Risk Of Progression Research Articles

Identification of Prodromal Parkinson Disease: We May Be Able to But Should We?

Parkinson disease (PD) remains a progressive and incurable disease. Research over the past decade provides strong evidence of a detectible phase before the clinical diagnosis, known as the prodromal phase of PD (pPD). In this article, we review the debate about disclosure of risk of progression to PD and related disorders to individuals through the perspectives of the pillars of medical ethics: beneficence, nonmaleficence, autonomy, and justice. There is evidence that lifestyle modification may have positive effects on onset and progression of PD, providing justification of potential benefit. From a societal perspective, a diagnosis of pPD could allow targeted recruitment to disease-modifying trials. Regarding nonmaleficence, direct evidence that catastrophic reactions are scarce is largely derived from studies of monogenic conditions, which may not be generalizable. Diagnosis of PD can be traumatic, and appropriate communication and evaluation of circumstances to weigh up disclosure is crucial. Future research should therefore examine the potential harms of early and of false-positive diagnoses and specifically examine these matters in diverse populations. Autonomy balances the right to know and the right not to know, so an individualized patient-centered approach and shared decision-making is essential, acknowledging that knowledge of being in the prodromal phase could prolong autonomy in the longer term. Distributive justice brings focus toward health care and related planning at the individual and societal level and affects the search for disease modification in PD. We must acknowledge that waiting for established disease states is likely to be too little, too late and results in failures of expensive trials and wasted participant and researcher effort. Ultimately, clinicians must arrive at a decision with the patient that solicits and integrates patients' goals, taking into account their individual life circumstances, perspectives, and philosophies, recognizing that one size cannot fit all.

Elevated subgingival temperature infers high bacterial pathogen counts in severe periodontitis.

Periodontal inflammation may be assessed by bleeding on probing and subgingival temperature. This pilot study evaluated the intrapatient relationship between subgingival temperature and selected bacterial groups/species in deep periodontal pockets with bleeding on probing. In each of eightadults, an electronic temperature probe identified three"hot" pockets with elevated subgingival temperature and three"cool" pockets with normal subgingival temperature among premolars/molars with 6‒10 mm probing depths and bleeding on probing. Microbial samples collected separately from the hot and cool periodontal pockets were cultured for selected periodontal pathogens. Hot compared to cool periodontal pockets revealed significantly higher absolute and normalized subgingival temperatures and yielded higher mean proportions of Porphyromonas gingivalis (10.2% for hot vs. 2.5% for cool, p = 0.030) and total red/orange complex periodontal pathogens (48.0% for hot vs. 24.6% for cool, p = 0.012). Hot versus cool deep periodontal pockets harbored significantly higher levels of major periodontal pathogens. Subgingival temperature measurements may potentially be useful to assess risk of periodontitis progression and the efficacy of periodontal therapy.

Prospective evaluation of patients with non-cirrhotic portal hypertension: A single centre study.

Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. We aimed to evaluate disease progression and outcomes in NCPH. Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.

Vaginal Rhabdomyosarcome: Case Report

Introduction: Rhabdomyosarcoma is a soft tissue sarcoma, most common in children, localised in the female genital tract and therefore rare in adults. Among its subtypes, it is most often distinguished as embryonal. It is an aggressive tumour, difficult to diagnose, is usually detected by CT or MRI and the diagnosis is confirmed by biopsy and treatment involving surgical excision, radiotherapy and chemotherapy. The authors present a case of embryonal rhabdomyosarcoma localised in the vagina, highlighting relevant aspects of the subject. Observation: We report the observation of a girl aged 2 years and 8 months, with no notable antecedents, from a 2nd degree consanguineous marriage. For 1 month she presented with a rapidly progressive vaginal mass associated with bleeding. Examination revealed a reddish, grape-like mass in the vulva. Abdomino-pelvic ultrasound revealed a vaginal tumour, abdomino-pelvic MRI revealed an endovaginal mass delivered through the vulva, suggesting a botryoid rhabdomyosarcoma, and biopsy of the vaginal mass with morphological appearance and immunohistochemical profile of an embryonal rhabdomyosarcoma. The extension work-up showed a vulvovaginal lesional process, with no secondary location on the thoraco-abdominal CT scan. The patient was classified as group C according to the RMS 2005 protocol and received 6 courses of IVA + vaginal brachytherapy + 3 courses of IVA with a good clinical and biological evolution. Conclusion: In view of the diagnostic difficulties and the risk of progression and rapid worsening of rhabdomyosarcoma, early positive diagnosis means that treatment can be started at an early stage with chemotherapy, surgery and radiotherapy.

Parkinson's disease with hyposmia and dysautonomia: does it represent a distinct subtype?

Olfactory dysfunction or dysautonomia is one of the earliest prodromal nonmotor symptoms of Parkinson's disease (PD). We aimed to investigate whether PD patients with dysautonomia and hyposmia at the de novo stage present different prognoses regarding PD dementia (PDD) conversion, motor complication development, and change in levodopa-equivalent doses (LED). In this retrograde cohort study, we included 105 patients with newly diagnosed PD patients who underwent cross-cultural smell identification test (CC-SIT), autonomic function tests (AFT), and dopamine transporter (DAT) scan at the de novo stage. PD patients were divided into Hyposmia + /Dysautonomia + (H + /D +) and Hyposmia - /Dysautonomia - (H - /D -) groups depending on the result of AFT and CC-SIT. Baseline clinical, cognitive, imaging characteristics, longitudinal risks of PDD development and motor complication occurrence, and longitudinal LED changes were compared between the two groups. When compared with the H - /D - group, the H + /D + group showed lower standardized uptake value ratios in all subregions, lower asymmetry index, and steeper ventral - dorsal gradient in the DAT scan. The H + /D + group exhibited poorer performance in frontal/executive function and a higher risk of PDD development. The risk of motor complications including levodopa-induced dyskinesia, wearing off, and freezing of gait, was comparable between the two groups. The analysis of longitudinal changes in LED using a linear mixed model showed that the increase of LED in the H + /D + group was more rapid. Our results suggest that PD patients with dysautonomia and hyposmia at the de novo stage show a higher risk of PD dementia conversion and rapid progression of motor symptoms.

Fully-automated CT derived body composition analysis reveals sarcopenia in functioning adrenocortical carcinomas

Determination of body composition (the relative distribution of fat, muscle, and bone) has been used effectively to assess the risk of progression and overall clinical outcomes in different malignancies. Sarcopenia (loss of muscle mass) is especially associated with poor clinical outcomes in cancer. However, estimation of muscle mass through CT scan has been a cumbersome, manually intensive process requiring accurate contouring through dedicated personnel hours. Recently, fully automated technologies that can determine body composition in minutes have been developed and shown to be highly accurate in determining muscle, bone, and fat mass. We employed a fully automated technology, and analyzed images from a publicly available cancer imaging archive dataset (TCIA) and a tertiary academic center. The results show that adrenocortical carcinomas (ACC) have relatively sarcopenia compared to benign adrenal lesions. In addition, functional ACCs have accelerated sarcopenia compared to non-functional ACCs. Further longitudinal research might shed further light on the relationship between body component distribution and ACC prognosis, which will help us incorporate more nutritional strategies in cancer therapy.

Exploring the mechanism of cardiorenal protection with finerenone based on network pharmacology.

Large prospective trials have demonstrated that finerenone could reduce the risk of cardiovascular death and progression of renal failure among patients with chronic kidney disease (CKD) associated heart failure (HF) and/or type 2 diabetes mellitus (T2DM). The aim of this study was to explore the molecular mechanism of finerenone in the treatment of cardiorenal diseases through network pharmacology. The STITH, SwissTargetPrediction, PharmMapper, DrugBank and ChEMBL databases were used to screen the targets of finerenone. The diseases-related targets were retrieved from the DisGeNET, GeneCards, CTD, OMIM and MalaCards databases. The protein-protein interaction (PPI) network was conducted with STRING database and Cytoscape software. The clusterProfiler R package was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The interactions of key targets and finerenone were analyzed by molecular docking in Autodock software. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. Histopathology of myocardial and renal tissues were observed by hematoxylin-eosin (HE) staining, and detection of protein expressions was conducted using western blotting. A total of 111 potential cardiorenal targets of finerenone were identified. The main mechanisms of action may be associated with lipid and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications and diabetic cardiomyopathy. The hub targets demonstrated by the PPI network were CASP3, ALB, MMP9, EGFR, ANXA5, IGF1, SRC, TNFRSF1A, IL2 and PPARG, and the docking results suggested that finerenone could bind to these targets with high affinities. HE staining revealed the cardiorenal protection of finerenone on diabetic mice. In addition, the protein expressions of CASP3 and EGFR were increased while ALB was decreased in myocardial and renal tissues in diabetic mice compared with control mice, which were reversed by finerenone. This study suggested that finerenone exerts cardiorenal benefits through multiple targets and pathways.

Ventricular arrhythmia burden during different physical activities in patients with arrhythmogenic right ventricular cardiomyopathy: preliminary analysis

Abstract Background Patients suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC) should avoid intense endurance exercise to reduce the risk of adverse cardiac events and disease progression. While an active lifestyle would be preferable to a sedentary one, evidence for safe levels of physical activity in ARVC, however, is scarce. Purpose This study aimed to describe the ventricular arrhythmia burden experienced during exercise and immediate recovery - estimated as the prevalence of premature ventricular contractions (PVC) - of different exercise modalities and intensities on ARVC patients. Methods This preliminary analysis includes four (1F, 33±12 yrs, BMI 24±4 kg/m2) ARVC patients harboring a pathogenic plakophilin-2 variant and carrying an implantable cardioverter-defibrillator that performed different exercises while monitored via 12-lead ECG. The order of modalities was randomized and participants instructed to stop when surpassing perceived exertion of 15 on the Borg 6-20 scale. Resistance exercises included two-legged squats and single arm biceps curls (20 repetitions and 2 min duration). Endurance exercise included 5 min of treadmill walking and 3-min cycling bouts at heart rates (HR) of 80, 100 and 120 bpm, as well as cycling at 120 bpm with 2 additional min of active cool down. Blood lactate concentration was assessed after each cycling bout. Results No adverse cardiac event or early termination for medical reasons occurred. Figure 1 summarizes the relationship between HR, perceived exertion and PVC burden. During walking (HR 76 ± 8 bpm), PVC burden was 11 ± 6% (range 4 – 18%). Cycling at 82 ± 4 bpm induced a PVC burden of 7 ± 5% (range 3 – 14%), which increased to 13 ± 8% (range 3 – 21%) at 93 ± 2 bpm and increased further to 16 ± 16% (range 7 – 37%) at 105 ± 3 bpm. In all three intensities the PVC burden was higher in the first 3 min of recovery than during the activity itself. Adding a 2-min active cool down increased the PVC burden to 25 ± 16% (range 6 – 45%). 2-legged squats (HR 101 ± 15 bpm) had a PVC burden of 9 ± 12%, which increased to 19 ± 14% at recovery. One arm biceps curls (HR 75 ± 13 bpm) had a PVC burden of 4 ± 3% during the activity and 9 ± 5% during recovery. Perception of effort varied widely when cycling at 80 bpm (range 6 – 12) or 100 bpm (range 8 – 14), but less so at 120 bpm (range 13 – 15). Blood lactate concentration when cycling at 120 bpm ranged between 2.2 and 3.5 mmol/L, typically associated with exercise in the "heavy" intensity domain. Conclusions PVC burden was high and seemingly intensity-dependent during exercise and immediate recovery. The wide range of PVC burden for physiological or subjective markers of effort call for personalized recommendations on physical activity. Exercises with small muscle mass such as biceps curls seem to minimize the PVC burden, thus, training the different muscles separately could be an interesting avenue to maintain physical fitness in ARVC patients.

Value of basal HV Interval prior TAVR as predictor of permanent pacemaker implantation

Abstract Background/Introduction Transfemoral aortic valve replacement (TAVR) is an effective and safe treatment for severe aortic stenosis (SAoS) even in low risk patients (1,2). As population ages, the volume of TAVR procedure increases and although improvements in technology and technique, new onset persistent disturbances in the electrocardiogram (ECG) are present up to 34,8% of patients at hospital discharge(3) and the secondary need of permanent pacemaker implantation (PPM) remains high, being of 4-24% with balloon-expanding valves (BEV) and 14.7-26.7% with self-expanding valves (SEV)(3). According to ESC guidelines, an electrophyisiologic study (EPS) centered in HV interval measure with a cutoff of ≥70ms is a useful tool to assess the risk of progression to high auriculoventricular block (HAVB) in specific groups with persistent ECG abnormalities to consider PPM(4-5), but this only applies in post TAVR scenario. Measuring HV interval at the intervention day prior procedure could help optimize and assess risk for PPM post TAVR. Purpose To measure basal HV interval prior TAVR and correlate it to risk of PPM implantation before discharge and 30 days after discharge. Methods Single-center prospective cohort study, patients with SAoS scheduled for TAVR, sinus rhythm at intervention day, without PPM or history of PPM indication were included. At time of TAVR, a tetrapolar catheter was placed at the septal aspect of tricuspid valve. A mobile polygraph was used to measure ECG parameters and HV interval before TAVR. Then, tetrapolar catheter was advanced to ventricle to perform rapid stimulation as part of habitual valve implantation protocol. After procedure, a rhythm monitorization for &amp;gt;48-72 hrs, was made to decide, PPM, HV interval measure or clinical daily ECG vigilance with posterior discharge was performed. A 30-day post discharge follow up was expected. Results 38 patients were enrolled, median age 83.5 ± 5.5 years, 23 females (60,5%). 37 patients had SEV implanted and 1 patient had BEV implanted. Median HV interval was 54.4ms. 18 patients (47.4%) had a mild abnormal HV interval, of whom 11 had a narrow QRS. Post TAVR procedure, 15 patients (39.5%) persisted with "de novo" LBB at discharge. 5 women and 7 men, had PPM implanted before discharge. 1 woman was implanted 6 days after discharge due to HAVB (66ms HV interval prior TAVR). In a multivariate analysis including sex, age, PR, QRS and HV interval &amp;gt;55ms, the RR (IC 95% 1.9-70.3) risk of PPM was 13.42 folds higher (p=0.008). At a bivariate quantitative HV analysis, a higher HV period persisted significantly related to PPM outcome (p=0.001). Conclusions In our study population, a pre-existing mild to moderate prolongation of HV interval prior TAVR substantially elevates the risk of requiring PPM before discharge. 61.1% of these basal mild prolongation HV interval patients had a narrow QRS prior TAVR.HV measure prior TAVR in narrow QRSTable 1

Metformin: Therapeutic profile in the treatment of type 2 diabetes.

Metformin (dimethyl-biguanide) can claim its origins in the use of Galega officinalis as a plant treatment for symptoms ascribed to diabetes. Since the first clinical use of metformin as a glucose-lowering agent in 1957, this medicine has emerged as a first-line pharmacological option to support lifestyle interventions in the management of type 2 diabetes (T2D). It acts through multiple cellular pathways, principally in the gut, liver and muscle, to counter insulin resistance and lower blood glucose without weight gain or risk of overt hypoglycaemia. Other effects include improvements in lipid metabolism, decreased inflammation and lower long-term cardiovascular risk. Metformin is conveniently combined with other diabetes medications, can be prescribed in prediabetes to reduce the risk of progression to T2D, and is used in some regions to assist glycaemic control in pregnancy. Consistent with its diversity of actions, established safety profile and cost-effectiveness, metformin is being assessed for further possible clinical applications. The use of metformin requires adequate renal function for drug elimination, and may cause initial gastrointestinal side effects, which can be moderated by taking with meals or using an extended-release formulation. Thus, metformin serves as a valuable therapeutic resource for use throughout the natural history of T2D.

#2610 Low skeletal muscle mass and low skeletal muscle quality are associated with thoracic aorta calcification in dialysis patients

Abstract Background and Aims Cardiovascular disease (CVD) is the leading cause of mortality in dialysis patients. Thoracic aorta calcification (TAC) is a common cardiovascular complication in dialysis patients and is independently associated with CVD. Sarcopenia, particularly low skeletal muscle mass, has been found to be associated with increased cardiovascular risk in dialysis patients. This study aims to explore the relationship between skeletal muscle quality and skeletal muscle mass at the first lumbar vertebra (L1) level determined by opportunistic CT scans (chest CT) and TAC, with the goal of providing valuable opportunities for identifying and intervening in high-risk CVD patients. Method We included 2514 patients for cross-sectional analysis, who underwent dialysis in four centers in China from 2020 to 2023 and all had chest CT scans including the L1 level. Additionally, we conducted a follow-up study on TAC in patients who initiated dialysis between 2014 and 2019 as part of the earlier research, including 215 patients who had undergone at least two chest CT scans for cohort analysis. At the L1 level, we assessed skeletal muscle quality [by skeletal muscle density (SMD), HU] and skeletal muscle mass [by skeletal muscle index (SMI), cm2/m2] in dialysis patients. Measurements of thoracic aorta calcification scores (TACS) and calcification scores for three segments of the thoracic aorta, including ascending aorta calcification score (ATACS), aortic arch calcification score (AoACS), and descending thoracic aorta calcification score (DTACS), were obtained in dialysis patients. Patients were divided based on their annual calcification score growth rate: those with a rate greater than or equal to the average annual increase were classified into the rapid progression group, while those with a rate less than the average were classified into the slow progression group (including those with no progression). Multivariable linear regression models were employed to assess the relationships between SMI and SMD with TACS. Multivariable logistic regression models were used to evaluate the associations of SMl and SMD with the risk of rapid progression of TACS. Results The mean (SD) age of participants was 56 (15) years, with 58.2% being male. The prevalence of TAC was 82.2%, while the prevalence of ascending thoracic aorta calcification (ATAC), aortic arch calcification (AoAC), and descending thoracic aorta calcification (DTAC) was 21.4%, 75.3%, and 68.8%, respectively. Over an average follow-up period of 3.22 years, the progression rate of TAC was 85.6%. Comparing the highest quartile of SMD to the lowest quartile, a significant inverse association was observed with TAC (beta −1.19, 95% CI −1.55— −0.83; P &amp;lt; 0.001). Similarly, comparing the highest quartile of SMI to the lowest quartile, a significant inverse association was found with TAC (beta −0.59, 95% CI −0.92— −0.26; P = 0.001). SMI and SMD, as continuous variables, were both significantly negatively correlated with TAC. Higher SMD was associated with a reduced risk of rapid progression of TAC; after full adjustment, for every 1 SD increase in SMD, the risk of TAC rapid progression decreased by 46% (aOR 0.54, 95% CI 0.32—0.91; P = 0.021). SMI showed no significant association with the rapid progression of TAC. The associations of SMI and SMD with AoAC and DTAC were consistent with their associations with TAC, except for ATAC. The ROC curve analysis indicated that incorporating SMD into the model enhanced the discriminative ability for stratifying the risk of rapid progression of thoracic aorta calcification. Conclusion After adjusting for cardiovascular risk factors and inflammatory markers, higher skeletal muscle quality and higher skeletal muscle mass were significantly associated with lower TAC. Improving skeletal muscle quality in initial dialysis patients may reduce the risk of rapid TAC progression.

#900 Endotrophin is associated with long-term risk of kidney function decline in normoalbuminuric persons with type 2 diabetes in the Joslin Kidney Study

Abstract Background and Aims Endotrophin is a pro-fibrotic and pro-inflammatory molecule derived from the post-translational processing of type VI collagen. Evidence for an association of increased circulating levels of endotrophin with increased risk of kidney and cardiovascular-related outcome and all-cause mortality in persons with type 2 diabetes have recently emerged. Here we want to investigate endotrophin as an early marker of kidney-related outcome risk in persons with type 2 diabetes with normal levels of albuminuria. Method Endotrophin was measured using the nordicPRO-C6TM assay (Nordic Bioscience, Herlev, Denmark) in serum of 1088 individuals with type 2 diabetes from the Joslin Diabetes Study. 635 individuals had normal to mildly increased albuminuria (&amp;lt;30 mg/g), 379 had moderately increased albuminuria (30-300 mg/g) and 74 had severely increased albuminuria (&amp;gt;300 mg/g). All patients had eGFR &amp;gt;60 and where hence classified as CKD stage 1 and 2. Risk of kidney disease progression was defined as a 40% decline in eGFR within 10 years. Results In the cohort (n = 1088), a total of 128 patients progressed to 40% eGFR decline. High levels of circulating endotrophin were associated with an increased risk of kidney disease progression in unadjusted logistic regression analysis (OR for T3 vs T1+T2 (PRO-C6): 2.1 [95% CI: 1.4-3.0], p = 0.0001) and after adjustment for eGFR, HbA1c, age and sex (OR for T3 vs T1+T2 (PRO-C6): 1.8 [95% CI: 1.1-2.6], p = 0.005). When looking at patients classified in albuminuria stages, endotrophin was significantly associated with kidney disease progression in the individuals with normal to mildly increased albuminuria (39 events) (OR for T3 vs T1+T2 (PRO-C6): 2.6 [95% CI: 1.3-4.9], p = 0.005 in unadjusted analysis and 2.3 [95% CI: 1.1-4.5], p = 0.02 after adjustment for eGFR, HbA1c, age and sex, but it was not significantly associated to kidney progression in the groups with moderately (49 events) and severely (40 events) increased albuminuria. Conclusion This study sheds further light on the potential of endotrophin as an early marker of long-term adverse kidney outcome in persons with type 2 diabetes. The association of circulating endotrophin with increased risk of kidney disease progression had already been reported both in CKD and DKD patients (for shorter-term outcome), and this study further expands on the applicability of endotrophin as a biomarker in persons with type 2 diabetes without an overt kidney disease, who will nevertheless progress to develop CKD in a 10-year time horizon.

#150 Effect of dapagliflozin in patients with CKD depending on primary kidney disease

Abstract Background and Aims Multiple trials have reported that SGLT2 inhibitors reduce the risk of its primary composite outcome of kidney disease progression or cardiovascular death in a wide range of patients with CKD. Our aim was to compare effects on kidney outcomes among the different types of kidney diseases. Method Eligible patients with eGFRs ≥30-45, or ≥45-90 ml/min/1.73 m2 with a urinary albumin-to-creatinine ratio of ≥300 mg/g, and receiving renin angiotensin system inhibitor, where indicated and tolerated were randomized to dapagliflozin 10 mg once daily vs placebo. Kidney disease progression was defined as a sustained ≥30% eGFR decline from randomization or to &amp;lt;10 mL/min/1.73 m2, start of maintenance dialysis or receipt of a kidney transplant, or renal death, and the effects of dapagliflozin were analyzed using a pre-specified Cox model. Testing for heterogeneity of effect between pre-specified kidney disease subgroups was performed, including exploratory analyses by specific glomerular disease etiologies. Results 362 participants were followed for a median of 2.0 years. 90 (24.8%) had diabetic kidney disease, 126 (34.8%) had glomerular disease, 94 (26%) had hypertensive or renovascular disease, and 52 (14.4%) had other or unknown causes. Overall, dapagliflozin reduced the risk of kidney disease progression by 34% (dapagliflozin 29/178 vs placebo 48/184; hazard ratio 0.62, 95% CI 0.51-0.78). This relative risk reduction appeared broadly similar in subgroup analyses by primary cause of kidney disease and by different types of glomerular disease. Conclusion Our study with a few numbers of patients with diabetic and non-diabetic causes of CKD showed that dapagliflozin reduced risk of kidney disease progression with relative risk reductions that were broadly similar across the different CKD etiologies.

#594 Long-term risk of incident/progressive chronic kidney disease, or end-stage kidney disease post-acute kidney injury: systematic review, meta-analysis

Abstract Background and Aims Little is known about which patients to follow-up after an episode of acute kidney injury (AKI) for future risks. The aim of this review is to assess the association between AKI and the incidence or progression of chronic kidney disease (CKD) or end-stage kidney disease (ESKD), stratified by subcategories of AKI-stages, -durations, and clinical settings. Method A systematic search of the literature in PubMed and Embase was performed by two reviewers to identify studies that examined CKD incidence (development of CKD stage ≥3), CKD progression (worsening of kidney function in patients with CKD stage ≥3), or ESKD, in patients with AKI versus patients without AKI. The risk of bias was assessed using the Newcastle-Ottawa Scale. Relative effect estimates (odds and hazard ratios) were pooled using a random effects model. Results In total, 48 retrospective and 13 prospective studies, encompassing 140.985 patients with AKI, were included in this review. All the studies were of moderate or high quality. The pooled effect ratio was 3.36 (95% confidence interval (CI) 2.68-4.03) for CKD incidence (n = 31 studies). This remained 3.40 (95% CI 1.79-5.00) in a sub analysis including patients with a recovered kidney function post-AKI, and 1.49 (95% CI 1.44-1.55) in a sub analysis including patients with an AKI lasting less than 3 days (Fig. 1). Overall, the effect ratio for CKD progression (n = 11 studies) was 1.70 (95% CI 1.38-2.01) and 3.81 (95% CI 2.58-5.04) for ESKD (n = 24 studies). The increased risk of these two outcomes were not seen in the sub analyses only including patients with AKI lasting less than 3 days. Overall, there is an observable higher risk for CKD incidence, CKD progression, and ESKD with increased AKI staging, although not always statistically significant. Minimal variations were observed across clinical settings. Conclusion In our review, including over 60 studies, we found that AKI was associated with an increased risk of CKD incidence, CKD progression, and ESKD. Patients with higher AKI-stages had even larger risks. Notably, even brief episodes of AKI (lasting less than 3 days) were associated with a higher risk of CKD incidence compared to patients without AKI. In contrary, the risk for ESKD is not enlarged in a sub analysis including patients with recovered kidney function compared to patients without AKI. These result warrant close monitoring of the kidney function post-AKI, specifically in patients with AKI lasting 3 days or longer. Future research should focus more on the risk of CKD progression in order to tailor follow-up care in these more vulnerable patients.

#2679 Prediction of acute eGFR decline after first initiation of RASI inhibitors and its impact on clinical outcomes

Abstract Background and Aims The objective of this study is to investigate the correlation between acute eGFR (estimated glomerular filtration rate) decline after initiation of ACEI (angiotensin-converting enzyme inhibitor)/ARB (angiotensin receptor blocker) medications and clinical outcomes in a real-world setting. Additionally, we aim to establish a risk prediction model to identify high-risk individuals who are more likely to experience a rapid decline in eGFR after drug initiation. Method A total of 2026 adult new users of ACEI/ARB were selected from the China Renal Data System (CRDS). Patients in acute clinical states and those using nephrotoxic drugs were excluded, and it was required that patients had at least one creatinine measurement during the baseline period and one week to four weeks after drug initiation. Cox proportional hazards models were used to compare the relative risks of adverse long-term outcomes in patients with different degrees of acute eGFR decline. A multivariable logistic regression model was employed to analyze the factors influencing acute eGFR decline. Lasso regression was used to select predictive factors, resulting in a logistic regression model with 18 predictive factors. Results Among the 2026 patients, 1148 (57%), 473 (23%), and 405 (20%) experienced eGFR decline &amp;lt;5% or increase, 5-20% decline, and ≥20% decline, respectively, after initiation of RASI (renin-angiotensin system inhibitor). Following adjustment for multiple variables, an eGFR decline ≥20% was found to be associated with a higher risk of long-term renal disease progression, with a hazard ratio of 1.84 (95% confidence interval 1.19-2.85), but not significantly associated with an increased risk of all-cause mortality and cardiovascular events. Factors associated with an eGFR decline ≥20% after RASI initiation included higher BMI and Charlson index, more severe proteinuria, lower hemoglobin levels, presence of hypertension, diabetic nephropathy, arrhythmias, and concomitant use of thiazide diuretics or loop diuretics. The predictive model had a C-statistic of 0.75. Conclusion This study demonstrates that a short-term eGFR decline after RASI initiation is associated with a higher risk of long-term renal disease progression but not significantly associated with increased risks of all-cause mortality and cardiovascular events. We have developed a prediction model to estimate the risk of eGFR decline ≥20% after the initial use of RASI, which can aid clinicians in identifying patients with poorer renal outcomes following RASI initiation and facilitate timely intervention.

#1200 Coronary artery calcium modifies the relationship between blood pressure and adverse kidney outcome: results from KNOW-CKD

Abstract Background and Aims Previous studies evidenced that elevated coronary artery calcium (CAC) score is associated with higher chronic kidney disease (CKD) progression. However, the use of CAC score to guide CKD management has not been adequately evaluated. Here, we evaluated whether presence of CAC modify the association between systolic blood pressure (SBP) and CKD progression in patients with CKD. Method We analyzed 1693 participants with CKD stages G1 to G5 from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Key exclusion criteria were kidney failure with replacement therapy (KFRT) and missing data for CAC and SBP information. We categorized participants according to baseline SBP and CAC score (Controlled BP, SBP &amp;lt; 120 mmHg; Elevated BP without CAC, SBP 120-140 mmHg and CAC score = 0; Elevated BP with CAC, SBP 120-140 mmHg and CAC score &amp;gt;0; Uncontrolled BP, SBP &amp;gt;140 mmHg) and compared the CKD progression. The CKD progression was defined as a composite of halving eGFR from baseline value or onset of KFRT. Results During 10,023 person-years of follow-up (median 6.2 years), the composite outcome occurred in 689 (40.7%) participants, and 108 (6.4%) participants died among the KNOW-CKD participants. There was significant interaction between CAC score and SBP for CKD progression (P &amp;lt; 0.001). There were 181/568 (31.9%), 167/424 (39.4%), 128/314 (40.8%) 213/387 (55.0%), composite outcomes in controlled BP, elevated BP without CAC, elevated BP with CAC, uncontrolled BP group, respectively. In crude Cox regression, compared to controlled BP, elevated BP with CAC group showed similar CKD progression risk (Hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.95-1.44), whereas other strata group showed increased risk of CKD progression (elevated BP with CAC; HR, 1.59; 95% CI 1.31-1.94 and uncontrolled BP, HR, 1.94; 95% CI 1.56-2.41). Similar elevated risk in elevated BP with CAC was observed even after adjustment of age, sex, diabetes mellitus, estimated glomerular filtration ratio, and proteinuria (HR, 1.26; 95% CI, 1.02-1.56). However, the risk of CKD progression in elevated BP without CAC group was comparable to controlled BP group (HR, 1.20; 95% CI, 0.87-1.66). Conclusion Elevated SBP was more strongly associated with an increased risk of adverse kidney outcomes in patients with coronary calcification.

#2546 CKD-PC risk model for CKD progression: validation and association with outcomes in the FIDELITY population

Abstract Background and Aims The Chronic Kidney Disease Prognosis Consortium (CKD-PC) recently developed risk models to predict the 3-year risk of a ≥40% decrease in estimated glomerular filtration rate (eGFR) or to predict kidney failure in the general population. Unlike the kidney failure risk equation, the CKD-PC model is valid for all levels of eGFR (above and below 60 mL/min/1.73 m2) and includes chronic kidney disease (CKD) progression risk factors besides age, sex, eGFR and albuminuria; namely: systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, body mass index, glycated hemoglobin, insulin use, and oral diabetes medication use [1]. We evaluated whether the CKD-PC model, developed using electronic health record data, is valid for use in a contemporary clinical population using the FIDELITY pooled dataset from international randomized clinical trials of finerenone [2]. Additionally, to inform clinical practice, we evaluated the efficacy of finerenone using categories of 3-year CKD progression risk as predicted by the model. Method FIDELITY was an individual, patient-level, prespecified, pooled efficacy and safety analysis of the phase III FIDELIO-DKD and FIGARO-DKD trials of patients with CKD and type 2 diabetes (T2D), randomized 1:1 to finerenone or placebo. The 3-year CKD progression risk of these patients was predicted and the validity of the CKD-PC model was evaluated using area under the curve (AUC) score (with higher scores indicating better risk prediction), Brier score (lower scores indicating better prediction), and by calibration plots of observed versus predicted risk by deciles of 3-year CKD progression risk. To evaluate the efficacy of finerenone, 3-year risk was categorized in quartiles and the effect of finerenone versus placebo on a kidney composite outcome, defined as kidney failure, a sustained ≥40% decrease in eGFR from baseline over ≥4 weeks, or renal death, was assessed. Results The FIDELITY population comprised 13,026 individuals with a mean eGFR of 58 mL/min/1.73 m2 and urine albumin-to-creatinine ratio of 515 mg/g. The median follow-up was 3 years and there were 1849 total kidney outcome events. Of 12,968 patients analyzed, the median 3-year risk of kidney failure was 15% (Q1–Q3: 9–24%). Overall, the model demonstrated good discrimination to predict a ≥40% kidney composite outcome for patients with CKD and T2D in FIDELITY: AUC score 0.726 (95% confidence interval [CI] 0.712–0.739) and Brier score 0.100 (95% CI 0.097–0.103). The predicted 3-year risk was generally slightly higher than the observed risk (Fig. 1). Finerenone was effective in preventing CKD progression across the risk quartiles (p-interaction = 0.094) with a trend towards greater efficacy in the higher risk quartiles (3-year risk of CKD progression ≥10%) (Fig. 2). All risk groups showed benefit with finerenone compared to placebo regarding eGFR decline in the chronic phase. Conclusion The CKD-PC risk model for CKD progression performed well in a large global clinical trial population of patients with CKD and T2D. Finerenone was effective across the range of baseline risk of CKD progression.

#1534 Risk of CKD progression taken into account of metabolic changes

Abstract Background and Aims The purpose of this study was to study the relationship between metabolic syndrome and the risk of progression of CKD in a representative sample of patients who were hospitalized in the nephrology department of the 3rd clinic of the Tashkent Medical Academy and in the department of cardiology and interventional cardiology of the Russian National Medical Research and Medical Center. Method In the retrospective part of the study, 1000 case histories of patients with CKD who were inpatient treatment from 2013 to 2019 in the nephrology department of the 3rd clinic of the Tashkent Medical Academy and in the department of cardiology and interventional cardiology of the Russian National Medical Research Center for Medical Sciences were studied. In the prospective part of the study, information on demographic characteristics, including age, gender, education, and profession, was collected during medical visits using a standard questionnaire. Metabolic syndrome was defined according to international guidelines as the presence of three or more of the following risk factors: waist circumference &amp;gt;102 cm in men or &amp;gt;88 cm in women; serum triglyceride level ≥1.70 mmol/L; HDL cholesterol &amp;lt; 1.04 mmol/L in men or &amp;lt; 1.30 mmol/L in women; Blood pressure ≥ 130/85 mm Hg, including achieved; serum glucose level ≥6.11 mmol/L. Metabolic syndrome definition criteria used Results The demographic characteristics of the patients are presented in the table. Mean serum creatinine was similar, but GFR was estimated to be lower among those with metabolic syndrome compared with those without. The percentage of individuals with CKD and elevated serum creatinine was statistically significantly higher among individuals with metabolic syndrome. Low HDL cholesterol, elevated plasma glucose, and abdominal obesity were found to be statistically significantly associated with the risk of developing C5 CKD and elevated serum creatinine. In addition, a significant relationship was observed between the number of metabolic syndrome components and the percentage of CKD C5 or elevated serum creatinine (P &amp;lt; 0.015 and P = 0.02, respectively). In the multivariate model, patients with 1, 2, 3 and 4 or 5 components of the metabolic syndrome had 1.51; 1.50; 2.13 and 2.72 times higher odds of CKD C5 CKD, respectively, compared with individuals without metabolic syndrome components. Overall, patients with metabolic syndrome had a 64% increased odds of CKD compared with a comparison group without metabolic syndrome. Conclusion The present study revealed a positive and significant association between metabolic syndrome and the risk of CKD C5 in those examined. The risk of CKD increased progressively with increasing number of metabolic syndrome components.

The Link between Abdominal Obesity Indices and the Progression of Liver Fibrosis: Insights from a Population-Based Study

There is currently no available information on the correlation between abdominal obesity indices and the risk of liver fibrosis progression. We aimed to investigate the relationship between the body mass index (BMI), waist circumference (WC), and the visceral adiposity index (VAI) with the progression of liver fibrosis. The study also evaluated the association between these indices and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. A total of 1403 subjects participated in the cross-sectional and longitudinal population-based study. Liver stiffness was assessed via transient elastography, at baseline and follow-up (median: 4.2 years). The subgroup with dysglycemia was also analyzed. In the cross-sectional study, the highest quartile of VAI, BMI ≥ 30 kg/m2, and abdominal obesity showed significant associations with the prevalence of MASLD and liver fibrosis, as well as with fibrosis progression. However, VAI showed no association with MASLD incidence. Among the dysglycemic subjects, there was no observed association between VAI and the incidence of MASLD or the progression of fibrosis. In conclusion, the BMI, WC, and the VAI are associated with an increased risk of progression to moderate-to-advanced liver fibrosis in the general population. However, the VAI does not perform better than the BMI and WC measurement.

#1042 A real-life experience with dapagliflozin in the treatment of patients with IgA Nephropathy at high risk of progression

Abstract Background and Aims Even though IgA nephropathy is the most common primary glomerular disease worldwide, being accounted with 22% of kidney biopsy results in Europe and despite great advances in comprehending its pathogenesis, little has changed in the standard of care over the last decades. According to recent studies, dapagliflozin reduced the progression of chronic kidney disease in chronic forms of IgA Nephropathy. The study sought to investigate the impact of dapagliflozin use in a compiled cohort of patients diagnosed with IgA Nephropathy. Method This is a prospective, observational study, that included 52 patients with IgA Nephropathy, based on a prior kidney biopsy, actively monitored from 2021 to 2023, in the Nephrology Department of Fundeni Clinical Institute, Bucharest. The inclusion criteria were: patients with IgA nephropathy diagnosed upon evaluation of a kidney biopsy, with GFR&amp;gt;30 ml/min/1.73 m2 and proteinuria above 0.3 g/day, who received dapagliflozin 10 mg, daily, with a follow-up of 6 and 12 months. The baseline parameters were considered those that were on the onset of SGLT2 inhibitors therapy with dapagliflozin. Results The study population had a mean age of 48 ± 11 years old and 69.2% were male. The mean value of baseline serum creatinine was 1.68 ± 0.75 mg/dl and the mean value of GFR was 54 ± 27 ml/min/1.73 m2, while the mean value of baseline proteinuria was 1.55 ± 2.1 g/day. Also, the risk of chronic kidney disease progression was very high in 59.6% cases, high in 34.6% cases and moderate in 5.8% cases. The majority of the study cohort (90.4%) already received a stable dose of angiotensin-converting-enzyme inhibitors or angiotensin receptor blocker. After 6 months of dapagliflozin administration, the absolute decline of proteinuria was 0.94 ± 1.9 g/day, while after 12 months was 1.06 ± 2.97 g/day, which in terms of percents translates as a decline of—44.7% and—50%, respectively. A mild decrease in GFR was observed, the absolute decline being represented by 4 (−6.25; 3) ml/min/1.73 m2 after 6 months and 3.5 (−9;2) ml/min/1.73 m2 after 12 months. Patients who had proteinuria less than 1 g/day at baseline experienced an absolute decline in GFR with 2.5 (−5.75; 3.75) ml/min/1.73 m2, while the study group with proteinuria above 1 g/day had an absolute decline in GFR of 5 (−7.2; 3) ml/min/1.73 m2 after 6 months, while after 12 months of treatment, the GFR drop was 4 (−8.5;1.5) ml/min/1.73 m2 and 3 (−9;2) ml/min/1.73 m2, respectively. A GFR decline over 30% was observed with a prevalence of 17.6% in the group with proteinuria above 1 g/day and 9.5% in the group with proteinuria under 1 g/day, while the prevalence was 8.7% in the group with GFR&amp;gt;45 ml/min/1.73 m2 and 20% among the group with GFR&amp;lt;45 ml/min/1.73 m2. The mean value of baseline proteinuria was 0.42 ± 0.21 g/day in the cohort with proteinuria&amp;lt;1 g/day and 3.09 ± 2.53 g/day in the cohort with proteinuria&amp;gt;1 g/day (p &amp;lt; 0.001). At 6 months, the absolute decrease of proteinuria was 0.18 ± 0.18 g/day in the group with proteinuria under 1 g/day and with 1.79 ± 2.53 g/day in the group with proteinuria above 1 g/day (p &amp;lt; 0.001), whereas after 12 months it was 0.15 ± 0.21 g/day and 2.17 ± 2.54 g/day (p &amp;lt; 0.001); also, after 12 months, proteinuria was reduced with 1.42 ± 2.37 g/day at patients with GFR&amp;gt;45 ml/min/1.73 m2 and with 0.48 ± 0.85 g/day at patients with GFR&amp;lt;45 ml/min/1.73 m2, a difference which tends to reach statistical significance. Conclusion There was a decline in proteinuria after 6 months and 12 months of dapagliflozin treatment, with a statistically significant difference between the two groups: the patients with proteinuria above 1 g/day experienced a more remarkable reduction than the group with proteinuria under 1 g/day. Patients with GFR&amp;gt;45 ml/min/1.73 m2 experienced a higher drop in proteinuria. A mild decrease of GFR was noticed during the follow-up period, with a higher prevalence of a GFR dip over 30% in the group with proteinuria above 1 g/day and with GFR&amp;lt;45 ml/min/1.73 m2, but the difference was not statistically significant.