From the Guidelines
Nephrotic range proteinuria, defined as a urine protein-to-creatinine ratio (UPC) greater than 3.5 g/g, requires prompt evaluation and management to prevent complications such as hyperlipidemia, hypercoagulability, and progressive kidney damage. When detected, initial steps should include a comprehensive workup with serum albumin, lipid panel, and kidney function tests, along with referral to nephrology 1. The goals of treatment, as outlined in the 2019 update of the joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations, aim for proteinuria <0.5–0.7 g/24 hours by 12 months (complete clinical response) 1.
Key Considerations
- Treatment typically begins with an angiotensin-converting enzyme inhibitor (ACE-I) like lisinopril (starting at 10mg daily) or an angiotensin receptor blocker (ARB) such as losartan (50mg daily), which reduce proteinuria by decreasing intraglomerular pressure.
- Dietary sodium restriction to less than 2g daily is also recommended.
- For significant edema, loop diuretics like furosemide (20-40mg daily) may be necessary.
- The underlying cause must be identified through additional testing, which may include kidney biopsy, as treatment will vary based on etiology (such as diabetic nephropathy, minimal change disease, or membranous nephropathy).
- In patients with lupus nephritis, immunosuppressive agents, administered in combination with glucocorticoids, are recommended in class IIIA or IIIA/C (±V) and IVA or IV A/C (±V) nephritis, with the goal of reducing proteinuria and preserving kidney function 1.
Management Approach
- For patients with nephrotic-range proteinuria at baseline, the time frames for achieving complete clinical response may be extended by 6–12 months, due to slower proteinuria recovery 1.
- Evidence of improvement in proteinuria (with GFR normalisation/stabilisation) should be noted by 3 months, and at least 50% reduction in proteinuria (partial clinical response) by 6 months.
- Consideration of decreasing proteinuria can avoid premature treatment changes.
- Since systemic diseases like SLE require immunosuppressive therapy to target remission or low disease activity from extra-renal domains, a comprehensive treatment plan should be developed in consultation with a nephrologist and rheumatologist, as necessary.
From the Research
Nephrotic Range Proteinuria on UPC
- Nephrotic range proteinuria is characterized by a significant loss of protein in the urine, typically greater than 3.5 grams per day 2.
- The urine protein-to-creatinine ratio (UPC) is a commonly used test to diagnose and monitor proteinuria, with a ratio of 3.5 or higher indicating nephrotic range proteinuria 2.
Causes and Consequences of Nephrotic Range Proteinuria
- Nephrotic range proteinuria can be caused by various diseases, including diabetic nephropathy, IgA nephropathy, and focal segmental glomerulosclerosis 3, 2.
- Proteinuria is not only a marker of kidney damage but also exacerbates it through various mechanisms involving the glomerular and tubulointerstitial compartments 2.
- Hyperlipidemia, which is common in patients with nephrotic syndrome, can further accelerate kidney damage and increase the risk of cardiovascular events 4, 5.
Treatment of Nephrotic Range Proteinuria
- Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are cornerstone treatments for reducing proteinuria and slowing kidney disease progression 3, 6, 2.
- Statins, which are commonly used to treat hyperlipidemia, may also have renoprotective effects and reduce the risk of thrombotic complications in patients with nephrotic syndrome 4, 5.
- Other treatments, such as sodium-glucose cotransporter 2 inhibitors and selective non-steroidal mineralocorticoid receptor antagonists, may also be effective in reducing proteinuria and slowing kidney disease progression 2.
Monitoring and Management of Nephrotic Range Proteinuria
- Regular monitoring of UPC and other markers of kidney function is essential to assess the effectiveness of treatment and adjust therapy as needed 3, 2.
- Lifestyle modifications, such as dietary changes and exercise, may also be beneficial in reducing proteinuria and slowing kidney disease progression 2.