Dataset Information

Inflammation and Progression of CKD: The CRIC Study.

ABSTRACT: CKD is a global public health problem with significant mortality and morbidity.We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-?, TGF-?, high-sensitivity C-reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants.Over a median follow-up time of 6.3 years, 899 participants reached the composite end point of ?50% decline in eGFR from baseline or onset of ESRD. Elevated plasma levels of fibrinogen, IL-6, and TNF-? and lower serum albumin were associated with a greater decline in eGFR over time. After adjusting for demographics, BP, laboratory variables, medication use, and baseline eGFR, hazard ratios for the composite outcome were greater for the patients in the highest quartile of fibrinogen (hazard ratio, 2.05; 95% confidence interval, 1.64 to 2.55; P<0.001), IL-6 (hazard ratio, 1.44; 95% confidence interval, 1.17 to 1.77; P<0.01), and TNF-? (hazard ratio, 1.94; 95% confidence interval, 1.52 to 2.47; P<0.001) compared with those in the respective lowest quartiles. The hazard ratio was 3.48 (95% confidence interval, 2.88 to 4.21; P<0.001) for patients in the lowest serum albumin quartile relative to those in the highest quartile. When also adjusted for albuminuria, the associations of fibrinogen (hazard ratio, 1.49; 95% confidence interval, 1.20 to 1.86; P<0.001), serum albumin (hazard ratio, 1.52; 95% confidence interval, 1.24 to 1.87; P<0.001), and TNF-? (hazard ratio, 1.42; 95% confidence interval, 1.11 to 1.81; P<0.001) with outcome were attenuated but remained significant.Elevated plasma levels of fibrinogen and TNF-? and decreased serum albumin are associated with rapid loss of kidney function in patients with CKD.

SUBMITTER: Amdur RL

PROVIDER: S-EPMC5012490 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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Inflammation and Progression of CKD: The CRIC Study.

Amdur Richard L RL Feldman Harold I HI Gupta Jayanta J Yang Wei W Kanetsky Peter P Shlipak Michael M Rahman Mahboob M Lash James P JP Townsend Raymond R RR Ojo Akinlolu A Roy-Chaudhury Akshay A Go Alan S AS Joffe Marshall M He Jiang J Balakrishnan Vaidyanathapuram S VS Kimmel Paul L PL Kusek John W JW Raj Dominic S DS

Clinical journal of the American Society of Nephrology : CJASN 20160623 9

<h4>Background and objectives</h4>CKD is a global public health problem with significant mortality and morbidity.<h4>Design, setting, participants, & measurements</h4>We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-α, TGF-β, high-sensitivity C-reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants.<h4>Results</h4>Over a median follow-up time of 6.3 years, 899 par ...[more]

PMID: 27340285

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Project description:Background and objectivesHyperlipidemia is common in patients with CKD. The objective of this study was to evaluate whether measures of plasma lipids and lipoproteins predict progression of kidney disease in patients with CKD.Design, setting, participants, & measurementsProspective cohort study in adults (n=3939) with CKD aged 21-74 years recruited between 2003 and 2008 and followed for a median of 4.1 years. At baseline, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), apoA-I , apoB, and lipoprotein(a) [Lp(a)] were measured. The outcomes were composite end point of ESRD or 50% decline in eGFR from baseline (rate of change of GFR).ResultsMean age of the study population was 58.2 years, and the mean GFR was 44.9 ml/min per 1.73 m(2); 48% of patients had diabetes. None of the lipid or lipoprotein measures was independently associated with risk of the composite end point or rate of change in GFR. However, there were significant (P=0.01) interactions by level of proteinuria. In participants with proteinuria<0.2 g/d, 1-SD higher LDL-C was associated with a 26% lower risk of the renal end point (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59 to 0.92; P=0.01), and 1-SD higher total cholesterol was associated with a 23% lower risk of the renal end point (HR, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In participants with proteinuria>0.2 g/d, neither LDL-C (HR, 0.98; 95% CI, 0.98 to 1.05) nor total cholesterol levels were associated with renal outcomes. Treatment with statins was reported in 55% of patients and was differential across lipid categories.ConclusionsIn this large cohort of patients with CKD, total cholesterol, triglycerides, VLDL-C, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) were not independently associated with progression of kidney disease. There was an inverse relationship between LDL-C and total cholesterol levels and kidney disease outcomes in patients with low levels of proteinuria.

Project description:Rationale & objectiveMatrix metalloproteinase 2 (MMP-2) plays an important role in the development of fibrosis, the final common pathway of chronic kidney disease (CKD). This study aimed to assess the relationship between repeated measures of MMP-2 and CKD progression in a large, diverse prospective cohort.Study designIn a prospective cohort of Chronic Renal Insufficiency Cohort (CRIC) participants (N = 3,827), MMP-2 was measured at baseline. In a case-cohort design, MMP-2 was additionally measured at year 2 in a randomly selected subcohort and cases of estimated glomerular filtration rate (eGFR) halving or kidney replacement therapy (KRT) (N = 1,439).Setting & participantsCRIC is a multicenter prospective cohort of adults with CKD.ExposureMMP-2 measured in plasma at baseline and at year 2.OutcomesA composite kidney endpoint (KRT/eGFR halving).Analytical approachWeighted Cox proportional hazards models for case-cohort participants.ResultsParticipants were followed for a median of 4.6 years from year 2 and 6.9 years from the baseline. Persistently elevated MMP-2 (≥300 ng/mL at both baseline and year 2) increased the hazard of the composite kidney endpoint (HR, 1.61; 95% CI, 1.07-2.42; P = 0.09) after adjusting for covariates. The relationship of persistently elevated MMP-2 was modified by levels of inflammation, with a 2.6 times higher rate of the composite kidney endpoint in those with high-sensitivity C-reactive protein < 2.5 g/dL at study entry. Heterogeneity of effect was found with proteinuria, with a baseline MMP-2 level of ≥300 ng/mL associated with an increased risk of the composite kidney endpoint (HR, 1.30; 95% CI, 1.09-1.54) only with proteinuria ≥ 442 mg/g.LimitationsThe observational study design limits causal interpretation.ConclusionsElevated MMP-2 is associated with CKD progression, particularly among those with low inflammation and those with proteinuria. Future investigations are warranted to confirm the reduction in risk of CKD progression among these subgroups of patients with CKD.

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Inflammation and Progression of CKD: The CRIC Study.

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Inflammation and Progression of CKD: The CRIC Study.

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