From the Guidelines
Hydrochlorothiazide is not recommended as a first-line treatment for patients with proteinuria, as it may potentially worsen proteinuria in some cases. For patients with proteinuria, ACE inhibitors (such as lisinopril or enalapril) or Angiotensin II Receptor Blockers (ARBs) like losartan or valsartan are typically preferred as first-line treatments, as they not only help control blood pressure but also specifically reduce protein excretion in the urine and provide kidney protection 1. These medications work by reducing pressure within the kidney's filtering units and decreasing the leakage of protein into the urine.
The most recent and highest quality study, published in 2023, recommends that all patients with proteinuria >0.5 g/d should have initial therapy with either an ACEi or ARB 1. This recommendation is based on the beneficial effects of these medications on kidney function and proteinuria.
If a diuretic is needed in addition to these medications, loop diuretics like furosemide may be more appropriate than hydrochlorothiazide, especially if the patient has reduced kidney function. Diuretics like hydrochlorothiazide may potentiate the beneficial effects of ACE inhibitors and ARBs in hypertensive patients with kidney disease, but they should be used with caution as they may increase vasopressin levels and have deleterious effects on estimated GFR (eGFR) in comparison to ACE inhibitors 1.
Any medication changes should be discussed with a healthcare provider who can evaluate the specific clinical situation, including the severity of proteinuria, kidney function, and other medical conditions. The healthcare provider can determine the best course of treatment based on the individual patient's needs and medical history.
Some key points to consider when treating patients with proteinuria include:
- ACE inhibitors and ARBs are preferred as first-line treatments due to their beneficial effects on kidney function and proteinuria
- Diuretics like hydrochlorothiazide may worsen proteinuria in some cases and should be used with caution
- Loop diuretics like furosemide may be more appropriate than hydrochlorothiazide in patients with reduced kidney function
- Medication changes should be discussed with a healthcare provider to determine the best course of treatment for the individual patient.
From the Research
Hydrochlorothiazide in Proteinuria
- Hydrochlorothiazide (HCTZ) is a diuretic that has been shown to have antiproteinuric properties 2.
- A study found that the combination of losartan and HCTZ reduced proteinuria more effectively than losartan alone in patients with chronic kidney disease and hypertension 3.
- Another study found that spironolactone plus HCTZ was effective in reducing proteinuria in type 2 diabetic nephropathy patients without increasing serum potassium 4.
- The antiproteinuric effect of HCTZ is thought to be independent of its blood pressure-lowering effect 3, 2.
- Thiazide diuretics, including HCTZ, have been shown to reduce proteinuria by more than 35% in several prospective controlled studies 2.
Comparison with Other Treatments
- Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are also effective in reducing proteinuria, but the combination of ACEIs and ARBs may be more effective in certain patients 5, 6.
- The combination of olmesartan and temocapril had the highest probability of being the most effective treatment to reduce proteinuria in normotensive CKD patients 5.
- Mineralocorticoid receptor antagonists, such as spironolactone, also have antiproteinuric properties and may be effective in reducing proteinuria in certain patients 2, 4.
Considerations for Use
- HCTZ may be a useful addition to other antiproteinuric treatments, such as ACEIs or ARBs, in patients with proteinuria 3, 6.
- The use of HCTZ should be balanced against potential harms, such as hypokalemia or increased serum creatinine 6.
- Further studies are needed to determine the long-term effects of HCTZ on proteinuria and kidney function 2.