Renal hyperfiltration as a risk factor for chronic kidney disease: A health checkup cohort study.
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ABSTRACT:
SUBMITTER: Oh SW
PROVIDER: S-EPMC7470278 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Project description:BackgroundRisk of infectious disease is increased among individuals with CKD. Fibroblast growth factor 23 (FGF23) is often elevated in CKD, and may impair immune function directly or indirectly through proinflammatory and vitamin D-suppressing pathways. Whether FGF23 is associated with risk of infection has not been evaluated in a CKD population.MethodsIn 3655 participants of the Chronic Renal Insufficiency Cohort study, we evaluated the association of baseline plasma levels of C-terminal FGF23 with time to first hospitalization with major infection, defined by hospital discharge with a diagnosis code for urinary tract infection, pneumonia, cellulitis/osteomyelitis, or bacteremia/septicemia. Multivariable Cox models were used to estimate hazard ratios (HRs) and adjust for confounding.ResultsDuring a median follow-up of 6.5 years, 1051 individuals (29%) were hospitalized with major infection. Multivariable Cox analysis indicated a graded increase in the risk of infection with higher levels of FGF23 (HR, 1.51; 95% CI, 1.23 to 1.85 with the highest quartile [≥235.9 RU/ml] versus lowest quartile [<95.3 RU/ml]; HR, 1.26; 95% CI, 1.18 to 1.35 per SD increment in log FGF23). The association was consistent across infection subtypes and demographic and clinical subgroups, and remained significant after additional adjustment for biomarkers of inflammation (IL-6, TNF-α, high-sensitivity C-reactive protein, fibrinogen, and albumin), and bone mineral metabolism (25-hydroxyvitamin D, phosphorus, calcium, and parathyroid hormone). The association was consistent across infection subtypes of urinary tract infection (482 cases), cellulitis/osteomyelitis (422 cases), pneumonia (399 cases), and bacteremia/septicemia (280 cases).ConclusionsAmong individuals with CKD, higher FGF23 levels were independently and monotonically associated with an increased risk of hospitalization with infection.
| S-EPMC7460903 | biostudies-literature
Project description:BACKGROUND:Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study. METHODS:Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance. RESULTS:Hematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin >?1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models. CONCLUSION:In a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction.
| S-EPMC6020240 | biostudies-literature
Project description:Background and purposeChronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors.MethodsThe study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates.ResultsIn 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin-angiotensin system did not decrease stroke risk in individuals with albuminuria.ConclusionsProteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation.
| S-EPMC4519405 | biostudies-literature
Project description:IntroductionThe independent role of serum uric acid (SUA) on kidney disease is controversial due to its association with metabolic syndrome. The objective of this study was to investigate the association of baseline SUA with development of chronic kidney disease and eGFR decline in normotensive, normoglycemic and non-obese individuals during follow up period.Materials and methodsWe included non-hypertensitive, non-diabetic, and non-obese 13,133 adults with estimated glomerular filtration rate (eGFR) ≥ 60ml/min/1.73m2 who had a voluntary health check-up during 2004-2017.ResultsSUA was positively related to adjusted means of systolic blood pressure (SBP), triglyceride, body mass index, and body fat percent. SUA was inversely associated with high density lipoprotein HDL (P for trend ≤0.001). SUA was an independent risk factor for the development of diabetes, hypertension, and obesity. During 45.0 [24.0-76.0] months of median follow up, the highest quartiles of SUA showed significant risks of 30% eGFR decline compared than the lowest quartile (RR:3.701; 95% CI: 1.504-9.108). The highest quartile had a 2.2 fold (95% CI: 1.182-4.177) increase in risk for incident chronic kidney disease (CKD).ConclusionsSUA is an independent risk factor for the development of diabetes, hypertension, and obesity in the healthy population. High SUA is associated with increased risk of CKD development and eGFR decline in participants with intact renal function.
| S-EPMC7840038 | biostudies-literature
Project description:Central pulse pressure (PP) can be noninvasively derived using the radial artery tonometric methods. Knowledge of central pressure profiles has predicted cardiovascular morbidity and mortality in several populations of patients, particularly those with known coronary artery disease and those receiving dialysis. Few data exist characterizing central pressure profiles in patients with mild-moderate chronic kidney disease who are not on dialysis. We measured central PP cross-sectionally in 2531 participants in the Chronic Renal Insufficiency Cohort Study to determine correlates of the magnitude of central PP in the setting of chronic kidney disease. Tertiles of central PP were <36 mm Hg, 36 to 51 mm Hg, and >51 mm Hg with an overall mean (+/-SD) of 46+/-19 mm Hg. Multivariable regression identified the following independent correlates of central PP: age, sex, diabetes mellitus, heart rate (negatively correlated), glycosylated hemoglobin, hemoglobin, glucose, and parathyroid hormone parathyroid hormone concentrations. Additional adjustment for brachial mean arterial pressure and brachial PP showed associations for age, sex, diabetes mellitus, weight, and heart rate. Discrete intervals of brachial PP stratification showed substantial overlap within the associated central PP values. The large size of this unique chronic kidney disease cohort provides an ideal situation to study the role of brachial and central pressure measurements in kidney disease progression and cardiovascular disease incidence.
| S-EPMC2941985 | biostudies-literature
Project description:BackgroundProtein carbamylation is a post-translational protein modification caused, in part, by exposure to urea's dissociation product cyanate. Carbamylation is linked to cardiovascular outcomes and mortality in dialysis-dependent end-stage kidney disease (ESKD), but its effects in earlier pre-dialysis stages of chronic kidney disease (CKD) are not established.MethodsWe conducted two nested case-control studies within the Chronic Renal Insufficiency Cohort Study. First, we matched 75 cases demonstrating CKD progression [50% estimated glomerular filtration rate (eGFR) reduction or reaching ESKD] to 75 controls (matched on baseline eGFR, 24-h proteinuria, age, sex and race). In the second study, we similarly matched 75 subjects who died during follow-up (cases) to 75 surviving controls. Baseline carbamylated albumin levels (C-Alb, a validated carbamylation assay) were compared between cases and controls in each study.ResultsAt baseline, in the CKD progression study, other than blood urea nitrogen (BUN) and smoking status, there were no significant differences in any matched or other parameter. In the mortality group, the only baseline difference was smoking status. Adjusting for baseline differences, the top tertile of C-Alb was associated with an increased risk of CKD progression [odds ratio (OR) = 7.9; 95% confidence interval (CI) 1.9-32.8; P = 0.004] and mortality (OR = 3.4; 95% CI 1.0-11.4; P = 0.05) when compared with the bottom tertile. C-Alb correlated with eGFR but was more strongly correlated with BUN.ConclusionsOur data suggest that protein carbamylation is a predictor of CKD progression, beyond traditional risks including eGFR and proteinuria. Carbamylation's association with mortality was smaller in this limited sample size.
| S-EPMC8719615 | biostudies-literature
Project description:IntroductionHuman studies report conflicting results on the predictive power of serum lipids on progression of chronic kidney disease (CKD). We aimed to systematically identify the lipids that predict progression to end-stage kidney disease.MethodsFrom the Chronic Renal Insufficiency Cohort, 79 patients with CKD stage 2 to 3 who progressed to ESKD over 6 years of follow up were selected and frequency-matched by age, sex, race, and diabetes with 121 non-progressors with less than 25% decline in estimated glomerular filtration rate (eGFR) during the follow up. The patients were randomly divided into Training and Test sets. We applied liquid chromatography-mass spectrometry-based lipidomics on visit year 1 samples.ResultsWe identified 510 lipids, of which the top 10 coincided with false discovery threshold of 0.058 in the Training set. From the top 10 lipids, the abundance of diacylglycerols (DAGs) and cholesteryl esters was lower, but that of phosphatidic acid 44:4 and monoacylglycerol (MAG) 16:0 was significantly higher in progressors. Using logistic regression models a multi-marker panel consisting of DAGs, and MAG independently predicted progression. The c-statistic of the multimarker panel added to the base model consisting of eGFR and urine protein-creatinine ratio (UPCR) as compared to that of the base model was 0.92 (95% Confidence Interval [CI]: 0.88-0.97), and 0.83 (95% CI: 0.76-0.90, P<0.01), respectively; an observation which was validated in the Test subset.ConclusionWe conclude that a distinct panel of lipids may improve prediction of progression of CKD beyond eGFR and UPCR when added to the base model.
| S-EPMC5402253 | biostudies-literature
Project description:The United States Renal Data System (USRDS) began in 1989 through US Congressional authorization under National Institutes of Health competitive contracting. Its history includes five contract periods, two of 5 years, two of 7.5 years, and the fifth, awarded in February 2014, of 5 years. Over these 25 years, USRDS reporting transitioned from basic incidence and prevalence of end-stage renal disease (ESRD), modalities, and overall survival, as well as focused special studies on dialysis, in the first two contract periods to a comprehensive assessment of aspects of care that affect morbidity and mortality in the second two periods. Beginning in 1999, the Minneapolis Medical Research Foundation investigative team transformed the USRDS into a total care reporting system including disease severity, hospitalizations, pediatric populations, prescription drug use, and chronic kidney disease and the transition to ESRD. Areas of focus included issues related to death rates in the first 4 months of treatment, sudden cardiac death, ischemic and valvular heart disease, congestive heart failure, atrial fibrillation, and infectious complications (particularly related to dialysis catheters) in hemodialysis and peritoneal dialysis patients; the burden of congestive heart failure and infectious complications in pediatric dialysis and transplant populations; and morbidity and access to care. The team documented a plateau and decline in incidence rates, a 28% decline in death rates since 2001, and changes under the 2011 Prospective Payment System with expanded bundled payments for each dialysis treatment. The team reported on Bayesian methods to calculate mortality ratios, which reduce the challenges of traditional methods, and introduced objectives under the Health People 2010 and 2020 national health care goals for kidney disease.
| S-EPMC4455192 | biostudies-other
Project description:Serum or plasma proteases have been associated with various diseases including cancer, inflammation, or reno-cardiovascular diseases. We aimed to investigate whether the enzymatic activities of serum proteases are associated with the estimated glomerular filtration rate (eGFR) in patients with different stages of chronic kidney disease (CKD). Our study population comprised 268 participants of the "Greifswald Approach to Individualized Medicine" (GANI_MED) cohort. Enzymatic activity of aminopeptidase A, aminopeptidase B, alanyl (membrane) aminopeptidase, insulin-regulated aminopeptidase, puromycin-sensitive aminopeptidase, leucine aminopeptidase 3, prolyl-endopeptidase (PEP), dipeptidyl peptidase 4 (DPP4), angiotensin I-converting enzyme, and angiotensin I-converting enzyme 2 (ACE2) proteases was measured in serum. Linear regression of the respective protease was performed on kidney function adjusted for age and sex. Kidney function was modeled either by the continuous Modification of Diet in Renal Disease (MDRD)-based eGFR or dichotomized by eGFR < 15 mL/min/1.73 m2 or <45 mL/min/1.73 m2, respectively. Results with a false discovery rate below 0.05 were deemed statistically significant. Among the 10 proteases investigated, only the activities of ACE2 and DPP4 were correlated with eGFR. Patients with lowest eGFR exhibited highest DPP4 and ACE2 activities. DPP4 and PEP were correlated with age, but all other serum protease activities showed no associations with age or sex. Our data indicate that ACE2 and DPP4 enzymatic activity are associated with the eGFR in patients with CKD. This finding distinguishes ACE2 and DPP4 from other serum peptidases analyzed and clearly indicates that further analyses are warranted to identify the precise role of these serum ectopeptidases in the pathogenesis of CKD and to fully elucidate underlying molecular mechanisms. Impact statement • Renal and cardiac diseases are very common and often occur concomitantly, resulting in increased morbidity and mortality. Understanding of molecular mechanisms linking both diseases is limited, available fragmentary data point to a role of the renin-angiotensin system (RAS) and, in particular, Ras-related peptidases. • Here, a comprehensive analysis of serum peptidase activities in patients with different stages of chronic kidney disease (CKD) is presented, with special emphasis given to RAS peptidases • The serum activities of the peptidases angiotensin I-converting enzyme 2 and dipeptidyl peptidase 4 were identified as closely associated with kidney function, specifically with the estimated glomerular filtration rate. The findings are discussed in the context of available data suggesting protective roles for both enzymes in reno-cardiac diseases. • The data add to our understanding of pathomechanisms underlying development and progression of CKD and indicate that both enzymes might represent potential pharmacological targets for the preservation of renal function.
| S-EPMC5367655 | biostudies-literature
Project description:Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease, before starting hemodialysis. We determined the association between SBP and mortality at advanced chronic kidney disease and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort participants with advanced chronic kidney disease followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants (1) had an estimated glomerular filtration rate <30 mL/min/1.73 m2 (n=1705), (2) initiated hemodialysis and had dialysis-unit SBP measures (n=403), and (3) initiated hemodialysis and had out-of-dialysis-unit SBP measured at a Chronic Renal Insufficiency Cohort study visit (n=326). Cox models were adjusted for demographics, cardiovascular risk factors, and dialysis parameters. A quadratic term for SBP was included to test for a U-shaped association. At advanced chronic kidney disease, there was no association between SBP and mortality (hazard ratio, 1.02 [95% confidence interval, 0.98-1.07] per every 10 mm Hg increase). Among participants who started hemodialysis, a U-shaped association between dialysis-unit SBP and mortality was observed. In contrast, there was a linear association between out-of-dialysis-unit SBP and mortality (hazard ratio, 1.26 [95% confidence interval, 1.14-1.40] per every 10 mm Hg increase). In conclusion, more efforts should be made to obtain out-of-dialysis-unit SBP, which may merit more consideration as a target for clinical management and in interventional trials.
| S-EPMC4268143 | biostudies-literature