Introduction
Acute glomerulonephritis (AGN) represents a group of rapidly progressive renal diseases characterized by sudden onset of glomerular inflammation, resulting in hematuria, proteinuria, hypertension, and acute kidney injury. Unlike chronic glomerulonephritis, which develops insidiously over months to years, acute GN presents as a clinical emergency requiring immediate recognition and intervention. The hallmark clinical presentation is the acute nephritic syndrome, a constellation of findings that reflects acute glomerular injury: hematuria with RBC casts, proteinuria, hypertension, edema, and azotemia.
The incidence and prevalence of AGN vary globally, with post-infectious glomerulonephritis being the most common cause worldwide, particularly in developing nations. In developed countries, ANCA-associated vasculitis and anti-GBM disease represent significant proportions of acute GN cases. Early diagnosis and treatment are critical determinants of renal outcomes, as untreated or delayed-treatment AGN can rapidly progress to end-stage renal disease (ESRD).
Etiology and Pathogenesis of Acute Glomerulonephritis
Classification Framework
Acute glomerulonephritis can be classified based on the underlying immunopathological mechanism:
1. Immune Complex-Mediated Acute GN
•Post-infectious glomerulonephritis (PIGN)
•Post-streptococcal glomerulonephritis (PSGN)
•Lupus nephritis (Class III and IV)
•Membranoproliferative glomerulonephritis (MPGN)
2. Pauci-Immune (ANCA-Associated) Acute GN
•Granulomatosis with polyangiitis (GPA)
•Microscopic polyangiitis (MPA)
•Eosinophilic granulomatosis with polyangiitis (EGPA)
3. Anti-GBM Disease (Linear IgG Deposition)
•Goodpasture’s syndrome (with pulmonary hemorrhage)
•Anti-GBM disease (renal-limited)
4. Other Forms of Acute GN
•IgA nephropathy (IgAN)
•C3 glomerulopathy
•Infection-associated GN (beyond streptococci)
Detailed Etiology and Immune Mechanisms
1. POST-STREPTOCOCCAL GLOMERULONEPHRITIS (PSGN)
Epidemiology:
•Most common cause of AGN in children worldwide
•Accounts for 50% of all GN in developing countries
•Peak incidence: 5-12 years of age
•Can occur at any age, with worse prognosis in adults
•Follows Group A Streptococcus (GAS) infection by 1-3 weeks
Etiological Agents:
•Group A Streptococcus (Streptococcus pyogenes) is the primary causative organism
•Specific nephritogenic strains exist (M types 1, 3, 4, 12, 25, 49, 60, 61)
•Infection may be pharyngeal (pharyngitis) or cutaneous (impetigo, pyoderma)
•Post-cutaneous PSGN has a longer latency period (3-6 weeks) compared to post-pharyngeal PSGN (1-3 weeks)
Pathogenic Mechanisms:
The pathogenesis of PSGN involves multiple immune mechanisms:
A. Immune Complex Formation and Deposition:
•Streptococcal antigens (such as streptococcal pyrogenic exotoxins and M protein) trigger humoral immune responses
•Circulating immune complexes form in the bloodstream containing streptococcal antigens and host antibodies (IgG, IgM, IgA)
•These complexes deposit in the glomerulus, particularly in the subepithelial space (characteristic “hump” appearance on electron microscopy)
•Subendothelial deposition also occurs, contributing to the proliferative pattern
B. Complement Activation:
•The alternative complement pathway is predominantly activated in PSGN
•Streptococcal antigens directly activate C3 through the alternative pathway
•Classical pathway activation also occurs through immune complex-bound C1q
•Complement activation leads to:
•Generation of C3a and C5a (potent chemotactic factors)
•Formation of the membrane attack complex (C5b-9)
•Recruitment of neutrophils and macrophages to the glomerulus
•Glomerular damage through complement-mediated cytotoxicity
C. Molecular Mimicry:
•Streptococcal antigens share epitopes with host glomerular antigens
•Cross-reactive antibodies against streptococcal M protein may bind to glomerular basement membrane (GBM) components
•This molecular mimicry perpetuates the autoimmune response even after bacterial clearance
D. In Situ Immune Complex Formation:
•Streptococcal antigens may directly bind to the GBM
•Host antibodies then bind to these deposited antigens
•This “planted antigen” mechanism leads to in situ immune complex formation
•Particularly important in the subepithelial space
Histopathology:
•Light Microscopy: Diffuse proliferative glomerulonephritis with increased cellularity (endocapillary proliferation), crescent formation in severe cases
•Immunofluorescence: Granular IgG, IgM, and C3 deposits in a diffuse pattern; C3 predominance is characteristic
•Electron Microscopy: Subepithelial “hump” deposits; subendothelial and mesangial deposits also present
Complement Findings:
•Low serum C3 (characteristic finding)
•Normal or near-normal C4 levels
•C3 typically normalizes within 6-8 weeks, correlating with clinical recovery
2. IgA NEPHROPATHY (IgAN)
Epidemiology:
•Most common primary glomerulonephritis worldwide
•Accounts for 10-15% of all GN in developed countries
•Higher prevalence in Asia and Mediterranean regions
•Peak incidence: 20-40 years of age
•Slight male predominance (1.5-2:1)
Pathogenic Mechanisms:
A. Abnormal IgA Production:
•Increased production of galactose-deficient IgA1 (Gd-IgA1) by bone marrow plasma cells
•Gd-IgA1 has increased susceptibility to aggregation and immune complex formation
•Genetic predisposition plays a significant role
B. Immune Complex Formation:
•Circulating IgA-dominant immune complexes form, often with IgA1 as the predominant subclass
•These complexes are larger and more likely to deposit in the glomerulus
•IgA complexes may contain IgG and IgM as well
C. Glomerular Deposition:
•IgA complexes preferentially deposit in the mesangium (mesangial-dominant pattern)
•Deposits are also present along the capillary wall
•Deposition is mediated by transferrin receptor (TfR) and other adhesion molecules
D. Complement Activation:
•IgA activates the alternative complement pathway predominantly
•C3 deposition is prominent, while C1q deposition is typically absent (distinguishing feature)
•Complement activation leads to mesangial proliferation and glomerular injury
E. Synpharyngitic Presentation:
•Hematuria typically occurs concurrently (1-2 days) with upper respiratory infection
•This timing distinguishes IgAN from PSGN (which presents 1-3 weeks after infection)
•Suggests direct immune response to mucosal antigens
Histopathology:
•Light Microscopy: Mesangial proliferation (most common), focal segmental proliferation, or diffuse proliferation in severe cases
•Immunofluorescence: Dominant or co-dominant IgA deposits in the mesangium; C3 is typically present; C1q is absent
•Electron Microscopy: Electron-dense deposits in the mesangium and subendothelial space
3. ANCA-ASSOCIATED VASCULITIS (AAV)
Epidemiology:
•Accounts for 10-20% of rapidly progressive GN
•Peak incidence: 50-70 years of age
•Includes three main entities: GPA, MPA, and EGPA
•Rapidly progressive if untreated; mortality >80% without treatment
Pathogenic Mechanisms:
A. ANCA Production:
•Autoantibodies directed against neutrophil cytoplasmic antigens
•Two main types:
•PR3-ANCA (c-ANCA): Associated with GPA; antibodies against proteinase-3
•MPO-ANCA (p-ANCA): Associated with MPA and EGPA; antibodies against myeloperoxidase
B. Neutrophil Activation:
•ANCA binds to PR3 or MPO on the surface of activated neutrophils
•This binding triggers:
•Neutrophil degranulation
•Release of cytotoxic enzymes (elastase, collagenase)
•Generation of reactive oxygen species (ROS)
•Massive inflammatory response
C. Glomerular Injury:
•Neutrophil infiltration of the glomerulus
•Release of proteolytic enzymes damages the GBM and causes crescent formation
•Minimal or absent immune complex deposition (hence “pauci-immune”)
•Complement activation occurs secondarily through the alternative pathway
D. Crescent Formation:
•Proliferation of parietal epithelial cells in response to glomerular injury
•Formation of fibrinoid necrosis in severe cases
•Crescents can be cellular, fibrocellular, or fibrous depending on disease stage
Histopathology:
•Light Microscopy: Necrotizing glomerulonephritis with crescent formation (often >50% of glomeruli); minimal proliferation
•Immunofluorescence: Pauci-immune pattern (minimal or absent immunoglobulin and complement deposition); may show fibrin deposition
•Electron Microscopy: Absence of electron-dense deposits; GBM necrosis; crescent formation
Clinical Presentation Variants:
•GPA (Granulomatosis with Polyangiitis): Upper respiratory tract involvement (sinusitis, nasal granulomas), lower respiratory tract involvement (pulmonary nodules, hemorrhage), and systemic vasculitis
•MPA (Microscopic Polyangiitis): Pulmonary-renal syndrome (pulmonary hemorrhage with GN); no upper respiratory involvement
•EGPA (Eosinophilic Granulomatosis with Polyangiitis): Asthma, eosinophilia, and vasculitis; cardiac involvement common
4. ANTI-GBM DISEASE (GOODPASTURE’S SYNDROME)
Epidemiology:
•Rare, accounting for 1-2% of rapidly progressive GN
•Peak incidence: 20-30 and 60-70 years of age
•Bimodal age distribution
•Male predominance (2-3:1)
•Rapidly progressive; >50% develop ESRD within weeks if untreated
Pathogenic Mechanisms:
A. Anti-GBM Antibody Production:
•Autoantibodies directed against the non-collagenous domain of type IV collagen (α3(IV)NC1 domain)
•Antibodies are predominantly IgG, with IgA and IgM also present
•Monovalent antibodies bind to epitopes on the GBM
•Antibodies are typically circulating but can also be produced locally in the kidney
B. Linear IgG Deposition:
•Antibodies bind directly to the GBM in a linear fashion along the basement membrane
•This linear pattern is pathognomonic for anti-GBM disease
•Deposition occurs throughout the glomerulus and also in the alveolar basement membrane (in Goodpasture’s syndrome)
C. Complement Activation:
•IgG binding to the GBM activates the classical complement pathway
•C1q, C4, C3, and C5b-9 are deposited in a linear pattern
•Complement activation leads to:
•Recruitment of neutrophils and macrophages
•Release of proteolytic enzymes
•GBM disruption and crescent formation
D. Pulmonary Involvement (Goodpasture’s Syndrome):
•Anti-GBM antibodies also bind to the alveolar basement membrane
•Results in pulmonary hemorrhage (hemoptysis, dyspnea, hemoptysis)
•Occurs in 50-60% of anti-GBM disease cases
•Represents a medical emergency
Histopathology:
•Light Microscopy: Necrotizing glomerulonephritis with extensive crescent formation (often >80% of glomeruli); minimal proliferation
•Immunofluorescence: Linear IgG deposition along the GBM; linear C3 deposition also present; IgA and IgM may be present
•Electron Microscopy: GBM thinning and disruption; absence of electron-dense deposits; crescent formation
Triggers:
•Pulmonary infection or inflammation
•Smoking (increases risk)
•Cocaine use (especially with levamisole contamination)
•Environmental exposures
•Autoimmune diseases (SLE, ANCA-associated vasculitis)
5. OTHER FORMS OF ACUTE GN
Lupus Nephritis (Class III and IV):
•Immune complex-mediated GN associated with systemic lupus erythematosus
•Characterized by anti-dsDNA antibodies and anti-nucleosome antibodies
•Complement activation (low C3, C4) is prominent
•Presents with hematuria, proteinuria, and hypertension
•Can rapidly progress to ESRD if untreated
C3 Glomerulopathy:
•Dysregulation of the alternative complement pathway
•Mutations in complement regulatory proteins (Factor H, Factor I, Membrane Cofactor Protein)
•C3 deposition without significant immunoglobulin deposition
•Can present acutely or progress slowly
•Often recurs after kidney transplantation
Infection-Associated GN (Beyond Streptococci):
•Bacterial Endocarditis: Immune complex GN associated with bacterial infection of heart valves
•Hepatitis B and C: Immune complex GN with HBsAg or HCV antigen deposition
•HIV-Associated GN: Direct viral involvement and immune complex deposition
•Syphilis: Immune complex GN in secondary syphilis
•Malaria: Immune complex GN in endemic areas
Pathophysiological Consequences of Acute GN
Glomerular Injury Mechanisms
1. Complement-Mediated Injury:
•C3a and C5a act as potent chemotactic factors, recruiting neutrophils and macrophages
•C5b-9 (membrane attack complex) forms pores in cell membranes, causing cell lysis
•Complement activation perpetuates inflammation even after antigen clearance
2. Neutrophil-Mediated Injury:
•Infiltrating neutrophils release:
•Serine proteases (elastase, cathepsin G)
•Collagenases (matrix metalloproteinases)
•Reactive oxygen species (superoxide, hydrogen peroxide)
•These mediators cause direct GBM damage and crescent formation
3. Macrophage-Mediated Injury:
•Resident glomerular macrophages and infiltrating monocytes produce:
•Pro-inflammatory cytokines (TNF-α, IL-6, IL-8)
•Growth factors (TGF-β, PDGF)
•Reactive oxygen species
•Perpetuates inflammation and promotes fibrosis
4. Endothelial Cell Injury:
•Glomerular endothelial cells are damaged by complement, proteases, and ROS
•Loss of endothelial integrity increases glomerular permeability
•Contributes to proteinuria and hematuria
Systemic Consequences
Acute Kidney Injury:
•Reduced glomerular filtration rate (GFR) due to:
•Reduced glomerular surface area (crescent formation, proliferation)
•Increased glomerular permeability
•Tubular dysfunction (from proteinuria and cellular debris)
•Oliguria (urine output <400 mL/day) in severe cases
•Rapid rise in serum creatinine and BUN
Fluid and Electrolyte Abnormalities:
•Sodium and water retention due to:
•Reduced GFR
•Activation of the renin-angiotensin-aldosterone system (RAAS)
•Increased sympathetic nervous system activity
•Hyperkalemia due to:
•Reduced renal excretion
•Cellular breakdown (rhabdomyolysis, hemolysis)
•Metabolic acidosis
•Hyperphosphatemia and hypocalcemia
Hypertension:
•Mechanisms:
•Sodium and water retention
•RAAS activation
•Increased sympathetic tone
•Endothelial dysfunction
•Can lead to hypertensive emergencies (encephalopathy, acute coronary syndrome)
Pulmonary Complications:
•Pulmonary edema from volume overload
•Pulmonary hemorrhage (in pulmonary-renal syndromes like Goodpasture’s and ANCA-associated vasculitis)
•Acute respiratory distress syndrome (ARDS) in severe cases
Clinical Presentation of Acute GN
Acute Nephritic Syndrome
The classic presentation of acute GN is the acute nephritic syndrome, characterized by:
1. Hematuria:
•Gross hematuria (tea-colored or cola-colored urine) is the most common presenting symptom
•Caused by RBC leakage through damaged glomeruli
•RBC casts in the urine are pathognomonic for glomerular hematuria
•Dysmorphic RBCs indicate glomerular origin
2. Proteinuria:
•Usually mild to moderate (0.5-3 g/day)
•Nephrotic-range proteinuria (>3.5 g/day) is less common in pure acute GN
•Foamy urine may be noted by patients
•Caused by increased glomerular permeability
3. Hypertension:
•Present in 50-80% of acute GN cases
•Due to sodium and water retention
•Can be severe (>160/100 mmHg) and lead to hypertensive emergencies
•May be the first sign of disease in some patients
4. Edema:
•Periorbital edema (around the eyes) is characteristic
•Peripheral edema (hands, feet, legs)
•Ascites in severe cases
•Due to sodium and water retention and reduced plasma oncotic pressure
5. Azotemia:
•Elevated serum creatinine and BUN
•Indicates reduced GFR
•Severity correlates with degree of glomerular injury
Associated Symptoms
Systemic Symptoms:
•Fatigue and malaise
•Nausea and vomiting
•Anorexia
•Flank pain (from renal capsule stretching)
Respiratory Symptoms:
•Dyspnea (from pulmonary edema)
•Orthopnea and paroxysmal nocturnal dyspnea
•Hemoptysis (in pulmonary-renal syndromes)
•Cough
Neurological Symptoms:
•Headache
•Altered mental status (from hypertensive encephalopathy)
•Seizures (in severe hypertension)
Specific Features by Etiology:
Post-Streptococcal GN:
•History of pharyngitis or skin infection 1-3 weeks prior
•More common in children
•Often preceded by fever and systemic symptoms
IgA Nephropathy:
•Hematuria concurrent with upper respiratory infection (synpharyngitic)
•Recurrent episodes of gross hematuria
•Asymptomatic microscopic hematuria between episodes
ANCA-Associated Vasculitis:
•Upper respiratory tract symptoms (sinusitis, nasal congestion)
•Lower respiratory tract symptoms (cough, hemoptysis)
•Systemic symptoms (fever, weight loss, arthralgia)
•Rapidly progressive course
Anti-GBM Disease:
•Hemoptysis (in 50-60% of cases)
•Dyspnea and respiratory distress
•Rapidly progressive renal failure
•Often presents as a medical emergency
Diagnostic Approach to Acute GN
Laboratory Investigations
Urinalysis:
•Hematuria: RBC casts (pathognomonic), dysmorphic RBCs
•Proteinuria: Usually <3 g/day
•Pyuria: May be present (from inflammation)
•Casts: RBC casts, granular casts, waxy casts
Serum Chemistry:
•Creatinine and BUN: Assess degree of renal dysfunction
•Electrolytes: Hyperkalemia, hyponatremia, hyperphosphatemia
•Calcium: Hypocalcemia (secondary to hyperphosphatemia)
•Albumin: Usually normal unless nephrotic-range proteinuria
Complement Studies:
•C3 and C4 levels: Essential for differential diagnosis
•Low C3 with normal C4: Suggests PSGN, C3 glomerulopathy, or membranoproliferative GN
•Normal C3 and C4: Suggests IgAN, ANCA-associated vasculitis, or anti-GBM disease
•Low C3 and C4: Suggests lupus nephritis or severe MPGN
Serological Testing:
For PSGN:
•ASO (Antistreptolysin O) titer: Elevated in post-pharyngeal PSGN
•Anti-DNase B: More sensitive than ASO, especially in post-cutaneous PSGN
•Throat culture: May be positive if infection is recent
For ANCA-Associated Vasculitis:
•PR3-ANCA (c-ANCA): Associated with GPA
•MPO-ANCA (p-ANCA): Associated with MPA and EGPA
•Positive in 90% of systemic vasculitis, 50-80% of renal-limited disease
For Anti-GBM Disease:
•Anti-GBM antibody (ELISA or radioimmunoassay): Highly specific
•Positive in >90% of active disease
For Lupus Nephritis:
•ANA (Antinuclear Antibody): Positive in >95% of SLE
•Anti-dsDNA: Specific for SLE
•Anti-nucleosome: Also specific for SLE
•Low C3 and C4: Correlates with disease activity
For IgA Nephropathy:
•Serum IgA levels: May be elevated, but not diagnostic
•No specific serological marker; diagnosis requires biopsy
Imaging Studies
Chest X-ray:
•Assess for pulmonary edema (bilateral infiltrates)
•Look for pulmonary hemorrhage (in pulmonary-renal syndromes)
•Evaluate for upper respiratory tract involvement (in GPA)
Renal Ultrasound:
•Assess kidney size and echotexture
•Rule out obstruction or other structural abnormalities
•Increased echogenicity may indicate acute inflammation
CT Chest/Abdomen:
•Indicated if pulmonary-renal syndrome is suspected
•Can visualize pulmonary hemorrhage, nodules, or cavitary lesions
•Assess for other systemic involvement
Kidney Biopsy
Indications:
•Diagnosis uncertain after serological testing
•Need to determine disease activity and chronicity
•Assess degree of crescent formation and scarring
•Guide immunosuppressive therapy decisions
Biopsy Findings by Type:
PSGN:
•Light Microscopy: Diffuse endocapillary proliferation
•Immunofluorescence: Granular IgG, IgM, C3 (C3-predominant)
•Electron Microscopy: Subepithelial “hump” deposits
IgAN:
•Light Microscopy: Mesangial proliferation
•Immunofluorescence: Dominant IgA deposits; C3 present; C1q absent
•Electron Microscopy: Mesangial and subendothelial deposits
ANCA-Associated Vasculitis:
•Light Microscopy: Necrotizing GN with crescents
•Immunofluorescence: Pauci-immune pattern (minimal Ig and complement)
•Electron Microscopy: Absence of electron-dense deposits
Anti-GBM Disease:
•Light Microscopy: Necrotizing GN with crescents
•Immunofluorescence: Linear IgG along GBM; linear C3
•Electron Microscopy: GBM thinning and disruption
Management of Acute GN
Supportive Care (Universal)
Fluid and Sodium Restriction:
•Sodium restriction to 1-2 g/day to control hypertension and edema
•Fluid restriction to 800-1000 mL/day plus urine output losses
•Strict monitoring of daily weights (best indicator of fluid status)
Diuretic Therapy:
•Loop diuretics (Furosemide) are first-line for fluid overload
•Dosing adjusted based on response and renal function
•Thiazide diuretics are less effective in advanced renal dysfunction
Blood Pressure Control:
•Target: <130/80 mmHg
•ACE inhibitors or ARBs are first-line (renoprotective)
•Avoid NSAIDs (worsen renal function)
•For hypertensive emergencies: IV agents (Labetalol, Hydralazine, Nicardipine)
Dietary Modifications:
•Protein restriction to 0.6-0.8 g/kg/day if azotemia is present
•Potassium restriction if serum K+ is elevated
•Phosphate restriction if hyperphosphatemia develops
•Adequate caloric intake to prevent catabolism
Monitoring:
•Daily weights and vital signs
•Frequent electrolyte monitoring (K+, Na+, Phos, Ca2+)
•Serial creatinine and BUN
•Urinalysis and urine protein quantification
Etiology-Specific Therapy
Post-Streptococcal GN:
•Antibiotics (Penicillin or alternatives) to eliminate residual bacteria
•Supportive care alone is often sufficient
•Immunosuppression is rarely needed
•Excellent prognosis in children (>95% recovery)
IgA Nephropathy:
•Supportive care is the foundation
•ACE inhibitors/ARBs for blood pressure control and renoprotection
•Immunosuppression (corticosteroids, MMF) for severe disease or rapid progression
•Fish oil (omega-3 fatty acids) may slow progression in some patients
ANCA-Associated Vasculitis:
•High-dose corticosteroids (IV Methylprednisolone pulses followed by oral taper)
•Immunosuppressive agents:
•Cyclophosphamide (for severe, rapidly progressive disease)
•Rituximab (anti-B cell therapy; increasingly used as alternative to cyclophosphamide)
•Mycophenolate mofetil (for maintenance therapy)
•Plasmapheresis for severe pulmonary hemorrhage or rapidly progressive renal failure
Anti-GBM Disease:
•High-dose corticosteroids (IV Methylprednisolone)
•Plasmapheresis to remove circulating anti-GBM antibodies
•Cyclophosphamide for severe disease
•Urgent treatment is critical; delayed treatment results in permanent renal failure
Lupus Nephritis:
•Corticosteroids (IV pulses for induction, oral for maintenance)
•Immunosuppressive agents:
•Cyclophosphamide (for severe proliferative disease)
•Mycophenolate mofetil (increasingly used as alternative to cyclophosphamide)
•Azathioprine (for maintenance)
•ACE inhibitors/ARBs for blood pressure control
Renal Replacement Therapy
Indications for Dialysis:
•Severe azotemia (BUN >100 mg/dL)
•Refractory hyperkalemia (K+ >6.5 mEq/L)
•Severe volume overload with pulmonary edema unresponsive to diuretics
•Symptomatic uremia (encephalopathy, pericarditis)
•Severe metabolic acidosis (pH <7.1)
Modalities:
•Intermittent hemodialysis (standard for stable patients)
•Continuous renal replacement therapy (CRRT) for hemodynamically unstable patients
Prognosis:
•Dialysis is often temporary in acute GN
•Recovery of renal function is possible as inflammation resolves
•Early initiation of dialysis prevents life-threatening complications
Prognosis and Outcomes
Post-Streptococcal GN
•Children: >95% achieve complete recovery with supportive care
•Adults: 50% complete recovery, 20% partial recovery, 20% chronic GN, 10% ESRD
•Predictors of poor prognosis: Older age, severe renal impairment at presentation, extensive crescent formation
IgA Nephropathy
•Variable course: 40% progress to ESRD over 20 years
•Predictors of poor prognosis: Proteinuria >1 g/day, hypertension, reduced GFR at presentation, advanced histological grade
•Treatment response: ACE inhibitors/ARBs slow progression; immunosuppression benefits selected patients
ANCA-Associated Vasculitis
•Untreated: >80% mortality within 2 years
•With treatment: >80% remission rate, but relapse is common (30-50% within 5 years)
•Renal outcomes: 10-20% require dialysis at presentation; 20-30% develop ESRD over 5 years
Anti-GBM Disease
•Worst prognosis: Rapid progression to ESRD if dialysis-dependent at presentation
•Renal recovery: Rare if patient is dialysis-dependent at diagnosis
•Pulmonary outcomes: Pulmonary hemorrhage is life-threatening but responds to treatment
Complications of Acute GN
Acute Phase Complications
Hypertensive Emergencies:
•Hypertensive encephalopathy (headache, altered mental status, seizures)
•Acute coronary syndrome
•Acute heart failure
Pulmonary Complications:
•Pulmonary edema (respiratory distress, hypoxia)
•Pulmonary hemorrhage (hemoptysis, hemodynamic instability)
•Acute respiratory distress syndrome (ARDS)
Metabolic Complications:
•Severe hyperkalemia (cardiac arrhythmias, cardiac arrest)
•Severe metabolic acidosis
•Hypocalcemia with tetany
Rapidly Progressive Renal Failure:
•Fulminant acute kidney injury requiring emergency dialysis
•Crescent formation in >50% of glomeruli
Long-Term Complications
Chronic Kidney Disease:
•Persistent proteinuria and hypertension
•Gradual decline in GFR
•Glomerulosclerosis and tubular atrophy
End-Stage Renal Disease:
•Requirement for long-term dialysis or transplantation
•Increased cardiovascular mortality
•Recurrence of disease in transplanted kidney (especially IgAN and ANCA-associated vasculitis)
Cardiovascular Disease:
•Accelerated atherosclerosis
•Left ventricular hypertrophy
•Increased risk of myocardial infarction and stroke
Summary
Acute glomerulonephritis represents a diverse group of rapidly progressive renal diseases with varied etiologies and immune mechanisms. The acute nephritic syndrome—characterized by hematuria, proteinuria, hypertension, edema, and azotemia—is the hallmark clinical presentation. Key etiologies include post-streptococcal GN (immune complex-mediated), IgA nephropathy (IgA-dominant immune complexes), ANCA-associated vasculitis (pauci-immune, neutrophil-mediated), and anti-GBM disease (linear IgG deposition).
Diagnosis relies on a combination of clinical presentation, serological testing (complement levels, ANCA, anti-GBM antibodies), and kidney biopsy. Management involves universal supportive care (fluid/salt restriction, diuretics, blood pressure control) combined with etiology-specific therapy (antibiotics for PSGN, immunosuppression for autoimmune forms). Early recognition and treatment are critical determinants of renal outcomes, as untreated acute GN can rapidly progress to ESRD.
Prognosis varies significantly by etiology and patient factors. Children with PSGN have excellent outcomes (>95% recovery), while adults have more variable outcomes. ANCA-associated vasculitis and anti-GBM disease are rapidly progressive and require urgent treatment. Long-term complications include chronic kidney disease, ESRD, and accelerated cardiovascular disease, necessitating close follow-up and monitoring even after apparent clinical recovery.
References
1.Sethi, S., Fervenza, F. C. (2022). Pathology of renal diseases associated with dysfunction of the alternative complement pathway. Kidney International, 102(1), 5-17.
2.Rawla, P., Padala, S. A., Ludhwani, D. (2023). Acute Glomerulonephritis. In StatPearls. Treasure Island (FL): StatPearls Publishing.
3.Fogo, A. B. (2015). AJKD Atlas of Renal Pathology: Postinfectious Glomerulonephritis. American Journal of Kidney Diseases, 67(2), e17-e18.
4.Couser, W. G. (2021). Rapidly progressive glomerulonephritis: Classification, pathophysiology, diagnosis, and management. American Journal of Kidney Diseases, 78(3), 389-407.
5.Jennette, J. C., Falk, R. J., Bacon, P. A., et al. (2013). 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis & Rheumatism, 65(1), 1-11.
6.Appel, G. B., Radhakrishnan, J., D’Agati, V. D. (2016). Secondary Glomerulonephritis. In Brenner and Rector’s The Kidney (10th ed., pp. 1268-1349). Philadelphia: Elsevier.
7.Kidney Disease: Improving Global Outcomes (KDIGO). (2021). KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney International, 100(4S), S1-S276.
8.Chadban, S. J., Atkins, R. C. (2005). Glomerulonephritis. The Lancet, 365(9473), 1797-1806.
9.Nasr, S. H., Markowitz, G. S. (2016). Acute Postinfectious Glomerulonephritis. In Comprehensive Clinical Nephrology (5th ed., pp. 312-325). Philadelphia: Elsevier.
10.Floege, J., Feehally, J., Tonelli, M. (Eds.). (2019). Comprehensive Clinical Nephrology (6th ed.). Philadelphia: Elsevier.