Glomerulonephritis: Symptoms, Types, Causes and Treatment

Glomerulonephritis (GN) is a group of kidney diseases marked by inflammation of the glomeruli—the tiny filtering units within the kidneys. This complex syndrome can affect people of all ages, often presenting with a wide range of symptoms and progressing to chronic kidney disease if not managed appropriately. Understanding GN is crucial, not only because it is a major cause of kidney failure worldwide, but also because it demands nuanced diagnosis and tailored therapy. This article will guide you through the symptoms, types, causes, and treatment options for glomerulonephritis, weaving together the latest research and clinical practice.

Symptoms of Glomerulonephritis

Glomerulonephritis can be insidious or acute, and its symptoms often overlap with those of other kidney diseases. Early recognition is vital to avert progressive kidney injury and related complications.

Symptom	Description	Frequency/Notability	Source(s)
Edema	Swelling, especially around eyes/ankles	Common in both acute and chronic GN	1, 6, 11
Hematuria	Blood in urine (may be microscopic)	Hallmark symptom, especially in IgA nephropathy	1, 8, 10
Proteinuria	Protein in urine	Can range from mild to nephrotic levels	1, 6, 10
Hypertension	Elevated blood pressure	Frequent, especially in nephritic forms	1, 3, 6
Oliguria	Reduced urine output	Especially in acute cases	1, 6
Renal Dysfunction	Decreased filtration rate	Seen in both acute and chronic cases	1, 3, 11

Table 1: Key Symptoms

Symptom Profiles in GN

The clinical presentation of GN is remarkably varied, often depending on the underlying type and stage:

Edema and Fluid Retention

• Edema is a classic sign and typically appears around the eyes (periorbital) or ankles. It is a result of salt and water retention due to impaired kidney function 1, 6.
• Severe cases can result in generalized swelling and even fluid accumulation in the lungs (pulmonary edema).

Hematuria and Proteinuria

• Hematuria, or blood in the urine, is a key early sign. In IgA nephropathy, it often manifests as visible blood in urine after infections, but can also be microscopic 8, 10.
• Proteinuria (protein in the urine) may be mild or progress to nephrotic levels, leading to frothy urine and worsening edema 6, 10.

Hypertension

• Increased blood pressure is common, particularly in nephritic syndromes and chronic GN 1, 3, 6.
• This may be the only presenting feature in some patients and is an important risk factor for kidney disease progression.

Oliguria and Renal Dysfunction

• Oliguria (reduced urine output) occurs in more severe or acute presentations, reflecting significant loss of filtering capacity 1.
• As GN progresses, decreased glomerular filtration rate (GFR) is nearly universal, leading to the accumulation of waste products and, eventually, symptoms of kidney failure 3, 11.

Other Symptoms

• Some forms may present with systemic symptoms such as fever, rash, or joint pain, especially when associated with autoimmune or vasculitic processes 2, 9.

Types of Glomerulonephritis

GN is a highly heterogeneous group of diseases, classified by underlying mechanisms, histological appearance, and clinical features. Understanding the major types is essential for diagnosis and therapy.

Type	Key Features	Age/Prevalence	Source(s)
IgA Nephropathy	Hematuria, IgA deposits, often after infection	Most common worldwide, young adults	5, 8, 10
Post-infectious GN	Acute onset, after infection, low C3	Children and adults	1, 2, 12
Membranoproliferative GN	Mixed nephritic/nephrotic features, low C3	Children (type II), adults (type I)	3, 5
Minimal Change Disease	Nephrotic syndrome, minimal changes on biopsy	Mainly children	5, 12
Focal Segmental Glomerulosclerosis (FSGS)	Nephrotic syndrome, segmental scarring	All ages, common cause of ESRD	5, 4, 12
Membranous Nephropathy	Nephrotic syndrome, immune complex deposits	Adults	5, 12
Lupus Nephritis	Systemic symptoms, autoantibodies, variable presentation	Young women	1, 5, 12
ANCA-associated Vasculitis	Rapidly progressive, systemic vasculitis	Older adults	12, 7
Anti-GBM Disease	Rapidly progressive, lung involvement possible	Rare	12
C3 Glomerulopathy	Complement-mediated, low C3	Rare, all ages	12, 5

Table 2: Main Types of Glomerulonephritis

Classification Systems

By Clinical Syndrome

• Nephritic Syndrome: Characterized by hematuria, mild-moderate proteinuria, hypertension, and decreased kidney function. Classical in post-infectious and proliferative GN 1, 6.
• Nephrotic Syndrome: Heavy proteinuria (>3.5 g/day), severe edema, low blood albumin, and hyperlipidemia. Seen in minimal change disease, membranous nephropathy, and some forms of FSGS 6.

By Histopathology

• Proliferative GN: Increased number of glomerular cells; includes post-infectious GN, lupus nephritis, and membranoproliferative GN 1, 3, 5.
• Non-proliferative GN: Less cellular proliferation, seen in minimal change disease, membranous nephropathy.

By Pathogenesis

• Immune Complex-Mediated: Most GN types involve immune complex deposition, such as IgA nephropathy, lupus nephritis, and post-infectious GN 7, 10.
• Complement-Mediated: Includes C3 glomerulopathy, where abnormal activation of complement pathway is central 12, 5.
• Pauci-immune: Minimal immune complex deposition, as in ANCA-associated vasculitis 12, 7.

Notable Types

IgA Nephropathy

• Most common worldwide. Features recurrent hematuria, often after upper respiratory infections. Risk of progression to ESRD 5, 8, 10.
• Pathology shows IgA deposits in the glomeruli.

Membranoproliferative GN (MPGN)

• Presents with hematuria, proteinuria, low C3. Divided into type I (classical) and type II (dense deposit disease), with type II more common in children 3, 5.
• Prognosis varies, but many develop chronic kidney disease.

FSGS and Minimal Change Disease

• Both can cause nephrotic syndrome; FSGS is more likely to progress to ESRD and can recur after transplantation 4, 5.

Vasculitic and Autoimmune GN

• Lupus nephritis and ANCA-associated vasculitis can cause rapidly progressive GN, requiring urgent therapy 12, 7.

Causes of Glomerulonephritis

GN arises from a variety of triggers that set off immune-mediated injury in the glomeruli. These can be broadly classified as primary (originating in the kidney) or secondary (as part of systemic disease).

Cause	Description	Example Types/Conditions	Source(s)
Infection-related	Follows infections, immune response triggers GN	Post-infectious GN, PSIGN	1, 2, 7, 12
Autoimmune	Body's immune system attacks own tissues	Lupus nephritis, ANCA vasculitis, IgA nephropathy	7, 12, 10, 9
Genetic Factors	Heritable predisposition	Familial IgA nephropathy	8, 10, 9
Alloimmune	Response to foreign tissue	GN after kidney transplant	4, 7
Monoclonal Gammopathy	Abnormal plasma cell proliferation	Rare, in older adults	7, 12
Unknown/Idiopathic	No identifiable cause	Minimal change disease, some MPGN	5, 3

Table 3: Causes of Glomerulonephritis

Immune-Mediated Mechanisms

Infection-Related GN

• Often triggered by a recent bacterial infection (like streptococcal throat infection), leading to immune complex deposition in the glomeruli 1, 2, 7, 12.
• Post-streptococcal GN is common in children. PSIGN (post-staphylococcus GN) can be seen in older adults 2.

Autoimmune and Vasculitic GN

• Lupus nephritis: Systemic lupus erythematosus generates antibodies that form immune complexes, depositing in kidneys 1, 12.
• ANCA-associated vasculitis: Autoantibodies attack blood vessels, leading to rapidly progressive GN 12, 7.
• IgA nephropathy and IgA vasculitis (Henoch-Schönlein purpura): Aberrant IgA1 immune complexes deposit in glomeruli, often after infections; genetics may play a role 8, 9, 10.

Genetic and Familial Factors

• Certain forms, like IgA nephropathy, show familial clustering and genetic susceptibility, particularly linked to chromosome 6q22–23 8, 10.
• Genetic predisposition may also modulate the immune response, complement pathway, and risk of progression 9, 10.

Alloimmune and Monoclonal Causes

• After kidney transplantation, the immune system may attack the new kidney, leading to recurrent or de novo GN 4, 7.
• Rarely, abnormal plasma cell or B cell clones (monoclonal gammopathy) produce proteins that deposit in glomeruli 7, 12.

Idiopathic and Other Causes

• Some forms, such as minimal change disease, arise without a clear external trigger and are termed idiopathic 5.
• Environmental and yet-unidentified factors may also contribute.

Treatment of Glomerulonephritis

Treatment strategies for GN are as diverse as its causes and types. The primary goals are to control symptoms, slow disease progression, and address the underlying cause when possible.

Approach	Main Interventions	Target Patient/Type	Source(s)
Supportive Care	Blood pressure control, salt restriction, diuretics, ACE inhibitors	All GN types, especially mild/moderate	12, 13, 14, 15
Immunosuppression	Corticosteroids, cytotoxic agents	Autoimmune/vasculitic, severe, rapidly progressive	2, 7, 12, 13, 14, 15
Infection Control	Antibiotics, treat underlying infection	Infection-related GN	1, 2, 7, 12
Plasma Exchange	Removal of pathogenic antibodies	Severe ANCA vasculitis, anti-GBM disease	12, 7
Targeted Therapy	Complement inhibitors, monoclonal antibodies	Specific subtypes (research/advanced)	7, 12
Renal Replacement	Dialysis, transplantation	End-stage renal disease	4, 11, 12

Table 4: Main Treatment Approaches

Supportive Care: The Foundation

• Control of blood pressure (with ACE inhibitors or ARBs) and salt restriction are the mainstay for most GN types, especially in the early stages 12, 13, 14.
• Diuretics help manage edema; statins may be used for hyperlipidemia.
• Proteinuria reduction is a key therapeutic target, as it correlates with slowing disease progression 13, 14.

Immunosuppression

• Indicated for immune-mediated and rapidly progressive forms (e.g., lupus nephritis, ANCA vasculitis, severe IgA nephropathy) 2, 7, 12, 13, 14, 15.
• Corticosteroids are commonly used; cytotoxic agents (e.g., cyclophosphamide) may be added for severe cases.
• The benefit of immunosuppression in mild-moderate IgA nephropathy is less clear and must be weighed against risks 13, 14, 15.

Infection Control

• In post-infectious GN, treating the underlying infection is crucial. Immunosuppression is generally avoided unless there is evidence of ongoing immune activation not linked to infection 1, 2, 7, 12.

Disease-Specific and Advanced Therapies

• Plasma exchange is reserved for severe, rapidly progressive types with antibody-mediated injury (e.g., anti-GBM disease, severe ANCA vasculitis) 12, 7.
• Complement inhibitors (e.g., eculizumab) and monoclonal antibodies are under investigation or used in select cases 7, 12.
• For monoclonal gammopathy-related GN, therapies target the abnormal plasma/B cell clone 7.

Renal Replacement Therapy

• In advanced or end-stage disease, dialysis or kidney transplantation is necessary. However, some forms of GN (e.g., FSGS, IgA nephropathy, MPGN) have a risk of recurrence even after transplantation 4, 11, 12.

Individualized and Evolving Care

• Management is increasingly personalized, based on disease type, severity, risk of progression, and patient comorbidities.
• Clinical guidelines (such as KDIGO) provide structured recommendations, but many decisions rely on expert opinion due to gaps in high-quality evidence 12, 14, 15.

Conclusion

Glomerulonephritis is a diverse group of kidney diseases with significant impact on health. Early recognition, correct classification, and tailored therapy are crucial for optimal outcomes. As our understanding of the immune mechanisms underlying GN deepens, more precise treatments are on the horizon.

Key Points:

• Glomerulonephritis causes a spectrum of symptoms, including hematuria, proteinuria, edema, hypertension, and reduced kidney function.
• There are multiple types, classified by clinical presentation, histology, and immunopathogenesis—each with unique features and prognosis.
• Causes range from post-infectious and autoimmune mechanisms to genetic predisposition and rare monoclonal disorders.
• Treatment focuses on supportive care, immunosuppression for selected types, infection control, and advanced therapies in severe cases.
• Many aspects of GN management are still evolving, with ongoing research aimed at improving outcomes and reducing side effects.

If you suspect glomerulonephritis or have risk factors, early evaluation by a healthcare provider is vital for timely intervention and preservation of kidney health.