Impact of progressive chronic kidney disease stage on postoperative outcomes in metabolic surgery-a propensity-matched analysis using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement database.

BACKGROUND: Metabolic surgery (MS) is effective in improving renal parameters for individuals with obesity and chronic kidney disease (CKD). Despite recognized benefits, concerns linger about the perioperative safety of patients with CKD undergoing MS. This study aimed to identify the CKD stage associated with the most significant increase in postoperative complications. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database (2017-2021) was used to identify patients undergoing laparoscopic gastric sleeve (SG) or Roux-en-Y gastric bypass (RYGB). Propensity matching was used to quantify the risk for adverse outcomes associated with progressive CKD stage. RESULTS: In total, 688,583 patients (483,898 without CKD and 204,685 with CKD stages I-V) were examined. Endpoints included length of stay (LOS) >5 days, infection, serious complications, major adverse cardiovascular events (MACE), and death. Both SG and RYGB exhibited a linear increase in risk of infection and death. For SG, patients who were stage IIIa/IIIb demonstrated the greatest risk for LOS >5 days (odds ratio [OR] 1.23; 95% confidence interval [CI] (1.05-1.45); P = .011), serious complications (OR 2.83; 95% CI 1.87-4.30; P < .001), and MACE (OR 2.82; 95% CI 1.81-4.37; P < .001). For RYGB, patients who were stage IIIa/IIIb the exhibited greatest risk of MACE (OR 1.67; 95% CI 1.06-2.62; P = .027). CONCLUSIONS: Although it is generally accepted that worsening CKD correlates with greater surgical risk, this analysis identified CKD stage III as a major inflection point for risk of LOS >5 days, serious complications, and MACE. These findings are useful for counseling and procedure selection and suggest a need for heightened attention to CKD stage III patients undergoing MS.

BMI ≥ 70: A Multi-Center Institutional Experience of the Safety and Efficacy of Metabolic and Bariatric Surgery Intervention.

PURPOSE: With the escalating prevalence of obesity, healthcare providers are increasingly managing patients with a body mass index (BMI) exceeding 70. The aim of this study was to describe the perioperative experiences of this demographic group at two institutions. METHODS: An analysis encompassing 84 patients presenting with BMI ≥ 70 kg/m2 from two institutions was conducted. Data included patient demographics, 30-day postoperative outcomes, and weight-loss at different intervals (30 days, 6 months, 1 year). Additionally, rates of emergency department (ED) utilization, readmission, and reoperation in the first postoperative year were examined. RESULTS: Most patients were black (66.7%) and female (86.9%) with a mean age of 41.7 years. The majority underwent laparoscopic sleeve gastrectomy (SG, 88.1%). Patients exhibited a marked decrease in BMI (7.84% at 30 days, 20.13% at 6 months, and 26.83% at 1 year). Average length of stay was comparable across procedure (F(3,80) = 0.016, p = .997). While 30-day complications were minimal (0.7%), 14.4% of patients experienced ED visits within 30 days, escalating to 19.6% by six months and 25% at 1 year. Readmission and reoperation rates at 1 year were 6.45% and 4.83%, respectively. CONCLUSION: With global obesity rates rising, clinicians are being challenged to care for patients with BMI ≥ 70 kg/m2. Analysis of two institutions demonstrated low rates of 30-days complications but increased readmission rates and ED utilization in this patient population. Despite increased resource utilization, the study suggests that BMI ≥ 70 kg/m2 alone should not be a deterrent for surgery, emphasizing the need for nuanced care in this expanding demographic.

Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. METHODS AND RESULTS: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation following RF-RDN. In addition, renal injury, oxidative stress, inflammation, and profibrotic biomarkers were evaluated to determine pathways associated with RDN. RF-RDN significantly reduced renal norepinephrine and tyrosine hydroxylase content in both study cohorts. RF-RDN therapy performed at 8 weeks of age attenuated cardiac dysfunction, reduced cardiorenal fibrosis, and improved endothelial-dependent vascular reactivity. These improvements were associated with reductions in renal injury markers, expression of renal NLR family pyrin domain containing 3/interleukin 1ß, and expression of profibrotic mediators. RF-RDN failed to exert beneficial effects when administered in the 20-week-old HFpEF cohort. CONCLUSIONS: Our data demonstrate that early RF-RDN therapy protects against HFpEF disease progression in part due to the attenuation of renal fibrosis and inflammation. In contrast, the renoprotective and left ventricular functional improvements were lost when RF-RDN was performed in later HFpEF progression. These results suggest that RDN may be a viable treatment option for HFpEF during the early stages of this systemic inflammatory disease.

Adjunctive therapy with an oral H2S donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction.

BACKGROUND AND PURPOSE: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (H2S), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and H2S donor in two preclinical models of cardiometabolic HFpEF was investigated. EXPERIMENTAL APPROACH: Nine-week-old C57BL/6N mice received L-NAME and a 60% high fat diet for five weeks. Mice were then randomized to either control, SGLT2i monotherapy or SGLT2i and H2S donor, SG1002, for five additional weeks. Ten-week-old ZSF1 obese rats were randomized to control, SGLT2i or SGLT2i and SG1002 for 8 weeks. SG1002 monotherapy was investigated in additional animals. Cardiac function (echocardiography and haemodynamics), exercise capacity, glucose handling and multiorgan pathology were monitored during experimental protocols. KEY RESULTS: SGLT2i treatment improved E/e' ratio and treadmill exercise in both models. Combination therapy afforded increases in cardiovascular sulphur bioavailability that coincided with improved left end-diastolic function (E/e' ratio), exercise capacity, metabolic state, cardiorenal fibrosis, and hepatic steatosis. Follow-up studies with SG1002 monotherapy revealed improvements in diastolic function, exercise capacity and multiorgan histopathology. CONCLUSIONS AND IMPLICATIONS: SGLT2i monotherapy remediated pathological complications exhibited by two well-established HFpEF models. Adjunctive H2S therapy resulted in further improvements of cardiometabolic perturbations beyond SGLT2i monotherapy. Follow-up SG1002 monotherapy studies inferred an improved phenotype with combination therapy beyond either monotherapy. These data demonstrate the differing effects of SGLT2i and H2S therapy while also revealing the superior efficacy of the combination therapy in cardiometabolic HFpEF.