Etiology Of Chronic Kidney Disease Research Articles

Primary glomerular diseases and long-term adverse health outcomes: A nationwide cohort study.

Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide, little is known about their long-term outcomes. In patients with chronic kidney disease (CKD) stage 3-5 enrolled in the Swedish Renal Registry, we compared risks of hospitalization, kidney replacement therapy (KRT), major cardiovascular events (MACE), and death of the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD], and membranous nephropathy [MN]), and patients with CKD due to the most common non-communicable diseases (control-CKD). We identified 2396 patients with glomerular disease (97% biopsy-proven, 69% men, 57 years, eGFR 29mL/min/1.73m2, uACR 88mg/mmol, 1524 with IgAN, 398 FSGS, 94 MCD, and 380 MN) and 37,697 controls (64% men, 74 years, eGFR 25mL/min/1.73m2, uACR 23mg/mmol), mainly with diabetic nephropathy and nephroangiosclerosis. The median follow-up was 6.3 (3.3; 9.9) years. Compared with control-CKD, patients with primary glomerular diseases generally had a lower risk of hospitalization, MACE (adjusted hazard ratios [HRs] ranging from 0.44 to 0.88 depending on the etiology) and death (HRs ranging 0.45-0.76). Patients with IgAN and FSGS had a faster eGFR decline and a higher rate of KRT (HRs 1.26 [95%CI: 1.15-1.37] and 1.34 [1.15-1.57], respectively). Conversely, patients with MN and MCD had a lower KRT rate and slower eGFR decline. Despite having a lower relative risk of hospitalization, cardiovascular events and mortality, patients with IgAN and FSGS are at higher risk of CKD progression than the most common etiologies of CKD, emphasizing the need for more stringent treatment strategies in these patients.

Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial.

Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) ≥25 ml min-1 1.73 m-2 and urine albumin-to-creatinine ratio (UACR) ≥30 and <3,500 mg g-1) and body mass index ≥27 kg m-2. Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g-1 (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min-1 1.73 m-2; and mean body mass index was 36.2 (s.d. 5.6) kg m-2. Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by -52.1% (95% confidence interval -65.5, -33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183 .

Hyperhomocysteinemia in Chronic Kidney Disease: A Meta-Analysis

Background: Hyperhomocysteinemia, an elevated level of homocysteine in the blood, has been implicated in the progression of chronic kidney disease (CKD). This meta-analysis aims to comprehensively evaluate the association between hyperhomocysteinemia and CKD and its potential impact on clinical outcomes. Methods: This study systematically searched electronic databases (PubMed, Embase, Cochrane Library) for studies published between 2018 and 2024 investigating the relationship between hyperhomocysteinemia and CKD. Studies reporting data on the association between hyperhomocysteinemia and CKD progression, cardiovascular events, or mortality were included. We extracted relevant data and performed a meta-analysis using random-effects models. Results: The meta-analysis included 25 studies comprising 5,672 patients with CKD. Hyperhomocysteinemia was significantly associated with an increased risk of CKD progression (pooled odds ratio [OR] 1.85, 95% confidence interval [CI] 1.52-2.24), cardiovascular events (pooled OR 1.63, 95% CI 1.31-2.02), and all-cause mortality (pooled OR 1.48, 95% CI 1.17-1.87) in CKD patients. Subgroup analyses revealed a consistent association across different CKD stages and etiologies. Conclusion: Hyperhomocysteinemia is an independent risk factor for CKD progression, cardiovascular events, and mortality. Monitoring and managing hyperhomocysteinemia may represent a potential therapeutic target to improve outcomes in CKD patients.

Endogenous bufadienolides, mineralocorticoid receptor antagonists and fibrosis in chronic kidney disease.

Every year millions die prematurely of complications related to chronic kidney disease (CKD). Main causes of death are connected with cardiovascular (CV) complications. There is no cure for CKD although current treatment can slow the progression of the disease if diagnosed early. Fortunately, last decades have witnessed an accelerating pace of discovery regarding the cellular and molecular basis for CKD and CV disease. Novel biomarkers, including amino-terminal type III procollagen peptide (PIIINP), carboxy-terminal type I procollagen peptide (PICP), FGF23, marinobufagenin, and several miRNAs, show promise for early detection and risk stratification. In this review, we provide an overview of recent advances in the "fibrotic concept" of the etiology and pathogenesis of CKD which involves system consisting of Na/K-ATPase and its endogenous ligands including marinobufagenin which inhibits Fli1 and stimulates synthesis of collagen-1 in the vasculature. A novel treatment of CKD already involves the use of mineralocorticoid receptor antagonists capable of impairing marinobufagenin-Na/K-ATPase interactions.

Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem.

In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Hepatitis C Virus Seroprevalence and Genotypic Distribution Among Hemodialysis Patients at a Teaching and Training Hospital in Western Rajasthan, India.

Background Hepatitis C virus (HCV) infection is a chronic hepatotropic blood-borne infection. The transmission of HCV in patients undergoing hemodialysis (HD) is more common in comparison to the general population due to factors such as frequent blood transfusions, prolonged vascular access, and the potential for nosocomial infections. Western Rajasthan in India is home to numerous teaching and training hospitals that cater to a large number of HD patients. Understanding the seroprevalence and genotypic distribution of HCV in this specific patient population is crucial for assessing the extent of infection within this vulnerable group for targeted surveillance and developing effectively tailored treatment protocolsin healthcare settings. Hence, this study was conducted with an aim to determine seroprevalence, seroconversion, and genotypes of HCV in HD patients at a tertiary care hospital. Methods This was a cross-sectional observational study. The duration of the study was from July 2019 to March 2022. In this study, the patients undergoing maintenance HD due to chronic kidney disease (CKD) were recruited. The data collected include patients' demographics, etiology of CKD, underlying other co-morbidities, duration of dialysis, and biochemical and blood count parameters. The patients recruited at the start of the study were screened for anti-HCV antibodies by HCV enzyme-linked immune sorbent assay (ELISA). The anti-HCV antibody-negative patients were followed up for the detection of anti-HCV antibodies. At the end of the follow-up period, all anti-HCV antibody negative samples in the pool of five and all anti-HCV antibody positive samples were subjected to a real-time polymerase chain reaction (RT-PCR) of 5' untranslated region (5'UTR) and core region, followed by line probe assay (LiPA). Results In this study, after applying inclusion and exclusion criteria, a total of 109 patients were recruited, out of which 64 (58.7%) were males and 45 (41.3%) were females. The age range of participants was 11-88 years with a mean and standard deviation of 46.75 and 16.35 years, respectively. A total of 39 patients (20 on screening, 19 on follow-up) were detected anti- HCV antibody positive. By RT-PCR, 24 patients tested HCV RNA positive (10 on screening, 14 on follow-up). Among 24 HCV RNA-positive samples, LiPA showed, HCV genotype 1a (n=21), genotype 3b (n=1), and two samples were detected to be inconclusive. Conclusion The increasing duration of dialysis is significantly associated with acquiring HCV infection. The majority of the cases of CKD in this geographical region are due to hypertensive nephropathy. There can be discordance between antibody and viral RNA positivity in HCV infection. The predominant HCV genotype identifiedin the dialysis ward of tertiary care hospital was genotype 1a.

Role of chronic kidney disease and risk factors in preeclampsia

BackgroundOur goal was to identify what impact chronic kidney disease (CKD) and its associated risk factors, such as body mass index (BMI), diabetes and hypertension, have on preeclampsia and other adverse pregnancy outcomes in the CKD population. MethodsThis was a population-based cohort study of women with CKD who had a pregnancy from 2010 to 2022 (n = 95). At the time of the woman’s pregnancy, data was collected on demographics, clinical measures, BMI, CKD etiology and other renal parameters. Outcomes included preeclampsia, pre-term delivery, and low birth weight. ResultsPre-pregnancy BMI increased over time in patients with CKD, with a median (interquartile range) BMI of 25 (22–29) prior to 2016 and 29 (25–34) after 2016 (p = 0.01). There were significant trends of increasing age at delivery and decreasing pre-pregnancy estimated glomerular filtration rate (eGFR) by delivery year. Preeclampsia affected nearly half of pregnancies in this cohort. In multivariate analyses, BMI and chronic hypertension did not impact the odds of preeclampsia, preterm delivery or low birth weight, though a CKD etiology of diabetes (19/20 with type I diabetes), was associated with a significant increase in preeclampsia risk (odds ratio (OR) 7.41 (95 % CI 2.1–26.1)). Higher pre-pregnancy eGFR was associated with a lower odds of preterm delivery (OR 0.81 (95 % CI 0.67–0.98)) per 10 ml/min/1.73 m2). ConclusionPre-pregnancy BMI significantly increased over time, similar to the general population. While preeclampsia was common in CKD patients, outcomes were associated with eGFR and CKD etiology as opposed to BMI and chronic hypertension.

Comprehensive Clinical Profile and Hemodialysis Outcomes in Patients Attending a Tertiary Care Hospital.

Background Chronic kidney disease (CKD) can lead to serious conditions such as anemia and cardiovascular disease, posing a growing global health challenge. End-stage renal disease (ESRD) requires treatments such as dialysis or kidney transplantation. Despite the widespread impact and rising prevalence of CKD and ESRD, comprehensive data remains limited in India. This study seeks to investigate the clinical, socio-demographic, and etiological profiles of CKD patients undergoing hemodialysis at a tertiary care hospital, with the goal of enhancing understanding and improving patient care. Methodology This retrospective cohort study, conducted at a tertiary care center, included 500 CKD patients undergoing hemodialysis, with comprehensive medical records. Data collected covered demographics (age, sex, education, and occupation), CKD etiology, disease duration, hemodialysis duration, viral marker status, blood transfusions, and vascular access details. With continuous variables reported as mean ± standard deviation (SD) and categorical variables as counts (percentages), statistical analysis was carried out using SPSS version 21 (IBM Corp., Armonk, New York, USA). The connections were examined using the Pearson Chi-square test, with P≤0.05 being deemed significant. Results The study revealed that hypertension was the primary cause of CKD in 58% of patients, followed by diabetes mellitus in 13%. A significant 93% of patients tested negative for viral markers such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B surface antigen (HBsAg). Hemodialysis duration varied, with 68% of patients undergoing dialysis for one to five years. Most patients had two (40%) or three (58%) dialysis sessions per week, and 84% had only one arteriovenous (AV) fistula surgery. Blood transfusions were common, with 62% of patients receiving between one and five transfusions. The gender distribution showed more males (372) than females (201), and the majority of patients were aged between 41 and 60 years. Conclusion This study highlights the importance of early detection and management of CKD, emphasizing preventive health measures, enhanced diagnostic capabilities, and sufficient resource allocation to reduce the disease burden. It also calls for further research into unknown CKD causes and strategies to improve patient care and outcomes.

Chronic Kidney Disease in a Tertiary Care Hospital in Nepal

Introduction: Chronic kidney disease (CKD) is an increasingly recognized major public health problem globally and in Nepal. It has a high prevalence in the population and is associated with high morbidity, mortality and health care costs. Here, we aimed to study the socio-demographic profiles, etiologies of CKD and associated co-morbidities in patients attending a referral hospital. Methods: We conducted a hospital based, descriptive, observational, cross-sectional study among adult patients with CKD attending Tribhuvan University Teaching Hospital (TUTH), Kathmandu. Patients younger than 16 years and renal allograft recipients were excluded from the study. A diagnosis of CKD was established by the treating nephrologist based on KDIGO 2012 clinical practice guideline. Prior informed consent was taken. Data was collected on clinical features, socio-demographic profiles, major co-morbidities, presumed etiology of CKD and hematological and biochemical parameters of the patients. SPSS version 24 (Chicago, IL, USA) was used for the analysis of data. The study protocol was approved by the Institutional Review Board (IRB) of Institute of Medicine (IOM). Results: A total of 401 patients with CKD were included in the study. The mean age of the patient was 50.92 years (SD=17.98), male to female ratio was 1.8:1. Among these patients, 86% were Hindu, 24.4% were farmers, 57% were from the Hilly region of Nepal, 51% were active smokers, and 51.6% were alcohol consumers. Chronic glomerulonephritis (CGN) (36.2%; n= 145), diabetes mellitus (31.9%; n= 128) and hypertension (21.7%; n=87) were the three most common identified causes of CKD. Among the biopsy proven CGN patients, IgA nephropathy was the most common cause. In a large proportion of patients (68.3%) cause of CGN was not known. Most of the patients were in CKD stage 5 (27%), and stage 5D (55.8%). Coronary artery disease (CAD) (in 7% patients), heart failure (in 2.7%) and stroke (in 2.2%) were the most common comorbidities. Anemia was prevalent in CKD from stage 3 onwards, the severity increased with increasing stage (p &lt;0.001). Hemodialysis was the predominant mode of renal replacement therapy (RRT) used by 98.2% of CKD 5D patients. Conclusion: Nepalese patients of CKD are younger; males are more affected than females. CGN, diabetes and hypertension are three most common causes of CKD; IgA nephropathy is the most common cause of biopsy proven CGN leading to CKD. Anemia is common from CKD stage 3 onwards. The most common associated co-morbidity is CAD.

Not Just Small Adults: Considerations for Pediatric Chronic Kidney Disease

Chronic kidney disease (CKD), including pediatric CKD, is a global public health concern. Pediatric CKD has lasting effects into adulthood. In this review, we focus on the etiology of pediatric CKD and unique aspects that should be considered in treating a child with CKD, such as ensuring adequate nutrition and assessing growth hormone axis dysregulation. We review risk factors for CKD progression and how clinical surveillance can be used to address modifiable factors. We address the issues of accurate glomerular filtration rate (GFR) estimation, cardiovascular disease, immunization, neurodevelopment, and planned transition to adult care. We also cover kidney failure preparation and global CKD care disparities affecting children worldwide.

Cardiovascular and Kidney Outcomes of Non-Diabetic CKD by Albuminuria Severity: Findings From the CRIC Study

The clinical trajectory of normoalbuminuric chronic kidney disease (CKD), particularly in the absence of diabetes, has not yet been well-studied. This study evaluated the association of kidney and cardiovascular outcomes with levels of albuminuria in a cohort of patients with nondiabetic CKD. Prospective cohort study. 1,463 adults with nondiabetic CKD without known glomerulonephritis and diagnosed with hypertensive nephrosclerosis or unknown cause of CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Albuminuria stage at study entry. Primary outcome: Composite kidney (halving of estimated glomerular filtration rate [eGFR], kidney transplantation, or dialysis), Secondary outcomes: (1) eGFR slope, (2) composite cardiovascular disease events (hospitalization for heart failure, myocardial infarction, stroke, or all-cause death), (3) all-cause death. Linear mixed effects and Cox proportional hazards regression analyses. Lower levels of albuminuria were associated with female sex and older age. For the primary outcome, compared with normoalbuminuria, those with moderate and severe albuminuria had higher rates of kidney outcomes (adjusted hazard ratio [AHR], 3.3 [95% CI, 2.4-4.6], and AHR, 8.6 [95% CI, 6.0-12.0], respectively) and cardiovascular outcomes (AHR, 1.5 [95% CI, 1.2-1.9], and AHR, 1.5 [95% CI, 1.1-2.0], respectively). Those with normoalbuminuria (<30μg/mg; n=863) had a slower decline in eGFR (-0.46mL/min/1.73m2 per year) compared with those with moderate (30-300μg/mg, n=372; 1.41mL/min/1.73m2 per year) or severe albuminuria (>300μg/mg, n=274; 2.63mL/min/1.73m2 per year). In adjusted analyses, kidney outcomes occurred, on average, sooner among those with moderate (8.6 years) and severe (7.3 years) albuminuria compared with those with normoalbuminuria (9.3 years) whereas the average times to cardiovascular outcomes were similar across albuminuria groups (8.2, 8.1, and 8.6 years, respectively). Self-report of CKD etiology without confirmatory kidney biopsies; residual confounding. Participants with normoalbuminuric nondiabetic CKD experienced substantially slower CKD progression but only modestly lower cardiovascular risk than those with high levels of albuminuria. These findings inform the design of future studies investigating interventions among individuals with lower levels of albuminuria. Diabetes and hypertension are the leading causes of chronic kidney disease (CKD). Urine albumin levels are associated with cardiovascular and kidney disease outcomes among individuals with CKD. However, previous studies of long-term clinical outcomes in CKD largely included patients with diabetes. As well, few studies have evaluated long-term outcomes across different levels of urine albumin among people without diabetes. In this study, we found individuals with nondiabetic CKD and low urine albumin had much slower decline of kidney function but only a modestly lower risk of a cardiovascular events compared with those with high levels of urine albumin. Individuals with low urine albumin were much more likely to have a cardiovascular event than progression of their kidney disease. These findings inform the design of future studies investigating treatments among individuals with lower levels of albuminuria.

Renin-angiotensin system inhibitor prescriptions in Chinese hospitalized chronic kidney disease patients

BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients. AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China. METHODS It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription. RESULTS A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age &lt; 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions. CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.

Causes of Chronic Kidney Disease and Their Associations with Cardiovascular Risk and Disease in a Sub-Saharan Low-Income Population.

The causes of chronic kidney disease (CKD) in people living in Sub-Saharan Africa await identification. Also, whether cardiovascular risk and disease extent differ among patients with different CKD etiologies is uncertain. In this prospective cross-sectional study, we examined the presumed causes of chronic kidney disease (CKD) and their relationships with cardiovascular risk and disease in 743 consecutive patients from a sub-Saharan low-income population. Hypertensive nephropathy (HNP) (60.2%), diabetic nephropathy (DNP) (24.4%), HIV associated CKD (20.0%) and glomerular disease (13.6%) comprised the major CKD etiologies upon enrolment at the hospital nephrology clinic. Pulse pressure was larger in patients with concurrent HNP and DNP than in those with HNP only (p<0.001). Pulse pressure and systolic blood pressure were larger in HNP or/and DNP patients than those with HIV associated CKD and glomerular disease (p=0.04 to <0.001). Cardiovascular disease was more prevalent in patients with HNP and concurrent HNP and DNP than those from other etiologic categories (p<0.05). HNP and DNP were associated with pulsatile pressures (pulse pressure and systolic blood pressure) independent of one another (p<0.01). In adjusted product of coefficient mediation analysis, mean arterial or distending pressure accounted fully for the potential impact of HNP on pulsatile pressures (103.9-115.7%) but not for that of DNP on the respective pressures (-2.0%-(-)7.5%). HNP is by far the most prevalent presumed cause of CKD in this African population. Cardiovascular risk and disease differ markedly across CKD etiological categories.

#2099 Long term outcomes in chronic kidney disease patients with heart failure with preserved ejection fraction

Abstract Background and Aims Heart failure (HF) is frequent in chronic kidney disease (CKD) and leads to high morbidity and mortality in this patient category. The aim of our study is to assess the clinical and biological profile, and outcomes in CKD patients with preserved left ventricular ejection fraction (LVEF). Method We prospectively enrolled CKD patients (pts) in pre-dialysis, stratified in two groups by the presence of heart failure symptoms: pts with NYHA class 1-2 (asymptomatic HF) versus pts with NYHA class 3-4 (symptomatic HF). Demographics, clinical history, co-morbidities, physical exam, ambulatory blood pressure monitoring, extensive blood chemistry, systemic inflammation and mineral bone disease parameters were recorded. Cardiac structure and systolic and diastolic function were assessed by echocardiography. Carotid Doppler ultrasound assessed intima media thickness (IMT). Al patients were followed until death of loss from records; patients with less than 6 months of surveillance were excluded. Primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality, a composite cardiac endpoint composite cardiac endpoint comprising coronary heart disease, heart failure hospitalization and new-onset arrhythmia, and reaching the end stage of renal disease (ESRD). Results We included 76 CKD patients (2 pts CKD stage 1, 9 pts CKD stage 2, 19 pts CKD stage 3a, 28 pts CKD stage 3b, 18 pts CKD stage 4) with LVEF ≥ 50%. Mean age 64.7 ± 11.4 years (yrs), men = 56 (73.7%). Mean follow up period was 86 ± 46.4 months (range 6-156 months). Patients with symptomatic HF (54 pts, 71.1%) were older (68 ± 9 vs 56 ± 12 yrs), hypertensive (98.1% vs 86.4%, p &amp;lt; 0.05), more frequent coronary artery disease (66.7% vs 27.3%, p &amp;lt; 0.05), had worse baseline biological profile: lower eGFR (36.9 ± 12.9 vs 55.5 ± 22.7 ml/min/1.73 m2, p &amp;lt; 0.05), lower serum albumin (4.1 ± 0.5 vs 4.4 ± 0.4 g/dl, p &amp;lt; 0.05), as well as higher levels of osteoprotegerin and fetuin A (p &amp;lt; 0.05). Also, symptomatic HF pts had more severe endothelial disease (higher IMT 0.81 ± 0.14 vs 0.63 ± 0.11 mm, p &amp;lt; 0.05), more severe subclinical LV dysfunction revealed by less negative global longitudinal strain GLS (−16.7 ± 2.66 vs −19.2 ± 2.95, p &amp;lt; 0.05) and higher ratio of mitral velocity to early diastolic velocity of the mitral annulus E/E` (12.64 ± 3.63 vs 9.68 ± 2.73, p &amp;lt; 0.05), as well as higher LV mass index (121.5 ± 31 vs 104.9 ± 22.7 g/m2, p &amp;lt; 0.05) and higher left atrial volume index LAVI (42.8 ± 16.8 vs 31.8 ± 11.3 ml/m2, p &amp;lt; 0.05) All-cause mortality was 17.1% (13 events), while cardiovascular mortality was 6.6% (5 events). All deaths were recorded in the symptomatic HF group. Also, a higher percent of pts from symptomatic HF group reached the composite cardiac endpoint (44.4% vs 22.7%) and ESRD (33.3% vs 18.2%) compared to asymptomatic HF group. Kaplan-Meier survival analysis showed significantly higher all-cause mortality (log rang = 0.008) and lower ESRD-free survival (log rank= 0.045) in symptomatic HF group. All-cause mortality was significantly correlated with NYHA class (p &amp;lt; 0.0001), etiology of CKD (p = 0.038), eGFR (p &amp;lt; 0.0001), proteinuria (p = 0.001), intact PTH (p = 0.008), osteocalcin (p = 0.012), osteopontin (p = 0.029), FGF23 (p = 0.044), IL6 (p = 0.037), GLS (p = 0.023), E/E` (p = 0.009). Cardiovascular mortality was significantly correlated with NYHA class (p = 0.019), etiology of CKD (p = 0.008), eGFR (p = 0.011), proteinuria (p = 0.001), intact PTH (p = 0.008), osteocalcin (p = 0.011), osteopontin (p = 0.006), FGF23 (p = 0.006). Cox regression analysis identified NYHA class (p = 0.004), FGF23 (p = 0.009) and IL6 (p = 0.025) as predictors for all-cause mortality, while E/E` (p = 0.032) and intact PTH (p-0.042) were predictors for cardiovascular mortality. Conclusion In our study, CKD pts with symptomatic HF carry a significant burden of morbidity and mortality, even in the case of preserved LV ejection fraction. This emphasizes the need for more comprehensive regular assessments of subclinical cardiac dysfunction in CKD pts. This approach might support targeted interventions, better symptom control, and improved long term outcomes.

#2817 Preliminary results of dapagliflozin in inactive lupus nephritis cross-over randomized trial

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD). Lupus nephritis (LN) patients in remission may continue with residual proteinuria due to scars and hyperfiltration. However, LN patients were excluded from the main trials with SGLT2 inhibitors. This trial aims to assess the effect and safety of dapagliflozin in inactive LN patients with residual proteinuria. Method For this cross-over randomized trial, we include adult patients with LN class III, IV (±V) without active nephritis but with proteinuria &amp;gt;500 mg/24 h or UPC &amp;gt; 200 mg/g and eGFR ≥ 20 ml/min, in the maintenance treatment with a RAAS and mycophenolate mofetil (&amp;lt;2g/day) in stable a dose for at least four weeks before the randomization. We excluded patients with other etiologies of CKD, those with active LN lesions on the recent biopsy (AI&amp;gt;2), use of induction therapy in the last 12 months (cyclophosphamide, mycophenolate mofetil &amp;gt;2g/day and calcineurin inhibitors) and prednisone dose ≥ 20 mg/day. Due to safety issues, we excluded patients with recurrent urinary infections (&amp;gt;3 times/year). Those included were randomized to receive dapagliflozin 10 mg on top of standard of care therapy (SoC) or not. After 24 weeks the groups were switched and those without dapagliflozin received it for the next 24 weeks. Primary endpoint is reduction of proteinuria compared to baseline at 6 and 12 months. Secondary endpoints are sustained reduction of eGFR&amp;gt;30%; occurrence of hypotension symptoms; and number of infections on dapagliflozin treatment versus exclusive SoC therapy. The sample size was calculated for 28 patients enrolled providing 80% power to detect a 25% relative risk reduction in proteinuria (α level of 0.05). Results From 97 screened class III, IV (± V) LN patients under maintenance therapy, we excluded 67 due to active nephritis, low proteinuria or low eGFR. We included 30 patients that were randomized 14 to start the treatment with dapagliflozin on top of SoC and 16 to remain with the usual therapy for 24 weeks. Six patients were excluded from the analysis due to new LN flare or lost to follow-up. We analyzed the data of 12 patients in the initial Dapa + SoC and 12 patients in the initial SoC group after 3 (n = 21), 6 (n = 18), 9 (n = 14) and 12 (n = 12) months. Patients in initial Dapa group had a significant decrease in proteinuria after 6 months (1159 to 882 mg/day; p = 0.017) but increased to 1105 mg/day 6 months after the drug withdrawal (Fig. 1A). This preliminary analysis shows a significant reduction in the proteinuria of –35.8% in patients after 6 mo of dapagliflozin as opposed to an increase in 7.2% for those in the SoC therapy at the end of a 6 mo period, p = 0.02 (Fig. 1C). The drug was well tolerated, but 4 (33.3%) of the patients reported hypotension symptoms during the first days of dapagliflozin. There was one case of urinary infection in each group, but in the same patient. Conclusion Preliminary results show a significant reduction in residual proteinuria in patients with inactive LN with dapagliflozin without an increase in infections.

#217 Renin-angiotensin-aldosterone system blockers effect in CKD progression in hypertensive elderly patients without proteinuria: PROERCAN trial

Abstract Background and Aims Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Method Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3-4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years (Figure). Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results 88 patients were included with a mean age of 77.9 ± 6.1 years and a follow up period of 3 years: 40 were randomised to RAAS group and 48 to standard treatment. Etiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown etiology. In the RAAS group eGFR slope during follow up was −4.3 ± 1.1 ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6 ± 0.4 ml/min), p = 0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusion In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression.

#382 Unexpected diagnoses of ADTKD-MUC1 with the help of VNtyper

Abstract Background and Aims Autosomal dominant tubulointerstitial kidney disease (ADTKD) due to pathogenic variants in the MUC1 gene is difficult to diagnose since these variants lie in a large variable number tandem repeats (VNTR) and require specialized genetic testing, such as SNaPshot minisequencing. We recently developed a computational pipeline, VNtyper, for easier reliable detection of MUC1 VNTR pathogenic variants and have applied this tool to a large cohort of patients with various phenotypes of kidney disease. The aim of this study is to clinically describe patients in whom MUC1 pathogenic variants were unexpectedly detected with the help of VNtyper. Method We applied a computational pipeline, VNtyper, to a large cohort of patients with suspected hereditary kidney disease referred for genetic testing, regardless of their phenotype. This cohort included patients evaluated from 2017 to 2023 in the Molecular Genetics Department of Necker-Enfants Malades Hospital (Paris, France). Clinical characteristics were collected from patients in whom we detected new MUC1 VNTR pathogenic variants. Results 44 out of 3735 patients tested (1.2%) were newly diagnosed with a MUC1 pathogenic variant. Of these patients, ADTKD was clinically suspected in only 31 out of 44 patients (70%). In 2 patients, there was a pathogenic variant in another gene that could explain the phenotype, in addition to the MUC1 pathogenic variant. In fact, one 52-year-old patient had polycystic kidneys, nephrolithiasis, hematuria and normal kidney function. Her mother also had kidney cysts with absence of chronic kidney disease (CKD). This patient had a pathogenic variant in IFT140 gene (c.2399+1G&amp;gt;T) which could explain her autosomal dominant polycystic kidney disease (ADPKD) phenotype. Whether the MUC1 variant contributes to her disease remains unclear, especially seeing as her kidney function is normal at the age of 52 years. On the other hand, one patient had kidney cysts discovered at 3 days of age. A heterozygous HNF1B deletion was detected which could explain the phenotype. The following detection of a pathogenic MUC1 variant was thus an incidental finding and seemed de novo, although parents declined to get tested. These incidental findings can be challenging, especially when it comes to counselling and follow-up. There was no family history of kidney disease in 7 out of 44 patients (16%), and in one patient, we were able to confirm de novo disease since her parents were tested and were negative. It was unfortunately not possible to get DNA from the parents of the other patients. This is the first case of proven de novo ADTKD-MUC1 described to our knowledge. De novo variants in ADTKD-MUC1 are not surprising since the 7C stretch found in VNTR is a hotspot for mutagenesis. Interestingly, these patients seemed to have a more severe clinical presentation with an early onset of disease (median age at diagnosis 28 years [18, 32]). However, this could be due to a selection bias. In fact, young age of onset of CKD may have prompted clinicians to refer these patients for genetic testing despite negative family history, whereas older patients with possible ADTKD-MUC1 and no family history of kidney disease might be presumed to have another etiology of CKD. One way to confirm this would be to test a large cohort of patients with CKD from unknown etiology with no family history of CKD. Considering the nonspecific clinical manifestations of ADTKD-MUC1 and the phenotypic variability, it has previously been suggested that the most important clue to diagnosis is the presence of CKD in first-degree family. The possibility of de novo cases makes the clinical diagnosis of ADKTD-MUC1 even more challenging. Conclusion With VNtyper, we were able to diagnose new cases of ADTKD-MUC1 in a large cohort of patients with various phenotypes, with a significant prevalence of 1.2%. ADTKD-MUC1 was not suspected in 30% of these patients who would have maybe never been diagnosed otherwise. This is also the first study in which we describe a proven de novo case of ADTKD-MUC1. Pathogenic variants in the MUC1 gene should thus be in the differential diagnosis of all unspecified CKD, even if there is no family history since de novo variants are also possible.

#2003 Genetic association in patients with chronic kidney disease of unknown etiology: an observational study

Abstract Background and Aims Chronic kidney disease (CKD), impacting over 850 million people worldwide, is a diverse group of inherited and acquired nephropathies. While only about 10% of adult CKD is hereditary, predominantly due to mutations in genes like PKD1, PKD2, and PKHD1, the etiology often remains unidentified, leading to challenges in management, especially in transplantation and genetic counseling contexts. This study used whole exome sequencing to investigate CKD of unknown origin, aiming to improve diagnostic yields and establish genetic associations. Our objective was to find the diagnostic yield of Whole exome sequencing in patients with CKD of unknown etiology and to establish genetic association for same. Method The study was conducted in the Department of Nephrology and the Institute of Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi. It was an observational cross-sectional analysis. All patients, both male and female of all age groups with Chronic Kidney Disease of unknown etiology who were willing to participate. All patients, both male and female of all age groups with Chronic Kidney Disease of known etiology were excluded as following: Results In the investigation of 56 chronic kidney disease samples with unknown etiology, genetic testing yielded 45 mutated gene variants in 37 subjects. The variants comprised 32 missense mutations, 8 deletions, 3 nonsense mutations, and 1 splice site mutation. Variant zygosity was as follows: 34 heterozygous, 6 homozygous, and 2 hemizygous. Pathogenic variants were detected in 9 patients (20%), likely pathogenic in 6 (13.33%), and variants of uncertain significance in 29 (64.44%). Eighteen subjects (32.14%) demonstrated no genetic mutations. A genetic diagnosis was established in 15 patients, representing a diagnostic yield of 26.78%. Stratified by disorder, the yield was 40% for glomerular, 100% for tubular, 50% for renal calculi, and 18.42% for undetermined CKD. Genetic testing facilitated a novel diagnosis or an alteration of the existing diagnosis in 6 patients (10.71%). Conclusion The results affirm the efficacy of genetic testing in elucidating the etiologies of chronic kidney disease where traditional diagnostic methods do not yield definitive causation. Genetic alterations were identified in a significant proportion of the patient population, indicating the presence of underlying genetic contributors to the disease. The identification of pathogenic and likely pathogenic variants highlights the potential of genetic testing to impact clinical decision-making and patient care.

#2692 Mayo Clinic Chronicity Score: a helpful tool to establish the prognosis of patients with chronic kidney disease

Abstract Background and Aims Kidney biopsy is a useful tool to establish the diagnosis and provide information about the activity and chronicity of kidney disease. Chronic changes are generally irreversible and act as a prognostic marker. The Mayo clinic chronicity score (MCCS) standardizes and semi-quantitatively classifies the degree of chronicity as minimal, mild, moderate, or severe, based on a score assigned according to the degree of glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. The objective of this study is to validate and assess whether the MCCS has prognostic value in predicting the initiation of kidney replacement therapy (KRT), death, or doubling of serum creatinine in a cohort of patients with various etiologies of chronic kidney disease (CKD). Method We conducted a single-center retrospective study including 101 patients with CKD who underwent native kidney biopsies. The degree of chronicity was classified according to MCCS into 4 categories: minimal (0–1), mild (2–4), moderate (5–7) and severe (8–10). The primary endpoint was defined as KRT, death, and/or a ≥50% increase in baseline creatinine. The kidney endpoint was defined as KRT or a ≥50% increase in baseline creatinine. Results The mean age of patients was 52.1 ± 16.8 years, 68.3% were male, with a median baseline creatinine of 1.4 mg/dL (IQR: 0.92-2.1), a median eGFR of 59.6 (33.7-96.8), and median proteinuria of 2.4 g/24 h (IQR: 0.98-3.9). The median follow-up time was 4 years (range: 1.9-6.4). Biopsies yielded a mean of 15.7 ± 8.6 glomeruli. The most frequent etiologies were IgA nephropathy (17.8%), Focal Segmental Glomerulosclerosis (13.9%), membranous nephropathy (11.9%), nephroangiosclerosis (10.9%) and diabetic kidney disease (9.9%). Median chronicity score was 3 (IQR: 1-5). 27 patients (26.7%) had a minimal chronicity score, 37 (36.6%) mild, 30 (29.7%) moderate, and 7 (6.9%) severe. Those patients with severe chronic damage had significantly higher baseline creatinine (p = 0.01), lower eGFR and were older (p = 0.01). During a median follow-up time of 4 years (IQR: 2-6.3), 10 patients died, 32 (61.9%) reached the primary endpoint, and 24 (28.6%) reached the kidney endpoint. According to the KM curves, patients in the severe chronicity group were at higher risk to meet the primary endpoint (Log-Rank: 21.03 p&amp;lt;0.001), and the kidney endpoint (Log-Rank: 24.9 p&amp;lt;0.001) compared to the other groups (Fig. 1). In the multivariable Cox regression analysis (adjusted for age, creatinine, sex, proteinuria), the chronicity index was significantly associated with the combined primary endpoint (HR: 6.5, 95% CI: 1.95-21.96, p: 0.002) and the kidney endpoint (HR: 8.6, 95% CI: 2.47-29.75, p: 0.001). The area under the ROC curve for the primary composite endpoint was 0.77 (95% CI: 0.68-0.87) and for the kidney endpoint was 0.79 (95% CI: 0.69-0.89). Conclusion The MCCS is a useful tool to predict the prognosis of patients undergoing kidney biopsy, regardless of the etiology of kidney disease. The MCCS could guide therapeutic management and help select patients who benefit from immunosuppressive treatment.

#511 Inadequate diagnostic investigations and low treatment rates in CKD anemia: an inertia that can only change with long-term follow-up

Abstract Background and Aims Anemia is observed from the early stages in the course of chronic kidney disease (CKD), and as the stage progresses, the severity of anemia and its impact on quality of life increase. Early diagnosis of anemia in chronic kidney disease, assessments related to its etiology, and treatment are therefore crucial. There is no comprehensive and long-term study in Turkey addressing the diagnostic and therapeutic management of anemia seen in the course of chronic kidney disease. The aim of this study is to investigate the frequency of anemia in different stages of CKD in patients diagnosed with Stage 3 and more advanced stages, to evaluate the effectiveness of diagnostic approaches, and management of iron parameters and anemia, and to investigate the effect of anemia on patient survival. We aim to present “real-life” data from this study to guide clinical practice and correct errors or deficiencies in anemia management. Method This study is a single-center, observational-descriptive retrospective study. 1321 outpatients with Stage 3A and advanced CKD and anemia who admitted to Hacettepe University Faculty of Medicine Nephrology Clinic between 2014 and 2018 were included in the study. Data for demographics, CKD etiologies and stages, anemia severities, comorbid diseases were collected from electronic health system (Table 1). Diagnostic investigations for anemia evaluation and therapeutic interventions such as administration of iron, folic acid, vitamin B12, erythropoiesis stimulating agents (ESA) were assessed. The long-term yield of diagnostic and therapeutic approaches and their effects on survival were also evaluated. The study investigated whether the severity of anemia and improvement in anemia had an effect on survival. Results Ferritin is the most commonly performed test for the etiology of anemia (76.4%). Request rates for tests such as B12, folic acid, transferrin saturation and reticulocyte are below 20%. More than half of the patients with anemia (59.4%) have not received any form of anemia treatment. Even among those whose ferritin test was checked and the value was &amp;lt;100 µg/dL, only 41.4% were given iron treatment. As the clinical follow-up period of the patients increased, it was observed that anemia treatment was applied better and target values were reached more frequently (p &amp;lt; 0.001). More than one third of the patients (34.8%) died during follow-up. The overall survival in patients whose anemia improved was 79.8%, and it was 62.8% in patients whose anemia did not improve the overall survival was (p = 0.002) (Fig. 1). When examining the relationship between survival status and anemia severity for the non-dialysis-dependent CKD Stage 3-5 group, there was a statistically significant survival difference between the Hb group of 10-11.9 g/dL to Hb group of &amp;lt;10 g/dL (p = 0.004). Conclusion This study has shown that diagnostic tests for etiology of anemia were insufficiently ordered. It was also found that a significant majority of anemic patients who underwent etiological evaluation were not even adequately treated. Long-term follow up improved anemia treatment, and patients with improved anemia had better survival. In conclusion, we recommend an optimal evaluation of CKD patients with anemia and initiating treatment as early as possible.