Thiazide diuretics are back in CKD: the case of chlorthalidone

Sodium and volume excess is the fundamental risk factor underlying hypertension in chronic kidney disease (CKD) patients, who represent the prototypical population characterized by salt-sensitive hypertension. Low salt diets and diuretics constitute the centrepiece for blood pressure control in CKD. In patients with CKD stage 4, loop diuretics are generally preferred to thiazides. Furthermore, thiazide diuretics have long been held as being of limited efficacy in this population. In this review, by systematically appraising published randomized trials of thiazides in CKD, we show that this class of drugs may be useful even among people with advanced CKD. Thiazides cause a negative sodium balance and reduce body fluids by 1-2 l within the first 2-4 weeks and these effects go along with improvement in hypertension control. The recent CLICK trial has documented the antihypertensive efficacy of chlorthalidone, a long-acting thiazide-like diuretic, in stage 4 CKD patients with poorly controlled hypertension. Overall, chlorthalidone use could be considered in patients with treatment-resistant hypertension when spironolactone cannot be administered or must be withdrawn due to side effects. Hyponatremia, hypokalaemia, volume depletion and acute kidney injury are side effects that demand a vigilant attitude by physicians prescribing these drugs. Well-powered randomized trials assessing hard outcomes are still necessary to more confidently recommend the use of these drugs in advanced CKD. Lay Summary Low salt diets and diuretic use constitute the cornerstones of blood pressure control in chronic kidney disease (CKD) patients due to their salt-sensitive hypertension. In patients with more advanced CKD, loop diuretics are generally preferred to thiazides because the latter have long been held as being of limited efficacy in this population. In this review, by systematically appraising published randomized trials of thiazides in CKD, we show that this class of drugs, in particular chlorthalidone, a long-acting thiazide-like diuretic, may be useful even among people with advanced CKD for improving hypertension control. Hyponatremia, hypokalaemia, volume depletion and acute kidney injury are side effects that demand a vigilant attitude by physicians prescribing these drugs. Well-powered randomized trials assessing hard outcomes are still necessary to more confidently recommend the use of these drugs in advanced CKD.

Automated summary

Low salt diets and diuretics are the key components for controlling blood pressure in chronic kidney disease patients. Loop diuretics are generally preferred to thiazides in patients with advanced CKD, but this review suggests that thiazides, particularly chlorthalidone, may still be useful in improving hypertension control in these patients. However, careful attention should be paid to potential side effects such as hyponatremia, hypokalemia, volume depletion, and acute kidney injury. Further well-powered randomized trials are needed to confidently recommend the use of these drugs in advanced CKD.