Fructose in the kidney: from physiology to pathology

The Warburg effect is a unique property of cancer cells, in which glycolysis is activated instead of mitochondrial respiration despite oxygen availability. However, recent studies found that the Warburg effect also mediates non-cancer disorders, including kidney disease. Currently, diabetes or glucose has been postulated to mediate the Warburg effect in the kidney, but it is of importance that the Warburg effect can be induced under nondiabetic conditions. Fructose is endogenously produced in several organs, including the kidney, under both physiological and pathological conditions. In the kidney, fructose is predominantly metabolized in the proximal tubules; under normal physiologic conditions, fructose is utilized as a substrate for gluconeogenesis and contributes to maintain systemic glucose concentration under starvation conditions. However, when present in excess, fructose likely becomes deleterious, possibly due in part to excessive uric acid, which is a by-product of fructose metabolism. A potential mechanism is that uric acid suppresses aconitase in the Krebs cycle and therefore reduces mitochondrial oxidation. Consequently, fructose favors glycolysis over mitochondrial respiration, a process that is similar to the Warburg effect in cancer cells. Activation of glycolysis also links to several side pathways, including the pentose phosphate pathway, hexosamine pathway, and lipid synthesis, to provide biosynthetic precursors as fuel for renal inflammation and fibrosis. We now hypothesize that fructose could be the mediator for the Warburg effect in the kidney and a potential mechanism for chronic kidney disease.

Comparison of Different Types of Oral Adsorbent Therapy in Patients with Chronic Kidney Disease:A Multicenter, Randomized, Phase IV Clinical Trial

Purpose@#Oral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD. @*Materials and Methods@#A seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels. @*Results@#Significantly more patients preferred DW-7202 than AST-120 (p<0.001). Patient adherence improved after switching from AST-120 to DW-7202; there was no apparent change in adherence after switching from DW-7202 to AST-120. Changes in eGFR and serum creatinine, cystatin C, and IS levels were not significantly different according to adsorbent type. There was also no significant difference in the incidences of adverse events during treatment with DW-7202 and AST-120. @*Conclusion@#DW-7202 can be considered as an alternative to AST-120 in patients who cannot tolerate or show poor adherence to granule type adsorbents. Further studies to evaluate factors affecting patient preferences and improved adherence are warranted (Clinical trial registration No. NCT02681952).

Loosening of the mesothelial barrier as an early therapeutic target to preserve peritoneal function in peritoneal dialysis

Phenotype transition of peritoneal mesothelial cells (MCs) including the epithelial-to-mesenchymal transition (EMT) is regarded as an early mechanism of peritoneal dysfunction and fibrosis in peritoneal dialysis (PD), producing proinflammatory and pro-fibrotic milieu in the intra-peritoneal cavity. Loosening of intercellular tight adhesion between adjacent MCs as an initial process of EMT creates the environment where mesothelium and submesothelial tissue are more vulnerable to the composition of bio-incompatible dialysates, reactive oxygen species, and inflammatory cytokines. In addition, down-regulation of epithelial cell markers such as E-cadherin facilitates de novo acquisition of mesenchymal phenotypes in MCs and production of extracellular matrices. Major mechanisms underlying the EMT of MCs include induction of oxidative stress, pro-inflammatory cytokines, endoplasmic reticulum stress and activation of the local renin-angiotensin system. Another mechanism of peritoneal EMT is mitigation of intrinsic defense mechanisms such as the peritoneal antioxidant system and anti-fibrotic peptide production in the peritoneal cavity. In addition to use of less bio-incompatible dialysates and optimum treatment of peritonitis in PD, therapies to prevent or alleviate peritoneal EMT have demonstrated a favorable effect on peritoneal function and structure, suggesting that EMT can be an early interventional target to preserve peritoneal integrity.

Physicians' perceptions of asymptomatic hyperuricemia in patients with chronic kidney disease: A questionnaire survey

BACKGROUND: Hyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians’ perceptions regarding the diagnosis and management of AHU in CKD patients. METHODS: Questionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology. RESULTS: A total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serum uric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines). CONCLUSION: Most Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebro-cardiovascular complications.

AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis

PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.

Technique failure in Korean incident peritoneal dialysis patients: a national population-based study

BACKGROUND: Technique failure is an important issue for peritoneal dialysis (PD) patients. In this study, we aimed to analyze technique failure rate in detail and to determine the predictors for technique failure in Korea. METHODS: We identified all patients who had started dialysis between January 1, 2005, and December 31, 2008, in Korea, using the Korean Health Insurance Review and Assessment Service database. A total of 7,614 PD patients were included, and the median follow-up was 24.9 months. RESULTS: The crude incidence rates of technique failure in PD patients were 54.1 per 1,000 patient-years. The cumulative 1-, 2-, and 3-year technique failure rates of PD patients were 4.9%, 10.3%, and 15.6%, respectively. However, those technique failure rates by Kaplan–Meier analysis were overestimated compared with the values by competing risks analysis, and the differences increased with the follow-up period. In multivariate analyses, diabetes mellitus and Medical Aid as a crude reflection of low socioeconomic status were independent risk factors in both the Cox proportional hazard model and Fine and Gray subdistribution model. In addition, cancer was independently associated with a lower risk of technique failure in the Fine and Gray model. CONCLUSION: Technique failure was a major concern in patients initiating PD in Korea, especially in diabetic patients and Medical Aid beneficiaries. The results of our study offer a basis for risk stratification for technique failure.

The Relationship between Magnesium and Endothelial Function in End-Stage Renal Disease Patients on Hemodialysis

PURPOSE: Chronic kidney disease (CKD) patients tend to have higher serum magnesium values than healthy population due to their positive balance of magnesium in kidney. Recent studies found that magnesium level is positively correlated with endothelial function. Therefore, this study was conducted to define the relationship between magnesium level and endothelial dysfunction in end stage renal disease (ESRD) patients on hemodialysis (HD). MATERIALS AND METHODS: A total of 27 patients were included in this cross-sectional study. Iontophoresis with laser-Doppler flowmetry, flow mediated dilation (FMD), and carotid intima-media thickness were measured. Patients' average serum magnesium levels were measured over previous three months, including the examination month. Pearson's correlation coefficient analysis and multivariate regression model were used to define the association between magnesium and endothelial function. RESULTS: In the univariate analysis, higher magnesium levels were associated with better endothelium-dependent vasodilation (EDV) of the FMD in ESRD patients on HD (r=0.516, p=0.007). When the participants were divided into two groups according to the median magnesium level (3.47 mg/dL), there was a significant difference in EDV of FMD (less than 3.47 mg/dL, 2.8±1.7%; more than 3.47 mg/dL, 5.1±2.0%, p=0.004). In multivariate analysis, magnesium and albumin were identified as independent factors for FMD (β=1.794, p=0.030 for serum magnesium; β=3.642, p=0.012 for albumin). CONCLUSION: This study demonstrated that higher serum magnesium level may be associated with better endothelial function in ESRD patients on HD. In the future, a large, prospective study is needed to elucidate optimal range of serum magnesium levels in ESRD on HD patients.

The Relationship between Magnesium and Endothelial Function in End-Stage Renal Disease Patients on Hemodialysis

PURPOSE: Chronic kidney disease (CKD) patients tend to have higher serum magnesium values than healthy population due to their positive balance of magnesium in kidney. Recent studies found that magnesium level is positively correlated with endothelial function. Therefore, this study was conducted to define the relationship between magnesium level and endothelial dysfunction in end stage renal disease (ESRD) patients on hemodialysis (HD). MATERIALS AND METHODS: A total of 27 patients were included in this cross-sectional study. Iontophoresis with laser-Doppler flowmetry, flow mediated dilation (FMD), and carotid intima-media thickness were measured. Patients' average serum magnesium levels were measured over previous three months, including the examination month. Pearson's correlation coefficient analysis and multivariate regression model were used to define the association between magnesium and endothelial function. RESULTS: In the univariate analysis, higher magnesium levels were associated with better endothelium-dependent vasodilation (EDV) of the FMD in ESRD patients on HD (r=0.516, p=0.007). When the participants were divided into two groups according to the median magnesium level (3.47 mg/dL), there was a significant difference in EDV of FMD (less than 3.47 mg/dL, 2.8±1.7%; more than 3.47 mg/dL, 5.1±2.0%, p=0.004). In multivariate analysis, magnesium and albumin were identified as independent factors for FMD (β=1.794, p=0.030 for serum magnesium; β=3.642, p=0.012 for albumin). CONCLUSION: This study demonstrated that higher serum magnesium level may be associated with better endothelial function in ESRD patients on HD. In the future, a large, prospective study is needed to elucidate optimal range of serum magnesium levels in ESRD on HD patients.

Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells

BACKGROUND: Peritoneal fibrosis is one of the major causes of technical failure in patients on peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) of the peritoneum is an early and reversible mechanism of peritoneal fibrosis. Human peritoneal mesothelial cells (HPMCs) have their own renin-angiotensin-aldosterone system (RAAS), however, it has not been investigated whether aldosterone, an end-product of the RAAS, induces EMT in HPMCs, and which mechanisms are responsible for aldosterone-induced EMT. METHODS: EMT of HPMCs was evaluated by comparing the expression of epithelial cell marker, E-cadherin, and mesenchymal cell marker, alpha-smooth muscle actin after stimulation with aldosterone (1-100nM) or spironolactone. Activation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) were assessed by western blotting and 2',7'-dichlorofluororescein diacetate staining, respectively. The effects of MAPK inhibitors or antioxidants (N-acetyl cysteine, apocynin, and rotenone) on aldosterone-induced EMT were evaluated. RESULTS: Aldosterone induced EMT in cultured HPMCs, and spironolactone blocked aldosterone-induced EMT. Aldosterone induced activation of both ERK1/2 and p38 MAPK from 1 hour. Either PD98059, an inhibitor of ERK1/2, or SB20358, an inhibitor of p38 MAPK, attenuated aldosterone-induced EMT. Aldosterone induced ROS in HPMCs from 5 minutes, and antioxidant treatment ameliorated aldosterone-induced EMT. N-acetyl cysteine and apocynin alleviated activation of ERK and p38 MAPK. CONCLUSION: Aldosterone induced EMT in HPMCs by acting through the mineralocorticoid receptor. Aldosterone-induced generation of ROS followed by activation of ERK, and p38 MAPK served as one of the mechanisms of aldosterone-induced EMT of HPMCs.

ABO-Incompatible Kidney Transplantation / 이화의대지

Kidney transplantation is the best treatment for end-stage renal disease patients. However, the relative shortage of organs for transplantation has led to ABO-incompatible kidney transplantation as an accepted method to expand the pool of kidney donors. Recent advances in immunosuppression and antibody removal methods have made ABO-incompatible kidney transplantation more feasible, and have increased the opportunities for patients to receive kidney transplantation, as well as for special patients with ABO-compatible donor. Indeed, the outcome of ABO-incompatible kidney transplantation has shown remarkable developments and is now comparable to that of ABO-compatible kidney transplantation during last decade. However, there are still some uncertain issues to be addressed in ABO-incompatible kidney transplantation. In this article, we reviewed the current status and protocol of ABO-incompatible kidney transplantation and listed the concerns to be addressed in near future.

Improving Survival Rate of Korean Patients Initiating Dialysis

PURPOSE: The aim of this study was to investigate whether the survival rate among Korean dialysis patients changed during the period between 2005 and 2008 in Korea. MATERIALS AND METHODS: A total of 32357 patients who began dialysis between January 1, 2005 and December 31, 2008 were eligible for analysis. Baseline demographics, comorbidities, and mortality data were obtained from the database of the Health Insurance Review & Assessment Service. RESULTS: Kaplan-Meier curves according to the year of dialysis initiation showed that the survival rate was significantly different (log-rank test, p=0.005), most notably among peritoneal dialysis (PD) patients (p<0.001), although not among hemodialysis (HD) patients (p=0.497). In multivariate analysis, however, patients initiating either HD or PD in 2008 also had a significantly lower risk of mortality compared to those who began dialysis in 2005. Subgroup survival analysis among patients initiating dialysis in 2008 revealed that the survival rate of PD patients was significantly higher than that of HD patients (p=0.001), and the survival benefit of PD over HD remained in non-diabetic patients aged less than 65 years after adjustment of covariates. CONCLUSION: Survival of Korean patients initiating dialysis from 2005 to 2008 has improved over time, particularly in PD patients. In addition, survival rates among patients initiating dialysis in 2008 were different according to patients' age and diabetes, thus we need to consider these factors when dialysis modality should be chosen.

Development of Metabolic Acidosis after Neobladder Reconstruction / 이화의대지

OBJECTIVES: Metabolic acidosis frequently develops in patients after neobladder reconstruction. However, the incidence of metabolic acidosis in patients with neobladder and the factors associated with the development of metabolic acidosis have not been well elucidated. We aimed to investigate the incidence and the potential predictors for the development of metabolic acidosis after neobladder reconstruction with intestinal segment. METHODS: We included patients who underwent neobladder reconstruction using intestinal segment at Ewha Womans University Mokdong Hospital between January 1, 2005 and December 31, 2014. A subgroup of patients according to the time of metabolic acidosis occurrence was further analyzed in order to characterize predictors for metabolic acidosis. RESULTS: Metabolic acidosis was encountered in 79.4% of patients with neobladder during follow up period. When patients were divided into 2 groups according to anion gap (AG), total CO2 (18.9+/-2.1 mEq/L vs. 20.0+/-1.3 mEq/L, P=0.001) and chloride (106.6+/-4.9 mE/L vs. 109.4+/-3.6 mEq/L, P12 and AG< or =12. Furthermore, when patients were divided into 3 groups; patients with metabolic acidosis at postoperative day (POD) 1; from POD 2 to 14 days; after 14 days, there was significant difference among those subgroups. CONCLUSION: Our study showed the rate of metabolic acidosis in patients underwent neobladder reconstruction and the difference between patients with metabolic acidosis and those without metabolic acidosis for the first time in Korea. In the future, well designed prospective study will be needed to prevent metabolic acidosis after neobladder reconstruction.

Uric Acid Puzzle: Dual Role as Anti-oxidantand Pro-oxidant

Hyperuricemia is known to be associated with the presence of cardiovascular and metabolic syndrome and with the development of incipient kidney disease and an accelerated renal progression. However, an elevated uric acid level was not generally regarded as a true etiology or mediator, but an indicator of these diseases. Uric acid has recently regained the clinical interest and popularity based on emerging data suggesting the causative role of hyperuricemia in cardiovascular and renal disease. Experimental data demonstrates oxidative stress is one of the earliest phenomena observed in vascular, renal, liver cells and adipocytes exposed to uric acid. Since uric acid is one of the major antioxidants of plasma acting as a free radical scavenger and a chelator of transitional metal ion, uric acid-induced oxidative stress seems paradoxical. Data regarding the clinical implication of hyperuricemia is even more confusing, which defines hyperuricemia as a useless parameter to be eliminated from routine follow-up or a major risk factor to be therapeutic target. With a review of experimental and epidemiologic data, the presence of molecular switch to regulate the role of uric acid as anti- or pro-oxidant in different compartment of our body is suggested, which may shed light on understanding the paradoxical role of uric acid and solving the "uric acid debate".

A case of membranoproliferative glomerulonephritis associated with metastatic colon cancer

No abstract available.

Hyperuricemia: A non-traditional risk factor for development and progression of chronic kidney disease?

No abstract available.

Association between vascular access failure and microparticles in hemodialysis patients

BACKGROUND: Vascular access failure, a major cause of morbidity in hemodialysis (HD) patients, occurs mainly at stenotic endothelium following an acute thrombotic event. Microparticles (MPs) are fragments derived from injured cell membrane and are closely associated with coagulation and vascular inflammatory responses. METHODS: We investigated the relationship between levels of circulating MPs and vascular access patency in HD patients. A total of 82 HD patients and 28 healthy patients were enrolled. We used flow cytometry to measure endothelial MPs (EMPs) identified by CD31+CD42- or CD51+ and platelet-derived MPs (PMPs) identified by CD31+CD42+ in plasma samples of participants. Vascular access patency was defined as an interval from the time of access formation to the time of first access stenosis in each patient. MP counts were compared according to access patent duration. RESULTS: The levels of EMP (both CD31+CD42- and CD51+) and CD31+CD42+PMP were significantly higher in patients than in healthy participants. Levels of CD31+CD42-EMP and CD31+CD42+PMP showed a positive correlation. In nondiabetic HD patients, CD31+CD42-EMPs and CD31+CD42+PMPs were more elevated in the shorter access survival group (access survival or = 4 years). CONCLUSION: Elevated circulating EMP or PMP counts are influenced by end-stage renal disease and increased levels of EMP and PMP may be associated with vascular access failure in HD patients.

Hydration Status in Elderly Hemodialysis Patients: Bioimpedance Analysis / 대한신장학회지

PURPOSE: This study was aimed to compare hydration status between young and elderly end-stage renal disease (ESRD) patients on hemodialysis (HD) and to analyze factors related to overhydration. METHODS: We measured fluid status before a mid-week HD session in clinically stable 47 patients on maintenance HD using bioimpedance spectroscopy (BIS) device. In addition, weight and blood pressure (BP) were recorded during the treatment. RESULTS: Participants were divided into young ( or =65 years, n=15) patients. In elderly patients, pre-HD diastolic BP, intracellular water (ICW), and lean tissue index (LTI) were significantly lower and extracellular water (ECW)/total body water (TBW) was significantly higher than in young patients. However, there were no differences in pre-HD body mass index (BMI), ultrafiltration volume, pre-HD systolic BP, TBW, ECW, and fat tissue index between the two groups. ECW/TBW ratio and LTI were significantly correlated with age. In a multivariate regression analysis, age and pre-HD pulse pressure were significantly associated with ECW/TBW. CONCLUSION: Although BMI and TBW of elderly ESRD patients were similar to those of young patients, ICW and LTI were lower and ECW/TBW was higher in elderly patients than in young patients. Therefore, clinical manifestations related to overhydration may develop more frequently in elderly patients compared with young patients.

Non-Dipper Status and Left Ventricular Hypertrophy as Predictors of Incident Chronic Kidney Disease

We have hypothesized that non-dipper status and left ventricular hypertrophy (LVH) are associated with the development of chronic kidney disease (CKD) in non-diabetic hypertensive patients. This study included 102 patients with an estimated glomerular filtration rate (eGFR) > or = 60 mL/min/1.73 m2. Ambulatory blood pressure monitoring and echocardiography were performed at the beginning of the study, and the serum creatinine levels were followed. During the average follow-up period of 51 months, CKD developed in 11 patients. There was a significant difference in the incidence of CKD between dippers and non-dippers (5.0% vs 19.0%, P < 0.05). Compared to patients without CKD, patients with incident CKD had a higher urine albumin/creatinine ratio (52.3 +/- 58.6 mg/g vs 17.8 +/- 29.3 mg/g, P < 0.01), non-dipper status (72.7% vs 37.4%, P < 0.05), the presence of LVH (27.3% vs 5.5%, P < 0.05), and a lower serum HDL-cholesterol level (41.7 +/- 8.3 mg/dL vs 50.4 +/- 12.4 mg/dL, P < 0.05). Based on multivariate Cox regression analysis, non-dipper status and the presence of LVH were independent predictors of incident CKD. These findings suggest that non-dipper status and LVH may be the therapeutic targets for preventing the development of CKD in non-diabetic hypertensive patients.

A More Appropriate Cardiac Troponin T Level That Can Predict Outcomes in End-Stage Renal Disease Patients with Acute Coronary Syndrome

PURPOSE: Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis. RESULTS: AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p or =0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality. CONCLUSION: Because ESRD patients with an initial cTnT concentration > or =0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are > or =0.35 ng/mL.

Does Hyperuricemia Play a Causative Role in the Development and/or Aggravation of Renal, Cardiovascular and Metabolic Disease? / 대한내과학회지

Although an elevation of serum uric acid level is often associated with kidney disease, cardiovascular disease and metabolic syndrome, it remains controversial whether hyperuricemia per se is a true risk factor for the development or aggravation of these diseases. Recent studies have demonstrated the independent role of uric acid in progression of renal disease and the development of new-onset hypertension and diabetes. Furthermore, lowering uric acid in these patients is found to stabilize renal function and decrease cardiovascular morbidity, suggesting the causative role of uric acid in renal, cardiovascular and metabolic disease, rather than an incidental association. In this manuscript, recent understanding about the role of uric acid in the development and/or aggravation of renal, cardiovascular and metabolic diseases will be reviewed based on the results from epidemiologic, clinical and experimental studies.