What is the optimal management for a patient with biopsy‑proven primary membranous nephropathy, sub‑nephrotic proteinuria (~1 g/day) and low‑normal blood pressure?

Management of Biopsy-Proven Primary Membranous Nephropathy with 1g Proteinuria and Low-Normal Blood Pressure

Conservative supportive care alone is the appropriate management for this patient—immunosuppressive therapy should NOT be initiated. 1, 2

Why Immunosuppression is Contraindicated

Patients with primary membranous nephropathy and proteinuria <3.5 g/day, serum albumin >30 g/L, and eGFR >60 mL/min/1.73 m² do not require immunosuppressive therapy. 1, 2 At 1 g/day proteinuria, this patient falls well below the nephrotic threshold and lacks any indication for immunosuppression. The risks of cyclophosphamide, calcineurin inhibitors, or rituximab—including serious infections, malignancy, nephrotoxicity, and infertility—clearly outweigh any potential benefit at this disease stage. 2

Approximately 30% of patients with sub-nephrotic proteinuria achieve spontaneous remission, particularly in women, supporting a conservative watch-and-wait approach. 2, 3 The probability of progression to end-stage renal disease is low when proteinuria remains <4 g/day. 2

Optimal Conservative Management Strategy

RAS Blockade

• Initiate ACE inhibitor or ARB immediately and uptitrate to maximally tolerated dose as first-line therapy for proteinuria reduction, regardless of blood pressure. 1, 4
• Monitor serum creatinine and potassium 1-2 weeks after initiation or dose adjustment. 1
• Accept up to 30% increase in serum creatinine if stable; discontinue only if kidney function continues to worsen or refractory hyperkalemia develops. 1

Blood Pressure Targets

• Target systolic blood pressure <120 mmHg using standardized office measurement, though this patient's low-normal BP may not require additional antihypertensive agents beyond RAS blockade. 1
• The goal of <130/80 mmHg is appropriate for patients with proteinuria, with consideration of <125/75 mmHg if proteinuria were higher. 1

Lifestyle and Dietary Modifications

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) to enhance the antiproteinuric effect of RAS blockade. 1
• Normalize weight, stop smoking, and encourage regular exercise. 1
• Consider intensifying sodium restriction if proteinuria fails to decline despite maximal medical therapy. 1

Lipid Management

• Initiate statin therapy for management of hyperlipidemia, which is common even in sub-nephrotic membranous nephropathy. 2

Monitoring Protocol

• Recheck urine protein-to-creatinine ratio (UPCR) and serum creatinine every 3-6 months to assess response to conservative therapy and detect progression. 4, 5
• Treatment goal is to reduce proteinuria to <0.5-1 g/day and maintain stable kidney function. 1, 5
• Anti-PLA2R antibody testing may be performed, but a single measurement should not dictate treatment decisions; serial trends over time are required for meaningful interpretation. 2

Criteria for Escalation to Immunosuppression

Immunosuppressive therapy should be considered only after ≥6 months of optimized conservative care and when any of the following develops: 1, 2

• Proteinuria persistently >4 g/day that remains >50% of baseline without progressive decline during the observation period
• Development of severe, disabling, or life-threatening nephrotic syndrome manifestations (marked edema, recurrent infections, thromboembolic events)
• Serum creatinine rises ≥30% within 6-12 months while eGFR remains ≥25-30 mL/min/1.73 m², with no alternative explanation

Critical Pitfalls to Avoid

• Never initiate immunosuppression based solely on kidney biopsy diagnosis without meeting the clinical criteria outlined above. 2
• Do not assume treatment failure before 12 months; remission may be delayed up to 18-24 months, with mean time to remission of approximately 15 months. 2
• Corticosteroid monotherapy has no demonstrated effect on renal survival or remission rates in membranous nephropathy. 2
• Do not delay RAS blockade; continued proteinuria causes tubular injury and interstitial inflammation that accelerates progression. 4

Prognosis with Conservative Management

With proteinuria at 1 g/day, this patient has an excellent prognosis. Waiting 6-12 months to observe the natural disease trajectory does not compromise long-term outcomes provided kidney function remains stable. 2 Overall, about one-third of membranous nephropathy patients experience spontaneous remission, one-third maintain stable proteinuria, and one-third progress slowly—but progression risk is substantially lower in the sub-nephrotic range. 2, 3