Proteinuria Explained: Could It Be Membranous Nephropathy?

Membranous nephropathy (MN) is a distinct type of kidney disease, quite different from other glomerular diseases. This video will discuss how MN is identified, how it presents itself, and the latest treatments available.

Hello, I'm Dr. Waesika from Expert Kans Clinic in Lahore, speaking from my home studio. Membranous nephropathy has been known for several decades. It was primarily diagnosed due to significant protein leakage in the urine. Most patients diagnosed with MN are usually over 50 years old. In older adults, the loss of protein in the urine may go unnoticed for some time. However, in children, symptoms like swelling around the eyes and feet alert parents quickly. Adults often ignore minor symptoms until the swelling becomes severe enough to affect daily activities, such as not being able to wear shoes.

Key Features of Membranous Nephropathy

The typical presentation and diagnostic process of MN are somewhat similar to other kidney diseases. However, its unique aspect is how it is identified. Until 2024, we only knew that something in the body was damaging the kidney's filtration system, causing excessive protein leakage. But in 2004, scientists discovered a specific molecule, known as the PLA2 receptor, found in the kidney's epithelial cell membrane. In patients with MN, the body mistakenly creates antibodies against this receptor. When these antibodies bind to the PLA2 receptor, it damages the basement membrane of the glomerulus, leading to increased protein leakage.

Primary vs. Secondary Membranous Nephropathy

MN is divided into two major categories: primary and secondary.

• Primary Membranous Nephropathy: Also known as idiopathic nephropathy, it was initially termed because the cause was unknown. Now, we understand that it involves the immune system reacting to the PLA2 receptor or other antigens. This form is the most common type of MN and usually involves the presence of PLA2R antibodies.

• Secondary Membranous Nephropathy: This form results from an external cause or insult to the kidney, such as infections (like hepatitis B or syphilis), certain medications (like NSAIDs), heavy metals, autoimmune diseases (like lupus), or cancers. Treating the underlying cause often leads to improvement in kidney function.

How MN Presents in Patients

MN typically presents differently than other glomerular diseases. It often affects adult males more than females and progresses slowly. Patients might show signs of heavy proteinuria (high levels of protein in urine), swelling in the legs and around the eyes, and sometimes high blood pressure. Occasionally, blood may appear in the urine, although this is rare. Due to the slow progression, by the time symptoms appear, the disease process might have been ongoing for months or even years.

Diagnosis and Management

Diagnosing MN usually involves examining a kidney biopsy under a microscope, which shows thickened capillary walls due to deposits. A special stain, known as a silver stain, helps identify these deposits more clearly. Electron microscopy might also be used to see dense deposits along the basement membrane.

Treatment Approaches

Treatment guidelines for MN are clear. Research shows that about 30% of patients improve on their own without specific treatment, another 30% respond well to treatment, and the remaining 30% may not respond at all and might eventually require dialysis.

For those in the first group (30% who improve on their own), a conservative approach is taken, involving close monitoring and supportive treatment, such as:

• Blood Pressure Management: Using angiotensin receptor blockers (ARBs) or ACE inhibitors to control blood pressure and reduce proteinuria.
• Lifestyle Modifications: Encouraging a healthy lifestyle, including regular exercise, adequate sleep, reduced salt intake, moderate protein consumption, and a balanced diet.

For patients who do not improve with conservative management, more aggressive treatments are initiated. This could include immunosuppressive therapies to reduce the immune response against the kidney.