Dialysate Sodium Levels, Ambulatory Aortic Blood Pressure and Arterial Stiffness in Hemodialysis Patients.

Increased aortic blood-pressure(BP) and arterial stiffness are associated with higher cardiovascular risk in hemodialysis. Previous works showed that lower dialysate sodium is associated with lower brachial-BP; data on aortic-BP and arterial stiffness are limited. This study aimed to investigate the effects of different dialysate sodium concentrations on 72-h aortic-BP and arterial stiffness parameters in hemodialysis patients. This analysis is part of a prospective, non-randomized interventional study. Twenty-five hemodialysis patients underwent a set of three periods of different dialysate sodium concentrations; six sessions with dialysate sodium of 137meq/L, followed consecutively by six sessions with 139meq/L and, finally, six sessions with 141meq/L. At the start of the sixth hemodialysis session on each sodium concentration, 72-h ABPM (Mobil-O-Graph) was performed to evaluate aortic-BP and arterial stiffness indices during the overall 72-h, different 24-h, day-time and night-time periods. Mean 72-h aortic SBP/DBP were higher with increasing dialysate sodium concentrations (137meq/L: 114.2±15.3/77.0±11.8mmHg vs 139meq/L: 115.4±17.3/77.9±14.0mmHg vs 141meq/L: 120.5±18.4/80.5±14.7mmHg, p=0.002/p=0.057, respectively). Wave-reflections parameters (AIx, AIx(75), AP) were not significantly different between the three dialysate sodium concentrations. Ambulatory PWV was significantly higher with increasing dialysate sodium concentrations (137meq/L: 8.5±1.7m/s vs 139meq/L: 8.6±1.6m/s vs 141meq/L: 8.8±1.6m/s, p<0.001). In generalized linear-mixed-models including 72-h brachial SBP as random covariate, the adjusted marginal-means of 72-h PWV were not significantly different between-groups. This study showed that lower dialysate sodium concentrations are associated with significant decreases in ambulatory aortic BP and PWV. This study showed that higher dialysate sodium concentrations are associated with significant increases in ambulatory aortic BP and PWV. These findings further support the need for modification of dialysate sodium concentration in hemodialysis.

Bratsiakou A ，Theodorakopoulou M ，Iatridi F ，Sarafidis P ，Davoulos C ，Goumenos DS ，Papachristou E ，Papasotiriou M ... -  《-》

Low dialysate sodium levels for chronic haemodialysis.

Cardiovascular (CV) disease is the leading cause of death in dialysis patients and is strongly associated with fluid overload and hypertension. It is plausible that low dialysate sodium ion concentration [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension and ultimately reducing CV morbidity and death. This is an update of a review first published in 2019. This review evaluated the harms and benefits of using a low (< 138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients. We searched the Cochrane Kidney and Transplant Register of Studies up to 1 October 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials (RCTs), both parallel and cross-over, of low (< 138 mM) versus neutral (138 to 140 mM) or high (> 140 mM) dialysate [Na+] for maintenance HD patients were included. Two authors independently screened studies for inclusion and extracted data. Statistical analyses were performed using the random-effects model, and results expressed as risk ratios (RR) for dichotomous outcomes, and mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI). Confidence in the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). We included 17 studies randomising 509 patients, with data available for 452 patients after dropouts. All but three studies evaluated a fixed concentration of low dialysate [Na+], with one using profiled dialysate [Na+] and two using individualised dialysate [Na+]. Five were parallel group studies, and 12 were cross-over studies. Of the latter, only six used a washout between intervention and control periods. Most studies were short-term with a median (interquartile range) follow-up of 4 (4 to 16) weeks. Two were of a single HD session and two of a single week's HD. Seven studies were conducted prior to 2000, and six reported the use of obsolete HD practices. Other than for indirectness arising from older studies, risks of bias in the included studies were generally low. Compared to neutral or high dialysate [Na+] (≥ 138 mM), low dialysate [Na+] (< 138 mM) reduces interdialytic weight gain (14 studies, 515 participants: MD -0.36 kg, 95% CI -0.50 to -0.22; high certainty evidence) and antihypertensive medication use (5 studies, 241 participants: SMD -0.37, 95% CI -0.64 to -0.1; high certainty evidence), and probably reduces left ventricular mass index (2 studies, 143 participants: MD -7.65 g/m2, 95% CI -14.48 to -0.83; moderate certainty evidence), predialysis mean arterial pressure (MAP) (5 studies, 232 participants: MD -3.39 mm Hg, 95% CI -5.17 to -1.61; moderate certainty evidence), postdialysis MAP (5 studies, 226 participants: MD -3.17 mm Hg, 95% CI -4.68 to 1.67; moderate certainty evidence), predialysis serum [Na+] (11 studies, 435 participants: MD -1.26 mM, 95% CI -1.81 to -0.72; moderate certainty evidence) and postdialysis serum [Na+] (6 studies, 188 participants: MD -3.09 mM, 95% CI -4.29 to -1.88; moderate certainty evidence). Compared to neutral or high dialysate [Na+], low dialysate [Na+] probably increases intradialytic hypotension events (13 studies, 15,764 HD sessions: RR 1.58, 95% 1.25 to 2.01; moderate certainty evidence) and intradialytic cramps (10 studies, 14,559 HD sessions: RR 1.84, 95% 1.29 to 2.64; moderate certainty evidence). Effect size for important outcomes were generally greater with low dialysate [Na+] compared to high compared with neutral dialysate [Na+], although formal hypothesis testing identifies that the difference was only certain for postdialysis serum [Na+]. Compared to neutral or high dialysate [Na+], it is uncertain whether low dialysate [Na+] affects intradialytic or interdialytic MAP, and dietary salt intake. It is also uncertain whether low dialysate [Na+] changed extracellular fluid status, venous tone, arterial vascular resistance, left ventricular volumes, or fatigue. Studies did not examine CV or all-cause death, CV events, or hospitalisation. Low dialysate [Na+] reduces intradialytic weight gain and probably blood pressure, which are effects directionally associated with improved outcomes. However, the intervention probably increases intradialytic hypotension and probably reduces serum [Na+], effects that are associated with an increased risk of death. The effect of the intervention on overall patient health and well-being is unknown. Further evidence is needed in the form of longer-term studies in contemporary settings, evaluating end-organ effects in small-scale mechanistic studies using optimal methods, and clinical outcomes in large-scale multicentre RCTs.

Marshall MR ，Wang MY ，Vandal AC ，Dunlop JL ... -  《Cochrane Database of Systematic Reviews》

Antihypertensive Drug Recommendations for Reducing Arterial Stiffness in Patients With Hypertension: Machine Learning-Based Multicohort (RIGIPREV) Study.

High systolic blood pressure is one of the leading global risk factors for mortality, contributing significantly to cardiovascular diseases. Despite advances in treatment, a large proportion of patients with hypertension do not achieve optimal blood pressure control. Arterial stiffness (AS), measured by pulse wave velocity (PWV), is an independent predictor of cardiovascular events and overall mortality. Various antihypertensive drugs exhibit differential effects on PWV, but the extent to which these effects vary depending on individual patient characteristics is not well understood. Given the complexity of selecting the most appropriate antihypertensive medication for reducing PWV, machine learning (ML) techniques offer an opportunity to improve personalized treatment recommendations. This study aims to develop an ML model that provides personalized recommendations for antihypertensive medications aimed at reducing PWV. The model considers individual patient characteristics, such as demographic factors, clinical data, and cardiovascular measurements, to identify the most suitable antihypertensive agent for improving AS. This study, known as the RIGIPREV study, used data from the EVA, LOD-DIABETES, and EVIDENT studies involving individuals with hypertension with baseline and follow-up measurements. Antihypertensive drugs were grouped into classes such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, diuretics, and combinations of diuretics with ACEIs or ARBs. The primary outcomes were carotid-femoral and brachial-ankle PWV, while the secondary outcomes included various cardiovascular, anthropometric, and biochemical parameters. A multioutput regressor using 6 random forest models was used to predict the impact of each antihypertensive class on PWV reduction. Model performance was evaluated using the coefficient of determination (R2) and mean squared error. The random forest models exhibited strong predictive capabilities, with internal validation yielding R2 values between 0.61 and 0.74, while external validation showed a range of 0.26 to 0.46. The mean squared values ranged from 0.08 to 0.22 for internal validation and from 0.29 to 0.45 for external validation. Variable importance analysis revealed that glycated hemoglobin and weight were the most critical predictors for ACEIs, while carotid-femoral PWV and total cholesterol were key variables for ARBs. The decision tree model achieved an accuracy of 84.02% in identifying the most suitable antihypertensive drug based on individual patient characteristics. Furthermore, the system's recommendations for ARBs matched 55.3% of patients' original prescriptions. This study demonstrates the utility of ML techniques in providing personalized treatment recommendations for antihypertensive therapy. By accounting for individual patient characteristics, the model improves the selection of drugs that control blood pressure and reduce AS. These findings could significantly aid clinicians in optimizing hypertension management and reducing cardiovascular risk. However, further studies with larger and more diverse populations are necessary to validate these results and extend the model's applicability.

Cavero-Redondo I ，Martinez-Rodrigo A ，Saz-Lara A ，Moreno-Herraiz N ，Casado-Vicente V ，Gomez-Sanchez L ，Garcia-Ortiz L ，Gomez-Marcos MA ，RIGIPREV Investigators Group ... -  《JOURNAL OF MEDICAL INTERNET RESEARCH》

Study of the association of markers of central and peripheral arterial stiffness with renal function in patients with arterial hypertension, diabetes mellitus and chronic kidney disease.

Increased aortic or central arterial stiffness (CAS) is a major factor in cardiovascular morbidity and mortality in patients with vascular risk factors. Decreased glomerular filtration rate (GFR) and increased urinary albumin excretion (uALB) are associated with lethal and non-lethal cardiovas-cular events. The pathophysiological mechanisms of this association are not fully defined. The aim of this study was: 1.- To analyse the CAS, comparing several markers, in subjects with arterial hypertension (HTN), diabetes mellitus (DM), chronic kidney disease (CKD) and their combination. 2.- To study the possible association of CAS with renal dysfunction (decrease in GFR and increase in uALB). A total of 286 subjects were included, divided into several groups: Control (n:38); HTN (n:51); DM without CKD (n:26); CKD without DM (n:77); CKD with DM (n:94). Several indices obtained by applanation tonometry were used to determine the CAS: carotid-femoral pulse velocity (VPc-f); central pulse pressure (cPP); augmentation index standardised to a cardiac frequency of 75 L/min (IA75); peripheral/aortic arterial stiffness gradient (ASGp-a). As a marker of peripheral arterial resistance, the carotid-radial pulse velocity (PVc-r) was determined. The ASGp-a was calculated from the PVc-r/PVc-f ratio. The subendocardial viability index (iBuckberg) was obtained from the aortic pulse wave. Multiple regression, binary logistic regression, and multinomial regression were used to study the association between arterial stiffness markers and renal function. The adjusted values of the PVc-f [(median (interquartile range) (m/s)] were significantly higher in subjects with DM [(9 (1.2)], CKD [(9.4 (0.7)] and DM with CKD [(10.9 (0.7)] than in the control group [(8.2 (1.3)] and group with HTN [(8.3 (0.9)], (p: 0.001). Patients with DM with CKD had higher PVc-f values than all other groups (p: 0.001). The ASGp-a of the patients was significantly lower than that of the controls, and the group with DM with CKD had significantly lower values than the other groups. The cPP in the DM with CKD group was significantly higher than in the other groups. All patients had an AI75 higher than the control group. When all aortic stiffness markers were introduced together in the regression, PV c-f was the only one that, after multivariate adjustment, was independently and inversely associated with GFR (β; -4, p: 0.001) and predicted the presence of GFR decrease (<60 mL/min/1.73 m2), [(OR (95%CI): 1.50 (1.17-1.92; p: 0.001]. The PVc-f was the only index directly associated with albuminuria (β: 0.15, p: 0.02) and predicted the existence of abnormal albuminuria (>30 mg/g), [(OR; 1.66 (1.25-2.20), p: 0.001)]. The PVc-f was also associated with the iBuckberg (β: -2.73, p: 0.01). Multinomial regression confirmed that PVc-f is a significant determinant of GFR and uALB. On the other hand, the increase in PVc-f and the presence of DM contribute significantly to the magnitude of albuminuria. Aortic stiffness increases in the presence of vascular risk factors such as hypertension, DM and CKD. This increase is greater when DM and CKD coexist. Increased aortic stiffness is inversely associated with GFR and directly with uALB, and is predictive of decreased GFR and abnormal uALB. The VPc-f is the parameter of aortic stiffness that is most consistently associated with renal dysfunction. Increased aortic stiffness could be one of the pathomechanisms linking renal dysfunction to cardiovascular events.

Perelló Martínez J ，Michán Doña A ，Santamaría Olmo R ，Hidalgo Santiago JC ，Gálvez Moral J ，Gómez-Fernández P ... -  《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》