Renal Events Research Articles

Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have a reliable hypoglycaemic and weight-loss effect that can intervene in obesity, which is the basis of type 2 diabetes pathology. GLP-1RA therapy has shown potential benefits in reducing the risk of major adverse cardiovascular events and improving kidney outcomes in patients with diabetes at high risk for cardiovascular disease. More recent evidence is expanding their benefits to heart failure with preserved ejection fraction and clinically important renal outcomes in patients with and without diabetes. Some sub-analyses of large clinical trials suggest that GLP-1RA and sodium-glucose cotransporter 2 inhibitor combination therapy may provide more significant reductions in heart failure hospitalization and renal composite events than each alone. Moreover, the addition of finerenone to this combination therapy could potentially provide stronger cardiorenal protective benefits. Further studies are needed to assess the potential cardiovascular and renal benefits of combination therapy and to determine suitable patient population for the therapy.

Acute kidney injury predicts the risk of adverse cardio renal events and all cause death in southeast Asian people with type 2 diabetes

Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction.

Patients' knowledge about renal secondary effects of anti-tumoral drugs and renal protection measures.

Onco-nephrology is an emerging subspecialty aiming to better understand and prevent renal events in cancer patients. We assessed patients' knowledge about (1) oncological/hematological treatments induced renal toxicity and (2) kidney protective measures. Adult patients receiving systemic anti-tumor treatments in multiple day hospital units in France answered a self-administered questionnaire about their knowledge and expectations related to treatment-associated renal toxicity. In total, 621 questionnaires were collected in 8 units from November 2021 to January 2022. Among respondents, 84.5% were treated for a solid tumor. Overall, 34.3% (n = 208) patients reported they had some knowledge about potential renal adverse events related to their anticancer treatment, and 38.5% (n = 234) about kidney protection measures. Their referring oncologist or hematologist represented the commonest source of knowledge (67.8%). Sufficient hydration was cited as a kidney protection measure by 93.2% (n = 218) of patients declaring some knowledge about renal toxicity; prevention of nausea/vomiting by 52.6% (n = 123). Consumption of still and alkaline water was chosen by respectively 64.4% (n = 400) and 16.8% (n = 104) of participants to correct dehydration. A majority of patients expressed strong interest for receiving more information about renal toxicity and prevention: median Likert scale score was 10/10 (Q1-Q3, 5-10), with online resources mentioned as the most desired source of information. One-third of patients declared they had some knowledge about potential renal toxicity of their oncologic treatment and the ways to prevent them, especially regarding hydration. However, a majority expressed interest for dedicated information, which conducted to the elaboration of free online educational sheets for patients.

A Nomogram Incorporating Inflammation and Nutrition Indexes for Predicting Outcomes in Patients with Acute Coronary Syndrome and Chronic Kidney Disease.

Inflammation, immunity, and nutriture are associated with prognosis in cardiovascular disease. We aimed to devise a novel nomogram model based on inflammation and nutrition indexes that accurately predicts Major adverse renal and cardiovascular events (MARCE) in patients diagnosed with acute coronary syndrome (ACS) and coexisting chronic kidney disease (CKD). We enrolled 685 individuals with ACS and CKD between January 2013 and August 2021. All patients were randomized into the training (70%) and validation (30%) cohorts. Univariable and multivariable Cox regression analyses were used to identify independent predictors for MARCE. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). The performance of the nomogram and GRACE score were compared. The nomogram included six variables: age, left ventricular ejection fraction, systemic immune-inflammatory index (SII), controlling nutritional status (CONUT) score, use of beta-blockers, and use of statins. The constructed nomogram demonstrated robust predictive performance, achieving ROC ranging from 0.830 to 0.935 in the training set and 0.793 to 0.889 in the validation set, respectively. Furthermore, the calibration curves exhibited excellent agreement between the predicted probabilities and the observed outcomes, indicating the reliability of the nomogram's predictions. Finally, the DCA confirmed the clinical value of the nomogram by demonstrating its potential to improve decision-making processes in the context of managing the condition under study. Compared with the GRACE score, the nomogram was superior in terms of both discrimination and reclassification ability. Our novel nomogram, which incorporates the CONUT score and SII, shows promising utility for predicting MARCE in patients with ACS and CKD. The identification of patients at heightened risk through our nomogram model is paramount as it serves as a cornerstone for the implementation of targeted interventions aimed at modifiable variables.

Cost-Utility of Real-Time Continuous Glucose Monitoring versus Self-Monitoring of Blood Glucose in People with Insulin-Treated Type 2 Diabetes in Spain.

Management of advanced type 2 diabetes (T2D) typically involves daily insulin therapy alongside frequent blood glucose monitoring, as treatments such as oral antidiabetic agents are therapeutically insufficient. Real-time continuous glucose monitoring (rt-CGM) has been shown to facilitate greater reductions in glycated hemoglobin (HbA1c) levels and improvements in patient satisfaction relative to self-monitoring of blood glucose (SMBG). This study aimed to investigate the cost-utility of rt-CGM versus SMBG in Spanish patients with insulin-treated T2D.. The analysis was conducted using the IQVIA Core Diabetes Model (CDM V9.5). Baseline characteristics of the simulated patient cohort and treatment efficacy data were sourced from a large-scale, United States-based retrospective cohort study. Costs were obtained from Spanish sources and inflated to 2022 Euros (EUR) where required. A remaining lifetime horizon (maximum 50 years) was used, alongside an annual discount rate of 3% for future costs and health effects. A willingness-to-pay (WTP) threshold of EUR 30,000 per quality-adjusted life year (QALY) was adopted, based on precedent across previous cost-effectiveness studies set in Spain. A Spanish payer perspective was adopted. Over patient lifetimes, rt-CGM yielded 9.933 QALYs, versus 8.997 QALYs with SMBG, corresponding to a 0.937 QALY gain with rt-CGM. Total costs in the rt-CGM arm were EUR 2347higher with rt-CGM versus SMBG (EUR 125,365 versus EUR123,017). The base case incremental cost-utility ratio was therefore EUR 2506 per QALY gained, substantially lower than the WTP threshold of EUR 30,000 per QALY. The analysis also projected a reduction in cumulative incidence of ophthalmic, renal, neurological, and cardiovascular events in rt-CGM users, with reductions of 16.03%, 13.07%, 7.34%, and 9.09%, respectively. Compared to SMBG, rt-CGM is highly likely to be a cost-effective intervention for patients living with insulin-treated T2D in Spain.

Uptitration of Sacubitril/Valsartan and Outcomes in Patients With Heart Failure - Insight From the REVIEW-HF Registry.

Guideline-directed medical therapy has become an important component of heart failure (HF) therapy, with sacubitril/valsartan as one of the recommended drugs; however, the real-world prognostic implications of sacubitril/valsartan uptitration are unclear. Patients with HF newly initiated on sacubitril/valsartan were registered in a retrospective multicenter study (REVIEW-HF). In all, 995 patients were divided into 3 groups according to the maximum dose achieved: high dose, sacubitril/valsartan 400 mg; intermediate dose, sacubitril/valsartan 200-<400 mg; and low dose, sacubitril/valsartan <200 mg. A total of 397 (39.9%) patients received high-dose sacubitril/valsartan; they had a significantly lower risk of mortality or HF hospitalization than patients in the low-dose (hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.29-0.53; P<0.001) and intermediate-dose (HR 0.64; 95% CI 0.45-0.94; P=0.03) groups. In the multivariable Cox regression model, higher systolic blood pressure and maintained geriatric nutritional risk index were significantly associated with a higher incidence of achieving a high dose of sacubitril/valsartan. Patients who did not receive high-dose sacubitril/valsartan experienced more hypotension during the follow-up period, whereas hyperkalemia, severe renal events, and angioedema did not differ across the achieved dose classifications. Patients who achieved sacubitril/valsartan uptitration had a better prognosis than those who did not. Before sacubitril/valsartan uptitration, patients need to monitor blood pressure closely to prevent worsening events.

Arterial hypertension-Current recommendations for action

Arterial hypertension (aHT) currently affects nearly 1 in every 3 persons in Germany and the number of those affected is steadily increasing. Only half of the patients treated show a controlled blood pressure in the follow-up. A suboptimal treatment involves the danger of cardiovascular and renal events that under certain circumstances can have a fatal course. The publication of the first national treatment guidelines (NVL) on hypertension and the new guidelines of the European Society of Hypertension (ESH) 2023 simultaneously represent two updates. Both emphasize the necessity to avoid hypertension-mediated organ damage (HMOD) and the identification of high blood pressure. The focussing on preventive measures and lifestyle recommendations as well as the simplification of target blood pressure values play important roles in the routine practice. This article provides a practical summary of the current recommendations of both guidelines on the diagnostics and treatment of aNT, discusses relevant differences and provides routinely applicable advice.

Clinical Recommendations for Managing Genitourinary Adverse Effects in Patients Treated with SGLT-2 Inhibitors: A Multidisciplinary Expert Consensus.

Background: SGLT-2 inhibitors (SGLT-2is) are considered to be a first-line treatment for common conditions like type 2 diabetes, chronic kidney disease, and heart failure due to their proven ability to reduce cardiovascular and renal morbidity and mortality. Despite these benefits, SGLT-2is are associated with certain adverse effects (AEs), particularly genitourinary (GU) events, which can lead to treatment discontinuation in some patients. Preventing these AEs is essential for maintaining the cardiorenal benefits of SGLT-2is. Methods: A multidisciplinary panel of experts from various medical specialties reviewed the best available evidence on GU AEs associated with SGLT-2i therapy. The panel focused on the prevention and management of genital mycotic infections, urinary tract infections, and lower urinary tract symptoms in both the general population and high-risk groups, such as renal and cardiac transplant recipients. Results: The panel found that permanent discontinuation of SGLT-2is results in a rapid loss of cardiorenal benefits. Preventive strategies, including identifying high-risk patients before initiating therapy, are critical for minimizing GU AEs. Clinical trials show that most GU infections linked to SGLT-2i therapy are mild to moderate in severity and typically respond to standard antimicrobial treatment, without the need for discontinuation. Conclusions: Routine discontinuation of SGLT-2is due to GU AEs is not recommended. Therapy should be resumed as soon as possible, unless severe or persistent conditions contraindicate their use, in order to preserve the significant benefits of SGLT-2is in reducing cardiovascular and renal events.

Development and validation of an early acute kidney injury risk prediction model for patients with sepsis in emergency departments

In this study, we aimed to develop and validate a nomogram to predicting the risk of sepsis-associated acute kidney injury (SA-AKI) in patients admitted to emergency departments (EDs). We randomly divided a retrospective dataset of 391 patients with sepsis into a 294-person training cohort and a 97-person validation cohort, and developed three predictive models using multivariate logistic regression analysis and clinical insight. No difference was observed between the three models using the DeLong test and Model 3 was selected as the risk prediction model based on the principle of least inclusion indicators. The use of vasopressor drugs, patient age, platelet count, procalcitonin, and D-dimer levels were included. The training and validation cohorts had a consistency index of 0.832 and 0.866, respectively, indicating high accuracy and stability in predicting SA-AKI risk. The area under the receiver operating characteristic curve was 0.832, showing excellent discrimination. The calibration curves for the training and validation cohorts showed excellent calibration. The decision curve and clinical impact curve analyses showed that the net clinical benefit of using the nomogram was greatest over a probability threshold of 0.05–0.90. In addition, the model showed moderate validity in predicting the 30-day survival and the incidence of major adverse renal events within 30 days. The nomogram developed for SA-AKI risk assessment in patients in EDs showed good discriminability and clinical utility. It can provide a theoretical basis for emergency physicians to prevent SA-AKI.

Integrated, person-centred care for patients with complex cardiovascular disease, diabetes mellitus and chronic kidney disease; a randomized trial

Abstract Background Patients with cardiovascular disease (CVD), diabetes mellitus (DM), and chronic kidney disease (CKD) often experience fragmented care, which negatively impacts outcomes and health-related quality of life (HRQoL). This study assessed whether multidisciplinary, person-centred care at an integrated clinic improves clinical outcomes and HRQoL. Methods This prospective, open, blinded-endpoint trial (CareHND; NCT03362983) included 131 patients with CVD, DM, and CKD stages 3–4, most of whom were enrolled during or shortly after acute hospitalization. The intervention group received person-centred care from cardiologists, nephrologists, endocrinologists, and specialist nurses at an integrated clinic; the control group received traditional care from separate specialists. Primary disease progression outcome was the composite of major adverse renal and cardiovascular events (MARCE) including death, heart failure (HF) readmission, myocardial infarction, PCI/CABG, acute or end-stage kidney failure, or TIA/stroke at 2 years. Co-primary person-centred outcomes was self-reported HRQoL by RAND-36. Results In a pre-specified interim analysis, patients randomized to integrated care had lower eGFR and higher NT-proBNP than traditional care. Follow-up ranged from 2.0 to 5.7 years. Kaplan-Meier analysis showed no difference in MARCE between groups. Cox-regression adjusting for baseline differences, indicated a trend towards reduced HF hospitalisations for integrated care (HR 0.53; CI 0.28–1.01; P = 0.054). Integrated care improved Role Physical and Social Function scores, and self-rated health (P = 0.021, P = 0.019, and P = 0.011, respectively). Conclusions Integrated care improved several dimensions of HRQoL but did not improve MARCE compared to traditional care in this small trial. We observed a trend towards reduced HF hospitalizations. Overall, integrated care presents a promising alternative.

Empaglifozin modifies the arterial stiffness in type-2 diabetic patients: a preliminary report.

Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated beneficial effects on cardiovascular and renal events in patients with type 2 diabetes mellitus. The mechanisms underlying these effects are not fully elucidated. Aim of this study was to investigate whether empagliflozin is able to modify the arterial stiffness in type 2 diabetic patients. Methods Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed before and after adding empagliflozin to a traditional antidiabetic treatment in 16 consecutive T2DM outpatients folowed for 3 months. Arterial stiffness were evaluted using SphygmoCor ECEL measuring the pulse waveform of the arterial pulse moving from tha descending aorta to the femoral artery (PWV). Data obtained from the diabetic population has been compared to 16 T2DM outpatients not treated with SGLT2 inhibitors. Results In the two groups differences according gender distribution or duration of diabetes mellitus did not emerge. However the empagliflozin group was younger compared to controls (64.1±8.68 vs 74.45±8.13, P &amp;lt; 0.05). Empagliflozin treatment significantly decreased HbA1c after 12 weeks of treatment (7.9±0.78 vs 7.04±1.09%, P &amp;lt; 0.008.). After 12 weeks’ treatment, empagliflozin significantly improved PWV compared to controls not treated with SGLT2-i (ΔPWVV -0.68±1.1 vs 0.89±1,6 p &amp;lt;0.004, P = 0.0065 with age and HbA1c as covariates). Moreover body weight significantly decreased in the empagliflozin group (86.75±16.16 vs 81.71±16.5 kg, p =0.001) compared to controls (in whom remained unchanged) as long as BMI (30.48±5.4 versus 28.75±5.66 kg/m2, P &amp;lt; 0.002) compared to controls (in whom remained unchanged). Estimated glomerular filtration rate (eGFR) remained unchanged in the two groups during the study whereas urine Albumin to Creatinine ratio significantly improved using empagliflozin (17.8±46.8 vs 12.2±35.7 mg/mmol, P = 0.049). Conclusion In this ‘real clinical practice’ experience, the potential effect of empagliflozin treatment on arterial stiffness in T2DM patients was extensively investigated. Arterial stiffness was significantly decreased adding empaglifozin to the traditional treatment and this result has been obtained after 3-month. Significantly improvement in urine Albumin to Creatinine ratio might suggest an amelioration of endothelial function in those patients that could be involved in reducing arterial stiffness.

Association between malnutrition and adverse renal outcomes in patients with type 2 diabetes.

Nutritional management is crucial in patients with chronic kidney disease. Therefore, it is important to assess nutritional status and detect malnutrition, especially in patients with diabetes. However, there is currently a lack of evidence regarding the relationship between nutritional indices and renal function in patients with type 2 diabetes. This study investigated whether the geriatric nutritional risk index (GNRI) is related to renal prognosis in type 2 diabetes patients. The study included 946 type 2 diabetes patients enrolled in the Fukushima Cohort Study. The primary endpoint of this study was a renal event, defined as a combination of a 50% decline in eGFR from baseline and end-stage kidney disease. All-cause death and new cardiovascular events were also measured as secondary outcomes. The association between GNRI and these endpoints was assessed using Cox regression analysis. The median patient age was 66 years, 57% were men, the median eGFR was 67.9 mL/min/1.73 m2, and the median GNRI was 100.0. Compared to patients in the highest GNRI tertile, patients in the lowest tertile had a significantly increased risk of therenal event (HR 5.15, 95% CI 2.51-10.6) and all-cause death (HR 2.30, 95% CI 1.20-4.42). A significant association was not observed between GNRI levels and cardiovascular events. We observed an association between poor nutritional status, assessed by GNRI, and adverse outcomes in patients with type 2 diabetes. Nutritional status assessment has potential utility as a prognostic tool for individuals with type 2 diabetes.

Finerenone: A Third-Generation MRA and Its Impact on Cardiovascular Health-Insights from Randomized Controlled Trials.

Introduction: Finerenone, a third-generation non-steroidal mineralocorticoid receptor antagonist (MRA), offers a targeted approach to managing cardiovascular outcomes, particularly in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Unlike traditional MRAs such as spironolactone and eplerenone, which can cause off-target hormonal side effects and hyperkalemia, Finerenone selectively binds to mineralocorticoid receptors, reducing these risks. Recent randomized controlled trials have demonstrated Finerenone's potential to improve cardiovascular outcomes, making it a promising alternative in the management of heart failure and other cardiovascular conditions associated with CKD and T2D. Methods: We conducted a scoping review using PRISMA guidelines. A search for "Finerenone" in the PubMed, Embase, and Cochrane Library databases included randomized controlled trials (RCTs), post hoc analyses, and relevant meta-analyses on cardiovascular outcomes. Data were synthesized narratively, assessing study quality through strengths and limitations. Discussion: Finerenone has shown significant benefits and a superior safety profile compared with traditional MRAs like spironolactone and eplerenone in managing CKD, T2D, and heart failure. It effectively reduces cardiovascular and renal events while minimizing risks such as hyperkalemia and hormonal side effects associated with steroidal MRAs. Future studies, including the REDEFINE-HF, FINALITY-HF, and CONFIRMATION-HF trials, will further explore Finerenone's potential across diverse heart failure phenotypes, including its role in heart failure with mildly reduced and preserved ejection fractions, potentially establishing it as a cornerstone therapy in heart failure management. Conclusions: Finerenone represents a significant advancement in MRA therapy, offering enhanced safety and efficacy in managing cardiovascular outcomes in CKD and T2D patients. The current evidence supports its use as a promising alternative to traditional MRAs, particularly in patients intolerant to steroidal MRAs. Further trials are needed to fully establish its potential across diverse patient populations, including those with varying heart failure phenotypes.

PD-1 immunology in the kidneys: a growing relationship.

In recent years, knowledge regarding immune regulation has expanded rapidly, and major advancements have been made in immunotherapy for immune-associated disorders, particularly cancer. The programmed cell death 1 (PD-1) pathway is a cornerstone in immune regulation. It comprises PD-1 and its ligands mediating immune tolerance mechanisms and immune homeostasis. Accumulating evidence demonstrates that the PD-1 axis has a crucial immunosuppressive role in the tumor microenvironment and autoimmune diseases. PD-1 receptors and ligands on immune cells and renal parenchymal cells aid in maintaining immunological homeostasis in the kidneys. Here, we present a comprehensive review of PD-1 immunology in various kidney disorders, including renal cell carcinoma, glomerulonephritis, kidney transplantation, renal aging, and renal immune-related adverse events secondary to PD-1 immunotherapy.

Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events and Safety Outcomes in Patients with Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-based Target Trial Emulation.

Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose co-transporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D). We performed an emulated clinical trial in an insurance-based cohort in the U.S., evaluating SGLT2i versus dipeptidyl peptidase 4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE patients and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PS) based on clinical and demographic factors. Hazard ratios (HR with 95% confidence intervals) were calculated using Cox models. Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39-0.63), chronic kidney disease (HR 0.61, 0.50-0.76), end-stage renal disease (HR 0.40, 0.20-0.80), heart failure (HR 0.72, 0.56-0.92), and emergency department visits (HR 0.90, 0.82-0.99). Risks of all-cause mortality (HR 0.89, 0.65-1.21), lupus nephritis (HR 0.67, 0.38-1.15), myocardial infarction (HR 0.81, 0.54-1.23), stroke (HR 1.03, 0.74-1.44), and hospitalizations (HR 0.76, 0.51-1.12) did not differ. Genital infection risk (HR 1.31, 1.07-1.61) was increased, but urinary tract infection risk (HR 0.90, 0.79-1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.065, 0.53-2.14) and fractures (HR 0.95, 0.66-1.36). In this emulated clinical trial, SGLT2i vs. DPP4i use was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.

Association of initial serum sodium change and clinical outcome in patients with diabetes receiving sodium-glucose cotransporter-2 inhibitor therapy: A multicentre database analysis in Taiwan.

The study aimed to assess the impact of varying degrees of initial serum sodium change among patients with type 2 diabetes (T2D) starting sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy and their subsequent clinical outcome. We used medical data from a multicentre health care provider in Taiwan and recruited 4400 patients with T2D with baseline normal serum sodium (135-145 mmol/L) and follow-up serum sodium measures available after 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2021. After a median of 2.9 (2.4, 3.4) months of SGLT2i treatment, overall, there was a minimal change in serum sodium levels (from 139.6 ± 2.4 to 139.5 ± 3.7 mmol/L). Most patients (87.8%) maintained normal sodium levels, while 8.6% (n = 378) experienced hyponatraemia (<135 mmol/L) and 3.6% (n = 158) hypernatraemia (>145 mmol/L). Factors independently associated with hyponatraemia included cancer history, chronic lung disease, insulin use, higher glycated haemoglobin, impaired liver function, lower baseline sodium and greater initial decline in kidney function. Conversely, factors linked to hypernatraemia included older age, absence of cancer history, loop diuretic and non-steroidal anti-inflammatory drug use, higher baseline sodium and a lesser initial decline in kidney function. Over a median of 26.0 months of follow-up, hyponatraemia shortly after starting SGLT2i therapy was associated with significantly increased risks of major adverse cardiovascular events [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.83-3.48], heart failure for hospitalization (HR: 1.66; 95% CI: 1.16-2.37), major adverse renal events (HR: 2.27; 95% CI: 1.73-2.96) and all-cause death (HR: 2.98; 95% CI: 2.17-4.11) after adjusting for clinically relevant factors. Non-linear analysis indicated that a more pronounced initial decline in serum sodium levels correlated steeply with higher risks of these adverse events. While most patients with T2D maintain stable serum sodium homeostasis on SGLT2i therapy, a subset may experience dysnatraemic events with potential worse clinical consequences. Physicians should be vigilant about monitoring sodium levels and considering the associated risks when initiating SGLT2i therapy in patients with risk.

Renal medullary perfusion differs from that in renal cortex in patients with sepsis associated acute kidney injury and correlates with renal function prognosis: A prospective cohort study.

Renal perfusion status remains poorly studied at the bedside during sepsis associated acute kidney injury (AKI). The aim of the study is to examine renal cortical and medullary perfusion using renal contrast enhanced ultrasound (CEUS) in septic patients. In this single-center, prospective longitudinal study, septic patients were enrolled. Renal ultrasonography was performed within 24 hours of ICU admission (D1), then repeated at D3, D5 and D7. Each measurement consisted of three destruction replenishment sequences that were recorded for delayed analysis with dedicated software (Vuebox). Renal cortex and medulla perfusion were quantified by measuring time to peak (TTP). Receiver operating characteristic (ROC) analysis was used to evaluate 28-day renal prognosis. The study included 149 septic patients, including 70 non-AKI patients and 79 AKI patients. Both renal cortical and medullary TTP was longer in the AKI group than in the non-AKI group. The difference of TTP between renal cortex and medulla in AKI group was higher than that in the non-AKI group (p = 0.000). Medullary TTP on day 3 had the best performance in predicting the prognosis of 28-day renal function (AUC 0.673, 95% confidence interval 0.528-0.818, p = 0.024), and its cut-off value was 45 s with a sensitivity 52.2% and a specificity of 82.1%. Cortical TTP on day 3 also had the performance in predicting the prognosis of 28-day renal function (AUC 0.657, 95% confidence interval 0.514-0.800, p = 0.039), and its cut-off value was 33 s with a sensitivity 78.3% and a specificity of 55.0%. Renal medullary perfusion alterations differ from those in cortex, with the medulla is worse. Simultaneous and dynamic assessment of cortical and medullary microcirculatory flow alterations necessary. TTP on day 3, especially medullary TTP, seems to be a relatively stable and useful indicator, which correlates with 28-day renal function prognosis in septic patients. Early correction of renal cortical and medullary perfusion alterations reduces the incidence of adverse renal events.

Risk factors for renal progression in patients with CKD and coexisting COPD.

Chronic diseases rarely occur in isolation, and chronic kidney disease (CKD) is no exception. There has been considerable research on the interplay between the heart and kidneys, but studies on the relationship between the lungs and kidneys are less common. The interaction between pulmonary and renal functions in areas such as acid-base metabolism, chronic inflammation, and bone metabolism is increasingly gaining clinical attention. In this cohort study, we examined 480 patients with stages 3-4 CKD and COPD (GOLD stages 1 and 2) to identify risk factors that contribute to the progression of renal function to a composite endpoint, which includes a 40% decline in estimated glomerular filtration rate (eGFR) and the onset of end-stage renal disease during follow-up periods. A Cox proportional hazards regression model was used to investigate the risk factors associated with the timing of renal event endpoints in the study population. Additionally, the restricted cubic spline method was used to explore the relationship between quantitative variables and survival risk. Our study included 480 eligible patients with an average follow-up period of 21.41 ± 14.90months, during which 224 individuals (46.7%) experienced the composite renal endpoints. Multivariable Cox regression analysis revealed that systolic blood pressure (SBP) [1.01 (1.00-1.02), p = 0.002], hemoglobin (Hb) [HR 0.89 (0.83-0.96), p = 0.002], albumin (Alb) [0.96 (0.93-0.99), p = 0.009], and edema [1.73 (1.29-2.33), p < 0.001] were independent risk factors for the renal endpoints. The adjusted multivariable Cox regression analysis demonstrated that elevated SBP and edema were factors that promoted the occurrence of composite endpoints, while higher levels of Hb and Alb were protective factors.

Pharmacological management of osteoarthritis: judicious use of nonsteroidal anti-inflammatory drugs

Background: Osteoarthritis (OA) is a chronic disease characterized by persistent pain and joint deformation. Effective pain management in patients with OA necessitates accurate diagnosis and appropriate treatment planning, considering the prolonged therapy required for OA. Although non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for pain management in patients with OA, their long-term use can lead to various adverse effects that warrant careful consideration.Current Concepts: NSAIDs inhibit cyclo-oxygenase (COX) enzymes and produce an anti-inflammatory and analgesic effect. However, this mechanism of action can produce adverse gastrointestinal, cardiovascular, and renal effects. The relative risk of gastrointestinal and cardiovascular adverse events depends on the COX selectivity of NSAIDs. Consequently, selective COX-2 inhibitor or concomitant proton pump inhibitor administration is recommended in patients at a high risk of gastrointestinal complications. Minimizing NSAID use is advised in patients at a high risk of cardiovascular adverse events; however, if this is unavoidable, short-term administration of naproxen or low-dose celecoxib should be considered. COX selectivity is not associated with adverse renal events. Therefore, acetaminophen is preferred in patients with impaired renal function, and short-term use of NSAID patches or topical formulations may be useful.Discussion and Conclusion: The choice of NSAIDs for OA should be tailored to patients’ needs, considering their risk factors, potential drug interactions, and other relevant factors. Additionally, incorporation of nonpharmacological interventions can minimize the NSAID dosage and reduce the risk of adverse effects, and regular monitoring is essential to identify adverse effects.

Effect of frail phenotype on cardiorenal risk and healthcare utilization in older patients with chronic kidney disease.

Introduction Limited data have addressed frailty's role in cardiorenal risk among older adult patients with chronic kidney disease (CKD). We investigated whether frailty could predict major renal and cardiovascular events, healthcare utilization, and mortality in these patients. Methods We conducted a prospective cohort enrolling patients ≥ 75 years with a stable estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73 m2. Frailty phenotype consists of shrinking, low activity, exhaustion, weakness, and slowness, scored 0 to 5. The primary composite renal outcome was a ≥ 25 % decrease in eGFR concurrent with CKD stage progression or dialysis initiation. Secondary outcomes included major adverse cardiovascular events (MACE), emergency room (ER) visits, all-cause mortality, and hospitalization. Using multivariate Cox models with/without competing risk analyses, we explored frailty's impact on these outcomes. Results Among 203 older CKD patients (mean age 81.6 ± 5.0 years, female 40.9 %, diabetes 33.0 %, body mass index 24.9 ± 3.7 kg/m2), 67.9% were frail. Over 3.47 years, 38.9% faced composite renal outcomes, 13.3% MACE, 15.3% mortality, and more than half utilized healthcare. Every one-point frailty elevated composite renal outcome risk by 28.0 % (HR: 1.28, 95% CI:1.03-1.59) and significantly increased secondary outcomes (hospitalization [HR: 1.24, 95% CI: 1.06-1.46], unexpected ER visit [HR: 1.20, [95% CI:1.03-1.39], and mortality [HR: 1.51, 95% CI: 1.06-2.16]) but not for MACE [HR: 1.43, 95% CI: 0.99-2.08]. Results were consistent across subgroups and competing risk analysis. Conclusion In CKD patients ≥ 75 years, frailty was associated with progressive kidney disease, increased mortality and healthcare utilization.