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      Serum Uric Acid Level Predicts Progression of IgA Nephropathy in Females but Not in Males

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          Abstract

          Background

          Immunoglobulin A nephropathy (IgAN) is one of most common forms of glomerulonephritis. At this point, the clinical impact of hyperuricemia on IgAN is not clear. The aim of the present study was to explore the clinical impact of hyperuricemia on the progression of IgAN.

          Study Design

          Multicenter retrospective cohort study.

          Setting & Participants

          935 IgAN patients who were diagnosed by kidney biopsy at Osaka University Hospital, Osaka General Hospital, and Osaka Rosai Hospital. were included in this study.

          Predictor

          Uric acid levels at renal biopsy.

          Outcomes

          The outcome of interest was the time from the kidney biopsy to the time when a 50% increase in the baseline serum creatinine level was observed, which was defined as "progression".

          Measurements

          The baseline characteristics according to the kidney biopsy at the time of diagnosis were collected from the medical records, and included age, gender, body mass index, hypertension, diabetes (use of antidiabetic drugs), serum levels of creatinine, urinary protein, smoking status, RAAS blockers and steroid therapy.

          Results

          An elevated serum uric acid level was an independent risk factor for progression in female patients (per 1.0 mg/dL, multivariate-adjusted incident rate ratio 1.33 [95% confidence interval 1.07, 1.64], P = 0.008) but not in male patients (1.02 [0.81, 1.29], P = 0.855). To control a confounding effect of renal function on an association between serum uric acid level and progression in female patients, age- and serum creatinine-matched and propensity score-matched analyses were performed, and these results also supported the effect by uric acid on kidney disease progression independent of basal kidney function.

          Limitations

          A cohort analyzed retorospectively.

          Conclusions

          This study revealed that an elevated uric acid level was an independent risk factor for ESKD in female IgAN patients. Therefore, uric acid might be a treatable target in female IgAN patients.

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          Most cited references27

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          Hyperuricemia and coronary heart disease: a systematic review and meta-analysis.

          The role of serum uric acid as an independent risk factor for cardiovascular disease remains unclear, although hyperuricemia is associated with cardiovascular disease such as coronary heart disease (CHD), stroke, and hypertension. A systematic review and meta-analysis using a random-effects model was conducted to determine the risk of CHD associated with hyperuricemia in adults. Studies of hyperuricemia and CHD were identified by searching major electronic databases using the medical subject headings and keywords without language restriction (through February 2009). Only prospective cohort studies were included if they had data on CHD incidences or mortalities related to serum uric acid levels in adults. Twenty-six eligible studies of 402,997 adults were identified. Hyperuricemia was associated with an increased risk of CHD incidence (unadjusted risk ratio [RR] 1.34, 95% confidence interval [95% CI] 1.19-1.49) and mortality (unadjusted RR 1.46, 95% CI 1.20-1.73). When adjusted for potential confounding, the pooled RR was 1.09 (95% CI 1.03-1.16) for CHD incidence and 1.16 (95% CI 1.01-1.30) for CHD mortality. For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR for CHD mortality was 1.12 (95% CI 1.05-1.19). Subgroup analyses showed no significant association between hyperuricemia and CHD incidence/mortality in men, but an increased risk for CHD mortality in women (RR 1.67, 95% CI 1.30-2.04). Hyperuricemia may marginally increase the risk of CHD events, independently of traditional CHD risk factors. A more pronounced increased risk for CHD mortality in women should be investigated in future research.
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            The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators.

            To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care. Prospective cohort study. Five US teaching hospitals between 1989 and 1994. A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories. Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results. By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49 300 ($17 000, $30 500, $56 600) with RHC and $35 700 ($11 300, $20 600, $39 200) without RHC. Mean length of stay in the ICU was 14.8 (5, 9, 17) days with RHC and 13.0 (4, 7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful. In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study.
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              Menopause, postmenopausal hormone use and serum uric acid levels in US women – The Third National Health and Nutrition Examination Survey

              Introduction Despite the substantial prevalence of gout in the ageing female population, female hormonal influence has not been comprehensively examined. We evaluated and quantified the potential independent association between menopause, postmenopausal hormone use and serum uric acid levels in a nationally representative sample of women. Methods Using data from 7662 women aged 20 years and older in the Third National Health and Nutrition Examination Survey (1988 to 1994), we examined the relation between menopause, postmenopausal hormone use and serum uric acid levels. We used multivariate linear regression to adjust for other risk factors for hyperuricaemia such as dietary factors, age, adiposity, alcohol use, renal function, hypertension and diuretic use. Results Menopause was associated with higher serum uric acid levels. After adjusting for covariates, serum uric acid levels among women with natural menopause and surgical menopause were greater than premenopausal women by 0.34 mg/dl (95% confidence interval [CI], 0.19 to 0.49) and 0.36 mg/dl (95% CI, 0.14 to 0.57), respectively. Current postmenopausal hormone use was associated with a lower serum uric acid level among postmenopausal women (multivariate difference, 0.24 mg/dl [95% CI, 0.11 to 0.36]). The serum uric acid levels increased with increasing age categories (crude difference between 20 to 29 years and 70 years and over = 1.03 mg/dl, p for trend < 0.001), but this increase was not present after adjusting for other covariates (p for trend = 0.66). Conclusions These findings from a nationally representative sample of US women indicate that menopause is independently associated with higher serum uric acid levels, whereas postmenopausal hormone use is associated with lower uric acid levels among postmenopausal women. The age-associated increase in serum uric acid levels in women may be explained by menopause and other age-related factors.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 August 2016
                2016
                : 11
                : 8
                : e0160828
                Affiliations
                [1 ]Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine 1–1 Mukogawa-Cho, Nishinomiya, Hyogo, Japan
                [2 ]Health Care Center, Osaka University, Toyonaka, Osaka, Japan
                [3 ]Department of Kidney Disease and Hypertension, Osaka General Medical Center, Osaka, Osaka, Japan
                [4 ]Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
                [5 ]Division of Nephrology, Department of Internal Medicine, Osaka Rosai Hospital, Sakai, Osaka, Japan
                University of Sao Paulo Medical School, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceived and designed the experiments: YN RY TS MS TM YI TN.

                • Performed the experiments: YN RY TS MS YH KN AY TH TK.

                • Analyzed the data: YN RY TS MS.

                • Contributed reagents/materials/analysis tools: YN RY TS MS YH TH TM YI TN.

                • Wrote the paper: YN RY TS MS YI TN.

                Article
                PONE-D-15-47590
                10.1371/journal.pone.0160828
                4999279
                27560997
                29da7ad1-a051-49ff-895e-b61ef6347b4c
                © 2016 Nagasawa et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 November 2015
                : 26 July 2016
                Page count
                Figures: 2, Tables: 7, Pages: 14
                Funding
                Funded by: Japan Society for promotion science
                Award ID: 26461247
                Award Recipient :
                This work was supported by Grant-in-Aid for Scientific Research(C) to YN (26461247) from Japan Society for promotion science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Uric Acid
                Biology and Life Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Anatomy
                Renal System
                Kidneys
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biopsy
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Creatinine
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Biology and Life Sciences
                Biochemistry
                Proteins
                Serum Proteins
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Custom metadata
                Data are available from the Osaka University Institutional Ethics Committee ( rinri@ 123456hp-crc.med.osaka-u.ac.jp , Osaka University Hospital, Future medical Center, Division of clinical Trial, Yamadaoka2-2, Suita, Osaka, Japan).

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