Does Chlorthalidone affect serum Creatinine levels?

From the Guidelines

Yes, chlorthalidone can affect creatinine levels in the blood, typically causing a small, reversible increase in serum creatinine levels, usually within the first few weeks of starting treatment. This thiazide-like diuretic reduces plasma volume and renal blood flow, which temporarily decreases glomerular filtration rate, leading to a modest increase in creatinine levels, around 0.1-0.3 mg/dL in most patients, though individual responses vary 1. The medication, commonly prescribed at doses of 12.5-25 mg daily for hypertension, may cause more significant creatinine elevations in patients with pre-existing kidney disease, the elderly, or those taking other medications that affect kidney function like ACE inhibitors or NSAIDs. This creatinine increase doesn't usually indicate actual kidney damage but rather reflects hemodynamic changes. However, if creatinine rises more than 30% from baseline or continues to increase over time, medical evaluation is warranted. Regular monitoring of kidney function is recommended when starting chlorthalidone, particularly in high-risk patients.

Some key points to consider when prescribing chlorthalidone include:

• Monitoring for hyponatremia and hypokalemia, uric acid and calcium levels 1
• Using with caution in patients with history of acute gout unless patient is on uric acid–lowering therapy 1
• Avoiding use in combination with ARBs or direct renin inhibitor 1
• Being aware of the increased risk of hyperkalemia, especially in patients with CKD or in those on K+ supplements or K+-sparing drugs 1
• Considering the risk of acute renal failure in patients with severe bilateral renal artery stenosis 1

It's also important to note that the ALLHAT study found no significant differences in end-stage renal failure between chlorthalidone and lisinopril groups, and that the slopes of the reciprocal of serum creatinine, as well as estimated creatinine clearance, were virtually identical in the chlorthalidone and lisinopril groups 1. However, more detailed information on the outcome of renal function is needed, above all as regards the presence of diabetic nephropathy, the amount of proteinuria, and the possible crossover to an ACE inhibitor in patients with diminished renal function.

Overall, chlorthalidone can be a effective treatment for hypertension, but it's essential to carefully monitor kidney function and adjust the treatment plan as needed to minimize the risk of adverse effects.

From the FDA Drug Label

If progressive renal impairment becomes evident, as indicated by a rising nonprotein nitrogen or blood urea nitrogen, a careful reappraisal of therapy is necessary with consideration given to withholding or discontinuing diuretic therapy.

Chlorthalidone may affect kidney function, as indicated by the potential for progressive renal impairment. However, there is no direct information about the effect of chlorthalidone on creatinine levels. The FDA drug label does not answer the question.

From the Research

Chlorthalidone and Creatinine Levels

• Chlorthalidone has been found to affect creatinine levels in some studies. For example, a study published in The New England Journal of Medicine 2 found that chlorthalidone therapy was associated with reversible increases in serum creatinine levels in patients with advanced chronic kidney disease.
• Another study published in JAMA Network Open 3 found that chlorthalidone use was associated with a higher risk of eGFR decline of 30% or greater compared to hydrochlorothiazide use in older adults with varying levels of kidney function.
• However, a study published in Archives of Internal Medicine 4 found that chlorthalidone was not superior to amlodipine or lisinopril in reducing the rate of development of end-stage renal disease or a 50% or greater decrement in GFR in hypertensive patients with reduced GFR.
• A study published in Nephron 5 found that doxazosin and captopril treatment were associated with significant rises in GFR in hypertensive non-insulin-dependent diabetic patients, but did not specifically examine the effects of chlorthalidone on creatinine levels.
• A review article published in Expert Opinion on Pharmacotherapy 6 discussed the pharmacokinetic features of chlorthalidone and its potential advantages as a diuretic and blood-pressure-lowering agent, but did not specifically address its effects on creatinine levels.

Key Findings

• Chlorthalidone may be associated with increases in serum creatinine levels, particularly in patients with advanced chronic kidney disease 2.
• Chlorthalidone use may be associated with a higher risk of eGFR decline compared to hydrochlorothiazide use in older adults with varying levels of kidney function 3.
• The effects of chlorthalidone on creatinine levels and kidney function may vary depending on the population being studied and the specific clinical context.