Diabetes Chronic Kidney Disease Research Articles

Distribution of Traditional Chinese Medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study.

To analyze the distribution of Traditional Chinese medicine (TCM) syndromes in patients with diabetic kidney disease (DKD) and its related factors. We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical Center, Chinese PLA General Hospital from April 2020 to August 2021. Analysis of their TCM syndromes and related factors was carried out. The 435 patients included 109, 117, 86, and 123 chronic kidney disease (CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome, and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend; the differences were statistically significant (P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio (OR) = 1.022, P = 0.005], albumin (OR = 1.058, P = 0.006), and estimated glomerular filtration rate (eGFR) (OR = 1.020, P < 0.001) but negatively correlated with male sex (OR = 0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin (OR = 1.056, P < 0.001) and eGFR (OR = 1.008, P = 0.022) but negatively correlated with age (OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age (OR = 1.028, P = 0.021) and glycosylated hemoglobin (OR = 1.223, P = 0.007) but negatively correlated with total cholesterol (OR = 0.792, P = 0.006). Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin (OR = 0.977, P < 0.001), albumin (OR = 0.891, P < 0.001), and eGFR (OR = 0.978, P < 0.001) but positively correlated with high density lipoprotein (OR = 3.376, P = 0.001). With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both Qi and Yin, liver-kidney Yin, and spleen-kidney Yang deficiency syndromes. TCM syndromes were correlated with laboratory test results.

2024 update in heart failure.

In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4mg once weekly administered for 1year decreased body weight and significantly improved quality of life and the 6min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article.

Effect of Avenciguat on Albuminuria in Patients with CKD: Two Randomized Placebo-Controlled Trials.

Avenciguat is a novel, potent soluble guanylate cyclase activator in development for CKD. Two trials investigated avenciguat in diabetic (NCT04750577) and non-diabetic (NCT04736628) CKD. A prespecified pooled analysis of two randomized, double-blind, placebo-controlled trials of identical design. Adults with CKD (eGFR ≥20 and <90 mL/min/1.73 m2, urine albumin-to-creatinine ratio [UACR] ≥200 and <3500 mg/g) were randomized to 20 weeks of placebo or avenciguat 1, 2, or 3 mg three times daily (TID; adjunctive to angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker. Primary endpoint: change from baseline in UACR in 10-hour urine at week 20, analyzed per protocol. Secondary endpoint: UACR change from baseline in first morning void urine at week 20. Safety was monitored throughout. Overall 500 patients (mean age 62 years [SD 13]; mean eGFR 44 mL/min/1.73 m2 [SD 18] and median 10-hour UACR 719 [interquartile range 379-1285] mg/g ) received placebo (n=122) or avenciguat 1 mg (n=125), 2 mg (n=126), or 3 mg (n=127) TID. All 243 patients in study one and 27/261 patients in study two had diabetes. Avenciguat 1, 2, and 3 mg TID reduced UACR in 10-hour and first morning void urine versus placebo throughout the treatment period. At week 20, placebo-corrected geometric mean changes (95% confidence interval) from baseline in UACR in 10-hour urine with avenciguat 1, 2, and 3 mg TID were -15.5% (-26.4, -3.0), -13.2% (-24.6, -0.1), and -21.5% (-31.7, -9.8), respectively, analyzed per protocol. Corresponding changes in first morning void urine were -19.4% (-30.0, -7.3), -15.5% (-26.9, -2.5), and -23.4% (-33.5, -11.8), respectively. Avenciguat was well tolerated, overall frequency of adverse events was low and similar to placebo. The number of patients who discontinued study drug due to adverse events with avenciguat 1, 2, and 3 mg TID were 5 (4%), 11 (9%), and 11 (9%), respectively, compared with 4 (3%) in the placebo group. Avenciguat lowered albuminuria, and was well tolerated in patients with CKD.

#2660 WWP2-induced pericytes to myofibroblast transition contributes to the progression of fibrosis in CKD in diabetes

Abstract Background and Aims CKD in diabetes can be characterized by different clinical and histological phenotypes, associated to different molecular pathways specifically involved in the progression of kidney disease. CKD in diabetes includes different phenotypes, commonly classified according to Mazzucco et al (PMID:11920336) as diabetic Nephropathy (DN), non-diabetic renal disease (NDRD) and mixed forms (DN+NDRD). Among these, DN represents the primary cause of end stage renal disease (ESRD) and our group demonstrated that renal damage in DN is characterized by a specific molecular feature, represented by the activation of lysine63 (K63)-ubiquitination (Ub) pathway. In particular, we demonstrated that accumulation of K63-Ub proteins is involved in the progression of renal fibrosis (PMID: 27881486). WWP2 is an E3 ubiquitin-protein ligase that modulates myofibroblast pro-fibrotic activation in cardiac fibrosis (PMID: 31399586), however its specific role in kidney fibrosis in diabetes and its subsequent involvement in K63-Ub pathway has not been described so far. Thus aim of this study was to evaluate the involvement of WWP2 in the progression of kidney fibrosis in diabetes and its involvement in K63-Ub pathway. Method WWP2, K-63Ub, alpha-sma and PDGFbeta-receptor expression were evaluated in: i) 22 kidney biopsies from patients with a biopsy proven diagnosis of DN (n = 11), NDRD (n = 6) and CKD without diabetes (n = 5), by immunohistochemistry and immunofluorescence; ii) streptozotocin (STZ)-treated DBA/2J mice, a model of human DN, in the presence or absence of a specific inhibitor of K63Ub (NSC697923) by immunohistochemistry (n = 3 for each group); iii) in HK2 tubular cells, EAHY926 endothelial cells and in human-derived pericytes under hyperglycemic conditions by western blotting and qPCR. Results Immunohistochemistry showed that WWP2 was expressed both in CKD and in DN patients’ biopsies when compared to patients with NDRD (p &amp;lt; 0.05 and p &amp;lt; 0.01 respectively), both at tubular, glomerular and in the vascular compartment. Immunofluorescence confirmed that WWP2 increased expression in DN patients compared to NDRD, was associated to accumulation of K63Ub proteins in the tubular compartment as well as in the vascular compartment in particular in pericytes, cells that envelop the surface of vessels and have been described as the major source of scar-forming myofibroblasts in CKD (PMID: 19008372). The involvement of WWP2 in the K63-Ub pathway was confirmed in vivo in DBA2J diabetic mice in which the specific inhibition by NSC697923 of the K63Ub pathway, significantly reduced WWP2 expression in kidney tissues from diabetic mice (p &amp;lt; 0.05). These results were confirmed in vitro where specific inhibition of K63Ub pathway by NSC697923 significantly reduced hyperglycaemia-induced WWP2 expression in HK2 cells by western blotting and qPCR (p &amp;lt; 0.01). Hyperglycaemic conditions did not influence WWP2 expression in EAHY926 endothelial cells (p = n.s.). Conversely, using qPCR, in pericytes we observed an hyperglycemia-induced expression of both WWP2 levels (RR&amp;gt;2) and alpha-sma levels (RR&amp;gt;3) at different time points. Moreover, western blotting showed that hyperglycemia also induced a decrease of PDGF-beta-receptor marker of pericytes, thus suggesting their transition to myofibroblasts. Conclusion These findings demonstrate the influence of WWP2 on the k63-Ub pathway thus driving fibrogenesis in DN patients, in particular through pericyte to myofibroblast transition. WWP2 could represent a potential novel target for therapeutic intervention in the treatment of chronic kidney disease in diabetes.

#3115 Effectiveness of SGLT2 inhibitors in patients with glomerulonephritis: a single center experience

Abstract Background and Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become widely used in recent years because of favorable outcomes on kidney function in people with diabetes mellitus and chronic kidney disease (CKD). The main effect of SGLT2 inhibitors is inhibiting sodium and glucose reabsorption, acting precisely in the early proximal tubule of the renal nephron. Although these drugs developed as glucose-lowering agents for their capability to induce glycosuria, cardiovascular outcome studies found that the reduction in kidney function was significantly delayed, and the incidence of severe decline in kidney function was reduced in patients taking SGLT2 inhibitors. Later on, these outcomes were confirmed by the results of the DAPA-CKD, EMPA-KIDNEY, and CREDENCE studies, which were specific outcome trials in patients with CKD. However, data about the use of SGLT2 inhibitors in patients with glomerulonephritis at routine clinical practice are still limited. The purpose of this study is to investigate the impact of SGLT2 inhibitors use in patients with glomerulonephritis. Method Patients diagnosed with biopsy-proven GN who continued their routine follow-up in Etlik City Hospital nephrology clinic were retrospectively examined. Patients with a steroid treatment history for GN were excluded from this study. We identified 29 patients who were treated with SGLT2 inhibitors for proteinuria. We analyzed the baseline characteristics, comorbidities, GN types, and laboratory parameters (baseline, sixth and twelfth months at the follow-up). Each patient was matched to the control with a similar baseline feature under conservative therapy (n = 29). Both patient groups were treated in line with the KDIGO glomerulonephritis guideline and were received RAAS blockers at the maximum tolerated dose. According to baseline levels, the reduction rate in proteinuria and eGFR of the sixth and twelfth months were calculated as percentages. The study was performed in accordance with the Declaration of Helsinki. The local ethical committee approved the study design. Results Our study involved 58 patients diagnosed with 32 (55%) IgA nephropathy, 16 (28%) with membranous nephropathy, and 10 (17%) with focal segmental glomerulosclerosis. In the treatment group, 23 (79%) patients used dapagliflozin, and 6 (21%) used empagliflozin as SGLT2 inhibitors. Baseline proteinuria levels at [1940 (1780-2700 mg/d) vs. 1890 (1670-2400 mg/d); p = 0.8], eGFRs [60 (44-82) vs. 64 (46-80) ml/min/1.73 m2; p = 0.8] and serum albumin levels (39.6 ± 0.3 vs. 39.1 ± 0.2; p = 0.4) were similar between both groups. The proteinuria reduction rate in the sixth month was 34% (27.3-40.5) for the treatment group and 12% (6.9-20.7) for the control group (&amp;lt;0.0001). Besides, the reduction rate was still higher in the treatment group at the 12th month [50.5% (39-52.6) vs. 26.3% (17.2-35.4); p ≤ 0.0001]. eGFR declining rate at 6th months and 12th months were lower in SGLT2 group than the control group [3.1% (0-6.2) vs. 8.6% (4.1-16.6); p = 0.004 and 0.8% (0-5) vs. 5.9% (3.3-15.2); 0.005, respectively] (Table 1). Proteinuria levels at 6th months were 1170 (970-1890) mg/d and 1730 (1180-2100) mg/d for treatment and control group, respectively. At 12th months, median proteinuria level of SGLT2 group was 940 (840-1480) mg/d and control group was 1250 (1120- 2040) mg/d (Fig. 1). Conclusion In this study with a well-matched control group, we found that SGLT2 inhibitors demonstrate efficacy in mitigating the decline in estimated GFR and reducing albuminuria in patients with GN. However, randomized-controlled trials are still required specific to patients with GN.

#1756 Development and internal validation of machine learning algorithms for mortality prediction model of people with DM and CKD

Abstract Background and Aims Diabetes Mellitus (DM) and Chronic Kidney Disease (CKD) are leading causes of morbidity and mortality, presenting challenges in patient management. The aim of this study is to develop a machine learning-based predictive model for mortality in DM and CKD patients, improving early intervention and treatment personalization. Method 3,637 participants with DM and CKD from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 were included. All-cause mortality was ascertained by linkage to National Death Index records through 31 December 2019 in NHANES. The dataset included clinical profiles, demographic details, and laboratory results of patients with DM and CKD. We performed 100 random groupings, dividing the data into a 75% training set and a 25% validation set each time. We then visualized the results of 100 AUC measurements using a boxplot. The objective was to forecast patient survival over 1, 3, 5, and 10-year horizons using a variety of machine learning algorithms. The algorithms tested included Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), K-Nearest Neighbors (KNN), Gaussian Naive Bayes (GNB), Multinomial Naive Bayes (MNB), Bayesian Network Classifier (BNC), AdaBoost (Ada), Gradient Boosting (Gradient), and Extreme Gradient Boosting (XG). The performance of each algorithm was evaluated based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC), with the results visualized in boxplot format. Results Upon result shown as the boxplots, it becomes evident that the Random Forest (RF) algorithm consistently exhibits one of the highest AUCs on average across all prediction intervals, suggesting a strong and stable predictive capacity. In the 1-year survival prediction, the RF algorithm demonstrates a highest AUC, implying consistent performance. The 3 and 5-year predictions reveal a slight dip in AUC for most models, including RF, but it still remains one of the top-performing algorithms with fewer outliers than XG and Gradient Boosting. The mean AUC of RF is particularly noteworthy at the 10-year mark, where most algorithms struggle with prediction accuracy, as indicated by lower median AUCs and greater variability. Notably, the RF algorithm identified six major factors for 1-year survival prediction: systolic blood pressure, uric acid, blood urea nitrogen, lactate dehydrogenase, lymphocyte count and total cholesterol, as well as three major factors for 10-year survival prediction: age, lymphocyte and gamma-glutamyl transferase. Conclusion Overall, the study indicates that while machine learning can be a powerful tool for survival prediction in patients with DM and CKD, the choice of algorithm is crucial, with RF standing out for its consistent and reliable performance.

#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&amp;lt;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&amp;lt;0.01) as in the expression of mRNA in PBCs (2.1 ± 1.26 vs. 1.87 ± 1.16 a.u.; p&amp;lt;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&amp;lt;0.0001), while it showed a positive association with ACR (r=0.416, p&amp;lt;0.001) and, interestingly, with proinflammatory cytokines including circulating TNFα (r=0.44, p&amp;lt;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&amp;lt;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.

#2500 Renal perfusion and SGLT2i

Abstract Background and Aims Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) have revolutionized treatment of type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), improving cardiovascular and renal endpoints. This improvement could be due to a decrease in renal perfusion (RP), attenuating glomerular hyperfiltration thus leading to kidney protection. This has been demonstrated in patients with type 1 diabetes and in animal studies, but not in patients with DM2 and it has never before been investigated in patients with CKD. Our aim was to examine the effects of the SGLT2i empagliflozin on RP in patients with DM2, DM2 and CKD and non-diabetic CKD, respectively. Methods We conducted three randomized, double-blind placebo controlled cross-over studies, including patients with: Participants were randomized to four weeks' treatment with empagliflozin 10 mg or matching placebo and were, after a washout period of at least two weeks, crossed over to four weeks of the opposite treatment. At the end of each treatment period we measured RP using 82Rb-PET/CT and standardized GFR using 99mTc-DTPA-clearence. We also measured 24-hour ambulatory blood pressure (BP), urinary albumin/creatinine ratio (UACR) and Hb1Ac. Results A total of 49 patients completed the studies, 16 in the DM2-group, 17 in the DM2-CKD-group and 16 in the CKD-group. In the combined study-population empagliflozin reduced RP compared to placebo by 4% (geometric mean ratio: 0.96, 95% CI: 0.94; 0.99, p = 0.0171). This change was most pronounced in the DM2-CKD-group, with a reduction of 6% (geometric mean ratio: 0.94, 95% CI: 0.91; 0.97), p &amp;lt; 0.001). There was a decrease of 4% in the DM2-group and 1% in the CKD-group, though these changes were not statistically significant (p = 0.29 and 0.72, respectively, see Fig. 1). In the 29 patients with a UACR &amp;gt; 30 mg/g, empagliflozin treatment led to a significant decrease in UACR in the combined study-population (geometric mean ratio: 0.61, 95% CI: 0.46; 0.80, p = 0.001), again primarily driven by a decrease in the DM2-CKD-group (geometric mean ratio: 0.51, 95% CI: 0.31; 0.85, p = 0.014), with non-significant decreases in the remaining groups. Empagliflozin decreased standardized GFR and BP in the combined population as well as in all sub-groups, while we found no change in Hb1Ac. For further details, see Table 1. Conclusion Short-term empagliflozin treatment reduces RP, GFR, BP and albumin excretion. Relative changes in RP and UACR were most pronounced in patients with concomitant DM2 and CKD, whereas changes in BP and GFR were seen in all groups.

#995 Effectiveness of Semaglutide once weekly as add-on to SGLT-2Is in T2DM and CKD: a single-center observational study with body composition assessment

Abstract Background and Aims To explore body composition and metabolic profile changes in type 2 diabetes mellitus and chronic kidney disease (T2DM-CKD) using Semaglutide added to sodium-glucose transporter 2 inhibitors (SGLT-2Is). Method The study was performed on patients with T2DM-CKD in West China Hospital of Sichuan University. The outcomes were changes in body composition and metabolic profile after 6 months among patients administrated Semaglutide based on SGLT-2Is (Semaglutide plus SGLT-2Is group) and the comparison with patients only administrated SGLT-2Is (SGLT-2Is group). Results 12 individuals with T2DM-CKD and BMI ≥28 kg/m2 were included in two groups, respectively. After 6 months, total fat mass was reduced by 0.9 kg (IQR −3.73, 0.4) vs. 0.7 kg (IQR −1.9, −0.37) with Semaglutide plus SGLT-2Is group and SGLT-2Is group (P = 0.908). Skeletal muscle mass was reduced by 0.97 kg (SD 0.86) vs. 0.5 kg (SD 0.93), respectively (P = 0.215). ACR (229.55 mg/g (IQR −389.7, −119.92) vs. 0.5 mg/g (IQR −104.6, 84.9), P = 0.032), HbA1c (−0.35% (IQR −0.85, 0) vs. 0.3% (IQR 0.15, 1.1), P = 0.024) and total cholesterol (−0.51 mmol/L (SD 1.1) vs. 0.75 mmol/L (SD 0.93), P = 0.015) significantly declined in Semaglutide plus SGLT-2Is group compared to SGLT-2Is group. Conclusion Semaglutide plus SGLT-2Is did not exacerbate muscle loss compared with SGLT-2Is alone in obese patients with T2DM-CKD, and improved glucolipid metabolism and albuminuria.

#2595 Evolution of hemoglobin and serum uric acid levels after SGLT2i initiation in patients with and without diabetic nephropathy

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are glucose-lowering drugs that inhibit glucose reabsorption in the proximal tubule, enhancing urinary glucose excretion. SGLT2i exhibit significant cardio- and renoprotective effects due to their capacity to increase diuresis and weight loss and reduce intraglomerular and blood pressure. Moreover, recent studies have described the potential of SGLT2i to improve additional cardiovascular risk factors, such as anemia or hyperuricemia. In this study, we aimed to describe the evolution of hemoglobin (Hb) and serum uric acid (SUA) levels in CKD patients with and without diabetic nephropathy before and after the initiation of SGLT2i therapy. Method CKD patients with and without diabetic nephropathy that were followed in the outpatient clinic of a tertiary referral academic hospital during January 2020 to September 2023 and that started SGLT2i therapy during that period were randomly recruited in the study. Patient characteristics, CKD staging, and levels of Hb and SUA before and after SGLT2i initiation were compared between groups. Hb and SUA levels were averaged considering all available laboratory controls during the last 12 months before treatment initiation and any available controls after treatment start. Results Demographic and clinical characteristics of enrolled patients are summarized in Fig. 1. Subjects with diabetic nephropathy were significantly older, more commonly hypertensive, presented worse kidney function, had received SGLT2i for a lengthier time and had lower hemoglobin values. We observed no change in hemoglobin levels after the initiation of SGLT2i in our sample, independently of diabetic nephropathy status or CKD stage (Fig. 2A, C). In contrast, SUA levels decreased significantly both in patients with and without diabetic nephropathy (Fig. 2B). This effect was observed across all the spectrum of CKD in our sample (Fig. 2D). Conclusion In our sample, SGLT2i initiation was associated with a significant decrease in SUA levels, both in patients with and without diabetic nephropathy and independently of CKD stage, which may help to explain its cardio- and nephroprotective effects. No change in Hb levels was observed, possibly due to a low prevalence of anaemia in our sample.

#2426 Diabetes treatment in CKD patients—do we treat according to the guidelines?

Abstract Background and Aims T2DM is a global pandemic, frequently complicated by DKD, that may result in ESRD and cardiovascular complications. Despite advancements in diabetes and cardiovascular risk management, the prevalence of DKD continues to grow. During the last years SGLT2i and GLP1RAs have demonstrated effectiveness in cardiorenal protection. The 2020 KDIGO guidelines recommend these treatments for cardiorenal protection in DKD patients. No data was published on the rate of implementing these guidelines. Identifying a gap between the guidelines and the actual treatment given to patients allows active intervention to enhance adherence to the guidelines and may improve health outcomes of patients. The aim of the study was to assess KDIGO guidelines implementation by nephrologists in a nephrology clinic, compared to a multidisciplinary diabetes-CKD clinic. This team includes a nephrologist, diabetologist, diabetes nurse and dietitian. The focus is on lifestyle modification education and advanced treatments for DKD. Method This study is a retrospective, descriptive, and quantitative convenience sample at a single medical centre. Study population included adult patients over 18 years, with T2DM and CKD, who were treated at the nephrology and diabetes-CKD clinics between May 2021 and May 2022. Type 1 diabetic patients and patients requiring dialysis were excluded. Demographic, diabetes and CKD related data were collected. Utilization of KDIGO recommended medications was analysed and compared between the two clinics. Results 587 and 100 patients from nephrology and diabetes-CKD clinics, respectively, were included. Baseline characteristics are described in Table 1. Recommended anti diabetic and other CKD treatments utilization is described in Table 2. Implementation of recommended medications, including SGLT2i and GLP1RAs, was significantly higher in the diabetes-CKD clinic, demonstrating a significant disparity in guideline adherence between the two clinics. Conclusion DKD is a common complication of T2DM that may progress to ESRD, and associated with increased cardiovascular risk. The evolving landscape of treatment is reflected in updated guidelines from various professional organizations, including KDIGO. These guidelines position SGLT2i and GLP1RAs as 1st and 2nd line treatments for patients with T2DM and CKD. Patients treated at the diabetes-CKD clinic were younger, had higher incidence of dyslipidemia and IHD and their diabetes was less controlled compared to the nephrology clinic patients. Despite the guidelines, underuse of recommended antidiabetic medications and other treatments persists in nephrology clinics. However, the multidisciplinary approach of the diabetes-CKD clinic, showed improved adherence to guidelines. In conclusion, the study provides insights into the challenges of implementing KDIGO guidelines in real world nephrology clinical settings. Further research is warranted to understand factors contributing to the low adherence. The findings suggest that a multidisciplinary approach may enhance guideline compliance and subsequently improve outcomes in managing DKD in T2DM.

#3004 Serum miRNAs as novel biomarkers and modulators of rapidly progressing chronic kidney disease in patients with diabetes

Abstract Background and Aims Chronic kidney disease (CKD) is very common in diabetes, occurring in around 40% of patients. Without treatment, CKD can lead to end stage renal disease (ESRD), which requires costly dialysis and transplantation. Current treatments aim to prevent CKD or slow down its progression to ESRD. The speed of CKD progression is patient-specific, and at present there are no biomarkers which can predict which patient with diabetes will develop CKD; level of albuminuria is an important but variably reliable biomarker of speed of CKD progression. The current methods for rapid identification of patients prone to accelerated CKD progression are limited, as they are based on measuring estimated glomerular filtration rate (eGFR) over prolonged periods of time, as well as albuminuria. Therefore, there is a clinical need for novel biomarkers that can predict early potential rapid CKD progression in patients. The aim of this project is to determine whether serum microRNAs (miRs) can be used as biomarkers to predict the speed of CKD progression in diabetes patients, and to identify potential treatment targets associated with such dysregulated miRs. Method miRs were isolated from sera of 34 patients with type 2 diabetes classed with either slow or fast progressing CKD by their eGFR (n = 17; obtained from the Salford Kidney Study sample collection). Several miRs were found to be significantly dysregulated in fast progressing patients by using Next Generation Sequencing (NGS) of miRs in individual serum samples. An additional 49 diabetic CKD patient serum samples (slow (n = 29) or fast progressors (n = 20)) were used to validate the potential miR biomarker panel by qPCR. Results The NGS miR analysis of the initial 34 CKD patient sera produced a panel of 16 miRs that were either significantly upregulated or downregulated in the fast-progressing patients compared to slow progressors. The qPCR validation of this initial panel in 49 additional CKD patient serum samples demonstrated that 6 miRs were significantly upregulated in the fast-progressing patients. The levels of these miRs correlated with demographic and clinical parameters. ROC curve analysis revealed that the individual predictive power of each of those 6 miRs to define either a slow or fast progressing CKD patient was between 63-75%. Determination of a miR combination the strongest predictive power is ongoing. Conclusion A potential biomarker panel of 6 miRs has been identified and validated by qPCR, with each miR having a predictive power of between 63-75% for fast progression of CKD. A panel of miRs that could accurately predict progression speed of CKD patients could lead to faster and earlier diagnosis of patients to enable better treatment. Work is ongoing to explore the predictive power of this miR biomarker panel, and potential novel therapeutic targets to prevent CKD or delay its progression to ESRD.

MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials.

Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.

Identification of renal protective gut microbiome derived-metabolites in diabetic chronic kidney disease: An integrated approach using network pharmacology and molecular docking

Metabolites from the gut microbiota define molecules in the gut-kidney cross talks. However, the mechanistic pathway by which the kidneys actively sense gut metabolites and their impact on diabetic chronic kidney disease (DCKD) remains unclear. This study is an attempt to investigate the gut microbiome metabolites, their host targeting genes, and their mechanistic action against DCKD.Gut microbiome, metabolites, and host targets were extracted from the gutMgene database and metabolites from the PubChem database. DCKD targets were identified from DisGeNET, GeneCard, NCBI, and OMIM databases. Computational examination such as protein–protein interaction networks, enrichment pathway, identification of metabolites for potential targets using molecular docking, hubgene-microbes-metabolite-samplesource-substrate (HMMSS) network architecture were executed using Network analyst, ShinyGo, GeneMania, Cytoscape, Autodock tools. There were 574 microbial metabolites, 2861 DCKD targets, and 222 microbes targeting host genes. After screening, we obtained 27 final targets, which are used for computational examination. From enrichment analysis, we found NF-ΚB1, AKT1, EGFR, JUN, and RELA as the main regulators in the DCKD development through mitogen activated protein kinase (MAPK) pathway signalling. The (HMMSS) network analysis found F.prausnitzi, B.adolescentis,and B.distasonisprobiotic bacteriafound in the intestinal epithelium, colonic region, metabolize the substrates like tryptophan, other unknown substrates might have direct interaction with the NF-kB1 and epidermal growth factor receptor (EGFR) targets. Docking of these target proteins with 3- Indole propionic acid (IPA) showed high binding energy affinity.From this study we identified, the 3 IPA produced byF. prausnitzi A2-165was found to have renal sensing properties inhibiting MAPK/NF-KB1 inflammatory pathway and would be useful in treating CKD in diabetics.

Factors influencing optimal diabetes care and clinical outcomes in Thai patients with type 2 diabetes mellitus: a multilevel modelling analysis

BackgroundIncreasing levels of poor glycaemic control among Thai patients with type 2 diabetes mellitus (T2DM) motivated us to compare T2DM care between urban and suburban primary care units (PCUs), to...

Retrospective Study on the Efficacy and Safety of Dulaglutide in Patients with Diabetes and Moderate-Advanced Chronic Kidney Disease

Retrospective Study on the Efficacy and Safety of Dulaglutide in Patients with Diabetes and Moderate-Advanced Chronic Kidney Disease

Comparative Cardiovascular Risks of Febuxostat and Allopurinol in Patients with Diabetes Mellitus and Chronic Kidney Disease

Comparative Cardiovascular Risks of Febuxostat and Allopurinol in Patients with Diabetes Mellitus and Chronic Kidney Disease

SGLT-2 Inhibitors: Focus on Dapagliflozin.

Dapagliflozin (trade name FARXIGA) is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor that has transcended its initial antidiabetic application to demonstrate benefits in cardiac and renal diseases. It was first approved by the food and department administration for type 2 diabetes in 2014. Since then, it has gained food and department administration approval for chronic kidney disease in 2021, heart failure with reduced ejection fraction in 2020, and heart failure with preserved ejection fraction in 2023. Thus, dapagliflozin plays a pivotal role in improving patient outcomes. By competitive binding to renal SGLT-2 cotransporters, dapagliflozin effectively prevents glucose and sodium reabsorption, leading to glucosuria. Its pharmacokinetic profile involves minimal cytochrome P450-induced metabolism, rapid absorption with an 18-hour duration of action, and stable effects. Clinical trials have revealed dapagliflozin's efficacy in glycemic control without the risk of hypoglycemia, making it an advantageous choice for patients insufficiently managed on other antidiabetic drugs. Comparative analysis with other SGLT-2 inhibitors suggests dapagliflozin's potential superiority in preventing heart failure. Compared to empagliflozin, it has more extended effects, contributing to stable sodium diuresis, reduced blood pressure fluctuations, and potentially lower cardiovascular disease risks. However, it leads to less urinary glucose excretion compared with canagliflozin. Dapagliflozin has specific contraindications, such as type 1 diabetes and end-stage chronic kidney disease. Adverse effects include an increased risk of genital infections, urinary tract infections, and Fournier's gangrene. A nuanced understanding of dapagliflozin's benefits and limitations is imperative for informed clinical decision-making in the management of diabetes and its complications.

Sodium-Glucose Cotransporter 2 Inhibitors for Chronic Kidney Disease: A Comprehensive Review

Chronic Kidney Disease (CKD) is a major global health burden. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated potential in slowing CKD progression. We evaluated the expanding role of SGLT2 inhibitors, emphasizing their renoprotective benefits in diabetic and non-diabetic CKD patients. We also investigated the underlying mechanisms, including the reduction of glomerular hypertension via modulation of tubuloglomerular feedback. Our study critically analyzed current indications for SGLT2 inhibitor therapy based on recent clinical trial data. To optimize patient outcomes, we present a comprehensive analysis of practical considerations for the prescription of SGLT2 inhibitors, including the potential initial decline in the estimated glomerular filtration rate and a review of adverse events.

Incidence of acute kidney injury in patients with acute ischaemic stroke undergoing CT angiography (CTA) and CT perfusion (CTP): a systematic review and meta-analysis

Background and purposeWe conducted a systematic review and meta-analysis to assess the incidence of acute kidney injury (AKI) in patients undergoing CT angiography (CTA) and CT perfusion (CTP) for acute...