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Association between serum albumin level and incidence of end-stage renal disease in patients with Immunoglobulin A nephropathy: A possible role of albumin as an antioxidant agent.

ABSTRACT: Serum albumin is the major intravascular antioxidant. Though oxidative stress plays an important role in the pathophysiology of Immunoglobulin A nephropathy (IgAN), the association between serum albumin and the progression of IgAN is not entirely understood. This retrospective cohort study of 1,352 participants with biopsy-proven IgAN determined the associations between serum albumin level and the incidence of end-stage renal disease (ESRD) using a Cox proportional hazards model. Patients were divided into three groups by tertiles of serum albumin level: Low, Middle, and High group (?3.9 g/dL, 4.0-4.3 g/dL, ?4.4 g/dL, respectively). During the median 5.1-year follow-up period, 152 patients (11.2%) developed ESRD. Participants in the Low group had a 1.88-fold increased risk for ESRD compared with those in the High group after adjustment for clinical parameters, including urinary protein excretion, and pathological parameters (Oxford classification). We also experimentally proved the antioxidant capacity of albumin on mesangial cells. The intracellular reactive oxygen species and mitochondrial injury, induced by hydrogen peroxide were significantly attenuated in albumin-pretreated mouse mesangial cells and human kidney cells compared with ?-globulin-pretreated cells. Low serum albumin level is an independent risk factor for ESRD in patients with IgAN. The mechanism could be explained by the antioxidant capacity of serum albumin.

SUBMITTER: Kawai Y

PROVIDER: S-EPMC5968404 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association between serum albumin level and incidence of end-stage renal disease in patients with Immunoglobulin A nephropathy: A possible role of albumin as an antioxidant agent.

Kawai Yasuhiro Y Masutani Kosuke K Torisu Kumiko K Katafuchi Ritsuko R Tanaka Shigeru S Tsuchimoto Akihiro A Mitsuiki Koji K Tsuruya Kazuhiko K Kitazono Takanari T

PloS one 20180524 5

Serum albumin is the major intravascular antioxidant. Though oxidative stress plays an important role in the pathophysiology of Immunoglobulin A nephropathy (IgAN), the association between serum albumin and the progression of IgAN is not entirely understood. This retrospective cohort study of 1,352 participants with biopsy-proven IgAN determined the associations between serum albumin level and the incidence of end-stage renal disease (ESRD) using a Cox proportional hazards model. Patients were d ...[more]

PMID: 29795559

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Project description:Background and objectivesThe mechanisms underlying erythropoietin resistance are not fully understood. Carbamylation is a post-translational protein modification that can alter the function of proteins, such as erythropoietin. The hypothesis of this study is that carbamylation burden is independently associated with erythropoietin resistance.Design, setting, participants, & measurementsIn a nonconcurrent prospective cohort study of incident hemodialysis patients in the United States, carbamylated albumin, a surrogate of overall carbamylation burden, in 158 individuals at day 90 of dialysis initiation and erythropoietin resistance index (defined as average weekly erythropoietin dose [U] per kg body weight per hemoglobin [g/dl]) over the subsequent 90 days were measured. Linear regression was used to describe the relationship between carbamylated albumin and erythropoietin resistance index. Logistic regression characterized the relationship between erythropoietin resistance index, 1-year mortality, and carbamylation.ResultsThe median percent carbamylated albumin was 0.77% (interquartile range=0.58%-0.93%). Median erythropoietin resistance index was 18.7 units/kg per gram per deciliter (interquartile range=8.1-35.6 units/kg per gram per deciliter). Multivariable adjusted analysis showed that the highest quartile of carbamylated albumin was associated with a 72% higher erythropoietin resistance index compared with the lowest carbamylation quartile (P=0.01). Increasing erythropoietin resistance index was associated with a higher risk of death (odds ratio per unit increase in log-erythropoietin resistance index, 1.69; 95% confidence interval, 1.06 to 2.70). However, the association between erythropoietin resistance index and mortality was no longer statistically significant when carbamylation was included in the analysis (odds ratio, 1.44; 95% confidence interval, 0.87 to 2.37), with carbamylation showing the dominant association with death (odds ratio for high versus low carbamylation quartile, 4.53; 95% confidence interval, 1.20 to 17.10).ConclusionCarbamylation was associated with higher erythropoietin resistance index in incident dialysis patients and a better predictor of mortality than erythropoietin resistance index.

Project description:OBJECTIVE:Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD. DESIGN AND METHODS:This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments. RESULTS:There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ?4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models. CONCLUSIONS:Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.

Project description:BackgroundPeritoneal dialysis (PD) is an easily implementable dialysis modality in end-stage renal disease (ESRD). PD may improve access to renal replacement therapy in low- and middle-income countries; however, these countries have a higher prevalence of protein-energy wasting in patients and poorer socioeconomic conditions. We evaluated the effects of HIV infection on serum albumin levels in ESRD patients starting continuous ambulatory PD (CAPD) and mortality outcomes.MethodsWe conducted a single-center prospective cohort study of consecutive incident CAPD patients recruited from two hospitals in Durban, South Africa, from September 2012 to February 2015. Seventy HIV-negative and 70 HIV-positive ESRD patients were followed monthly for serum albumin levels and mortality events during the first 18 months of CAPD therapy.ResultsThe HIV-positive cohort recorded 28 deaths (40%) among patients with a functional CAPD catheter at 18 months and 13 deaths (18.6%) in the HIV-negative cohort (p = 0.005). The mean serum albumin levels were lower in the HIV-positive cohort than in the HIV-negative cohort during the 18-month follow-up. The mean difference in serum albumin levels between the two cohorts was 4.24 g/L (95% confidence interval [CI] 2.02-6.46, p<0.001) at baseline and 3.99 g/L (95% CI 1.19-6.79, p = 0.006) at 18 months. HIV-positive status (adjusted regression coefficient -2.84, CI -5.00--0.67, p = 0.011), diabetes (adjusted coefficient -2.85; CI, -5.58--0.12; p = 0.041), and serum C-reactive protein and blood hemoglobin levels were independent predictors of serum albumin levels on multivariable linear regression. Baseline serum albumin <25 g/L (subdistribution-hazard ratio [SHR] 13.06, 95% CI 3.09-55.14, p<0.001) and CD4+ cell count <200 cells/?L (SHR 3.2, CI 1.38-7.45, p = 0.007) were independent predictors of mortality in our competing risk model.ConclusionsHIV infection can adversely affect serum albumin levels in ESRD patients managed with CAPD, while low baseline serum albumin levels and impaired immunity reliably predict mortality.

Project description:BackgroundDespite several clinical trials, the use of corticosteroid therapy for treating immunoglobulin A nephropathy (IgAN) remains controversial. We aimed to describe the use of corticosteroid therapy combined with supportive therapy in Norwegian patients with IgAN who had progressed to end-stage kidney disease.MethodsWe conducted a retrospective cohort study using data from the Norwegian Renal Registry. Overall, 143 patients with primary IgAN who progressed to end-stage kidney disease were divided into two groups: the corticosteroid group, who had been treated with corticosteroids and supportive therapy, and the non-corticosteroid group, which had underwent only supportive therapy. The kidney function, time to end-stage kidney disease, and adverse effects were described. The observation period lasted from the diagnostic kidney biopsy until the initiation of kidney replacement therapy.ResultsOf the 143 included patients, 103 underwent supportive therapy alone, and 40 were treated with corticosteroids. Most patients (94%) were treated with renin-angiotensin-system blockade, and all patients reached end-stage kidney disease after a median of 5 years (interquartile range; 2-9 years). Time from diagnosis until end-stage kidney disease was similar in the two study groups (p = 0.98). During 6 months of corticosteroid therapy, median eGFR declined from 21 (interquartile range; 13-46) mL/min/1.73 m2 to 20 (interquartile range; 12-40) mL/min/1.73 m2, and median proteinuria decreased from 5.5 g/24 h to 3.0 g/24 h. Most patients (87.5%) treated with corticosteroids reported adverse events. In our linear regression analysis investigating the time to ESKD, we found that age (β = -0.079, p = 0.008) and proteinuria at diagnosis (β = -0.50, p = 0.01) exhibited statistically significant associations with a delay in the progression to ESKD.ConclusionsIn this cohort of Norwegian patients with IgAN, corticosteroid therapy did not affect the time from diagnosis until end-stage kidney disease among a cohort of patients who all reached end-stage kidney disease. The treatment was also associated with adverse effects.

Dataset Information

Association between serum albumin level and incidence of end-stage renal disease in patients with Immunoglobulin A nephropathy: A possible role of albumin as an antioxidant agent.

Publications

Association between serum albumin level and incidence of end-stage renal disease in patients with Immunoglobulin A nephropathy: A possible role of albumin as an antioxidant agent.

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