Chronic Kidney Disease Outcomes Research Articles

Factors associated with risk analysis for asymptomatic left ventricular diastolic dysfunction in nondialysis patients with chronic kidney disease

Heart failure (HF) constitutes a major determinant of outcome in chronic kidney disease (CKD) patients. The main pattern of HF in CKD patients is preserved ejection fraction (HFpEF), and left ventricular diastolic dysfunction (LVDD) is a frequent pathophysiological mechanism and specific preclinical manifestation of HFpEF. Therefore, exploring and intervention of the factors associated with risk for LVDD is of great importance in reducing the morbidity and mortality of cardiovascular disease (CVD) complications in CKD patients. We designed this retrospective cross-sectional study to collect clinical and echocardiographic data from 339 nondialysis CKD patients without obvious symptoms of HF to analyze the proportion of asymptomatic left ventricular diastolic dysfunction (ALVDD) and its related factors associated with risk by multivariate logistic regression analysis. Among the 339 nondialysis CKD patients, 92.04% had ALVDD. With the progression of CKD stage, the proportion of ALVDD gradually increased. The multivariate logistic regression analysis revealed that increased age (OR 1.237; 95% confidence interval (CI) 1.108–1.381, per year), diabetic nephropathy (DN) and hypertensive nephropathy (HTN) (OR 25.000; 95% CI 1.355–48.645, DN and HTN vs chronic interstitial nephritis), progression of CKD stage (OR 2.785; 95% CI 1.228–6.315, per stage), increased mean arterial pressure (OR 1.154; 95% CI 1.051–1.268, per mmHg), increased urinary protein (OR 2.825; 95% CI 1.484–5.405, per g/24 h), and low blood calcium (OR 0.072; 95% CI 0.006–0.859, per mmol/L) were factors associated with risk for ALVDD in nondialysis CKD patients after adjusting for other confounding factors. Therefore, dynamic monitoring of these factors associated with risk, timely diagnosis and treatment of ALVDD can delay the progression to symptomatic HF, which is of great importance for reducing CVD mortality, and improving the prognosis and quality of life in CKD patients.

#2526 Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate

Abstract Background and Aims Chronic kidney disease (CKD) is a growing global health concern. In recent years, studies have increasingly focused on the differential risk profile of diseases between men and women. Current evidence suggests that sex-linked biological and behavioral differences may play a key role in influencing the incidence, prevalence, and outcomes of diseases. Similarly, previous studies have demonstrated a differential risk profile in the prevalence, progression, and outcomes of CKD between men and women. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. Method We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73 m². The outcomes were CKD-related complications (hypertension, anemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. Values of eGFR over which the log-odds (for CKD-related complications outcomes) or log-hazard (for all-cause and cause-specific mortality outcomes) was found to be significantly different from zero (i.e., 95% CI for the smooth term did not contain zero) were identified as thresholds of statistical significance. Results The study included 49, 562 participants (50.31% women, 49.68% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modeling eGFR as a natural spline revealed varied significance thresholds between sexes for anemia and hyperparathyroidism. We found a significantly (P < 0.05) higher proportion of women with anemia downstream an eGFR cut-off of 69 mL/min per 1.73 m2, which was lower than the cut-off in men; a significantly higher proportion of men with anemia was observed downstream an eGFR cut-off of 76 mL/min per 1.73 m2. However, the relationship was more pronounced in women than in men; thus, at an eGFR cut-off of 41 mL/min per 1.73 m2, the proportion of women with anemia was significantly higher (P < .05) (Figure). Similarly, a higher proportion of women with hyperparathyroidism were observed downstream an eGFR cut-off of 73 mL/min per 1.73 m2, which was lower than in men; a significantly higher proportion of men (P < .05) was observed downstream an eGFR cut-off of 89 mL/min per 1.73 m2 (Figure). Furthermore, although no sex differences were observed in terms of eGFR thresholds for hyperphosphatemia, a more pronounced relationship was observed in men. Thus, at an eGFR cut-off of 38 mL/min per 1.73 m2, the proportion of men with hyperphosphatemia was significantly higher (P < .05) than that of women (Figure). We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR Conclusion Research shows sex disparities in most CKD-related complications. Men develop anemia and hyperparathyroidism earlier, women show steeper anemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

#1471 The role of genealogy in patients with CKD in primary health care

Abstract Background and Aims Improving the risk prediction of adverse outcomes of chronic kidney disease at the level of primary care physicians, through early diagnosis of chronic kidney disease, can help reduce the progression of the disease, improve the clinical condition of patients and the prognosis of the disease, reduce the number of patients with terminal stage, reduce disability rates and reduce lethality. The aim of our study is to explore the role of genealogical analysis in patients with CKD at the primary care level. Method In primary healthcare settings, 217 patients with CKD were under observation, with an average age of 46.17±0.63 years, predominantly of Uzbek nationality. A control group of 20 healthy people of Uzbek nationality of the same age without signs of CKD. After compiling the legend of 217 families, a pedigree was compiled and a genealogical analysis was carried out. In order to identify the severity of CKD, the data obtained were compared with the results of an analysis of pedigrees of individuals (n=20) in a healthy population. Using the genealogical method, 893 first-degree relatives (parents, siblings) of patients with CKD were examined for the presence of renal pathology. A detailed pedigree was compiled, which included information about diseases in 2-3 generations of the family. Genetic material was collected from both parental lines by cross-questioning both parents, and sometimes grandparents. A total of 1761 people were analyzed in the model population. Results The data obtained were compared with the generalized family response of 20 practically healthy people, in the model population of which 172 people were analyzed, of which the incidence of renal pathology was 2.13%. A comparative analysis of a generalized family portrait of patients with CKD with a generalized family portrait of a population of practically healthy people revealed a more frequent incidence of renal pathology in relatives with CKD (11.07%%). In families of probands, renal pathology in generations in relation to the total number of patients of each concentration is III - 7.49%; II - 11.06%; I- 17.43%. The burden in the population of practically healthy people was observed significantly less: III - 0%; II- 0.15%; I- 0%. It turned out that renal pathology more often affects first-degree relatives (130 (14.56%), which in relation to the total number of patients in this concentration is 7.38%. Hereditary burden of renal pathology was observed more often on the father's side in 46 (10.60±0.34%) than on the mother's side in 19 (4.38±0.34%). Conclusion The results of our study indicate a significant prevalence of CKD in families of probands, but with a predominance of first-degree relatives being affected. Pedigree analysis confirms the absence of a monogenically inherited disease, such as simple recessive or dominant inheritance. Along with this, the widespread prevalence of renal pathology in the population suggests that only a predisposition to the development of CKD is inherited. Thus, according to our data, it is necessary to recommend the study of genealogical analysis of patients at the level of primary healthcare. Moreover, this is more accessible in primary health care with family doctors.

#985 Disease outcomes of chronic kidney disease: a Phenome-wide association study

Abstract Background and Aims Chronic kidney disease (CKD) is one of the prevalent diseases worldwide leading to increasing global disease burden, however, comprehensive studies of the subsequently developed disease outcomes are lacking. We aimed to explore the associations between CKD and a broad range of following disease conditions. Method Polygenic risk score (PRS) of 347308 white participants in UK Biobank were calculated using PLINK1.9 software with summing of risk alleles weighted by the effect sizes of. Genome-wide association study (GWAS) summary statistical data of CKD from CKDGen consortium was utilized as base data. The phenome codes of disease outcomes were derived from the primary and secondary diagnoses of ICD-10 and ICD-9 codes in the HSE records in the U.K. Biobank. Then, the association between genetically predicted eGFR and following disease outcomes were evaluated using logistic regression adjusting for age (continuous variables), sex (male/female), assessment cancer (category variables), and the first 10 genetic principal components (PCs) (continuous variables). PRS of eGFR was scaled to a unit reflecting one SD (equals to 1) decrease of PRS. We applied the Bonferroni correction (P threshold = 0.05/665 phecodes = 7.52 × 10−5) to correct for multiple testing. Results Totally, 261,254 SNPs (pruned by r2 < 0.1 within the 250 kb region, P < 0.4) from base data were retained for PRS calculation. Our PheWas identified that one standard deviation (SD) increase in the PRS of CKD significantly associated with chronic renal failure (OR = 1.16, 95% CI: 1.14-1.18, P = 2.01 × 10−66), essential (primary) hypertension (OR = 1.05, 95% CI: 1.04-1.06, P = 2.12 × 10−29), hypertensive renal disease (OR = 1.22, 95% CI: 1.16-1.29, P = 3.81 × 10−14), gout (OR = 1.09, 95% CI: 1.07-1.12, P = 6.57 × 10−13), intestinal malabsorption (OR = 1.12, 95% CI: 1.08-1.16, P = 6.71 × 10−9), acute renal failure (OR = 1.05, 95% CI: 1.03-1.07, P = 2.08 × 10−8), disorders of lipoprotein metabolism and other lipidaemias (OR = 1.03, 95% CI: 1.01-1.04, P = 9.11 × 10−7), non-insulin-dependent diabetes mellitus (OR = 1.03, 95% CI: 1.02-1.04, P = 3.11 × 10−6), obesity (OR = 1.03, 95% CI: 1.02-1.05, P = 3.13 × 10−6), unspecified renal failure (OR = 1.11, 95% CI: 1.06-1.16, P = 1.18 × 10−5), chronic ischaemic heart disease (OR = 1.03, 95% CI: 1.01-1.04, P = 1.52 × 10−5). Conclusion Increased risk of CKD significantly associated with a series of subsequent conditions, providing evidence for prevention of following diseases in patients with CKD.

#2509 Longitudinal haemoglobin levels and mortality in an elderly population with advanced chronic kidney disease: insights from the EQUAL Study

Abstract Background and Aims The relationship between haemoglobin (Hb) levels and clinical outcomes in chronic kidney disease (CKD) is more intricate than previously understood, as both low and high values can have detrimental effects. Although the association between Hb and patient outcomes is widely reported, few studies have focused on older patients with advanced CKD or have explored this relationship both before and after kidney replacement therapy (KRT) initiation. The primary objective of this study is to describe the relationship between Hb levels and mortality in older patients with advanced CKD in the continuum from pre-KRT phase to subsequent KRT initiation, and to evaluate any effect modification by KRT initiation. Method We used data from the European QUALity Study on treatment in advanced CKD (EQUAL) cohort which includes patients aged ≥65 years and eGFR ≤20 ml/min per 1.73 m2 from six European countries. The association between Hb and all-cause and cause-specific mortality (cardiovascular [CV] and non-cardiovascular [non-CV] mortality) was explored in three separate CKD populations: pre-KRT, KRT and transition-CKD (transition phase surrounding the start of KRT) population. Multivariable adjusted time-dependent Cox regression models and natural cubic splines were used to investigate the association between longitudinal Hb levels (as categorical and continuous variable) and mortality risk in the pre-KRT and KRT population. The area under the Hb trajectory (AUC Hb) before KRT initiation was calculated to evaluate the relationship between the cumulative exposure of Hb before KRT initiation and all-cause mortality after KRT initiation in the transition-CKD population. We evaluated effect modification by pre-specified variables on the relationship between Hb and mortality. Results Overall, 1716 CKD patients were included in the study. During a median follow up of 3.0 years (IQR 2.6), 614 patients died, resulting in a 5-year survival probability of 51% (95% CI 48, 55). Low Hb levels were consistently associated with increased mortality risk in all study populations (Figure). A U-shaped association between both the lowest and highest levels of Hb and mortality risk was observed (Figure). A similar association was observed for non-CV mortality, with lower Hb values associated with an increased mortality risk (Figure). Conversely, a trend towards higher risk of cardiovascular death was observed as Hb levels increase, especially in the whole population and pre-KRT population (Figure), albeit not statistically significant. Low cumulative exposure of Hb in the transition-CKD population was associated with increased mortality risk after transitioning to KRT (p = 0.047). In subgroup analysis diabetic patients were more susceptible to low Hb levels (p-value for interaction = 0.003) while patients on ESA therapy (p-value for interaction = 0.005) or initiating KRT (p-value for interaction = 0.024) showed increased mortality risk for high Hb levels. Conclusion The relationship between Hb levels and mortality in advanced CKD patients is complex. Low Hb levels consistently indicate an increased risk of mortality, while high Hb levels also appear to have a negative effect, increasing mortality risk, particularly in patients receiving ESA therapy and after KRT initiation. Our work emphasizes how different stages of advanced kidney disease (i.e., before and after initiating KRT), as well as comorbidities such as diabetes or medications such as ESA therapy can significantly influence the relationship between Hb and mortality.

#1215 Association between dietary magnesium intake and incident chronic kidney disease

Abstract Background and Aims Recent studies suggest a close association between low serum magnesium levels and kidney injury. However, whether dietary magnesium intake relates with kidney function is not well known. In this study, the relationship of dietary magnesium intake with the development of chronic kidney disease (CKD) was evaluated. Method This observational prospective study screened 210,965 European adults aged 40-70 who underwent dietary questionnaire from April 2009 to June 2012 in UK Biobank cohort. Participants with underlying CKD (baseline eGFR < 60 mL/min/1.73 m² or urine albumin-to-creatinine ratio >30 mg/g/Cr) or implausible energy intake (reported energy intake < 1.1 × basal metabolic rate [BMR] or 2.5 × BMR) were excluded. Dietary magnesium intake was assessed through online 24-hour recall dietary questionnaire and adjusted for energy intake using residual method. The participants were categorized into quartile according to energy-adjusted dietary magnesium intake. Primary outcome was incident CKD diagnosed through ICD-10 and OPCS-4 codes. Incident CKD defined as eGFR < 60 mL/min/1.73 m² was also assessed as an additional primary outcome in the sub-cohort with primary care creatinine follow-up data. Results A total of 114,916 participants was included in the final analysis. The median age was 57.0 (IQR, 50.0-63.0) years and 56.8% were female. Median magnesium intake amount per person was 345.6 (IQR, 296.8-402.5) mg/day. During a 1,095,128.6 person-year follow-up, CKD outcome occurred in 3,337 patients. Incidence of CKD was progressively lower in patients with higher magnesium intake (3.2%, 2.9%, 2.8%, and 2.7% in Q1-4, respectively). Cox regression analysis revealed that the hazard ratios (HRs) for incident CKD decreased in a stepwise manner towards higher magnesium intake quartiles (2Q: HR, 0.89; 95% CI, 0.81-0.98; 3Q: HR, 0.87; 95% CI, 0.0.79-0.95; 4Q: HR, 0.84; 95% CI, 0.76-0.92) relative to 1Q (P for trend < 0.001). This association was maintained even after adjustments were made for confounding factors. Similar results were observed with eGFR-defined CKD outcome (2Q: adjusted HR [AHR], 0.75; 95% CI, 0.64-0.89; 3Q: AHR, 0.73; 95% CI, 0.61-0.87; 4Q: AHR, 0.70; 95% CI, 0.58-0.85) relative to 1Q (P for trend < 0.001). Conclusion Higher intake of dietary magnesium may relate with lower risk of incident CKD in adults with normal kidney function.

#2677 A propensity score-matched analysis of kidney replacement therapy outcomes for older adults stratified by frailty severity

Abstract Background and Aims Older people living with frailty who receive kidney replacement therapy (KRT) experience higher mortality and hospital readmission compared to their non-frail counterparts [1–3]. Shared decision making with older people regarding the optimal KRT modality (haemodialysis [HD], peritoneal dialysis [PD], or kidney transplant [TX]) can present challenges due to the lack of research comparing KRT modalities stratified by frailty severity. The Hospital Frailty Risk Score (HFRS), which uses routinely collected clinical data to categorise frailty severity, has been shown to predict outcomes in advanced chronic kidney disease (CKD) [4]. However, the HFRS has not been used to compare outcomes across KRT modalities. This single-centre project aims to explore outcomes between KRT modalities for older people stratified by HFRS frailty severity. Method Adults aged 60 years or older starting KRT at our institution between December 2012 and January 2022 were included. HFRS was calculated at first estimated glomerular filtration rate (eGFR) result below 15 mL/min/1.73 m2 and at start of KRT. Patients were stratified by KRT modality and their frailty severity (categorized as low, intermediate, or high according to their HFRS score). TX patients were then matched to 1:2 to HD patients and 1:1 to PD patients, based on patient age, HFRS category, and Charlson Comorbidity Index (CCI) at KRT start. Outcomes of interest were hospital readmission and mortality, both overall and within 1 year of KRT initiation. Descriptive statistics compared HD, PD, and TX groups. Results Twenty TX, 20 PD, and 40 HD matched patients were included. Age (HD vs PD vs TX: 68.5 vs 67.6 vs 68.3 years, p = 0.50), proportion of males (57.5% vs 70.0% vs 55.0%, p = 0.66), and CCI (15.0 vs 13.0 vs 13.0, p = 0.95) were similar between cohorts. Frailty, as assessed by the HFRS, worsened or remained the same for most patients in all 3 cohorts between first eGFR < 15 and KRT start (81.0% vs 93.0% vs 83.0%, p = 0.61). All patients were either of low (85.0% vs 80.0% vs 85.0%) or intermediate (15.0% vs 20.0% vs 15.0%) frailty status at time of KRT start and the proportion of patients in each category did not vary with modality (p = 0.92). Re-hospitalization within 1 year of starting KRT was similar between groups (32.5% vs 25.0% vs 10.0%, p = 0.12). Kaplan-Meier survival analyses also demonstrated similar survival among groups at 1 year (75.0% vs 95.0% vs 90.0%, log-rank p = 0.09), but better survival among TX patients overall (0.0% vs 66.1% vs 79.4%, log-rank p = 0.02). Overall and 1 year Kaplan-Meier survival for patients stratified by KRT modality and HFRS are shown in Fig. 1. Conclusion TX may optimize longer term survival for older people with low and intermediate frailty status and kidney failure. Furthermore, the HFRS appears to be a useful prognostic tool that could inform shared decision making with older patients regarding KRT modality choice.

#3095 Pinpointing specific circulating microRNAs as putative biomarkers for chronic kidney disease and cardiovascular outcomes

Abstract Background and Aims Chronic kidney disease (CKD) affects over 10% of the worldwide population and entails a significant risk for cardiovascular disease (CVD), leading to an up to 500-fold increase in cardiovascular mortality in advanced stages. However, the pathophysiological mechanisms underlying kidney-heart intercommunication remain unknown. In recent years, microRNAs (miRNAs) emerged as critical regulators of gene expression and numerous miRNAs that have been implicated in both CKD and CVD pathogenesis. Still, so far, their role in kidney-heart crosstalk has not been addressed. In this study, we evaluated the expression of a panel of miRNAs in plasma from pre-dialysis CKD patients and explored their association with main comorbidities and significant outcomes in a 5-year follow up. Method The expression levels of miR-30c-5p, miR-132-3p, miR-199a-5p, and miR-324-3p was assessed by real time qRT-PCR in plasma samples from two cohorts of pre-dialysis CKD patients followed up at the Nephrology Department of Centro Hospitalar Universitário de São João (CHSJ, Porto, Portugal).The discovery cohort was established between November 2014 and August 2018 and comprises 52 CKD patients while the validation cohort comprises samples from 43 CKD patients who underwent a kidney biopsy for diagnostic purposes from November 2019 to December 2022. Patients with acute kidney injury, neoplasia diagnosis, recent infections (<1 week), or known psychiatric disorders were excluded from the study. Plasma samples from 38 healthy blood donors, recruited at the Immunohemotherapy Department of CHSJ, in which creatinine values were measured and considered normal were used as controls. Participants with a history of cancer, inflammatory, or infectious diseases and who were being treated with anti-inflammatory or anti-depressive drugs, were excluded. MiRs expression in comparison with the controls was validated in both cohorts and its expression in the Discovery cohort was correlated with the patients clinical data in a 5 year follow up. Results Results show that miR-30c-5p and miR-132-3p were downregulated in CKD patients compared with healthy controls, presenting a significant power to discriminate the disease condition. Still, considering the stratification of CKD in early/moderate (1-3) and advanced stages (4-5), only miR-30c-5p presented a decreased expression in the initial stages of the disease, showing a significant diagnostic value as an early biomarker for CKD, independently of eGFR. When analyzing the major disease outcomes in a 5 year time, miR-199a-5p was associated with increased frequency of CVD and mortality while miR-324-3p was downregulated in CKD patients that progressed to worse stages. Conclusion These findings highlight miR-30c-5p as a potential biomarker for the diagnosis of CKD in early stages of the disease and identify, for the first time, the enrollment of miR-199a-5p and miR-324-3p in kidney-heart pathophysiological crosstalk, paving the way for the putative establishment of new biomarkers and therapeutic targets for CKD and its outcomes.

#1986 Incidence of renal anemia among patients with atrial fibrillation and chronic kidney disease stage IIIb-V

Abstract Background and Aims According to the QICKD study, the prevalence of anemia in stage IIIb-V chronic kidney disease (CKD) is 22%. The incidence of renal anemia ranges from 8.4% in patients with stage I CKD to 83.7% in patients with stage V CKD. In patients on program hemodialysis, anemia develops in 94.5% of cases. The problem is associated with an increased risk of unfavorable outcome of CKD, therefore, the study of aspects of anemia among patients receiving anticoagulant therapy with atrial fibrillation (AF) and CKD remains the most relevant today. The purpose of the study is to study the prevalence of renal anemia among patients with AF and CKD stages IIIb-V. Method 794 patients were admitted to the cardiology department with a diagnosis of AF and late stages of CKD—IIIb (glomerular filtration rate (GFR) 45–30 ml/min/1.73 m2), IV (GFR 29–15 ml/min/1.73 m2), V (GFR <15 ml/min/1.73 m2), for the first identified sustained decrease in glomerular filtration rate (FISD in GFR) of less than 45 ml/min/1.73 m2. The classification of renal anemia was carried out according to the recommendations of the World Health Organization. Results Renal anemia was diagnosed in 505 (63%) patients with AF and GFR less than 45 ml/min/1.73 m2. In total, among patients with CKD stage IIIb, anemia was detected in 207 (59%) patients, with CKD stage IV—in 110 (89%), with CKD stage V—in 43 (97%), with FISD in GFR—in 145 (51%). A mild degree of anemia (hemoglobin (Hb) in men 110-129 g/l, in women 110-119 g/l) was diagnosed in 39% of patients, with CKD stage IIIb in 85 (24%) patients, with CKD stage IV in 28 (22%) patients, with CKD stage V in 9 (20%) patients, with FISD in GFR in 75 (26%) patients. A moderate degree of anemia (Hb 81-109 g/l) was detected in 47.3% of cases, with CKD stage IIIb in 86 (25%) patients, with CKD stage IV in 60 (48%) patients, with CKD stage V in 29 (66%) patients, with FISD in GFR in 64 (23%) patients. Severe anemia (Hb 81-109 g/l) was detected in 47.3% of patients, with CKD stage IIIb in 36 (10%) patients, with CKD stage IV in 22 (19%) patients, with CKD stage V in 5 (11%) patients, with FISD in GFR in 6 (2%) patients. Conclusion Every fourth patient in the cardiology department with AF and GFR <45 ml/min/1.73 m2 was diagnosed with renal anemia, and its prevalence increases with a decrease in GFR. The above results indicate that a more careful selection of anticoagulant therapy is recommended for this patient population due to the high risk of progression of renal anemia in this cohort of patients.

#1054 Dietary manganese intake and risk of chronic kidney disease: insights from the UK Biobank Study

Abstract Background and Aims Manganese, an essential trace element crucial for various physiological processes, has been linked to metabolic syndrome and cardiovascular health. Despite these associations, the relationship between dietary manganese intake and incident chronic kidney disease (CKD) remains unclear. In this study, the connection between dietary manganese consumption and the development of CKD in individuals with normal kidney function was investigated. Method A total of 135,577 participants enrolled in the UK Biobank were assessed. Dietary manganese intake was determined through a 24-hour dietary recall questionnaire and categorized into quartiles. Individuals with prevalent CKD or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline were excluded. The primary outcome was incident CKD diagnosed using ICD-10 and OPCS-4 codes. Incident CKD, defined as eGFR <60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio (UACR) ≥30 mg/g, was also evaluated in a sub-cohort that included eGFR and UACR follow-up data. Results During a follow-up period of 1,492,228 person-years (median, 11.2 years), incident CKD occurred in 4,900 (3.6%) participants. The incidence of CKD exhibited a progressive increase among individuals with low manganese intake (2.3, 3.0, 3.6, and 4.2 events per 1000 person-years in Q4–Q1, respectively). In a multivariate Cox proportional hazard model, the adjusted hazard ratios (95% confidence intervals) for the lowest, second, and third quartiles were 1.39 (1.26–1.54), 1.22 (1.11–1.34), and 1.12 (1.02–1.23), respectively, compared to the highest quartile. Similar findings were observed in relation to eGFR or UACR-defined CKD outcomes. Conclusion Lower dietary manganese consumption was found to be associated with an elevated risk of incident CKD in adults with normal kidney function. This implies that a deficiency in dietary manganese intake may contribute to an increased risk of CKD development.

#1306 Online medical education advances physicians’ understanding of the clinical benefits of SGLT 2 inhibition in chronic kidney disease management

Abstract Background and Aims Patients with chronic kidney disease (CKD) have a substantially impaired cardio-renal health prognosis and a reduced life expectancy. Several recent cardio-renal outcomes trials have demonstrated the clinical benefits conveyed by Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors with respect to improved cardiovascular (CV) risk and reduced decline in kidney function. The goal of this online medical education activity was for learners to be better able to detect CKD early in clinical practice and integrate reno-protective therapies, such as SGLT2 inhibitors, into their management of suitable patients with CKD. Method Five nephrology experts participated in a 30-min online video program with synchronized slides and written transcript. Educational effect was assessed using a repeated-pair design with pre-/post-assessment. 3 multiple choice questions assessed knowledge/competence, 1 question rated on a Likert-type scale assessed confidence. A paired samples t-test was conducted on overall average number of correct responses and for confidence rating, a McNemar's test was conducted at the question level (5% significance level). Cohen's d with correction for paired samples estimated the effect size of the education on number of correct responses. Data collection from 28 December 2022 to 1 March 2023. Results Conclusion Participation of PCP in an online video expert program improved their understanding of the close association between metabolic, renal, and cardiovascular diseases, the latest results of CKD outcome trials with SGLT2 inhibition in CKD management, as well as their competence in the practical use of these reno-protective medications in suitable patients with CKD.

Risk Factors and Outcomes Associated With Heart Failure With Preserved and Reduced Ejection Fraction in People With Chronic Kidney Disease.

Heart failure (HF) is associated with poor outcomes in people with chronic kidney disease, yet it is unknown whether outcomes differ by HF subtype. This study aimed to examine associations of incident HF with preserved ejection fraction (HFpEF) versus HF with reduced ejection fraction (HFrEF) with progression to end-stage kidney disease (ESKD) and mortality. We studied individuals with chronic kidney disease in the CRIC study (Chronic Renal Insufficiency Cohort) who were free of HF at cohort entry. Incident HF hospitalizations were adjudicated and classified into HFpEF (ejection fraction, ≥50%) or HFrEF (ejection fraction, <50%) based on echocardiograms performed during the hospitalization or at a research study visit. ESKD was defined as need for chronic dialysis or kidney transplant. Cox proportional hazards were used to evaluate the association of time-updated HF subtype with risk of ESKD and mortality, adjusting for demographics, comorbidities, and medication use. Among the 3557 study participants without HF at cohort entry, mean age was 57 years and mean estimated glomerular filtration rate was 45 mL/min per 1.73 m2. A total of 682 participants had incident HF. Incidence rates for HFpEF and HFrEF were 0.9 (95% CI, 0.8-1.0) and 0.7 (95% CI, 0.6-0.8) per 100 person-years, respectively (Pdifference=0.005). Associations of incident HF with progression to ESKD were not statistically different for HFpEF (hazard ratio, 2.06 [95% CI, 1.66-2.56]) and HFrEF (hazard ratio, 1.80 [95% CI, 1.36-2.38]; P=0.42). The associations with mortality were stronger for HFrEF (hazard ratio, 2.73 [95% CI, 2.24-3.33]) compared with HFpEF (hazard ratio, 1.99 [95% CI, 1.65-2.40]; P=0.0002). In a chronic kidney disease population, the rates of HFpEF hospitalizations were greater than that of HFrEF. Risk of ESKD was high but not statically different across HF subtypes. There was a stronger association of HFrEF with mortality. Prevention and treatment of both HFpEF and HFrEF should be central priorities to improve outcomes in chronic kidney disease.

Personalized nutritional management in the transition from non-dialysis dependent chronic kidney disease to dialysis.

Dialysis has been the dominant treatment regimen in end-stage kidney disease as a means to remove uremic waste products and to maintain electrolyte, acid base, and fluid balance. However, given that dialysis may not always provide a survival benefit nor improved quality of life in certain subpopulations, there is growing recognition of the need for conservative and preservative management as an alternative treatment strategy for advanced chronic kidney disease (CKD). Personalized nutritional management tailored to patient's sociodemographics, social needs, psychological status, health literacy level, and preferences is a key component of conservative and preservative care, as well as in the management of patients transitioning from non-dialysis dependent CKD to dialysis. In this review, we discuss the nutritional and metabolic alterations that ensue in CKD; the rationale for low-protein diets in the conservative and preservative management of advanced CKD; the role of plant-based diets in kidney health; emerging data on dietary potassium and sodium intake on CKD outcomes; and the practical implementation of dietary interventions in advanced kidney disease.

Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (β = -0.609, p = .039; β = -2.298, p < .001; β = -0.936, p = .048; β = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.

Identification and outcomes of KDIGO-defined chronic kidney disease in 1.4 million U.S. Veterans with heart failure.

According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.

Association of soluble suppression of tumorigenicity 2 with mortality and adverse outcomes in chronic kidney disease: a systematic review and meta-analysis.

Early risk stratification is necessary to prevent chronic kidney disease progression and complications. This systematic review aims to evaluate the association of soluble suppression of tumorigenicity 2 (sST2), a member of the interleukin-1 receptor family, with all-cause mortality, cardiovascular disease and renal function deterioration among chronic kidney disease patients. PubMed, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched from inception to December 20, 2023. Cohort studies examining the prognostic role of sST2 levels in pre-dialysis and dialysis patients were included. In case of 3 or more studies per outcome, conventional and dose-response meta-analyses were conducted. Overall, 21 studies were included comprising 15,100 patients. In pre-dialysis patients, the qualitative synthesis of studies suggested that high sST2 is associated with significantly increased all-cause mortality, while evidence regarding cardiovascular events or kidney disease progression was conflicting. In the dialysis population, high sST2 was linked to an elevated risk of all-cause (Hazard ratio-HR: 3.00, 95% confidence intervals-CI: 1.95-4.61) and cardiovascular (HR: 2.38, 95% CI: 1.69-3.34) mortality. Dose-response meta-analysis suggested a log-linear association of sST2 with both all-cause (χ2: 34.65, p value < 0.001) and cardiovascular (χ2: 29.14, p value < 0.001) mortality, whereas findings regarding cardiovascular events were limited with mixed results. High sST2 values are associated with an increased risk of all-cause mortality in pre-dialysis and dialysis patients, as well as with an elevated risk of cardiovascular mortality in the dialysis population. Further studies are needed to elucidate its potential association with cardiovascular events and kidney disease progression.

Inequalities in emergency care use across transition from paediatric to adult care: a retrospective cohort study of young people with chronic kidney disease in England.

Sociodemographic inequalities in emergency secondary care usage were evident in this cohort across the transition period, independent of age, with some variation between admissions and A&E use, and evidence of effect modification by transfer. Such inequalities likely have multifactorial origin, but importantly, could represent differential meetings of care needs. • In chronic kidney disease (CKD), transfer from paediatric to adult healthcare is associated with declining health outcomes. • Known differences in CKD outcomes by sociodemographic factors have limited prior exploration in the context of transfer. • Population-level data was used to examine the impacts of transfer and sociodemographic factors on unplanned secondary care utilisation in CKD. • Healthcare utilisation trends may not reflect known CKD pathophysiology and there may be unexplored sociodemographic inequalities in the experiences of young people across transfer.

Correlation between Urinary Angiotensinogen (AGT) and Albuminuria in Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) is a global health concern associated with significant morbidity and mortality. Albuminuria, a hallmark of kidney damage, is a strong predictor of CKD progression and adverse outcomes. Recent research has focused on understanding the correlation between urinary angiotensinogen (AGT) levels, a component of the renin-angiotensin system (RAS), and albuminuria in CKD patients. This review article synthesizes evidence from various studies exploring this correlation and elucidates its mechanistic insights and clinical implications. Clinical studies consistently demonstrate a positive correlation between urinary AGT levels and albuminuria in CKD patients. Elevated urinary AGT levels are associated with increased albuminuria, independent of traditional risk factors, suggesting a potential role for AGT in the pathogenesis of kidney damage and proteinuria in CKD. Mechanistic insights suggest that increased intrarenal RAS activity may lead to enhanced AGT production and secretion, contributing to glomerular hypertension, inflammation, and fibrosis, ultimately promoting albuminuria and CKD progression. The clinical implications of this correlation are profound. Elevated urinary AGT levels may serve as a non-invasive biomarker for assessing intrarenal RAS activity and predicting CKD progression and adverse outcomes. Furthermore, interventions targeting the RAS pathway, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), may help reduce urinary AGT levels and mitigate albuminuria, offering promising therapeutic opportunities for improving patient outcomes in CKD. In conclusion, the correlation between urinary AGT and albuminuria in CKD represents a complex interplay between renal physiology, RAS activation, and kidney damage. By elucidating this correlation, we gain valuable insights into the pathogenesis of CKD and identify urinary AGT as a potential biomarker and therapeutic target for personalized CKD management. Further research is warranted to validate these findings, explore the clinical utility of urinary AGT measurement, and develop targeted interventions aimed at mitigating albuminuria and slowing CKD progression. Through continued investigation, we can strive to improve outcomes and quality of life for patients living with CKD.

Are there lost opportunities in chronic kidney disease? A region-wide cohort study

ObjectivesIdentify the windows of opportunity for the diagnosis of chronic kidney disease (CKD) and the prevention of its adverse outcomes and quantify the potential population gains of such prevention.Design and...

Is mild dehydration a risk for progression of childhood chronic kidney disease?

Children with chronic kidney disease (CKD) can have an inherent vulnerability to dehydration. Younger children are unable to freely access water, and CKD aetiology and stage can associate with reduced kidney concentrating capacity, which can also impact risk. This article aims to review the risk factors and consequences of mild dehydration and underhydration in CKD, with a particular focus on evidence for risk of CKD progression. We discuss that assessment of dehydration in the CKD population is more challenging than in the healthy population, thus complicating the definition of adequate hydration and clinical research in this field. We review pathophysiologic studies that suggest mild dehydration and underhydration may cause hyperfiltration injury and impact renal function, with arginine vasopressin as a key mediator. Randomised controlled trials in adults have not shown an impact of improved hydration in CKD outcomes, but more vulnerable populations with baseline low fluid intake or poor kidney concentrating capacity need to be studied. There is little published data on the frequency of dehydration, and risk of complications, acute or chronic, in children with CKD. Despite conflicting evidence and the need for more research, we propose that paediatric CKD management should routinely include an assessment of individual dehydration risk along with a treatment plan, and we provide a framework that could be used in outpatient settings.