Decline In Renal Function Research Articles

Ambient ozone pollution impairs glucose homeostasis and contributes to renal function decline: Population-based evidence

Particulate matter pollution could increase the risk of kidney disease, while evidence for ozone exposure is less well-established. Here, we aimed to evaluate the effect of ozone pollution on renal function and explore mechanisms. We first conducted a cross-sectional study based on Wuhan Chronic Disease Cohort Study baseline information. We recruited 2699 eligible participants, estimated their residential ozone concentrations, collected fasting peripheral blood samples for biochemical analysis and calculated the estimated glomerular filtration rate (eGFR). The linear regression model was applied to evaluate the long-term association between ozone pollution and eGFR. Then, we recruited another 70 volunteers as a panel with 8 rounds follow-up visits. We calculated the eGFR and measured fasting blood glucose and lipid levels. The linear mixed-effect model along with mediation analysis were performed to confirm the short-term association and explore potential mechanisms, respectively. For the long-term association, a 10.95 μg/m3 increment of 3-year ozone exposure was associated with 2.96 mL/min/1.73 m2 decrease in eGFR (95%CI: −4.85, −1.06). Furthermore, the drinkers exhibited a pronounced declination of eGFR (−7.46 mL/min/1.73 m2, 95%CI: −11.84, −3.08) compared to non-drinkers in relation to ozone exposure. Additionally, a 19.02 μg/m3 increase in 3-day ozone concentrations was related to 2.51 mL/min/1.73 m2 decrease in eGFR (95%CI: −3.78, −1.26). Hyperglycemia and insulin resistance mediated 12.2% and 16.5% of the aforementioned association, respectively. Our findings indicated that higher ozone pollution could affect renal function, and the hyperglycemia and insulin resistance linked to ozone might be the underlying mechanisms.

Prostacyclin Mitigates Renal Fibrosis by Activating Fibroblast Prostaglandin I 2 Receptor.

Renal fibrosis is a common pathologic process of progressive CKD. We have provided strong evidence that PGI 2 is an important component in the kidney injury/repairing process by reducing fibrosis and protecting renal function from declining. In our study, administration of a PGI 2 analog or selective PTGIR agonist after the acute injury ameliorated renal fibrosis. Our findings provide new insights into the role of PGI 2 in kidney biology and suggest that targeting PGI 2 /PTGIR may be a potential therapeutic strategy for CKD. Prostanoids have been demonstrated to be important modulators to maintain tissue homeostasis in response to physiologic or pathophysiologic stress. Prostacyclin (PGI 2 ) is a member of prostanoids. While limited studies have shown that PGI 2 is involved in the tissue injury/repairing process, its role in renal fibrosis and CKD progression requires further investigation. Prostacyclin synthase ( Ptgis )-deficient mice, prostaglandin I 2 receptor ( Ptgir )-deficient mice, and an oral PGI 2 analog and selective PTGIR agonist were used to examine the role of PGI 2 in renal fibrosis in mouse models. We also analyzed the single-cell RNA-Seq data to examine the PTGIR -expressing cells in the kidneys of patients with CKD. Increased PTGIS expression has been observed in fibrotic kidneys in both humans and mice. Deletion of the PTGIS gene aggravated renal fibrosis and decline of renal function in murine models. A PGI 2 analog or PTGIR agonist that was administered after the acute injury ameliorated renal fibrosis. PTGIR, the PGI 2 receptor, deficiency blunted the protective effect of the PGI 2 analog. Fibroblasts and myofibroblasts were the major cell types expressing PTGIR in the kidneys of patients with CKD. Deletion of PTGIR in collagen-producing fibroblastic cells aggravated renal fibrosis. The protective effect of PGI 2 was associated with the inhibition of fibroblast activation through PTGIR-mediated signaling. PGI 2 is an important component in the kidney injury/repairing process by preventing the overactivation of fibroblasts during the repairing process and protecting the kidney from fibrosis and decline of renal function. Our findings suggest that PGI 2 /PTGIR is a potential therapeutic target for CKD.

The estimated glomerular filtration rate was U-shaped associated with abdominal aortic calcification in US adults: findings from NHANES 2013-2014.

The high incidence of abdominal aortic calcification (AAC) is well-documented in individuals with severe renal function decline. However, there is limited research on the historical relationship between estimated glomerular filtration rate (eGFR) and the risk of AAC occurrence in the general population undergoing routine medical examinations. The main objective of this study was to investigate the historical relationship between eGFR and AAC in the general population of the United States. We performed a cross-sectional study using the National Health and Nutrition Examination Survey 2013-2014 database. Weighted multivariate linear regression models were used to estimate the associations of eGFR with AAC score. Smooth curve fitting and two-piecewise linear regression were employed to explore the potential non-linear relationship. A total of 2,978 participant (48.22% were male) aged 40-80 years were included in this study. The fully-adjusted model demonstrated a negative correlation between eGFR and AAC score (β = -0.015, 95% CI: -0.023 to -0.006). However, when applying the smooth curve fitting method, a U-shaped relationship was identified, and the inflection point was calculated at 76.43 ml/min/1.73 m2 using the two-piecewise linear regression model. There was a U-shaped association between eGFR and AAC score in general US adults, with an inflection point at about 76.43 ml/min/1.73 m2.

Identification and analysis of diverse cell death patterns in diabetic kidney disease using microarray-based transcriptome profiling and single-nucleus RNA sequencing

BackgroundDiabetic kidney disease (DKD) is the most lethal complication of diabetes. Diverse programmed cell death (PCD) has emerged as a crucial disease phenotype that has the potential to serve as an indicator of renal function decline and can be used as a target for researching drugs for DKD. MethodsMicroarray-based transcriptome profiling and single-nucleus transcriptome sequencing (snRNA-seq) related to DKD were retrieved from the Gene Expression Omnibus (GEO) database. 13 PCD-related genes (including alkaliptosis, apoptosis, autophagy-dependent cell death, cuproptosis, disulfidptosis, entotic cell death, ferroptosis, lysosome-dependent cell death, necroptosis, netotic cell death, oxeiptosis, parthanatos, and pyroptosis) were obtained from various public databases and reviews. The gene set variation analysis (GSVA) analysis was used to explore the pathway activity of these 13 PCDs in DKD, and the pathway activity of these PCDs in different renal cells was studied based on DKD-related snRNA-seq data. To identify the core PCDs that play a significant role in DKD, we analyzed the relationships between different types of PCD and immune infiltration, fibrosis-related gene expression levels, glomerular filtration rate (GFR), and diagnostic efficiency in DKD. Using the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm, we screened for core death genes among the core PCDs and constructed a cell death-related signature (CDS) risk score based on the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, we validated the predictive performance of the CDS risk score in an independent validation set. ResultsWe identified 4 core PCD pathways, namely entotic cell death, apoptosis, necroptosis, and pyroptosis in DKD, and further applied the WGCNA algorithm to screen 4 core death genes (CASP1, CYBB, PLA2G4A, and CTSS) and constructed a CDS risk score based on these genes. The CDS risk score demonstrated high diagnostic efficiency for DKD patients, and those with higher scores had higher levels of immune cell infiltration and poorer GFR. ConclusionOur study sheds light on the fact that multiple PCDs contribute to the progression of DKD, highlighting potential therapeutic targets for treating this disease.

Identification of ferroptosis-related genes in acute kidney injury by bioinformatic analysis

ABSTRACT Background: Acute kidney injury (AKI) is a rapid decline in renal function characterized by a decrease in glomerular filtration rate in a short period. Ferroptosis affects the development of various kidney diseases. Therefore, searching for genes related to ferroptosis is crucial for understanding the occurrence and development of AKI. Methods: We obtained data from 18 samples (8 with acute kidney injury and 10 non-pathological tissue) in GSE53769 and 48 samples (39 with acute kidney injury and 9 non-pathological tissue) in GSE139061. We obtained differentially expressed genes (DEGs) of AKI/Control samples from both two datasets and intersected them with known ferroptosis-related genes (FRGs) to obtain ferroptosis-related DEGs (FRDEGs). GO annotation, KEGG pathway analysis, and GSEA analysis were conducted on the FRDEGs to understand their enriched biological functions and pathways. Next, we constructed the protein-protein interaction (PPI) network. Results: A total of 312 genes were obtained, which were abnormally expressed in both two datasets. After intersecting with known FRGs, 14 FRDEGs were obtained, namely ACSF2, ADIPOR1, ARF6, ATF3, ATF6, DPEP1, FH, GLRX5, MIOX, NAP1L1, NDRG1, PPARA, SPHK1, YY1AP1. The results of the immune infiltration analysis showed that multiple gene expressions among 14 genes are correlated with immune cell infiltration. Conclusion: Fourteen ferroptosis genes (ACSF2, ADIPOR1, ARF6, ATF3, ATF6, DPEP1, FH, GLRX5, MIOX, NAP1L1, NDRG1, PPARA, SPHK1, YY1AP1) are involved in the occurrence and development of AKI, among which NDRG1 might be the core functional gene, and PPARA is expected to become the most effective therapeutic target gene.

Incidence and predictors of clinically significant renal function decline among non-valvular atrial fibrillation patients on Warfarin: A multicenter study

Incidence and predictors of clinically significant renal function decline among non-valvular atrial fibrillation patients on Warfarin: A multicenter study

Incidence and predictors of clinically significant renal function decline among non-valvular atrial fibrillation patients on non-vitamin K oral anticoagulant: A multicenter study

Incidence and predictors of clinically significant renal function decline among non-valvular atrial fibrillation patients on non-vitamin K oral anticoagulant: A multicenter study

How might Low Carb and Ketogenic Diets affect the Progression of Chronic Kidney Disease?

Background: Obesity, an ever-increasing cause for deaths in the American population, often leads to complications such as Type II Diabetes Mellitus. Both obesity and diabetes predispose to renal disease, which can be ameliorated by treatment of both disorders. Ketogenic and Low Carb diets (KD/LCD) can lower blood sugar of T2DM patients and accelerate weight loss. Diet is a potential factor in slowing the rate of decline in kidney function. Yet, high diet acid loads, as from keto acid, may promote renal damage. Here, we evaluate existing studies on the benefits or harms of KD/LCD on factors associated with renal disease progression. 
 Methods: Reviews and analysis of existing studies on chronic kidney disease and Ketogenic diets. We analyzed eGFR, the measure of the rate of change in decline of renal function to infer the effects of Ketogenic and Low Carb diets.
 Results: Nine of the 22 papers reviewed were analyzed. Studies included from 18 to 1797 participants and included healthy subjects, those with diabetes and /or obesity, and those with normal renal function or moderate kidney failure (eGRF ranged from 94 ± 12 mL/min/ to 40 ml/min/1.73m2). Study duration ranged from 5 weeks to 6 years. Several studies demonstrated improvements, including decreases in serum creatinine, urinary albumin, weight loss, and eGFR.
 Conclusions: Renal function improved in shorter studies of diabetics who demonstrated weight loss. Longer studies or those in nondiabetics demonstrated no change in renal function.

Ambient particulate matter and renal function decline in people with HIV/AIDS.

We aimed to explore the effect of particulate matter exposure on renal function in people with HIV/AIDS (PWHA). A total of 37 739 repeated measurements were conducted on eGFR levels, serum creatinine (Scr), and the triglyceride-glucose (TyG) index in 6958 PWHAs. The relationship between 1 and 28 day moving averages of particulate matter concentrations with Scr and eGFR was assessed using linear mixed-effects models. Modified Poisson regression models were employed to assess the associations of cumulative particulate matter exposure with the incidence of chronic kidney disease (CKD). Mediation analyses were used to examine the role of TyG index. Short-term exposure to particulate matter was related to reduced renal function. The strongest associations between exposure to particulate matter (PM) 1 , PM 2.5 , and PM 10 and percentage changes in eGFR were observed at 7-day moving average exposure windows, with a respective decrease of 0.697% (-1.008%, -0.386%), 0.429% (-0.637%, -0.220%), and 0.373% (-0.581%, -0.164%) per IQR increment. Long-term exposure to PM 1 , PM 2.5 , and PM 10 was positively linked with the incidence of CKD, with each IQR increment corresponding to fully adjusted RRs (95% CIs) of 1.631 (1.446-1.839), 1.599 (1.431-1.787), and 1.903 (1.665-2.175), respectively. TyG index-mediated 8.87, 8.88, and 7.58% of the relationship between cumulative exposure to PM 1 , PM 2.5 , and PM 10 and increased risk of CKD, respectively. Exposure to particulate matter among PWHAs is linked to reduced renal function, potentially contributing to increased CKD incidence, where the TyG index might serve as a partial mediator.

Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.

Longitudinal changes in renal function in patients with chronic hepatitis B on antiviral treatment.

Patients with chronic hepatitis B (CHB) on nucleos(t)ide analogues (NUCs) often experience renal function decline. Conflicting results regarding the impact of NUC use and renal function have recently been reported. To examine longitudinal changes in renal function according to the NUC treatment type compared with untreated patients METHODS: From 2014 to 2022, we retrospectively analysed 10,642 patients with CHB. The primary outcome was chronic kidney disease (CKD) progression, which was defined as a minimum one-stage elevation. We applied propensity score (PS) matching for outcome comparisons. In the PS-matched cohort of 1996 pairs, the NUC-treated group (7.6/100 person-years [PYs]) had a significantly higher CKD progression risk than the untreated group (4.4/100 PYs), with a hazard ratio (HR) of 1.70 (p < 0.001). The tenofovir disoproxil fumarate (TDF)-treated group (7.9/100 PYs) showed a 1.76-fold increased CKD progression risk compared with the untreated group (4.5/100 PYs) in the PS-matched cohort (p < 0.001). Both the entecavir- and tenofovir alafenamide (TAF)-treated groups showed CKD progression risks comparable to those of the untreated group in the PS-matched cohorts of 755 and 426 pairs, respectively (p = 0.132 and p = 0.120, respectively). No significant CKD progression risk was found between the entecavir- (6.0/100 PYs) and TAF-treated (5.2/100 PYs) groups in the PS-matched cohort of 510 pairs (p = 0.118). NUC-treated patients, especially those on TDF, faced a higher CKD progression risk than untreated patients. Entecavir- and TAF-treated patients had comparable CKD progression risks to untreated patients. No difference was observed between entecavir and TAF in the risk of CKD progression.

Tweak/Fn14 system is involved in rhabdomyolysis-induced acute kidney injury

BackgroundRhabdomyolysis is a severe clinical syndrome associated to acute kidney injury (AKI) and chronic kidney disease (CKD). TWEAK/Fn14 signaling axis regulates renal inflammation and tubular cell death. However, the functional role of TWEAK/Fn14 in rhabdomyolysis remains unknown. MethodsRhabdomyolysis was induced in wild-type, TWEAK- and Fn14-deficient mice or mice treated with TWEAK blocking antibody. Renal injury, inflammation, fibrosis and cell death were assessed. Additionally, we performed in vivo and in vitro studies to explore the possible signalling pathways involved in Fn14 regulation. FindingsFn14 renal expression was increased in mice with rhabdomyolysis, correlating with decline of renal function. Mechanistically, myoglobin (Mb) induced Fn14 expression via ERK and p38 pathway, whereas Nrf2 activation diminished Mb-mediated Fn14 upregulation in cultured renal cells. TWEAK or Fn14 genetic depletion ameliorated rhabdomyolysis-associated loss of renal function, histological damage, tubular cell death, inflammation, and expression of both tubular and endothelial injury markers. Deficiency of TWEAK or Fn14 also decreased long-term renal inflammation and fibrosis in mice with rhabdomyolysis. Finally, pharmacological treatment with a blocking TWEAK antibody diminished the expression of acute renal injury markers and cell death and lessened residual kidney fibrosis and chronic inflammation in rhabdomyolysis. InterpretationTWEAK/Fn14 axis participates in the pathogenesis of rhabdomyolysis-AKI and subsequent AKI-CKD transition. Blockade of this signaling pathway may represent a promising therapeutic strategy for reducing rhabdomyolysis-mediated renal injury. FundingSpanish Ministry of Science and Innovation, ISCIII and Junta de Andalucía.

Chemoradiotherapy treatment with gemcitabine improves renal function in locally advanced cervical cancer patients with renal dysfunction

BackgroundCervical cancer (CC) in Mexico is diagnosed mainly in locally advanced (LACC) and advanced (ACC) stages, where ureteral obstruction is more frequent. The standard treatment for this population is concurrent chemoradiotherapy (CCRT) with cisplatin, which is nephrotoxic and could lead to further deterioration of renal function in LACC patients with renal function decline. We aimed to evaluate the effect of CCRT with Gemcitabine on renal function in LACC patients. MethodsThis retrospective study included LACC patients treated with CCRT with Gemcitabine as a radiosensitizer from February 2003 to December 2018. Data were collected from medical archives and electronic records. We assessed renal function before and after CCRT treatment and analyzed the patient's response to treatment and survival. Results351 LACC patients treated were included and stratified into two groups: 198 with Glomerular Filtration Rate (GFR) ≥60ml/min (group A) and 153 with GFR<60ml/min (group B). An improvement in GFR was observed after CCRT in patients in group B, from 33 ml/min to 57.5 ml/min (p<0.001). Complete response was observed in 64.1% of patients in Group A and 43.8% in Group B (p<0.0001). Factors associated with increased risk of death included having a GFR of 15-29 ml/min (HR: 2.17; 1.08-4.35), having GFR<15 ml/min (HR: 3.08; 1.63-5.79), and receiving Boost treatment (HR: 2.09; 1.18-3.69). On the other hand, receiving brachytherapy is a positive predictor for OS (HR:0.51; 0.31-0.84). ConclusionCCRT with gemcitabine is an appropriate treatment option for patients diagnosed with LACC who present impaired renal function due to the disease's obstructive nature or other comorbidities.

Intracellular tacrolimus concentration correlates with impaired renal function through regulation of the IS-AHR-ABC transporter in peripheral blood mononuclear cells

BackgroundsTacrolimus (TAC) concentration in peripheral blood mononuclear cells (PBMCs) is regarded as a better predictor of its immunosuppressive effect than the TAC concentration in whole blood. However, whether the exposure of TAC in PBMCs or WB was altered in post-transplant recipients with renal impairment remains unclear. MethodsWe investigated the relationship of trough TAC concentration in WB and PBMCs with renal functions in post-transplant recipients. The pharmacokinetic profiles of TAC in PBMCs and WB in the two chronic kidney disease (CKD) rat models were examined using UPLC-MS/MS. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to analyze the expression of proteins and mRNAs related to TAC metabolism and transport, respectively. In addition, the effects of uremic toxins on human PBMCs were investigated using whole-transcriptome sequencing (RNA sequencing [RNA-seq]). ResultsWe observed a decrease in the trough TAC concentration in PBMCs in the recipients with estimated glomerular filtration rate (eGFR) < 90 mL/min, compared with those of recipients with eGFR > 90 mL/min, but there was no difference in blood based on TAC concentrations (C0Blood). In a 150-patient post-transplant cohort, no significant relationship was observed between PBMCs and WB concentrations of TAC, and the eGFR value was correlated with TAC C0PBMCs but not with TAC C0Blood. In two CKD rat models, the TAC pharmacokinetic profile in the PBMCs was significantly lower than that in the control group; however, the blood TAC pharmacokinetic profiles in the two groups were similar. Transcriptome results showed that co-incubation of human PBMCs with uremic toxins upregulated the expression of AHR, ABCB1, and ABCC2. Compared to control rats, plasma IS increased by 1.93- and 2.26-fold and the expression of AHR, P-gp, and MRP2 in PBMCs was higher in AD and 5/6 nephrectomy (NX) rats, without modifying the expression of other proteins related to TAC exposure. ConclusionThe pharmacokinetics of TAC in PBMCs changed with a decline in renal function. Uremic toxins accumulate during renal insufficiency, which activates AHR, upregulates the expression of P-gp and MRP2, and affects their intracellular concentrations. Our findings suggest that monitoring TAC concentrations in PBMCs is more important than monitoring WB concentrations in post-transplant recipients with renal impairment.

Inflammation and renal function decline in chronic coronary syndrome: a prospective multicenter cohort study

BackgroundRenal function decline is a frequently encountered complication in patients with chronic coronary syndrome. Aside from traditional cardiovascular risk factors, the inflammatory burden emerged as the novel phenotype that compromised renal prognosis in such population.MethodsA cohort with chronic coronary syndrome was enrolled to investigate the association between inflammatory status and renal dysfunction. Levels of inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor-α (TNF-α), adiponectin, matrix metalloproteinase-9, interleukin-6, lipoprotein-associated phospholipase A2, were assessed. Renal event was defined as > 25% decline in estimated glomerular filtration rate (eGFR). Inflammatory scores were calculated based on the aggregate of hs-CRP, TNF-α, and adiponectin levels.ResultsAmong the 850 enrolled subjects, 145 patients sustained a renal event during an averaged 3.5 years follow-up. Multivariate analysis with Cox regression suggested elevations in hs-CRP, TNF-α, and adiponectin levels were independent risk factors for the occurrence of a renal event. Whereas, Kaplan-Meier curve illustrated significant correlation between high TNF-α (P = 0.005), adiponectin (P < 0.001), but not hs-CRP (P = 0.092), and eGFR decline. The aggregative effect of these biomarkers was also distinctly correlated with renal events (score 2: P = 0.042; score 3: P < 0.001).ConclusionsInflammatory burden was associated with eGFR decline in patients with chronic coronary syndrome.

Hypericum perforatum L. protects against renal function decline in ovariectomy rat model by regulating expressions of NOS3 and AKT1 in AGE-RAGE pathway

BackgroundHypericum perforatum L. (HPL) is a potential traditional Chinese medicine. It could promotes menopausal 'kidney-yin deficiency syndrome' that characterized by renal function decline. However, its potential pharmacological effect and mechanism remains unknown. ObjectiveThe aim of this study was to investigate whether HPL can improve menopausal renal function decline and to explore its mechanism of action. MethodsThe mainly ingredients of HPL were identified using UPLC-Q-TOF-MS/MS approach, and the potential therapeutic targets of HPL for renal function decline were chose via network pharmacology technique. The key therapeutic metabolites were selected through non-targeted metabolomic and chemometric methods. Then, the network were constructed and the key targets and metabolites were screened. At last, the validation experiments and mechanism exploring were adopted by using Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting assays. Resultsmainly ingredients of HPL were identified and determined 17 compounds and 29 targets were chose as mainly active compounds and potential therapeutic targets. Based on OVX induced renal decline rat model, after chemometric analysis, 59 endo-metabolites were selected as key therapeutic metabolites, and AGE-RAGE signal pathway in diabetes complications was enriched as the key pathway. By constructing a "disease-component-target" network, Hyperoside, Quercetrin, and quinic were selected as the key therapeutic compounds, and the AKT1 and NOS3 were selected as the key therapeutic targets. The results of ELISA, RT-PCR and western blot experiments indicated that HPL could rescue the abnormal expressions both of AKT1 and NOS3, as well as their related metabolites distortion. ConclusionOur findings indicated that HPL regulated expression of AKT1 and NOS3 through modulating AGE-RAGE signaling pathway in OVX stimulated rats` renal dysfunction, implicating the potential values of HPL in menopause syndromes therapy.

Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular outcomes in patients with atrial fibrillation and type 2 diabetes mellitus

Abstract Background A sodium-glucose cotransporter-2 inhibitor (SGLT2i) improves clinical outcomes in patients with type 2 diabetes (T2DM) and cardiovascular disease. Also use of SGLT2i was associated with a reduction of atrial fibrillation (AF) burden. We investigated the effect of SGLT2is on clinical outcomes in patients with T2DM and AF. Methods This was a retrospective study using a clinical data warehouse (CDW) constructed from 7 medical centers. We analyzed 11,043 patients with AF and T2DM. The patients were classified to the SGLT2i group and the control group according to the SGLT2i use. We performed 1:2 propensity score matching analysis. The primary endpoint was a composite of all-cause death or hospitalization due to heart failure events. The secondary endpoints were acute myocardial infarction, stroke, renal function decline and an initiation of dialysis. Results The propensity score matched population consisted of 467 patients in the SGLT2i group and 848 patients in the control group. During a mean follow up of 31.8 (± 21.0) months, the incidence of the primary endpoint was significantly lower in the SGLT2i group (9.6% vs. 16.9%, hazard ratio [HR] 0.624 [0.446 – 0.873]). SGLT2i was associated with reduced all-cause death (HR 0.292 [0.144 – 0.591]) and non-significantly lower risk of heart failure hospitalization (HR 0.734 [0.509 – 1.060]). There was no significant difference in the incidence of myocardial infarction, ischemic stroke, renal function decline and an initiation of dialysis between the two groups. In multivariate analysis, age, renal dysfunction, prior heart failure, and the absence of SGLT2i were independent predictors for the worse outcome. Conclusion SGLT2 inhibitor was associated with a lower incidence of all-cause mortality or heart failure hospitalization in patients with AF and T2DM.Freedom from the primary endpoint in the

Short and long-term renal function changes with direct oral anticoagulants in elderly patients with atrial fibrillation

Abstract Background Atrial Fibrillation (AF) and chronic kidney disease (CKD) frequently coexist in elderly patient. Previous evidence showed that vitamin K antagonists (VKAs) may be associated with an accelerated decrease of estimated glomerular filtration rate (eGFR) compared to direct oral anticoagulants (DOACs). However, there is little evidence on DOACs in the elderly population and in real life settings; the evidence available to us comes from randomized clinical trials with younger populations. Purpose The main objective of this study was to investigate the medium to long term renal function changes in older AF patients treated with DOACs and VKAs. Methods Enrolled patients underwent 3 eGFR measurements during follow-up, and the between arms difference in eGFR lost over time was investigated by 1) the Linear Mixed Models (LMM) and 2) group-based trajectory model (GBTM) analyses. Analysis was done according to short-term (3.2 years) and long-term follow-up (6.7 years). During the study period 420 enrolled AF patients (77.0±6.0 years, 136 on VKAs and 284 on DOACs) underwent 1260 eGFR assessments. Results After a median follow-up of 4.9 years, in the whole sample eGFR decreased from 67.4±18.2 ml/min/1.73 m2 to 47.1±14.3 ml/min/1.73 m2, p&amp;lt;0.001. Patients on DOACs experienced a significantly lower eGFR decrease that those treated with VKAs (-21.3% vs -45.1%, p&amp;lt;0.001). The benefit of DOACs compared with VKAs was evident both in the short term (eGFR decline -6.6 (95% CI: -9.1 to -4.0) ml/min/1.73 m2 vs -19.9 (95% CI: -23.6 to -16.2) ml/min/1.73 m2 respectively) and in the long-term, (eGFR -13.5 (95% CI: -16.1 to -11.0) ml/min/1.73 m2 in DOACs group vs -34.2 (95% CI: -37.9 to -30.5) ml/min/1.73 m2), respectively). After stratifying our study population into 5 groups according to trajectories of renal function decline, from the first (lowest decline in eGFR) to the fifth (greatest decline in eGFR), the first trajectory consisted of 80% patients on DOACs therapy. Logistic regression showed that the group on DOACs therapy was 3.03- to 4.24-fold more likely to belong to the trajectory with less eGFR decline than the VKAs group. Conclusions In conclusion, DOACs were associated with less long term decline in renal function in elderly patients with AF compared with VKAs.

Impact of worsening renal function in patients with incident heart failure across the spectrum of ejection fraction: a population-based longitudinal study

Abstract Background Renal dysfunction is a common occurrence in patients with heart failure (HF) and may impact on HF treatment and outcomes. HF clinical trial data suggest that worsening renal function (WRF) is associated with worse prognosis, however many of the medications used in HF cause a short-term decline in renal function that may improve in the longer-term. The real-world incidence and implications of WRF following an initial diagnosis of HF across the spectrum of ejection have not been well-characterised. Purpose The present study was designed to establish the incidence and outcomes associated with WRF in patients with incident HF on the risk of mortality and HF hospitalisation (hHF) in a real-world setting. Methods Electronic health records were linked to echocardiography data between 2016 to 2021 to define incident HF with reduced/mildly reduced/preserved EF (HFrEF/HFmrEF/HFpEF). Incidence of WRF at 6 months was determined as a composite endpoint of (i) having two consecutive eGFR declined by 40% or greater; (ii) having an eGFR &amp;lt;15 mL/min/1.73m^2; (iii) on sustained dialysis; or (iv) receiving kidney transplantation. Incidence of hHF and all-cause mortality were compared in HF patients with versus without WRF. We performed a stratified analysis according to baseline renal function (eGFR: &amp;gt;60, 45-59, 30-44, 15-29, or &amp;lt;15 mL/min/1.73m2). Results 4254 individuals were identified, 1100 HFrEF, 650 HFmrEF, 1252 HFpEF, and 1252 HF with unknown EF. Within 6 months of HF diagnosis, 592 patients died and 349 had WRF. Baseline eGFR &amp;lt;60 was present in 32% of individuals with HFrEF, 32% in HFpEF, 27% in HFmrEF, and 37% in HF with unknown EF. The incidence of WRF was similar in HFrEF (20.7 [95% CI: 16.9 – 25.1] per 100 person-years) and in HF with unknown EF (20.9 [17.1 – 25.3]), but was significantly lower in HFmrEF (13.6 [9.8 – 18.4]) and HFpEF (16.8 [13.7 – 20.5]). Patients with WRF were more likely to be female (adjusted hazard ratio [aHR]: 1.32 [1.06 – 1.64], p=0.014), having diabetes (1.34 [1.07 – 1.69], p = 0.012), and with lower baseline renal function (eGFR categories 45-59, 30-44, 15-29, or &amp;lt;15 compared with &amp;gt;60: aHR 1.75 [1.29 – 2.38], p&amp;lt;0.001; 1.64 [1.12 – 2.42], p=0.012; 5.65 [4.06 – 7.87], p&amp;lt;0.001; 90.74 [63.2 – 130.28], p&amp;lt;0.001). Individuals with WRF had significantly higher incidence of subsequent hHF (HR adjusted for age, sex, baseline renal function, and diabetes: 1.79 [1.35 – 2.39], p&amp;lt;0.001) and all-cause death (2.18 [1.66 – 2.88], p&amp;lt;0.001), compared to those without WRF. This was driven by patients diagnosed with HFrEF (2.46 [1.45 – 4.18], p&amp;lt;0.001) or HFpEF (3.45 [2.21 – 5.40], p&amp;lt;0.001), but was not seen in HFmrEF (1.91 [0.91 – 3.99], p=0.086) or HF within unknown EF (1.28 [0.65 – 2.52], p=0.484). Conclusion WRF is an important and common consequence following initial diagnosis of HF across the spectrum of EF with associated severe clinical outcomes in HF. Priority should be given to prevention of WRF in patients with incident HF.Impact of WRF on Clinical Outcomes

Real world data on adopting guideline directed medical therapy post 2021 ESC HF guidelines and effect on renal function

Abstract Introduction This single-centre cohort study aims to compare the use of guideline-directed medical therapies (GDMT) before and after the 2021 ESC HF guidelines and the effect on renal function. There has been good adoption of these guidelines worldwide following the publication in 2021. We know HF patients will have less decline in renal function when GDMT is better optimised. This study aims to compare renal function on admission (adm) and discharge (dc) following acute heart failure admission. Methods Our database is composed of 460 patients with AHF admitted to our HF unit from 01/08/2020 till 31/07/2022inclusive. We divided this group into two; Group A was composed of 187 patients from August 2020 to Aug 2021(pre-ESC guidelines) and Group B included 273 patients from August 2021 to Aug 2022 (post-ESC guidelines). We compared the number of patients initiated on the 4 pillars of HF medication on admission and discharge. Both groups were analysed based on their ejection fraction (HFrEF, HFmrEF and HFpEF). Baseline parameters were were similar between the two groups. We analyzed eGFR (mL/min) on admission (adm), eGFR on discharge (dc), K+ (mmol/l) on dc and the 8 medications for HFrEF and HFmrEF. We also reviewed three medications for HFpEF. Results Group A (Aug 2020-Aug 2021): HFrEF patients had an average eGFR of 52.4 on adm and 47,0 at dc, average K+ was 4.34 on dc. HFmrEF subgroup had an average eGFR of 48.8 on adm and 45.4 at dc, average K+ was 4.23 on dc. HFpEF subgroup had an average eGFR of 51.2 on adm and 44.2 at dc, average K+ was 4.24 on dc. Group B (Aug 2021-Aug 2022): HFrEF patients had an average eGFR of 53.5 on adm and 50.7 dc, average K+ was 4.38 on dc. HFmrEF subgroup had an average eGFR of 49.4 on adm and 47.0 at dc, average K+ was 4.34 on dc. HFpEF subgroup had an average eGFR of 45.9 on adm and 41.7 at dc, average K+ was 4.35 on dc. Group A and B comparison (Table1): In Group A, HFrEF patients had a drop of eGFR of 5.4 between adm and dc. However, HFrEF patients in Group B, where they had their GDMT optimized, had an eGFR drop of only 2.8 (less by 2.6). In Group A, HFmrEF patients had an eGFR drop of 3.4 in comparison to HFmrEF patients in Group B where eGFR dropped by 2.4 (less by 1.0). In Group A, HFpEF subgroup had an eGFR drop of 7.0 versus Group B HFpEF where eGFR dropped by 4.2 only (less by 2.8). Despite better GDMT in group B, K+ was comparable to group A. Conclusions Patients with AHF managed in the HF Unit have better optimization of GDMT post 2021 HF ESC guidelines. In Group B, all patient subgroups (HFrEF; HFmrEF and HFpEF) in the year following publication of the ESC HF guidelines had a reduced decline in eGFR i.e. less worsening of renal function despite higher dose and a greater percentage of patients on the 4 pillars of GDMT. This study demonstrates that renal function of patients admitted with AHF is better preserved with optimization of GMDT during their admission.MEDICATIONS (GDMT)RENAL FUNCTION