Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia

Reungjui, Sirirat; Pratipanawatr, Thongchai; Johnson, Richard J.; Nakagawa, Takahiko

doi:10.1097/mnh.0b013e328305b9a5

Cited by 60 publications

(38 citation statements)

References 74 publications

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“…No change was noted in our LH group. Usually, when thiazide therapy is initiated, a modest increase in creatinine levels may occur due to volume contraction [Reungjui et al 2008], and such an effect was found in the Nishiwaki trial [Nishiwaki et al 2013], but not by our group.…”

Section: Discussionmentioning

confidence: 89%

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Effect of losartan combined with amlodipine or with a thiazide on uric acid levels in hypertensive patients

Rubio-Guerra¹,

Garro-Almendaro

Elizalde-Barrera

et al. 2016

Therapeutic Advances in Cardiovascular Disease

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Hyperuricemia leads to endothelial dysfunction and insulin resistance, and has been associated with diseases such as hypertension. Antihypertensive drugs modify serum uric acid levels, however, few data are available about their combinations on uricemia. In this study we evaluate the effect of two combinations of losartan, with amlodipine or with hydrochlorothiazide, on serum uric acid levels in hypertensive patients. Methods: A total of 60 hypertensive patients were randomized in two groups; group LA received losartan/amlodipine (100/5 mg) once a day, whereas LH group received losartan hydrochlorothiazide (100/12.5 mg) once a day for 3 months. In both groups serum uric acid levels were measured at the beginning and end of the study. Patients were evaluated monthly for blood pressure (BP) and adverse events. Statistical analysis was performed with a two-way analysis of variance (ANOVA) for repeated measures. Results: All patients experienced a significant reduction of BP to the same extent (LA 155/94 to 123/79, LH 157/92 to 124/78 mmHg, p > 0.05). In the LA group, serum uric acid decreased from 6.5 ± 1.6 to 4.6 ± 1.3 mg/ml (p = 0.0001), whereas in the LH group there was a nonsignificant increase from 5.82 ± 1.4 to 5.85 ± 1.5 mg/ml, (p = 0.936). When both groups were compared, we found a significant reduction (p < 0.00013) on serum uric acid levels in the LA group. Conclusions: Both combinations decrease BP values to the same extent, however, LA combination showed a reduction on serum uric acid levels, which may contribute to a reduction in the metabolic risk in hypertensive patients.

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Section: Discussionmentioning

confidence: 89%

“…Tsouli and colleagues reported that nifedipine and verapamil have no effect, whereas amlodipine and felodipine decrease serum uric acid levels [Tsouli et al 2006]. Recent studies suggest that hyperuricemia induced by thiazides can be associated with increased cardiovascular risk [Reungjui et al 2008].…”

Section: Introductionmentioning

confidence: 99%

Effect of losartan combined with amlodipine or with a thiazide on uric acid levels in hypertensive patients

Rubio-Guerra¹,

Garro-Almendaro

Elizalde-Barrera

et al. 2016

Therapeutic Advances in Cardiovascular Disease

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“…Low S K levels affect myocardial resting membrane potential, which increases the probability of ventricular arrhythmias and sudden cardiac death (11). Hypokalemia can also predispose patients to developing diastolic dysfunction, digoxin toxicity, and insulin resistance, all of which increase the risk for cardiovascular events and death (12)(13)(14)(15)(16). Dietary potassium depletion has been linked to the genesis of hypertension, and supplementation can improve BP control (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Serum Potassium and Outcomes in CKD

Korgaonkar¹,

Tilea²,

Gillespie³

et al. 2010

Clinical Journal of the American Society of Nephrology

201

159

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Background and objectives:The relationship between serum potassium (S K ) and mortality in chronic kidney disease (CKD) has not been systematically investigated.Design, setting, participants, & measurements: We examined the predictors and mortality association of S K in the Renal Research Institute CKD Study cohort, wherein 820 patients with CKD were prospectively followed at four US centers for an average of 2.6 years. Predictors of S K were investigated using linear and repeated measures regression models. Associations between S K and mortality, the outcomes of ESRD, and cardiovascular events in time-dependent Cox models were examined.Results: The mean age was 60.5 years, 80% were white, 90% had hypertension, 36% had diabetes, the average estimated GFR was 25.4 ml/min per 1.73 m 2 , and mean baseline S K was 4.6 mmol/L. Higher S K was associated with male gender, lower estimated GFR and serum bicarbonate, absence of diuretic and calcium channel blocker use, diabetes, and use of angiotensinconverting enzyme inhibitors and/or statins. A U-shaped relationship between S K and mortality was observed, with mortality risk significantly greater at S K <4.0 mmol/L compared with 4.0 to 5.5 mmol/L. Risk for ESRD was elevated at S K <4 mmol/L in S K categorical models. Only the composite of cardiovascular events or death as an outcome was associated with higher S K (>5.5).Conclusions: Although clinical practice usually emphasizes greater attention to elevated S K in the setting of CKD, our results suggest that patients who have CKD and low or even low-normal S K are at higher risk for dying than those with mild to moderate hyperkalemia.

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“…These nutrients have been shown to counter the effects of fructose in animal models, and controlling for these factors can be difficult. 30,31 Contrary to natural fruits, because dried fruits are deprived of their natural content of vitamins and antioxidants and yet maintain a high fructose content when processed, they were included in the analysis. For each questionnaire, the total intake of grams of fructose per day was determined.…”

Section: Primary Predictor and Outcomementioning

confidence: 99%

Increased Fructose Associates with Elevated Blood Pressure

Jalal¹,

Smits²,

Johnson³

et al. 2010

Journal of the American Society of Nephrology

186

158

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The recent increase in fructose consumption in industrialized nations mirrors the rise in the prevalence of hypertension, but epidemiologic studies have inconsistently linked these observations. We investigated whether increased fructose intake from added sugars associates with an increased risk for higher BP levels in US adults without a history of hypertension. We conducted a cross-sectional analysis using the data collected from the National Health and Nutrition Examination Survey (NHANES 2003(NHANES to 2006 involving 4528 adults without a history of hypertension. Median fructose intake was 74 g/d, corresponding to 2.5 sugary soft drinks each day. After adjustment for demographics; comorbidities; physical activity; total kilocalorie intake; and dietary confounders such as total carbohydrate, alcohol, salt, and vitamin C intake, an increased fructose intake of Ն74 g/d independently and significantly associated with higher odds of elevated BP levels: It led to a 26, 30, and 77% higher risk for BP cutoffs of Ն135/85, Ն140/90, and Ն160/100 mmHg, respectively. These results suggest that high fructose intake, in the form of added sugar, independently associates with higher BP levels among US adults without a history of hypertension.

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Do thiazides worsen metabolic syndrome and renal disease? The pivotal roles for hyperuricemia and hypokalemia

Cited by 60 publications

References 74 publications

Effect of losartan combined with amlodipine or with a thiazide on uric acid levels in hypertensive patients

Effect of losartan combined with amlodipine or with a thiazide on uric acid levels in hypertensive patients

Serum Potassium and Outcomes in CKD

Increased Fructose Associates with Elevated Blood Pressure

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