in an underpowered trial with poor ethnic diversity taking twice as long as planned to complete. We have explored the data in secondary analyses that indicate that, despite these difficulties, the findings were reliable.

The benefits of aldosterone receptor antagonism in chronic kidney disease trial found no evidence to support adding low-dose spironolactone (25 mg daily) in patients with chronic kidney disease stage 3b: there were no changes to cardiovascular events during the trial follow-up, either for the combined primary or individual components. There was also no evidence of benefit observed in rates of renal function decline over the trial, but much higher initial creatinine rise and estimated glomerular filtration rate decline, and to a higher percentage rate, in the intervention arm in the first few weeks of spironolactone treatment, which resulted in a high proportion of participants discontinuing spironolactone treatment at an early stage. These higher rates of negative renal change reduced in scale over the study but did not equalise between arms. The addition of 25 mg of spironolactone therefore provided no reno- or cardio-protection and was associated with an increase in adverse events.

These findings might not be applicable to different mineralocorticoid receptor antagonists.

Current Controlled Trials ISRCTN44522369.

This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/01/52) and is published in full in Health Technology Assessment; Vol. 29, No. 5. See the NIHR Funding and Awards website for further award information.

Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.

Data from the Angiotensin II Antagonist Losartan Study (RENAAL) and Irbesartan type II Diabetic Nephropathy Trial (IDNT) were used. The kidney outcome was time to first event of end-stage kidney disease or doubling of serum creatinine. The cardiovascular outcome was time to first event of a composite of stroke, myocardial infarction, cardiovascular death or hospitalisation for heart failure. Sex differences were assessed by a sex × treatment interaction term in Cox proportional hazards models.

Included were 1737 male participants and 924 female participants. The beneficial effect of angiotensin receptor blockers on the kidney outcome was similar between male and female participants (HR in male participants 0.72 [95% CI 0.59, 0.86] vs HR in female participants 0.86 [95% CI 0.69, 1.06]; sex × treatment interaction HR 1.19 [95% CI 0.89, 1.59]). For the cardiovascular outcome, angiotensin receptor blockers lowered the risk in male but not in female participants (HR in male participants 0.81 [95% CI 0.69, 0.95] vs HR in female participants 1.11 [95% CI 0.88, 1.40]; sex × treatment interaction HR 1.37 [95% CI 1.03, 1.82]).

This study in individuals with type 2 diabetes and diabetic kidney disease suggests that the beneficial effects of angiotensin receptor blockers are similar in male and female participants for the kidney outcome but not for the cardiovascular outcome. More attention to sex differences in angiotensin receptor blockers' efficacy and underlying mechanisms of differences in response is needed.

ClinialTrials.gov NCT00308347.

Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant.

A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30-≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined.

Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a "reset point," signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups ( P  < 0.0001).

The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.

Contrast-induced nephropathy (CIN), which can develop after procedures involving contrast agents, is a significant cause of patient morbidity and mortality. This study aims to investigate the role of pre-procedural pan-immune-inflammation value (PIV) in predicting CIN development in patients undergoing percutaneous coronary intervention (PCI) due to non-ST segment elevation myocardial infarction (NSTEMI). A total of 1006 NSTEMI patients were included in the study. CIN was defined as an increase of at least 0.5 mg/dl or 25% in serum baseline creatinine level 72 h after the procedure. Patients were divided into two groups: those with and without CIN. NSTEMI patients who developed CIN, glucose level (P = .01), platelet count (P < .01), monocyte count (P < .001), neutrophil-to-lymphocyte ratio (NLR) (P < .001), systemic immune inflammation index (SII) score (P < .001), and PIV (P < .001) were higher compared with those without CIN. In the multivariate analysis of all these parameters, the Odds ratios of PIV and SII were similar and slightly lower than NLR. Receiver operating characteristic curve analysis (ROC) showed a PIV cut-off value of 448.43 with a sensitivity of 83.1% and a specificity of 72.8% in patients with CIN. Our study demonstrated an independent relationship between PIV at admission and CIN development in NSTEMI patients.

Comprehensive studies about renal-function changes in the context of out-of-hospital cardiac arrest (OHCA) have been lacking. Therefore, we investigated the impact of renal function on clinical outcomes among patients with OHCA.

This retrospective cohort study enrolled consecutive patients with OHCA between June 2017 and December 2021. Acute kidney injury (AKI) was defined based on the "Kidney Disease: Improving Global Outcomes (KDIGO)" guidelines. AKI recovery was defined as a decrease in serum creatinine below the level determined in the definition of AKI. Clinical outcomes included neurological outcomes and all-cause mortality.

A total of 258 patients were enrolled, including 35 patients with underlying end-stage renal disease (ESRD). Among patients without ESRD, 82.5% developed AKI, of which 31.0% achieved AKI recovery, while 61.0% were discharged with impaired renal function. Multivariable analysis using regression models revealed that unfavorable neurological outcomes at discharge and higher mortality at 2 years were associated with AKI (odds ratio [OR] 7.684, 95% confidence interval (CI) 2.683-22.010, P < 0.001; hazard ratio [HR] 2.159, 95% CI 1.272-3.664, P = 0.004), AKI without recovery (OR 5.275, 95% CI 2.049-13.583, P < 0.001; HR 5.470, 95% CI 3.304-9.862, P < 0.001), and impaired pre-discharge renal function (OR 3.164, 95% CI 1.442-6.940, P = 0.004; HR 2.876, 95% CI 1.861-4.443, P < 0.001). Compared to those without ESRD, patients with underlying ESRD had similar neurological outcomes and mortality.

AKI, AKI without recovery, and impaired pre-discharge renal function were significantly correlated with worse clinical outcomes in OHCA among patients without ESRD, while underlying ESRD did not lead to worse clinical outcomes.

The use of serum creatinine (SCr) for drug dosing has significant limitations and is influenced by many non-kidney factors. Cystatin C (cysC) is an alternative or additional marker of kidney function that is less affected by non-kidney factors. Although cysC may be useful in hospitalized patients, the use of cysC to calculate drug dosing in critically ill patients has been incompletely investigated.

The objective of this study was to determine the rate of discordance in estimated glomerular filtration rate (eGFR) between SCr-based calculations and SCr/cysC-based calculations that affect drug dosing in critically ill patients.

This was a single-center, retrospective, observational cohort study at an academic medical center including critically ill adult patients admitted in 2023 with SCr and cysC ordered. Data were collected via chart review. Demographic data were analyzed via descriptive statistics. Discordance, defined as the percentage of times at which there is at least one discrepancy in kidney dosing for a medication using Cockcroft-Gault (CG) creatinine clearance versus Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR creatinine-cystatin C (eGFRcr-cys) equations, was analyzed via Wilcoxon matched pair signed ranked sum. eGFR calculations were normalized for patients' body surface area for comparison.

The study population included 232 patients (53.02% female; mean age 58.7 +/- 14.9 years; with 62.5% in medical, 23.28% in surgical, and 8.62% in neurological intensive care) with a median SCr of 0.94 mg/dL IQR [0.57-1.58] and median cysC of 1.92 mg/L IQR [1.27-2.77]. The median clearance rates were 68.5 mL/min (45.3-111.5) for CG and 53.9 mL/min (30.9-80.7) for CKD-EPI eGFRcr-cys; p < 0.001. The discordance rate across all study drugs was 32.3% (75/232). The four most common study drugs demonstrating discordance were cefepime 40.6% (52/128), vancomycin 38.3% (46/120), levetiracetam 35.1% (13/37), and piperacillin/tazobactam 11.6% (5/43).

Clinically significant discordance exists between SCr and SCr/cysC-based estimates of kidney function. This study established a discordance rate, as defined by drug dosing, of 32.3% in adult patients admitted to the ICU.

Adverse cardiovascular events often recur after acute coronary syndrome (ACS), despite secondary prevention measures. Residual risk involves various inflammatory, metabolic and renal factors as well as lipid and thrombotic processes. This cohort study investigates the relationship between four risk biomarkers at 1 month after ACS and all-cause death within 3 years in patients treated with early invasive strategy and high-intensity statins from admission.

Levels of residual risk for the biomarkers were: low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dl; high-sensitivity C reactive protein (hs-CRP) ≥ 2 mg/l; glycosylated hemoglobin (HbA1c) ≥ 7% in diabetic and ≥ 5.7% in non-diabetic patients; decrease in estimated glomerular filtration rate (eGFR) ≥ 25% compared to baseline. The association between the four biomarkers and all-cause death within 3 years was evaluated with Cox proportional analysis.

This study included 1099 patients (68±12 years; 70.3% males). At 1 month the majority of patients had levels of LDL-C, hs-CRP and/or HbA1c above the risk cut-points, and only 7% of cases presented reduced eGFR. Reduced eGFR and hs-CRP ≥ 2 mg/l at 1 month were the sole independent biomarker predictors of 3-year mortality (adjusted hazard ratios 3.03 and 2.66, respectively).

In this population on high-intensity statin therapy only hsCRP and eGFR were independently associated with medium-term mortality. Diversification of secondary preventive measures based on routine evaluations of inflammation and kidney function markers, not only LDL-C, could lead to better targeted reduction of residual risk after ACS.

Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide(TAF) are first-line nucleos(t)ide analogs (NUCs) with chronic hepatitis B (CHB). This study aimed to assess the renal safety profile in NUC-experienced CHB patients who received ETV, TDF or TAF therapy.

This retrospective observational cohort study investigated factors related to renal function in 154 patients with NUC-experienced CHB who received ETV, TDF, and TAF therapy for 48 weeks. Changes in UREA, uric acid (UA), creatinine (Cr), and estimated glomerular filtration rate (eGFR) were analyzed using a one-way analysis of variance. A linear mixed-effects model for repeated measures was used to evaluate the correlation between baseline information and eGFR changes 48 weeks following treatment initiation. The model considered sex, baseline age, viral load, aminotransferases, renal function, and treatment group as fixed effects, and incorporated random effects for individual subjects.

There were no significant differences in UA or Cr levels during therapy over time. The eGFR level was elevated in ETV-treated patients (117.5 ± 16.65 mL/min/1.7m2 vs 109.8 ± 15.69 mL/min/1.7m2, P=0.027), whereas it did not change significantly in TDF- (123.6 ± 28.54 mL/min/1.7m2 vs 115.5 ± 20.44 mL/min/1.7m2, P=0.070) and TAF-treated (121.6 ± 23.44 mL/min/1.7m2 vs 113.4 ± 16.90 mL/min/1.7m2, P=0.053) patients. Younger patients (<30 years) and those with higher HBV DNA (> 7 log10IU/mL) and lower alanine aminotransferase levels (<5 × upper limit of normal) showed a significant improvement in eGFR elevation during NUCs therapy. The linear mixed-effects model showed that the baseline HBV DNA level was an important positive predictor of eGFR elevation at 48 weeks following treatment initiation (estimate was 1.437 and 2.449, P<0.001).

In real-life experience, ETV, TDF, and TAF therapy may not be associated with eGFR changes in NUC-experienced CHB patients without baseline renal impairment.

This study examined the involvement of fibroblast growth factor-23 (FGF-23) in primary aldosteronism (PA), a condition characterized by elevated aldosterone levels and hypertension. We recruited patients with unilateral PA (uPA) and observed increased levels of C-terminal FGF-23 (cFGF-23) and C-terminal to intact FGF-23 (iFGF-23) in patients with uPA compared with essential hypertension control participants. Elevated preoperative cFGF-23 levels were associated with adverse outcomes, including mortality and cardiovascular or kidney events. Plasma cFGF-23 levels demonstrated a nonlinear rise with aldosterone, but iFGF-23 levels were not correlated with plasma aldosterone concentration. Higher cFGF-23 levels independently predicted hypertension remission after adrenalectomy for patients with uPA. Patients with uPA, who exhibited elevated cFGF-23 levels, had decreased levels after adrenalectomy. In cell cultures, aldosterone enhanced cleavage of iFGF-23, leading to increased levels of cFGF-23 fragments, an effect mitigated by silencing of family with sequence similarity 20, member C (FAM20C). However, the enhancement of cFGF-23 levels remained unaffected by the furin inhibitor. The study suggests that aldosterone influences FGF-23 phosphorylation by interacting with FAM20C, with docking experiments indicating aldosterone's binding to FAM20C. This work highlights that patients with uPA with elevated cFGF-23 levels are associated with cardiovascular risks, and adrenalectomy reduces cFGF-23. Aldosterone likely promotes cFGF-23 production through FAM20C-mediated phosphorylation of iFGF-23.

Background and Objectives: Chronic kidney disease (CKD) remains a public health threat and a major cause of morbidity and mortality worldwide. A bidirectional relationship is found between sleep disorders and CKD worldwide. However, to our knowledge, this study is the first to assess the prevalence of obstructive sleep apnea (OSA) and to evaluate its impact on the progression of other comorbidities among Lebanese patients with CKD. Materials and Methods: The study is an observational cross-sectional study, carried out between September and November 2021. Lebanese patients with any stage of CKD were included. Patients' characteristics were collected via electronic health record and baseline questionnaires. We screened for obstructive sleep apnea using the STOP-Bang questionnaire. Results: We included 168 patients. The prevalence of OSA among our patients was 47.6%. The prevalence of OSA is higher in males compared with females (81.2% vs. 18.8%, p=0.002). Obesity was more prevalent in patients with OSA compared with patients without OSA (42.5% vs. 19.3%, p=0.002). Among the 168 patients, 69.6% had hypertension, with a significantly higher prevalence among those with OSA compared with those without OSA (81.2% vs. 59.1%, p=0.003). Patients with OSA reported significantly lower scores compared with those without OSA in several domains of physical and emotional health, including physical functioning (54.06 vs. 66.88, p=0.002), role limitations due to physical health (42.19 vs. 63.07, p=0.001), role limitations due to emotional problems (49.17 vs. 69.32, p=0.004), pain (61.31 vs. 70.45, p=0.019), and physical component score (52.53 vs. 69.53, p=0.002). All the abovementioned parameters were also examined in two subpopulations: patients with CKD and ESRD. Similarly, some comorbidities and a lower physical QOL score were observed more in patients with OSA in these two subpopulations. Conclusion: Patients with OSA in our study have higher probability of being male, obese, and hypertensive as well as poorer QOL compared with their counterparts without OSA. Implementing more effective screening and treatment of OSA in CKD patients is necessary.

The secondary prevention strategy for cardiovascular disease (CVD) does not include anti-inflammatory treatment, which may lead to long-term inflammation in some patients. The aim of this study was to assess the association between inflammatory risk based on the Glasgow Prognostic Score (GPS) and long-term mortality risk in patients with CVD. This study included 3833 patients (≥ 20 years old) with CVD in the National Health and Nutrition Survey from 1999 to 2010 in the United States. The mortality rate was determined by correlation with the National Death Index on December 31, 2019. The GPS consists of the serum C-reactive protein and the serum albumin. The primary outcome was all-cause death, which included cardiac death and non-cardiac death. Cox proportional hazards adjusted for demographic factors and traditional cardiovascular risk factors were used to test the impact of the GPS on mortality. The sensitivity analysis was conducted on subsets within the cohort of patients with CVD, including congestive heart failure, coronary artery disease, angina, heart attack, and stroke. Among 3833 CVD patients with a median follow-up of 9.6 years, 2431 (63.4%) all-cause deaths, 822 (21.4%) cardiac deaths, and 1609 (41.9%) non-cardiac deaths were recorded. After full model adjustment, compared with those of the GPS (0) group, the hazard ratios (HRs) of all-cause death for GPS (1) and GPS (2) were 1.66 (95% confidence interval (CI), 1.48-1.86) and 2.75 (95% CI 2.01-3.75), respectively (P for trend < 0.001). Compared with those of the GPS (0) group, the HRs of cardiac death for the GPS (1) and GPS (2) groups were 1.69 (95% CI 1.39-2.05) and 2.18 (95% CI 1.22-3.91), respectively (P for trend < 0.001). Compared with those of the GPS (0) group, the HRs of non-cardiac death for the GPS (1) and GPS (2) groups were 1.65 (95% CI 1.44-1.89) and 3.05 (95% CI 2.11-4.40), respectively (P for trend < 0.001). The results of the sensitivity analysis were similar to those of the overall cohort. In our analysis of the United States National Database, we discovered that the GPS, a measure of inflammatory risk, was significantly associated with an increased risk of mortality among patients with CVD. Specifically, we observed that patients with a higher GPS had significantly higher risks of all-cause, cardiac, and non-cardiac mortality compared to those with a lower score. These findings suggest that the GPS, comprising easily obtainable biomarkers, could serve as a valuable tool for risk stratification in CVD patients and may contribute to the improvement of patient outcomes.

Blood cell-derived indices are potential predictors of clinical outcomes in coronary artery disease. This study assessed the prognostic value of the pan-immune-inflammatory value (PIV) for predicting 1-year major adverse cardiovascular events (MACEs) in patients with non-ST-segment elevation acute coronary syndrome (ACS). A retrospective cohort of 1651 patients receiving percutaneous coronary intervention was analyzed. PIV, calculated from blood cell counts, was categorized with a cut-off value of 256.3 (sensitivity 60.7%, specificity 59.3%) based on receiver operating characteristic curve analysis. MACEs were operationalized as a composite of all-cause mortality, myocardial infarction (MI), stroke, any revascularization, and rehospitalization for heart failure. The incidence of MACEs was 5.0% in patients with low PIV and 9.7% in those with high PIV (log-rank p < 0.001). Multivariate analysis identified age 65 > years, renal dysfunction (eGFR < 60 mL/min/1.73 m2), and high PIV (>256.3) (HR 1.49, 95% CI 1.01-2.22, p = 0.048) as independent predictors of MACEs. Subgroup analyses revealed no statistically significant interaction between MI status or C-reactive protein levels and PIV. PIV was an independent predictor of 1-year MACEs in patients with non-ST-segment elevation ACS. It may serve as a reliable prognostic marker independently of MI or C-reactive protein levels.

Both triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and low-density lipoprotein cholesterol (LDL-C) are independent risk factors for long-term prognosis among patients with cardio-renal-metabolic (CRM) disease. However, the co-exposures of TyG index and LDL-C to mortality is unclear. The aim of this study is to investigate the joint effects and risk stratification of the TyG index and LDL-C on all-cause and cardiovascular mortality in CRM patients. We analyzed CRM patients from the National Health and Nutrition Examination Survey (NHANES) database (1999-2018), calculating TyG index as Ln[fasting triglyceride (mg/dL)×fasting glucose (mg/dL)/2] and using multivariable Cox regression models to assess the joint effects of TyG index and LDL-C on all-cause and cardiovascular mortality. The interaction between the TyG index and LDL-C to mortality was also evaluated. During a median follow-up of 7.6 years, 22.8% and 8.4% of patients died from all-cause and cardiovascular causes, respectively. Among patients with LDL-C < 2.6 mmol/L, no significant differences were observed in all-cause and cardiovascular mortality when comparing higher TyG index to the lowest tertile (T1). Specifically, the hazard ratio (HR) for all-cause mortality in the second (T2) and third tertiles (T3) were 0.81 (95% confidence interval(CI): 0.59-1.09) and 0.87 (95%CI: 0.62-1.22), respectively, with a P for trend of 0.468. For cardiovascular mortality, the HR for T2 and T3 compared to T1 were 0.80 (95%CI: 0.48-1.32) and 0.72 (95%CI: 0.45-1.15), respectively, with a P for trend of 0.173. However, elevated TyG index was related to markedly increased risk of all-cause and cardiovascular mortality in patients with LDL-C ≥ 2.6 mmol/L. Specifically, for all-cause mortality, HR for T2 and T3 compared to T1 were 1.01 (95%CI: 0.79-1.28) and 1.38 (95%CI: 1.07-1.79), respectively, with a P for trend of 0.009. For cardiovascular mortality, the HR was 1.09 (95% CI: 0.72-1.65) for T2 and 1.80 (95% CI: 1.18-2.75) for T3, with a P for trend of 0.005. Interactive analysis also demonstrated that a significant association of TyG index and LDL-C with the risk of all-cause (P for interaction = 0.011) and cardiovascular (P for interaction = 0.050) mortality was observed. The findings highlight that elevated TyG index can significantly increase the risk of all-cause and cardiovascular mortality only among CRM patients with LDL-C ≥ 2.6 mmol/L, but not among patients with LDL-C < 2.6 mmol/L.

Background: Patients with idiopathic pulmonary fibrosis (IPF) have a high prevalence of cardiovascular (CV) risk factors and an increased CV disease burden. The aim of this study was to investigate the prognostic role of the ascending aorta (AA) diameter in patients with mild-to-moderate IPF and to identify the main determinants of AA dilatation. Methods: All IPF patients without severe pulmonary hypertension who underwent a multi-instrumental evaluation, comprehensive of high-resolution computed tomography (HRCT) and transthoracic echocardiography (TTE), between September 2017 and November 2023, were retrospectively analyzed. The primary endpoint was the composite of "all-cause mortality or re-hospitalization for all causes", over a medium-term follow-up. The secondary endpoint was to evaluate the independent predictors of AA dilatation. Additionally, Bland-Altman analysis was used to assess the accuracy and precision of echocardiography-derived AA diameters compared with non-ECG gated HRCT measurements. Results: A total of 105 IPF patients and 102 age-, sex-, and CV risk factor-matched controls without IPF were evaluated retrospectively. Over a follow-up of 3.9 ± 1.9 yrs, 31 patients died and 47 were re-hospitalized. AA/height (HR 1.15, 95% CI 1.06-1.25, p < 0.001) was independently associated with the primary endpoint, whereas unindexed AA (HR 1.01, 95% CI 0.96-1.06, p = 0.83) and AA/BSA (HR 1.00, 95% CI 0.89-1.11, p = 0.39) were not. An AA/height > 20 mm/m showed 100% sensitivity and 63% specificity (AUC = 0.78) for predicting the primary endpoint. C-reactive protein (OR 1.87; 95% CI 1.21-2.89, p = 0.005) and left ventricular mass index (OR 1.13, 95% CI 1.04-1.24, p = 0.006) were independently associated with an AA/height > 20 mm/m in the whole study group. The Bland-Altman analysis revealed a bias of +2.51 mm (with the 95% limits of agreement ranging from -3.62 to 8.65 mm) for AA estimation, suggesting a general overestimation of the AA diameter by TTE in comparison to HRCT. Conclusions: AA dilatation is predictive of poor outcomes in IPF patients without advanced lung disease over a mid-term follow-up. The AA/height assessment may improve the prognostic risk stratification of IPF patients.