Mortality In Chronic Kidney Disease Patients Research Articles

The U-shape relationship between insulin resistance-related indexes and chronic kidney disease: a retrospective cohort study from National Health and Nutrition Examination Survey 2007–2016

BackgroundThere is ongoing debate on the correlation between chronic kidney disease (CKD) and insulin resistance (IR)-related indices. Our objective was to explore the prognostic ability of IR-related indexes for the prevalence of CKD, as well as the mortality from all causes and cardiovascular disease (CVD) in CKD patients.MethodsThe data used in this study came from the National Health and Nutrition Examination Survey (NHANES). Binary logistic regression analysis, Cox proportional hazards model, and restricted cubic spline (RCS) were used to analyze the relationship between IR-related indexes, including metabolic score of IR (METS-IR), homeostatic model assessment for IR (HOMA-IR), triglyceride glucose index (TyG), triglyceride glucose-waist-to-height ratio (TyG-WHtR), triglyceride glucose-body mass index (TyG-BMI), with CKD and its all-cause mortality and CVD mortality. Subgroup analysis was performed to test the stability of the results. Finally, the predictive power of IR-related indexes for CKD was tested by the receiver operating characteristic (ROC) curve.ResultsAmong the recruited 10,660 participants, 15.42% were CKD patients. All IR-related indexes were found to be nonlinearly correlated to the prevalence of CKD in the study. When the TyG index was higher than 9.05, it was positively associated with CKD (OR: 1.77, 95% CI 1.44–2.18). Moreover, increased TyG-WHtR level was correlated with a greater prevalence of CKD when it was higher than 4.3 (OR: 1.31, 95% CI 1.19–1.45). Other IR-related indexes (METS-IR, HOMA-IR, and TyG-BMI) showed fewer notable correlations with CKD. The association of IR-related indexes and the prevalence of CKD remained consistent in most subgroups (P for interactions > 0.05). TyG-WHtR was also the predictor of all-cause mortality in CKD patients (HR: 1.34, 95% CI 1.14–1.58), while other IR-related indexes were not correlated with the all-cause mortality or CVD mortality in CKD patients (P > 0.05). Otherwise, ROC curves showed that TyG-WHtR had more robust diagnostic efficacy than other IR-related indexes (METS-IR, HOMA-IR, TyG, and TyG-BMI) in predicting CKD (area under the curve: 0.630, 95% CI 0.615–0.644).ConclusionsIR-related biomarkers (METS-IR, HOMA-IR, TyG, and TyG-BMI) were positively correlated with the prevalence of CKD. Moreover, TyG-WHtR enhanced CKD and its all-cause mortality prediction. In patients with elevated levels of IR-related indexes, the early detection and intervention of IR may reduce the occurrence of CKD and the prognosis of CKD patients.

#2477 Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: analyses from the EQUAL cohort

Abstract Background and Aims Serum bicarbonate (SBC) disorders have been consistently linked to mortality in chronic kidney disease (CKD) patients. Low SBC levels have been extensively associated with increased mortality in CKD patients, possibly due to the detrimental effects of acidosis on various organs and systems. Likewise, several studies have identified high levels of SBC as a risk factor for mortality in the CKD population. To date, most studies have focused on the association between SBC levels and patient survival during the pre-kidney replacement therapy (KRT) period or the period after KRT initiation, considered separately. None have explored this association across the continuum of CKD (e.g., from pre-KRT to post-KRT start), which is relevant since metabolic acidosis is expected to be managed through dialysis in the KRT population, and thus its clinical outcomes might change after KRT initiation. To provide new insights on this topic, we aimed to explore the relationship between SBC and mortality in advanced CKD during three distinct treatment periods: during the pre-KRT period, during the transition phase surrounding the start of KRT (transition-CKD), and during KRT. Method Using the European QUALity Study on treatment in advanced CKD (EQUAL) cohort, which includes patients aged ≥65 years and eGFR ≤20 ml/min per 1.73 m2 from six European countries, we explored the association between longitudinal SBC and all-cause mortality in three separate CKD populations: pre-KRT, transition-CKD and in the KRT populations, using multivariable time-dependent Cox regression models. The cumulative time-averaged, the cumulative exposure of SBC, and the slope of the SBC trajectory during the pre-KRT phase were calculated and evaluated for association with all-cause mortality in the transition-CKD population. Subgroup analysis were used to evaluate the effect modification by pre-specified variables on the relationship between SBC and mortality. Results We included 1485 patients with a median follow-up of 2.9 (IQR 2.7) years, during which 529 (35.6%) patients died. A U-shaped relationship between SBC levels and all-cause mortality was observed in the pre-KRT population (p = 0.03; Fig.). Low cumulative exposure, defined as the area under the SBC trajectory before KRT initiation, was associated with increased mortality risk after transitioning to KRT (p = 0.01). Similarly, in the KRT population, low SBC levels showed a trend towards increased mortality risk (p = 0.13). We observed effect modification on the relationship between SBC and mortality by subjective global assessment category (p-value for interaction = 0.02) and KRT initiation (p-value for interaction = 0.02). Conclusion Our study has provided important insights into the relationship between SBC and mortality in advanced CKD patients. A U-shaped relationship describes the association between SBC and mortality in the advanced CKD pre-KRT population, whereas in patients that initiate KRT only low SBC levels are associated with an increased mortality risk. Our findings suggest that the relationship between SBC and mortality varies across different stages of CKD and that this relationship is modified by KRT initiation. From this point of view, it would be appropriate to consider a personalized management of acid-base balance disorders based on a comprehensive evaluation of the clinical status of the patient.

#2009 FGF23 in patients with diabetic kidney disease and atherosclerosis

Abstract Background and Aims Diabetes mellitus (DM) and chronic kidney disease (CKD) are risk factors for vascular atherosclerosis, a pathological process with an important inflammatory component. The coexistence of these conditions in patients with diabetic kidney disease (DKD) has additive effects with worst cardiovascular mortality and morbidity rates when compared to non-diabetic CKD patient on cardiovascular outcomes. Accumulating research has shown that increased levels of bone-derived fibroblast growth factor 23 (FGF23), the major phosphate-regulating hormone, constitute a novel predictor of cardiovascular and all-cause mortality in CKD patients, with potential effects on disorders of glucose metabolism as well. The objective of this comparative study is to determine the differences in FGF23 levels in two groups of patients with CKD, with and without DM, matched by age, sex and renal function, all of them with clinical atherosclerotic disease. We also evaluated the relationships of FGF23 with several inflammatory markers and parameters of glucose metabolism. Method Sixty-six patients with CKD stages 3-4 (33 of them with DM) and diagnosed with peripheral vascular disease were included in the study. Whole blood and serum samples were obtained from all participants. CRP values, neutrophil/lymphocyte (N/L) ratio, HbA1c (%), fasting glucose, and Triglycerides and glucose (TyG) index, among other parameters, were obtained using standardized routine methods. Circulating levels of the intact form of FGF23, tumor necrosis factor (TNF) α, interleukin (IL) 6, and IL10 were determined by ELISA immunoassays in both groups. We also performed gene expression analysis for these three cytokines in peripheral blood cells (PBCs) using qPCR. Results The mean values of eGFR, ACR and phosphate were 37.6 ± 11.2 ml/min/1.73 m2; 294.1 ± 271.2 mg/g; 3.8 ± 0.82 mg/dL; respectively without differences between patients with and without DM The median circulating FGF23 values were higher in the DM group (51.59 [37.73-89.68] vs. 38.1 [33-54.14] pg/mL; p<0.001). Likewise, patients with DM presented higher levels of TNFα both in serum concentration (1.78 [0.72-2.47] vs. 1.28 [1.01-1.88] pg/mL; p<0.01) as in the expression of mRNA in PBCs (2.1 ± 1.26 vs. 1.87 ± 1.16 a.u.; p<0.05). No differences were observed for IL6 and IL10 levels, nor for CRP concentration or N/L ratio. As expected, fasting glucose, HbA1c and TyG index were higher in the group of subjects with DM. FGF23 was inversely correlated with eGFR (r=−0.435, p<0.0001), while it showed a positive association with ACR (r=0.416, p<0.001) and, interestingly, with proinflammatory cytokines including circulating TNFα (r=0.44, p<0.001), circulating IL6 (r=0.27, p=0.04), and TNF mRNA expression in PBCs (r=0.245, p=0.047). Furthermore, circulating FGF23 was also direct and significantly correlated with HbA1c (r=0.34, p<0.01). Conclusion These results suggest that FGF23 levels are higher in DKD than in non-DM CKD patients with similar renal function. DKD patients also had higher levels of the proinflammatory cytokine TNFα. Our results also show positive correlations of FGF23 with the inflammatory cytokines TNFα and IL6, as well as with HbA1c. Previous studies, shown that elevated TNFα and glucose promote FGF23 production, which may help to explain the higher levels of FGF23 in patients with DM Future studies should clarify whether FGF23 is simply a marker of atherosclerosis disease severity or a contributing factor to this complication in CKD.

Periodontitis and risk of mortality in patients with chronic kidney disease: A systematic review with meta-analysis.

Studies examining the link between periodontitis and survival outcomes have yielded conflicting results in patients with chronic kidney disease (CKD). This systematic review with meta-analysis aims to assess the association between periodontitis and cardiovascular or all-cause mortality in CKD patients. A thorough search was conducted on the PubMed, Web of Science, and Embase databases for studies investigating the association between periodontitis and survival outcomes in CKD patients. Two authors independently scanned the titles or abstracts and then identified the eligible full-text article based on the PECOS criteria: Participants (CKD patients), Exposure (periodontitis), Comparison (mild/no periodontitis), Outcomes (cardiovascular or all-cause mortality), and Study design (retrospective or prospective cohort). Six cohort studies, including 7731 patients, were identified. The included studies had low-to-moderate risk of bias. The mean/median follow-up duration ranged from 18.1 months to 8.67 years. The all-cause mortality rate was 44.8% for patients with periodontitis and 28.0% for controls. Meta-analysis showed that periodontitis, defined through clinical attachment loss (CAL), was significantly associated with an increased risk of all-cause (adjusted hazard ratio [HR] 1.24; 95% confidence intervals [CI] 0.89-1.72; I2 = 80.9%) and cardiovascular mortality (HR 1.57; 95% CI 1.08-2.27; I2 = 34.0%). Additionally, a significant association between periodontitis and the risk of cardiovascular or all-cause mortality was observed in studies with a predominance of females, follow-up duration ≥5 years, all stages of CKD, and low risk of bias subgroups. Periodontitis is significantly associated with an increased risk of all-cause and cardiovascular mortality in CKD patients within low risk of bias subgroup or based on defining periodontitis through CAL. Registration number: PROSPERO CRD42018512391.

Association of systemic inflammation response index with all-cause mortality as well as cardiovascular mortality in patients with chronic kidney disease.

Chronic Kidney Disease (CKD) stands as a formidable health challenge, recognized not only for its growing prevalence but also for its association with elevated mortality rates. Emerging evidence suggests that CKD is inherently linked to inflammatory processes, marking it as an inflammatory disorder. In this landscape, the systemic inflammatory response index (SIRI) emerges as a novel inflammation marker, yet to be applied for assessing the risk of mortality in CKD patients. This study aims to investigate the prognostic significance of the SIRI in all-cause and cardiovascular disease (CVD) mortality among patients with CKD. This study conducted a retrospective observational study using the National Health and Nutrition Examination Survey (NHANES) database, encompassing data from 1999 to 2018. This analysis included 9,115 CKD patients, categorized based on SIRI quartiles. Key outcomes were all-cause and CVD mortality, analyzed using Kaplan-Meier survival curves, restricted cube splines (RCS) and cox proportional hazards models. In this study of 9,115 CKD patients, the Kaplan-Meier survival analysis revealed a greater incidence of all-cause death among groups with higher SIRI (P-log rank <0.001). In the fully adjusted model (Model 3), each unit increase in SIRI led to a 20% increase in the risk of all-cause mortality. Additionally, higher SIRI quartiles (Q3 and Q4) were associated with increased risk compared to the lowest quartile (Q1) (Q3: HR: 1.16, 95% CI: 1.01-1.34; Q4: HR: 1.63, 95% CI: 1.40-1.90; P for trend <0.001). Similarly, for CVD mortality, each unit increase in SIRI in Model 3 increased the risk by 33%, with Q3 and Q4 showing higher risk than Q1 (Q3: HR: 1.39, 95% CI: 1.11-1.70; Q4: HR: 2.26, 95% CI: 1.72-2.98; P for trend <0.001). SIRI was positively associated with all-cause and CVD mortality in patients with CKD.

Epidemiology of tobacco use in dialysis patients in France and survey of nephrologists' involvement in counseling ontobacco discontinuation.

Tobacco smoking is an independent risk factor for chronic kidney disease (CKD) and increases morbidity and mortality in CKD patients. The primary objective of the study was to investigate the epidemiology of smoking in patients undergoing maintenance dialysis in France. A second objective was to assess the involvement of nephrologists in supportingpatients forsmoking cessation. Data on the smoking history of prevalent patients on maintenance dialysis in France between 2010 and 2020 were obtained from the REIN database (Renal Epidemiology and Information Network),updated by all French nephrology and dialysiscenters. As for the support to smoking discontinuation, a questionnaire on smoking cessation assistance was sent to all members of the French Society of Nephrology, Dialysis and Transplantation (SFNDT). The proportion of current smokers among patients on maintenance dialysis was 10.4% in 2010, 11.2% in 2015 and 11.6% in 2020. A total of 228 nephrologists among the 790 members of the SFNDT participated in the survey (28.9%). Most respondents were women (57.3%), worked at a public hospital (61.1%), were under 40years of age (51.3%) and had no history of smoking (60.8%). The majority reported asking patients about their smoking status and offering brief advice. Among respondents, 72.8% offered help with smoking cessation, 46.3% referred their smoking patients to a tobacco specialist, 51.8% reported prescribing drugs to quit tobacco, and 81.6% requested further training in howtosupport patients forsmoking cessation. Smoking cessation training for nephrologists and dedicated programs for patients in nephrology units could improve our practices and decrease the high prevalence of smoking in patients with ESKD.

Cardiac Device Therapy in Patients with Chronic Kidney Disease: An Update.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy are scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms, and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy with defibrillator (CRT-D) is preferred in patients who meet the established criteria. The need for cardiac pacing is increased three-fold in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

The association between dietary antioxidant quality score and uric acid related mortality in patients with chronic kidney disease.

Antioxidants diet is beneficial for the prognosis of chronic kidney disease (CKD). However, the relationship between the Dietary Antioxidant Quality Score (DAQS), a measure of overall quality on antioxidant diet, and hyperuricemia related mortality is unclear. This study aimed to investigate the relationship between the DAQS and hyperuricemia mortality in CKD patients. In this cohort study, data were collected in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. The DAQS was calculated based on the six dietary antioxidants. Mortality status were determined by NHANES-linked National Death Index public access files through December 31, 2019. Weighted Cox proportional hazard models were used to investigate the association between the DAQS and hyperuricemia related mortality. A total of 3,684 participants were included. During the median follow-up of 63.83 months, 820 deaths were recorded. The results showed that higher dietary antioxidants intake associated with lower hyperuricemia related mortality risk among CKD patients (HR = 1.28, 95%CI: 1.07 to 1.54). In subgroup analyses, the association of antioxidants intake and hyperuricemia related mortality risk remained exist in groups of aged ≥65 years (HR = 1.23, 95%CI: 1.01 to 1.52), with hypertension (HR = 1.26, 95%CI: 1.02 to 1.55), with dyslipidemia (HR = 1.30, 95%CI: 1.07 to 1.58), with CVD (HR = 1.31, 95%CI: 1.03 to 1.67), and diabetes (HR = 1.62, 95%CI: 1.24 to 2.12). Higher antioxidants intake associated with lower odds of hyperuricemia related mortality in CKD patients. Future interventional studies are needed to elucidate the beneficial effect of antioxidants diets.

Functional iron deficiency anemia was associated with higher mortality in chronic kidney disease patients: the NHANES III follow-up study

Anemia, a common complication of chronic kidney disease (CKD), is associated with poor prognosis. However, it is not completely clear whether this association is caused by anemia per se or other comorbidities. Whether different types of iron deficiency anemia can predict the outcomes of CKD remains unclear. The dataset from NHANES III was analyzed and Cox multivariate regression models and propensity score matching (PSM) method were used to evaluate the effect of anemia on mortality. Of 4103 patients with CKD, 14.6% had anemia. Among those with anemia, 38.8% had absolute iron deficiency (AID), and 19.8% had functional iron deficiency (FID). During the median follow-up time of 13.8 years, 2964 deaths and 804 cardiovascular deaths were observed. Anemia was robustly associated with a high risk of all-cause mortality in CKD patients after adjusting covariates by two multivariate regression models (Model 1: HR = 1.485, 95%CI:1.340–1.647, p < 0.001; Model 2: HR = 1.391, 95%CI:1.250–1.546, p < 0.001). In the PSM cohort, anemia was still an independent risk factor for all-cause mortality (Model 1: HR = 1.443, 95%CI: 1.256–1.656, p < 0.001; Model 2: HR = 1.357, 95%CI:1.177–1.564, p < 0.001). In the CKD population, anemia patients with FID had the highest risk of mortality than the other anemia groups (p < 0.05), while AID had a mortality rate similar to those without anemia (p > 0.05). In conclusion, anemia was associated with a worse prognosis in patients with CKD, which may be attributed to the higher mortality risk of FID rather than AID. AID wasn’t associated with a higher mortality rate compared with CKD patients without anemia.

Chronic Kidney Disease and Its Impact on The Gastrointestinal Tract: A Prospective Observational Study

Chronic kidney disease (CKD) is a pervasive and progressive condition that wreaks havoc on renal function, but its far-reaching impact extends beyond the kidneys. In this article, we explore the intricate relationship between CKD and the Gastrointestinal Tract (GIT), shedding light on the underreported and multifaceted digestive pathologies that afflict CKD patients. We conducted a study involving 80 CKD patients admitted between June 2022 and June 2023, revealing that 85% of these patients experienced various GI symptoms, with nausea, vomiting, and anorexia being the most common. These symptoms may stem from urea and metabolic waste accumulation or dialysis-related effects. Endoscopic examinations unveiled abnormalities in 86% of the cases, primarily localized in the stomach, with gastritis being the predominant lesion. Gastric and duodenal ulcers were relatively rare, aligning with previous studies. Gastrointestinal bleeding occurred in 8% of cases, often linked. to erosive gastritis or angiodysplasia. Interestingly, hiatus hernia prevalence was higher in conservative management patients rather than those undergoing haemodialysis. Most patients were in Stage V CKD, with 80% receiving conservative treatment. Our findings suggest a correlation between the severity of renal impairment and the likelihood of upper GI lesions. In conclusion, CKD profoundly affects the GI tract, causing a spectrum of symptoms and potential complications, including underreported upper GI lesions. Early recognition through upper GI endoscopy and prompt management is crucial to reduce morbidity and mortality in CKD patients. This study highlights the need for increased awareness and vigilance in managing the intricate interplay between CKD and the GIT, benefitting both patients and healthcare professionals in their battle against this multifarious condition.

Impact on Kidney Function and Medium-Term Outcomes of Transcatheter Aortic Valve Replacement in Patients With Chronic Kidney Disease

Transcatheter aortic valve replacement (TAVR) is now widely approved for the treatment of aortic stenosis, regardless of the patients' surgical risk. However, the outcomes of TAVR and their determinants in patients with chronic kidney disease (CKD) beyond 1year of follow-up are unknown. We aimed to assess the medium-term outcomes of TAVR in CKD, develop a risk score to estimate the 2-year mortality in patients with CKD, and evaluate the changes in kidney function at discharge after TAVR. Adults who underwent TAVR were retrospectively identified. The CKD stage was determined using the Chronic Kidney Disease Epidemiology 2021 creatinine formula. Improved kidney function was defined as post-TAVR creatinine ≤50% of pre-TAVR creatinine or decrease in creatinine of ≥0.3mg/100ml compared with pre-TAVR creatinine. Overall, 1,523 patients (median age 82years; 59% men; 735 with CKD stage II or less, 661 with CKD III, 83 with CKD IV, and 44 with CKD V [of whom 40 were on dialysis]) were included. The all-cause mortality was higher in CKD stages IV and V on the multivariable analysis (p <0.001) at median follow-up of 2.9 (interquartile range 2.0 to 4.2) years. Moderate or severe tricuspid regurgitation, anemia, right ventricular systolic pressure >40mm Hg and CKD stages IV and V were independent predictors of 2-year mortality and were used to develop a risk score. At hospital discharge, persisting acute kidney injury after TAVR occurred in 88 of 1,466 patients (6%), whereas improved kidney function occurred in 170 of 1,466 patients (12%). In conclusion, CKD stage was an independent determinant of mortality beyond 2years after TAVR. Kidney function was more likely to improve than worsen at the time of hospital discharge after TAVR.

Study of the association between serum levels of kynurenine and cardiovascular outcomes and overall mortality in chronic kidney disease.

Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate an association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality in CKD patients. The CKD-REIN study is a prospective cohort of people with CKD having an estimated glomerular filtration rate (eGFR) <60ml/min/1.73m². Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome. Of the 2406 included patients (median age: 68 years; median eGFR: 25ml/min/1.73m2), 52% had a history of cardiovascular disease. A doubling of serum-free kynurenine levels was associated with an 18% increased hazard of cardiovascular events [466 events, HR (95%CI):1.18(1.02,1.33)], independently of eGFR, serum-free tryptophan level or other uremic toxins, cardioprotective drugs, and traditional cardiovascular risk factors. Serum-free kynurenine was significantly associated with non-atheromatous cardiovascular events [HR(95%CI):1.26(1.03,1.50)], but not with atheromatous cardiovascular events [HR(95%CI):1.15(0.89,1.50)]. The association of serum-free kynurenine with cardiovascular mortality was also independently significant [87 events; adjusted HR(95%CI):1.64(1.10,2.40)]. However, the association of serum-free kynurenine with all-cause mortality was no more significant after adjustment on serum-free tryptophan [311 events, HR(95%CI):1.12(0.90, 1.40)]. Our findings imply that serum-free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events; in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies.

Serum amyloid A and risks of all-cause and cardiovascular mortality in chronic kidney disease: a systematic review and dose-response meta-analysis

Backgrounds The available literature on the correlation between serum amyloid A (SAA) and prognosis of chronic kidney disease (CKD) are limited, and the findings from existing studies are inconclusive. This meta-analysis aimed to evaluate the available evidence regarding the link between SAA and risks of all-cause and cardiovascular mortality in CKD patients. Additionally, we aimed to investigate the potential dose-response relationships, provided that adequate data is accessible. Methods Pubmed and Embase were searched for related literature (last update: 12 July 2023). The pooled effect estimates were calculated using random- or fixed-effects models depending on heterogeneity among studies. Results This meta-analysis incorporated 8 studies encompassing 2331 CKD patients. The findings revealed an 85% increase in all-cause mortality risk [hazard risk (HR) 1.85, 95% confidence interval (CI) 1.29–2.65] and a 39% increase in cardiovascular mortality risk (HR 1.07, 95% CI 1.07–1.80) when comparing the highest tertile of baseline SAA levels to the lowest tertile. Furthermore, a positive linear relationship between SAA and all-cause mortality risk was observed (P non-linearity = 0.959), with a 17.7% increase in risk for each 10 mg/L SAA increase (HR 1.177, 95% CI 1.055–1.313). Similarly, a linear relationship between SAA and cardiovascular mortality risk was identified (P non-linearity = 0.477) with a 19.3% increase in risk for each 10 mg/L SAA increase (HR 1.193, 95% CI 1.025–1.388). Conclusions This meta-analysis provided evidence that SAA levels are positively and linearly associated with risks of all-cause and cardiovascular mortality among CKD patients.

Association of oral iron replacement therapy with kidney failure and mortality in CKD patients.

Oral iron is the predominant route of iron replacement (IRT) but its benefits and safety are unclear in patients with chronic kidney disease (CKD). We examined the association of oral IRT vs no IRT with end-stage kidney disease (ESKD) and mortality in a national cohort of US Veterans. We identified 17413 incident new users of oral IRT with estimated glomerular filtration rates <60mL/min/1.73 m2 and 32530 controls who did not receive any IRT during 2004-18. We used propensity score-overlap weighting to account for differences in key baseline characteristics associated with the use of oral IRT. We examined associations using competing risk regression and Cox models. In the cohort of 49943 patients, 1616 (3.2%) patients experienced ESKD and 28711 (57%) patients died during a median follow-up of 1.9 years. Oral IRT was not associated with ESKD [subhazard ratio (HR) (95% confidence interval, CI) 1.00 (0.84-1.19), P=.9] and was associated with higher risk of all-cause mortality [HR (95% CI) 1.06 (1.01-1.11), P=.01]. There was significant heterogeneity of treatment effect for mortality, with oral IRT associated with higher mortality in the subgroups of patients without congestive heart failure (CHF), anemia or iron deficiency. In patient with blood hemoglobin <10g/dL oral IRT was associated with significantly lower mortality. Oral IRT was associated with lower mortality only in patients with anemia. In patients without anemia, iron deficiency or CHF, the risk-benefit ratio of oral IRT should be further examined.

Elevated Crude Mortality in Obese Chronic Kidney Disease Patients with Loss of Exercise Habit: A Cohort Study of the Japanese General Population.

Background The relationship between obesity and risk of death in chronic kidney disease (CKD) patients remains controversial. In addition, no clear evidence has been accumulated regarding whether or not exercise improves mortality in CKD patients. Materials and Methods The original cohort was based on a Japanese general population of 685,889 people from 40 to 74 years old who had undergone annual specific health checkups. The number of all-cause deaths during follow-up (mean, 4.7 years) in this study was 1,490. Information on walking and exercise habits was obtained by questionnaires. The study population was divided into 4 categories by the combination of CKD and obesity [body mass index (BMI) ≥25.0 kg/m2]. Changes in the BMI and walking and exercise habits were determined by results for the first year and following year. Results Obese CKD patients with weight gain (BMI increase by more than +1.0 kg/m2/year) showed a higher crude mortality (1.32%) than those with a stable BMI (within ±1.0 kg/m2/year; 0.69%). In the obese CKD population, mortality was higher with loss of exercise habits (0.96%) than in those continuously maintaining exercise habits (0.52%). The age- and sex-adjusted hazard ratio for all-cause death was 2.23 in the group with weight gain compared to the group with stable weight (p<0.01) and 2.08 in the group with loss of exercise habits compared to those who maintained exercise habits (p<0.01). Conclusions This observational cohort study suggested that loss of exercise habits as well as weight gain of more than 1 kg/m2/year might worsen all-cause mortality in the obese CKD population.

Modified Nutrition Risk in Critically Ill (m-NUTRIC) score to assess nutritional status and outcome in patients of chronic kidney disease: 2-year cross-sectional study

Introduction: Chronic kidney disease (CKD) is a major health concern in India and has high prevalence, morbidity, and mortality due to significant percentages of subjects with poor socioeconomic status as well as poor management of health resources. Many apparatuses are available to assess nutrition status among patients of CKD. This study was conducted to identify nutritional risk in CKD patients using a modified Nutrition Risk in Critically ill (m-NUTRIC) score without using interleukin-6 values. Method: This prospective observational study was conducted at a tertiary care teaching hospital for a time period of 2 years from 2020 to 2022. The modification of diet in renal disease approach was used for the staging of the CKD. m-NUTRIC scores were calculated and scores ≥5 were graded in high-risk categories and were associated with adverse outcomes, whereas scores &lt;5 were categorized as low risk. Result: Among 250 patients with CKD enrolled, 65 patients were in the age group 18 to 40 years having a mean m-NUTRIC score of 4.46 ± 1.76; in the age group 40 to 60 years 5.18 ± 1.67; and in the age group older than 60 years 5.88 ± 1.77. The mean (standard deviation [SD]) m-NUTRIC score in hemodialysis group was 5.69 ± 1.63 and in nonhemodialysis group was 4.15 ± 1.66. At m-NUTRIC cutoff of 5, predicted hemodialysis is having 66% specificity and 77% sensitivity. It predicts mortality with a sensitivity of 93% and a specificity of 89% at a cutoff of m-NUTRIC of 6. Conclusion: This study showed that m-NUTRIC score may be an important tool that determines requirement of hemodialysis and mortality in CKD patients. Moreover, these scores were higher in stages 4 and 5 of CKD.

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.

Experimental renal transplantation in rats improves cardiac dysfunction caused by chronic kidney disease while LVH persists.

Chronic kidney disease (CKD) causes congestive heart failure (CHF) with systolic dysfunction and left ventricular hypertrophy (LVH), which is a major contributor to increased mortality in CKD patients. It remains unclear whether cardiovascular changes that occur during the course of CKD can be reversed when renal function is restored by transplantation. To investigate this, chronic kidney disease was established in F344 rats by subtotal nephrectomy (SNx) for 8 weeks, followed by transplantation of a functional kidney from an isogenic F344 donor. SNx rats without transplantation and sham-operated animals served as controls. Renal function was assessed before and throughout the experiment. In addition, cardiac ultrasound was performed at weeks 0, 8, 12 and 16. At the end of the experiment, intra-arterial blood pressure was measured and kidneys and hearts were histologically and molecularly examined. Eight weeks after SNx, rats developed marked renal dysfunction associated with significant glomerulosclerosis and tubulointerstitial fibrosis, but also an increase in left ventricular mass. After transplantation, renal function normalized but relative heart weight and ventricular mass as assessed by ultrasound scans showed no reduction compared with SNx controls. However, left ventricular wall thickness, fractional shortening and ejection fraction was normalized by renal transplantation. At 8 weeks after kidney transplantation, cardiac expression of BNP and FGF23 was also at levels comparable to healthy controls, whereas these factors were significantly increased in SNx rats. Cardiac fibrosis, as measured by fibronectin mRNA expression, was completely normalized, whereas cardiac fibronectin protein was still slightly but not significantly increased in transplanted animals compared to controls. In addition, the myofibroblast marker collagen 1, as assessed by immunohistochemistry, was significantly increased in SNx rats and also normalized by renal transplantation. Interestingly, CD68+ macrophages were significantly reduced in the hearts of SNx rats and in transplanted animals at slightly higher levels compared to controls. Restoration of renal function by kidney transplantation normalized early cardiac changes at most functional and molecular levels, but did not completely reverse LVH. However, further studies are needed to determine whether restoration of renal function can also reverse LVH at a later time point.

Clinico-pathological correlation study in chronic kidney disease patients undergoing hemodialysis

Chronic Kidney Disease (CKD) is a global health problem and associated with increased morbidity and mortality. Hemodialysis is the most common mode of renal replacement in end stage kidney disease. Variation in hematological and biochemical parameters are the prime factors responsible for morbidity and mortality in CKD patients. Normocytic Normochromic Anemia is a typical morphology seen in CKD patients resulting due to erythropoietin deficiency. Early detection and treatment of these pathologies can improve the quality of life in CKD patients.: 1) To evaluate the clinical manifestations and various pathological changes associated with CKD patients on hemodialysis. 2) To compare and correlate various clinico-pathological parameters in CKD patients on hemodialysis, with special emphasis on diabetic kidney disease.: One year eleven months retrospective study was done at CIMS hospital, which included 50 CKD patients. Complete clinical data were recorded and correlated with various hematological and biochemical parameters. Statistical analysis was performed by chi square test and student’s T test. Out of 50 CKD patients, 86% were male, age group of 41-50 years (62%). The commonest co-morbidity was combined hypertension with diabetes in 44%. Majority (72%) had BP between 140-159mmHg. Most (64%) of the CKD patients were known cases of diabetes. Significantly lower levels of RBC count, hemoglobin, hematocrit and platelet count were found with normocytic normochromic anemia being the commonest morphological type. Significantly increased WBC counts, ESR, serum urea, creatinine and serum phosphate levels were noted in CKD patients. DKD patients showed significant risk compared to NDKD patients. CKD is a progressive, irreversible disease. We found alterations in various haematological and biochemical parameters, which were more severe among DKD patients compared to NDKD patients. Early recognition and management of these changes will have an important impact in improving the quality of life.

#6379 EFFECTS OF SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITORS ON CARDIOVASCULAR MORTALITY INCHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background and Aims In studies of patients with chronic kidney disease (CKD), recommended nephroprotective therapy with ACE-inhibitors or ARBs has not been shown to reduce cardiovascular (CV) events or mortality. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce cardiovascular events and death in patients with diabetes and established CV disease; evidence from studies in populations with CKD has been inconsistent. The aim of this meta-analysis was to evaluate the effect of SGLT-2 inhibitors on cardiovascular (CV) mortality in patients with CKD. Method Studies were identified by search in major electronic databases (PubMed/MEDLINE, Scopus, Cochrane Library and Web of Science) (PROSPERO ID: CRD42022382863). We included randomized controlled trials assessing the effect of SGLT-2 inhibitors on the primary outcome, time to cardiovascular death, in patients with CKD at baseline. Secondary outcomes included all-cause mortality and major adverse cardiac events (MACE). Results Eleven studies with 83,203 participants with CKD were eligible for inclusion in the meta-analysis. Treatmentwith SGLT-2 inhibitors, compared to placebo, reduced the risk of CV death by 14% (hazard ratio [HR] 0.86;95%CI 0.79-0.94), of all-cause death by 15% (HR 0.85; 95%CI 0.79-0.91) and of MACE by 13% (HR 0.87; 95%CI0.81-0.93). A consistent treatment effect on the primary outcome was observed with all SGLT-2 inhibitors(canagliflozin: HR 0.84; 95%CI 0.69-1.02, dapagliflozin: HR 0.89; 95%CI 0.78-1.01, empagliflozin: HR 0.82;95%CI 0.69-0.97 sotagliflozin: HR 0.90; 95%CI 0.73-1.12) studied (p-subgroup-differences = 0.85). Sensitivity analysis pooling data from studies including only diabetic patients with CKD yielded similar results (HR 0.86;95%CI 0.77-0.97). Conclusion Treatment with SGLT-2 inhibitors led to a significant reduction in the risk for CV and all-cause mortality in CKD patients. These findings support the use of these agents also for protection against cardiovascular events and death in CKD.