Mortality In Chronic Kidney Disease Research Articles

MDRD is the eGFR equation most strongly associated with 4-year mortality among patients with diabetes in Colombia

IntroductionWe compared the association of glomerular filtration rate (GFR) estimated with the Cockcroft-Gault, Modification of Diet in Renal Disease study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or the new...

Neutrophil-Lymphocyte Ratio as Predictor of Mortality in Regular Hemodialysis Patients at Tabanan General Hospital

The risk of mortality in chronic kidney disease (CKD) patients is higher than in normal population. Inflammation has an important role in the high mortality in CKD patients undergoing hemodialysis (HD). The neutrophil lymphocyte ratio (NLR) is a simple parameter and has been widely associated with poor outcomes in HD patients but has not been widely implemented in Indonesia, especially in Bali. This research prospectively analyzed survival of 186 patients aged 18-90 years undergoing regular HD 2x/week for at least 3 months. NLR was calculated by dividing the absolute number of neutrophils and lymphocytes. The Survival test was performed by the Kaplan-Meier method and compared with the log-rank test. Univariate and multivariate tests were performed to assess the prognostic impact of NLR and other clinical factors on all-cause mortality in HD patients. Mortality was found higher in the group with high NLR values (p-value 0.003). High NLR was significantly associatedwith all-causemortality (HR 3.206; 95% CI 1.467 – 7.004; p value 0.003) and remained an independent factor on mortality in routine HD patients after adjustment toothervariables(aHR 2.696, 95% CI 1.176 –6.182, p-value: 0.019). Inconclusion, HighNLR is independently associated with all-cause mortality in CKD patients undergoing regular HD. NLR can be used as an inflammation marker that is considered easy and affordable and can be used to help determine populations that require special attention in order to reduce the mortality of patients with HD.

38-LB: Ex Vivo Immune Cell Function Analysis in Patients with CKD Undergoing Dialysis Treatment Monitors Exercise Treatment Effects on Immunosurveillance

Chronic kidney disease (CKD) is marked by a pre-aging and dysfunctional immune system and chronic inflammation. Recent research indicates that chronic physical exercise training (ET) increases regulatory monocytes and T-cells thus modulating the inflammatory status associated with cardio-metabolic diseases. In particular, ET primes monocytes and T-cells towards a less inflammatory phenotype. We hypothesized that intradialytic ET is beneficial to patients with CKD by improving certain immune cell features and decreasing systemic inflammation. We isolated PBMCs from a subset of 18 patients with CKD (58-90 years, 38 % females) enrolled in the prospective intervention trial DiaTT (Dialysis Training Therapy; ClinicalTrials.gov: NCT03885102) at the beginning and after a 12-months intradialytic ET intervention (aerobic endurance + resistance training). Circulating immune cell populations were characterized by FACS. Ex-vivo basal and PMA-induced T-cell activation was determined by cell surface expression analysis of CD69. We found that ET reversed the shift towards intermediate monocytes, a known marker for CKD morbidity and mortality, and nonclassical monocytes in patients with CKD undergoing dialysis treatment. We observed an increase in naïve T-cells and Recent Thymic Emigrants (RTE) indicating an improvement of T-cell function. On T-cells, basal CD69 expression was significantly enhanced and PMA-induced CD69 expression was severely impaired in patients with CKD compared to healthy control subjects (n= 7). When patients with CKD underwent ET this specific T-cell function was restored to normal levels. Here, we show that even in these severely sick patients certain circulating immune cell functions can be regained potentially leading to an enhanced immunosurveillance. Our ex-vivo immune cell characterization and function analysis can be used to monitor exercise treatment effects on systemic inflammation. Disclosure S. M. Hofmann: None. S. M. Dinges: None. M. Walter: None. P. Vonkorn: None. G. D. Vongersdorff: None. K. Anding-rost: None. M. Halle: Advisory Panel; Abbott, Speaker's Bureau; Boehringer Ingelheim (Canada) Ltd., Daiichi Sankyo, Amgen Inc., BMS.

Cardiovascular mortality in patients with advanced chronic kidney disease with and without diabetes: a nationwide cohort study

BackgroundCardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels.MethodsIn a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate < 30 mL/min/1.73m2 between 2002 and 2018. Patients with advanced CKD were age- and sex-matched with four individuals from the general Danish population. Cause-specific Cox regression models were used to estimate the 1-year risk of cardiovascular mortality standardized to the distribution of risk factors in the cohort.ResultsWe included 138,583 patients with advanced CKD of whom 32,698 had diabetes. The standardized 1-year risk of cardiovascular mortality was 9.8% (95% CI 9.6–10.0) and 7.4% (95% CI 7.3–7.5) for patients with and without diabetes, respectively, versus 3.1% (95% CI 3.1–3.1) in the matched cohort. 1-year cardiovascular mortality risks were 1.1- to 2.8-fold higher for patients with diabetes compared with those without diabetes across the range of advanced CKD stages and age groups. Albuminuria and anemia were associated with increased cardiovascular mortality risk regardless of diabetes status. LDL-cholesterol was inversely associated with cardiovascular mortality risk in patients without diabetes, while there was no clear association in patients with diabetes.ConclusionsDiabetes, albuminuria, and anemia remained important risk factors of cardiovascular mortality whereas our data suggest a limitation of LDL-cholesterol as a predictor of cardiovascular mortality in advanced CKD.

#6405 PROGRESSION TO END-STAGE RENAL DISEASE AND ONE-YEAR MORTALITY IN ACUTE CARDIORENAL SYNDROME

Abstract Background and Aims Approximately 25% of patients with chronic congestive heart failure (CHF) present a reduction in glomerular filtration rate (GFR) independent of the left ventricular ejection fraction (LVEF). A meta-analysis of 80,000 patients revealed that patients with lower GFR (&amp;lt;53 mL/min) had a higher one-year mortality rate (51% versus 38%). Therefore, this reduction in GFR seems to have an important impact on both morbidity and mortality. The aim of this study was to analyze the factors associated with progression to advanced chronic kidney disease (CKD) and one-year mortality in a retrospective cohort of patients hospitalized due to acute decompensation of cardiorenal syndrome (CRS). Method Patients hospitalized for CRS between September-2013 and June-2020 who presented acute kidney injury (AKI) associated with CHF. Clinical, analytical and echocardiographic data were analyzed. Results The study included 100 patients with a majority of males (64%) and a median age of 79.5 years (72.3-85.0). Around 38% of the patients were dependent, 49% had ischemic heart disease, 51% were diabetic, 27% had left ventricular hypertrophy, 56% had moderate to severe pulmonary hypertension, and 59% had moderate to severe valve disease. In terms of LVEF, 27% showed severe dysfunction while 42% had preserved function. The median baseline creatinine was 1.6 mg/dl (1.3-2.0) with an estimated glomerular filtration rate (eGFR) of 36 ml/min (29.0-46.5). At the time of acute renal failure (ARF), creatinine was 3.3 mg/dl (2.8-4.0) and at hospital discharge the eGFR (CKD-EPI) was 29.5 ml/min (20.1-40.0). After one year of follow-up, 49 patients had died, 7 were admitted?? for chronic hemodialysis, and 6 showed a drop in eGFR greater than 40%. A logistic regression analysis was conducted for the outcome variable of "death or severe progression of CKD (considering entry into CKD grade V or loss of more than 40% of GFR)". Hyperphosphatemia (76% death/progression vs 48%, p=0.004), discharge eGFR less than 30 ml/min (74% vs 50%, p=0.013), and renin-angiotensin system (RAS) blockade (48.1% vs 77.1%) were significantly associated with the outcome. Systolic dysfunction was associated with 70.4% of death/progression (52.2% p=0.06). In the multivariate analysis, variables with a trend in the univariate analysis (p&amp;lt;0.2), such as prolonged hospital stay, non-revascularized coronary disease, hyponatremia, and proteinuria, were included. The analysis showed that five variables were significantly associated with the risk of death/CKD progression: proteinuria (OR 2.8, 95% CI 1.03-7.37, p=0.04), discharge eGFR (OR 2.7, 95% CI 1.05-6.82, p=0.04), LVEF (OR 0.97, 95% CI 0.94-1.00, p=0.06), hyponatremia (OR 0.89, 95% CI 0.80-0.99, p=0.04), and RAS blockade (OR 0.19, 95% CI 0.07-0.53, p=0.001). The predictive model had an area under the curve of 0.79 (95% CI 0.70-0.88) with a p-value of 0.047 and a global accuracy of 77%. Conclusion In conclusion, our study found that hyponatremia and proteinuria were significantly associated with a poorer outcome in terms of CKD progression and mortality in patients with cardiorenal syndrome. Conversely, higher left ventricular ejection fraction and a higher estimated glomerular filtration rate at discharge from the decompensation episode were linked to a lower risk. Our findings support the use of RAS-blocking drugs as beneficial in this population.

#4914 LOW LEAN BODY TISSUE IS AN INDEPENDENT RISK FACTOR FOR KIDNEY DISEASE PROGRESSION AND MORTALITY IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Lean tissue mass is a marker of good health and is associated with a lower risk of death in patients without chronic kidney disease (CKD). A potentially underestimated risk factor for impaired renal function is low serum albumin concentration. Previous studies have shown that even small decreases in serum albumin concentration levels are strongly associated with cardiovascular disease, heart failure, impaired kidney function, and mortality in vulnerable populations. An association between low lean body tissue with mortality in patients with stage 4 and 5 CKD has recently been demonstrated. The aim of this study was to evaluate the effect of lean body tissue index (LTI) measured by multifrequency bioelectrical impedance analysis (BIA) on kidney disease progression and mortality in a cohort of patients with stage 4 and 5 CKD. Method We performed a retrospective observational cohort study that included patients with stage 4 and 5 CKD who were referred to the Advanced Chronic Kidney Disease outpatient clinic at our centre between January 2014 and December 2020, in whom a baseline measurement of body composition by using BIA was performed in the first 6 months of follow-up. Baseline clinical and laboratory parameters (serum creatinine, glomerular filtration rate, serum albumin, hemoglobin, cholesterol, triglycerides, calcium, phosphorus, PTH and CRP) were defined as those observed at the time of BIA measurement. Low lean tissue was defined as having LTI values below the 10th centile adjusted by age and sex. Renal survival was defined as the absence of need of renal replacement therapy (RRT) at the end of follow-up. Results The study included 145 patients who had a mean age of 72 ± 11.8 years, 69.7% were males, with a mean GFR measured by CKD-EPI of 20.4 ± 4.7 ml/min, mean albumin of 4.1 ± 0.3 g/dl and median urine albumin-creatinine ratio (uACR)of 413 mg/g (IQR 98-1341). The mean body mass index of the population was 30.1 ± 6.1 kg/m2, and BIA showed a mean LTI of 15.4 ± 3.9 kg/m2 and fat tissue index (FTI) of 14.1 ± 6.8 kg/m2. Nineteen patients (13.1%) had low LTI. Patients with low LTI were younger (65.9 ± 12.8 vs 73 ± 11.4 years, p = 0.013) and had higher uACR (1444 [484-1815] vs 318 [68-1188] mg/g, p = 0.002) with no differences in sex, GFR, and other laboratory parameters. After a mean follow-up of 27.7 months (IQR 15.3-45.4), 72 (49.7%) showed CKD progression to RRT and 55 patients (37.9%) died. The Kaplan-Meier survival analysis showed that patients with low LTI had a worse renal survival (log-rank 5.5, p = 0.019) and overall survival (log-rank 7.6, p = 0.006). The multivariate Cox regression analysis showed that low LTI (HR 2.28, 95% CI 1.12-4.62), lower GFR (HR 0.86, 95% CI 0.81-0.92) and higher uACR (HR 1.001, CI 95% 1-1.001) were independent risk factors for CKD progression to ESKD, while low LTI (HR 3.16, 95% CI 1.42-7.05), age (HR 1.09, CI 95% 1.05-1.13) and serum albumin (HR 0.31, CI 95% 0.13-0.77) were the factors that were independently associated with mortality. Conclusion Low lean body tissue index measured by multifrequency bioelectrical impedance analysis is and independent risk factor for CKD progression and mortality in stage 4-5 CKD. Close monitoring of nutritional status by BIA should be followed in these patients to provide timely and adequate nutritional interventions that might help in improving patient outcomes.

Associations of low-carbohydrate with mortality in chronic kidney disease

Background Diet management is an effective way to retard the progression of chronic kidney disease (CKD). However, very few studies investigated the influence of carbohydrate intake on CKD patients. In this prospective cohort study, the associations between carbohydrate intake and all-cause mortality were investigated in US adult CKD patients. Methods Multivariable Cox proportional hazard models and iso-caloric replacement analysis were used to investigate the associations between the macronutrients and the all-cause mortality risk. Total 3683 US adult CKD patients 20 years or older from the National Health and Nutrition Examination Survey (NHANES, 2003–2014) were analyzed (mean age ± SD, 62.4 ± 17.1; 56.5% female), of which 1082 participants with CKD died with a median follow-up time of 67 (IQR 36–99) months. Results Most macronutrients were non-linearly associated with all-cause mortality risk, including carbohydrates and sugar. Participants with CKD had lower mortality risk when consuming 30–45% energy from carbohydrates (average HR 0.76, 95%CI 0.62–0.93, compared with 60%), 5–20% energy from sugar (average HR 0.75, 95% CI 0.59–0.96 compared with 40%). Replacing the energy intake from carbohydrates with protein (up to 30%) and/or replacing the sugar with non-sugar carbohydrates (up to 55%) reduced the all-cause mortality risk, while the total energy intake remained constant. Conclusions Diet advice should be given according to the current diet status, and constituents of carbohydrates should also be taken into consideration.

Post-Operative and Mid-Term Renal Function Impairment Following Elective Fenestrated Endovascular Aortic Repair for Complex Aortic Aneurysms: Incidence and Risk Factors Analysis.

Background. The aim of this study was to assess the incidence of two post-operative acute kidney injury (AKI) stages according to the Risk, Injury, Failure, Loss of function, End-stage (RIFLE) criteria in patients undergoing fenestrated endovascular aortic repair (FEVAR) for complex aortic aneurysms. Furthermore, we analyzed predictors of post-operative AKI and mid-term renal function deterioration and mortality. Methods. We included all patients who underwent elective FEVAR for abdominal and thoracoabdominal aortic aneurysms between January 2014 and September 2021, independently from their preoperative renal function. We registered cases of post-operative acute kidney injury (AKI) both at risk (R-AKI) and injury stage (I-AKI) according to the RIFLE criteria. Estimated glomerular filtration rate (eGFR) was noted preoperatively, at the 48th post-operative hour, at the maximum post-operative peak, at discharge, and then during follow-up approximately every six months. Predictors of AKI were analyzed with univariate and multivariate logistic regression models. Predictors of mid-term chronic kidney disease (CKD) (stage ≥ 3) onset and mortality were analyzed using univariate and multivariate Cox proportional hazard models. Results. Forty-five patients were included in the present study. Mean age was 73.9 ± 6.1 years and 91% of patients were males. Thirteen patients (29%) presented with a preoperative CKD (stage ≥ 3). Post-operative I-AKI was detected in five patients (11.1%). The aneurysm diameter, thoracoabdominal aneurysms and chronic obstructive pulmonary disease were identified as predictors of AKI in univariate analysis (OR 1.05, 95% CI [1.005-1.20], p = 0.030; OR 6.25, 95% CI [1.03-43.97], p = 0.046; OR 7.43, 95% CI [1.20-53.36], p = 0.031; respectively), yet none of these factors were significative on multivariate analysis. Predictors of CKD onset (stage ≥3) during follow-up on multivariate analysis were age (HR 1.16, 95% CI [1.02-1.34], p = 0.023), post-operative I-AKI (HR 26.82, 95% CI [4.18-218.10], p < 0.001) and renal artery occlusion (HR 29.87, 95% CI [2.33-309.05], p = 0.013), while aortic-related reinterventions where not significantly associated with this outcome in univariate analysis (HR 0.66, 95% CI [0.07-2.77], p = 0.615). Mortality was influenced by preoperative CKD (stage ≥3) (HR 5.68, 95% CI [1.63-21.80], p = 0.006) and post-operative AKI (HR 11.60, 95% CI [1.70-97.51], p = 0.012). R-AKI did not represent a risk factor for CKD (stage ≥ 3) onset (HR 1.35, 95% CI [0.45-3.84], p = 0.569) or for mortality (HR 1.60, 95% CI [0.59-4.19], p = 0.339) during follow-up. Conclusions. In-hospital post-operative I-AKI represented the main major adverse event in our cohort, influencing CKD (≥ stage 3) onset and mortality during follow-up, which were not influenced by post-operative R-AKI and aortic-related reinterventions.

Hospital overcrowding caused by covid-19 and chronic kidney disease mortality

The coronavirus disease (COVID-19) pandemic has been the largest public health emergency in recent decades. While there have been many epidemiology studies on this pandemic, less research has been done to examine its indirect impact on mortality. This paper utilizes Kolmogorov-Zurbenko (KZ) filter to examine chronic kidney disease (CKD) mortality trend in Florida hospitals and finds an indirect impact of the pandemic, namely the excess Florida CKD deaths due to pandemic-period hospital over-crowding. The results show that kidney disease patients suffer higher mortality from hospital overcrowding, thus prompting the need to allocate healthcare resource to more vulnerable patients. This paper also proposes a measurement method of hospital overcrowding with KZ filter. The strong correlation between CKD mortality and hospital overcrowding confirms that the level of healthcare has a significant influence on the wellness of CKD patients.

Associations Between Frailty and the Increased Risk of Adverse Outcomes Among 38,950 UK Biobank Participants With Prediabetes: Prospective Cohort Study.

Compared with adults with normal glucose metabolism, those with prediabetes tend to be frail. However, it remains poorly understood whether frailty could identify adults who are most at risk of adverse outcomes related to prediabetes. We aimed to systematically evaluate the associations between frailty, a simple health indicator, and risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), diabetes-related microvascular disease, cardiovascular disease (CVD), chronic kidney disease (CKD), eye disease, dementia, depression, and all-cause mortality in late life among middle-aged adults with prediabetes. We evaluated 38,950 adults aged 40 years to 64 years with prediabetes using the baseline survey from the UK Biobank. Frailty was assessed using the frailty phenotype (FP; range 0-5), and participants were grouped into nonfrail (FP=0), prefrail (1≤FP≤2), and frail (FP≥3). Multiple adverse outcomes (ie, T2DM, diabetes-related microvascular disease, CVD, CKD, eye disease, dementia, depression, and all-cause mortality) were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Several sensitivity analyses were performed to test the robustness of the results. At baseline, 49.1% (19,122/38,950) and 5.9% (2289/38,950) of adults with prediabetes were identified as prefrail and frail, respectively. Both prefrailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <.001). For instance, compared with their nonfrail counterparts, frail participants with prediabetes had a significantly higher risk (P<.001) of T2DM (hazard ratio [HR]=1.73, 95% CI 1.55-1.92), diabetes-related microvascular disease (HR=1.89, 95% CI 1.64-2.18), CVD (HR=1.66, 95% CI 1.44-1.91), CKD (HR=1.76, 95% CI 1.45-2.13), eye disease (HR=1.31, 95% CI 1.14-1.51), dementia (HR=2.03, 95% CI 1.33-3.09), depression (HR=3.01, 95% CI 2.47-3.67), and all-cause mortality (HR=1.81, 95% CI 1.51-2.16) in the multivariable-adjusted models. Furthermore, with each 1-point increase in FP score, the risk of these adverse outcomes increased by 10% to 42%. Robust results were generally observed in sensitivity analyses. In UK Biobank participants with prediabetes, both prefrailty and frailty are significantly associated with higher risks of multiple adverse outcomes, including T2DM, diabetes-related diseases, and all-cause mortality. Our findings suggest that frailty assessment should be incorporated into routine care for middle-aged adults with prediabetes, to improve the allocation of health care resources and reduce diabetes-related burden.

Prospective association between physical activity and mortality in patients with chronic kidney disease

Objective: To investigate the prospective association of physical activity with all-cause, cardiovascular disease (CVD), and chronic kidney disease (CKD) mortality in CKD patients in China. Methods: Cox proportional hazard models were used to evaluate the association of total, domain-specific, and intensity-specific physical activity with the risk of all-cause, CVD, and CKD mortality based on data from the baseline survey of China Kadoorie Biobank. Results: During a median follow-up of 11.99 (11.13, 13.03) years, there were 698 deaths in 6 676 CKD patients. Compared with the bottom tertile of total physical activity, participants in the top tertile had a lower risk of all-cause, CVD, and CKD mortality, with hazard ratios (HRs) (95%CIs) of 0.61 (0.47-0.80), 0.40 (0.25-0.65), and 0.25 (0.07-0.85), respectively. Occupational, commuting, and household physical activity were negatively associated with the risk of all-cause and CVD mortality to varying degrees. Participants in the top tertile of occupational physical activity had a lower risk of all-cause (HR=0.56, 95%CI: 0.38-0.82) and CVD (HR=0.39, 95%CI: 0.20-0.74) mortality, those in the top tertile of commuting physical activity had a lower risk of CVD mortality (HR=0.43, 95%CI: 0.22-0.84), and those in the top tertile of household physical activity had a lower risk of all-cause (HR=0.61, 95%CI: 0.45-0.82), CVD (HR=0.44, 95%CI: 0.26-0.76) and CKD (HR=0.03, 95%CI: 0.01-0.17) mortality, compared with the bottom tertile of corresponding physical activity. No association of leisure-time physical activity with mortality was observed. Both low and moderate-vigorous intensity physical activity were negatively associated with the risk of all-cause, CVD and CKD mortality. The corresponding HRs (95%CIs) were 0.64 (0.50-0.82), 0.42 (0.26-0.66) and 0.29 (0.10-0.83) in the top tertile of low intensity physical activity, and the corresponding HRs (95%CIs) were 0.63 (0.48-0.82), 0.39 (0.24-0.64) and 0.23 (0.07-0.73) in the top tertile of moderate-vigorous intensity physical activity. Conclusion: Physical activity can reduce the risk of all-cause, CVD, and CKD mortality in CKD patients.

Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease.

High salt intake is a primary cause of over-hydration in chronic kidney disease (CKD) patients. Inflammatory markers are predictors of CKD mortality; however, the pathogenesis of inflammation remains unclear. Sodium storage in tissues has recently emerged as an issue of concern. The binding of sodium to tissue glycosaminoglycans and its subsequent release regulates local tonicity. Many cell types express tonicity-responsive enhancer-binding protein (TonEBP), which is activated in a tonicity-dependent or tonicity-independent manner. Macrophage infiltration was observed in the heart, peritoneal wall, and para-aortic tissues in salt-loading subtotal nephrectomized mice, whereas macrophages were not prominent in tap water-loaded subtotal nephrectomized mice. TonEBP was increased in the heart and peritoneal wall, leading to the upregulation of inflammatory mediators associated with cardiac fibrosis and peritoneal membrane dysfunction, respectively. Reducing salt loading by a diuretic treatment or changing to tap water attenuated macrophage infiltration, TonEBP expression, and inflammatory marker expression. The role of TonEBP may be crucial during the cardiac fibrosis and peritoneal deterioration processes induced by sodium overload. Anti-interleukin-6 therapy improved cardiac inflammation and fibrosis and peritoneal membrane dysfunction. Further studies are necessary to establish a strategy to regulate organ dysfunction induced by TonEBP activation in CKD patients.

High Fructose Corn Syrup Accelerates Kidney Disease and Mortality in Obese Mice with Metabolic Syndrome.

The presence of obesity and metabolic syndrome is strongly linked with chronic kidney disease (CKD), but the mechanisms responsible for the association are poorly understood. Here, we tested the hypothesis that mice with obesity and metabolic syndrome might have increased susceptibility to CKD from liquid high fructose corn syrup (HFCS) by favoring the absorption and utilization of fructose. We evaluated the pound mouse model of metabolic syndrome to determine if it showed baseline differences in fructose transport and metabolism and whether it was more susceptible to chronic kidney disease when administered HFCS. Pound mice have increased expression of fructose transporter (Glut5) and fructokinase (the limiting enzyme driving fructose metabolism) associated with enhanced fructose absorption. Pound mice receiving HFCS rapidly develop CKD with increased mortality rates associated with intrarenal mitochondria loss and oxidative stress. In pound mice lacking fructokinase, the effect of HFCS to cause CKD and early mortality was aborted, associated with reductions in oxidative stress and fewer mitochondria loss. Obesity and metabolic syndrome show increased susceptibility to fructose-containing sugars and increased risk for CKD and mortality. Lowering added sugar intake may be beneficial in reducing the risk for CKD in subjects with metabolic syndrome.

Environmental and Social Factors Associated with High Chronic Kidney Disease Mortality Rates in Municipalities of Guatemala: An Ecological Study of Municipal-Level Mortality Data

The purpose of this study was to determine the association between social and environmental indicators and high mortality rates from chronic kidney disease (CKD) in municipalities of Guatemala. An ecological study of municipal-level factors associated with CKD mortality in Guatemala was conducted. Crude mortality rates were calculated for the 2009-2019 period for each of the country's 340 municipalities, by gender and age groups. Municipal-level social and environmental indicators were used as independent variables. Linear regression was used for bivariate and multivariate analysis. A total of 28,723 deaths from CKD were documented for the 2009-2019 period. Average crude mortality rate for all ages for the country's 340 municipalities was 70.66 per 100,000 [0-502.99]. Very highly positive associations with high mortality rates were found in two agrarian territories where land use is mainly for permanent crops (e.g., sugar cane, coffee, rubber, banana, plantain, African palm) and pastures for cattle, with very low percentages of land covered by forests or protected areas. Social factors related to poverty and environmental factors related to agricultural use of land may play a role in the high CKD mortality rates documented in a cluster of municipalities of Guatemala.

Changes in gut microbial community upon chronic kidney disease.

With the increasing incidence and mortality of chronic kidney disease (CKD), targeted therapies for CKD have been explored constantly. The important role of gut microbiota on CKD has been emphasized increasingly, it is necessary to analyze the metabolic mechanism of CKD patients from the perspective of gut microbiota. In this study, bioinformatics was used to analyze the changes of gut microbiota between CKD and healthy control (HC) groups using 315 samples from NCBI database. Diversity analysis showed significant changes in evenness compared to the HC group. PCoA analysis revealed significant differences between the two groups at phylum level. In addition, the F/B ratio was higher in CKD group than in HC group, suggesting the disorder of gut microbiota, imbalance of energy absorption and the occurrence of metabolic syndrome in CKD group. The study found that compared with HC group, the abundance of bacteria associated with impaired kidney was increased in CKD group, such as Ralstonia and Porphyromonas, which were negatively associated with eGFR. PICRUSt2 was used to predict related functions and found that different pathways between the two groups were mainly related to metabolism, involving the metabolism of exogenous and endogenous substances, as well as Glycerophospholipid metabolism, which provided evidence for exploring the relationship between gut microbiota and lipid metabolism. Therefore, in subsequent studies, special attention should be paid to these bacteria and metabolic pathway, and animal experiments and metabolomics studies should be conducted explore the association between bacterial community and CKD, as well as the therapeutic effects of these microbial populations on CKD.

Designing adsorptive membranes for removing protein-bound uremic toxins via π-π and cation-π interaction

Protein-bound uremic toxins (PBUTs) are recently thought to critically influence overall organ dysfunction, morbidity, and mortality of chronic kidney disease (CKD) patients. However, traditional hemodialysis and/or hemoperfusion processes fail to remove PBUTs efficiently due to their strong affinity with albumins. Herein, we fabricated a novel adsorptive membrane incorporating amine/polyphenol/bimetal ions complexation in the polysulfone membrane substrate, which has a higher affinity with hippuric acid, p-cresol sulfate, and indoxyl sulfonate. The complexation is a synergy of polyelectrolyte (polyethyleneimine-tannic acid) and metal-phenolic (tannic acid/metals) networks. The adsorption behavior of those three uremic toxins on the optimized adsorptive membrane was investigated by kinetic and adsorption isotherm studies. From X-ray photoelectron spectroscopy analysis assisted by Fourier transform infrared reflection spectrum, we attribute the high adsorption capacity to π-π and/or cation-π interaction with aromatic ring groups of uremic toxins. The adsorptive membrane could effectively remove albumin bounded uremic toxins and water-soluble urea through a continuous dialysis process. Besides, the membrane showed excellent hemocompatibility and minimized immune responses by suppressing complement activation. The above results showed the potential clinical application of adsorptive membranes.

The Effect of Chronic Kidney Disease or End-stage Kidney Disease on Perioperative Outcomes and Healthcare Utilization in Patients Undergoing Bariatric Surgery.

As chronic kidney disease (CKD) has a higher prevalence in patients with obesity, there is an increasing need to understand the safety of bariatric surgery for patients with advanced CKD. This study determined if short-term bariatric surgical outcomes and healthcare utilization differ in patients with advanced CKD. A retrospective analysis of the Healthcare Cost and Utilization Project National Inpatient Sample (NIS) was performed. Patients with obesity who underwent bariatric surgery from 2015 to 2019 were included. Patients without CKD, with CKD, and end-stage kidney disease (ESKD) were compared for outcome differences. Univariate and multivariable regression was used to determine the association between perioperative outcomes to CKD status. The unadjusted analysis found significantly higher mortality and overall complication rate in CKD and ESKD patients, however, after adjustment for confounders, only the ICU admission rate remained significantly higher for patients CKD compared to non-CKD patients (odds ratio 4.21, 95% CI [3.29-5.39]). Length of stay was longer for patients with CKD (mean difference (MD) 0.14days, 95% CI, [0.04, 0.23]) and patients with ESKD (MD 0.27days, 95% CI, [0.10, 0.43]) compared to non-CKD patients. Patients with ESKD had higher admission costs compared to non-CKD patients (MD $1982.65). Patients with CKD and ESKD have increased healthcare utilization and higher rates of ICU admission after bariatric surgery compared to non-CKD patients. Otherwise, there is no significant difference in other post-operative complications and mortality. Bariatric surgery may therefore be safely offered to this patient population in hospitals with on-site ICU capacity.

Longitudinal uric acid has nonlinear association with kidney failure and mortality in chronic kidney disease

We investigated the shape of the relationship between longitudinal uric acid (UA) and the hazard of kidney failure and death in chronic kidney disease (CKD) patients, and attempted to identify thresholds associated with increased hazards. We included CKD stage 3–5 patients from the CKD-REIN cohort with one serum UA measurement at cohort entry. We used cause-specific multivariate Cox models including a spline function of current values of UA (cUA), estimated from a separate linear mixed model. We followed 2781 patients (66% men, median age, 69 years) for a median of 3.2 years with a median of five longitudinal UA measures per patient. The hazard of kidney failure increased with increasing cUA, with a plateau between 6 and 10 mg/dl and a sharp increase above 11 mg/dl. The hazard of death had a U-shape relationship with cUA, with a hazard twice higher for 3 or 11 mg/dl, compared to 5 mg/dl. In CKD patients, our results indicate that UA above 10 mg/dl is a strong risk marker for kidney failure and death and that low UA levels below 5 mg/dl are associated with death before kidney failure.

Serum sclerostin in vascular calcification in CKD: a meta-analysis

Vascular calcification (VC) is recognized as a predictor of all-cause and CVD mortality in chronic kidney disease (CKD). VC in CKD is possibly associated with serum sclerostin. The study systematically investigated the role of serum sclerostin in VC in CKD. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, a systematic search was performed of the PubMed, Cochrane Library, and EMBASE databases from inception to 11 November 2022, to identify relevant eligible studies. The data were retrieved, analyzed, and summarized. The hazard ratios (HRs) and odds ratios (ORs) with their corresponding confidence intervals (CIs) were derived and pooled. Thirteen reports (3125 patients) met the inclusion criteria and were included. Sclerostin was associated with the presence of VC (pooled OR = 2.75, 95%CI = 1.81–4.19, p < 0.01) and all-cause mortality (pooled HR = 1.22, 95%CI = 1.19–1.25, p < 0.01) among patients with CKD, but with a decreased risk of cardiovascular events (HR = 0.98, 95%CI = 0.97–1.00, p = 0.02). This meta-analysis suggests that serum sclerostin is associated with VC and all-cause mortality among patients with CKD.

Predictors of mortality in heart failure with reduced ejection fraction: interaction between diabetes mellitus and impaired renal function.

The harmful effect of diabetes mellitus (DM) on mortality in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial. Furthermore, it seems that no consistent conclusion on whether chronic kidney disease (CKD) modifies the relationship of DM and poor prognosis in patients with HFrEF. We analyzed the individuals with HFrEF from the Cardiorenal ImprovemeNt (CIN) cohort between January 2007 and December 2018. The primary endpoint was all-cause mortality. The patients were divided into four groups (control vs. DM alone vs. CKD alone vs. DM and CKD). Multivariate Cox proportional hazards analysis was conducted to examine the association among DM, CKD and all-cause mortality. There were 3,273 patients included in this study (mean age: 62.7 ± 10.9years, 20.4% were female). During a median follow-up of 5.0years (interquartile range: 3.0-7.6years), 740 (22.6%) patients died. Patients with DM have a higher risk of all-cause mortality (HR [95% confidence interval (CI)]:1.28[1.07-1.53]) than those without DM. In patients with CKD, DM had a 61% (HR [95% CI]:1.61[1.26-2.06]) increased adjusted risk of death relative to non-DM, while in patients with non-CKD, there was no significantly difference in risk of all-cause mortality (HR [95% CI]:1.01[0.77-1.32]) between DM and non-DM (p for interaction = 0.013). Diabetes is a potent risk factor for mortality in patients with HFrEF. Furthermore, DM had a substantially different effect on all-cause mortality depending on CKD. The association between DM and all-cause mortality was only observed in patients with CKD.