-
Alzheimer's Research & Therapy Aug 2023Associations between kidney function and dementia risk are inconclusive. Chronic kidney disease (CKD) severity is determined by levels of both estimated glomerular...
BACKGROUND
Associations between kidney function and dementia risk are inconclusive. Chronic kidney disease (CKD) severity is determined by levels of both estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (ACR). However, whether there is a graded increase in dementia risk for worse eGFR in each ACR category is unclear. Also, whether genetic risk for dementia impacts the associations is unknown. The current study aims to investigate the associations between eGFR and albuminuria with dementia risk both individually and jointly, whether the associations vary by different follow-up periods, and whether genetic factors modified the associations.
METHODS
In 202,702 participants aged ≥ 60 years from the UK Biobank, Cox proportional-hazards models were used to examine the associations between eGFR and urine albumin creatinine ratio (ACR) with risk of incident dementia. GFR was estimated based on serum creatinine, cystatin C, or both. The models were restricted to different follow-up periods (< 5 years, 5-10 years, and ≥ 10 years) to investigate potential reverse causation.
RESULTS
Over 15 years of follow-up, 6,042 participants developed dementia. Decreased kidney function (eGFR < 60 ml/min/1.73m) was associated with an increased risk of dementia (Hazard Ratio [HR] = 1.42, 95% Confidence Interval [CI] 1.28-1.58), compared to normal kidney function (≥ 90 ml/min/1.73m). The strength of the association remained consistent when the models were restricted to different periods of follow-up. The HRs for incident dementia were 1.16 (95% CI 1.07-1.26) and 2.24 (95% CI 1.79-2.80) for moderate (3-30 mg/mmol) and severely increased ACR (≥ 30 mg/mmol) compared to normal ACR (< 3 mg/mmol). Dose-response associations were observed when combining eGFR and ACR, with those in the severest eGFR and ACR group having the greatest risk of dementia (HR = 4.70, 95% CI 2.34-9.43). APOE status significantly modified the association (p = 0.04), with stronger associations observed among participants with a lower genetic risk of dementia. There was no evidence of an interaction between kidney function and non-APOE polygenic risk of dementia with dementia risk (p = 0.42).
CONCLUSIONS
Kidney dysfunction and albuminuria were individually and jointly associated with higher dementia risk. The associations were greater amongst participants with a lower genetic risk of dementia based on APOE, but not non-APOE polygenic risk.
Topics: Humans; Albuminuria; Biological Specimen Banks; Creatinine; Dementia; Albumins; Kidney; United Kingdom
PubMed: 37605228
DOI: 10.1186/s13195-023-01248-z -
Journal of the American Society of... Mar 2014Recent data highlight the role of the proximal tubule (PT) in reabsorbing, processing, and transcytosing urinary albumin from the glomerular filtrate. Innovative... (Review)
Review
Recent data highlight the role of the proximal tubule (PT) in reabsorbing, processing, and transcytosing urinary albumin from the glomerular filtrate. Innovative techniques and approaches have provided exciting insights into these processes, and numerous investigators have shown that selective PT cell defects lead to significant albuminuria, even reaching nephrotic range in animal models. Thus, the mechanisms of albumin reabsorption and transcytosis are undergoing intense study. Working in concert with megalin and cubilin, a nonselective multireceptor complex that predominantly directs proteins for lysosomal degradation, the neonatal Fc receptor (FcRn) located at the brush border of the apical membrane has been implicated as the "receptor" mediating albumin transcytosis. The FcRn pathway facilitates reabsorption and mediates transcytosis by its pH-dependent binding affinity in endosomal compartments. This also allows for selective albumin sorting within the PT cell. This reclamation pathway minimizes urinary losses and catabolism of albumin, thus prolonging its serum half-life. It may also serve as a molecular sorter to preserve and reclaim normal albumin while allowing "altered" albumin to be catabolized via lysosomal pathways. Here, we critically review the data supporting this novel mechanism.
Topics: Albuminuria; Animals; Endocytosis; Histocompatibility Antigens Class I; Humans; Kidney Tubules, Proximal; Low Density Lipoprotein Receptor-Related Protein-2; Receptors, Cell Surface; Receptors, Fc
PubMed: 24408874
DOI: 10.1681/ASN.2013090950 -
Hormone Research in Paediatrics 2017In adults, lower vitamin D has been associated with increased albuminuria. This association has not been extensively studied in youth with or without type 1 diabetes. (Clinical Trial)
Clinical Trial
BACKGROUND/AIMS
In adults, lower vitamin D has been associated with increased albuminuria. This association has not been extensively studied in youth with or without type 1 diabetes.
METHODS
We examined the cross-sectional association between vitamin D and albuminuria (urine albumin to creatinine ratio ≥30 mg/g) in 8,789 participants of the National Health and Nutrition Survey 2001-2006 (NHANES), who were 6-19 years old. Further, we examined the association between vitamin D and albuminuria in 938 participants from the SEARCH Nutritional Ancillary Study (SNAS), a longitudinal cohort of youth with type 1 diabetes.
RESULTS
Of the NHANES participants, 5.3, 19.5, and 53.7% had vitamin D levels <30, 50 and 80 nmol/L, respectively. Albuminuria was present in 12.8% and was more common in younger children, females, non-Hispanic whites, non-obese children, and children with hypertension. After adjustments, there was no association between vitamin D and albuminuria. Among the SNAS participants with type 1 diabetes, we also found no association between baseline vitamin D and subsequent albuminuria in unadjusted or adjusted analyses.
CONCLUSION
We did not find an association between serum vitamin D and albuminuria in either non-diabetic youth or those with type 1 diabetes. Further research is needed to more fully understand this relationship.
Topics: Adolescent; Adult; Age Factors; Albuminuria; Child; Diabetes Complications; Diabetes Mellitus, Type 1; Female; Humans; Male; Sex Factors; Vitamin D
PubMed: 28554178
DOI: 10.1159/000475711 -
Journal of the American Heart... Jan 2024Albuminuria, an established biomarker of the progression of chronic kidney disease, is also recognized as a biomarker for the risk of cardiovascular disease. Elevated... (Review)
Review
Albuminuria, an established biomarker of the progression of chronic kidney disease, is also recognized as a biomarker for the risk of cardiovascular disease. Elevated urinary albumin excretion indicates kidney damage and systemic vascular disease, including myocardial capillary disease and arterial stiffness. Albuminuria is associated with an increased risk of coronary artery disease, stroke, heart failure, arrhythmias, and microvascular disease. There are now several therapeutic agents that can lead to albuminuria lowering and a reduction in cardiovascular risk. However, screening for albuminuria is still low. Considering the importance of multidisciplinary management of patients with cardiovascular disease, it is crucial that health care professionals managing such patients are aware of the benefits of albuminuria surveillance and management.
Topics: Humans; Cardiovascular Diseases; Albuminuria; Risk Factors; Renal Insufficiency, Chronic; Biomarkers
PubMed: 38214258
DOI: 10.1161/JAHA.123.030131 -
Journal of Diabetes Research 2017
Topics: Albuminuria; Diabetic Nephropathies; Humans
PubMed: 29201920
DOI: 10.1155/2017/2379432 -
Nephron 2023Hypokalemia is associated with an increased risk of chronic kidney disease (CKD) and is a risk factor for mortality. Albuminuria is an early manifestation of CKD. We...
INTRODUCTION
Hypokalemia is associated with an increased risk of chronic kidney disease (CKD) and is a risk factor for mortality. Albuminuria is an early manifestation of CKD. We investigated the association between hypokalemia and the prevalence of albuminuria in a Japanese general population.
METHODS
We analyzed the data of 18,289 subjects who underwent annual health checkups in 2018. We categorized them into four groups according to their concentration of serum potassium (sK) and performed a multivariate logistic regression analysis to determine the association between hypokalemia and the prevalence of albuminuria in this population. Hypokalemia was defined as having an sK = 3.1-3.5 mEq/L. After dividing the subjects into those with/without renal dysfunction, those with/without hypertension, and those with/without hyperglycemia, we examined the association between hypokalemia and albuminuria in each group.
RESULTS
Compared to the subjects with sK = 4.1-4.5 mEq/L, the subjects with hypokalemia had a significantly high prevalence of albuminuria: multivariable-adjusted odds ratio (OR) = 2.70 (95% confidence interval [CI] 1.84-3.96). The subgroup analyses showed the following multivariable-adjusted ORs (95% CIs) of the subjects: without renal dysfunction, 3.08 (2.00-4.73); with renal dysfunction, 2.05 (0.89-4.69); without hypertension, 2.89 (1.36-6.16); with hypertension, 2.60 (1.67-4.04); without hyperglycemia, 2.49 (1.62-3.84); and with hyperglycemia, 3.55 (1.43-8.79).
CONCLUSIONS
Hypokalemia was significantly associated with the high prevalence of albuminuria in general population. Regardless of the presence/absence of renal dysfunction, hypertension, or hyperglycemia, hypokalemia was positively associated with the prevalence of albuminuria, and the associations were significant except for the subjects with renal dysfunction.
Topics: Humans; Hypokalemia; Albuminuria; East Asian People; Renal Insufficiency, Chronic; Hypertension; Risk Factors; Hyperglycemia; Prevalence; Glomerular Filtration Rate
PubMed: 36724744
DOI: 10.1159/000529424 -
Association between weight-adjusted-waist index and chronic kidney disease: a cross-sectional study.BMC Nephrology Sep 2023We aimed to investigate the potential association between weight-adjusted-waist index (WWI) and chronic kidney disease (CKD).
AIMS
We aimed to investigate the potential association between weight-adjusted-waist index (WWI) and chronic kidney disease (CKD).
DESIGN AND METHODS
This research examined data collected from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2020. CKD was defined as the low estimated glomerular filtration rate (eGFR) or the existence of albuminuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30mg/g). Low-eGFR was described as eGFR < 60 mL/min/1.73m. The associations between WWI with CKD, albuminuria, and low-eGFR were examined using generalized additive models and weighted multivariable logistic regression models. We also analyzed the associations of other obesity indicators with CKD, albuminuria, and low-eGFR, including body mass index (BMI), waist-to-height ratio (WHtR), waist circumference(WC), height, and weight. The receiver operating characteristic (ROC) curves were used to assess and compare their diagnostic abilities.
RESULTS
Males made up 48.26% of the total 40,421 individuals that were recruited. The prevalences of CKD, albuminuria, and low-eGFR were 16.71%, 10.97%, and 7.63%, respectively. WWI was found to be positively linked with CKD (OR = 1.42; 95% CI: 1.26, 1.60). A nonlinear connection between WWI and CKD was found using smooth curve fitting. Additionally, a higher prevalence of albuminuria is linked to a higher level of WWI (OR = 1.60; 95% CI: 1.40, 1.82). Different stratifications did not substantially influence the connection between WWI and CKD, albuminuria, and low-eGFR, according to subgroup analysis and interaction tests. We observed higher height was related to higher low-eGFR prevalence (OR = 1.05; 95% CI: 1.03, 1.06). ROC analysis revealed that WWI had the best discrimination and accuracy for predicting CKD and albuminuria compared to other obesity indicators (BMI, WHTR, WC, height and weight). In addition, height had the highest area under the curve (AUC) value for predicting low-eGFR.
CONCLUSION
WWI is the best obesity indicator to predict CKD and albuminuria compared to other obesity indicators (BMI, WHTR, WC, height, and weight). WWI and CKD and albuminuria were found to be positively correlated. Furthermore, height had the strongest ability to predict low-eGFR. Therefore, the importance of WWI and height in assessing kidney health in US adults should be emphasized.
Topics: Adult; Male; Humans; Female; Cross-Sectional Studies; Nutrition Surveys; Albuminuria; Renal Insufficiency, Chronic; Obesity
PubMed: 37691097
DOI: 10.1186/s12882-023-03316-w -
Blood Advances Nov 2023It is critical to characterize the natural history of albuminuria in patients with sickle cell anemia (SCA); however, these data are currently lacking and affecting...
It is critical to characterize the natural history of albuminuria in patients with sickle cell anemia (SCA); however, these data are currently lacking and affecting evidence-based guidelines. We performed a natural history study of the development of pediatric albuminuria. We identified participants with hemoglobin SS/SB0 thalassemia ≥5 years with albumin to creatinine ratio (ACR) measurements performed at a steady-state clinic visit. Participants were characterized as either persistent, intermittent, or never albuminuria. We determined the prevalence of persistent albuminuria, use of ACR ≥100 mg/g as a predictor, and variation in ACR measurements. We mirrored this study to determine the variation in albuminuria measurements in the SCA murine model. Among 355 participants with HbSS/SB0 thalassemia with 1728 ACR measurements, we identified 17% with persistent and 13% with intermittent albuminuria. Thirteen percent of participants with persistent albuminuria developed an abnormal ACR before 10 years of age. A single ACR measurement ≥100 mg/g was associated with 55.5 times (95% confidence interval, 12.3-527) higher odds of having persistent albuminuria. Among participants with ACR ≥100 mg/g, we identified significant variability in the results of repeated measurements. The median ACR at the initial and next measurements were 175.8 mg/g (interquartile range [IQR], 135-242) and 117.3 mg/g (IQR, 64-292). The human variability in ACR was mirrored by ∼20% variability in albuminuria in murine model. This evidence suggests adopting standards for repeating ACR measurements, consider screening for ACR before 10 years of age, and using an ACR >100 mg/g as a risk factor for progression. Pediatric and murine renoprotective clinical trials need to consider the high variability in repeated ACR measurements.
Topics: Humans; Child; Animals; Mice; Albuminuria; Disease Models, Animal; Glomerular Filtration Rate; Creatinine; Anemia, Sickle Cell; Hemoglobin, Sickle; Thalassemia
PubMed: 37428862
DOI: 10.1182/bloodadvances.2023010101 -
Journal of Clinical Hypertension... Sep 2020High-normal albuminuria is related to the morbidity and mortality of cardiovascular disease. Arterial stiffness has been regarded as a predictor of cardiovascular...
High-normal albuminuria is related to the morbidity and mortality of cardiovascular disease. Arterial stiffness has been regarded as a predictor of cardiovascular disease. However, the relationship between high-normal albuminuria and arterial stiffness is uncertain in Chinese population. A total of 1343 Chinese participants (aged 58.9 ± 12.1 years, 63.53% male) were included in this study. High-normal albuminuria was defined as urinary albumin-to-creatinine ratio (UACR) above the median within normal albuminuria. Based on the level of UACR, all participants were divided into low-normal albuminuria group (UACR < 6.36 mg/g, n = 580), high-normal albuminuria group (6.36 mg/g ≤ UACR < 30 mg/g, n = 581), microalbuminuria (30 mg/g ≤ UACR < 300 mg/g, n = 162), and macroalbuminuria (UACR ≥ 300 mg/g, n = 20). Arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (cfPWV). With the increment of UACR, the level of cfPWV was increased gradually (P < .001). Stepwise multiple regression analysis showed that systolic blood pressure, age, serum creatinine, heart rate, logarithmic (LG)-transformed UACR, and fasting plasma glucose were independently associated with cfPWV in all subjects (P < .001). LG-UACR was found to be related to cfPWV in high-normal albuminuria and macroalbuminuria subjects. After further stratification in the high-normal albuminuria subjects, their relation remained in male, elderly over 65 years old, or normotensives. In summary, UACR is associated with arterial stiffness in subjects with proteinuria excretion in high normal level. High-normal albuminuria might be an early indicator of arterial stiffness, especially in male, elderly, or normotensives in Chinese population. Furthermore, age and blood pressure are still observed to be the most important risk factor of arterial stiffness.
Topics: Aged; Albuminuria; China; Creatinine; Female; Humans; Hypertension; Male; Middle Aged; Pulse Wave Analysis; Vascular Stiffness
PubMed: 33284512
DOI: 10.1111/jch.13979 -
Cerebrovascular Diseases (Basel,... 2010Gross albuminuria is associated with increased stroke risk, but it is unclear whether stroke incidence varies by level of albuminuria. We meta-analyzed prospective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gross albuminuria is associated with increased stroke risk, but it is unclear whether stroke incidence varies by level of albuminuria. We meta-analyzed prospective cohort studies to investigate the impact of various albuminuria levels and continuous urinary albumin excretion (UAE) change on stroke risk.
METHODS
Systematic search for studies reporting quantitative estimates of the multivariate-adjusted relative risk (RR) and 95% CI for stroke risk associated with microalbuminuria (UAE 30-300 mg/day or nearest equivalent interval) and macroalbuminuria (UAE >300 mg/day) and studies that analyzed the relation of stroke with UAE continuously. Estimates were combined using a random-effect model.
RESULTS
We identified seven studies comprising 46,638 participants with 1,479 stroke events. Incident stroke risk was greater for macroalbuminuria (RR 2.65, 95% CI 2.25-3.14) than microalbuminuria (RR 1.58, 95% CI 1.39-1.80), a difference that was significant (p for heterogeneity < 0.001, I(2) = 96%). In addition, risk of stroke increased proportionally with rising UAE (p < 0.001), even for UAE within normal range (beginning from levels as low as 2-4 mg/g).
CONCLUSIONS
Higher albuminuria level confers greater stroke risk. These findings provide additional weight to evidence that albuminuria is strongly linked to stroke risk, and suggest that persons with elevated UAE levels may especially benefit from more intensive vascular risk reduction.
Topics: Aged; Albuminuria; Cohort Studies; Humans; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Severity of Illness Index; Stroke
PubMed: 20733300
DOI: 10.1159/000317069