Glomerulonephritis: Primary and Secondary Subtypes

Introduction to Glomerulonephritis

Glomerulonephritis is a significant kidney disorder characterized by inflammation of the glomeruli, the tiny filtering units within the kidneys. These structures play a critical role in the body’s ability to rid itself of waste and excess substances while maintaining fluid and electrolyte balance. When glomeruli become damaged or inflamed, their filtering capacity is compromised, leading to various renal dysfunctions. Glomerulonephritis can manifest in several ways and may develop as either a primary condition, directly affecting the kidneys, or as a secondary condition, resulting from systemic diseases such as diabetes or lupus.

Early diagnosis of glomerulonephritis is crucial for effective treatment and management. Symptoms can be subtle or indistinct in the early stages, which can complicate timely intervention. Typical symptoms include hematuria (blood in urine), proteinuria (excess protein in urine), edema (swelling), and hypertension (high blood pressure). If left untreated, the progression of glomerulonephritis may lead to chronic kidney disease and ultimately kidney failure, necessitating more severe treatments such as dialysis or kidney transplantation. Therefore, understanding the nature and implications of glomerulonephritis not only aids in recognizing the signs but also highlights the importance of seeking medical attention promptly.

Furthermore, ongoing research into glomerulonephritis has illuminated various therapeutic approaches aimed at addressing both the underlying causes and the symptoms. The significance of regular monitoring for individuals at risk cannot be overstated, as proactive management can profoundly influence outcomes. Overall, glomerulonephritis serves as a reminder of the delicate balance involved in kidney health and the potential consequences of neglecting renal function. By fostering knowledge and awareness about this condition, we can improve patient outcomes and maintain kidney health more effectively.

Types of Glomerulonephritis:

1. Primary glomerulonephritis: The disease begins in the kidney without an identifiable systemic cause.
2. Secondary Glomerulonephritis: Result of systemic diseases or conditions affecting the kidneys.

 

 Primary glomerulonephritis:

 

These are intrinsic kidney diseases in which glomerular pathology is the primary or predominant feature. Some common subtypes include:

 

1. Minimum Conversion Disease (MCD):

– Epidemiology: common in children; Can also affect adults.

– Pathology: loss of podocyte foot processes on electron microscopy, but normal glomeruli under light microscopy.

– Clinical features: often manifests with nephrotic syndrome (massive proteinuria, hypoalbuminemia, edema).

– Treatment: responds well to corticosteroids (prednisone).

 

2. Focal Segmental Glomerulosclerosis (FSGS):

– Epidemiology: Common cause of nephrotic syndrome in adults.

– Pathology: scarring (sclerosis) in some, but not all, glomeruli and only parts (segments) of affected glomeruli.

– Clinical Features: Presents with proteinuria, nephrotic syndrome, hypertension, and possibly decreased renal function.

– Treatment: corticosteroids, immunosuppressants; May progress to chronic kidney disease (CKD).

 

3. Membranous Nephropathy (MN):

– Epidemiology: Most common cause of nephrotic syndrome in adults.

– Pathology: thickening of the glomerular basement membrane with subepithelial immune deposits.

– Clinical Features: Nephrotic syndrome (massive proteinuria), possible development of kidney failure.

– Treatment: immunosuppressive therapy, rituximab, calcineurin inhibitors.

 

4. IgA Nephropathy (Berger’s disease):

– Epidemiology: Most common form of GN worldwide, more common in young adults and males.

– Pathology: Accumulation of IgA in glomeruli, often seen with mesangial proliferation.

– Clinical Features: Recurrent episodes of hematuria, sometimes following upper respiratory infections. CKD may progress.

– Treatment: ACE inhibitors/ARBs, corticosteroids in severe cases.

 

5. Membranoproliferative glomerulonephritis (MPGN):

– Epidemiology: Rare, can affect children and adults.

– Pathology: Proliferation of mesangial and endothelial cells, with a double appearance of the glomerular basement membrane (tram tracks).

– Clinical features: Nephrotic-nephritic syndrome with hematuria and proteinuria.

– Treatment: Steroids, immunosuppressants, can progress to CKD.

 Secondary glomerulonephritis:

Secondary forms are due to systemic conditions affecting the kidneys. Some of the main reasons include:

 

1. Post-infectious glomerulonephritis:

– Cause: Follows infection, especially streptococcal throat infection (post-streptococcal GN), other bacterial, viral, or parasitic infections.

– Pathology: Immune complex accumulation in glomeruli.

– Clinical Features: Acute onset of hematuria, proteinuria, edema, hypertension, and often low C3 complement levels.

– Treatment: supportive care, management of hypertension, antibiotics if infection persists.

 

2. Lupus Nephritis (LN):

– Cause: Systemic lupus erythematosus (SLE), an autoimmune disease.

– Pathology: Immune complex accumulation (IgG, IgA, IgM) in glomeruli, leading to different patterns of damage (classification I-VI).

– Clinical features: Varies from asymptomatic hematuria to severe nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN).

– Treatment: immunosuppressive therapy (steroids, cyclophosphamide, mycophenolate mofetil), biologics (rituximab, belimumab).

 

3. Diabetic Nephropathy:

– Cause: Long-standing diabetes mellitus (DM), both type 1 and type 2.

– Pathology: thickening of the glomerular basement membrane, mesangial enlargement, nodular glomerulosclerosis (Kummelstahl-Wilson nodules).

– Clinical features: proteinuria (initially microalbuminuria), progression to nephrotic syndrome, CKD.

– Treatment: Blood sugar control, ACE inhibitors/ARBs, cardiovascular risk management.

 

4. Good Pasteur Syndrome (Anti-GBM Disease):

– Cause: Autoimmune attack against glomerular basement membrane (GBM) and pulmonary alveoli.

– Pathology: Linear accumulation of anti-GBM antibodies with GBM.

– Clinical features: Rapidly progressive glomerulonephritis (RPGN) with hematuria and lung involvement (hemoptysis).

– Treatment: plasmapheresis, corticosteroids, cyclophosphamide.

5. ANCA-associated vasculitis (eg, granulomatous with polyangitis):

– Cause: Small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA).

– Pathology: Pauci-immune glomerulonephritis (minimal immune deposits).

– Clinical features: RPGN, hematuria, proteinuria, systemic symptoms such as weight loss, fever, and lung involvement.

– Treatment: immunosuppression (corticosteroids, rituximab, cyclophosphamide).

 

6. Amyloidosis:

– Cause: Accumulation of amyloid protein (often secondary to chronic inflammation or multiple myeloma).

– Pathology: Congo red stain shows amyloid deposits in glomeruli.

– Clinical Features: Nephrotic syndrome, progressive renal failure.

– Treatment: Treat the underlying cause (eg, chemotherapy for multiple myeloma).

 

7. HIV Associated Nephropathy (HIVAN):

– Cause: Direct effect of HIV infection on kidneys.

– Pathology: Focal segmental glomerulosclerosis-like lesions.

– Clinical Features: Rapid progression of kidney failure in HIV-positive individuals.

– Treatment: Antiretroviral therapy (ART), ACE inhibitors/ARBs

 

 Clinical Presentation of Glomerulonephritis:

 

Patients with GN may present with symptoms varying in severity and type:

– Nephritic syndrome: hematuria (often microscopic), proteinuria (mild), hypertension, oliguria, edema, elevated serum creatinine.

– Nephrotic syndrome: massive proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, severe edema.

– asymptomatic hematuria/proteinuria: incidental finding on urinalysis, often mild or asymptomatic.

– rapidly progressive glomerulonephritis (RPGN): a severe, rapidly deteriorating renal function, often requiring urgent intervention.

 

 Diagnosis:

– Urinalysis: detects hematuria, proteinuria, RBC casts (in nephritic syndrome).

– Serology: complement (C3, C4), ANA, anti-GBM antibodies, ANCA, ASO titers.

– Renal biopsy: gold standard to identify the exact type of GN and guide treatment.

 

 Administration:

– General: Blood pressure control (ACE inhibitors/ARBs), dietary changes (low salt, protein), management of underlying cause (for secondary GN).

– Immunosuppressive Therapy: Corticosteroids, cyclophosphamide, rituximab, depending on type and severity.

– Plasmapheresis: for rapidly progressive forms (eg, Goodpasture’s syndrome).

– Dialysis/Transplant: for advanced CKD or ESRD.

 

Prognosis:

Prognosis depends on the underlying type of GN, response to treatment, and severity at diagnosis. Some forms, such as minimal conversion disease, respond well to treatment, while others (eg, FSGS, RPGN) may progress to chronic kidney disease (CKD) or end-stage renal disease (ESRD).