Change in Novel Filtration Markers and Risk of ESRD Rebholz, Casey M., PhD, MS, MPH; Grams, Morgan E., MD, PhD, MHS; Matsushita, Kunihiro, MD, PhD ...
American journal of kidney diseases,
07/2015, Letnik:
66, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background Chronic kidney disease progression is a risk factor for end-stage renal disease (ESRD). A 57% decline in creatinine-based estimated glomerular filtration rate (eGFRcr ) is an established ...surrogate outcome for ESRD in clinical trials, and a 30% decrease recently has been proposed as a surrogate end point. However, it is unclear whether change in novel filtration marker levels provides additional information for ESRD risk to change in eGFRcr. Study Design Cohort study. Setting & Participants Atherosclerosis Risk in Communities (ARIC) Study participants from 4 US communities. Predictors Percent change in levels of filtration markers (eGFRcr , cystatin C−based eGFR eGFRcys , the inverse of β2 -microglobulin concentration 1/B2M) over a 6-year period. Outcome Incident ESRD. Measurements Cox proportional hazards regression with adjustment for demographics, kidney disease risk factors, and first measurement of eGFRcr. Results During a median follow-up of 13 years, there were 142 incident ESRD cases. In adjusted analysis, declines > 30% in eGFRcr , eGFRcys , and 1/B2M were associated significantly with ESRD compared with stable concentrations of filtration markers (HRs of 19.96 95% CI, 11.73-33.96, 16.67 95% CI, 10.27-27.06, and 22.53 95% CI, 13.20-38.43, respectively). Using the average of declines in the 3 markers, >30% decline conferred higher ESRD risk than that for eGFRcr alone (HR, 31.97 95% CI, 19.40-52.70; P = 0.03 vs eGFRcr ). Limitations Measurement error could influence estimation of change in filtration marker levels. Conclusions A >30% decline in kidney function assessed using novel filtration markers is associated strongly with ESRD, suggesting the potential utility of measuring change in cystatin C and B2M levels in settings in which improved outcome ascertainment is needed, such as clinical trials.
Galectin-3 has been proposed as a novel biomarker of heart failure and cardiac fibrosis, and may also be associated with fibrosis of other organs such as the kidney. To determine this, we ...prospectively analyzed data from 9,148 Atherosclerosis Risk in Communities (ARIC) Study participants with measured plasma galectin-3 levels (baseline, visit 4, 1996-98) and without prevalent chronic kidney disease (CKD) or heart failure. We identified 1,983 incident CKD cases through December 31, 2013 over a median follow-up of 16 years. At baseline, galectin-3 was cross-sectionally associated with estimated glomerular filtration rate and urine albumin-to-creatinine ratio; both significant. The results were adjusted for age, sex, race-center, education, physical activity, smoking status, body mass index, systolic blood pressure, anti-hypertensive medication use, history of cardiovascular disease, diabetes, fasting blood glucose, and rs4644 (a single nucleotide polymorphism of galactin-3). There was a significant, graded, and positive association between galectin-3 and incident CKD (quartile 4 vs. 1 hazard ratio: 2.22 95% confidence interval: 1.89, 2.60). The association was attenuated but remained significant after adjustment for estimated glomerular filtration rate, urine albumin-to-creatinine ratio, troponin T, and N-terminal pro-brain natriuretic peptide (quartile 4 vs. 1 hazard ratio: 1.75 95% confidence interval: 1.49, 2.06), and was stronger among those with hypertension at baseline (significant interaction). Thus, in this community-based population, higher plasma galectin-3 levels were associated with an elevated risk of developing incident CKD, particularly among those with hypertension.
Background People with advanced chronic kidney disease are at risk for the development of end-stage renal disease (ESRD), but also many other adverse outcomes, including cardiovascular disease (CVD) ...events and death. Determination of risk factors that explain the variability in prognosis and timing of these adverse outcomes can aid patient counseling and medical decision making. Study Design Prospective research cohort. Setting & Participants 1,798 participants with estimated glomerular filtration rates (eGFRs) < 30 mL/min/1.73 m2 in the CRIC Study were followed up for a median of 5.5 years. Predictors Age, race, sex, eGFR, proteinuria, diabetes mellitus, body mass index, ejection fraction, systolic blood pressure, history of CVD, and smoking history. Outcomes ESRD, CVD (congestive heart failure, stroke, myocardial infarction, and peripheral artery disease), and death. Results Baseline age of the cohort was 60 years, 46% were women, and 46% were African American. Although 52.3% of participants progressed to ESRD during follow-up, the path by which this occurred was variable. For example, predicted 1-year probabilities for a hypothetical 60-year-old white woman with eGFR of 30 mL/min/1.73 m2 , urine protein excretion of 1.8 g/d, and no diabetes or CVD (risk characteristics similar to the average participant) were 3.3%, 4.1%, and 0.3%, for first developing CVD, ESRD, and death, respectively. For a 40-year-old African American man with similar characteristics but higher systolic blood pressure, the corresponding 1-year probabilities were 2.4%, 13.2%, and 0.1%. For all participants, the development of ESRD or CVD increased the risk for subsequent mortality, with no differences by patient race or body mass index. Limitations The CRIC population was specifically recruited for kidney disease, and the vast majority had seen a nephrologist. Conclusions The prognosis and timing of adverse outcomes in chronic kidney disease vary by patient characteristics. These results may help guide the development of personalized approaches for managing patients with advanced CKD.
Current dietary guidelines recommend that patients with chronic kidney disease (CKD) restrict individual nutrients, such as sodium, potassium, phosphorus, and protein. This approach can be difficult ...for patients to implement and ignores important nutrient interactions. Dietary patterns are an alternative method to intervene on diet. Our objective was to define the associations of 4 healthy dietary patterns with risk for CKD progression and all-cause mortality among people with CKD.
Prospective cohort study.
2,403 participants aged 21 to 74 years with estimated glomerular filtration rates of 20 to 70mL/min/1.73m2 and dietary data in the Chronic Renal Insufficiency Cohort (CRIC) Study.
Healthy Eating Index-2015, Alternative Healthy Eating Index-2010, alternate Mediterranean diet (aMed), and Dietary Approaches to Stop Hypertension (DASH) diet scores were calculated from food frequency questionnaires.
(1) CKD progression defined as≥50% estimated glomerular filtration rate decline, kidney transplantation, or dialysis and (2) all-cause mortality.
Cox proportional hazards regression models adjusted for demographic, lifestyle, and clinical covariates to estimate hazard ratios (HRs) and 95% CIs.
There were 855 cases of CKD progression and 773 deaths during a maximum of 14 years. Compared with participants with the lowest adherence, the most highly adherent tertile of Alternative Healthy Eating Index-2010, aMed, and DASH had lower adjusted risk for CKD progression, with the strongest results for aMed (HR, 0.75; 95% CI, 0.62-0.90). Compared with participants with the lowest adherence, the highest adherence tertiles for all scores had lower adjusted risk for all-cause mortality for each index (24%-31% lower risk).
Self-reported dietary intake.
Greater adherence to several healthy dietary patterns is associated with lower risk for CKD progression and all-cause mortality among people with CKD. Guidance to adopt healthy dietary patterns can be considered as a strategy for managing CKD.
Determining whether a change in estimated glomerular filtration rate (eGFR) or albuminuria is clinically significant requires knowledge of short-term within-person variability of the measurements, ...which few studies have addressed in the setting of chronic kidney disease.
Cross-sectional study with multiple collections over less than 4 weeks.
Clinically stable outpatients with chronic kidney disease (N=50; mean age, 56.8 years; median eGFR, 40mL/min/1.73m2; median urinary albumin-creatinine ratio (UACR), 173mg/g).
Repeat measurements from serially collected samples across 3 study visits.
Measurements of urine albumin concentration (UAC), UACR, and plasma creatinine, cystatin C, β2-microglobulin (B2M), and beta trace protein (BTP).
We calculated within-person coefficients of variation (CVw) values and corresponding reference change positive and negative (RCVpos and RCVneg) values using log-transformed measurements.
Median CVw (RCVpos; RCVneg) values of filtration markers were 5.4% (+16%; −14%) for serum creatinine, 4.1% (+12%; −11%) for cystatin C, 7.4% (+23%; −18%) for BTP, and 5.6% (+17%; −14%) for B2M. Results for albuminuria were 33.2% (+145%; −59%) for first-morning UAC, 50.6% (+276%; −73%) for random spot UAC, 32.5% (+141%; −58%) for first-morning UACR, and 29.7% (124%; −55%) for random spot UACR. CVw values for filtration markers were comparable across the range of baseline eGFRs. CVw values for UAC and UACR were comparable across the range of baseline albuminuria values.
Small sample size limits the ability to detect differences in variability across markers. Participants were recruited and followed up in a clinical and not research setting, so some preanalytical factors could not be controlled.
eGFR markers appear to have relatively low short-term within-person variability, whereas variability in albuminuria appears to be high, making it difficult to distinguish random variability from meaningful biologic changes.
To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes.
Systematic ...umbrella review of existing meta-analyses.
MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023.
Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing ("class I"), highly suggestive ("class II"), suggestive ("class III"), weak ("class IV"), or no evidence ("class V"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as "high," "moderate," "low," or "very low" quality.
The search identified 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the pre-specified evidence classification criteria, convincing evidence (class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality.
Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research.
PROSPERO CRD42023412732.
Obstructive sleep apnea may be associated with development of CKD through hypoxia, inflammation, and oxidative stress. Individuals with this sleep disorder are also at increased risk for established ...CKD risk factors, including obesity, hypertension, and type 2 diabetes.
We examined the association between obstructive sleep apnea, other sleep characteristics, and risk of incident CKD (stage 3 or higher) in 1525 participants (mean age, 62.5 years; 52.4% women) in the Atherosclerosis Risk in Communities (ARIC) study who completed in-home polysomnography assessments. We used the apnea-hypopnea index (events per hour) to define obstructive sleep apnea severity (normal, <5.0; mild, 5.0-14.9; moderate, 15.0-29.9; and severe, ≥30.0) and defined incident CKD (stage 3 or higher) as eGFR<60 ml/min per 1.73 m
and ≥25% decline from baseline, CKD-related hospitalization or death, or ESKD. Cox proportional hazards regression was used to estimate obstructive sleep apnea severity with risk of incident CKD, adjusting for demographics, lifestyle behaviors, and cardiometabolic conditions.
During 19 years (median) of follow-up, 461 CKD events occurred. After adjustment for demographics and lifestyle behaviors, severe obstructive sleep apnea associated with increased risk of CKD (hazard ratio HR, 1.51; 95% confidence interval 95% CI, 1.08 to 2.10), which was attenuated after adjustment for body mass index (HR, 1.07; 95% CI, 0.75 to 1.52). No other sleep characteristics associated with incident CKD.
We found a link between obstructive sleep apnea and an elevated risk of stage 3 CKD or higher, but this association was no longer significant after adjusting for obesity, a risk factor for both conditions. Given the high prevalence of obstructive sleep apnea and CKD among adults, further investigation is warranted.
The authors conducted a meta-analysis of randomized controlled trials to evaluate the association of dietary protein intake with blood pressure. To identify articles published before April 2011, the ...authors searched electronic databases, conducted a manual bibliography review, and consulted experts in the field. Forty trials (including 3,277 participants in total) met the eligibility criteria and were included. Using a standardized form, 2 investigators independently abstracted data on study design, participant characteristics, and treatment outcomes. Net change estimates were pooled across trials using random-effects models. Compared with carbohydrate, dietary protein intake was associated with significant changes in mean systolic and diastolic blood pressure of -1.76 mm Hg (95% confidence interval (CI): -2.33, -1.20) and -1.15 mm Hg (95% CI: -1.59, -0.71), respectively (both P 's < 0.001). Both vegetable protein and animal protein were associated with significant blood pressure changes of -2.27 mm Hg (95% CI: -3.36, -1.18) and -2.54 mm Hg (95% CI: -3.55, -1.53), respectively, for systolic blood pressure (both P 's < 0.001) and -1.26 mm Hg (95% CI: -2.26, -0.26) and -0.95 mm Hg (95% CI: -1.72, -0.19), respectively, for diastolic blood pressure (both P 's = 0.014). Blood pressure reduction was not significantly different when vegetable protein was compared directly with animal protein. These findings indicate that partially replacing dietary carbohydrate with protein may be important for the prevention and treatment of hypertension.
Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma ...biomarkers can help identify these high-risk individuals.
In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of <60 ml/min per 1.73 m
at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, and mixed-effects models estimated biomarker relationships with rate of eGFR change.
Median follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR-2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline.
Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR-2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.
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