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Prabhahar A, Batta A, Hatwal J, Kumar V, Ramachandran R, Batta A. Endothelial dysfunction in the kidney transplant population: Current evidence and management strategies. World J Transplant 2025; 15:97458. [PMID: 40104196 PMCID: PMC11612885 DOI: 10.5500/wjt.v15.i1.97458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 09/04/2024] [Accepted: 11/04/2024] [Indexed: 11/26/2024] Open
Abstract
The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators. Endothelial dysfunction (ED), characterized by impaired vasodilation, inflammation, and thrombosis, triggers future cardiovascular (CV) diseases. Chronic kidney disease, a state of chronic inflammation caused by oxidative stress, metabolic abnormalities, infection, and uremic toxins damages the endothelium. ED is also associated with a decline in estimated glomerular filtration rate. After kidney transplantation, endothelial functions undergo immediate but partial restoration, promising graft longevity and enhanced CV health. However, the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED, culminating in poor CV health and graft survival. ED in kidney transplant recipients is an under-recognized and poorly studied entity. CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts. ED contributes to the pathogenesis of many of the CV diseases. Various biomarkers and vasoreactivity tests are available to study endothelial functions. With an increasing number of transplants happening every year, and improved graft rejection rates due to the availability of effective immunosuppressants, the focus has now shifted to endothelial protection for the prevention, early recognition, and treatment of CV diseases.
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Affiliation(s)
- Arun Prabhahar
- Department of Telemedicine (Internal Medicine and Nephrology), Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Akshey Batta
- Department of Urology and Renal Transplant, Neelam Hospital, Rajpura 140401, Punjab, India
| | - Juniali Hatwal
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Vivek Kumar
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Raja Ramachandran
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Akash Batta
- Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
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Vareldzis R, Perez A, Reisin E. Hyperuricemia: An Intriguing Connection to Metabolic Syndrome, Diabetes, Kidney Disease, and Hypertension. Curr Hypertens Rep 2024; 26:237-245. [PMID: 38270791 DOI: 10.1007/s11906-024-01295-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2024] [Indexed: 01/26/2024]
Abstract
PURPOSE OF THE REVIEW Our review explores the epidemiology, physiology, and clinical data surrounding the connection between hyperuricemia and metabolic syndrome, chronic kidney disease, and hypertension. RECENT FINDINGS Compelling physiologic mechanisms have been proposed to explain a causal relationship between hyperuricemia and metabolic syndrome, chronic kidney disease, and hypertension but clinical studies have given mixed results in terms of whether intervening with hyperuricemia using urate-lowering therapy has any beneficial effects for patients with these conditions. Despite the large amount of research already put into this topic, more randomized placebo-controlled trials are needed to more firmly establish whether a cause-effect relationship exists and whether lowering uric acid levels in patients with these conditions is beneficial.
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Affiliation(s)
- Ramzi Vareldzis
- Section of Nephrology and Hypertension, Louisiana State University Health Science Center, New Orleans, LA, USA
| | - Annalisa Perez
- Section of Nephrology and Hypertension, Louisiana State University Health Science Center, New Orleans, LA, USA
| | - Efrain Reisin
- Section of Nephrology and Hypertension, Louisiana State University Health Science Center, New Orleans, LA, USA.
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3
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Multiple Gouty Arthritis With Tophi Formation in a Patient With End-Stage Kidney Disease Treated After Kidney Transplant. Transplant Proc 2022; 54:528-532. [DOI: 10.1016/j.transproceed.2021.10.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 10/28/2021] [Indexed: 11/18/2022]
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New-Onset Gout as an Independent Risk Factor for Returning to Dialysis After Kidney Transplantation. Transplant Direct 2020; 6:e634. [PMID: 33225059 PMCID: PMC7673774 DOI: 10.1097/txd.0000000000001081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 09/13/2020] [Indexed: 11/25/2022] Open
Abstract
Background. The causal relationship between gout and renal transplant outcomes is difficult to assess due to multiple interacting covariates. This study sought to estimate the independent effect of new-onset gout on renal transplant outcomes using a methodology that accounted for these interactions. Methods. This study analyzed data on patients in the US Renal Data System (USRDS) who received a primary kidney transplant between 2008 and 2015. The exposure was new-onset gout, and the primary endpoint was returning to dialysis >12 months postindex date (transplant date). A marginal structural model (MSM) was fitted to determine the relative risk of new-onset gout on return to dialysis. Results. 18 525 kidney transplant recipients in the USRDS met study eligibility. One thousand three hundred ninety-nine (7.6%) patients developed new-onset gout, and 1420 (7.7%) returned to dialysis >12 months postindex. Adjusting for baseline and time-varying confounders via the MSM showed new-onset gout was associated with a 51% increased risk of return to (RR, 1.51; 95% CI, 1.03-2.20). Conclusions. This finding suggests that new onset gout after kidney transplantation could be a harbinger for poor renal outcomes, and to our knowledge is the first study of kidney transplant outcomes using a technique that accounted for the dynamic relationship between renal dysfunction and gout.
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Erkmen Uyar M, Sezer S, Bal Z, Guliyev O, Tutal E, Kulah E, Genctoy G, Ozdemir Acar N, Haberal M. Post-transplant Hyperuricemıa as a Cardıovascular Risk Factor. Transplant Proc 2016; 47:1146-51. [PMID: 26036541 DOI: 10.1016/j.transproceed.2015.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Revised: 02/15/2015] [Accepted: 03/04/2015] [Indexed: 11/17/2022]
Abstract
PURPOSE Uric acid is known to impair endothelial cell function and to stimulate the development of renal interstitial fibrosis. The aim of this study was to evaluate the association between first-year hyperuricemia with graft dysfunction and the development of cardiovascular risk disorders in renal transplant recipients. METHODS One hundred kidney transplant recipients (31 female, 45.9 ± 9.6 post-transplantation months) with normal graft functions were enrolled. The clinical biochemical parameters in the first post-transplantation year were retrospectively recorded and searched for the predictive value in yearly determined graft function and association with cross-sectionally analyzed cardiovascular parameters, including body composition analyses, ambulatory blood pressure monitoring data, and pulse wave velocity. Hyperuricemia was defined as an uric acid level of ≥ 6.5 mg/dL that persisted for at least 2 consecutive tests. RESULTS One year after transplantation, 37% of subjects had hyperuricemia. According to cross-sectional data, sagittal abdominal diameter (P = .002) and hip circumferences (P = .013) were significantly higher in hyperuricemic patients than in normouricemic ones. Hyperuricemic patients had higher fat (P = .014) and muscle mass (P = .016) than normouremic patients. Hyperuricemic patients had significantly higher mean systolic BP (P = .044) than normouremic patients. Hyperuricemic patients had significantly higher pulse wave velocity levels (P = .0001) and left ventricular mass index (P = .044) than normouremic patients. The yearly decline in estimated glomerular filtration rate levels was significantly higher in hyperuricemic patients (P = .0001) than in normouricemic ones. CONCLUSION Post-transplantation hyperuricemia is associated with hypertension, arterial stiffness, and dyslipidemia; it should be accepted not only as a marker for renal allograft dysfunction but also as a cardiovascular risk factor in renal transplant recipients.
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Affiliation(s)
- M Erkmen Uyar
- Department of Nephrology, Baskent University, Antalya, Turkey.
| | - S Sezer
- Department of Nephrology, Baskent University, Antalya, Turkey
| | - Z Bal
- Department of Nephrology, Baskent University, Antalya, Turkey
| | - O Guliyev
- Department of Nephrology, Baskent University, Antalya, Turkey
| | - E Tutal
- Department of Nephrology, Baskent University, Antalya, Turkey
| | - E Kulah
- Department of Nephrology, Baskent University, Antalya, Turkey
| | - G Genctoy
- Department of Nephrology, Baskent University, Antalya, Turkey
| | - N Ozdemir Acar
- Department of Nephrology, Baskent University, Antalya, Turkey
| | - M Haberal
- Department of General Surgery, Baskent University, Ankara, Turkey
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Thomas B, Weir MR. The Evaluation and Therapeutic Management of Hypertension in the Transplant Patient. Curr Cardiol Rep 2015; 17:95. [DOI: 10.1007/s11886-015-0647-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Bellomo G. Asymptomatic hyperuricemia following renal transplantation. World J Nephrol 2015; 4:324-329. [PMID: 26167455 PMCID: PMC4491922 DOI: 10.5527/wjn.v4.i3.324] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2015] [Revised: 03/19/2015] [Accepted: 04/20/2015] [Indexed: 02/06/2023] Open
Abstract
Evidence is accumulating indicating a role for uric acid in the genesis and progression of kidney disease, and a few studies are beginning to show a possible beneficial effect of urate-lowering therapy. Whether this holds true for renal allograft recipients is not clear. In this short review evidence from epidemiological as well as intervention studies is summarized and discussed, with some practical considerations presented at the end.
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EXP CLIN TRANSPLANTExp Clin Transplant 2015; 13. [DOI: 10.6002/ect.mesot2014.p49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register]
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Sibunruang C, Ingsathit A, Kantachuvesiri P, Radinahamed P, Rattanasiri S, Pootracool P, Kijvikai K, Sumethkul V, Kantachuvesiri S. Increased urine transforming growth factor β1 (TGF-β1) and serum uric acid are associated with an early decline of glomerular filtration rate in kidney transplant recipients. Transplant Proc 2015; 47:304-308. [PMID: 25769564 DOI: 10.1016/j.transproceed.2014.11.037] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 10/23/2014] [Accepted: 11/19/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND The renin-angiotensin system (RAS) and transforming growth factor β1 (TGF-β1) may play a role in the pathogenesis of fibrosis in kidney allografts. Experimental hyperuricemia shows activation of intrarenal RAS. However, the association between uric acid (UA), RAS, and TGF-β1 in allograft recipients has not been demonstrated. Therefore we investigated the association between serum UA levels, RAS, and TGF-β1 in kidney transplant recipients during the 1st year after transplantation. METHODS Sixty-two transplant recipients were included in the study. Serum UA level, plasma renin activity (PRA), and urine TGF-β1 concentration were studied at 3, 6, and 12 months after transplantation. Statistical correlation was demonstrated with the use of Spearman rank correlation coefficient. Receiver operating characteristic curve analysis and area under the curve were performed to assess the diagnostic performance to discriminate between estimated glomerular filtration rate (eGFR) <60 and ≥ 60 mL/min/1.73 m(2). RESULTS For all 62 patients, urine TGF-β1 and serum UA had a tendency to increase during the 1-year follow-up period, despite no statistically significant change in eGFR. We found that increased urine TGF-β1 was correlated with rising serum UA levels and a decrease of the eGFR (r = 0.27 [P = .01]; r = -0.38 [P = .0003]). In contrast, there was no significant change in PRA and it was not correlated with eGFR or TGF-β1 (r = -0.01; P = .93). CONCLUSIONS Increased urine TGF-β1 and serum UA level during the 1st year after transplantation correlated with a decline in eGFR. The evaluation of these parameters in the early post-transplantation period may identify patients at risk of allograft dysfunction.
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Affiliation(s)
- C Sibunruang
- Renal Division, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - A Ingsathit
- Renal Division, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Clinical Epidemiology and Biostatistics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - P Kantachuvesiri
- Renal Division, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - P Radinahamed
- Renal Division, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - S Rattanasiri
- Clinical Epidemiology and Biostatistics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - P Pootracool
- Vascular and Organ Transplantation Division, Department of Surgery, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - K Kijvikai
- Urology Division, Department of Surgery, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - V Sumethkul
- Renal Division, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - S Kantachuvesiri
- Renal Division, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
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Kim ED, Famure O, Li Y, Kim SJ. Uric acid and the risk of graft failure in kidney transplant recipients: a re-assessment. Am J Transplant 2015; 15:482-8. [PMID: 25612498 DOI: 10.1111/ajt.13000] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Revised: 08/19/2014] [Accepted: 09/03/2014] [Indexed: 01/25/2023]
Abstract
The association of hyperuricemia with kidney allograft outcomes remains controversial. We studied this problem in 1170 kidney transplants from January 2000 to December 2010. The primary endpoint was total graft failure (i.e. graft loss or death). Conventional, time-dependent and marginal structural Cox proportional hazards models were fitted, the latter accounting for kidney function as a time-varying confounder affected by prior uric acid levels. Uric acid level was associated with an increased risk of total graft failure in time-fixed and time-varying models (HR 1.02 [95% CI: 1.003-1.04] and HR 1.02 [95% CI: 1.01-1.03], respectively, for every 10 µmol/L increase in uric acid). In contrast, the marginal structural model showed a modestly protective effect (HR 0.90 [95% CI: 0.85-0.94] for every 10 µmol/L increase in uric acid). Similar results were observed for death-censored graft failure and death with graft function. In summary, the absence of a deleterious association between elevated uric acid and graft outcome after accounting for graft function as a time-varying confounder suggests that uric acid is not an independent risk factor for graft failure. The modestly protective effect of uric acid may be an indicator of nutritional status but further study is warranted.
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Affiliation(s)
- E D Kim
- Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Weng SC, Shu KH, Wu MJ, Cheng CH, Chen CH, Yu TM, Chuang YW, Huang ST, Tarng DC. Hyperuricemia predicts kidney disease progression after acute allograft dysfunction. Transplant Proc 2014; 46:499-504. [PMID: 24655999 DOI: 10.1016/j.transproceed.2013.09.040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Accepted: 09/20/2013] [Indexed: 01/31/2023]
Abstract
BACKGROUND Hyperuricemia is associated with the development of new cardiovascular events and chronic allograft nephropathy in patients with decreased allograft function. This study investigates whether hyperuricemia in kidney transplant recipients should be considered as an independent predictor of kidney disease progression after acute allograft dysfunction. METHODS Between September 1, 2010, and December 31, 2012, 124 patients who underwent kidney graft biopsy for acute allograft dysfunction were enrolled. Participants were divided into 2 groups: A hyperuricemic group (n = 57) and a normouricemic group (n = 67). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia on the composite end point (CEP) of doubling of serum creatinine and graft failure by using Cox regression and Kaplan-Meier plots. RESULTS Over a mean follow-up of 14.27 months, the hyperuricemic group had a poor cumulative survival and easily reached the CEP of doubling of serum creatinine and graft failure (P = .025) with a first-year cumulative incidence of 29.84% and a second-year cumulative incidence of 35.09%. Cox regression models revealed that age at biopsy (unadjusted hazard ratio [HR], 1.03; 95% CI, 1.00-1.06), hyperuricemia (HR, 2.24; 95% CI, 1.13-4.46), and interstitial fibrosis and tubular atrophy (IF/TA), including <25% of parenchyma affected (HR, 3.71; 95% CI, 1.34-10.31) and ≥ 25% of parenchyma affected (HR, 5.10; 95% CI, 1.83-14.19), were highly associated with poor outcome. After adjusting different variables, hyperuricemia and IF/TA were still significant. CONCLUSION Persistently high serum UA and IF/TA both contribute to the risk of kidney disease progression after acute allograft dysfunction.
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Affiliation(s)
- S-C Weng
- Center for Geriatrics and Gerontology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung; Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung
| | - K-H Shu
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung; School of Medicine, Chung Shan Medical University, Taichung
| | - M-J Wu
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung; Institute of Clinical Medicine, National Yang-Ming University, Taipei; School of Medicine, Chung Shan Medical University, Taichung; School of Medicine, College of Medicine, China Medical University, Taichung
| | - C-H Cheng
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung; School of Medicine, Chung Shan Medical University, Taichung; School of Medicine, College of Medicine, China Medical University, Taichung; Department of Biotechnology, Hung Kuang University, Taichung
| | - C-H Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung
| | - T-M Yu
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung
| | - Y-W Chuang
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung
| | - S-T Huang
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung
| | - D-C Tarng
- Institute of Clinical Medicine, National Yang-Ming University, Taipei; Department and Institute of Physiology, National Yang-Ming University, Taipei; Division of Nephrology, Department of Medicine, and Immunology Research Center, Taipei Veterans General Hospital, Taipei, Taiwan.
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Dousdampanis P, Trigka K, Musso CG, Fourtounas C. Hyperuricemia and chronic kidney disease: an enigma yet to be solved. Ren Fail 2014; 36:1351-1359. [PMID: 25112538 DOI: 10.3109/0886022x.2014.947516] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation.
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Uric acid and allograft loss from interstitial fibrosis/tubular atrophy: post hoc analysis from the angiotensin II blockade in chronic allograft nephropathy trial. Transplantation 2014; 97:1066-71. [PMID: 24503762 DOI: 10.1097/01.tp.0000440952.29757.66] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Uric acid has been linked to the progression of native kidney disease. Studies evaluating its contribution to allograft function in kidney transplant recipients, among whom hyperuricemia is common, have yielded mixed results. METHODS We evaluated the association between baseline uric acid and the primary composite outcome of doubling of interstitium or ESRD from interstitial fibrosis and tubular atrophy (IF/TA) in the Angiotensin II Blockade for Chronic Allograft Nephropathy (ABCAN) Trial participants. Subjects underwent uric acid, iothalamte GFR, and urine albumin to creatinine (ACR) measurements annually for 5 years in addition to an allograft biopsy at baseline and 5 years. RESULTS Baseline uric acid was 5.57±1.48 mg/dL; male sex, higher BMI, diuretic use, and lower GFR were associated with higher uric acid, whereas older age, less than 3 HLA matches and having a female donor were associated with lower levels. In multivariate analysis adjusting for baseline GFR, uric acid was associated with doubling of interstitium or ESRD from IF/TA (OR 1.83, 95% CI, 1.06-3.17, P=0.03). Over time, a 1 mg/dL increase in time-varying uric acid was associated with a 2.39 mL/min lower final GFR (P<0.001) but not with the secondary outcome of creatinine doubling, ESRD, or death. CONCLUSIONS These data suggest that uric acid is associated with IF/TA and thus may be a viable target for intervention.
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Tainio J, Qvist E, Hölttä T, Pakarinen M, Jahnukainen T, Jalanko H. Metabolic risk factors and long-term graft function after paediatric renal transplantation. Transpl Int 2014; 27:583-92. [PMID: 24606122 DOI: 10.1111/tri.12300] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2013] [Revised: 12/28/2013] [Accepted: 03/03/2014] [Indexed: 11/27/2022]
Abstract
The aim of this study was to evaluate metabolic risk factors and their impact on long-term allograft function in paediatric renal transplant (RTx) patients. We reviewed the medical records of 210 RTx patients who underwent transplantation at a median age of 4.5 years (range 0.7-18.2) and a median follow-up of 7.0 years (range 1.5-18.0). Data on lipid and glucose metabolism, uric acid levels, weight and blood pressure were collected up to 13 years post-RTx, and the findings were correlated with the measured glomerular filtration rate (GFR). Beyond the first year, GFR showed gradual deterioration with a mean decline of 2.4 ml/min/1.73 m(2)/year. Metabolic syndrome, overweight, hypertension and type 2 diabetes were diagnosed in 14-19%, 20-23%, 62-87% and 3-5% of the patients, respectively. These entities showed only mild association with the concomitant or long-term GFR values. Dyslipidaemia was common and hypertriglyceridaemia associated with a lower GFR at 1.5 and 5 years post-RTx (P = 0.008 and P = 0.017, respectively). Similarly, hyperuricaemia was frequent and associated significantly with GFR (P < 0.001). Except for hyperuricaemia and hypertriglyceridaemia, metabolic risk factors beyond the first postoperative year associated modestly with the long-term kidney graft function in paediatric RTx patients.
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Affiliation(s)
- Juuso Tainio
- Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
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15
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The association between serum uric acid levels at 3 months after renal transplantation and the graft outcome in living donor renal transplantation. Transplant Proc 2013; 45:1548-52. [PMID: 23726617 DOI: 10.1016/j.transproceed.2012.10.062] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Revised: 09/12/2012] [Accepted: 10/09/2012] [Indexed: 12/22/2022]
Abstract
BACKGROUND Hyperuricemia is a common complication in renal transplant recipients in the era of cyclosporine-based immunosuppression. The evidence regarding the impact of hyperuricemia on allograft survival is controversial. The aim of this study was to investigate the association between serum uric acid levels and renal allograft outcomes. MATERIALS AND METHODS Between April 1991 and May 2011, adult renal transplants recipients were assessed retrospectively comparing serum creatinine levels at 3, 12, and 36 months, acute rejection rates, and long-term allograft survivals among normouricemic versus hyperuricemic (>7 mg/dL) patients at 3 months after renal transplantation. RESULTS Of 378 patients, 152 (40.21%) showed hyperuricemia and 226 (59.79%) showed normouricemia. Mean serum creatinine levels were 1.48 ± 0.38, 1.72 ± 2.68 and 1.64 ± 1.24 mg/dL at 3, 12, and 36 months after renal transplantation, respectively. Serum uric acid levels correlated negatively with serum creatinine levels at 12 months (P = .028). Graft survival rates at 10 years after renal transplantation were 88.6% among the normouricemic versus 78.8% among the hyperuricemic patients (P = .040). CONCLUSIONS High serum uric acid levels measured at 3 months after renal transplantation were associated with poorer long-term graft function.
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Dahle DO, Jenssen T, Holdaas H, Leivestad T, Vårdal M, Mjøen G, Reisaeter AV, Toft I, Hartmann A. Uric acid has a J-shaped association with cardiovascular and all-cause mortality in kidney transplant recipients. Clin Transplant 2013; 28:134-40. [PMID: 24372653 DOI: 10.1111/ctr.12290] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2013] [Indexed: 12/15/2022]
Abstract
The association between serum uric acid and kidney graft and recipient survival is uncertain. During 2000-2011, we measured serum uric acid at week 10 after transplantation. Of 2748 transplanted patients, 2200 (80.1%) attended this visit. After a median follow-up of 7.4 yr, 378 patients had died, 143 from a cardiovascular cause, and 185 patients lost their graft. The third quintile of uric acid levels (357-405 μM) had the lowest mortality risk and was used as reference group. In Cox proportional hazard models adjusting for graft and patient characteristics, the fifth quintile of uric acid levels (>474 μM) was independently associated with cardiovascular mortality (hazard ratio [HR] = 2.87 [1.55-5.32], p = 0.001) and all-cause mortality (HR = 1.57 [1.09-2.25], p = 0.02). Also, the lowest quintile of uric acid levels (<309 μM) showed a trend toward increased risk of cardiovascular mortality (HR = 1.79 [0.90-3.58], p = 0.10) and all-cause mortality (HR = 1.31 [0.89-1.93], p = 0.18). The increased risk at low uric acid levels was confined to diabetic recipients. Uric acid was not associated with death-censored graft loss. In conclusion, uric acid has a J-shaped association with cardiovascular and all-cause mortality in kidney transplant recipients.
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Affiliation(s)
- Dag Olav Dahle
- Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Einollahi B, Einollahi H, Nafar M, Rostami Z. Prevalence and risk factors of hyperuricemia among kidney transplant recipients. Indian J Nephrol 2013; 23:201-5. [PMID: 23814419 PMCID: PMC3692146 DOI: 10.4103/0971-4065.111849] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Hyperuricemia is common in renal transplant patients (RTRs), especially those on cyclosporine (CsA)-based therapy. We conducted a retrospective study to determine the prevalence of hyperuricemia and its risk factors among RTRs. A total of 17,686 blood samples were obtained from 4,217 RTRs between April 2008 and January 2011. Hyperuricemia was defined as an uric acid level of ≥7.0 mg/dl in men and of ≥6 mg/dl in women that persisted for at least two consecutive tests. Majority (68.2%) of RTRs were normouricemic. Hyperuricemia was more frequent in younger and female RTRs. On multivariate logistic regression, we found high trough level of cyclosporine to be a risk factor for hyperuricemia. In addition, female gender, impaired renal function, and dyslipidemia (hypercholesterolemia, hypertriglyceridemia, and elevated LDL) were also associated with higher probability of hyperuricemia. Hyperuricemia is a common complication after renal transplantation. Risk factors implicated in post-transplant hyperuricemia include high trough level of cyclosporine, female gender, renal allograft dysfunction, and dyslipidemia.
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Affiliation(s)
- B Einollahi
- Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, I.R. Iran
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Bellomo G. Uric acid and chronic kidney disease: A time to act? World J Nephrol 2013; 2:17-25. [PMID: 24175261 PMCID: PMC3782226 DOI: 10.5527/wjn.v2.i2.17] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2013] [Revised: 03/25/2013] [Accepted: 04/11/2013] [Indexed: 02/06/2023] Open
Abstract
A role for uric acid in the pathogenesis and progression of renal disease had been proposed almost a century ago, but, too hastily dismissed in the early eighties. A body of evidence, mostly accumulated during the last decade, has led to a reappraisal of the influence of uric acid on hypertension, cardiovascular, and renal disease. The focus of this review will be solely on the relationship between serum uric acid and renal function and disease. We will review experimental evidence derived from animal and human studies, evidence gathered from a number of epidemiological studies, and from the few (up to now) studies of uric-acid-lowering therapy. Some space will be also devoted to the effects of uric acid in special populations, such as diabetics and recipients of kidney allografts. Finally we will briefly discuss the challenges of a trial of uric-acid-lowering treatment, and the recent suggestions on how to conduct such a trial.
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Malheiro J, Almeida M, Fonseca I, Martins LS, Pedroso S, Dias L, Henriques AC, Cabrita A. Hyperuricemia in adult renal allograft recipients: prevalence and predictors. Transplant Proc 2013; 44:2369-72. [PMID: 23026595 DOI: 10.1016/j.transproceed.2012.07.033] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hyperuricemia is a common complication after kidney transplantation that may adversely affect graft survival. OBJECTIVE Our aim was to determine the prevalence of hyperuricemia in a sample of adult kidney graft recipients and to investigate its predictors. METHODS A total of 302 patients were included in the study. We used univariate analyses to compare clinical characteristics between the hyper-and normouricemic groups. We used multivariate adjusted logistic regression to detect independent predictors of hyperuricemia. Hyperuricemia was defined as serum uric acid ≥6.5 mg/dL in women and ≥7.0 mg/dL in men or allopurinol use. RESULTS The patients had a mean age of 49.6 ± 13.4 years, a median posttransplantation time of 7.6 years, and a mean estimated glomerular filtration rate (eGFR) of 51.9 ± 18.46 mL/min. The prevalence of hyperuricemia was 42.1% (n = 127). Hyperuricemic patients were predominately male (P = .004), older (P = .038), and with lower eGFR (P < .001). They also had a higher prevalence of hypertension (P = .001), dyslipidemia (P = .004) and proteinuria (P = .001). Multivariate adjusted regression model showed as significant predictors of hyperuricemia: male gender (odds ratio [OR], 2.46; P = .002); impaired renal function (OR 1.33 for every 10 mL/min reduction in eGFR; P < .001), higher body weight (OR 1.09 for every 1 kg/m(2) increase of body mass index; P = .044), prednisolone use (OR 2.12; P = .035), and cyclosporine versus tacrolimus use (OR 2.44; P = .039). CONCLUSIONS The prevalence of posttransplant hyperuricemia was high, particularly in patients with classical cardiovascular risk factors and lower eGFR. However, our findings suggest that modifiable immunosuppression options could play a role in its management.
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Affiliation(s)
- J Malheiro
- Nephrology and Kidney Transplant Unit, Centro Hospitalar do Porto, Porto, Portugal.
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Rangel EB. The metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation. Expert Opin Drug Metab Toxicol 2012; 8:1531-1548. [DOI: 10.1517/17425255.2012.724058] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Einollahi B, Einollahi H, Rostami Z. Hyperuricemia beyond 1 year after kidney transplantation in pediatric patients: Prevalence and risk factors. Indian J Nephrol 2012; 22:280-4. [PMID: 23162272 PMCID: PMC3495350 DOI: 10.4103/0971-4065.101248] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Hyperuricemia is frequent among adult renal transplant recipients; however, data among pediatric kidney recipients are scarce. This study is designed to estimate the prevalence and risk factors of late post-transplant hyperuricemia in pediatric recipients. A retrospective observational multicenter study on 179 pediatric renal recipients (5–18 years) was conducted between April 2008 and January 2011 from five kidney transplant centers of Tehran, Iran. All recipients were followed up for more than 1 year (5.9 ±3.3 years) after transplantation. A total of 17686 blood samples were obtained for serum uric acid (SUA). The normal range of SUA was defined as SUA 1.86–5.93 mg/dl for children between 2 and 15 years in both genders; 2.40–5.70 mg/dl for girls aged >15 years; 3.40–7.0 mg/dl for boys aged >15 and more than 6 and 7 mg/dl in boys and girls older than 15 years old. The median age of the children was 13 years. Male recipients were more popular than female (male/female 59/41%). Hyperuricemia was detected in 50.2% of patients. Mean SUA concentration was 5.9±1.7 mg/dl and mean SUA concentration in hyperuricemic patients was 7.7±1.2 mg/dl. While at multivariate logistic regression elevated serum creatinine concentration (P<0.001) and the time span after renal transplantation (P=0.02) had impact on late post-transplant hyperuricemia. High cyclosporine level (C0 and C2) was not risk factor for huperuricemia. Late post-transplant hyperuricemia was found in about half of pediatric renal recipients, and was associated with impaired renal allograft function.
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Affiliation(s)
- B Einollahi
- Departments of Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
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Nashar K, Fried LF. Hyperuricemia and the progression of chronic kidney disease: is uric acid a marker or an independent risk factor? Adv Chronic Kidney Dis 2012; 19:386-91. [PMID: 23089273 DOI: 10.1053/j.ackd.2012.05.004] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2012] [Revised: 05/07/2012] [Accepted: 05/08/2012] [Indexed: 02/07/2023]
Abstract
Hyperuricemia is seen when kidney function declines. Whether elevated uric acid (UA) levels play a role in the initiation and progression of kidney disease is a subject of a great debate. Animal studies demonstrate that elevated UA level is a risk factor for kidney disease. In humans, the relationship between UA and kidney disease is more complicated. Cross-sectional studies show an association of hyperuricemia with the presence of CKD; however, from cross-sectional studies, one cannot determine which came first-the elevated UA level or the kidney disease. UA levels are also associated with other risk factors for kidney disease, including hypertension, metabolic syndrome, and microalbuminuria, but it is not clear whether these are mediators or confounders of a relationship. Observational studies suggest a relationship of UA level with incident CKD, but studies evaluating the relationship with decline in kidney function in established CKD are conflicting. Finally, small clinical trials using allopurinol to lower UA levels provide weak, but potentially promising, evidence that lowering UA levels may retard the progression of CKD. In this article, we will review the evidence of the association of hyperuricemia and CKD.
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Jalal DI, Chonchol M, Chen W, Targher G. Uric acid as a target of therapy in CKD. Am J Kidney Dis 2012; 61:134-46. [PMID: 23058478 DOI: 10.1053/j.ajkd.2012.07.021] [Citation(s) in RCA: 202] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2012] [Accepted: 07/11/2012] [Indexed: 02/07/2023]
Abstract
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.
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Affiliation(s)
- Diana I Jalal
- Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Denver, CO 80045, USA.
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Curiel RV, Guzman NJ. Challenges Associated with the Management of Gouty Arthritis in Patients with Chronic Kidney Disease: A Systematic Review. Semin Arthritis Rheum 2012; 42:166-78. [DOI: 10.1016/j.semarthrit.2012.03.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2011] [Revised: 03/13/2012] [Accepted: 03/18/2012] [Indexed: 02/07/2023]
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Abstract
Hyperuricemia is a common complication in organ transplant recipients, with a higher incidence in kidney and heart recipients. Risk factors for post-transplant hyperuricemia include reduced glomerular filtration rate, diuretic use, cyclosporine therapy, increasing age at transplant, obesity, and metabolic syndrome, as well as the presence of pretransplant hyperuricemia. The impact of hyperuricemia in patient and graft survival is unclear because uric acid only recently has been considered a risk factor for cardiovascular disease and graft survival. The effect of uric acid on graft function remains controversial, with studies suggesting that uric acid is an independent risk factor for chronic allograft dysfunction, contrasting with other studies suggesting that hyperuricemia is only a marker of reduced glomerular filtration rate. Strategies to reduce uric acid levels include reduction or avoidance of cyclosporine treatment, adequacy of antihypertension treatment, avoidance of diuretics, nutritional management, and use of uric acid-lowering agents. In this article, we review the incidence and risk factors for the development of post-transplant hyperuricemia, the effect of different immunosuppressive regimens in uric acid handling, and recent results from studies comparing uric acid levels and renal function in organ transplant recipients that try to identify which comes first: hyperuricemia or chronic allograft dysfunction?
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Haririan A, Metireddy M, Cangro C, Nogueira JM, Rasetto F, Cooper M, Klassen DK, Weir MR. Association of serum uric acid with graft survival after kidney transplantation: a time-varying analysis. Am J Transplant 2011; 11:1943-50. [PMID: 21812917 DOI: 10.1111/j.1600-6143.2011.03613.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The association of serum uric acid (UA) with kidney transplant outcomes is uncertain. We examined the predictive value of UA during the first year posttransplant as a time-varying factor for graft survival after adjustment for time-dependent and independent confounding factors. Four hundred and eighty-eight renal allograft recipients transplanted from January 2004 to June 2006 and followed for 41.1 ± 17.7 months were included. Data on UA, estimated glomerular filtration rate (eGFR), tacrolimus level, mycophenolate mofetil (MMF) and prednisone doses, use of allopurinol, angiotensin-converting enzyme-inhibitor/angiotensin-receptor-blocker (ACEi/ARB) and diuretics at 1, 3, 6, 9 and 12 months were collected. Primary endpoint of the study was graft loss, defined as graft failure and death. Cox proportional hazard models and generalized estimating equations were used for analysis. UA level was associated with eGFR, gender, retransplantation, decease-donor organ, delayed graft function, diuretics, ACEi/ARB and MMF dose. After adjustment for these confounders, UA was independently associated with increased risk of graft loss (HR: 1.15, p = 0.003; 95% CI: 1.05-1.27). Interestingly, UA interacted with eGFR (HR: 0.996, p < 0.05; 95% CI: 0.993-0.999 for interaction term). Here, we report a significant association between serum UA during first year posttransplant and graft loss, after adjustment for corresponding values of time-varying variables including eGFR, immunosuppressive drug regimen and other confounding factors. Its negative impact seems to be worse with lower eGFR.
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Affiliation(s)
- A Haririan
- Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
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The effect of hyperuricemia on endothelial biomarkers and renal function in kidney allograft recipients. Transplant Proc 2011; 42:4074-7. [PMID: 21168631 DOI: 10.1016/j.transproceed.2010.09.069] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2010] [Accepted: 09/16/2010] [Indexed: 12/26/2022]
Abstract
BACKGROUND Uric acid may play a pathogenic role in hypertension, cardiovascular morbidity, and kidney disease. The aim of this study was to assess the effect of serum uric acid on biomarkers of endothelial activation and renal function in kidney allograft recipients during 30 months of follow-up. METHODS The study included 100 allograft recipients with stable renal function (estimated glomerular filtration rate (eGFR) >60 mL/min). The study was performed 34 ± 12 months after transplantation. The patients were followed prospectively for 30 months. Seventy patients displayed hyperuricemia (uric acid 7.5 ± 1.0 mg/dL) and 30 normouricemia (5.5 ± 0.9 mg/dL). Concentrations of plasma resistin, soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble CD146, and high-sensitivity C-reactive protein (hs-CRP) were assessed in patients at the beginning and after 30 months of follow-up. Clinical outcomes and biomarker values were analyzed in these groups and compared to a control group of 26 healthy volunteers. RESULTS Concentrations of resistin and CD146 were increased among the hyperuricemia versus the normouricemic group (P < .05). Serum uric acid level correlated with sVCAM-1, hs-CRP, resistin, and sCD146 concentration in both groups of kidney recipients (P < .01). Serum creatinine concentrations correlated with sVCAM-1, resistin, and sCD146 concentrations (P < .01). There were significant direct correlations between uric acid and the number of antihypertensive agents (P < .001) and inverse correlations between eGFR (P < .001) and high-density lipoprotein cholesterol (P < .04). Pulse pressure increased in hyperuricemic patients during follow-up (P < .05). The decrease in eGFR during the 30-month follow-up was similar in both groups. No subject progressed to kidney allograft failure. Patient and graft survivals were 98% among hyperuricemic and 96.7% among normouricemic individuals. CONCLUSIONS Hyperuricemia may injure endothelial function via resistin-dependent mechanisms. It represents a risk factor for arterial stiffness. The elevated serum uric acid may not have a causal role in the progression of renal transplant injury over 30 months of follow-up.
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Kim JH, Park SJ, Yoon SJ, Lim BJ, Jeong HJ, Lee JS, Kim PK, Shin JI. Predictive factors for ciclosporin-associated nephrotoxicity in children with minimal change nephrotic syndrome. J Clin Pathol 2011; 64:516-9. [DOI: 10.1136/jclinpath-2011-200005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
AimsTo identify the predictive factors for ciclosporin A (CyA)-associated nephrotoxicity (CAN) in children with minimal change nephrotic syndrome (MCNS).MethodsThe clinical and laboratory findings of 58 children (median age 3.2 years, range 1.1–13.1 years, male:female 48:10) with MCNS who were treated with CyA from 1992 to 2002 were analysed retrospectively. Forty-eight (83%) of them were steroid dependent and 10 (17%) were steroid resistant. The starting dose of CyA was 5 mg/kg per day, and the desired drug level was kept at 100–200 ng/ml. Serial renal biopsies were performed before and after CyA therapy.ResultsTwenty-two patients (38%) had CAN (group I) and 36 (62%) did not (group II). There were no differences in the age at onset, sex, initial response to steroids, duration of CyA therapy and relapse rates. However, the median CyA trough levels were significantly higher in group I than in group II (218.0±15.2 vs 171.8±6.7 ng/ml, p=0.01). Changes in creatinine clearance were more decreased in group I than in group II (−39.4±8.2 vs 2.7±4.3 ml/min per 1.73 m2, p<0.0001). Multiple logistic regression analysis also revealed the median CyA trough level was an independent risk factor for the development of CAN (OR 1.025, 95% CI 1.007 to 1.044, p=0.007).ConclusionsThe median CyA trough level was an independent and significant risk factor for the development of CAN in children with MCNS receiving moderate-dose CyA.
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Kim KM, Kim SS, Han DJ, Yang WS, Park JS, Park SK. Hyperuricemia in kidney transplant recipients with intact graft function. Transplant Proc 2011; 42:3562-7. [PMID: 21094816 DOI: 10.1016/j.transproceed.2010.07.104] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2010] [Accepted: 07/15/2010] [Indexed: 11/16/2022]
Abstract
OBJECTIVES The aim of this study was to investigate the prevalence of hyperuricemia and factors predicting its occurrence, and to establish the relationship over time between serial changes in estimated glomerular filtration rate (eGFR) and uric acid (UR) concentration in kidney transplant (KT) recipients with eGFR >60 mL/min/1.73 m(2). METHODS Adult patients who underwent KT at the Asan Medical Center between 1990 and 2008 and maintained eGFR >60 mL/min/1.73 m(2) were retrospectively assessed. Clinical and laboratory data were obtained from inpatient and outpatient charts and from the hospital electronic database. RESULTS Of 356 patients, 301 (84.55%) had normal UR levels and 55 (15.45%) had hyperuricemia. After multivariate adjustment, transplant duration, male gender, eGFR, diabetes mellitus (DM), and calcium level were associated with higher mean UR levels. Mean UR level increased significantly and mean eGFR decreased significantly during the first year after transplantation, but there were no significant differences over the next 4 years. Serial UR and eGFR levels changed almost simultaneously. CONCLUSIONS Transplantation duration, male gender, eGFR level, DM, and serum calcium level were risk factors for hyperuricemia in kidney recipients with intact graft function. Increased uric acid after KT did not significantly affect graft function.
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Affiliation(s)
- K M Kim
- Division of Nephrology, Department of Internation Medicine, Asan Medical Center, Seoul, South Korea
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Abstract
Observational studies have shown that asymptomatic hyperuricemia is associated with increased risks of hypertension, chronic kidney disease (CKD), end-stage renal disease, cardiovascular events, and mortality. Whether these factors represent cause, consequence or incidental associations, however, remains uncertain. Hyperuricemia could be a consequence of impaired kidney function, diuretic therapy or oxidative stress, such that elevated serum urate level represents a marker, rather than a cause, of CKD. On the other hand, small, short-term, single-center studies have shown improvements in blood-pressure control and slowing of CKD progression following serum urate lowering with allopurinol. An adequately powered randomized controlled trial is required to determine whether uric-acid-lowering therapy slows the progression of CKD. This article discusses the rationale for and the feasibility of such a trial. International collaboration is required to plan and conduct a large-scale multicenter trial in order to better inform clinical practice and public health policy about the optimal management of asymptomatic hyperuricemia in patients with CKD.
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Christians U, Klawitter J, Klawitter J, Brunner N, Schmitz V. Biomarkers of immunosuppressant organ toxicity after transplantation: status, concepts and misconceptions. Expert Opin Drug Metab Toxicol 2011; 7:175-200. [PMID: 21241200 PMCID: PMC3079351 DOI: 10.1517/17425255.2011.544249] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION A major challenge in transplantation is improving long-term organ transplant and patient survival. Immunosuppressants protect the transplant organ from alloimmune reactions, but sometimes also exhibit limiting side effects. The key to improving long-term outcome following transplantation is the selection of the correct immunosuppressive regimen for an individual patient for minimizing toxicity while maintaining immunosuppressive efficacy. AREAS COVERED Proteomics and metabolomics have the potential to develop sensitive and specific diagnostic tools for monitoring early changes in cell signal transduction, regulation and biochemical pathways. Here, we review the steps required for the development of molecular markers from discovery, mechanistic and clinical qualification to regulatory approval, and present a critical discussion of the current status of molecular marker development as relevant for the management and individualization of immunosuppressive drug regimens. EXPERT OPINION Although metabolomics and proteomics-based studies have yielded several candidate molecular markers, most published studies are poorly designed, statistically underpowered and/or often have not gone beyond the discovery stage. Most molecular marker candidates are still at an early stage. Due to the high complexity of and the resources required for diagnostic marker development, initiatives and consortia organized and supported by funding agencies and regulatory agencies will be critical.
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Affiliation(s)
- Uwe Christians
- University of Colorado, Department of Anesthesiology, 1999 North Fitzsimons Parkway, Bioscience East, Suite 100, Aurora, CO 80045-7503, USA.
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Abstract
Purinergic receptors are important for the regulation of inflammation, muscle contraction, neurotransmission and nociception. Extracellular ATP and its metabolites are the main ligands for these receptors. Occasional reports on beneficial results of ATP administration in human and animal studies have suggested the bioavailability of oral ATP supplements. We investigated whether prolonged daily intake of oral ATP is indeed bioavailable. Thirty-two healthy subjects were randomised to receive 0, 250, 1250 or 5000 mg ATP per d for 28 d by means of enteric-coated pellets. In addition, on days 0 and 28, all thirty-two subjects received 5000 mg ATP to determine whether prolonged administration would induce adaptations in the bioavailability of ATP. ATP supplementation for 4 weeks did not lead to changes in blood or plasma ATP concentrations. Of all ATP metabolites, only plasma uric acid levels increased significantly after the administration of 5000 mg of ATP. Prolonged administration of ATP was safe as evidenced from liver and kidney parameters. We conclude that oral administration of ATP only resulted in increased uric acid concentrations. On the basis of these findings, we seriously question the claimed efficacy of oral ATP at dosages even lower than that used in the present study.
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The independent association between serum uric acid and graft outcomes after kidney transplantation. Transplantation 2010; 89:573-9. [PMID: 19997058 DOI: 10.1097/tp.0b013e3181c73c18] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Improving long-term outcomes of kidney transplantation depends on identifying novel risk factors that lead to poor outcomes. We sought to evaluate the predictive value of mean uric acid (UA) level during the first 6 months posttransplant for graft survival and function. METHODS Two hundred twelve recipients of living donor kidneys transplanted during January 2000 to December 2001 were included. The study outcome included graft and patient survival and graft function at 1 year posttransplant. Regression models were used to adjust for the confounding variables including graft function during first 6 months. RESULTS During 68.3 + or - 27.2 months follow-up, UA level (mg/dL) and hyperuricemia (n=45) were associated with graft loss (hazard ratio [HR]=1.26, P=0.026, 95% confidence interval [CI]=1.03-1.53, and HR=1.92, P=0.029, 95% CI=1.1-3.4, respectively) independent of graft function and other confounders. UA also seemed to be associated with risk of death with borderline significance (HR=1.2, P=0.096, 95% CI=0.97-1.46). Examining the predictive value for graft function, UA level and hyperuricemia were independent predictors of 1-year serum creatinine (beta=0.10, P=0.013, 95% CI=0.02-0.18, and beta=0.25, P<0.04, 95% CI=0.01-0.49, respectively). Similarly, both were associated with 1-year estimated glomerular filtration rate (beta=-3.9, P<0.001, 95% CI=-5.7 to -1.5 for UA, and beta=-7.6, P<0.02, 95% CI=-13.6 to -1.5 for hyperuricemia). Notably, these associations were all independent of renal function during first 6 months. CONCLUSION The results of this study suggest that mean UA level during the first 6 months posttransplant is an independent predictor of long-term graft survival and short-term graft function. Further investigations are needed to evaluate its causal association with chronic allograft injury and cardiovascular disease.
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Meier-Kriesche HU, Schold JD, Vanrenterghem Y, Halloran PF, Ekberg H. Uric acid levels have no significant effect on renal function in adult renal transplant recipients: evidence from the symphony study. Clin J Am Soc Nephrol 2009; 4:1655-60. [PMID: 19713295 DOI: 10.2215/cjn.02700409] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND AND OBJECTIVES Uric acid (UA) has been linked to renal damage in experimental models of kidney failure. In humans, no definitive link between UA and renal function has been established, but several epidemiologic studies have suggested that higher UA levels are associated with accelerated loss of renal function, higher incidence of dialysis, and death. Many of the associations have been limited by the colinearity between UA levels and renal function. Renal transplantation is no exception, and limited information is available concerning the independent role of UA on progression of renal function in transplant recipients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS We investigated the association between UA and renal function progression during the first 3 yr after transplantation, adjusted for baseline renal function, in 1645 patients who were enrolled in the Symphony study. RESULTS When corrected for baseline renal function, UA levels 1 mo after transplantation were not associated with 3-yr renal function (P = 0.62). There was a strong colinearity between calculated renal function and UA levels 1 mo after transplantation. In fact, when not corrected for baseline renal function, there was a significant association between UA and renal function at 3 yr (P = 0.005). CONCLUSIONS Low renal function is associated with higher UA levels, but higher UA levels are not independently associated with progression of renal dysfunction after kidney transplantation.
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Park JT, Kim DK, Chang TI, Kim HW, Chang JH, Park SY, Kim E, Kang SW, Han DS, Yoo TH. Uric acid is associated with the rate of residual renal function decline in peritoneal dialysis patients. Nephrol Dial Transplant 2009; 24:3520-5. [PMID: 19491381 DOI: 10.1093/ndt/gfp272] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Uric acid (UA) is known to play a pathogenic role in chronic kidney disease (CKD). However, its effect in end-stage renal disease (ESRD) has not yet been elucidated. We explored the prevalence of hyperuricaemia and the relationship between UA and residual renal function (RRF) in peritoneal dialysis (PD) patients. METHODS The subjects of this study were 134 PD patients who started dialysis at the Yonsei University Health System between January 2000 and December 2005. Timed urine collections were performed within 1 month of PD commencement and at 6-month intervals thereafter. The slope of decline of RRF over time was calculated by linear regression analysis of serial urinary urea and creatinine clearances for each patient. Biochemical and clinical data at the time of initial urine collection were considered as baseline. RESULTS At baseline, 32.8% of the PD patients had hyperuricaemia (UA >or=7.0 mg/dl). A significant majority of patients with hyperuricaemia were diabetic (P = 0.02). Hypertensive patients had a higher UA level (P = 0.002) compared to normotensive patients. The overall reduction rate of RRF in hyperuricaemic patients was significantly higher than in the normouricaemic group (P = 0.001). In the multiple linear regression analysis, hyperuricaemia and history of DM showed a significant negative correlation with the reduction rate of RRF after adjusting for demographic data, comorbid conditions, body mass index, baseline RRF and medications (P = 0.001). CONCLUSIONS Hyperuricaemia is common among PD patients and is significantly associated with the rate of decline of RRF.
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Affiliation(s)
- Jung Tak Park
- Department of Internal Medicine, College of Medicine, Brain Korea 21 for Medical Science, Yonsei University, Seoul, Korea
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Bandukwala F, Huang M, Prasad G. Role of Uric Acid in Post-Renal Transplantation Hypertension. Transplant Proc 2009; 41:1634-6. [DOI: 10.1016/j.transproceed.2009.01.098] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2008] [Revised: 07/08/2008] [Accepted: 01/08/2009] [Indexed: 10/20/2022]
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Zawiasa A, Szklarek-Kubicka M, Fijałkowska-Morawska J, Nowak D, Rysz J, Mamełka B, Nowicki M. Effect of oral fructose load on serum uric acid and lipids in kidney transplant recipients treated with cyclosporine or tacrolimus. Transplant Proc 2009; 41:188-91. [PMID: 19249511 DOI: 10.1016/j.transproceed.2008.10.038] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2008] [Accepted: 10/29/2008] [Indexed: 11/19/2022]
Abstract
Hyperuricemia, frequently observed following kidney transplantation, may adversely affect graft survival. Although hyperuricemia is a well-known adverse effect of cyclosporine (CsA), a similar effect of tacrolimus (Tac) remains debatable. Hyperuricemia is also seen after oral fructose intake in beverages and processed foods. This sugar is blamed for the epidemic of obesity and metabolic syndrome. The aim of our study was to compare the effects of CsA and Tac on an acute oral fructose load in terms of plasma uric acid, serum lipids, and blood pressure in kidney transplant patients. Thirty-two kidney transplant recipients treated with CsA- or Tac-based triple (calcineurin inhibitor + mycophenolate mofetil + prednisone) immunosuppressive therapy displaying stable allograft function (mean glomerular filtration rate = 53 mL/min/1.73m(2)) received an oral challenge with 70 g of fructose. Serum uric acid, lipids, and blood pressure were measured before as well as 60, 120, 180, and 240 minutes after fructose administration. A significant increase in serum uric acid was observed in both groups after oral fructose administration (P < .001). A peak increase in serum uric acid was recorded at 120 minutes after fructose intake. Serum total, LDL, and HDL cholesterol also significantly decreased and serum triglycerides increased to a similar extent in both CsA and Tac groups. No significant changes in blood pressure were observed after fructose consumption. Oral fructose intake induced an acute rise in serum uric acid and triglycerides and decrease in serum cholesterol among kidney transplant recipients. Those changes were similar among patients treated with CsA or Tac.
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Affiliation(s)
- A Zawiasa
- Medical University of Lodz, Department of Nephrology, Hypertension, and Kidney Transplantation, Lodz, Poland
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Min SI, Yun IJ, Kang JM, Park YJ, Min SK, Ahn C, Kim SJ, Ha J. Moderate-to-severe early-onset hyperuricaemia: a prognostic marker of long-term kidney transplant outcome. Nephrol Dial Transplant 2009; 24:2584-90. [PMID: 19395726 DOI: 10.1093/ndt/gfp192] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Hyperuricaemia commonly occurs in renal transplant recipients (RTRs), but the effects of post-transplant hyperuricaemia on kidney transplant outcome have not been clearly established. This work was designed to explore the impact of hyperuricaemia on renal transplant outcome. METHODS The authors examined this issue by analysing the clinical outcome of 281 RTRs. Hyperuricaemia (defined as UA > 7.0 mg/dl in men and >6.0 mg/dl in women for at least two consecutive tests, n = 121) was classified as early onset (within 1 year of transplant, n = 90) or late onset (n = 31). Graft function was estimated using the MDRD Study Equation 7 (eGFR(MDRD)). RESULTS As late-onset hyperuricaemia was found to be induced by a progressive decline in the graft function (P < 0.01), data from early-onset hyperuricaemic recipients were used. Early-onset moderate-to-severe hyperuricaemia (defined as UA >or= 8.0 mg/dl) was found to be a significant risk factor for chronic allograft nephropathy (P = 0.035) and a poorer graft survival (P = 0.026) by multivariate analysis, whereas mild hyperuricaemia was not. The impact of moderate-to-severe hyperuricaemia on renal transplant survival was dependent on the duration of exposure. Likewise, the detrimental effect of early-onset hyperuricaemia on the graft function was dependent on UA levels and exposure time. After control of the baseline graft function by analysis of only recipients with a good graft function at 1 year post-transplantation (eGFR(MDRD) > 60 ml/min), moderate-to-severe early-onset hyperuricaemia was also found to be a marker of long-term graft dysfunction and failure. CONCLUSION Moderate-to-severe early-onset hyperuri- caemia may be a prognostic marker of the long-term graft outcome in RTRs, which needs further investigation.
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Affiliation(s)
- Sang Il Min
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Bandukwala F, Huang M, Zaltzman JS, Nash MM, Prasad GR. Association of uric acid with inflammation, progressive renal allograft dysfunction and post-transplant cardiovascular risk. Am J Cardiol 2009; 103:867-71. [PMID: 19268747 DOI: 10.1016/j.amjcard.2008.11.042] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2008] [Revised: 11/13/2008] [Accepted: 11/13/2008] [Indexed: 12/26/2022]
Abstract
Hyperuricemia is common after kidney transplantation. Although its risk factors are well established, its relation to inflammation, progressive renal dysfunction, and cardiovascular events is unknown. In this study, 405 stable renal transplant recipients with > or = 3 uric acid (UA) and C-reactive protein measurements from January 2005 to April 2008 were identified to determine the relations between UA and C-reactive protein and between UA and the rate of decrease in the estimated glomerular filtration rate (eGFR; using the Modification of Diet in Renal Disease equation) and cardiovascular events. Hyperuricemia was defined as UA >7.1 mg/dl (420 micromol/L) in men and >6.1 mg/dl (360 micromol/L) in women. The prevalence of hyperuricemia was 44% (180 of 405). Hyperuricemia was negatively associated with eGFR (p <0.0001) and positively associated with diuretic use (p = 0.013), time since transplantation (p = 0.014), and triglycerides (p = 0.04). Although UA was correlated with C-reactive protein (p = 0.003), adjustment for eGFR rendered this relation nonsignificant (p = 0.225). The slope of eGFR was +0.144 +/- 0.85 ml/min/1.73 m(2)/month (95% confidence interval 0.032 to 0.257) in those with normal UA levels and -0.091 +/- 0.93 ml/min/1.73 m(2)/month (95% confidence interval -0.235 to +0.054) in patients with hyperuricemia (p = 0.003). There were 17 cardiovascular events in the patients with hyperuricemia and 4 in those with normal UA levels (p = 0.001). In conclusion, hyperuricemia is associated with a decrease in renal allograft function and may be an independent cardiovascular risk factor in transplant recipients. Further studies are needed to establish its role in post-transplantation cardiovascular disease.
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Lee SR, Kim IG, Lee JO, Han BH. Changes and Implications of Serum Uric Acid Levels After Living-Donor Nephrectomy. Korean J Urol 2009. [DOI: 10.4111/kju.2009.50.11.1144] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- So Ri Lee
- Department of Urology, Maryknoll Hospital, Busan, Korea
| | - In Gon Kim
- Department of Urology, Maryknoll Hospital, Busan, Korea
| | - Jeong Oh Lee
- Department of Urology, Maryknoll Hospital, Busan, Korea
| | - Bo Hyun Han
- Department of Urology, Maryknoll Hospital, Busan, Korea
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Hyperuricemia is associated with the development of the composite outcomes of new cardiovascular events and chronic allograft nephropathy. Transplantation 2008; 86:652-8. [PMID: 18791445 DOI: 10.1097/tp.0b013e3181814f5b] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND To investigate the prevalence and the predictors for the development of hyperuricemia at 6 months after kidney transplantation, and its association with clinical outcomes including patient and graft survival, the development of new cardiovascular events and chronic allograft nephropathy (CAN). MATERIALS AND METHODS Adult patients who underwent kidney transplantation at Mount Sinai Medical Center between January 1, 2001 and December 30, 2004 were included in the study. New cardiovascular events and biopsy-proven CAN were investigated. RESULTS Of the 307 patients, 163 patients (53%) had normal uric acid levels and 144 patients (47%) had hyperuricemia. After adjustment for age, race, and sex, receiving a cadaveric kidney, having an estimated glomerular filtration rate (eGFR) less than 50 mL/min, and taking diuretics or cyclosporine were associated with hyperuricemia at 6 months after transplantation. Over a mean 4.3 years of follow-up, 83 patients had one, or more, of the events, 4 died, 20 had graft failure, 40 had new cardiovascular events, and 41 developed CAN. Kaplan-Meier survival curves showed that these events occurred more frequently in patients with hyperuricemia (P<0.001). Among transplant recipients with an eGFR less than 50 mL/min, 45% of hyperuricemic and 21% of normouricemic patients had an event (P=0.038). For patients with an eGFR more than 50 mL/min, event rates were similar for patients with and without hyperuricemia, 25.0% vs. 19.4%, respectively. CONCLUSIONS These results suggest an important association between hyperuricemia at 6 months after kidney transplantation and new cardiovascular events and CAN in patients with decreased allograft function.
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Abstract
Rheumatologists care for patients with gouty arthritis, a condition caused by chronic and uncontrolled hyperuricaemia. Hyperuricaemia, gout and renal dysfunction are often bedfellows, raising the possibility of the former causing the latter. We sought the answer to the question 'Among patients with normal measures of glomerular filtration, does hyperuricaemia predict future renal disease'? We identified prospective cohort studies evaluating the relationship between serum uric acid and chronic kidney function from the past 20 yrs, through MEDLINE, Cochrane Library and EMBASE searches and bibliography cross-referencing. Nine cohort studies that met the selection criteria were found. Because of the extreme heterogeneity, a statistical meta-analysis was not performed. Most (eight out of nine) studies found an independent risk factor for deterioration of kidney function. Nearly all published prospective studies support the role of hyperuricaemia as an independent risk factor for renal dysfunction. In the absence of large randomized controlled trials of uric acid reduction, it remains uncertain if this relation is causal or merely an epiphenomenon. Regardless, our review suggests that hyperuricaemia is a useful, inexpensively measured, widely available and useful early marker for chronic kidney disease.
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Affiliation(s)
- Z Avram
- Division of Rheumatology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
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Akgul A, Bilgic A, Ibis A, Ozdemir FN, Arat Z, Haberal M. Is uric acid a predictive factor for graft dysfunction in renal transplant recipients? Transplant Proc 2007; 39:1023-6. [PMID: 17524881 DOI: 10.1016/j.transproceed.2007.03.028] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Hyperuricemia is a common complication in renal transplant recipients, and uric acid (UA) may play a role in renal dysfunction. The aim of this study was to evaluate the effects of UA on chronic allograft nephropathy (CAN) in renal transplant recipients. The 133 study subjects included 34 women and 99 men of overall mean age of 34.7 +/- 9.9 years. They underwent renal transplantation between 1998 and 2000. Serum UA levels were measured in the first month after transplantation and then at yearly intervals throughout a 3-year follow-up. In the first month after transplantation, 55.3% of recipients had hyperuricemia (UA >7 mg/dL in men; UA >6 mg/dL in women), but, 3 years after transplantation, 84.6% of the subjects had that disorder (P<.001). CAN was diagnosed in 31.5% of the patients at a mean onset of 31.8 +/- 14.3 months after transplantation. Fifty-two percent of these individuals experienced graft failure within 43.3 +/- 20.8 months after transplantation. UA levels were recorded before the development of CAN. There was no association between UA levels and CAN according to a Cox regression analysis (P>.05; relative risk, 1.082; 95% confidence interval [CI] 0.9-1.3). We concluded that the prevalence of hyperuricemia was higher among recipients than in healthy individuals, but that the UA level did not affect the development of CAN during first 3 years after transplantation.
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Affiliation(s)
- A Akgul
- Department of Nephrology, Baskent University Hospital, Ankara, Turkey.
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de A Coutinho T, Turner ST, Kullo IJ. Serum uric acid is associated with microvascular function in hypertensive individuals. J Hum Hypertens 2007; 21:610-5. [PMID: 17541391 DOI: 10.1038/sj.jhh.1002193] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
We investigated the relationship of serum uric acid (UA) with resting forearm blood flow (FBF), reactive hyperaemia (RH) and flow-mediated dilation (FMD) of the brachial artery in hypertensive adults (n=506, mean age 62 years, 59% women). UA was measured by a colorimetric method. FBF, RH and FMD were measured by brachial artery ultrasound. Regression analyses were used to assess whether UA was associated with FBF, RH and FMD before and after adjustment for age, sex, systolic BP, diabetes, total and high-density lipoprotein cholesterol, smoking, body mass index (BMI), C-reactive protein (CRP), serum creatinine, alcohol intake, statin and diuretic use and brachial artery diameter (BAD). UA was significantly associated with FBF (P<0.0001) and RH (P=0.0001) but not with FMD (P=0.43). After adjustment for the covariates listed above, higher UA level remained independently associated with a higher FBF (P=0.012) and lower RH (P=0.004). The independent predictors were as follows: (a) higher FBF: lower age, higher BMI, history of smoking, statin use, higher CRP, higher BAD and higher UA levels; (b) lower RH: higher BMI, diabetes and higher UA levels; (c) lower FMD: greater age, male sex, higher BMI, history of smoking, statin use and higher BAD. We conclude that in hypertensive individuals, higher UA levels are associated with higher resting FBF and lower RH, markers of microvascular function, but not with brachial artery FMD.
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Affiliation(s)
- T de A Coutinho
- Department of Internal Medicine, Mayo Clinic Foundation, Rochester, MN, USA
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Abstract
PURPOSE OF REVIEW The success of any given kidney transplant is closely tied to the ability to monitor patients and responsively change their medications. Transplant monitoring is still, however, dependent on relatively old technologies: serum creatinine levels, urine output, blood pressure, blood glucose and histopathology of biopsy samples. These older technologies do not offer sufficient specificity, sensitivity, or accuracy to allow appropriate and timely interventions. Using the tools of genomics, proteomics and metabolomics new biomarkers are being found that may greatly improve transplant monitoring and significantly enhance graft survival. This review describes the basic principles of metabolomics and summarizes a number of recent developments in the use of metabolite biomarkers and metabolomics to monitor kidney transplants. RECENT FINDINGS Changes in the concentration profiles of a number of small molecule metabolites found in either blood or urine can be used to localize organ damage, identify organs at risk of rejection, assess organs suffering from ischemia-repurfusion injury or identify organs that have been damaged by immunosuppressive drugs. SUMMARY The application of metabolomics to kidney transplant monitoring is still very much in its infancy. Nevertheless, there are a number of easily measured metabolites in both urine and serum that can provide reliable indications of organ function, organ injury, and immunosuppressive drug toxicity. As the field matures, metabolomics may eventually lead to the development of rapid, inexpensive and noninvasive approaches to assist clinicians in monitoring kidney transplants.
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Affiliation(s)
- David S Wishart
- Department of Biological Sciences, University of Alberta, Canada.
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