From the Guidelines
Nephrotic and subnephrotic range proteinuria require prompt management to prevent kidney damage and reduce morbidity, with the primary goal of reducing proteinuria to less than 0.5-0.7 g/24 hours by 12 months, as evidenced by the 2020 EULAR/ERA-EDTA recommendations 1.
Causes and Implications
Nephrotic range proteinuria refers to protein excretion in urine exceeding 3.5 grams per 24 hours, while sub-nephrotic range proteinuria involves protein excretion between 150 mg and 3.5 grams per 24 hours. The underlying causes of these conditions may include diabetes, hypertension, glomerulonephritis, or other kidney diseases.
- Key factors contributing to the progression of kidney disease in patients with proteinuria include:
- Uncontrolled blood pressure
- Persistent proteinuria
- Hyperlipidemia
- Diabetes
Management Approach
For nephrotic range proteinuria, treatment typically includes:
- Renin-angiotensin system blockade with ACE inhibitors or ARBs, as recommended by the 2024 KDIGO clinical practice guideline for the management of lupus nephritis 1
- Combined immunosuppressive treatment with glucocorticoid and one other agent (e.g., mycophenolic acid analogs, cyclophosphamide)
- Hydroxychloroquine
- Diuretics like furosemide may be needed to manage edema, and statins to control hyperlipidemia For subnephrotic range proteinuria, ACE inhibitors or ARBs are still first-line treatments but at potentially lower doses, with careful blood pressure monitoring.
Monitoring and Dietary Recommendations
Regular monitoring of kidney function, electrolytes, and proteinuria levels is essential, with tests every 1-3 months initially.
- Dietary recommendations include:
- Sodium restriction (less than 2 grams daily)
- Moderate protein intake (0.8-1.0 g/kg/day) These interventions aim to reduce glomerular pressure, decrease protein filtration, and protect kidney function by blocking the renin-angiotensin-aldosterone system, which otherwise contributes to kidney damage when chronically activated by persistent proteinuria. The most recent and highest quality study, the 2024 KDIGO clinical practice guideline for the management of lupus nephritis 1, recommends a comprehensive approach to managing nephrotic range proteinuria, including renin-angiotensin system blockade, immunosuppressive treatment, and hydroxychloroquine, to improve patient outcomes and reduce morbidity and mortality.
From the FDA Drug Label
To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus The causes of nephrotic and subnephrotic range proteinuria include:
- Idiopathic type
- Lupus erythematosus The implication of proteinuria is that it can be treated with prednisone to induce a diuresis or remission, specifically in the nephrotic syndrome without uremia. 2
From the Research
Causes of Nephrotic and Subnephrotic Range Proteinuria
- Nephrotic syndrome is defined by a triad of clinical features: edema, substantial proteinuria (> 3.5 g/24 hours), and hypoalbuminemia (< 30 g/L) 3
- The most common causes of nephrotic syndrome in children are idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS), while in adults, FSGS and membranous nephropathy (MN) are the most common primary causes 4
- Secondary causes of nephrotic syndrome include diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections 4, 3
- Diabetic nephropathy is the most common multisystem disease that can cause nephrotic syndrome 3, 5
Implications of Nephrotic and Subnephrotic Range Proteinuria
- Nephrotic syndrome is often associated with hyperlipidemia, thromboembolism, and an increased risk of infection 3
- Patients with nephrotic syndrome are at risk of developing venous thromboembolism, acute renal failure, and serious bacterial infection 5
- The amount of proteinuria at kidney biopsy is linearly associated with renal and overall survival in patients with subnephrotic proteinuria 6
- Nephrotic range proteinuria is associated with the highest frequency of primary glomerulopathies, followed by subnephrotic and low-grade proteinuria 6
Diagnosis and Management
- Diagnosis of nephrotic syndrome involves confirming the presence of proteinuria, hypoalbuminemia, and hyperlipidemia, as well as assessing for secondary causes 4, 3
- Renal biopsy is typically indicated for diagnosis, except in patients with positive test results for serum anti-phospholipase A2 receptor antibodies, which is diagnostic of MN 4
- Management of nephrotic syndrome involves reduction of proteinuria with glucocorticoids, as well as alternative therapies for frequent recurrences and/or steroid-resistant cases 4, 7
- Long-term management includes dietary sodium restriction, edema management, and blood pressure control, as well as consideration of thromboembolism prophylaxis for high-risk patients 4, 5