Risk Of Kidney Disease Research Articles

The Actin and Microtubule Network Regulator WHAMM Is Identified as a Key Kidney Disease Risk Gene

The Actin and Microtubule Network Regulator WHAMM Is Identified as a Key Kidney Disease Risk Gene

Correlation between triglyceride-glucose index and diabetic kidney disease risk in adults with type 1 diabetes mellitus

BackgroundThe triglyceride-glucose (TyG) index is identified as an alternative indicator of insulin resistance (IR) and is associated with macro- and micro-vascular diseases among patients with type 2 diabetes mellitus. The relationship between the TyG index and IR and its impact on diabetic kidney disease (DKD) remains unclear among adults with type 1 diabetes mellitus(T1DM).MethodsThis study comprised a cross-sectional analysis using data from the Guangdong T1DM Translational Medicine Study (GTT) and a longitudinal analysis using data from the type 1 diabetes (T1D) Exchange registry study. Correlation analysis was used to investigate the association between the TyG index and IR. Logistic regression and Cox proportional hazards regression were performed to explore the impact of the TyG index on DKD risk.ResultsThe GTT Study included 836 adults (216 with DKD and 620 without DKD). A significant correlation existed between the TyG index and the estimated glucose disposal rate (r=-0.64, p < 0.01). The TyG index was a risk factor for DKD after confounder adjustment (OR = 1.34, 95% CI:1.03–1.74). The T1D Exchange registry study included 8,771 adults (2,050 with DKD and 6,721 without DKD). After adjusting confounding factors, the TyG index was identified as an independent risk factor for DKD at enrollment, with the highest risk of DKD incidence observed in the highest TyG tertile group (OR = 1.92, 95%CI:1.67–2.20). During a median follow-up of 44.58(21.84, 67.09) months, the risk of developing DKD was increased by 32% at every 1 SD increase of the TyG index over time among participants without DKD at enrollment.ConclusionsThe TyG index could be used to assess IR and was identified as an independent risk factor of DKD among adults with T1DM.

Designing Equitable Care for Kidneys (DECK): Community-Based Interventions for Addressing Social Determinants of Health and Kidney Disease Risk Factors

Designing Equitable Care for Kidneys (DECK): Community-Based Interventions for Addressing Social Determinants of Health and Kidney Disease Risk Factors

Разработка интеллектуальной системы поддержки принятия врачебных решений для прогнозирования хронической болезни почек у детей.

Introduction. Chronic kidney disease is often diagnosed too late. Currently, the diagnostic accuracy is 44.1%, which highlights the urgent need to improve diagnostic methods. The purpose of the study: to develop a model – a system of support of medical decisions to predict chronic kidney disease in children. Materials and methods. А one-center retrospective cohort study (2011–2022) of children with chronic kidney disease of 1–4 stages in the age from 1 to 17 years. To construct a predictive model for diagnosing chronic kidney disease in children, an ensemble learning method was used, using which the models obtained by machine learning algorithms were combined: multi-factor logistic regression and decision tree. The models use five variables: asthenic physique in a child, loss of protein and red blood cells with urine, ESR and blood serum sodium. Results. The study involved 158 patients. The main group includes 128 children with chronic kidney disease of stage 1–4 aged 1–17. The comparison group was 30 children with no diagnosed kidney pathology aged 1 to 17. The children of the two groups did not differ statistically by sex and age. A model has been obtained to predict chronic kidney disease in children on a test sample with an accuracy of 93.5% [87.1; 100.0]%; a sensitivity of 92.0% [82.1; 100.0]; a specificity of 100.0% [100.0; 100.0.0]; ROC-AUC = 98.7%;100.0].0. Obtained model of excellent quality (&gt;90%). The model describes 90.3% [83.8; 96.1]% variance. Conclusion. The proposed model demonstrates excellent predictive ability and may be of important clinical importance for predicting the chronic process in primary health care, where symptoms associated with the risk of chronic kidney disease, may be overlooked. Predicting and developing early nephroprotective strategies can lead to better treatment outcomes and prolong life.

Genetically predicted frailty index and risk of chronic kidney disease

Previous findings have reported the association between frailty and chronic kidney disease. However, the causality remains ambiguous. This study aimed to determine whether frailty index is causally associated with chronic kidney disease. We obtained the frailty genome-wide association study (GWAS) data and chronic kidney disease GWAS data from the FinnGen R5 (total n = 216,743; case = 3902, control = 212,841) as the exposure and outcome, respectively. A two-sample Mendelian randomization (MR) analysis was primarily conducted using the inverse-variance weighted (IVW), weighted median and MR-Egger regression analyses. Multivariable MR analysis (MVMR) was conducted for additional adjustment. In the two-sample Mendelian randomization analyses, a total of 14 single nucleotide polymorphisms (SNPs) were recognized as effective instrumental variables. The IVW method showed evidence to support a causal association between frailty index and chronic kidney disease (beta = 1.270; 95% CI 0.608 to 1.931; P < 0.001). MR-Egger revealed a causal association between frailty index and chronic kidney disease (beta = 3.612; 95% CI 0.805 to 6.419; P = 0.027). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = − 0.053; P = 0.119). The weighted median approach and weighted mode method also demonstrated a causal association between frailty index and chronic kidney disease (beta = 1.148; 95% CI 0.278 to 2.019; P = 0.011; beta = 2.194; 95% CI 0.598 to 3.790; P = 0.018). Cochran’s Q test and the funnel plot indicated no directional pleiotropy. MVMR analysis revealed that the causal association between frailty index and chronic kidney disease remained after adjusting for potential confounders, body-mass index, inflammatory bowel disease, waist-hip ratio, and C-reactive protein. Our study provides evidence of causal association between frailty and chronic kidney disease from genetic perspectives.

Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF. Urinary total protein, albumin, and markers of kidney injury and neutrophil activation, normalized to creatinine, as well as urinary immune cells, were quantified in CF (n = 48) and healthy (n = 33) cohorts. Infection burden and chronicity were defined by sputum culture and serum titers of anti-bacterial antibodies. PwCF had increased urinary protein levels, consisting of low-molecular-weight tubular injury markers, independent of glomerular filtration rate (eGFR). This finding suggests subclinical renal injury processes. Urinary analysis of the CF cohort identified different associations of urinary injury markers with aminoglycoside exposure, lung function, and neutrophil activation. High urinary KIM-1 levels and increased prevalence of neutrophils among urine immune cells correlated with decreased lung function in PwCF. The relationship between tubular injury and decreased lung function was most prominent in patients harboring chronic Pseudomonas aeruginosa infection. Increased urinary tubular injury markers in PwCF suggest early subclinical renal injury not readily detected by eGFR. The strong association of high urinary KIM-1 and neutrophils with diminished lung function and high Pseudomonas aeruginosa burden suggests that pulmonary disease may contribute to renal injury in CF.

Adult-Onset IgA Vasculitis Complicated by Kidney Failure at Disease Onset in a Nepalese Patient: A Case Report

Introduction: Immunoglobulin A (IgA) vasculitis, previously known as Henoch-Schönlein purpura, is an immune complex-mediated small vessel vasculitis primarily affecting children. While rare in adults, it can present with more severe manifestations, particularly involving the kidneys. This case report details the presentation and management of adult-onset IgA vasculitis with significant renal involvement.  Case Report: A 43-year-old male with a history of bipolar disorder presented with facial swelling, shortness of breath, and decreased urine output following an upper respiratory infection. Initial investigations revealed elevated blood pressure and renal impairment. Despite supportive treatment, his condition worsened, leading to a referral to a tertiary care center. He exhibited symptoms consistent with IgA vasculitis, including joint pain, rash, and nephrotic-range proteinuria. The diagnosis was confirmed through a skin biopsy and 24-hour urine collection. The patient was treated with intravenous methylprednisolone, oral prednisone, and an ACE inhibitor. His renal function improved with this regimen.  Discussion: Adult-onset IgA vasculitis can present with severe kidney involvement, including nephrotic-range proteinuria and elevated serum creatinine, which are associated with poorer outcomes compared to pediatric cases. The patient's management, involving glucocorticoids and an ACE inhibitor, aligns with current treatment recommendations for significant renal involvement. Long-term prognosis in adults remains challenging, with a higher risk of end-stage kidney disease compared to children. Vigilant monitoring and tailored treatment strategies are crucial for improving outcomes.  Conclusion: This case underscores the potential severity of adult- onset IgA vasculitis and highlights the importance of early diagnosis and aggressive management to mitigate long- term renal complications. Ongoing research is necessary to refine treatment approaches and enhance outcomes for adults with this condition.

Medullary Nephrocalcinosis

Medullary nephrocalcinosis is a clinical variant of chronic kidney disease characterized by diffuse deposition of calcium and phosphate salts in the parenchyma, leading to inflammatory-dystrophic changes and the development of chronic renal failure. Medullary nephrocalcinosis is divided into primary (develops in previously unaltered kidneys and initially affects the proximal part of the nephron) and secondary (simultaneously affects all parts of the renal glomeruli, causing nephrosclerosis and increasing the risk of chronic kidney disease). The article describes two clinical cases of medullary nephrocalcinosis with different etiological factors. In the first case, the disease developed against the background of regular use of third-generation cephalosporins (ceftriaxone), while in the second case, it resulted from lipid and purine metabolism disorders. The genetic and etiopathogenetic aspects of medullary nephrocalcinosis are discussed. Given the importance of determining the causes and pathogenetic mechanisms of medullary nephrocalcinosis, the need for thorough diagnostics in adult patients with changes in the renal parenchyma accompanied by hyperparathyroidism, hyper- or normocalcemia, hypophosphatemia, hypomagnesemia, and hypercalciuria is emphasized. Diagnostic workup should include genetic, metabolic, and iatrogenic components of kidney damage.

Investigation of end-stage kidney disease risk prediction in an ethnically diverse cohort of people with type 2 diabetes: use of kidney failure risk equation

IntroductionThe four variable kidney failure (KF) risk equation (KFRE) is recommended to estimate KF risk (ie, need for dialysis or kidney transplantation). Earlier referral to clinical kidney services for people...

Valuing a Reduction in the Risk of Chronic Kidney Disease: A Large-Scale Multi-Country Stated Preference Approach

Valuing a Reduction in the Risk of Chronic Kidney Disease: A Large-Scale Multi-Country Stated Preference Approach

Homelessness and Risk of End-Stage Kidney Disease and Death in Veterans With Chronic Kidney Disease

Adults experiencing homelessness in the US face numerous challenges, including the management of chronic kidney disease (CKD). The extent of a potentially greater risk of adverse health outcomes in the population with CKD experiencing homelessness has not been adequately explored. To evaluate the association between a history of homelessness and the risk of end-stage kidney disease (ESKD) and death among veterans with incident CKD. This retrospective cohort study was conducted between January 1, 2005, and December 31, 2017. Participants included veterans aged 18 years and older with incident stage 3 to 5 CKD utilizing the Veterans Health Administration health care network in the US. Patients were followed-up through December 31, 2018, for the occurrence of ESKD and death. Analyses were performed from September 2022 to October 2023. History of homelessness, based on utilization of homeless services in the Veterans Health Administration or International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Homelessness was measured during the 2-year baseline period prior to the index date of incident CKD. The primary outcomes were ESKD, based on initiation of kidney replacement therapy, and all-cause death. Adjusted hazard ratios (HRs) were calculated to compare veterans with a history of homelessness with those without a history of homelessness. Among 836 361 veterans, the largest proportion were aged 65 to 74 years (274 371 veterans [32.8%]) or 75 to 84 years (270 890 veterans [32.4%]), and 809 584 (96.8%) were male. A total of 26 037 veterans (3.1%) developed ESKD, and 359 991 (43.0%) died. Compared with veterans who had not experienced homelessness, those with a history of homelessness showed a significantly greater risk of ESKD (adjusted HR, 1.15; 95% CI, 1.10-1.20). A greater risk of all-cause death was also observed (HR, 1.48; 95% CI, 1.46-1.50). After further adjustment for body mass index, comorbidities, and medication use, results were attenuated for all-cause death (HR, 1.09; 95% CI, 1.07-1.11) and were no longer significant for ESKD (HR, 1.04; 95% CI, 0.99-1.09). In this cohort study of veterans with incident stage 3 to 5 CKD, a history of homelessness was significantly associated with a greater risk of ESKD and death, underscoring the role of housing as a social determinant of health.

Estimates of eskd risk and timely kidney replacement therapy education

BackgroundKidney replacement therapy (KRT) needs preparation and its timing is difficult to predict. Nephrologists’ predictions of kidney failure risk tend to be more pessimistic than the Kidney Failure Risk Equation (KFRE) predictions. We aimed to explore how physicians’ risk estimate related to referral to KRT education, vs. the objective calculated KFRE.MethodsProspective observational study of data collected in chronic kidney disease (CKD) clinics of the Veterans Affairs Medical Center San Diego and the University of California, San Diego. The study included 257 participants who were aged 18 years or older, English speaking, prevalent CKD clinic patients, with estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m2 (MDRD equation). The exposure consisted of end stage kidney disease (ESKD) risk predictions. Nephrologists’ kidney failure risk estimations were assessed: “On a scale of 0–100%, without using any estimating equations, give your best estimate of the risk that this patient will need dialysis or a kidney transplant in 2 years.” KFRE was calculated using age, sex, eGFR, serum bicarbonate, albumin, calcium, phosphorus, urine albumin/creatinine ratio. The outcomes were the pattern of referral to KRT education (within 90 days of initial visit) and kidney failure evaluated by chart review. The population was divided into groups either by nephrologists’ predictions or by KFRE. Referral to KRT education was examined by group and sensitivity and specificity were calculated based on whether participants reached kidney failure at 2 years.ResultsA fifth were referred for education by 90 days of enrollment. Low risk patients by both estimates had low referral rates. In those with nephrologists’ predictions ≥ 15% (n = 137), sensitivity was 71% and specificity 76%. In those with KFRE ≥ 15% (n = 55), sensitivity was 85% and specificity 41%.ConclusionsAlthough nephrologists tend to overestimate patients’ kidney failure risk, they do not appear to act on this overestimation, as the rates of KRT education referrals are lower than expected when a nephrologist identifies a patient as high risk.Clinical Trial NumberNot applicable

Prediction factors and models for chronic kidney disease in type 2 diabetes mellitus: A review of the literature

AbstractDiabetes mellitus (DM) has become a major chronic disease seriously affecting human health. Type 2 diabetes mellitus (T2DM) accounts for about 90% of DM patients, which is the largest type. Approximately 25–35% of T2DM patients develop kidney disease, which not only impacts the survival rate and quality of life but also, to the family and society, are of great economic burden. Early identification of high‐risk T2DM patients with kidney disease is crucial for initiating targeted prevention and treatment measures in time to reduce or delay the occurrence and progression of diabetic kidney disease. Previous studies have identified a variety of clinical predictors for the progression of renal function in T2DM patients, including proteinuria, estimated glomerular filtration rate, blood glucose, blood pressure, serum uric acid, dyslipidemia, obesity, smoking, duration of DM, age, gender, race, family history of DM, and diabetic retinopathy. Clinical prediction models based on conventional clinical indicators are instrumental in evaluating the risk of kidney disease in T2DM patients, assisting in patient risk stratification. This article systematically reviews the clinical prediction factors and prediction models associated with the progression of renal function in T2DM patients, providing a comprehensive and current reference for improved clinical assessment of the risk of renal function progression.

Association of dietary iron intake with diabetic kidney disease among individuals with diabetes.

The current study investigated the correlation between dietary iron intake and diabetic kidney disease among diabetic adults. This cross-sectional study enrolled 8118 participants who suffered from diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Dietary iron intake was obtained from 24 h recall interviews, and diabetic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or albumin creatinine ratio (ACR) ≥ 30 mg/g. Three weighted logistic regression models were utilized to investigate odd ratio (OR) and 95% CIs for diabetic kidney disease. Stratified analyses were performed by gender, age, BMI, HbA1c, hypertension status, and smoking status, and diabetes types. Among 8118 participants (51.6% male, mean age 61.3 years), 40.7% of participants suffered from diabetic kidney disease. With the adjustment of potential covariates, we found that ≥ 12.59 mg of dietary iron was related to a lower risk of diabetic kidney disease (OR = 0.78, 95% CI: 0.63 to 0.96; OR = 0.79, 95% CI: 0.63 to 0.98). In stratified analyses, higher iron intake was negatively related to diabetic kidney disease, especially among those who were male, < 60 years, those with hypertension, those with HbA1c < 7.0%, and those who were ex-smokers. The result remained robust in sensitivity analyses. We found that ≥ 12.59 mg of dietary iron is associated with a lower risk of diabetic kidney disease, especially in those who were male, younger, heavier weight, have better blood sugar control, and those who were ex-smokers.

Abstract P337: Impact of a population health approach using smartphone-enabled home albuminuria testing to improve screening in patients with hypertension or diabetes

Background: Screening for albuminuria with urine albumin/creatinine ratio (ACR) testing among at risk patients is critical as guideline-based therapies can be used to decrease the risk of cardiovascular and kidney disease. However, adherence to testing remains very low, especially for hypertension. Here, we report the results from a prospective pilot study involving a smartphone-enabled home albuminuria testing quality improvement. Methods: We randomly selected 4000 adult individuals (50% with hypertension but no diabetes and 50% with diabetes +/- hypertension) receiving primary care at a large healthcare system in Central and Northeastern Pennsylvania who had not undergone ACR testing in the past 12 months to receive Minuteful Kidney, an FDA-cleared, smartphone-enabled home urine albuminuria screening kit using the vendor’s (Healthy.io) standard workflow. The home testing group was matched 1:1 to 4000 controls who received usual care using propensity score matching addressing imbalances in sociodemographics and comorbidities. The primary outcome was completion of ACR test (either laboratory based ACR or Minuteful Kidney) within 100 days of the index date. Results shown are as of May 1, 2024 (86 days after the index date). Results: Overall, completion of any ACR test was higher in the home testing group than matched controls (50.2% vs. 19.1%; p&lt;0.001). The impact on ACR testing was higher for the hypertension subgroup (50.4% vs. 11.2%; p&lt;0.001) than the diabetes subgroup (49.9% vs. 26.9%; p&lt;0.001). Among the home testing group, 1542/4000 (38.7%) completed the smartphone ACR test, with a higher proportion of completions in non-diabetic hypertension (848/2000 [42.4%] than the diabetes subgroup (663/2000 [33.2%]). Adherence rates were similar across age groups and geographic location. Satisfaction was high among individuals in the home testing group (53+ Net Promoter Score; 94% rated the test as easy or very easy to complete; 88% stated preference for at home testing). Home-based albuminuria screening detected mild to moderate albuminuria (30-300 mg/g) in 33.2% and severe albuminuria (&gt;300 mg/g) in 8.1%. Abnormal results were fairly similar for the diabetes subgroup (33.8% 30-300 mg/g, 10.8% &gt;300 mg/g) and the hypertension subgroup (32.6% 30-300 mg/g, 5.9% &gt;300 mg/g). Conclusions: A population health approach using smartphone-enabled home albuminuria testing is effective in increasing albuminuria screening among individuals with hypertension or diabetes.

Identifying subtypes of type 2 diabetes mellitus based on real-world electronic medical record data in China

AimsTo replicate the European subtypes of type 2 diabetes mellitus (T2DM) in the Chinese diabetes population and investigate the risk of complications in different subtypes. MethodsA diabetes cohort using real-world patient data was constructed, and clustering was employed to subgroup the T2DM patients. Kaplan–Meier analysis and the Cox models were used to analyze the association between diabetes subtypes and the risk of complications. ResultsA total of 2,652 T2DM patients with complete clustering data were extracted. Among them, 466 (17.57 %) were classified as severe insulin-deficient diabetes (SIDD), 502 (18.93 %) as severe insulin-resistant diabetes (SIRD), 672 (25.34 %) as mild obesity-related diabetes (MOD), and 1,012 (38.16 %) as mild age-related diabetes (MARD). The risk of chronic kidney disease (CKD) and diabetic retinopathy (DR) were different in the four subtypes. Compared with MARD, SIRD had a higher risk of CKD (HR 2.40 [1.16, 4.96]), and SIDD had a higher risk of DR (HR 2.16 [1.11, 4.20]). The risk of stroke and coronary events had no difference. ConclusionsThe European T2DM subtypes can be replicated in the Chinese diabetes population. The risk of CKD and DR varied among different subtypes, indicating that proper interventions can be taken to prevent specific complications in different subtypes.

Abstract P116: Hypertension Treatment and Control in Canadians with Diabetes

Introduction: 3 million Canadians and 23 million Americans have concurrent hypertension and diabetes. Blood pressure (BP) control reduces the risk of heart attacks, strokes, retinopathy, and kidney disease. We investigated hypertension control rates in patients with diabetes, responses to uncontrolled BP measurements, and use of antihypertensive drug classes. Methods: We performed an observational study of adults with diabetes and hypertension drawing from the IQIVA primary care database (contains data on 1.2 million Canadians). Our first outcome was mean BP at 3, 6, 12, and 24 months after inclusion. Our second outcome was the number of uncontrolled BP measurements (≥130/80) followed by a physician BP check, medication dose/frequency increase, or new medication in the subsequent 6 weeks. Our third outcome (for a subset of individuals with medication data available) was the number of individuals prescribed renin-angiotensin-aldosterone-system inhibitors (RAASi), dihydropyridine calcium channel blockers (DHP-CCBs), or thiazide/thiazide-like diuretics. Results: We identified 10,814 individuals identified with both diabetes and hypertension. Mean BP (in mmHg) remained largely unchanged over 24 months: 136.7/78.6 at 3 months, 135.5/82.2 at 6 months, 137.2/82.8 at 12 months, and 136.6/82.3 at 24 months. Over the two years of follow-up there were 55,381 uncontrolled BP events, and in the subsequent 6 weeks only 27,877 (50.3%) were followed by ≥1 physician BP checks. Among individuals with medication data, there were 16,364 uncontrolled BP events, 33.4% followed by a new antihypertensive medication and 18.2% followed by an antihypertensive dose/frequency change. Of the 6,919 individuals for whom we had medication data, 6,216 (89.8%) were prescribed a RAASi, 2,371 (34.3%) were prescribed a DHP-CCB, and 1,672 (24.2%) were prescribed thiazide/thiazide like diuretic. Conclusion: Over two-thirds (68.8%) of people with diabetes and hypertension had uncontrolled blood pressure that persisted over 2 years during which half of uncontrolled BPs were followed by a physician BP check in 6 weeks, and one-fifth by a antihypertensive dose/frequency change. While almost 90% were treated with RAASi, over a third were on a DHP-CCB and less than one quarter were treated with a thiazide/thiazide like diuretic. Therapeutic inertia and under-prescribing of dual and triple therapy contribute to persistently high BP thus represent opportunities for improvement.

Improving the management of chronic kidney disease in primary care by enhancing laboratory reports with additional information and follow-up procedures

Identifying people at risk for progressive chronic kidney disease and connecting them with recommended care is crucial for providing timely and optimal treatment. The ASSIST-CKD (A programme to Spread eGFR [estimated glomerular filtration rate] graph Surveillance for the early identification, Support and Treatment of people with progressive CKD [chronic kidney disease]) trial evaluated the effect of graphical eGFR reporting to primary care physicians on late presentation to a nephrologist in the United Kingdom. Trial data were obtained from the UK Renal Registry. Although the results were neutral, the data generated from the ASSIST-CKD trial are informative and provide useful estimates of the intervention effect. The trial also provides valuable insights into the challenges of implementing complex interventions in busy health care environments, which can be used to guide the designs of future interventions.

Metabolically healthy obesity and chronic kidney disease risk: exploring the dynamics.

Obesity represents a prevalent global health concern with significant implications for various diseases, including chronic kidney disease (CKD). Within this landscape, the phenomenon of metabolically healthy obesity has emerged, challenging traditional notions about the health risks associated with excess weight. While traditional CKD risk factors involve obesity, metabolic syndrome, diabetes, and hypertension, the metabolically healthy obese (MHO) subgroup disrupts these assumptions. Our main objective in this study is to integrate existing literature on CKD in MHO individuals. In this endeavor, we delve into the pathophysiological foundations, the transition between obesity phenotypes and their impact on renal health, examine the implications of their metabolic resilience on mortality within a renal context, and explore potential management strategies specifically designed for MHO individuals. Offering a comprehensive overview of the pathophysiology, we cover various factors contributing to the risk of CKD in the metabolically healthy obese setting, including inflammation, cytokines, hemodynamics, and the renin-angiotensin-aldosterone system, gastrointestinal microbiota, diet, exercise, adipose distribution, and lipotoxicity. Through this synthesis, we aim to provide a comprehensive understanding of the risk of CKD in those classified as MHO.

O40 TELOMERE LENGTH AS A BIOMARKER FOR KIDNEY HEALTH: EVIDENCE FROM A MENDELIAN RANDOMISATION STUDY

Background and Objective: Chronic kidney disease (CKD) is a significant public health challenge, often progressing undetected until advanced stages. Early detection through biomarkers can enhance CKD management and improve patient outcomes. Previous studies suggested a link between telomeres and kidney health, but these results were inconsistent. This study aims to clarify the association between telomere length, kidney function and disease, and assess its causality using Mendelian randomisation (MR). Methods: Using the UK Biobank data, we examined the relationship between leukocyte telomere length (LTL) and kidney health. We performed multiple linear and logistic regression analyses using estimated glomerular filtration rate (eGFR) measures and reported kidney disease diagnoses, adjusting for age, sex, white blood cell count, body mass index, and hypertension. The causality of associations was tested using MR with established genetic instruments. Results: 338,143 participants were included in our analysis. The cohort had an average age of 56.52 years, with 54.41% being females. LTL was associated with eGFR from serum creatinine (eGFRcrea, beta = 0.001, p &lt;0.01), serum cystatin C (eGFRcys, beta = 0.004, p &lt;0.0001), and their combination (eGFRcreacys, beta = 0.003, p &lt;0.0001). Additionally, longer LTL was associated with reduced odds of CKD (OR = 0.94 [95% CI 0.93-0.96], p &lt;0.0001). Significant associations were also observed between LTL and acute renal failure (OR = 0.95 [95% CI 0.93-0.97], p &lt;0.0001), and hypertensive kidney disease (OR = 0.91 [95% CI 0.86-0.96], p &lt;0.001). MR analysis supported a causal effect of LTL on eGFRcrea (Effect size = 0.006, Bonferroni corrected p = 0.04). However, no causal effect was observed between LTL and CKD or other kidney diseases. Bi-directional MR analysis revealed that the relationship between LTL and kidney function is unidirectional. Conclusions: Longer LTL correlates with better kidney function and reduced kidney disease risk. MR findings suggest a potential causal relationship between LTL and kidney function, highlighting telomeres as promising biomarkers for early detection of CKD.