Glomerular Diseases: Symptoms, Types, Causes and Treatment

Glomerular diseases encompass a diverse group of kidney disorders that primarily affect the glomeruli—the tiny filtering units in the kidneys responsible for removing waste and excess fluids from the blood. When the glomeruli are damaged, it can lead to a spectrum of symptoms, complications, and long-term health challenges. In this article, we’ll explore the key symptoms, types, causes, and treatment options for glomerular diseases, drawing on the latest research and clinical guidelines to provide a comprehensive and engaging overview.

Symptoms of Glomerular Diseases

Most glomerular diseases don’t announce themselves with dramatic symptoms at first. Instead, they often begin subtly, with changes that may only be discovered during routine urine tests. Yet, understanding the telltale signs—and their underlying mechanisms—can empower patients and clinicians to seek early diagnosis and prompt treatment.

Symptom	Description	Commonality	Source
Hematuria	Blood in urine (microscopic or visible)	Very common	1 2 11
Proteinuria	Protein in urine	Very common	2 11
Edema	Swelling, often in legs or around eyes	Common	2 11
Hypertension	High blood pressure	Frequent	2 11
Decreased GFR	Reduced kidney filtering ability	Variable	2 11

Table 1: Key Symptoms

Understanding the Key Symptoms

Hematuria: Micro and Macro

• Microscopic hematuria may only be detectable under a microscope, while macroscopic (gross) hematuria can turn urine visibly red or brown. Persistent microhematuria is not just a benign finding—it is now linked to the progression of kidney damage due to the toxic effects of hemoglobin and iron on kidney tubules, which can trigger inflammation and injury 1 11.

Proteinuria and Edema

• Proteinuria, the presence of excess protein in urine, is a hallmark of glomerular diseases. When the glomerular barrier is compromised, proteins like albumin leak into the urine, which can lead to edema—swelling, typically in the legs, ankles, or around the eyes—due to low blood protein levels disrupting fluid balance 2 11.

Hypertension and Decreased Kidney Function

• Many glomerular diseases cause high blood pressure. The damaged glomeruli disrupt the kidney’s role in blood pressure regulation, leading to persistent or even difficult-to-treat hypertension 2 11.
• Decreased glomerular filtration rate (GFR) reflects reduced kidney filtering capacity, which may progress to chronic kidney disease if left untreated 2 11.

Other Symptoms

• Depending on the underlying disease, patients may also experience fatigue, foamy urine, or even symptoms related to systemic involvement (such as rashes or joint pain in lupus nephritis) 2 11.

Types of Glomerular Diseases

Glomerular diseases are not a single entity—they comprise a wide range of specific disorders, each with its own features, underlying mechanisms, and implications for treatment. Advances in pathology and molecular medicine have led to a more nuanced, cause-based classification that guides modern clinical practice.

Type/Disorder	Main Feature/Mechanism	Typical Presentation	Source
IgA Nephropathy	Immune complex deposition	Hematuria, proteinuria	2 3 7 11
FSGS	Podocyte injury, scarring	Nephrotic syndrome	3 13
Minimal Change Disease	Podocyte dysfunction	Nephrotic syndrome (children)	3 13
Lupus Nephritis	Autoimmune, immune complexes	Proteinuria, hematuria	3 7 13
C3 Glomerulopathy	Complement dysregulation	Hematuria, proteinuria	3 5 13
Membranous Nephropathy	Immune complex on GBM	Nephrotic syndrome	3 7 11
Anti-GBM Disease	Autoantibody to GBM	Rapidly progressive GN	2 6
ANCA-Associated GN	Small vessel vasculitis	Rapid renal loss, hematuria	2 3 6 13

Table 2: Main Types of Glomerular Diseases

Breaking Down the Types

Immune-Complex Mediated Diseases

• IgA Nephropathy: The most common primary glomerulonephritis worldwide, caused by deposition of IgA immune complexes. It often presents with episodic hematuria, sometimes following respiratory infections 2 3 11.
• Lupus Nephritis: Seen in systemic lupus erythematosus (SLE), with diverse histological patterns and often significant proteinuria and hematuria 3 7 13.
• Membranous Nephropathy: Immune complexes form on the glomerular basement membrane (GBM), causing thickening seen on biopsy. Typically presents with heavy proteinuria and edema 3 7 11.

Podocytopathies

• Minimal Change Disease (MCD): Common in children, it causes dramatic proteinuria (nephrotic syndrome) but minimal changes under light microscopy. The cause is often immune, and it responds well to steroids 3 13.
• Focal Segmental Glomerulosclerosis (FSGS): Marked by scarring (sclerosis) in parts of some glomeruli, often leading to progressive kidney dysfunction. It can be primary (idiopathic), genetic, adaptive (due to reduced nephron number), or secondary to other insults 3 13.

Complement-Mediated Glomerulopathies

• C3 Glomerulopathy: Includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). Both are driven by dysregulation of the complement system, leading to C3 deposition in the glomeruli 5 13.

Vasculitic and Autoimmune Diseases

• Anti-GBM Disease: Rare but severe, caused by antibodies targeting the GBM, leading to rapidly progressive kidney failure and, often, lung hemorrhage 2 6.
• ANCA-Associated Vasculitis: Autoantibodies (ANCA) attack small vessels, including those in the kidneys, causing rapidly progressive glomerulonephritis 2 3 13.

Other Notable Types

• Infection-Related Glomerulonephritis: Seen after infections, especially in children 2 3 7.
• Monoclonal Immunoglobulin-Associated GN: Caused by abnormal plasma cell clones producing damaging antibodies 2 13.

Epidemiological Variations

• The frequency of each type varies by region and ethnicity. For example, IgA nephropathy is most common in Asia and Europe, while FSGS and diabetic glomerulosclerosis predominate in North America 4.

Causes of Glomerular Diseases

Understanding what triggers glomerular diseases is key to diagnosis and prevention. Causes range from immune system dysfunctions to genetic mutations, infections, and environmental factors.

Cause/Trigger	Description/Example	Disease(s) Involved	Source
Immune Complexes	Antigen-antibody deposits	IgA nephropathy, lupus nephritis, infection-related GN	2 3 7 11 13
Autoantibodies	Direct attack on kidney structures	Anti-GBM, ANCA-GN	2 6 13
Complement Activation	Dysregulated complement pathways	C3 glomerulopathy	3 5 13
Genetic Mutations	Inherited defects (e.g., COL4A1)	FSGS, HANAC syndrome	10 13
Infections	Bacterial, viral, or parasitic causes	Post-infectious GN	2 3 7
Drugs and Toxins	Medications, illicit drugs, toxins	Secondary FSGS, others	13
Systemic Diseases	Diabetes, SLE, vasculitis	Diabetic nephropathy, lupus nephritis, ANCA-GN	2 3 4 7 13

Table 3: Common Causes of Glomerular Diseases

Delving Into the Causes

Immune-Mediated Mechanisms

• Many glomerular diseases are autoimmune in nature. The immune system mistakenly targets kidney structures, either by forming immune complexes that deposit in the glomeruli or by generating autoantibodies that directly attack glomerular components (e.g., anti-GBM disease) 2 3 6 7 11 13.
• Immune complexes are central to IgA nephropathy, lupus nephritis, and post-infectious glomerulonephritis.

Complement Pathway Dysregulation

• Abnormal activation or control of the complement system—a part of the immune response—undermines the integrity of the glomerulus. This is the primary mechanism in C3 glomerulopathy, with either autoantibodies stabilizing complement convertases or genetic mutations in complement regulatory proteins 5 13.

Genetic and Hereditary Factors

• Some glomerular diseases are linked to mutations in genes encoding essential structural proteins, such as COL4A1 in HANAC syndrome and certain forms of FSGS. These mutations can compromise the stability and function of the glomerular basement membrane or podocytes, leading to disease 10 13.
• Childhood-onset nephrotic syndrome and steroid-resistant cases often prompt genetic testing 13.

Systemic and Environmental Triggers

• Infections (especially streptococcal) can trigger glomerular inflammation, particularly in children 2 3.
• Drugs and toxins (including some painkillers, antibiotics, or illicit drugs) can induce glomerular injury, especially FSGS 13.
• Chronic diseases (e.g., diabetes) and systemic autoimmune conditions (e.g., SLE) are major contributors to secondary glomerular diseases 2 3 4 7 13.

Environmental and Lifestyle Factors

• Geographic and ethnic differences in disease prevalence suggest that environmental, dietary, and lifestyle factors also play a role in glomerular disease epidemiology 4.

Treatment of Glomerular Diseases

Treatment for glomerular diseases is tailored to the specific type, underlying cause, and severity of the condition. Recent advances have shifted strategies toward targeted, evidence-based therapies that aim for remission, preserve kidney function, and minimize side effects.

Treatment Approach	Example/Method	Indication/Comment	Source
Immunosuppression	Steroids, cyclophosphamide, MMF	Immune-mediated GN, nephrotic syndrome	3 11 13
Targeted Biologics	Rituximab, complement inhibitors	Refractory cases, C3G, membranous nephropathy	3 12 13
Supportive Therapy	BP control, RAS blockade, diuretics	All types (slow progression)	3 11 13
Plasma Exchange	Removal of autoantibodies	Anti-GBM disease, severe vasculitis	6 13
Anticoagulation	Prevent clots in nephrotic syndrome	High-risk patients	11
Lifestyle	Salt/protein restriction, vaccines	All types	11 13
Renal Replacement	Dialysis, transplantation	End-stage disease	3 11

Table 4: Main Treatment Strategies

Exploring Treatment Strategies

Immunosuppressive Therapy

• First-line for many immune-mediated glomerular diseases:
  • Corticosteroids are the mainstay in minimal change disease, FSGS, and lupus nephritis 3 11 13.
  • Other immunosuppressants: Cyclophosphamide, mycophenolate mofetil (MMF), calcineurin inhibitors, and newer biologics like rituximab are used depending on the disease and patient characteristics 3 11 13.
  • Plasma exchange is critical in anti-GBM disease and severe ANCA-associated vasculitis to rapidly remove pathogenic antibodies 6 13.

Targeted Biologic and Novel Therapies

• Rituximab (anti-CD20) is increasingly used in steroid-resistant or relapsing nephrotic syndrome and membranous nephropathy 3 13.
• Complement inhibitors (e.g., eculizumab) hold promise for C3 glomerulopathies and atypical hemolytic uremic syndrome 5 13.
• Emerging therapies aim to directly stabilize the glomerular filtration barrier and podocyte health 12.

Supportive and Symptom-Focused Care

• Blood pressure management (using ACE inhibitors or ARBs) not only controls hypertension but reduces proteinuria and slows kidney disease progression 11.
• Diuretics for managing edema; statins for hyperlipidemia 11.
• Anticoagulation may be considered for patients with nephrotic syndrome at high risk of thrombosis 11.

Lifestyle and Preventive Measures

• Dietary sodium and protein restriction can help manage hypertension and proteinuria, though recommendations are individualized 11.
• Vaccinations (influenza, pneumococcal, hepatitis B) are vital, particularly in immunosuppressed patients 13.
• Patient education for medication adherence, diet, and recognizing infection risks is crucial 11 13.

Renal Replacement and Advanced Care

• Dialysis and transplantation are options for end-stage kidney disease 3 11.
• Disease recurrence after transplantation (especially in C3 glomerulopathy, FSGS) remains a challenge 5 13.

Monitoring and Future Directions

• Frequent monitoring of proteinuria, kidney function, and blood pressure is essential to guide therapy and assess response 11.
• Ongoing research is developing new biomarkers, risk prediction tools, and personalized therapies 3 11 12 13.

Conclusion

Glomerular diseases are a complex and diverse group of disorders with significant health impacts. Advances in research and clinical practice now enable more precise diagnosis, targeted therapies, and improved patient outcomes. Key take-home points include:

• Early signs such as hematuria, proteinuria, and edema are crucial for detection.
• Disease types are diverse, ranging from immune-complex and podocyte diseases to complement-mediated and vasculitic disorders.
• Causes include immune mechanisms, genetic mutations, infections, drugs, and systemic illnesses.
• Treatment is personalized, combining immunosuppression, supportive care, targeted therapies, and lifestyle interventions.

A multidisciplinary approach—integrating the latest science, patient-centered care, and ongoing research—offers hope for better management and outcomes in glomerular diseases.