Primary Treatment Options for Primary Nephrotic Syndrome: A Comprehensive Guide
Managing primary nephrotic syndrome largely depends on identifying the underlying pathological subtype, as treatment strategies vary significantly based on histological findings. Accurate diagnosis through kidney biopsy is essential to guide appropriate therapeutic decisions and improve long-term outcomes.
Treatment Based on Pathological Subtypes
One of the most common causes of primary nephrotic syndrome in adults and children is minimal change disease (MCD). In such cases, corticosteroids remain the first-line treatment. The standard approach involves administering a sufficient initial dose—typically prednisone at 1 mg/kg/day (or up to 60–80 mg daily) for adults—over a period of 4 to 6 weeks. This ensures maximal suppression of immune-mediated podocyte injury.
Corticosteroid Management Principles
To optimize efficacy and reduce relapse rates, clinicians follow three key principles: sufficient starting dose, slow tapering, and prolonged maintenance. After achieving remission—confirmed by sustained reduction in proteinuria and improved serum albumin levels—the steroid dosage should be gradually reduced over several months. Abrupt discontinuation increases the risk of relapse. Response to therapy is closely monitored using serial measurements of 24-hour urinary protein excretion and serum albumin concentration, which help determine whether dose adjustments or alternative therapies are needed.
Management of Membranous Nephropathy
In patients with nephrotic syndrome caused by primary membranous nephropathy (MN), treatment decisions depend heavily on individual risk stratification. For those classified as low-risk—defined as having urine protein less than 4 grams per 24 hours, preserved kidney function (eGFR >60 mL/min/1.73m²), and no signs of progressive disease—a conservative "watchful waiting" strategy is recommended for approximately six months.
During this observation period, regular monitoring includes assessment of proteinuria trends, renal function, and potential complications such as thromboembolism or hyperlipidemia. Notably, about 30% of low-risk MN patients experience spontaneous remission without immunosuppressive therapy, making early intervention unnecessary in these cases.
Immunosuppressive Therapy for High-Risk Patients
If significant proteinuria persists beyond six months or if the patient is initially categorized as high-risk (e.g., rising creatinine, nephrotic-range proteinuria, or rapid decline in eGFR), immunosuppressive therapy becomes necessary. The preferred regimens often include a combination of corticosteroids and cyclophosphamide, administered over several months. Alternatively, protocols involving cyclosporine A may be used, especially in patients who cannot tolerate alkylating agents. These treatments aim to induce complete or partial remission, thereby reducing long-term risks of end-stage renal disease.
Supportive Care and Blood Pressure Control
Regardless of the underlying pathology, all patients with nephrotic syndrome require comprehensive supportive care. One of the most critical components is blood pressure management. Maintaining blood pressure below 130/80 mmHg has been shown to slow disease progression and reduce cardiovascular risk.
The use of ACE inhibitors (angiotensin-converting enzyme inhibitors) or ARBs (angiotensin II receptor blockers) is strongly recommended due to their dual benefits: effective antihypertensive action and reduction of proteinuria via modulation of intraglomerular pressure. These medications also offer renoprotective effects that extend beyond blood pressure control alone.
In addition to pharmacologic interventions, lifestyle modifications—including sodium restriction, moderate protein intake, lipid-lowering therapy when indicated, and vaccination against encapsulated organisms—are integral parts of a holistic treatment plan. Regular follow-up with a nephrologist ensures timely detection of complications and optimization of therapy tailored to each patient's clinical course.