From the Guidelines
The primary medications recommended for treating proteinuria are angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). According to the most recent guideline, patients with proteinuria >0.5 g/d should be treated with either an ACEi or ARB as initial therapy 1. Common ACE inhibitors include lisinopril (10-40 mg daily), enalapril (5-40 mg daily), and ramipril (2.5-20 mg daily), while frequently prescribed ARBs include losartan (25-100 mg daily), valsartan (80-320 mg daily), and irbesartan (150-300 mg daily).
Key Considerations
- Treatment typically begins with a lower dose that is gradually increased to achieve optimal protein reduction while monitoring for side effects.
- These medications work by reducing pressure within the kidneys' filtering units (glomeruli) and decreasing inflammation, which helps prevent protein leakage into urine.
- They also provide kidney protection independent of their blood pressure-lowering effects.
- Patients should have their kidney function and potassium levels monitored regularly, especially when starting therapy or adjusting doses.
Additional Therapies
In cases where proteinuria persists despite ACE inhibitors or ARBs, additional medications like aldosterone antagonists (spironolactone 25-50 mg daily), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or non-dihydropyridine calcium channel blockers may be added 1. The underlying cause of proteinuria, such as diabetes or hypertension, must also be treated concurrently for optimal results.
Recent Findings
Recent studies have shown that the addition of SGLT2 inhibitors to ACEI or ARB has positive long-term potential for kidney outcomes, with a significant decrease in the primary outcome of 50% reduction in eGFR or onset of kidney failure 1. However, there are no data to support dual ACEI and ARB therapy for patients with IgAN, and safety issues pertaining to hyperkalemia are a potential concern.
From the FDA Drug Label
The RENAAL study was a randomized, placebo-controlled, double-blind, multicenter study conducted worldwide in 1513 patients with type 2 diabetes with nephropathy (defined as serum creatinine 1.3 to 3.0 mg/dL in females or males ≤60 kg and 1.5 to 3. 0 mg/dL in males >60 kg and proteinuria [urinary albumin to creatinine ratio ≥300 mg/g]). Treatment with losartan resulted in a 16% risk reduction in this endpoint (see Figure 4 and Table 4) Treatment with losartan also reduced the occurrence of sustained doubling of serum creatinine by 25% and ESRD by 29% as separate endpoints, but had no effect on overall mortality (see Table 4). Compared with placebo, losartan significantly reduced proteinuria by an average of 34%, an effect that was evident within 3 months of starting therapy, and significantly reduced the rate of decline in glomerular filtration rate during the study by 13%, as measured by the reciprocal of the serum creatinine concentration
Losartan is recommended for treating proteinuria in patients with type 2 diabetes with nephropathy, as it has been shown to reduce proteinuria by an average of 34% and slow the progression of renal disease 2.
- Key benefits of losartan in treating proteinuria include:
- Reduced risk of doubling of serum creatinine
- Reduced risk of end-stage renal disease (ESRD)
- Slowed decline in glomerular filtration rate
- Losartan should be considered as part of the treatment plan for patients with proteinuria and type 2 diabetes with nephropathy.
From the Research
Medications for Treating Proteinuria
The following medications are recommended for treating proteinuria:
- Angiotensin-converting enzyme inhibitors (ACEIs) such as lisinopril, enalapril, and temocapril 3, 4, 5
- Angiotensin receptor blockers (ARBs) such as olmesartan, losartan, valsartan, and irbesartan 3, 4, 6
- Combination therapy of ACEIs and ARBs, such as olmesartan+temocapril 3, 4
Specific Medications for Different Conditions
- For IgA nephropathy, the combination therapy of olmesartan+temocapril is recommended 3
- For diabetic nephropathy, monotherapy with the ACEI enalapril or the combination of an ACEI and an ARB is recommended 3, 4, 7
- For normotensive CKD patients, the combination therapy of olmesartan+temocapril or temocapril alone is recommended 3
Mechanism of Action
- ACEIs and ARBs work by blocking the renin-angiotensin system, which reduces proteinuria and slows the progression of kidney disease 3, 4, 6, 5
- ACEIs also cause efferent (postglomerular) vasodilation, which reduces intraglomerular capillary pressure and proteinuria 5