Diabetes Chronic Kidney Disease Research Articles

Factors Associated With Adverse Outcomes Among Patients Undergoing Endovascular Revascularization for Iliac Artery Lesions TASC II A and B: A Single-Center Study.

This prospective study from October 2016 to September 2020 aimed to identify the factors associated with non-revascularization and mortality rates in patients who underwent endovascular interventions for Trans-Atlantic Inter-Society Consensus (TASC) II A/B iliac artery occlusions at the Department of Vascular Surgery. Patients with TASC II A/B iliac artery occlusions who underwent endovascular intervention, including balloon angioplasty and stent placement, were included. The primary outcomes were factors associated with non-revascularization and mortality rate. A total of 133 patients were enrolled in this study. Univariable analysis revealed significant associations between non-revascularization and diabetes (hazard ratio [HR]=2.61, 95% confidence interval [CI], p=0.03), chronic kidney disease (HR=16.2, 95% CI, p=0.01), and severe calcifications (HR=8.56, 95% CI, p<0.001). Subsequent multivariable analysis confirmed the significance of these factors, showing HRs of 3.04 (95% CI, p=0.02), 13.12 (95% CI, p=0.03), and 8.62 (95% CI, p<0.001), respectively. The overall mortality rate observed was 20.3%. Severe calcifications emerged as a significant risk factor for mortality in both univariable (HR=2.47, 95% CI, p=0.02) and multivariable (HR=3.01, 95% CI, p<0.001) analyses. Severe calcifications correlate with non-revascularization and mortality, while comorbidities like diabetes mellitus and chronic kidney disease are also associated with non-revascularization. Recognizing these identified factors holds substantial promise in enhancing patient selection and procedural approaches, potentially bolstering the success rates of endovascular interventions. However, further research aimed at comprehending the underlying mechanisms and devising strategies to mitigate these risks is imperative for continued improvement in patient outcomes. The study provides valuable insights into patient selection and procedural planning for endovascular interventions in TASC II A/B iliac artery occlusions. Identifying severe calcifications, diabetes, and chronic kidney disease as key risk factors for non-revascularization and mortality equips clinicians with essential predictive tools, potentially improving outcomes by tailoring treatment approaches. The innovation lies in highlighting the impact of comorbidities and calcification severity, offering a pathway to refine patient eligibility criteria and optimize procedural decisions. This underscores the importance of further research to develop strategies that mitigate these risk factors and enhance intervention success rates.

Abstract 4134384: Sotagliflozin, a Dual Inhibitor of Sodium-Glucose Transporters 1 and 2, Elicits Cardioprotective Effects Through Attenuation of Platelet Activation and Thrombosis

Sodium-glucose cotransporter (SGLT) inhibitors are used in the treatment of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). In the SCORED trial, sotagliflozin (SOTA), a dual SGLT1/2 inhibitor, demonstrated significant reductions in both myocardial infarction (MI) and stroke in patients with T2DM and CKD. These results suggest a cardiovascular (CV) benefit of SOTA in patients with T2DM and CKD who are at increased risk of thromboembolic disease. To investigate the underlying mechanism of CV protection, we evaluated the effects of SOTA on platelet activation and thrombus formation, in both in vivo and ex vivo models, to understand its effects on MI and stroke. Washed human platelets treated with SOTA were stimulated with various agonists and platelet activation was assessed via lumi-aggregometry and flow cytometry. In whole blood, SOTA was evaluated for its potential to reduce platelet adhesion and thrombus formation in the perfusion flow chamber and Total Thrombus formation Analysis System (TTAS) assays. In vivo , mice dosed with SOTA were assessed for thrombus formation at the site of injury in real-time in the cremaster arteriole injury model. To determine the effect of SOTA on hemostasis, we assessed coagulation parameters ex vivo in human whole blood using thromboelastography. Finally, bleeding time was measured in vivo in mice dosed with SOTA using the tail bleeding assay. In washed platelets, SOTA inhibits platelet activation and aggregation in a dose-dependent manner. Similarly, a dose-dependent decrease in platelet adhesion and thrombus formation was observed in whole blood assays. In vivo , platelet accumulation and fibrin formation were decreased in mice dosed with SOTA, however no effect is observed in coagulation parameters or bleeding time. SOTA inhibits platelet activation and thrombus formation with no impact on coagulation parameters or bleeding potential. These findings highlight a potential mechanism through which SOTA reduces the risk of stroke and MI in patients with T2DM and CKD, underscoring the importance of further investigation into the role of SOTA in CV protection, particularly in patients suffering from both T2DM and CKD at high risk of thromboembolic events.

Abstract 4122290: Association between SGLT2 inhibitors and risk of Dementia and Parkinson’s Disease: A Meta-analysis of 12 Randomized Controlled Trials.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy’s potential effects on the risks of dementia and Parkinson’s disease are not well established, with conflicting results based on observational studies. Objective: We sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson’s disease in patients with type 2 diabetes mellitus (T2DM), heart failure, or chronic kidney disease. Methods: We performed a systematic literature search on PubMed, Scopus, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until March 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 12 RCTs with 74, 442 patients (40784 in the SGLT2i group and 33658 in the control group) were included in the analysis. The mean age of patients in SGLT2i and control was 65.3 and 65.2 years respectively. The mean follow-up duration was 2.9 years. Pooled analysis showed that there is no significant association between SGLT2i and the risk of dementia (OR, 1.37 (95%CI: 0.70-2.69), P= 0.36, I2=0%), dementia Alzheimer’s type (OR, 2.62 (95%CI: 0.47-14.49), P= 0.27, I2=0), vascular dementia (OR, O.52 (95%CI: 0.09-2.98), P= 0.46, I2=0%), and Parkinson’s disease (OR, 0.75 (95%CI: 0.25-2.25), P= 0.61, I2=0%) was comparable between SGLT2i and control groups. Conclusion: Our study suggest that there is no significant association between SGLT2i and the risk of dementia, its subtypes, and Parkinson’s disease. Further large-power randomized trials are needed to strengthen the understanding of neuropsychiatric beneficial effects of SGLT2i.

Physical activity and renal outcome in diabetic and non-diabetic patients with chronic kidney disease stage G3b to G5

The association of physical activity with renal outcome and mortality in advanced chronic kidney disease (CKD; i.e., estimated glomerular filtration rate [eGFR] < 45 ml/min/1.73m2) is poorly studied. We examined this association in patients with advanced CKD in Japan. We used the Rapid Assessment of Physical Activity to assess baseline physical activity and classify patients as active or inactive. CKD progression was defined as 40% decline in eGFR, eGFR < 10, or requiring dialysis or transplantation. Among the 1,808 eligible patients, after adjusting for possible confounders, hazard ratios (HRs) for poor renal outcome in the active group were 0.68 (95% CI, 0.44–1.04), 1.09 (0.86–1.38), and 1.01 (0.82–1.25) in CKD stage G3b, G4, and G5, respectively, suggesting a renal benefit of exercise in CKD stage G3b. Adjusted HRs for death were 0.79 (0.40–1.57), 0.55 (0.38–0.80), and 0.75 (0.44–1.26) in stage G3b, G4, and G5, respectively. While the adjusted HRs of death were 0.84 (0.52–1.38) and 0.60 (0.43–0.83) in diabetic and non-diabetic patients, suggesting that exercise may reduce mortality in non-diabetic patients. Our study suggests that exercise is associated with better survival in non-diabetic patients with CKD stage G3b-5, and better renal outcome in diabetic and non-diabetic CKD stage G3b.

Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy.

Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF. We included 81 patients with stage D HF (ICM, n=44; DCM, n=37) undergoing left ventricular assist device implantation (n=59) or heart transplantation (n=22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3+ cells/mm2 relevant inflammation. Patients with ICM or DCM did not differ regarding age (61.5±5.7 vs. 56.5±12.7years, P=0.164), sex (86% vs. 84% male, P=0.725), type 2 diabetes mellitus (34% vs. 18%, P=0.126) or chronic kidney disease (8% vs. 11%, P=0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6±41.4 vs. 141.9±59.9pmol/(s*mg), P=0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59±0.28 vs. 0.69±0.36pmol/(s*ml), P=0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6±164.1 vs. 503.0±198.5nmol/min/mg protein, P=0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P=0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r=-0.296, P=0.019). Fibrosis was more prevalent in ICM (20.9±21.2 vs. 7.2±5.6% of area, P=0.002), but not associated with oxidative capacity (r=-0.13, P=0.327). More than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM.

Association of soluble ST2 with heart failure and other comorbidities in patients with severe coronary heart disease

Abstract Background Circulating levels of soluble suppression of tumorigenicity-2 (sST2) reflect vascular congestion, inflammation, and fibrosis. sST2 has been proposed as a useful biomarker to predict the mortality and hospitalization due to heart failure. However, there is limited evidence regarding the relationship between sST2 and heart failure, as well as other comorbidities, in severe coronary heart disease (CAD). Purpose This study aims to measure the circulating levels of soluble ST2 (sST2) in a large population of patients with severe CAD to determine its association with heart failure, cardiac function, inflammation, and other important comorbidities. Methods This subanalysis is part of the ongoing perspective observational study. Available serum samples from 520 patients undergoing elective coronary artery bypass grafting (CABG) were analysed for sST2 levels. The inclusion criteria were written informed consent and age between 18-85 years. Exclusion criteria for this analysis were severe valvular disease, severe chronic obstructive pulmonary disease, oxygen therapy, nocturnal positive airway pressure support or mechanical ventilation, and the need for catecholamines or circulatory assist devices. The circulating levels of human sST2 were measured from frozen serum (-80°C) using commercially available ELISA kits. The plasma was diluted 100 times to detect sST2 levels (assay range of 31.2 - 2,000 pg/mL). Two measurements were taken to account as means for intra-assay variabilities. Logarithmic transformation was used to convert non-normal distributed data. Student t' test and linear regression were applied to categorical or continuous variables as appropriate. Results sST2 levels (median 20.4 ng/ml, [IQR 15.5 – 28.8]) significantly predict worse left ventricular ejection fraction (β = -0.164, p = 0.006), and significantly correlate with levels of NT-proBNP (β = 3.263, p &amp;lt; 0.001), hs-Troponin T (β = 3.391, p &amp;lt; 0.001), high-sensitivity C-reactive protein (β = 2.472, p = 0.014) and heart failure (p= 0.002). Interestingly, common comorbidities such as chronic kidney disease (estimated glomerular filtration rate &amp;lt; 60 mL/min/1.73 m2, p = 0.004), diabetes mellitus (p = 0.001) and higher levels of glycated haemoglobin (HbA1c, β = 3.615, p &amp;lt; 0.001) showed also a significant association with sST2 levels. No significant association of sST2 was observed with arterial hypertension (p = 0.190), atrial fibrillation (p = 0.289), obesity (BMI ≥ 30 kg/m2, p = 0.302), sleep apnoea (apnoea-hypopnoea index ≥ 15/h, p = 0.068), peripheral artery disease (p = 0.823), or previous stroke (p = 0.861). Conclusion(s) Circulating levels of sST2 significantly correlate with heart failure, NT-proBNP, hs-TnT, and hs-CRP in patients with severe CAD. Additionally, sST2 levels were found to be elevated in patients with diabetes mellitus and chronic kidney disease.

Association Between the Use of Proton Pump Inhibitors and Severe Clinical Outcomes in COVID-19 Patients: A Retrospective Observational Study.

Background Proton pump inhibitors (PPIs) increase the risk of pneumonia secondary to PPI-induced hypochlorhydria. We aim to investigate the association between PPI and disease severity in coronavirus disease 2019 (COVID-19)-positive patients and the risk of hospitalizations in Muscat, Oman. Methodology COVID-19-positive patients aged 18 years and above at the time of diagnosis were included in this retrospective observational study. The details of the patients were retrieved from the electronic health records of the Al Shifa Hospital Information Management System and Tarassud. The composite primary endpoint was COVID-19 admission to a government tertiary hospital ward or intensive care within 14 days of diagnosis. Results A total of 506 COVID-19-positive patients were identified during the specified period. The mean age was 44 ± 15 years. The majority of the patients were Omani, and a female preponderance was observed. Overall, 104 (20.4%) patients were current PPI users. Admission due to COVID-19 was significantly associated with the presence of comorbid conditions such as diabetes mellitus (p = 0.001), hypertension (p = 0.001), and chronic kidney disease (p < 0.001). However, current PPI use (p = 0.140) was not significantly associated with an increased risk of hospitalization. Conclusions This data suggests that the use of PPIs during COVID-19 infection did not increase the risk of severe COVID-19 infection and poor outcomes leading to hospitalization in Muscat, Oman. However, the presence of other medical comorbidities, such as diabetes and hypertension, was associated with a higher risk of adverse clinical symptoms that resulted in hospitalization.

Impact of High-Intensity Statin on Atrial Fibrillation After Off-Pump Coronary Artery Bypass.

There is uncertainty regarding the impact of high-intensity statins on postoperative outcomes in patients undergoing surgical myocardial revascularization. This study was conducted to evaluate the impact of high-intensity statin treatment on the occurrence rate of new-onset postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB). Six hundred thirteen patients (66.8±9.8 years, male:female = 476:137) who underwent isolated OPCAB were retrospectively enrolled. Hypertension (n = 409, 66.7%), diabetes mellitus (n = 343, 59.6%) and chronic kidney disease (n = 138, 22.5%) were common comorbidities. Statins and beta-blockers were administered to all patients until the day of surgery and resumed within 6 hours after surgery. Risk factors associated with POAF were analyzed, including the use of high-intensity statins (atorvastatin 40 mg-80 mg or rosuvastatin 20 mg), as well as baseline characteristics and preoperative risk factors. High-intensity statins were used in 158 patients (25.8%). POAF occurred in 184 patients (30.0%). The use of high-intensity statins was not correlated with preoperative levels of low-density lipoprotein (P = 0.135) or high sensitivity C-reactive protein (P = 0.365). Multivariate logistic regression analysis revealed that the use of high-intensity statins was significantly associated with a reduced occurrence of POAF (P = 0.022, odds ratio [95% confidence interval] = 0.592 [0.378-0.926]). Age, acute coronary syndrome, insulin-dependent diabetes mellitus and chronic kidney disease were also significantly associated with POAF. Preoperative administration of high-intensity statins was associated with a 41% reduction in the occurrence rate of POAF in patients who underwent OPCAB.

Metabolic/Bariatric Surgery is Safe and Effective in People with Obesity, Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Obesity, type 2 diabetes (T2D), and chronic kidney disease (CKD) are thought to increase surgical risks and reduce weight loss after metabolic/bariatric surgery (MBS). Electronic databases were searched between January 2013 and August 2023 for randomized controlled trials (RCT) of MBS reporting data on the safety, total weight loss (TWL), and metabolic control in patients with and without CKD. Forty-four out of 2904 articles were analyzed, representing 1470 patients. No significant differences were found in TWL after 1year (- 19%, CI - 0.19 to - 0.18 vs.: - 15%, CI - 0.20 to - 0.09, p = 0.13) or after 5years (- 20%, CI - 0.21 to - 0.18 vs. Group - 16%, CI - 0.28 to - 0.04, p = 0.50).Similarly, there were no significant differences in HbA1c at 1year (- 1.06, CI - 1.37 to - 0.76 vs. Group 2: - 1.52, CI - 2.25 to - 0.79, p = 0.26) or after 5years (- 0.97, CI - 1.53 to 0.41 vs. Group 2: - 1.09, CI - 2.21 to 0.03, p = 0.85). For fasting plasma glucose, no differences were seen at 2years (- 30.43, CI - 60.47 to 0.39 vs. - 35.11, CI - 48.76 to - 21.46, p = 0.78) or after 5years (- 11.24, CI - 53.38 to 30.89 vs. - 5.4, CI 20.22 to 9.42, p = 0.80). In terms of total cholesterol, no significant differences were found after 1year (- 10.36, CI - 32.94 to 12.22 vs. - 19.80, CI - 39.46 to - 0.14, p = 0.54) or after 5years (- 7.43, CI - 25.09 to 5.23 vs. - 21.30, CI - 43.08 to 0.49, p = 0.15). For triglycerides, both showed similar reductions after 1year (- 76.21, CI - 112.84 to - 39.59 vs. - 78.00, CI - 100.47 to - 55.53, p = 0.94) and after 5years (- 79.65, CI - 121.09 to - 38.21 vs. - 53.15, CI - 71.14 to - 35.16, p = 0.25). The presence of CKD in patients with obesity and T2D does not reduce the safety and efficacy of MBS.

Molecular mechanism of ectopic lipid accumulation induced by methylglyoxal via activation of the NRF2/PI3K/AKT pathway implicates renal lipotoxicity caused by diabetes mellitus.

Patients with chronic kidney disease (CKD) have a high incidence of dyslipidemia comprising high triglyceride (TG) and low high-density lipoprotein (HDL)-cholesterol levels. An abnormal increase of TGs within cells can lead to intracellular lipid accumulation. In addition to dyslipidemia, hyperglycemia in diabetes may elicit ectopic lipid deposition in non-adipose tissues. Hyperglycemia increases intracellular levels of methylglyoxal (MG) leading to cellular dysfunction. A deficit of glyoxalase I (GLO1) contributes to dicarbonyl stress. Whether dicarbonyl stress induced by MG causes renal lipotoxicity through alteration of lipid metabolism signaling is still unknown. In this study, mice with high fat diet-induced diabetes were used to investigate the renal pathology induced by MG. NRK52E cells treated with MG were further used in vitro to delineate the involvement of lipogenic signaling. After treatment with MG for 12 weeks, plasma TG levels, renal fatty changes, and tubular injuries were aggravated in diabetic mice. In NRK52E cells, MG activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and sterol regulatory element-binding protein 1 (SREBP1), resulting in stimulation of fatty acid synthase. The intracellular accumulation of lipid droplets was mainly contributed by TGs, which increased the oxidative stress accompanied by high Nrf2 expression. In addition, MG time-dependently activated cyclin D, cyclin-dependent kinase 4 (CDK4), and cleaved caspase-3, evidencing that G0/G1 arrest was associated with apoptosis of NRK52E cells. In conclusion, our studies revealed the mechanism of lipotoxicity caused by MG. The target of such dicarbonyl stress may become a promising therapy for diabetic CKD.

Benefit of combination therapy with dapagliflozin and eplerenone on cardiac function and fibrosis in rats with non-diabetic chronic kidney disease

Patients with chronic kidney disease (CKD) are at a high risk of cardiovascular (CV) complications. In these patients, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce CV events. Mineralocorticoid receptor antagonists (MRAs) exert similar benefits in diabetic CKD, though their effects in non-diabetic CKD remain unclear. This study aimed to evaluated whether the combination of Dapagliflozin (DAPA) and Eplerenone (EPLE) would have positive effects on cardiorenal functions in a non-diabetic CKD model. CKD was induced in rats via 5/6 nephrectomy, followed by treatment with DAPA (5 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination for 3 months following CKD induction. Cardiorenal functions were assessed after the treatment period. All treated groups showed reduced kidney fibrosis though plasma creatinine and urea levels remained unchanged. Compared to untreated CKD, EPLE or DAPA/EPLE reduced left ventricle (LV) end-diastolic pressure and LV end-diastolic pressure volume relationship, whereas DAPA alone did not achieve significant reductions. Compared to untreated CKD, EPLE and DAPA/EPLE improved cardiac perfusion but DAPA alone did not. Cardiac fibrosis in CKD was blunted by either DAPA or EPLE alone, with the combination showing an additive effect. In conclusion, co-treatment with DAPA and EPLE enhances diastolic function, cardiac perfusion and reduces myocardial fibrosis in non-diabetic CKD rats.

Body composition as a potential imaging biomarker for predicting the progression risk of chronic kidney disease

PurposeTo investigate whether the body composition parameters can be employed as potential biomarkers for predicting the progression risk of chronic kidney disease (CKD).Materials and methodsFour hundred sixteen patients diagnosed with CKD were included in this retrospective study. Patients with a greater than 50% decline in estimated glomerular filtration rate or progression to end-stage kidney disease were in the high-risk group, otherwise, they were in a low-risk group. Body composition area, the index, and radiodensities in the Hounsfield unit (HU), which reflect the degree of X-ray absorption, were measured on abdominal CT images. Risk factors in body composition and clinical parameters of CKD were identified by Cox regression and utilized to construct the nomogram. The performance of the nomogram was assessed using time receiver operating characteristics curves, calibration curves, and decision curve analysis.ResultsThere were 254 patients in low-risk group and 162 in high-risk group (268 males, 148 females, mean age: 55.89 years). Urea, diabetes, 24 h-urinary protein, mean arterial pressure, and subcutaneous adipose tissue radiodensity (SATd) were valuable indicators for predicting the high-risk group. The area under curve values for the nomogram of training/validation set at 1 year, 2 years, and 3 years were 0.805/0.753, 0.784/0.783, and 0.846/0.754, respectively. For diabetic CKD patients, extra attention needs to be paid to visceral to subcutaneous fat ratio and renal sinus fat radiodensity.ConclusionSATd was the most valuable noninvasive indicator of all body composition parameters for predicting high-risk populations with CKD. The nomogram we constructed has generalization with easily obtainable indicators, good performance, differentiation, and clinical practicability.Critical relevance statementRadiodensity rather than an area of adipose tissue can be used as a new biomarker of prognosis for CKD patients, providing new insights into risk assessment, stratified management, and treatment for CKD patients.Key PointsObesity is an independent risk factor for the development and prognosis of CKD.Adipose tissue radiodensity is more valuable than fat area in prognosticating for kidney disease.Parameters that prognosticate in diabetic CKD patients are different from those in other CKD patients.Graphical

8722 Sodium-Glucose Cotransporter 2 Inhibitors And The Risk Of Kidney Cancer Among Patients With Type 2 Diabetes: A Population-Based Cohort Study

Abstract Disclosure: M. Lee: None. H. Kim: None. R. Kim: None. Y. Yang: None. S. Lee: None. E. Kang: None. There is an important need to develop clinical strategies to reduce the risk of incident kidney cancer, especially in patients with type 2 diabetes (T2D) and concomitant chronic kidney disease. Here, we investigated kidney cancer risk associated with sodium-glucose cotransporter 2 (SGLT2) inhibitor use in patients with T2D, using a nationwide cohort of the Korean National Health Insurance claims and health examination database. After 1:1 propensity score matching, 83,531 SGLT2 inhibitor users and 83,531 non-users on other oral glucose-lowering drugs were selected from 814,685 cancer-free participants, aged 20 to 79 years, who started oral glucose-lowering drugs for T2D from 2014 to 2018. During 559,738 person-years of follow-up, 143 (25.5 per 100,000 person-years) new kidney cancer events occurred. SGLT2 inhibitor use was associated with a 37% reduced risk of kidney cancer compared with other oral glucose-lowering drug use (18.1 vs. 29.9 per 100,000 person-years; hazard ratio [HR], 0.63; 95% CI, 0.43 to 0.92). The reduced kidney cancer risk by SGLT2 inhibitor use was consistent even after additional adjustment for all variables composing the propensity scores (HR, 0.64; 95% CI, 0.43 to 0.93) and regardless of age, sex, BMI, comorbidities, or diabetic complications including nephropathy (all p &amp;gt; 0.1 for interaction). SGLT2 inhibitor use may be a preferable option for patients with T2D at high risk of kidney cancer. Presentation: 6/3/2024

7335 Myxedema Coma in an Adolescent Patient: A rare, lethal manifestation of profound hypothyroidism

Abstract Disclosure: C. Rodriguez: None. E.M. Mejias: None. L.R. Berrios: None. C. Currais: None. Myxedema coma is a rare, life-threatening condition that represents the most severe manifestation of profound hypothyroidism. It is characterized by extensive end-organ dysfunction. Therefore, it is crucial to have a high index of suspicion in order to identify it promptly and initiate treatment. We report a case of an adolescent patient with past medical history of Type 1 Diabetes Mellitus and hypothyroidism who was initially admitted to pediatric wards due to hypertension, constipation and acute kidney injury (AKI). The patient was transferred to the pediatric intensive care unit (PICU) after he developed multi-organ failure secondary to myxedema coma. His laboratory work up was remarkable for severe hypothyroidism with a thyroid-stimulating hormone (TSH) &amp;gt; 679, uncontrolled diabetes mellitus (Glycosylated Hemoglobin 13.1%) and chronic kidney disease (Creatinine 2.56). During his hospital course, he required long term hemodialysis, mechanical ventilation and underwent cardiorespiratory resuscitation multiple times. Since myxedema coma is an uncommon manifestation of pediatric hypothyroidism, pediatric guidelines are not available. We aim to reinforce the awareness of myxedema coma and encourage physicians to have a high index of suspicion as the widespread availability of TSH assays and its use can aid in the diagnosis and treatment of these patients. Furthermore, we emphasize an interdisciplinary approach to avoid mortality and long-term complications. Presentation: 6/1/2024

6853 A Curious Case of MACS

Abstract Disclosure: M. Dillon: None. A. Syeda: None. V. Kantorovich: None. Introduction: Mild autonomous cortisol secretion (MACS) is characterized by biochemical evidence of mild hypercortisolemia inducing metabolic comorbidities without any obvious phenotypic stigmata of Cushing’s syndrome (CS). This case highlights the challenges faced in the diagnosis and management of MACS. Case: A 76-year-old female with past medical history of class II obesity (BMI 31.83 kg/m2), type 2 diabetes mellitus, hypertension, hyperlipidemia, osteoporosis and chronic kidney disease stage IIIb was diagnosed with MACS after an overnight 1 mg dexamethasone suppression test (DST) showed unsuppressed 8 AM cortisol of 2.4 mcg/dL (&amp;lt;1.8 mcg/dL). Dexamethasone level was appropriate at 355 ng/dL (180-550 ng/dL), ACTH was &amp;lt;5 pg/mL (6-50 pg/mL) and DHEA-S was normal. Late night salivary cortisol (LNSC) levels were elevated to 0.12 mcg/dL (&amp;lt; 0.09 mcg/dL). The 24-hour urine cortisol level was normal. Baseline 8 AM cortisol level was 17 mcg/dL and ACTH was 19 pg/mL. Abdominal CT scan showed a 1 cm left adrenal nodule of 25 HU density and a normal right adrenal with no atrophy. Phaeochromocytoma and primary hyperaldosteronism work up was negative. She started on Mifepristone 300 mg daily and titrated up to 600 mg daily. She presented to our institution one month later with 1 week of nausea, vomiting and muscle weakness. Laboratory studies revealed acute kidney injury with creatinine of 6.69 mg/dL (baseline Cr 1.5 mg/dL) and rhabdomyolysis with creatinine kinase level of 12,819 U/L (24-173 U/L) and urine myoglobin level of 888 ng/mL (0-13 ng/mL). It was evident that her catastrophic presentation was from development of adrenal insufficiency in the setting of Mifepristone glucocorticoid receptor blockade. The drug was discontinued immediately. She was treated with intravenous hydration and intermittent diuretics. Over 10 days, her clinical status gradually improved and creatinine decreased to baseline levels. Discussion: MACS is a challenging diagnosis as cortisol levels are affected by several variables including obesity, drugs, and poorly controlled diabetes. Hence, a meticulous evaluation is mandated before confirming the diagnosis. Our patient’s baseline cortisol and ACTH levels were normal, and her DST and LNSC levels were mildly elevated. Unilateral cortisol producing adenoma causes contralateral gland atrophy due to suppressed ACTH. This was not evident in our patient, thus making the diagnosis questionable. Adrenalectomy is the treatment of choice in MACS with adrenal adenoma. Off label medical management with Mifepristone, a glucocorticoid receptor antagonist, is being pursued in select cases and was trialed due to our patient's age and surgical risk. Mifepristone is approved for the treatment of hyperglycemia due to CS. The data supporting its use in MACS is sparse. Therefore, it is important to be aware of associated risks of Mifepristone when advising patients. Presentation: 6/3/2024

Male Sex and Ageing are Independent Risk Factors for Sarcopenia Stage in Patients With Chronic Kidney Disease Not Yet on Dialysis.

The risk of sarcopenia in older adults with chronic kidney disease (CKD) not yet on dialysis is controversial. The aims of this study were to investigate the association among sarcopenia, diabetes and predialysis CKD and evaluate the impact of gender and ageing on the risk of sarcopenia statuses in older patients with predialysis CKD. The participants aged ≥60 years old were recruited from the community of New Taipei City, Taiwan. Handgrip strength, appendicular skeletal muscle mass and the 6-m walk were measured. The diagnosis of sarcopenia was established based on the consensus of Asian Sarcopenia Working Group 2019. These older adults were categorised into G1, G2 and G3-5 according to the guidelines of Kidney Disease Improving Global Outcomes (KDIGO) after calculating the estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation. The Chi-square test and ANOVA were used to estimate the difference of categorical and continuous variables, respectively. Polytomous logistic regression was employed to assess the odds ratio (OR) and 95% confidence intervals (CIs) of the sarcopenia status and sarcopenia-associated risk factors in the predialysis CKD patients. All tests were two-sided, and p < 0.05 was defined as statistical significance. Among the 3648 older adults (mean age: 71.9 ± 6.07 years), including 1701 males and 1947 females, 870 (23.9%), 94 (2.58%) and 48 (1.32%) had possible sarcopenia, sarcopenia and severe sarcopenia, respectively. After adjustment, the risk for possible sarcopenia, sarcopenia and severe sarcopenia significantly increased with ageing (OR = 1.11, 1.10 and 1.23; 95% CI = 1.10-1.13, 1.07-1.15 and 1.18-1.30, respectively) and male gender (OR = 2.26, 20.3 and 25.4; 95% CI = 1.87-2.73, 11.5-36.0 and 11.3-57.2, respectively). Compared with KDIGO G1, no significant association between KDIGO G3-5 and the statuses of sarcopenia was observed (OR = 0.97, 0.88 and 0.91; 95% CI = 0.75-1.26, 0.43-1.78 and 0.37-2.27, p = 0.821, 0.718, 0.838, for possible sarcopenia, sarcopenia and severe sarcopenia, respectively). Ageing and male gender indicated a significant risk for higher sarcopenia status in older patients with predialysis CKD (0.027-fold/year and 0.284-fold, respectively) (p < 0.0001). This study illuminated the importance of the male sex and the ageing process on the risk of sarcopenia progression in patients with predialysis CKD. Early clinical screening and aggressive treatment for the prevention of higher sarcopenia status in advanced older male adults with predialysis CKD are recommended.

Protocolo terapéutico de la diabetes mellitus tipo 2 con nefropatía

The protocol describes the therapeutic management of patients with type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), a frequent complication in 20%–40% of individuals with DM2. Treatment is based on blood pressure control (target<130/80mmHg); angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs) are recommended. For glycemic control, the glycosylated hemoglobin (HbA1c) level sought is individualized for each patient, but is generally below 7%, adjusting the medication according to the patient's estimated glomerular filtration rate (eGFR). Sodium-glucose cotransporter-2 (SGLT-2i) inhibitors and glucagon-like peptide-1 agonists (GLP-1a) are recommended for their renal and cardiovascular benefits. In addition, patients with CKD and DM2 should be treated with statins to reduce cardiovascular risk, avoiding drugs that increase the risk of hypoglycemia. Individualized treatment and frequent monitoring are essential, especially in patients with decreased eGFR and persistent albuminuria.

A Study on the Systemic Inflammatory Index (SII) and Related Factors in Patients with Malignant Otitis Externa

Purpose: This study aims to investigate the relationship between systemic inflammatory index and various clinical and microbiological factors in patients with malignant otitis externa (MOE). Materials and Methods: In this retrospective study, patients diagnosed with MOE and treated between January 2017 and March 2023 were examined. The data include clinical evaluations, laboratory tests, and imaging results. All patients underwent computed tomography of the temporal bone, and MOE was staged according to Tengku's radiological classification .SII was calculated using neutrophil, platelet, and lymphocyte counts. Results: 11 patients were examined retrospectively, including 8 males (72.7%) and 3 females (27.3%). The mean age of the patients was 72.3±7.5 years. Comorbidities such as Diabetes Mellitus (DM) and Chronic Kidney Disease (CKD) were associated with higher SII values. CT phases and cranial nerve involvement were also related to high SII values. Microbiological analyses showed that pathogens such as Pseudomonas aeruginosa and Candida tropicalis were associated with high SII values. Conclusion: SII is an important biomarker in evaluating the prognosis and treatment response in MOE. Early diagnosis, a multidisciplinary approach, and personalized treatment strategies are critical in managing MOE. Further studies involving larger patient groups will contribute to validating these relationships and improving treatment processes.

CLINICAL OUTCOMES OF PRIMARY PERCUTANEOUS CORONARY INTERVENTION USING DES VS BMS In ACUTE CORONARY SYNDROME PATIENTS WITH LEFT ANTERIOR DESCENDING ARTERY INVOLVEMENT: A COMPARATIVE STUDY

Acute coronary syndrome (ACS) with left anterior descending (LAD) artery involvement often leads to more extensive myocardial infarction. Choosing between drug-eluting stents (DES) and bare-metal stents (BMS) for revascularisation in these patients is a topic of clinical relevance. While drug-eluting stents are the gold standard, bare-metal stents remain an essential option for patients with specific considerations such as an inability to complete the recommended duration of DAPT, advanced age, concomitant oral anticoagulation, cancer, affordability issues, increased bleeding risk, and planned noncardiac surgery within the next year. Objective: This study aimed to compare the clinical outcomes of ACS patients with LAD involvement treated with either DES or BMS during primary PCI.Methods: A retrospective cohort study was conducted between January 1, 2021, and December 31, 2023, at a tertiary care center. A total of 200 ACS patients with LAD involvement who underwent primary PCI were included. Patients were grouped based on the type of stent used (DES or BMS). Data on patient demographics, comorbidities, procedural details, and outcomes were collected. Major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction (MI), and target lesion revascularisation (TLR), were assessed. Kaplan-Meier survival analysis and Cox proportional hazards models were used to analyse outcomes. Results: MACE occurred in 48 patients (24%) during the one-year follow-up. Patients treated with DES experienced significantly fewer events (p &lt; 0.001) compared to those receiving BMS. Diabetes mellitus and chronic kidney disease were independent predictors of adverse outcomes (p = 0.006 and p &lt; 0.001, respectively).Conclusion: Primary PCI using DES in ACS patients with LAD involvement is associated with better clinical outcomes compared to BMS, particularly in high-risk populations. These findings suggest that DES should be the preferred stent type for this patient group to reduce adverse events and improve long-term survival.

Echocardiographic findings and subsequent risk of native valve endocarditis

Aim: The association of echocardiographic findings and subsequent risk of left-sided native valve endocarditis (LS-NVE) is undefined. The aim of this study was to determine if transthoracic echocardiography (TTE) measurements are associated with the subsequent development of LS-NVE in patients without cardiac predisposing conditions. Methods: Institutional databases were evaluated for adults diagnosed with LS-NVE from 2008 to 2020. Patients with prosthetic valves, cardiovascular implantable electronic devices, intracardiac devices, injection drug use, and predisposing cardiac conditions were excluded. Only patients who had a TTE performed 6 months to 3 years before the development of LS-NVE were included as cases. Controls were patients within the same Mayo location with a TTE report and were matched in a 1:3 ratio according to age, gender, Charlson comorbidity index, and echocardiography date. Results: There were 148 cases and 431 matched controls. As compared to controls, infective endocarditis (IE) cases had a higher prevalence of diabetes mellitus (46.6% vs. 30.4%) and chronic kidney disease (46.6% vs. 28.1%) (P &lt; 0.001). Left ventricular outflow tract velocity (P = 0.017), left ventricular ejection fraction (P = 0.018), and E:e’ ratio (P = 0.050) were associated with LS-NVE. Conclusions: Echocardiographic measurements were associated with subsequent LS-NVE development in this pilot study. A larger cohort of LS-NVE patients, however, is needed to validate these findings.