From the Guidelines
Treatment of nephrotic range proteinuria should prioritize renin-angiotensin system blockade and blood pressure control, combined immunosuppressive treatment with glucocorticoid and one other agent, and hydroxychloroquine, as recommended by the KDIGO 2024 clinical practice guideline for the management of lupus nephritis 1. The goal of treatment is to reduce proteinuria, manage symptoms, and prevent complications.
- Renin-angiotensin system blockade can be achieved with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), which reduce proteinuria by decreasing intraglomerular pressure.
- Combined immunosuppressive treatment with glucocorticoid and one other agent, such as mycophenolic acid analogs or cyclophosphamide, is recommended for patients with nephrotic-range proteinuria.
- Hydroxychloroquine is also recommended as part of the treatment regimen. Key considerations in treatment include:
- Monitoring kidney function, proteinuria levels, and electrolytes to assess treatment response and adjust therapy accordingly.
- Managing edema with diuretics and hyperlipidemia with statins.
- Restricting dietary sodium to less than 2 grams daily. The 2019 update of the joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis also emphasizes the importance of reducing proteinuria and achieving a complete clinical response, defined as a urine protein-to-creatinine ratio (UPCR) below 500-700 mg/g by 12 months 1.
From the FDA Drug Label
Losartan is indicated for the treatment of diabetic nephropathy with an elevated serum creatinine and proteinuria (urinary albumin to creatinine ratio ≥300 mg/g) in patients with type 2 diabetes and a history of hypertension Nephrotic range proteinuria treatment with losartan is indicated in patients with diabetic nephropathy and proteinuria.
- The treatment is specifically for patients with type 2 diabetes and a history of hypertension.
- Losartan reduces the rate of progression of nephropathy as measured by the occurrence of doubling of serum creatinine or end stage renal disease [see CLINICAL STUDIES (14.3)] 2.
From the Research
Treatment Options for Nephrotic Range Proteinuria
- The optimal antiproteinuric dose of losartan in nondiabetic patients with nephrotic range proteinuria is 100 mg, as it reduces proteinuria by 30% 3.
- Treatment of nephrotic syndrome should include fluid and sodium restriction, oral or intravenous diuretics, and angiotensin-converting enzyme inhibitors 4.
- Corticosteroid treatment may be beneficial for some adults with nephrotic syndrome, although research data are limited 4.
- Renal biopsy may be useful in some cases to confirm an underlying disease or to identify idiopathic disease that is more likely to respond to corticosteroids 4, 5.
Role of ACE Inhibitors in Treatment
- ACE inhibitors, such as enalapril and lisinopril, have been shown to reduce proteinuria in patients with nephrotic range proteinuria 6, 7.
- The antiproteinuric effect of ACE inhibitors is dose-related, with higher doses resulting in greater reductions in proteinuria 7.
- ACE inhibitors may also have a beneficial effect on renal function, with increased renal plasma flow and decreased filtration fraction 7.
Specific Patient Populations
- In patients with polycystic kidney disease, renal biopsy may be necessary to diagnose underlying diseases such as IgA nephropathy, and treatment with prednisolone, ACE inhibitors, and angiotensin II receptor blockers may be effective in reducing proteinuria and stabilizing renal function 5.
- In patients with high renin hypertension, treatment with ACE inhibitors may be effective in reducing proteinuria, even in the absence of hypertension 6.