Three-Month Excessive Body Weight Loss < 37.7% as a Predictor of Mid-term Suboptimal Outcomes Postlaparoscopic Sleeve Gastrectomy: Risk Factors and the Impact of Neutrophil-to-Lymphocyte Ratio on Adipocyte Function.

INTRODUCTION: This study aimed to evaluate the impact of achieving < 37.7% excess body-weight loss (EBWL) within 3 months of postlaparoscopic sleeve gastrectomy (LSG) on clinical outcomes and its correlation with adipocyte function. METHODS: Patients (n = 176) who underwent LSG between January 2019 and January 2023 were included. Weight loss and status of health markers were monitored postoperatively. The cohort was stratified based on EBWL < 37.7% at 3 months or not. Variables including neutrophil-to-lymphocyte ratio (NLR), insulin resistance, and comorbidities were analyzed. Omental visceral and subcutaneous adipose tissue samples were used to analyze the differences in adipocyte function by western blot. RESULTS: Patients with EBWL < 37.7% at 3 months post-LSG (suboptimal group) comprised less likelihood of achieving ≥ 50% EBWL than those who achieved ≥ 37.7% EBWL (optimal group) at 6 months (42.55% vs. 95.52% in optimal group, p < 0.001), 12 months (85.11% vs. 99.25% in optimal group, p < 0.001) and 24 months (77.14% vs. 94.74% in optimal group, p = 0.009) post-LSG. High BMI (OR = 1.222, 95% CI 1.138-1.312, p < 0.001), NLR ≥ 2.36 (OR = 2.915, 95% CI 1.257-6.670, p = 0.013), and female sex (OR = 3.243, 95% CI 1.306-8.051, p = 0.011) significantly predicted EBWL < 37.7% at 3 months post-LSG. Patients with NLR ≥ 2.36 had significantly lower adipose triglyceride lipase in omental fat (p = 0.025). CONCLUSION: EBWL < 37.7% at 3 months post-LSG is a strong predictor of subsequent suboptimal weight loss. High BMI, NLR ≥ 2.36, and female sex are risk factors in predicting EBWL < 37.7% at 3 months post-LSG. These findings may offer a reference to apply adjuvant weight loss medications to patients who are predisposed to suboptimal outcomes.

Urinary Klotho Excretion: A Key Regulator of Sodium Homeostasis in Chronic Kidney Disease Stage 2-4.

BACKGROUND Soluble alpha-klotho (klotho) is considered an important regulator of mineral homeostasis in patients with chronic kidney disease (CKD). Since the mineral transport proteins are located on the apical membrane of renal tubular cells, we hypothesized that urine klotho may also be involved in their homeostasis. We aimed to investigate the associations between serum and urine klotho and their impacts on mineral homeostasis in patients with stage 2 to 4 CKD. MATERIAL AND METHODS Serum, spot urine, and 24-h urine of klotho were measured by using enzyme-linked immunosorbent assay. Fractional excretion of sodium, potassium, calcium, phosphate, magnesium, and klotho were calculated. RESULTS A total of 53 patients with CKD stages 2 to 4 were enrolled in this cross-sectional study. The mean age was 71.1±10.5 years, and 68% were men. Linear regression analysis showed that serum log-transformed klotho was negatively associated with log-transformed fractional excretion of klotho (log-FEKlotho) (ß=-0.085, P=0.02), showing that urinary klotho excretion could negatively regulate serum klotho levels. Moreover, our multivariate stepwise regression showed log-fractional excretion of sodium was positively associated with log-FEKlotho (ß=0.138, P=0.032). This implied urinary klotho excretion positively regulated urinary sodium excretion. CONCLUSIONS Our study showed that urine klotho excretion resulted in decreased serum klotho levels and enhanced urinary sodium excretion in patients with CKD stages 2 to 4. In addition to serum klotho, we found, for the first time, that urine klotho also played a significant role in sodium homeostasis.

Evaluation of the Impact of Remote Monitoring Using the Sharesource Connectivity Platform on Adherence to Automated Peritoneal Dialysis in 51 Patients.

BACKGROUND This study from a single center in Taiwan aimed to evaluate the impact of remote patient monitoring (RPM) using the Sharesource connectivity platform on adherence to automated peritoneal dialysis (APD) in 51 patients. MATERIAL AND METHODS We analyzed data on 51 patients with end-stage renal disease (ESRD) under APD. They were treated with a traditional APD machine HomeChoice (phase 1), changed to new APD machine HomeChoice Claria for 12 weeks (phase 2), then connected to the Sharesource platform for another 12 weeks (phase 3), and were followed up for 1 year. The non-adherence rate was compared between the 3 phases. The secondary outcomes included peritonitis rate, hospitalization rate, and hospitalization days, 1 year before and after receiving a new APD machine. Patients were subdivided into good and poor adherence (>1 episode of non-adherence in phase 1) groups for further analysis. RESULTS The average non-adherence rates were 10.5%, 5.1%, and 4.9% in phases 1, 2, and 3, respectively, although differences were not significant. Serum potassium (P<0.0001) and C-reactive protein (CRP) (P=0.026) levels significantly decreased in phase 3. The 1-year peritonitis rate, hospitalization rate, and number of days of hospitalization showed no significant changes. Subgroup analysis revealed that the non-adherence rate in the poor adherence group decreased from 48.4% in phase 1 to 14.2% and 12.4% in phases 2 and 3, respectively (P=0.007). CONCLUSIONS Remoting monitoring using the Sharesource connectivity platform increased dialysis adherence in APD treatment, especially in patients with poor adherence. Serum potassium level and inflammation status were also improved by this system.

The serial changes of Neutrophile-Lymphocyte Ratio and correlation to weight loss after Laparoscopic Sleeve Gastrectomy.

Purpose: This study aims to identify the pre- and postoperative changes in the neutrophil-lymphocyte ratio (NLR) and its correlations to clinical characteristics in obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Method: Retrospectively, we included patients who has undergone LSG in our institution between January 2019 and April 2021. A total of 100 patients whose body mass index over 32.5 and received primary laparoscopic sleeve gastrectomy without infectious condition were included. Results: There was a significant decline in NLR (T0 vs. POM3 2.21 vs. 1.78, p = 0.005), neutrophil (T0 vs. POM3 5369 vs. 4050, p < 0.001) and lymphocyte count (T0 vs. POM3 2440: 2100, p < 0.001, respectively) at postoperative 3 months (POM3) compared to preoperative (T0) levels, but similar between POM3 and POM6. The declined counts (Neutrophile vs. Lymphocyte 1445.5/µl vs. 323.5/µl, p < 0.001) and percentage (Neutrophile vs. Lymphocyte 25.11% vs. 13.07%, p < 0.001) of neutrophile are higher than lymphocyte from T0 to POM3, but similar in POM3 and POM6. Preoperative NLR has a significant correlation with the preoperative body weight, preoperative insulin level, and excessive body weight loss (EBWL) at POM3. Preoperative NLR <2.36 had a sensitivity of 67.6% and a specificity of 62.5% in predicting successful weight loss (EBWL > 37.7%) at POM3 (AUC = 0.635, p = 0.032). Conclusion: There was a significant decline in NLR, neutrophil, and lymphocyte count from T0 to POM3, but similar between POM3 and POM6. The declined counts and percentage of neutrophile are higher than lymphocyte. Preoperative NLR shows the potential to be used as a prognostic biomarker for predicting successful weight loss at POM3 after LSG. Further studies could be designed to evaluate the value of prediction in successful outcome after LSG and figure out the relationship between the changes of neutrophil function and oncogenesis.

Antibody Response and Adverse Events of AZD1222 COVID-19 Vaccination in Patients Undergoing Dialysis: A Prospective Cohort Study.

This study observed the antibody response and adverse events of AZD1222 (Oxford/AstraZeneca) vaccination in dialysis patients. A prospective cohort study was conducted in E-Da Healthcare Group hospitals between 1 July and 30 November 2021. Patients receiving hemodialysis (HD, n = 204) or peritoneal dialysis (PD, n = 116) were enrolled alongside healthy subjects (control, n = 34). Anti-SARS-CoV-2 S1 RBD IgG antibodies were measured before the first vaccination (T0), four to six weeks afterwards (T1), one week before the second dose (T2), and four to six weeks afterwards (T3). Adverse events were recorded one week after each dose. The positive IgG rates in the HD (T1: 72%; T2: 62%) and PD (T1: 69%; T2: 70%) groups were lower than the control group (T1: 97%; T2: 91%), with lower median antibody titers. At T3, the positive antibody response rates (HD: 94%; PD: 93%; control: 100%) and titers were similar. Titers were higher after the second dose in all groups. Adverse events were more severe after the first dose and less common with HD than PD or controls. Dialysis patients exhibited lower antibody responses than controls after the first dose of the AZD1222 vaccine but achieved similar responses after consecutive vaccination. Age, health status, two vaccine doses, and alcohol consumption may influence antibody levels.

Dapagliflozin Ameliorates Lipopolysaccharide Related Acute Kidney Injury in Mice with Streptozotocin-induced Diabetes Mellitus.

Sepsis, which is a serious medical condition induced by infection, has been the most common cause of acute kidney injury (AKI) and is associated with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral antidiabetic drug that has greatly improved the cardiovascular and renal outcomes in patients with type 2 diabetes independent of its sugar lowering effect, possibly by attenuation of the inflammatory process. We investigated the effect of the SGLT2 inhibitor dapagliflozin on lipopolysaccharide (LPS)-induced endotoxic shock with AKI in streptozotocin-induced diabetic mice. Endotoxin shock with AKI was induced by intravenous injection of 10 mg/kg LPS in C57BL6 mice with streptozotocin-induced diabetic mellitus with or without dapagliflozin treatment. Observation was done for 48 hours thereafter. In addition, NRK-52E cells incubated with LPS or dapagliflozin were evaluated for the possible mechanism. Treatment with dapagliflozin attenuated LPS-induced endotoxic shock associated AKI and decreased the inflammatory cytokines in diabetic mice. In the in vitro study, dapagliflozin decreased the expression of inflammatory cytokines and reactive oxygen species and increased the expressions of AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor, and heme oxygenase 1. These results demonstrated that dapagliflozin can attenuate LPS-induced endotoxic shock associated with AKI; this was possibly mediated by activation of the AMPK pathway.

Serum osteocalcin concentration as an independent biomarker of osteoporosis in patients with chronic kidney disease.

OBJECTIVES: Osteocalcin, an osteoblast-derived hormone, is associated with the development of osteoporosis and arteriosclerosis in the general population. However, its role on the pathogenesis of osteoporosis and vascular calcification in patients with chronic kidney disease (CKD) is unclear. Here, we investigated the connection between osteocalcin, bone mineral density (BMD), and abdominal aortic calcification (AAC) in CKD patients. MATERIALS AND METHODS: In total, 95 patients with stage 2 to stage 5 CKD were enrolled. Serum osteocalcin levels were measured using an electrochemiluminescence immunoassay. BMD was determined by dual-energy X-ray absorptiometry, and AAC scores were generated from lateral lumbar radiograph findings. RESULTS: 95 patients were assigned into normal bone density (30.5%, n = 29), osteopenia (45.3%, n = 43), and osteoporosis (24.2%, n = 23) groups. The osteoporosis group was characterized by older age, higher female-to-male ratio, phosphorous levels, calcification scores, osteocalcin levels, and intact parathyroid hormone (PTH) levels, while with lower hemoglobin levels as compared to normal and osteopenia groups. Multivariate multinominal regression analysis showed age, female sex, intact PTH, and serum osteocalcin level were independent determinants of osteoporosis severity in CKD patients. Furthermore, serum osteocalcin level is positively correlated to intact PTH in multivariate linear regression model, indicating that osteocalcin might be a bone turnover marker in patients with CKD. Multivariate stepwise linear regression analysis revealed that age, diabetes mellitus, poorer renal function, rather than osteocalcin, have independent associations with AAC score. CONCLUSION: Elevated serum osteocalcin levels could be considered as a marker of osteoporosis rather than that of vascular calcification in patients with CKD.

Bariatric Surgery Decreases the Risk of Non-traffic Accident-Related Fractures in Patients with Obesity: Real-world Data from Taiwan.

OBJECTIVES: The aim of this study is to investigate the impact of bariatric surgery on non-traffic accident-related fractures in patients with obesity. METHODS: This retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. Patients aged 18 to 55 years with obesity diagnosis between 2003 and 2008 were enrolled and divided into two groups: non-surgical and bariatric surgery groups. Patients with endocrine bone disease and malignancy history were excluded. Healthy patients were also randomly selected from the database and assigned to the general population group. The development of fracture was the primary end point. All patients were followed until the end of 2013 or death, whichever came first. RESULTS: After propensity score matching, 1322, 1322, and 4359 subjects were included in the bariatric surgery (BS), non-surgical (NS), and general population (GP) groups, respectively. Based on multivariate analysis, the risk of overall fractures is similar between the BS group (hazard ratio [HR] = 0.774, p = 0.164) and the NS group; nevertheless, the risk of overall fractures was higher in the BS group (HR = 2.210, p<0.001) than in the GP group. The BS group had a significantly lower risk of non-traffic accident-related fractures (HR = 0.542, p = 0.010) than the NS group but a higher risk of non-traffic accident-related fractures (HR = 1.693, p = 0.023) than the GP group. CONCLUSIONS: Bariatric surgery may decrease the risk of non-traffic accident-related fractures; however, the risk remains higher in patients with obesity than in the general population.

Serum leptin levels are positively associated with aortic stiffness in patients with chronic kidney disease stage 3-5.

Leptin potentially exerts atherogenic effects.This study evaluated the relationship between serum leptin levels and aortic stiffness in patients with stage 3-5 chronic kidney disease (CKD). Totally 205 participants were enrolled. Fasting blood sample were checked and serum leptin were measured by enzyme immunoassay. Aortic stiffness was measured as the carotid-femoral pulse wave velocity (cfPWV). 73 (35.6%) of 205 patients showed cfPWV >10 m/s were defined as aortic stiffness group. Compared with the remaining patients, the aortic stiffness group had high prevalence of diabetes mellitus, older age, higher waist circumference, body fat mass, systolic blood pressure, fasting glucose, and higher serum leptin level. In multivariable logistic regression analysis the independent predictors of cfPWV >10 m/s included leptin levels (odds ratio [OR]: 1.061, 95% confidence interval [CI]: 1.027-1.095, P < 0.001), age (OR: 1.064, 95% CI: 1.033-1.096, P< 0.001), and systolic blood pressure (OR: 1.021, 95% CI: 1.006-1.037, P = 0.006). Multivariable forward stepwise linear regression analysisshowed a positive association between log-transformed leptin levels and log-cfPWV (ß = 0.192, adjusted R2 change = 0.042, P = 0.001). Thus, aortic stiffness is positively correlated with serum leptin levels in patients with stage 3-5 CKD.Abbreviations: BUN, blood urea nitrogen; cfPWV, carotid-femoral pulse wave velocity; CI, confidence interval; CKD, chronic kidney disease; Cre, creatinine; DBP, diastolic blood pressure; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; LDL-C, low-density lipoprotein cholesterol; OR, odds ratio; SBP, systolic blood pressure; TCH, total cholesterol; TG, triglycerides.

Osteocalcin and carotid-femoral pulse wave velocity in patients on peritoneal dialysis.

OBJECTIVE: Vascular calcification is a cardiovascular risk factor in dialysis patients. Vascular calcification involves a complex process of biomineralization resembling osteogenesis, which leads to arterial stiffness. Osteocalcin is the most abundant noncollagenous protein in the bone matrix. It is synthesized in the bone by osteoblasts and reflects the rate of bone formation. The aim of this study was to evaluate the relationship between serum osteocalcin levels and the carotid-femoral pulse wave velocity (cfPWV) in peritoneal dialysis (PD) patients. MATERIALS AND METHODS: Serum intact osteocalcin and cfPWV were measured in 62 PD patients. Those with CfPWV values >10 m/s were defined as the high central arterial stiffness group, while those with values ≤10 m/s were regarded as the low central arterial stiffness group, according to the European Society of Hypertension and of the European Society of Cardiology guidelines. RESULTS: Seventeen of the 62 PD patients (27.4%) were in the high central arterial stiffness group. The high central arterial stiffness group were older (P = 0.002), had a longer PD vintage (P = 0.018), and had higher serum osteocalcin levels (P = 0.001) than those in the low group. Multivariate logistic regression analysis showed that the osteocalcin level (odds ratio: 1.069, 95% confidence interval (CI): 1.005-1.137, P = 0.035), PD vintage (odds ratio: 1.028, 95% CI: 1.010-1.048, P = 0.003), and age (odds ratio: 1.081, 95% CI: 1.005-1.162, P = 0.035) were independently associated with central arterial stiffness in PD patients. Among these patients, cfPWV (ß: 0.216, P = 0.001) values and log-transformed intact parathyroid hormone (ß: -'0.447, P < 0.001) levels were independently associated with the osteocalcin level in PD patients after multivariate forward stepwise linear regression analysis. CONCLUSION: Older PD patients with a longer PD vintage and higher serum osteocalcin levels had higher central arterial stiffness as measured by cfPWV. The serum osteocalcin level is an independent marker of central arterial stiffness in PD patients.

Relationship between resistin and mortality in maintenance hemodialysis patients.

AIMS: Determine the relationship of serum resistin level with outcome in maintenance hemodialysis (HD) patients. MATERIALS AND METHODS: This 49-month prospective study enrolled 101 HD patients and examined their clinical and demographic characteristics. RESULTS: 23 of the 87 patients in the cohort died. Survivors were younger, had higher body mass index, diastolic blood pressure, and serum levels of albumin, creatinine, potassium, and phosphate, and lower serum levels of resistin. Receiver operating characteristic (ROC) curve analysis indicated the optimal cut-off value of resistin for prediction of mortality was 127.4 ng/mL (area under the curve (AUC) = 0.667, p = 0.01). Cox proportional-hazards regression analysis indicated that advanced age (p < 0.001) and resistin level above 127.4 ng/mL (p = 0.004) were associated with increased mortality risk. Albumin (p = 0.048), creatinine (p = 0.014), potassium (p = 0.023), calcium (p = 0.021), and phosphate (p = 0.001) were associated with decreased mortality risk. Multivariate regression analysis indicated that advanced age (adjusted hazard ratio (aHR) = 1.11, p < 0.0001) and elevated resistin concentration (aHR = 2.442, p = 0.0387) increased the risk for mortality. CONCLUSIONS: Advanced age and serum resistin concentration above 127.4 ng/mL are independent risk factors for mortality in patients undergoing maintenance HD.

Renal MALT lymphoma associated with Waldenström macroglobulinemia.

Mucosa associated lymphoid tissue lymphoma (MALT lymphoma) is mostly seen in the gastrointestinal tract; origin from the kidney is extremely rare. Waldenström macroglobulinemia (WM) is a clinicopathologic syndrome denoted by the presence of monoclonal gammopathy in the serum, typically caused by lymphoproliferative disorder. Literature review did not find any report of renal MALT lymphoma accompanied by WM. Herein, for the first time, we report a 72 year-old female patient with a history of chronic kidney disease, presenting with solitary renal mass; MALT lymphoma was confirmed by pathological examination. A serology study identified the presence of WM. No manifestation of hyperviscosity syndrome was noted. Bone marrow biopsy disclosed the concurrent systemic involvement. Her treatment response was uneventful and the renal mass responded with regressive change in size after chemotherapy. The renal function remained stable during follow-up. MALT lymphoma should be considered as an underlying pathology of isolated renal mass. Furthermore, patients with MALT lymphoma should be screened for Waldenström macroglobulinemia and hyperviscosity syndrome.

Survey of depression by Beck Depression Inventory in uremic patients undergoing hemodialysis and hemodiafiltration.

High prevalence of depression has been reported in patients with end stage kidney disease and depression is associated with increased morbidity and mortality. We aimed to investigate the prevalence of depression in patients receiving standard hemodialysis (SHD) and hemodiafiltration (HDF) and compare the associated factors between these treatment modalities. The Beck Depression Inventory (BDI) was used to survey for major depressive symptoms. Demographic and biochemical data were reviewed and collected. Point prevalence of depression in HDF patients was significantly lower than SHD patients (23.9% vs. 43.1%, P < 0.05). The BDI score was also higher in SHD than HDF group (13.2 ± 11.6 vs. 8.7 ± 11.2, P < 0.05). SHD patients with major depressive symptoms had significantly lower levels of hemoglobin, albumin, creatinine, sodium and hand grip strength but had higher prevalence of diabetes and high sensitivity C-reactive protein (hs-CRP) levels. In HDF patients, phosphorus level was significantly lower in patients with major depressive symptoms. Logistic regression analysis revealed that hs-CRP, serum sodium and hand grip strength were significantly associated with major depressive symptoms in patients treated with SHD; while serum phosphorus was identified in HDF groups. We concluded that prevalence of depression was high in dialysis patients. Patients receiving HDF had a lower mean BDI score and a nearly 50% lower prevalence rate of major depressive symptoms than that of SHD. Factors associated with depression were different between two modalities.

Albuminuria, proteinuria, and urinary albumin to protein ratio in chronic kidney disease.

BACKGROUND: Both albuminuria and proteinuria are important disease markers of chronic kidney disease (CKD). Their relationship and the ratio between urinary albumin and protein in patients with CKD have not been investigated. Whether clinical features can affect these measurements is not clear. METHODS: We conducted a cross-sectional study in 602 CKD patients. Demographic data, including age, gender, and co-morbidity such as diabetes, hypertension, hyperuricemia, and hyperlipidemia, were reviewed and recorded. Their urinary albumin, total protein, and creatinine were determined and urinary albumin to creatinine ratio (UACR), total protein to creatinine ratio (UPCR), and albumin to total protein ratio (UAPR) were calculated. Their estimated glomerular filtration rate (eGFR) was calculated according to serum creatinine. The correlation between UACR and UPCR was thus analyzed. We also investigated factors associated with these urinary measurements. RESULTS: UACR and UPCR increased progressively as renal function deteriorated, while UAPR increased to a plateau in CKD stage 4. There was direct relationship between UACR and UPCR. UAPR rose exponentially with the increase of both UACR and UPCR when UACR <500 mg/g or UPCR <1,000 mg/g. Multivariate regression analysis revealed diabetes and hyperuricemia were associated with increased UACR and UPCR, while both urinary parameters were inversely related to male gender and eGFR. Diabetes and hyperuricemia were associated with increased UAPR and UAPR was negatively correlated with age and eGFR. CONCLUSION: There was a significant association between UACR and UPCR in patients with CKD. Characteristics of patients, renal function, and co-morbidities all affected UACR, UPCR, and UAPR.

Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells.

AIMS: Endothelial dysfunction is a common manifestation of chronic kidney disease (CKD). The protein-bound uremic toxins have emerged as important factors associated with cardiovascular disease and the outcome of CKD. The effect of indoxyl sulfate (IS) on endothelial cells remains unclear. MAIN METHODS: Human umbilical endothelial cells (HUVEC) were incubated using IS at two concentrations: 100 µM and 1000 µM over two periods of time: 16 and 48 h. HUVEC were also pre-treated with simvastatin to examine its effect. RT-PCR was used to assess changes in the gene expression of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), Monocyte chemotactic protein-1 (MCP-1), E-selectin, and angiotensin receptor type 1 (AT1R). Protein abundance of the investigated molecules was assessed by immunoblotting. KEY FINDINGS: Treatment with 100 µM IS for 16 h induced a 2-fold increase in the expression of ICAM-1, VCAM-1, and MCP-1. At a concentration of 1000 µM, there was a 2-3-fold increase. An extended treatment period at low concentrations was associated with a 2-3 fold increase and the increase of ICAM-1 and VCAM-1 was more prominent under high concentration. Results of immunoblotting confirmed an increase in the abundance of ICAM-1, VCAM-1 and MCP-1. No significant change was noted in E-selectin and AT1R according to concentration or treatment duration. Pre-treatment with simvastatin did not alter IS-induced changes. SIGNIFICANCE: IS increased the expression of adhesion molecules of endothelial cells exhibiting a concentration and duration dependent pattern. Simvastatin did not demonstrate any effect on IS-associated endothelial activation.