Urate Transporter ABCG2 Function and Asymptomatic Hyperuricemia: A Retrospective Cohort Study of CKD Progression.

RATIONALE & OBJECTIVE: Treatment of asymptomatic hyperuricemia is not commonly implemented. However, it is unclear whether urate deposition that begins during asymptomatic hyperuricemia can induce nephropathy. Dysfunction of ATP-binding cassette subfamily G member 2 (ABCG2), a urate efflux transporter, leads to elevated serum uric acid concentration (SUA). We investigated the association between asymptomatic hyperuricemia and decreased estimated glomerular filtration rate (eGFR), and the impact of ABCG2 on this relationship. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 1,885 Japanese adults undergoing routine health care follow-up between 2007 and 2017 who had eGFR ≥60 mL/min/1.73 m2, of which 311 had asymptomatic hyperuricemia (SUA >7.0 mg/dL). Study participants were classified into 3 categories of estimated ABCG2 function (full, 75%, and ≤50% function). PREDICTORS: Baseline SUA and estimated ABCG2 function. OUTCOME: Change in eGFR over time. ANALYTICAL APPROACH: Linear mixed-effect models were used to analyze the relationship between asymptomatic hyperuricemia, ABCG2 function, and eGFR decline. RESULTS: Asymptomatic hyperuricemia was negligibly associated with eGFR decline overall. However, among those with eGFR 60-89 mL/min/1.73 m2 and ≤50% ABCG2 function, eGFR decline was associated with asymptomatic hyperuricemia (P = 0.03). ABCG2 was not associated with eGFR reductions when the SUA was <6.0 mg/dL. Among participants with SUA ≥6.0 mg/dL and eGFR 60-89 mL/min/1.73 m2, ≤50% ABCG2 function was associated with approximately 1.2-fold faster eGFR decline compared with fully functional ABCG2 (P = 0.02). Among the participants with SUA ≥6.0 mg/dL and eGFR 60-89 mL/min/1.73 m2, the adjusted eGFR slopes (given as mean ± standard error of the mean, in mL/min/1.73 m2 per year) were -0.946 ± 0.049, -1.040 ± 0.046, and -1.148 ± 0.069 for full, 75%, and ≤50% ABCG2 function, respectively. LIMITATIONS: Lack of measurement of urinary urate and uremic toxins that are known to be transported by ABCG2, and no independent validation cohort. CONCLUSIONS: Asymptomatic hyperuricemia was not associated with eGFR decline, except when in the presence of ≤50% ABCG2 function. PLAIN-LANGUAGE SUMMARY: The urate transporter ABCG2 is a protein that regulates serum urate concentrations; when dysfunctional, it can lead to elevated serum concentrations of this compound (ie, hyperuricemia). Although persistent hyperuricemia induces gout and kidney injury, the effects on organs during the asymptomatic phase have yet to be established. Therefore, to clarify the relationship between ABCG2, asymptomatic hyperuricemia, and kidney function, we conducted a retrospective cohort study of 1,885 healthy participants, including 311 participants with asymptomatic hyperuricemia. We found that the coexistence of asymptomatic hyperuricemia and severe ABCG2 dysfunction was associated with the age-dependent decline in kidney function. We concluded that asymptomatic hyperuricemia represents a risk factor for chronic kidney disease, at least in individuals with highly dysfunctional ABCG2. This new finding highlights the potential importance of ABCG2 in the pathogenesis of hyperuricemia-induced kidney injury.

Association between polymorphism at IGF-1 rs35767 gene locus and long-term decline in renal function: a Japanese retrospective longitudinal cohort study.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) acts on glucose and protein metabolism and human growth and also influences blood pressure and renal function. This study investigated whether the single-nucleotide polymorphism of IGF-1, rs35767, plays a role in metabolic syndrome indicators, including blood pressure, glucose metabolism, uric acid levels, and renal function. METHODS: In this retrospective longitudinal cohort study, blood samples from 1506 Japanese individuals were collected and used for genotyping for variant rs35767: T > C in the IGF-1 upstream promoter. Data were analyzed to identify associations between IGF-1 genotypes and patient biochemical parameters, including the components of metabolic syndrome and the long-term change in renal function. RESULTS: The cohort rs35767 genotypes included 650 CC carriers (43.2%), 687 TC carriers (45.6%), and 169 TT carriers (11.2%). Multiple regression analysis revealed no association between IGF-1 genotype and blood pressure, glycated hemoglobin level, and serum uric acid level. However, in females, blood pressure was negatively correlated with the TT genotype. Longitudinal observation revealed that the decline in eGFR over 10 years was greater in TT (- 18.51 ± 1.04 mL/min/1.73m2) than in CC carriers (- 16.38 ± 0.52 mL/min/1.73m2; P < 0.05). CONCLUSION: The present study suggests that renal function declines faster in individuals with the TT genotype at the IGF-1 rs35767 locus than in those with the CC genotype, suggesting that the TT genotype is associated with the long-term chronological decline in renal function.

Correction to: Dotinurad: a novel selective urate reabsorption inhibitor as a future therapeutic option for hyperuricemia.

In the original publication of the article the presentation of Table 1 was incorrectly published.

Dotinurad: a novel selective urate reabsorption inhibitor as a future therapeutic option for hyperuricemia.

Gout is a chronic inflammatory disease caused by precipitation of urate crystals in the joints, kidneys, and urinary tract. Independent of urate deposition disorders, recent studies have shown a positive association between circulating uric acid (UA) levels and cardiovascular (CV) diseases. These results indicate that UA is a precipitating factor of both gout and the progression of CV diseases, including hypertension and/or chronic kidney disease (CKD). A large body of evidence has shown that UA-lowering therapies are effective in preventing the progression of hypertension/CKD and that a causal relationship exists between serum UA level and CV diseases. Despite the urgent need for effective UA-lowering drugs that can be used to obtain better therapeutic outcomes and prognosis, only few drugs have been developed in the past decades. Recently, febuxostat and topiroxostat, which are xanthine oxidoreductase inhibitors, were developed and used in clinical practice. Of note, after the approval of lesinurad, which is a urate transporter-1 (URAT-1) inhibitor, in the United States in 2015, dotinurad (Fig. 1), a novel promising drug with selective UA reabsorption inhibitory property, was recently developed in Japan in 2018. Dotinurad is indicated for patients with hyperuricemia/gout as most patients with hyperuricemia are classified into "underexcretion type", which requires the inhibition of URAT-1 to excrete excess UA via the kidney. Focusing on dotinurad, the present study highlighted the multifaceted preliminary new trials that assessed for drug efficacy and safety, pharmacokinetics (PK) according to age and gender, the presence or absence of liver and kidney disorders, drug interactions with NSAID, and non-inferiority of dotinurad to either febuxostat or benzbromarone. A series of studies included in this supplemental review indicate that dotinurad reduces serum UA levels, and its efficacy and safety are similar to those of other UA-lowering agents currently used even in hyperuricemic patients with various clinical conditions. Moreover, two exploratory studies with a small sample size were conducted to compare PK parameters between patients with overproduction- and underexcretion-type hyperuricemia, and results showed that the effects of UA-lowering agents were comparable between the two subtype groups.Fig. 1Chemical structural formula of dotinurad.

A Potential Mechanism of Cardio-Renal Protection with Sodium-Glucose Cotransporter 2 Inhibitors: Amelioration of Renal Congestion.

BACKGROUND: This review considers anew the etiology of the cardio-renal protective effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors by extending the discussion to renal congestion, inherent in diabetic kidney disease (DKD) even at an early stage of nephropathy in which heart failure (HF) or salt and water accumulation is asymptomatic. SUMMARY: The interstitial fluid (IF) space of the kidney space plays a crucial role for tubulointerstitial inflammation, renal hypoxia, and ischemic injury, which often leads to renal progression. In DKD, as a result of hyperglycemic milieu, excessive salt and water can be accumulated in the IF space, creating renal congestion. I hypothesize that SGLT2 inhibitors cause a shift in extracellular water from the IF space to the intravascular space to compensate for the SGLT2 inhibitor-induced hypovolemia. This decrease in IF volume ameliorates the IF space milieu and may reduce inflammation, hypoxia, and ischemic injury. Message: The present review proposes a novel theory; unlike other hypoglycemic agents or diuretics, SGLT2 inhibitor could protect DKD from failing by improving latent renal congestion even without symptomatic HF.

Protection of the kidney with sodium-glucose cotransporter 2 inhibitors: potential mechanisms raised by the large-scaled randomized control trials.

This communication provides a current overview on the renal protective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in diabetics. Following the epoch-making publications, the CANVAS Program and the EMPA-REG OUTCOME trial, numerous literature has discussed the mechanisms by which SGLT2 inhibition exerts its cardio-renal protective effects. Some of them reached agreement, while others did not. This review focuses on the hemodynamic aspect and the remaining potential factors relevant to the renal protection which have not been so much taken up by other review papers. Questions unanswered include factors of uric acid, lipids, erythropoiesis and oxidative stress, salt and sympathetic nerve, and the Na-H exchanger in heart and kidney.

Gender interaction of uric acid in the development of hypertension.

AIM: The present study explored the gender interaction on the risk of uric acid in the new development of hypertension. STUDY DESIGN: A longitudinal retrospective cohort. SUBJECTS & METHODS: A total of 5,807 individuals with an average age of 38 ± 7 years old were recruited. Individuals whose blood pressure rose more than 140/90mmHg or those who newly commenced antihypertensive treatment were defined as a new onset of hypertension. Cox regression analysis was employed for the analysis. RESULTS: During the 10-years follow-up, 42.8% of men and 22.2% of women had developed hypertension. Factors to predict the hypertension development were male gender, older age, higher BMI, higher uric acid, and higher mean blood pressure. An association between higher uric acid levels and higher incidence of hypertension remained statistically significant in women in a multivariate model adjusted for various clinical variables (Hazard ration (HR), 1.180; 95%CI, 1.018 to 1.369), whereas such association was not found in men (HR, 1.034; 95%CI, 0.994 to 1.075). The interaction between the two genders reached statistical significance (p for interaction = 0.007). CONCLUSION: Higher uric acid is associated with the incident hypertension in the both genders. Women are more susceptible to the development of hypertension than men.

Effectiveness of a fixed combination formula of ombitasvir/paritaprevir/ritonavir for hepatitis C virus infection in patients on maintenance haemodialysis.

A fixed-dose formula that combines Ombitasvir (OBV), Paritaprevir (PTV) and Ritonavir (RTV) has been launched into the field of anti-HCV therapy in Japan for patients infected with HCV genotypes 1 and 2 in 2015. However, little is yet known as to the efficacy and safety of this novel therapy in patients on maintenance haemodialysis (HD). The present report describes a preliminary experience in 10 patients (five males and five females) who underwent maintenance HD. All of them had HCV genotype 1b, without having the resistance-associated variants at Y93 or L31 in the nonstructural proteins 5A (NS5A) region. After the treatment, eight patients successfully achieved virus eradication and sustained a virological response at 12 weeks (SVR12). In addition, mac-2 binding protein glycosylation isomer (M2BPGi), a biomarker for liver fibrosis, was reduced after the therapy. Two patients withdrew from the therapy due to the development of erythema multiforme and a strong drowsiness, respectively. These results suggest that triple therapy combining OBV, PTV and RTV is effective in achieving SVR12 in most of the HCV-infected patients on HD. In addition, this combination therapy contributed to retard the progression of liver fibrosis. However, we suggest that further trial will be required to establish its clinical efficacy and safety.

Successful long-term effects of direct renin inhibitor aliskiren in a patient with atherosclerotic renovascular hypertension.

A 64-year-old man visited our hospital with complaints of misty vision and ophthalmalgia. On admission, his blood pressure (BP) was high at 220/135 mmHg with no past history of hypertension, and he had choked discs. He was tentatively diagnosed as having idiopathic intracranial hypertension, and was later found to have atherosclerotic unilateral renovascular hypertension (RVH) based upon the extremely high plasma renin activity together with the radiological image tests. On day 3, combined antihypertensive therapies consisting of oral angiotensin II receptor blocker (ARB) and Ca channel blocker (CCB) along with intravenous CCB induced an abrupt BP lowering which led to deterioration of his renal function, progressing into acute kidney injury (AKI). Cessation of the ARB and reduction of the CCB dose ameliorated the AKI-related decline in renal function. On day 17, as he was reluctant to receive surgical intervention, he was treated with a direct renin inhibitor, aliskiren, combined with a half-dose CCB as a maintenance antihypertensive therapy. The therapy has proven not only successful to chronically maintain his renal function but was also capable of controlling his BP in the neighborhood of 130/85 mmHg over a period of 2 years. The present case suggests that the direct renin inhibition with aliskiren can be a safe and useful antihypertensive option to control hypertension and to preserve renal function in patients with atherosclerotic unilateral RVH.

Usefulness of combination therapy with Daclatasvir plus Asunaprevir in chronic hepatitis C patients with chronic kidney disease.

AIM: Combination therapy with Daclatasvir (DCV) plus Asunaprevir (ASV) has been proven effective in patients with chronic hepatitis C virus (HCV) infection. However, little is known as to the effect of this therapy in patients with reduced renal function. Focusing on CKD patients whose renal function has declined, the present trial addresses the efficacy and safety of this combination therapy in CKD patients with reduced estimated glomerular filtration rate (eGFR). MATERIALS AND METHODS: The study design is a single-center, retrospective longitudinal observational study enrolling 106 patients with (n = 29) or without (n = 77) CKD. After the treatment with combined DCV with ASV for chronic HCV genotype 1b, patients were followed for a total of 48 weeks and the comparison was made in clinical parameters between the two groups. RESULTS: (1) The majority of patients in both groups achieved sustained virological response at 24 weeks (90.8 % in the non-CKD group, and 93.1 % in the CKD). (2)The reduction rate in HCV-RNA levels 2 weeks after commencing the treatment was faster in the CKD group than that in the non-CKD group (81.8 vs. 79.2 %, p < 0.01). (3) Three patients in the CKD group and 6 patients in the non-CKD group withdrew from the treatment because of the adverse events. CONCLUSION: Combination therapy with DCV plus ASV for chronic HCV genotype 1b infection is useful and tolerable, not only in patients with normal eGFR, but also in those with CKD with declined eGFR. Viral eradication at an early phase of the treatment appears to be faster in CKD patients.

Serum uric acid and the incidence of CKD and hypertension.

BACKGROUND: Uric acid (UA) levels correlate positively with the prevalence of chronic kidney disease (CKD) and/or hypertension. We tested the hypothesis that UA may also have a link to a new incidence of CKD and hypertension. METHODS: Study design is a cohort study and the predictor is UA levels. Of the 15,470 screened cases, 8223 participants without CKD were eligible for the analysis of the incidence of CKD. Among these CKD candidates, 7569 participants were eligible for the analysis of the new development of hypertension. The observation period was 4 years. RESULTS: Relationship of UA with new cases of CKD. Higher UA levels had a closer association with the new development of CKD; 1.1 % (UA < 5 mg/dL), 1.5 % (5.0-5.9 mg/dL), 1.7 % (6.0-6.9 mg/dL), and 3.4 % (≧7 mg/dL), respectively (p < 0.001 by the Chi-square test). Cox proportional hazard analysis showed that the estimates of the CKD development were eGFR [Hazard Ratio (HR) 0.816, 95 % confidence intervals (CI) 0.791-0.840] and male gender (HR 0.562, 95 % CI 0.322-0.982). UA levels and new development of hypertension. Higher UA levels had a closer association with the new development of hypertension; 5.0 % (UA < 5 mg/dL), 8.9 % (5.0-5.9 mg/dL), 10.6 % (6.0-6.9 mg/dL), and 11.8 % (≧7 mg/dL), respectively (p < 0.001 by the Chi-square test). Cox proportional hazard analysis showed that the estimates of the hypertension development were BMI (HR 1.190, 95 % CI 1.155-1.226), age (HR 1.021, 95 % CI 1.010-1.032), HDL-cholesterol (HR 1.013, 95 % CI 1.007-1.019), male gender (HR 1.791, 95 % CI 1.338-2.395), UA level (HR 1.112, 95 % CI 1.024-1.207), and eGFR (HR 1008, 95 % CI 1.002-1.013). Furthermore, the logistic analysis showed that the odds ratio (OR) to estimate hypertension in the high UA group (UA ≧ 7 mg/dL; OR 1.33, 95 % CI 1.01-1.80) was greater than that in the low UA group (UA < 5 mg/dL). Kaplan-Meier analysis also confirmed the finding that the higher the UA levels the greater the hypertension development (p < 0.001 by the Log-rank test and Cox proportional hazard analysis). CONCLUSION: High UA levels are associated with the new development of hypertension, but not with the incidence of CKD.

Combined therapy with peritoneal dialysis and hemodialysis: a multicenter retrospective observational cohort study in Japan.

BACKGROUND/AIMS: Combining peritoneal dialysis (PD) and hemodialysis (HD) has been common treatment option in Japan. METHODS: In this retrospective, multicenter, observational study, the clinical characteristics and outcomes of 104 patients (57 ± 11 years, males 72%) who had switched from PD alone to combined therapy with PD and HD were studied. Clinical parameters were measured at baseline and after 3 months of combined therapy. RESULTS: At baseline, urine volume, dialysate-to-plasma ratio of creatinine (D/P Cr), and total Kt/V were 150 ml/day (range: 0-2,000 ml/day), 0.67 ± 0.11, and 1.8 ± 0.4, respectively. During the first 3 months of combined therapy, body weight, urine volume, serum creatinine level, and D/P Cr decreased, whereas hemoglobin levels increased. CONCLUSIONS: In patients where PD does not result in acceptable outcomes, combined therapy with PD and HD may have potential benefits in terms of dialysis adequacy and hydration status. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=368389

Monitoring of body water composition by the simultaneous use of bioelectrical impedance analysis and Crit-Line(®) during hemodialysis.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a non-invasive method to estimate total body water (TBW) and extracellular water (ECW) volume. Crit-Line(®) (CL), on the other hand, assesses intravascular water (IVW) volume. We evaluate continuous changes in body water composition during hemodialysis (HD) with concurrent use of BIA and CL. METHODS: BIA at the start and the end of the HD session was measured using a BIA device. To investigate the shifting pattern of body water composition, patients were subjected to simultaneous monitoring of BIA with CL. RESULTS: Both TBW resistance (Rt) and ECW resistance (Re) increased in response to changes in the ultrafiltration (UF) ratio. There was a positive correlation between ΔRe/Rt and the UF ratio, and the ratio of Re/Rt at the end of HD was significantly higher than that at the start of HD. Simultaneous monitoring of BIA with CL showed a parallel shift of the change in the Re (ΔRe) and the change in hematocrit (ΔHt). In one patient with increasing inflammatory response, change in ΔHt was dissociated from change in ΔRe. One hyponatremic patient showed a different pattern of changing ΔRe between the first half and the latter half of the HD session. CONCLUSION: Our study suggests that the concurrent use of BIA and CL may be a useful technique to simulate water shift patterns across the different compartments in HD.

[Relationship between serum uric acid levels and muscle strength/volume: a new insight from a large-scale survey].

AIM: Serum uric acid (UA) concentration is regulated by its production in the liver and/or intestine and its rate of excretion from the kidneys. However, little is known about skeletal muscle involvement in determining the physiological UA level. The present trial explores whether muscle strength and/or muscle volume is associated with UA levels. MATERIAL & METHODS: Muscle strength was evaluated in terms of grasping power calculated as an average of right and left hand measurements in relation to other parameters in 14,333 subjects (median age; 41.2 years), who were recruited to the study. Skeletal muscle volume was calculated based on the bioimpedance method by subtracting estimated fat volume plus estimated bone weight from the total body weight. RESULTS: 1) Multiple regression analyses to explain the association with UA levels (dependent variable) revealed that BMI, BUN, triglyceride, muscle strength, AST, age and sex are independent variables. 2) Higher UA levels (assessed as 4 UA quartiles) are associated with higher muscle volume, muscle strength, BMI, DBP, and serum creatinine (Cr) concentration. 3) Greater DBP (assessed as 2 UA categories) was associated with higher BMI, muscle strength, muscle volume, UA levels and serum Cr concentration. 4) Regression coefficient "t" for muscle strength was the largest among the other parameters including serum Cr concentration in the UA level ranging from 5.5 to 6.5 mg/dL. CONCLUSION: There was an association between muscle strength/volume and UA levels in the near physiological UA range, suggesting that the circulating UA levels can be, at least in part, controlled by its production in the skeletal muscles.

Effect of aliskiren in chronic kidney disease patients with refractory hypertension undergoing hemodialysis: a randomized controlled multicenter study.

BACKGROUND: Applying a direct renin inhibitor (DRI) to advanced stage chronic kidney disease (CKD) patients is a matter of controversy. The purpose of this study was to evaluate the effect of the DRI, aliskiren, in patients with therapy-resistant hypertension undergoing hemodialysis (HD). METHODS: The study was a prospective, randomized multicenter trial exploring the antihypertensive effect of aliskiren in comparison with amlodipine, a calcium channel blocker, in patients undergoing HD. A total of 83 participants whose blood pressure (BP) had previously been treated with more than one antihypertensive agent and not having achieved the BP goal of <140/90 mmHg were randomly assigned to either aliskiren 150 mg or amlodipine 5 mg as an add-on therapy. RESULTS: A significant decrease in pre-dialysis clinic BP and home BP was found only in the amlodipine group and not in the aliskiren group. In contrast, there was a significant decrease in atrial natriuretic peptide (ANP) in the aliskiren group but not in the amlodipine group. N-terminal pro-B-type natriuretic hormone remained unchanged in both groups. Aliskiren significantly reduced angiotensin I and II, plasma renin activity, and increased plasma renin content. However, such changes were not observed in the amlodipine group. CONCLUSION: Amlodipine, not aliskiren, effectively reduces BP in CKD patients with refractory hypertension undergoing HD. Aliskiren suppresses the renin-angiotensin system and reduces ANP. Whether the DRI is beneficial in improving cardiovascular events in patients undergoing HD remains to be elucidated in future studies.

Severe hyponatremia caused by secondary adrenal insufficiency in a patient with giant pituitary prolactinoma.

A 55-year-old-man was admitted to Saiseikai Central Hospital, Tokyo, Japan, complaining of nausea and appetite loss, and was found to have severe hyponatremia. Despite severe hyponatremia and plasma hypo-osmolarity, urinary sodium excretion was not reduced. A brain magnetic resonance imaging (MRI) scan revealed a giant pituitary prolactinoma, and endocrinological tests showed a markedly increased prolactin level. Despite the observation that the basal plasma ACTH level was normal, serum cortisol and urinary cortisol excretion levels were low. Rapid ACTH loading sufficiently stimulated an increase in serum cortisol levels, suggesting secondary adrenal insufficiency. Notably, loading of CRH induced a good ACTH response; however, the serum cortisol response remained low. In contrast, the continuous daily administration of exogenous ACTH dramatically increased serum cortisol levels. These discrepant responses may have been caused by the low biological activity of innate ACTH. Following partial resection of the prolactinoma, postoperative adjuvant therapy with cabergoline effectively reduced prolactin levels, but did not improve the hyponatremia. In contrast, hydrocortisone replacement therapy recovered the serum sodium level to the normal range. The present case is the first report describing a link between severe hyponatremia and biologically inactive circulating ACTH as a likely result of giant prolactinoma.

Effects of combined antihypertensive therapy with losartan/hydrochlorothiazide on uric acid metabolism.

OBJECTIVE: The Jikei Optimal Antihypertensive Treatment (JOINT) study originally evaluated the effect of a fixed-dose formulation of losartan (LOS) (50 mg) plus 12.5 hydrochrolthiazide (HCTZ) for achieving better blood pressure (BP) control in patients with uncontrolled hypertension. This study is a sub-analysis of the JOINT study, focusing on the effect of LOS/HCTZ on the uric acid (UA) metabolism. METHODS: Among 228 participants in the JOINT study, a total of 164 patients whose blood and urinary UA specimens were available were included in the present analyses. RESULTS: Six months after switching from the prior antihypertensive agent(s) to a single tablet formulation of LOS/HCTZ, the overall serum UA concentration (sUA) increased from 6.0 ± 1.6 mg/dL to 6.2 ± 1.6 mg/dL (p=0.029). The urinary UA/creatinine (Cr) ratio increased from 0.45 +/- 0.21 to 0.50 +/- 0.25 (p=0.014), and the fractional excretion of UA (FEUA) also increased, from 7.1 +/- 3.6 to 7.0 +/- 4.3, p=0.04). Multivariate regression analyses of the basal parameters showed the change in sUA (ΔUA) to correlate with the basal sUA (ß=-0.483, p<0.001), estimated glomerular filtration rate (eGFR) (ß=-0.202, p=0.007) and systolic BP (ß=0.147, p=0.038). In addition, the ΔUA also correlated with the changes in the estimated glomerular filtration rate (ΔeGFR) (ß=-0.332, p<0.001). When the patients were classified into two groups depending on their basal sUA, those with a basal sUA ≥ 7 mg/dL exhibited a decrease in their sUA, whereas the rest of those with a sUA <7 mg/dL experienced an increase. Furthermore, patients who had previously been treated with LOS alone had a greater increase in the sUA than those treated with an angiotensin II blocker (ARB) other than LOS alone. CONCLUSION: Antihypertensive therapy with a single tablet formulation of LOS/HCTZ is considered to be a useful option for controlling both BP and sUA, especially in uncontrolled hypertensive patients with hyperuricemia.