Hyperhomocysteinemia predicts renal function decline: a prospective study in hypertensive adults.
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ABSTRACT:
SUBMITTER: Xie D
PROVIDER: S-EPMC4639775 | biostudies-other | 2015 Nov
REPOSITORIES: biostudies-other
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Project description:Chronic kidney disease (CKD) is characterized by increased risks of morbidity and mortality. Upper-body subcutaneous fat, which is commonly estimated from the neck circumference (NC), was revealed to be the main reservoir of circulating nonesterified fatty acids in overweight patients. Despite a close association between NC and metabolic complications, the relationship of NC with renal function has not been fully investigated. In this study, the impact of NC on the development of incident CKD was elucidated.The data were retrieved from the Korean Genome and Epidemiology Study cohort. The subjects were followed at 2-year intervals from 2003 to 2011. Overweight was defined as a body mass index of ≥23 kg/m. A total of 4298 cohort subjects were screened. After exclusion, 2268 overweight subjects were included for the final analysis. The primary end point was incident CKD, which was defined as a composite of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m or the development of proteinuria.The mean patient age was 36.3 ± 3.0 years, and 1285 (56.7%) were men. They were divided into 2 groups according to the median NC in male and female subjects, separately. In both sexes, hypertension (men, P < 0.001; women, P = 0.009) and diabetes (men, P = 0.002; women, P < 0.001) were significantly more prevalent in the big NC group than in the small NC group. In contrast, eGFR was significantly lower only in male subjects of the big NC group (P < 0.001), whereas it was comparable between the small and big NC groups (P = 0.167). In multivariate Cox proportional hazards regression analysis, NC values were independently associated with incident CKD development in female subjects after adjusting for multiple confounding factors (per 1 cm increase, hazard ratio [95% confidence interval] = 1.159 [1.024-1.310], P = 0.019) but not in male subjects.NC is independently associated with the development of CKD in overweight female subjects, suggesting that it could be a practical risk factor for CKD.
| S-EPMC5023926 | biostudies-literature
Project description:Diabetic nephropathy accounts for most of the excess mortality in individuals with diabetes, but the molecular mechanisms by which nephropathy develops are largely unknown. Here we tested cytosine methylation levels at 397,063 genomic CpG sites for association with decline in the estimated glomerular filtration rate (eGFR) over a six year period in 181 diabetic Pima Indians. Methylation levels at 77 sites showed significant association with eGFR decline after correction for multiple comparisons. A model including methylation level at two probes (cg25799291 and cg22253401) improved prediction of eGFR decline in addition to baseline eGFR and the albumin to creatinine ratio with the percent of variance explained significantly improving from 23.1% to 42.2%. Cg22253401 was also significantly associated with eGFR decline in a case-control study derived from the Chronic Renal Insufficiency Cohort. Probes at which methylation significantly associated with eGFR decline were localized to gene regulatory regions and enriched for genes with metabolic functions and apoptosis. Three of the 77 probes that were associated with eGFR decline in blood samples showed directionally consistent and significant association with fibrosis in microdissected human kidney tissue, after correction for multiple comparisons. Thus, cytosine methylation levels may provide biomarkers of disease progression in diabetic nephropathy and epigenetic variations contribute to the development of diabetic kidney disease.
| S-EPMC5973533 | biostudies-literature
Project description:The ability of current tests to predict chronic kidney disease (CKD) complicating diabetes is limited. This study investigated the prognostic utility of a novel blood test, PromarkerD, for predicting future renal function decline in individuals with type 2 diabetes from the CANagliflozin CardioVascular Assessment Study (CANVAS). PromarkerD scores were measured at baseline in 3568 CANVAS participants (n = 1195 placebo arm, n = 2373 canagliflozin arm) and used to predict incident CKD (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 during follow-up in those above this threshold at baseline) and eGFR decline ?30% during the 4 years from randomization. Biomarker concentrations (apolipoprotein A-IV (apoA4), CD5 antigen-like (CD5L/AIM) and insulin-like growth factor-binding protein 3 (IGFBP3) measured by mass spectrometry were combined with clinical data (age, serum high-density lipoprotein (HDL)-cholesterol, eGFR) using a previously defined algorithm to provide PromarkerD scores categorized as low-, moderate- or high-risk. The participants (mean age 63 years, 33% females) had a median PromarkerD score of 2.9%, with 70.5% categorized as low-risk, 13.6% as moderate-risk and 15.9% as high-risk for developing incident CKD. After adjusting for treatment, baseline PromarkerD moderate-risk and high-risk scores were increasingly prognostic for incident CKD (odds ratio 5.29 and 13.52 versus low-risk, respectively; both p < 0.001). Analysis of the PromarkerD test system in CANVAS shows the test can predict clinically significant incident CKD in this multi-center clinical study but had limited utility for predicting eGFR decline ?30%.
| S-EPMC7600174 | biostudies-literature
Project description:Whether elevated serum uric acid levels (SUA) predict renal dysfunction remains controversial in the elderly. Therefore, we investigated the association between SUA and early renal function decline defined as an estimated glomerular filtration rate (eGFR) reduction ≥30% over 2 years. From 2001 to 2010, we conducted a longitudinal cohort study comprising 44,078 participants aged ≥65 years in the Taipei City Elderly Health Examination Database. Participants were classified by 1-mg/dL increment of SUA. We used multivariable logistic and Cox regression analyses to compare the risk of early renal function decline in different SUA groups. Compared to the reference SUA group of 5.0-5.9 mg/dL, hyperuricemic participants had increased risks of eGFR decline, starting at SUA ≥6.0 mg/dL (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] = 1.00-1.45). The risk progressively elevated as SUA increased, with the highest in the SUA ≥10.0 mg/dL group (aOR = 3.20, CI = 2.39-4.28). Multivariable Cox regression further confirmed that hyperuricemia was 1.12-fold (CI = 1.03-1.22, SUA ≥6.0 mg/dL) to 1.6-fold (CI = 1.37-1.86, SUA ≥10.0 mg/dL) more likely to develop early eGFR decline. Hyperuricemia-associated increased risks for early eGFR decline were consistent across subgroup and sensitivity analyses. Collectively, SUA ≥6.0 mg/dL independently predicted early renal dysfunction with eGFR decline ≥30% over 2 years in older people.
| S-EPMC6353916 | biostudies-literature
Project description:IntroductionSoluble urokinase-type plasminogen activator receptor (suPAR) strongly predicts outcomes and incident chronic kidney disease (CKD) in patients with cardiovascular disease (CVD). Whether the association between suPAR and CKD is a reflection of its overall association with chronic inflammation and poor CVD outcomes is unclear. We examined whether CVD biomarkers, including high-sensitivity C-reactive protein (hs-CRP), fibrin-degradation products (FDPs), heat-shock protein 70 (HSP-70), and high-sensitivity troponin I (hs-TnI) were associated with a decline in kidney function in the Emory Cardiovascular Biobank cohort, in which suPAR levels were shown to be predictive of both incident CKD and CVD outcomes.MethodsWe measured suPAR, hs-CRP, HSP-70, FDP, and hs-TnI plasma levels in 3282 adults (mean age 63 years, 64% male, 75% estimated glomerular filtration rate [eGFR] >60 ml/min per 1.73 m2). Glomerular filtration rate was estimated using Chronic Kidney Disease-Epidemiology Collaboration (eGFR) at enrollment (n = 3282) and follow-up (n = 2672; median 3.5 years). Urine protein by dipstick at baseline was available for 1335 subjects.ResultsThere was a weak correlation among biomarkers (r range: 0.17-0.28). hs-CRP, FDPs, hs-TnI, and suPAR were independently associated with baseline eGFR and proteinuria. The median yearly decline in eGFR was -0.6 ml/min per 1.73 m2. hs-CRP (β: -0.04; P = 0.46), FDPs (β: -0.13; P = 0.08), HSP-70 (β: 0.05; P = 0.84), or hs-TnI (β: -0.01; P = 0.76) were associated with eGFR decline. suPAR remained predictive of eGFR decline even after adjusting for all biomarkers.Discussionhs-CRP, FDP, HSP-70, and hs-TnI were not associated with eGFR decline. The specific association of suPAR with eGFR decline supported its involvement in pathways specific to the pathogenesis of kidney disease.
| S-EPMC5678674 | biostudies-literature
Project description:Hyponatremia is one of the most common electrolyte disorders observed in hospitalized and ambulatory patients. Hyponatremia is associated with increased falls, fractures, prolonged hospitalisation and mortality. The clinical importance of hyponatremia in the renal transplant field is not well established, so the aim of this study was to determine the relationships between hyponatremia and mortality as main outcome and renal function decline and graft loss as secondary outcome among a prospective cohort of renal transplant recipients. This prospective cohort study included 1315 patients between 1 May 2008 and 31 December 2014. Hyponatremia was defined as sodium concentration below 136 mmol/L at 6 months after transplantation. The main endpoint was mortality. A secondary composite endpoint was also defined as: rapid decline in renal function (≥5 mL/min/1.73 m2 drop of the eGFR/year), graft loss or mortality. Mean sodium was 140 ± 3.08 mmol/L. 97 patients displayed hyponatremia with a mean of 132.9 ± 3.05 mmol/L. Hyponatremia at 6 months after transplantation was associated neither with mortality (HR: 1.02; p = 0.97, 95% CI: 0.47-2.19), nor with the composite outcome defined as rapid decline in renal function, graft loss or mortality (logrank test p = 0.9). Hyponatremia 6 months after transplantation is not associated with mortality in kidney allograft patients.
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Project description:BackgroundLimited health literacy is associated with worse physical function in cross-sectional studies. We aimed to determine if health literacy is a risk factor for decline in physical function among older adults.MethodsA longitudinal cohort of 529 community-dwelling American adults aged 55-74?years were recruited from an academic general internal medicine clinic and federally qualified health centres in 2008-2011. Health literacy (Newest Vital Sign), age, gender, race, education, chronic conditions, body mass index, alcohol consumption, smoking status and exercise frequency were included in multivariable analyses. The 10-item PROMIS (Patient-Reported Outcomes Measurement Information System) physical function scale was assessed at baseline and follow-up (mean=3.2?years, SD=0.39).ResultsNearly half of the sample (48.2%) had either marginal (25.5%) or low health literacy (22.7%). Average physical function at baseline was 83.2 (SD=16.6) of 100, and health literacy was associated with poorer baseline physical function in multivariable analysis (p=0.004). At follow-up, physical function declined to 81.9 (SD=17.3; p=0.006) and 20.5% experienced a meaningful decline (>0.5 SD of baseline score). In multivariable analyses, participants with marginal (OR 2.62; 95%CI 1.38 to 4.95; p=0.003) and low (OR 2.57; 95%CI 1.22 to 5.44; p=0.013) health literacy were more likely to experience meaningful decline in physical function than the adequate health literacy group. Entering cognitive abilities to these models did not substantially attenuate effect sizes. Health literacy attenuated the relationship between black race and decline in physical function by 32.6%.ConclusionsLower health literacy increases the risk of exhibiting faster physical decline over time among older adults. Strategies that reduce literacy disparities should be designed and evaluated.
| S-EPMC4413744 | biostudies-literature
Project description:BackgroundHypertensive urgency is associated with a high risk for cardiovascular events and mortality in the United States and Europe, but data from low-income countries and interventions to improve outcomes are lacking.MethodsWe conducted a 1-year prospective study of the prevalence and outcomes of hypertensive urgency (blood pressure (BP) ≥180 mm Hg/120 mm Hg without end-organ damage) in a busy outpatient clinic in Tanzania.ResultsOf 7,600 consecutive adult outpatients screened with 3 unattended automated BP measurements according to standard protocol, the prevalence of hypertensive crisis was 199/7,600 (2.6%) (BP ≥180 mm Hg/120 mm Hg) and the prevalence of hypertensive urgency was 164/7,600 (2.2%). Among 150 enrolled patients with hypertensive urgency, median age was 62 years (54-68), 101 (67.3%) were women, and 53 (35%) were either hospitalized or died within 1 year. In a multivariate model, the strongest predictor of hospitalization/death was self-reported medication adherence on a 3 question scale (hazard ratio: 0.06, P < 0.001); 90% of participants with poor adherence were hospitalized or died within 1 year.ConclusionsPatients with hypertensive urgency in Africa are at high risk of poor outcomes. Clinicians can identify the patients at highest risk for poor outcomes with simple questions related treatment adherence. New interventions are needed to improve medication adherence in patients with hypertensive urgency.
| S-EPMC7947971 | biostudies-literature
Project description:ObjectiveAvailable biomarkers for monitoring primary glomerulonephritides (GNs), often lack the ability to assess longitudinal changes and have great variability with poor sensitivity. Accruing evidence has demonstrated that Neutrophil Gelatinase-Associated Lipocalin (NGAL), holds promising capacities in predicting renal function worsening in various renal diseases. We aimed at analyzing urinary NGAL (uNGAL) levels in a cohort of individuals with biopsy-proven GNs in order to evaluate its ability to reflect the entity of renal damage and to predict disease evolution overtime.MethodsWe enrolled 61 consecutive GNs patients still naïve to pathogenic therapy. uNGAL levels were measured at baseline and patients prospectively followed until the manifestation of a combined outcome of doubling of baseline serum creatinine and/or end-stage kidney disease requiring permanent dialysis support.ResultsMedian uNGAL levels were 107[35-312] ng/mL. At univariate and multivariate analyses an inverse correlation was found between eGFR and uNGAL levels (p = 0.001). Progressor subjects showed exceedingly increased baseline uNGAL values as compared with non-progressors (p < 0.001). Twenty-one patients (34%) reached the composite renal endpoint. Subjects with uNGAL values above the optimal, ROC-derived, cut-off of 107 ng/mL experienced a more rapid progression to the renal endpoint (p < 0.001; HR: 5.47; 95% CI 2.31-12.95) with a mean follow-up time to progression of 73.4 vs 83.5 months.ConclusionIn patients affected by primary glomerulonephritides, uNGAL may represent a real-time indicator of renal damage and an independent predictor of renal disease progression. Further studies on larger populations are warranted to confirm these findings.
| S-EPMC7272710 | biostudies-literature
Project description:BACKGROUND:While histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN. METHODS:In this longitudinal cohort study, we studied 50 adults diagnosed with biopsy-proven DN. We analyzed the histopathologic parameters of each patient's kidney biopsy, as defined by the Renal Pathology Society classification system for DN, and tracked all available eGFR measurements post-biopsy. We additionally collected baseline clinical parameters (at the time of biopsy), including eGFR, albumin-to-creatinine ratio (ACR), and hemoglobin A1c. Multivariable linear regression was used to assess the relationship between histologic and clinical parameters at the time of the biopsy and eGFR slope. Kaplan-Meier curves and Cox regression were used to evaluate the association between histologic and clinical parameters and ESKD incidence. RESULTS:Progression to ESKD was associated with worsening interstitial fibrosis score (p?=?0.05), lower baseline eGFR (p?=?0.02), higher ACR (p?=?0.001), and faster eGFR decline (p?<?0.001). The rate of eGFR decline did not associate with any histologic parameter. Baseline ACR was the only studied variable correlating with eGFR slope (rho?=?-?0.41). CONCLUSIONS:Renal histology predicts ultimate progression to ESKD, but not the rate of progression. Future work is required to identify novel predictors of rapid functional decline in patients with diabetic nephropathy.
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