What is the management and treatment of proteinuria?

From the Guidelines

The management of proteinuria should focus on uptitrating an ACEi or ARB 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.

Key Considerations

• Initial treatment includes lifestyle modifications such as reducing sodium intake, maintaining a healthy weight, exercising regularly, and avoiding nephrotoxic medications.
• Angiotensin-converting enzyme inhibitors (ACEIs) like enalapril or lisinopril, and angiotensin II receptor blockers (ARBs) such as losartan or valsartan, are first-line medications, as they reduce proteinuria by decreasing intraglomerular pressure.
• For resistant cases, combining an ACEI with an ARB may be considered, though this requires careful monitoring for hyperkalemia and acute kidney injury.
• Adding a sodium-glucose cotransporter-2 (SGLT2) inhibitor like empagliflozin or dapagliflozin provides additional kidney protection, particularly in diabetic patients.
• Blood pressure should be controlled to below 130/80 mmHg.

Specific Conditions

• Immunosuppressants may be considered for glomerulonephritis, particularly for patients with persistent proteinuria despite optimized supportive care, including ACE-I or ARBs and blood pressure control 1.
• Glycemic control for diabetes, aiming for HbA1c <7%, and statins for hyperlipidemia, are also important considerations.

Monitoring and Adjustment

• Regular monitoring of kidney function, electrolytes, and urine protein levels is essential to assess treatment response and adjust therapy accordingly.
• These interventions work by reducing glomerular hyperfiltration, decreasing inflammation, and minimizing the progressive damage caused by persistent proteinuria, as supported by the KDIGO practice guideline on glomerulonephritis 1.

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 (hospitalization for heart failure, myocardial infarction, revascularization, stroke, hospitalization for unstable angina, or cardiovascular death) 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

The management and treatment of proteinuria with losartan includes:

• Reducing proteinuria: Losartan significantly reduced proteinuria by an average of 34% compared to placebo.
• Slowing renal disease progression: Losartan reduced the rate of decline in glomerular filtration rate by 13%.
• Blood pressure control: Losartan was used in conjunction with conventional antihypertensive therapy to achieve a blood pressure goal of 140/90 mmHg.
• Monitoring: Regular monitoring of serum creatinine, proteinuria, and blood pressure is necessary to assess the effectiveness of losartan in managing proteinuria 2.

From the Research

Management and Treatment of Proteinuria

The management and treatment of proteinuria involve a comprehensive approach to reduce protein excretion and slow disease progression.

• The clinical picture and pattern of proteinuria are crucial in evaluating the severity of the patient's disease 3.
• Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are effective in reducing proteinuria in patients with chronic kidney disease (CKD), even in the absence of hypertension 4.
• A Bayesian network meta-analysis found that the combination therapy of olmesartan and temocapril had the highest probability of being the most effective treatment to reduce proteinuria in normotensive CKD patients 4.

Treatment Strategies

Different treatment strategies are available for managing proteinuria, including:

• ACEIs, which have been shown to reduce proteinuria more effectively than other antihypertensives 5.
• ARBs, which can be used alone or in combination with ACEIs to reduce proteinuria 4.
• The choice of treatment should be based on the underlying cause of proteinuria and the patient's individual needs 4, 5.

Assessment of Proteinuria

Accurate assessment of proteinuria is essential for the evaluation and management of CKD.

• Total urinary protein can be assessed using dipstick, precipitation, and electrophoresis methods 6.
• Urinary albumin can be assessed using an albumin-specific dipstick, immunochemical techniques, and size-exclusion high-performance liquid chromatography 6.
• Spot urine protein- or albumin-to-creatinine ratios are preferred to a 24-hour urine sample in routine practice 6.