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

Curr Opin Nephrol Hypertens. 2008 Sep;17(5):470-6. doi: 10.1097/MNH.0b013e328305b9a5.


Purpose of review: The aims of this article are to review the current controversies related to the use of thiazide diuretics as first-line treatment of hypertension and to discuss the causal roles for hyperuricemia and hypokalemia on the adverse consequences of thiazide usage.

Recent findings: Thiazides significantly reduce morbidity and mortality in hypertensive subjects. There remains, however, debate about thiazide usage as first-line treatment of hypertension. This negative impact of thiazides may be partially attributed to the ability of thiazides to exacerbate features of metabolic syndrome or increase the risk for developing diabetes. Several clinical trials suggest that thiazide-induced hyperuricemia and hypokalemia may account for some of these negative effects. Thiazide treatment is also associated with a decline of renal function in spite of a lowering blood pressure. In this review, we discuss the clinical and experimental evidence supporting a potential role of hyperuricemia and hypokalemia on the development of renal injury and worsening of the metabolic syndrome.

Summary: Hyperuricemia and hypokalemia may have pivotal roles in the exacerbation of the metabolic syndrome in response to thiazides. We propose that controlling serum uric acid and serum potassium could improve thiazide efficacy and also reduce its risk for inducing metabolic syndrome or diabetes.

Publication types

  • Review

MeSH terms

  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Hyperuricemia / chemically induced*
  • Hyperuricemia / metabolism
  • Hypokalemia / chemically induced*
  • Hypokalemia / metabolism
  • Kidney / drug effects
  • Kidney Diseases / metabolism
  • Kidney Diseases / physiopathology*
  • Metabolic Syndrome / blood
  • Sodium Chloride Symporter Inhibitors / adverse effects*
  • Sodium Chloride Symporter Inhibitors / therapeutic use


  • Sodium Chloride Symporter Inhibitors