Risk Of Chronic Kidney Disease Research Articles

Early postnatal nutrition and renal consequences in preterm infants.

Perinatal nutritional factors may lead to decreased nephron endowment, decreased kidney function, and long-term development of chronic kidney disease and non-communicable diseases. At the same time, optimal postnatal nutrition and catch-up growth are associated with better neurodevelopmental outcomes in preterm infants. Therefore, nutritional management of preterm infants is a major challenge for neonatologists. In this context, the Section of Nutrition, Gastroenterology and Metabolism reviewed the current knowledge on nutritional issues related to kidney function. This narrative review discusses the clinical impact of early postnatal nutrition on long-term kidney function. In preterm infants, data are largely lacking to determine the extent to which early nutrition contributes to nephrogenesis and nephron endowment. However, some nutritional principles may help clinicians better protect the developing kidney in preterm infants. IMPACT: Clinical data show that preterm infants are an emerging population at high risk for chronic kidney disease. Both undernutrition and overnutrition can alter long-term kidney function. In preterm infants, data are largely lacking to determine the extent to which early postnatal nutrition contributes to nephrogenesis, nephron endowment and increased risk for chronic kidney disease. Some nutritional principles may help clinicians better protect the developing kidney in preterm infants: avoiding extrauterine growth restriction; providing adequate protein and caloric intakes; limiting exposure to high and prolonged hyperglycaemia; avoiding micronutrient deficiencies and maintaining acid-base and electrolyte balance.

Comparing the Performance of Machine Learning Models in Predicting the Risk of Chronic Kidney Disease

Background: Chronic kidney disease (CKD) poses a significant health burden worldwide, affecting approximately 10 - 15% of the global population. As one of the leading non-communicable diseases, CKD is a major cause of morbidity and mortality. Early identification of CKD is crucial for reducing its adverse effects on patient health. Prompt detection can significantly lessen the harmful consequences and enhance health outcomes for individuals with CKD. Objectives: This study aimed to evaluate and compare the effectiveness of various machine learning models in predicting the occurrence of CKD. Methods: The study involved the collection of data from a sample of 400 patients. We applied the well-established cross-industry standard process (CRISP) methodology for data mining to analyze the data. As part of this process, we efficiently handled missing data using the mode approach and addressed outliers through the interquartile range (IQR) method. We utilized sophisticated techniques, such as CatBoost (CB), random forest (RF), and artificial neural network (ANN) models to predict outcomes. For evaluation, we used the receiver operating characteristic (ROC) curve and calculated the area under the curve (AUC). Results: An analysis of 400 patient records in this study identified that variables like serum creatinine, packed cell volume, specific gravity, and hemoglobin were most influential in predicting CKD. The results indicated that the CB and RF models surpassed the ANN in predicting the disease. Ten critical predictors were pinpointed for accurate disease prediction. Conclusions: The ensemble models in this study not only showcased remarkable speed but also demonstrated superior accuracy. These findings suggest the potential of ensemble models as an effective tool for enhancing predictive performance in similar studies.

Impact of heat and a rest-shade-hydration intervention program on productivity of piece-paid industrial agricultural workers at risk of chronic kidney disease of nontraditional origin.

Assess the impact of environmental heat and a rest-shade-hydration (RSH) intervention against heat stress on productivity of piece-paid Mesoamerican sugarcane cutters. These workers are at a high risk of chronic kidney disease of non-traditional origin (CKDnt), from the severe heat stress they experience due to heavy work under hot conditions. RSH interventions in these populations improve kidney health outcomes, but their impact on productivity has yet to be examined. We accessed routine productivity data from seed (SC, N = 749) and burned (BCC, N = 535) sugarcane cutters observed over five harvest seasons with increasing RSH intervention at a large Nicaraguan sugarcane mill. Hourly field-site wet-bulb globe temperature (WBGT) was recorded by mill staff and summarized as a daily mean. Mixed linear regression was used to model daily productivity, adjusting for age (18-29, 30-44, and >45 years), sex, WBGT (<28, 28-29, 29-30, 30-31, and >31 °C) on the same and preceding day, harvest season (2017-18 to 2021-22), month, and acclimatization status (<1, 1-2, and >2 weeks). There was an inverse dose-response relationship between SC productivity and WBGT on the same and preceding days, decreasing by approximately 3%/°C WBGT. Productivity increased during the study period, i.e. coinciding with RSH scale-up, by approximately 19% in SC and 9% in BCC. Agricultural worker productivity was expected lower on hotter days, strengthening the interest in all stakeholders to mitigate increasing global temperatures and their impact. Despite decreasing the total time allocated for work each day, an RSH intervention appears to result in increased productivity and no apparent loss in productivity.

Association between ambient PM1 and the prevalence of chronic kidney disease in China: A nationwide study

Particulate of diameter ≤ 1 µm (PM1) presents a novel risk factor of adverse health effects. Nevertheless, the association of PM1 with the risk of chronic kidney disease (CKD) in the general population is not well understood, particularly in regions with high PM1 levels like China. Based on a nationwide representative survey involving 47,204 adults and multi-source ambient air pollution inversion data, the present study evaluated the association of PM1 with CKD prevalence in China. The two-year average PM1, particulate of diameter ≤ 2.5 µm (PM2.5), and PM1–2.5 values were accessed using a satellite-based random forest approach. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2 or albuminuria. The results suggested that a 10 μg/m3 rise in PM1 was related to a higher CKD risk (odds ratio [OR], 1.13; 95% confidence interval [CI] 1.08–1.18) and albuminuria (OR, 1.11; 95% CI, 1.05–1.17). The association between PM1 and CKD was more evident among urban populations, older adults, and those without comorbidities such as diabetes or hypertension. Every 1% increase in the PM1/PM2.5 ratio was related to the prevalence of CKD (OR, 1.03; 95% CI, 1.03–1.04), but no significant relationship was found for PM1–2.5. In conclusion, the present study demonstrated long-term exposure to PM1 was associated with an increased risk of CKD in the general population and PM1 might play a leading role in the observed relationship of PM2.5 with the risk of CKD. These findings provide crucial evidence for developing air pollution control strategies to reduce the burden of CKD.

Association between Whole Grain Intake and Chronic Kidney Disease

BackgroundThe relationship between whole grain intake and chronic kidney disease (CKD) remains uncertain. ObjectiveThis study aimed to evaluate the association between whole grain intake and risk of CKD in Chinese adults. MethodsThe present cross-sectional study used data from the China Health and Nutrition Survey conducted in 2009. Whole grain intake was measured using 3 consecutive 24-h dietary recalls and a household food inventory. A multivariable logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of CKD. In addition, a restricted cubic spline was used to investigate the dose‒response relationship between whole grain and risk of CKD. ResultsA total of 6747 participants were included, 728 of whom had CKD. Compared with those in the lowest whole grain intake group, those in the higher grain intake group had an inverse association with risk of CKD (Q2: adjusted OR 0.70, 95% CI: 0.54, 0.89; Q3: adjusted OR 0.54, 95% CI: 0.42, 0.69; and Q4: adjusted OR 0.29, 95% CI: 0.21, 0.41). The association between whole grain intake and CKD seems to be stronger for individuals who were male (P for interaction = 0.008) or smokers (P for interaction = 0.013). In addition, the restricted cubic spline suggested an obvious L-shaped correlation. ConclusionsIncreased whole grain intake was associated with a decreased risk of CKD in Chinese adults.

Associations of long-term exposure to ambient sulfur dioxide, carbon monoxide, ozone, and benzene with risk of incident chronic kidney disease in the UK

Limited studies have examined associations of gaseous air pollutants exposure with chronic kidney disease (CKD) in Europe. This study aimed to calculate the relationships between long-term exposure to ambient sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), and benzene and CKD in the UK. We included 502 369 participants from the UK biobank cohort. Associations of SO2, CO, O3, and benzene with CKD were estimated using Cox proportional hazards model. The shape of the exposure-response association between each air pollutant and CKD was then depicted using the shape constrained health impact function. We finally estimated the incidence of CKD attributable to each air pollutant by linking the constructed exposure-response association to the 2019 Global Burden of Disease data. Our results suggested SO2, high O3 days (daily max 8 hr O3 concentration > 120 µg m−3), CO, and benzene were positively associated with the risk of incident CKD. The hazard ratios (HRs) of CKD for SO2, CO, and benzene were 1.058 (95% CI: 1.039–1.078), 1.003 (95% CI: 1.001–1.005), and 1.619 (1.433–1.829) for every 1 μg m−3 increase in the concentration, respectively. For high O3 days, the HR of CKD was 1.044 (95% CI: 1.032–1.056) for every 1 d increase, but correlation to O3 concentration did not reach the statistical significance in the time-varying model. The risk of CKD increased non-linearly with increasing SO2, high O3 days, and CO, and linearly with increasing benzene. We estimated that 7.9%, 16.0%, 8.0% of incident CKD cases in the UK in 2021 could be attributed to exposure to SO2, O3, and benzene, respectively. We concluded that exposure to SO2, CO, O3, and benzene were all positively associated with increased CKD risk. Our findings highlight the importance of considering air pollution while making strategies targeting on CKD management.

Exploring multifaceted factors in chronic kidney disease risk: A comprehensive analysis of biochemistry, lifestyle, and inflammation in elderly Chinese individuals.

This letter praises a recent article in the World Journal of Clinical Cases (Roles of biochemistry data, lifestyle, and inflammation in identifying abnormal renal function in old Chinese), examining factors affecting abnormal renal function in elderly Chinese using advanced machine learning. It highlights the importance of uric acid, age, hemoglobin, body mass index, sport hours, and systolic blood pressure. The study's holistic approach, integrating lifestyle and inflammation, offers a nuanced understanding of chronic kidney disease risk factors. The letter suggests exploring mechanistic pathways of hyperuricemia, the link between anemia and renal function, and the connection between body mass index and estimated glomerular filtration rate. It advocates investigating physical activity's impact on renal health and the independent effects of blood pressure. The study significantly contributes to chronic kidney disease understanding, proposing avenues for further exploration and interventions. Commendations are extended to the authors and the journal.

A Prospective Study of the Association Between Plasma Calprotectin Levels and New-Onset CKD in the General Population

IntroductionSystemic inflammation has been associated with chronic kidney disease (CKD). In this study, we aimed to investigate a potential association between the plasma biomarker of inflammation calprotectin and new-onset CKD in a population-based cohort study. MethodsIndividuals without CKD at baseline (n=4,662) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma calprotectin levels were assessed in samples that had been stored at -80°C. Occurrence of new-onset CKD was defined as a composite outcome of an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2, urinary albumin excretion (UAE) >30 mg/24-h, or both. ResultsBaseline median [IQR] plasma calprotectin levels were 0.49 [0.35-0.68] mg/l and baseline median eGFR was 95.9 [IQR: 85.0-105.7] ml/min/1.73m2. After median follow-up of 8.3 [7.8-8.9] years, 467 participants developed new-onset CKD. Baseline plasma calprotectin levels were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.28 [95% CI: 1.14-1.44], P<0.001), independent of potentially confounding factors (HR 1.14 [95% CI: 1.01-1.29], P=0.034), except for baseline hs-CRP (HR 1.05 [0.91-1.21], P=0.494). In secondary analyses, the association between plasma calprotectin and occurrence of UAE >30 mg/24-h remained significant (HR 1.17 [1.02-1.34], P=0.027), but not significantly so for the incidence of eGFR <60 ml/min/1.73m2 as individual outcome (HR 1.15 [0.92-1.43], P=0.218). ConclusionHigher plasma calprotectin levels are associated with an increased risk of developing CKD in the general population. This association is mitigated after adjustment for hs-CRP, and more pronounced with new-onset CKD defined by UAE.

Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study

Rationale & ObjectiveWhile urine excretion of nitrogen estimates total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of six protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD). Study DesignProspective cohort study. Setting & Participants3,726 participants from the Atherosclerosis Risk in Communities (ARIC) study without CKD at baseline. ExposureDietary intake of six protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, poultry), serum metabolites. OutcomesIncident CKD [eGFR <60 mL/min/1.73 m2 with ≥25% eGFR decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease. Analytical ApproachMultivariable linear regression models estimated cross-sectional associations between protein-rich foods and serum metabolites. C-statistics assessed the metabolites’ ability to improve discrimination of highest versus lower three quartiles of intake of protein-rich foods beyond covariates (demographics, clinical factors, health behaviors, and intake of nonprotein food groups). Cox regression models identified prospective associations between protein-related metabolites and incident chronic kidney disease (CKD). ResultsThirty significant associations were identified between protein-rich foods and serum metabolites (fish, n=8; nuts, n=5; legumes, n=0; red and processed meat, n=5; eggs, n=3; poultry, n=9). Metabolites collectively significantly improved discrimination of high intake of protein-rich foods compared to covariates alone (difference in C-statistics=0.033, 0.051, 0.003, 0.024, and 0.025 for fish, nuts, red and processed meat, eggs, and poultry-related metabolites, respectively; p<1.00 x 10-16 for all). Dietary intake of fish was positively associated with 1-docosahexaenoylglycerophosphocholine (22:6n3), which was inversely associated with incident CKD (HR 0.82, 95% CI 0.75-0.89, p=7.81×10-6). LimitationsResidual confounding and sample storage duration. ConclusionsWe identified candidate biomarkers of fish, nuts, red and processed meat, eggs, and poultry. A fish-related metabolite, 1-docosahexaenoylglycerophosphocholine (22:6n3), was associated with lower risk of CKD.

Multiple factors influence decision making for the surgical treatment in patients with renal cell carcinoma.

Surgical strategy in renal cell carcinoma (RCC) is considered based on the renal function. Partial nephrectomy (PN) preserves kidney function better than radical nephrectomy (RN), lowering risk of chronic kidney disease (CKD). The aim was to evaluate whether renal function and other clinical variables were important for surgical treatment selection. Patients with RCC, surgically treated between 1994 and 2018 were included. There were 663 patients in all stages, 265 women and 398 men, mean age 66 years. estimated glomerular filtration rate (eGFR), WHO performance status (WHO-PS), Charlson comorbidity index (CCI), surgery, T-stage, M-stage, RCC type, tumor size, age, and gender were extracted from the medical records. Statistical analysis included Mann-Whitney U, X2-test, and logistic regression analysis. Of 663 patients, 455 were treated with RN and 208 with PN. In all patients, preoperative eGFR was significantly higher in PN (80.8) than in RN (77.1, p = 0.015). Using logistic regression tumor size (odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.95-0.98, T-stage (OR: 0.46; 95% CI: 0.33-0.65), WHO-PS (OR: 0.39; 95% CI: 0.04-0.57), and CCI (OR: 1.23; 95% CI: 1.05-1.44), associated to treatment selection, while eGFR, M-stage, age, and gender did not. In cTa subgroup, eGFR was also higher in PN (84.6) than in RN (75.0, p = 0.007). Using logistic regression, tumor size (OR: 0.93; 95% CI: 0.83-0.98) and WHO-PS (OR: 0.36; 95% CI: 0.20-0.66) associated to treatment selection, while eGFR, CCI, age, and gender did not. Tumor size, CCI scores, T-stage, and WHO-PS, all had an impact on the surgical strategy for all RCC patients. In patients with T1a RCC, tumor size and WHO-PS associated independently with treatment decision. After adjusted analysis, renal function lost its independent association with the treatment strategy in RCC patients.

Mannose and glycine: Metabolites with potentially causal implications in chronic kidney disease pathogenesis.

Chronic Kidney Disease (CKD) represents a global health challenge, with its etiology and underlying mechanisms yet to be fully elucidated. Integrating genomics with metabolomics can offer insights into the putatively causal relationships between serum metabolites and CKD. Utilizing bidirectional Mendelian Randomization (MR), we assessed the putatively causal associations between 486 serum metabolites and CKD. Genetic data for these metabolites were sourced from comprehensive genome-wide association studies, and CKD data were obtained from the CKDGen Consortium. Our analysis identified four metabolites with a robust association with CKD risk, of which mannose and glycine showed the most reliable causal relationships. Pathway analysis spotlighted five significant metabolic pathways, notably including "Methionine Metabolism" and "Arginine and Proline Metabolism", as key contributors to CKD pathogenesis. This study underscores the potential of certain serum metabolites as biomarkers for CKD and illuminates pivotal metabolic pathways in CKD's pathogenesis. Our findings lay the groundwork for potential therapeutic interventions and warrant further research for validation.

Gonadal dysfunction in women with diabetes mellitus.

It is well known that both type 1 and type 2 diabetes mellitus (DM) are related to increased risk for cardiovascular (CV) and chronic kidney disease (CKD). However, besides these prominently presented complications, DM has also been associated with reproductive dysfunctions. It seems that these disorders are met in up to 40% of women with DM and consist of delayed menarche, all types of menstrual disorders, such as amenorrhea, oligomenorrhea, menstrual irregularity, as well as menorrhagia, infertility, characteristics of polycystic ovary syndrome (PCOS) and early (or rarely late) menopause. In type 1 DM (T1DM), insulin treatment, although it has reduced the rates of insulinopenic-induced hypogonadotropic hypogonadism, an entity commonly presented in many women with the disease in the past decades, when it is used in excess it can also promote hyperandrogenism. Regarding type 2 DM (T2DM), insulin resistance (IR) and hyperinsulinemia have mainly been implicated in the pathogenesis of reproductive dysfunctions, as insulin can act as gonadotropin on the theca cells of the ovary and can lead to hyperandrogenism and inhibition of proper ovulation. This review aims to detail the reproductive dysfunctions associated with DM and provide scientific data to enlighten the underlying pathogenetic mechanisms.

Higher potassium intake is associated with a lower risk of chronic kidney disease: population-based prospective study

BackgroundHigh-potassium intake is associated with a lower risk of cardiovascular disease. However, the association between potassium intake and the development of chronic kidney disease (CKD) remains unclear. ObjectiveThe objective of this study was to investigate whether potassium intake is associated with outcomes of incident CKD. MethodsThis is a population-based prospective observational cohort study from the UK Biobank cohort between 2006 and 2010. We included 317,162 participants without CKD from the UK Biobank cohort. The main predictor was spot urine potassium-to-creatinine ratio (KCR). The primary outcome was incident CKD, which was defined by the International Classification of Disease 10 codes or Operating Procedure Codes Supplement 4 codes. ResultsAt baseline, individuals with higher KCR had lower blood pressure, body mass index, and inflammation, and were less likely to have diabetes and hypertension. During a median follow-up of 11.9 y, primary outcome events occurred in 15,246 (4.8%) participants. In the cause-specific model, the adjusted hazard ratio (aHR) per 1-standard deviation increase in KCR for incident CKD was 0.90 [95% confidence interval (CI): 0.89, 0.92]. Compared with quartile 1 of KCR, the aHRs (95% CIs) for quartiles 2–4 were 0.98 (0.94, 1.02), 0.90 (0.86, 0.95), and 0.80 (0.76, 0.84), respectively. In sensitivity analysis with different definitions of CKD, the results were similar. In addition, further analysis with dietary potassium intake also showed a negatively graded association with the primary outcome. ConclusionsHigher urinary potassium excretion and intake were associated with a lower risk of incident CKD.

Evaluating Osteoporosis in Chronic Kidney Disease: Both Bone Quantity and Quality Matter.

Bone strength is determined not only by bone quantity [bone mineral density (BMD)] but also by bone quality, including matrix composition, collagen fiber arrangement, microarchitecture, geometry, mineralization, and bone turnover, among others. These aspects influence elasticity, the load-bearing and repair capacity of bone, and microcrack propagation and are thus key to fractures and their avoidance. In chronic kidney disease (CKD)-associated osteoporosis, factors traditionally associated with a lower bone mass (advanced age or hypogonadism) often coexist with non-traditional factors specific to CKD (uremic toxins or renal osteodystrophy, among others), which will have an impact on bone quality. The gold standard for measuring BMD is dual-energy X-ray absorptiometry, which is widely accepted in the general population and is also capable of predicting fracture risk in CKD. Nevertheless, a significant number of fractures occur in the absence of densitometric World Health Organization (WHO) criteria for osteoporosis, suggesting that methods that also evaluate bone quality need to be considered in order to achieve a comprehensive assessment of fracture risk. The techniques for measuring bone quality are limited by their high cost or invasive nature, which has prevented their implementation in clinical practice. A bone biopsy, high-resolution peripheral quantitative computed tomography, and impact microindentation are some of the methods established to assess bone quality. Herein, we review the current evidence in the literature with the aim of exploring the factors that affect both bone quality and bone quantity in CKD and describing available techniques to assess them.

Glomerular hyperfiltration as a therapeutic target for CKD.

The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR) or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin-angiotensin system blockers to mineralocorticoid receptor blockers to sodium-glucose cotransporter-2 inhibitors to tolvaptan, induced an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predates current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.

Ambient PM2.5 components and prevalence of chronic kidney disease: a nationwide cross-sectional survey in China.

Chronic kidney disease (CKD) is a global public health concern, and accumulating evidence has indicated that air pollution increases the odds of CKD. However, a limited number of studies have examined the long-term effects of ambient fine particulate matter (PM2.5) components on the risk of CKD among general population; thus, major knowledge gaps remain. Using data from a nationwide representative cross-sectional survey in China and a validated PM2.5 composition dataset, we established generalized linear models to quantify the association between five major components of PM2.5 and CKD prevalence. There were significant associations between long-term exposure to three PM2.5 components [including black carbon (BC), sulfate (SO42-), organic matter (OM)] and increased odds of CKD prevalence. Along with an interquartile range (IQR) increment in BC (3.3 μg/m3), SO42- (9.7 μg/m3), and OM (16.2 μg/m3) at a 4-year moving average, the odds ratios (ORs) for CKD prevalence were 1.28 (95% CI 1.07, 1.54), 1.23 (95% CI 1.03, 1.45), and 1.23 (95% CI 1.02, 1.47), respectively. We did not detect any significant association of the other two PM2.5 components [nitrate (NO3-) or ammonium (NH4+)] with CKD prevalence. Stratified analyses revealed no differences (P ≥ 0.05) in the effect estimates of subgroups based on administrative region, sex, age, and other demographic characteristics. For instance, along with an IQR increment in BC at a 4-year moving average, the ORs of CKD prevalence among males and females were 1.30 (95% CI 0.98, 1.73) and 1.29 (95% CI 1.01, 1.65), respectively. The odds of CKD were generally higher with increasing PM2.5 composition concentration. Our study demonstrated that long-term exposure to specific PM2.5 components including BC, SO42-, and OM increased CKD risk in the general population. This study could provide new insights into source-directed PM2.5 control and CKD prevention.

Mitochondrial genetic variation and risk of chronic kidney disease and acute kidney injury in UK Biobank participants

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of common mitochondrial genetic variation on kidney health. We sought to evaluate associations of inherited mitochondrial DNA (mtDNA) variation with risk of CKD and AKI in a large population-based cohort. We categorized UK Biobank participants who self-identified as white into eight distinct mtDNA haplotypes, which were previously identified based on their associations with phenotypes associated with mitochondrial DNA copy number, a measure of mitochondrial function. We used linear and logistic regression models to evaluate associations of these mtDNA haplotypes with estimated glomerular filtration rate by serum creatinine and cystatin C (eGFRCr-CysC, N = 362,802), prevalent (N = 416 cases) and incident (N = 405 cases) end-stage kidney disease (ESKD), AKI defined by diagnostic codes (N = 14,170 cases), and urine albumin/creatinine ratio (ACR, N = 114,662). The mean age was 57 ± 8 years and the mean eGFR was 90 ± 14 ml/min/1.73 m2. MtDNA haplotype was significantly associated with eGFR (p = 2.8E−12), but not with prevalent ESKD (p = 5.9E−2), incident ESKD (p = 0.93), AKI (p = 0.26), or urine ACR (p = 0.54). The association of mtDNA haplotype with eGFR remained significant after adjustment for diabetes mellitus and hypertension (p = 1.2E−10). When compared to the reference haplotype, mtDNA haplotypes I (β = 0.402, standard error (SE) = 0.111; p = 2.7E−4), IV (β = 0.430, SE = 0.073; p = 4.2E−9), and V (β = 0.233, SE = 0.050; p = 2.7E−6) were each associated with higher eGFR. Among self-identified white UK Biobank participants, mtDNA haplotype was associated with eGFR, but not with ESKD, AKI or albuminuria.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes

Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. Prospective observational cohort study. 78,950 participants without CKD (cohort 1) and 7,233 participants with CKD (cohort 2) in the UK Biobank Study with PUFA levels measured between 2007 and 2010. Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total fatty acid. Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. Cox proportional hazards regression analyses, including a cause-specific competing risk model. In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios (HR) (95% CIs) for quartiles 2, 3, and 4 were 0.83 (0.75-0.92), 0.85 (0.76-0.96), 0.71 (0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although, total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. Among individuals without CKD, higher plasma PUFA levels and all four PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT.

Branched-chain amino acid levels are inversely associated with incident and prevalent chronic kidney disease in people with type 2 diabetes.

To investigate the association of plasma metabolites with incident and prevalent chronic kidney disease (CKD) in people with type 2 diabetes and establish whether this association is causal. The Hoorn Diabetes Care System cohort is a large prospective cohort consisting of individuals with type 2 diabetes from the northwest part of the Netherlands. In this cohort we assessed the association of baseline plasma levels of 172 metabolites with incident (Ntotal = 462/Ncase = 81) and prevalent (Ntotal = 1247/Ncase = 120) CKD using logistic regression. Additionally, replication in the UK Biobank, body mass index (BMI) mediation and causality of the association with Mendelian randomization was performed. Elevated levels of total and individual branched-chain amino acids (BCAAs)-valine, leucine and isoleucine-were associated with an increased risk of incident CKD, but with reduced odds of prevalent CKD, where BMI was identified as an effect modifier. The observed inverse effects were replicated in the UK Biobank. Mendelian randomization analysis did not provide evidence for a causal relationship between BCAAs and prevalent CKD. Our study shows the intricate relationship between plasma BCAA levels and CKD in individuals with type 2 diabetes. While an association exists, its manifestation varies based on disease status and BMI, with no definitive evidence supporting a causal link between BCAAs and prevalent CKD.

Abstract WP159: Chronic Kidney Disease and Risk of Intracerebral Hemorrhage: The Role of Hypertension as a Mediator

Introduction: Chronic kidney disease (CKD) is a well-established risk factor for spontaneous intracerebral hemorrhage (ICH). However, the biological pathway underlying this association remains unclear. We therefore conducted a phenome-wide association study (PheWAS) to assess for mediators of the association between CKD and ICH risk. Methods: We conducted a PheWAS using data from the UK Biobank (UKB), a large cohort study that enrolled over 500,000 Britons aged 40-69. We first developed a polygenic risk score that contained 27 independent (r2 &lt;0.1) genetic risk variants known to be associated with CKD at genome-wide significant levels (p&lt;5x10 -8 ). We subsequently tested for associations between this CKD genetic risk score and the 1,840 disease phenotypes available through the UKB baseline assessment. We used a Bonferroni corrected p&lt;2.7x10 -5 as our threshold for significance. For all phenotypes that reached statistical significance in the PheWAS, we obtained summary results from previously published genome-wide association studies and implemented multivariable Mendelian Randomization (MR) to evaluate the proportion of the total effect of CKD on ICH risk mediated through these phenotypes. The indirect effect of CKD on ICH risk via mediators was calculated by subtracting the direct effect of CKD obtained from multivariable MR from the total effect of CKD obtained from univariable MR. Results: Excluding renal-related diseases, hypertension was the only significant phenotype in the PheWAS (p=3.2x10 -21 ). Genetically determined CKD was associated with a total increase in ICH risk of 38% in univariable MR (OR 1.38; 95% CI 1.12-1.71; p=0.002). This association was reduced to a 19% increase in ICH risk after adjusting for hypertension in multivariable MR (OR 1.19; 95% CI 1.03-1.39; p=0.021). The proportion of the total effect of CKD on ICH risk mediated through hypertension was estimated to be 55%. Conclusions: Hypertension accounts for approximately 55% of the total effect of CKD on ICH risk in genetic analyses. This aligns with existing knowledge that CKD worsens hypertension by causing renal retention of sodium and increased sympathetic activity. Further studies are needed to identify other pathways that mediate the remaining effect of CKD on ICH risk.