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      Predictors of Hyperuricemia after Kidney Transplantation: Association with Graft Function

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          Abstract

          Background and objectives: In kidney transplant recipients (KTR), hyperuricemia (HU) is a commonly-observed phenomenon, due to calcineurin inhibitors and reduced kidney graft function. Factors predicting HU, and its association with graft function, remains equivocal. Materials and Methods: We conducted a retrospective longitudinal study to assess factors associated with HU in KTR, and to determine risk factors associated with graft function, measured as glomerular filtration rate (GFR). Moreover, GFR > 60 mL/min/1.73 m 2 was considered normal. HU was defined as a serum uric acid level of > 416 μmol/L (4.70 mg/dL) in men and >357 μmol/L (4.04 mg/dL) in women, or xanthine-oxidase inhibitor use. We built multiple logistic regression models to assess predictors of HU in KTR, as well as the association of demographic, clinical, and biochemical parameters of patients with normal GFR after a three-year follow-up. We investigated the effect modification of this association with HU. Results: There were 144 patients (mean age 46.6 ± 13.9), with 42.4% of them having HU. Predictors of HU in KTR were the presence of cystic diseases (OR = 9.68 (3.13; 29.9)), the use of diuretics (OR = 4.23 (1.51; 11.9)), and the male gender (OR = 2.45 (1.07; 5.56)). Being a younger age, of female gender, with a normal BMI, and the absence of diuretic medications increased the possibility of normal GFR. HU was the effect modifier of the association between demographic, clinical, and biochemical factors and a normal GFR. Conclusions: Factors associated with HU in KTR: Presence of cystic diseases, diuretic use, and male gender. HU was the effect modifier of the association of demographic, clinical, and biochemical factors to GFR.

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          Most cited references37

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          Elevated uric acid increases the risk for kidney disease.

          Recent epidemiologic studies suggest that uric acid predicts the development of new-onset kidney disease, but it is unclear whether uric acid is an independent risk factor. In this study, data from 21,475 healthy volunteers who were followed prospectively for a median of 7 yr were analyzed to examine the association between uric acid level and incident kidney disease (estimated GFR [eGFR] or =9.0 mg/dl) was associated with a tripled risk (odds ratio 3.12; 95% confidence interval 2.29 to 4.25). These increases in risk remained significant even after adjustment for baseline eGFR, gender, age, antihypertensive drugs, and components of the metabolic syndrome (waist circumference, HDL cholesterol, blood glucose, triglycerides, and BP). In a fully adjusted spline model, the risk for incident kidney disease increased roughly linearly with uric acid level to a level of approximately 6 to 7 mg/dl in women and 7 to 8 mg/dl in men; above these levels, the associated risk increased rapidly. In conclusion, elevated levels of uric acid independently increase the risk for new-onset kidney disease.
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            Clinical practice. Autosomal dominant polycystic kidney disease.

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              Uric acid as a target of therapy in CKD.

              The prevalence of chronic kidney disease (CKD) has increased and will continue to increase in the United States and worldwide. This is alarming considering that CKD is an irreversible condition and patients who progress to chronic kidney failure have reduced quality of life and high mortality rates. As such, it is imperative to identify modifiable risk factors to develop strategies to slow CKD progression. One such factor is hyperuricemia. Recent observational studies have associated hyperuricemia with kidney disease. In addition, hyperuricemia is largely prevalent in patients with CKD. Data from experimental studies have shown several potential mechanisms by which hyperuricemia may contribute to the development and progression of CKD. In this article, we offer a critical review of the experimental evidence linking hyperuricemia to CKD, highlight gaps in our knowledge on the topic as it stands today, and review the observational and interventional studies that have examined the potential nephroprotective effect of decreasing uric acid levels in patients with CKD. Although uric acid also may be linked to cardiovascular disease and mortality in patients with CKD, this review focuses only on uric acid as a potential therapeutic target to prevent kidney disease onset and progression. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                25 February 2020
                March 2020
                : 56
                : 3
                : 95
                Affiliations
                [1 ]Faculty of Medicine, Univeristy of Latvia, LV-1004 Riga, Latvia; liliana.tz@ 123456gmail.com (L.T.); folkmane.elizabete@ 123456gmail.com (E.F.); elina.glaudina@ 123456gmail.com (E.V.)
                [2 ]Pauls Stradins Clinical University Hospital, Centre of Nephrology of Latvia, LV-1002 Riga, Latvia; viktorija.kuzema@ 123456stradini.lv (V.K.); aivars.petersons@ 123456stradini.lv (A.P.)
                [3 ]Holon Institute of Technology, Holon 5810201, Israel
                [4 ]St. Bonifatius Hospital, 49808 Lingen (Ems), Germany
                [5 ]Faculty of medicine, Riga Stradins University, LV-1007 Riga, Latvia
                Author notes
                [* ]Correspondence: folkmane.inese@ 123456inbox.lv ; Tel.: +37-128806805
                Article
                medicina-56-00095
                10.3390/medicina56030095
                7143203
                32106421
                9e690eb6-1c35-4938-b184-b86da58b6905
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 January 2020
                : 21 February 2020
                Categories
                Article

                hyperuricemia,uric acid,kidney transplantation,glomerular filtration rate

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