American Board of Internal Medicine (ABIM) Certification Practice Exam

At what stage of chronic kidney disease do thiazide diuretics lose their effectiveness?

1. Stage 2

2. Stage 3

3. Stage 4

4. Stage 5

The correct answer is: Stage 4

Thiazide diuretics lose their effectiveness primarily in Stage 4 chronic kidney disease (CKD), which is characterized by a significant decrease in glomerular filtration rate (GFR). Thiazides work by inhibiting sodium reabsorption in the distal convoluted tubule, which requires an adequate GFR for the drugs to effectively reach their site of action. As kidney function declines, particularly past a GFR of around 30 mL/min, the ability of thiazides to cause diuresis diminishes. In earlier stages of CKD, such as Stage 1, Stage 2, and Stage 3, thiazide diuretics can still be effective. Stage 1 involves only mild impairment and thiazides can still work well, while Stage 2 and Stage 3 maintain enough kidney function for thiazides to exert their diuretic effects. However, as patients progress to Stage 4 CKD and into Stage 5, where GFR falls below 15 mL/min, the renal compensatory mechanisms are overwhelmed, and thiazides are typically ineffective, thus necessitating the use of alternative diuretics like loop diuretics, which are effective even in advanced renal failure.