From the Guidelines
ACE inhibitors and ARBs reduce proteinuria by decreasing intraglomerular pressure in the kidneys, and the most effective approach is to uptitrate these medications to maximally tolerated or allowed daily dose as first-line therapy, as recommended by the 2021 KDIGO clinical practice guideline for the management of glomerular diseases 1. The mechanism of action of these medications involves blocking the renin-angiotensin-aldosterone system (RAAS), with ACE inhibitors preventing the conversion of angiotensin I to angiotensin II, while ARBs block angiotensin II receptors. This blockade causes dilation of the efferent arterioles in the glomeruli, reducing the pressure gradient across the glomerular membrane and decreasing protein filtration. Some key points to consider when using ACE inhibitors and ARBs to reduce proteinuria include:
- Starting treatment at lower doses and titrating upward while monitoring blood pressure, serum potassium, and kidney function
- Combining these medications with dietary sodium restriction to enhance their effectiveness in reducing proteinuria, as supported by earlier studies 1
- Being aware that maximum antiproteinuric effects may take several weeks to develop
- Considering the use of common ACE inhibitors such as lisinopril, enalapril, and ramipril, and effective ARBs such as losartan, valsartan, and irbesartan.
From the FDA Drug Label
The secondary endpoints of the study were change in proteinuria, change in the rate of progression of renal disease, and the composite of morbidity and mortality from cardiovascular causes... Compared with placebo, losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy...
Ace/Arbs reduce proteinuria by blocking the action of angiotensin II on the kidneys, which leads to a decrease in intraglomerular pressure and a reduction in proteinuria.
- The exact mechanism is not fully explained in the provided text, but the study shows that losartan significantly reduced proteinuria by an average of 34% 2.
- This effect was evident within 3 months of starting therapy.
- The reduction in proteinuria is likely due to the decrease in intraglomerular pressure and the reduction in the rate of decline in glomerular filtration rate.
From the Research
Mechanism of Action
- ACE inhibitors and angiotensin receptor blockers (ARBs) reduce proteinuria by blocking the renin-angiotensin system, which plays a significant role in renal and cardiovascular pathophysiology 3.
- The antiproteinuric effect of ACE inhibitors seems to be independent of the underlying renal disease and is mediated by a specific, not yet fully elucidated mechanism 4.
Efficacy of ACEIs and ARBs
- Both ACEIs and ARBs have been shown to reduce proteinuria more effectively than other antihypertensives 4.
- Combination therapy with an ACE inhibitor and an ARB resulted in a further decrease in proteinuria compared with an ACE inhibitor alone 5.
- ACEIs and ARBs showed no significant differences in reducing urinary protein excretion in primary hypertension 6.
Clinical Applications
- ACEIs and ARBs are essential drugs for nephroprotection, reducing blood pressure values and albuminuria, both related to cardiovascular damage and CKD progression 3.
- The initial eGFR fall, if not more than 30%, should be considered as a marker of long-term success of renal protection 3.
- In selected and closely monitored cases, it is also possible to consider dual RAAS blockade 3.
Specific Treatment Regimens
- The combination therapy of olmesartan+temocapril had the highest probability of being the most effective treatment to reduce proteinuria in normotensive CKD patients 7.
- For IgA nephropathy, the combination therapy of olmesartan+temocapril also had the highest probability of being the best antiproteinuric treatment 7.
- In normotensive diabetic nephropathy, monotherapy with the ACEI enalapril seems to be the most efficacious intervention for reducing albuminuria 7.