Glomerulonephritis

1. Clinical Overview

Definition and Significance

Glomerulonephritis (GN) represents a heterogeneous group of immune-mediated kidney diseases characterised by inflammation of the glomeruli, the filtering units of the kidney. GN is the third leading cause of end-stage renal disease (ESRD) globally, following diabetes mellitus and hypertension. [1]

Clinical Significance: GN accounts for 10-15% of chronic kidney disease (CKD) cases worldwide, with marked geographic variation. [2] The annual incidence of primary glomerulonephritis ranges from 0.2 to 2.5 cases per 100,000 population in developed countries. [3] Rapidly progressive glomerulonephritis (RPGN) can lead to irreversible renal failure within days to weeks if untreated, making early recognition and treatment critical.

The spectrum of glomerular diseases extends from asymptomatic urinary abnormalities to severe acute kidney injury (AKI) requiring dialysis. Prognosis varies dramatically by histological subtype, ranging from near-complete recovery in post-streptococcal GN to > 50% progression to ESRD in focal segmental glomerulosclerosis (FSGS) and RPGN. [4]

Key Disease Associations

Most Common Primary Glomerulonephritides:

• IgA Nephropathy: Accounts for 30-40% of primary GN worldwide, with highest prevalence in East Asia (40-50% of biopsies). [5]
• Focal Segmental Glomerulosclerosis (FSGS): Leading cause of nephrotic syndrome in adults, particularly in African American populations (relative risk 4-5 compared to Caucasians). [6]
• Membranous Nephropathy: Most common cause of idiopathic nephrotic syndrome in Caucasian adults aged 40-60 years. [7]
• Minimal Change Disease: Predominant in children (80% of nephrotic syndrome) but accounts for 10-15% of adult nephrotic syndrome. [8]

Secondary Glomerular Diseases:

• Post-infectious glomerulonephritis (particularly post-streptococcal)
• Lupus nephritis (affects 50-60% of SLE patients)
• ANCA-associated vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis)
• Anti-GBM disease (Goodpasture syndrome)
• Diabetic nephropathy
• Amyloidosis

"Do Not Miss" Warnings

⚠️ CRITICAL RED FLAGS:

1. Rapidly Progressive Glomerulonephritis (RPGN):

   • Rise in serum creatinine by ≥50% within 3 months, or dialysis requirement within weeks.
   • Requires urgent renal biopsy (within 24-48 hours) and immediate immunosuppression.
   • Without treatment, 80-90% progress to irreversible ESRD within 6 months. [9]

2. Pulmonary-Renal Syndrome:

   • Hemoptysis + AKI = medical emergency.
   • Think: Granulomatosis with polyangiitis (GPA), anti-GBM disease, SLE.
   • Requires urgent plasma exchange + immunosuppression.
   • Mortality without treatment: 50-90% within 1 year. [10]

3. Nephrotic Syndrome with Acute Kidney Injury:

   • Suggests crescentic transformation (poor prognosis).
   • Consider minimal change disease in adults (10% develop AKI) or membranous GN with crescents.
   • Risk of renal vein thrombosis (5-10% in nephrotic syndrome with albumin less than 20 g/L). [11]

4. Thromboembolism in Nephrotic Syndrome:

   • Venous thromboembolism risk: 10-40% (especially with albumin less than 20 g/L).
   • Consider prophylactic anticoagulation. [12]

2. Epidemiology & Risk Factors

Incidence and Prevalence

Global Burden:

• Primary GN incidence: 0.2-2.5 per 100,000 per year (geographic variation). [3]
• IgA Nephropathy: Most common primary GN globally (30-40% of biopsies), highest in Asia (40-50% Japan/China), lowest in Africa (less than 5%). [5]
• FSGS: Accounts for 35-40% of primary nephrotic syndrome in adults (US data). Incidence rising (2.5-fold increase over past 3 decades). [6]
• Membranous Nephropathy: Incidence 1.2 per 100,000, peak age 40-60 years. [7]
• Post-Streptococcal GN: Declining in developed countries (improved sanitation, early antibiotic treatment). Persists in developing regions (incidence 10-15 per 100,000 children). [13]
• RPGN: 10-15% of all GN cases. Annual incidence 0.9-1.8 per million. [9]

Demographics

Age Patterns:

• Children: Minimal change disease (80%), post-streptococcal GN.
• Adults 20-40: IgA nephropathy, FSGS, lupus nephritis.
• Adults 40-60: Membranous nephropathy, FSGS.
• Elderly > 60: ANCA-associated GN, membranous (malignancy-associated).

Sex Distribution:

• Male predominance: IgA nephropathy (2:1 M:F), FSGS (1.5:1), ANCA vasculitis (slight male excess).
• Female predominance: Lupus nephritis (9:1 F:M), minimal change disease in adults (slight female excess).

Ethnicity:

• IgA Nephropathy: Highest in Asians (40-50% primary GN), intermediate in Caucasians (30%), lowest in Africans (less than 5%).
• FSGS: 4-5 times higher in African Americans (genetic association with APOL1 gene variants). [14]
• Membranous: More common in Caucasians.

Risk Factors

3. Aetiology & Pathophysiology

Classification by Immunopathogenesis

Glomerulonephritis is fundamentally an immune-mediated disease. Three major immunological mechanisms underlie most forms:

1. Immune Complex-Mediated GN

Mechanism:

• Circulating immune complexes (antigen-antibody) or in situ immune complex formation.
• Deposition in glomerular capillaries (subendothelial, subepithelial, mesangial).
• Complement activation (classical pathway: C1q → C3 → C5-9 membrane attack complex).
• Neutrophil and macrophage recruitment → inflammatory mediator release.
• Glomerular injury: basement membrane damage, podocyte foot process effacement, capillary wall disruption.

Immunofluorescence Pattern: Granular ("starry sky") deposition of IgG, IgA, IgM, and/or C3.

Examples:

• Post-streptococcal GN: Streptococcal antigens (nephritis-associated plasmin receptor, streptococcal pyrogenic exotoxin B) form immune complexes with IgG. Subepithelial "humps" on electron microscopy. Low C3, normal C4 (alternative pathway). [15]
• IgA Nephropathy: Galactose-deficient IgA1 (Gd-IgA1) forms circulating complexes → mesangial deposition. Mesangial IgA dominant on immunofluorescence. Associated with mucosal infections (URTI). [16]
• Lupus Nephritis: Anti-dsDNA antibodies, nucleosomal antigens form complexes. Variable patterns (mesangial, subendothelial, subepithelial). Low C3 and C4. [17]
• Membranoproliferative GN (MPGN): Type I (immune complex), Type II (dense deposit disease/C3 glomerulopathy). Associated with hepatitis C, cryoglobulinemia. [18]
• Membranous Nephropathy: 70% idiopathic (anti-PLA2R antibodies in 70-80% of primary cases). Subepithelial immune deposits form in situ (antigen on podocyte foot processes). "Spike and dome" appearance. [19]

2. Anti-Glomerular Basement Membrane (Anti-GBM) Disease

Mechanism (Type II Hypersensitivity):

• Autoantibodies against α3 chain of type IV collagen in glomerular basement membrane.
• Linear binding along GBM → complement activation → neutrophil-mediated injury.
• Pulmonary basement membranes also targeted → alveolar hemorrhage (Goodpasture syndrome).

Immunofluorescence Pattern: Linear IgG deposition along GBM (pathognomonic).

Electron Microscopy: No electron-dense deposits (antibody against structural component).

Clinical Features:

• Rapidly progressive GN (90% have crescents on biopsy).
• Pulmonary hemorrhage (50-60% of cases).
• Bimodal age distribution: peaks at 20-30 years and 60-70 years.
• Associated with smoking, pulmonary infection, hydrocarbon exposure. [20]

3. Pauci-Immune (ANCA-Associated) GN

Mechanism:

• Anti-neutrophil cytoplasmic antibodies (ANCA) target myeloperoxidase (MPO) or proteinase 3 (PR3).
• ANCA binds primed neutrophils → degranulation → release of reactive oxygen species, proteases.
• Necrotizing small-vessel vasculitis → glomerular capillary necrosis → crescent formation.

Immunofluorescence Pattern: Pauci-immune (little to no immune complex deposition).

ANCA Patterns:

• c-ANCA (cytoplasmic): Anti-PR3 antibodies → Granulomatosis with polyangiitis (GPA, formerly Wegener's).
• p-ANCA (perinuclear): Anti-MPO antibodies → Microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss).

Clinical Features:

• Rapidly progressive GN (50-80% have crescents).
• Systemic vasculitis: pulmonary hemorrhage, sinusitis, skin vasculitis, neuropathy.
• 10% are ANCA-negative (diagnose by histology + clinical syndrome). [21]

Exam Detail: ### Molecular Pathophysiology (Advanced)

Podocyte Biology in Glomerular Disease:

• Podocytes are highly differentiated epithelial cells with foot processes that form the filtration barrier.
• Podocyte injury → foot process effacement → proteinuria.
• Podocyte loss: Cannot regenerate; loss > 20% → FSGS progression.
• Key proteins: Nephrin, podocin (NPHS2), α-actinin-4 (mutations cause familial FSGS).

Complement Dysregulation:

• Classical pathway (C1q → C4 → C3): SLE, post-streptococcal GN.
• Alternative pathway (C3 direct activation): C3 glomerulopathy, atypical MPGN.
• Terminal pathway (C5b-9): Membrane attack complex formation → cell lysis.
• Therapeutic target: Eculizumab (anti-C5 antibody) for atypical hemolytic uremic syndrome, C3 glomerulopathy.

Cytokine and Chemokine Networks:

• IL-1, TNF-α, IL-6: Promote mesangial cell proliferation, matrix deposition.
• TGF-β: Profibrotic cytokine → glomerulosclerosis, interstitial fibrosis.
• VEGF: Dysregulation in diabetic nephropathy, preeclampsia.

Genetic Susceptibility:

• IgA Nephropathy: GWAS identified > 20 loci (HLA-DQ, complement factor H).
• FSGS: APOL1 G1/G2 variants (African ancestry), NPHS2 mutations, INF2, TRPC6.
• Membranous: HLA-DQA1 (primary), association with PLA2R polymorphisms.

Histopathological Classification

Clinical Syndromes

Nephritic Syndrome:

• Hallmarks: Hematuria (dysmorphic RBCs, red cell casts), hypertension, oliguria, edema, mild proteinuria (less than 3 g/day).
• Pathophysiology: Inflammatory glomerular injury → impaired GFR → salt/water retention → hypertension, edema.
• Examples: Post-streptococcal GN, IgA nephropathy, RPGN, lupus nephritis (proliferative).

Nephrotic Syndrome:

• Hallmarks: Heavy proteinuria (> 3.5 g/day), hypoalbuminemia (less than 30 g/L), edema, hyperlipidemia.
• Pathophysiology: Loss of glomerular charge selectivity → albumin leak → hypoalbuminemia → reduced oncotic pressure → edema + compensatory hepatic lipoprotein synthesis.
• Examples: Minimal change disease, membranous GN, FSGS, diabetic nephropathy.
• Complications: Thromboembolism (loss of antithrombin III, protein C/S), infection (loss of immunoglobulins), hyperlipidemia (atherogenic).

Mixed Nephritic-Nephrotic:

• Some GN presents with features of both syndromes.
• Examples: Lupus nephritis, MPGN, severe IgA nephropathy with crescents.

Rapidly Progressive Glomerulonephritis (RPGN):

• Definition: Rapid decline in GFR (50% increase in creatinine within 3 months).
• Histology: Crescents in > 50% of glomeruli (epithelial cell proliferation in Bowman's space).
• Three types: Type I (anti-GBM, 10-20%), Type II (immune complex, 40-50%), Type III (pauci-immune/ANCA, 40-50%). [9]

4. Clinical Presentation

Symptoms

Nephritic Syndrome Presentation:

• Macroscopic hematuria: "Cola-colored," "tea-colored," or "smoky" urine. Suggests active glomerular inflammation.
• Oliguria: Reduced urine output (less than 400 mL/day). Reflects impaired GFR.
• Fluid retention: Periorbital edema (morning), pedal edema, dyspnea (pulmonary edema).
• Hypertension symptoms: Headache, visual disturbance, nausea.
• Malaise, fatigue: Systemic inflammatory response.

Nephrotic Syndrome Presentation:

• Frothy urine: Reflects heavy proteinuria.
• Edema: Periorbital edema (characteristic, especially morning), pedal edema, ascites, pleural effusion (severe cases).
• Fatigue, malaise: Hypoalbuminemia, anemia.
• Increased infections: Loss of immunoglobulins (particularly IgG).
• Thrombotic events: Deep vein thrombosis, pulmonary embolism, renal vein thrombosis (sudden flank pain, hematuria).

Rapidly Progressive GN (RPGN) Presentation:

• Rapidly declining renal function: Days to weeks.
• Oliguria/anuria: Severe cases.
• Malaise, nausea, vomiting: Uremic symptoms.
• Hemoptysis: Pulmonary-renal syndrome (GPA, anti-GBM, SLE).

Systemic Features (Suggest Secondary GN):

• Rash: Malar rash (SLE), palpable purpura (IgA vasculitis/Henoch-Schönlein purpura, cryoglobulinemia), vasculitic lesions (ANCA vasculitis).
• Arthralgia/Arthritis: SLE, post-streptococcal GN, reactive arthritis.
• Hemoptysis: Pulmonary-renal syndrome (GPA, anti-GBM, MPA, SLE).
• Sinusitis, nasal crusting, epistaxis: GPA (c-ANCA).
• Peripheral neuropathy: ANCA vasculitis, cryoglobulinemia.
• Fever: Infection-related GN, SLE, vasculitis.

Signs

General Inspection:

• Hypertension: Essential for diagnosis of nephritic syndrome.
• Pallor: Anemia (CKD, hemolysis in SLE).

Cardiovascular:

• Hypertension: Present in 80% of nephritic syndrome. May be severe (hypertensive emergency).
• Jugular venous pressure (JVP): Elevated (fluid overload).
• Heart sounds: S3 gallop (fluid overload, heart failure).
• Peripheral edema: Pitting edema (legs, sacrum).

Respiratory:

• Crackles: Pulmonary edema (fluid overload).
• Hemoptysis: Pulmonary-renal syndrome.
• Pleural effusion: Severe nephrotic syndrome.

Skin:

• Palpable purpura: IgA vasculitis (Henoch-Schönlein purpura), cryoglobulinemia.
• Malar rash: SLE (butterfly distribution).
• Vasculitic lesions: ANCA vasculitis (necrotic skin lesions).

Abdominal:

• Ascites: Severe nephrotic syndrome (hypoalbuminemia).

Joints:

• Arthritis: SLE, post-streptococcal reactive arthritis.

Differential Diagnosis

Approach: Distinguish GN from other causes of hematuria, proteinuria, and AKI.

Key Differentiating Features:

Critical Point: Red cell casts are pathognomonic for glomerulonephritis. Their presence mandates further investigation for GN.

5. Clinical Examination

Structured Approach (OSCE/PACES)

Introduction: "I would like to examine this patient with suspected glomerulonephritis. I will assess volume status, look for signs of renal impairment and systemic features suggesting secondary causes."

General Inspection:

• Pallor (anemia).
• Respiratory distress (pulmonary edema).

Vital Signs:

• Blood pressure: Hypertension (nephritic syndrome).
• Pulse: Volume status assessment.
• Respiratory rate: Pulmonary edema, metabolic acidosis (Kussmaul breathing).

Cardiovascular Examination:

• JVP: Elevated (fluid overload).
• Heart sounds: S3 gallop, murmurs (endocarditis → GN).
• Peripheral pulses: Vascular disease (atherosclerosis in CKD).

Respiratory Examination:

• Crackles: Bibasal (pulmonary edema).
• Hemoptysis: Pulmonary-renal syndrome.
• Pleural effusion: Dullness to percussion, reduced breath sounds.

Abdominal Examination:

• Ascites: Shifting dullness, fluid thrill.
• Palpable kidneys: Enlarged (polycystic kidney disease, hydronephrosis), small (CKD).
• Renal bruit: Renal artery stenosis.

Skin Examination:

• Rashes: Malar rash (SLE), palpable purpura (vasculitis), vasculitic lesions.
• Nail changes: Leukonychia (hypoalbuminemia in nephrotic syndrome).

Joint Examination:

• Arthritis: SLE, post-streptococcal reactive arthritis.

Neurological Examination (if systemic vasculitis suspected):

• Peripheral neuropathy: ANCA vasculitis, cryoglobulinemia.
• Mononeuritis multiplex: Vasculitis.

To Complete Examination:

• "I would like to perform urinalysis and urine microscopy, check blood pressure, review recent creatinine trends, and examine for signs of systemic disease."

6. Investigations

Bedside Tests

Urinalysis (Dipstick):

• Blood: +++ to ++++ (hematuria). Universal in GN.
• Protein: + to ++++ (proteinuria). Quantify with PCR or 24-hour collection.
• Leukocytes: May be positive (sterile pyuria in TIN, GN with inflammation).
• Glucose: Exclude diabetic nephropathy.

Urine Microscopy (Critical):

• Dysmorphic RBCs: Glomerular origin (vs. non-dysmorphic from lower urinary tract). Sensitivity 70-90%. [22]
• Red cell casts: Pathognomonic for GN. Formed when RBCs traverse inflamed tubules. Diagnostic specificity > 95%.
• White cell casts: Active glomerular inflammation, lupus nephritis.
• Granular casts: Non-specific; suggest tubular injury.

Laboratory Investigations

Blood Tests:

Renal Function:

• Urea & Electrolytes (U&E): Elevated creatinine (AKI/CKD), urea (reflects GFR and catabolic state).
• eGFR: Assess severity of renal impairment. CKD staging: G1 (≥90), G2 (60-89), G3a (45-59), G3b (30-44), G4 (15-29), G5 (less than 15 mL/min/1.73m²).
• Bicarbonate: Metabolic acidosis (advanced CKD).

Full Blood Count (FBC):

• Anemia: Normocytic normochromic (CKD, chronic disease). Microangiopathic hemolytic anemia (TMA).
• Leukocytosis: Infection (post-streptococcal GN), active SLE.
• Thrombocytopenia: SLE, TMA.

Albumin:

• less than 30 g/L: Diagnostic of nephrotic syndrome (in context of proteinuria > 3.5 g/day).

Lipid Profile:

• Hyperlipidemia: Characteristic of nephrotic syndrome (compensatory hepatic synthesis).

Complement Levels (Critical for Diagnosis):

• Low C3 + Low C4: SLE, post-streptococcal GN (classical pathway), cryoglobulinemia.
• Low C3, Normal C4: Alternative pathway activation → Post-streptococcal GN (late phase), MPGN type II (C3 glomerulopathy), shunt nephritis.
• Normal C3 + C4: ANCA vasculitis, anti-GBM disease, IgA nephropathy, minimal change, FSGS, membranous.

Immunology Panel:

Serology for Infectious Causes:

• Hepatitis B Surface Antigen (HBsAg): Membranous GN, polyarteritis nodosa.
• Hepatitis C Antibody: MPGN, cryoglobulinemic GN.
• HIV: HIV-associated nephropathy (HIVAN, FSGS pattern), immune complex GN.

Urine Tests:

Quantification of Proteinuria:

• Spot Urine Protein:Creatinine Ratio (PCR): Preferred (correlates with 24-hour protein).
  • "Nephrotic range: PCR > 350 mg/mmol (or > 3.5 g/day)."
  • "Nephritic range: PCR less than 300 mg/mmol."
• 24-Hour Urine Protein: Gold standard but cumbersome. > 3.5 g/day = nephrotic range.

Imaging

Renal Ultrasound:

• Indications: All patients with suspected GN (baseline assessment).
• Findings:
  • "Kidney size: Normal (10-12 cm). Small kidneys (less than 9 cm) suggest chronic disease (CKD) → biopsy may not change management."
  • "Echogenicity: Increased echogenicity (chronic scarring)."
  • "Exclude obstruction: Hydronephrosis."
  • Assess for masses, cysts (polycystic kidney disease).

Chest X-Ray:

• Pulmonary edema: Fluid overload.
• Pulmonary hemorrhage: GPA, anti-GBM disease (diffuse alveolar shadowing).
• Assess for infections: Immunosuppressed patients.

CT Chest (if pulmonary-renal syndrome suspected):

• Diffuse alveolar hemorrhage (ground-glass opacities).
• Cavitating lesions: GPA.

Renal Biopsy (Gold Standard Diagnosis)

Indications:

1. Unexplained AKI with glomerular features (hematuria, proteinuria, RBC casts).
2. Nephrotic syndrome (adults; children with atypical features).
3. Rapidly progressive GN (urgent within 24-48 hours).
4. Persistent proteinuria > 1 g/day without clear cause.
5. Lupus nephritis (for classification and prognosis).

Contraindications (Relative):

• Uncontrolled hypertension (BP > 160/100 mmHg).
• Bleeding diathesis (platelets less than 50,000, INR > 1.5).
• Single functioning kidney.
• Small kidneys (less than 8 cm, advanced CKD) → low diagnostic yield, high complication risk.
• Uncooperative patient.

Technique:

• Percutaneous needle biopsy: Ultrasound or CT-guided. 16-18 gauge needle.
• Adequacy: Minimum 8-10 glomeruli for light microscopy, 2 cores for immunofluorescence and electron microscopy.

Analysis (Three Modalities):

1. Light Microscopy (LM):

   • Hematoxylin & Eosin (H&E): Cellularity, necrosis, crescents.
   • Periodic Acid-Schiff (PAS): Basement membrane, mesangium.
   • Silver stain: GBM outline ("spike and dome" in membranous GN).
   • Trichrome: Fibrosis, sclerosis.

2. Immunofluorescence (IF):

   • Direct immunofluorescence for IgG, IgA, IgM, C3, C1q, κ/λ light chains.
   • Patterns:
     • Linear IgG: Anti-GBM disease.
     • Granular IgG/IgA/C3: Immune complex GN.
     • Mesangial IgA dominant: IgA nephropathy (diagnostic).
     • Pauci-immune (negative/trace): ANCA vasculitis.

3. Electron Microscopy (EM):

   • Electron-dense deposit location:
     • Subepithelial: Membranous GN, post-streptococcal GN ("humps").
     • Subendothelial: SLE, MPGN.
     • Mesangial: IgA nephropathy, SLE.
   • Foot process effacement: Minimal change disease, FSGS.
   • GBM thickness, lamellation.

Complications:

• Hematuria (macroscopic): 5-10% (usually self-limiting).
• Perinephric hematoma: 10-15% (most asymptomatic).
• Transfusion-requiring bleeding: 0.5-1%.
• Nephrectomy/arterial embolization: less than 0.1%.

Exam Detail: ### Diagnostic Algorithm for GN

Step 1: Urinalysis + Microscopy → Confirm glomerular hematuria (dysmorphic RBCs, RBC casts).

Step 2: Quantify proteinuria (PCR or 24-hour urine) → Classify as nephritic (less than 3.5 g/day) or nephrotic (> 3.5 g/day).

Step 3: Assess renal function (creatinine, eGFR) → Identify AKI, RPGN, CKD.

Step 4: Serological workup:

• All patients: Complement (C3, C4), ANCA, anti-GBM, ANA.
• If low complement: Consider SLE (anti-dsDNA), post-streptococcal GN (ASO titre), cryoglobulins.
• If nephrotic: Anti-PLA2R (membranous), serum free light chains (amyloid).
• If systemic features: Hepatitis B/C, HIV, ANA/dsDNA (SLE).

Step 5: Imaging (renal ultrasound) → Assess kidney size, exclude obstruction.

Step 6: Renal biopsy (if diagnosis unclear or RPGN) → Definitive histological diagnosis.

7. Classification & Staging

RPGN Classification (Immunopathology)

Lupus Nephritis Classification (ISN/RPS 2003, Revised 2018)

IgA Nephropathy (Oxford Classification - MEST-C Score)

Prognostic histological features:

• M: Mesangial hypercellularity (> 50% glomeruli with > 3 mesangial cells).
• E: Endocapillary hypercellularity.
• S: Segmental glomerulosclerosis.
• T: Tubular atrophy/interstitial fibrosis (T0: less than 25%; T1: 25-50%; T2: > 50%).
• C: Crescents (C0: none; C1: less than 25%; C2: ≥25%).

Higher scores (particularly T2, C2) predict progression to ESRD. [16]

8. Management

General Principles

Urgent Management:

• RPGN: Urgent renal biopsy (within 24-48 hours) + empirical immunosuppression if high suspicion.
• Pulmonary-renal syndrome: ICU admission, plasmapheresis + immunosuppression.
• Severe fluid overload: Loop diuretics, dialysis (ultrafiltration).
• Hypertensive emergency: IV antihypertensives (labetalol, nicardipine), avoid rapid BP drops.

Supportive Management (All GN):

1. Blood Pressure Control: Target less than 130/80 mmHg (KDIGO 2021). [1]
2. Proteinuria Reduction: ACE inhibitor or ARB (first-line).
3. Fluid and Salt Management: Sodium restriction less than 2 g/day.
4. Diuretics: Loop diuretics (furosemide) for edema.
5. CKD Complications: Treat anemia (ESAs, iron), bone disease (vitamin D, phosphate binders), metabolic acidosis (bicarbonate).

Management Algorithm

       [SUSPECTED GLOMERULONEPHRITIS]
                   ↓
         ┌─────────────────────┐
         │  Urinalysis         │
         │  (Dysmorphic RBCs,  │
         │   RBC casts)        │
         │  + Creatinine       │
         └──────────┬──────────┘
                    ↓
          Confirm GN Features
                    │
         ┌──────────┴──────────┐
         │                     │
     NEPHRITIC              NEPHROTIC
     (Hematuria,            (Proteinuria > 3.5g,
      HTN, ↓GFR,             Hypoalbuminemia,
      less than 3g protein/day)       Edema, Hyperlipidemia)
         │                     │
         ↓                     ↓
  Is it RPGN?            Serology + Imaging
  (Cr ↑50% in 3mo,           │
   Oliguria)                 ↓
         │               RENAL BIOPSY
    ┌────┴────┐          (Determine type)
   YES       NO               │
    │         │               ↓
    ↓         ↓          ┌────────────────┐
  URGENT   Serology     │ Histology:     │
  BIOPSY   + Biopsy     │ - Minimal      │
    │                   │ - FSGS         │
    ↓                   │ - Membranous   │
  Check Type:          │ - IgA          │
  - ANCA               └─────┬──────────┘
  - Anti-GBM                 │
  - Complement               ↓
    │                   SPECIFIC
    ↓                   TREATMENT
  ┌────────────────────┐
  │ IMMUNOSUPPRESSION  │
  │                    │
  │ Type I (Anti-GBM): │
  │ - Plasmapheresis   │
  │ - Cyclophosphamide │
  │ - Methylpred       │
  │                    │
  │ Type II (Immune):  │
  │ - Treat underlying │
  │   (SLE: MMF/Cyclo) │
  │                    │
  │ Type III (ANCA):   │
  │ - Rituximab OR     │
  │   Cyclophosphamide │
  │ - Methylpred       │
  └────────────────────┘

Specific Immunosuppressive Regimens

1. Post-Streptococcal GN

Principle: Self-limiting; supportive care only.

Management:

• Antibiotics: Penicillin V 500 mg QDS × 10 days (if active infection or positive throat swab). Does NOT alter GN course but prevents transmission.
• Blood pressure control: ACEi/ARB, diuretics (fluid overload).
• Salt restriction: less than 2 g/day.
• Prognosis: 95% complete recovery in children; 50-70% in adults (higher risk of chronic sequelae). [13]

2. IgA Nephropathy

Risk Stratification:

• Low risk (proteinuria less than 0.5 g/day, normal eGFR, minimal histology): ACEi/ARB + BP control. Monitor.
• Moderate risk (proteinuria 0.5-1 g/day): Optimize RAAS blockade (max-tolerated ACEi/ARB). Consider SGLT2 inhibitor.
• High risk (proteinuria > 1 g/day despite RAAS blockade, declining eGFR):
  • "Steroids: Methylprednisolone 0.6-0.8 mg/kg/day (max 48 mg) on alternate days × 2 months, then taper over 4-6 months. [23]"
  • "Caution: STOP-IgAN trial (2015) showed no benefit of immunosuppression vs. RAAS blockade alone, but significant steroid side effects. Current approach: Reserve for progressive disease. [24]"
• RPGN/Crescentic IgA: Methylprednisolone IV 500 mg-1 g × 3 days, then oral prednisolone + cyclophosphamide.

Adjunctive:

• Omega-3 fatty acids: 4 g/day (anti-inflammatory). Modest benefit in some trials.
• Tonsillectomy: Controversial; some Asian studies suggest benefit in recurrent URTI-triggered hematuria.

3. Minimal Change Disease

First-Line:

• Prednisolone: 1 mg/kg/day (max 80 mg) for 4-8 weeks (until remission + 2 weeks), then taper over 6 months.
• Remission: 80-90% achieve complete remission within 8-12 weeks. [8]
• Relapse: 30-50% relapse after steroid withdrawal.

Relapse Management:

• Repeat steroids (often responsive).
• Frequent relapses/steroid-dependent:
  • "Calcineurin inhibitors: Tacrolimus 0.05-0.1 mg/kg/day (target trough 5-10 ng/mL) OR Ciclosporin 3-5 mg/kg/day."
  • "Rituximab: 375 mg/m² weekly × 4 doses (steroid-sparing, effective in 60-70%). [25]"

4. Membranous Nephropathy

Risk Stratification:

• Low risk (non-nephrotic, proteinuria less than 4 g/day, stable eGFR): Conservative management (ACEi/ARB, monitor). 30% spontaneous remission. [19]

• High risk (nephrotic syndrome, proteinuria > 8 g/day, declining eGFR, anti-PLA2R > 150 RU/mL):

  First-Line (MENTOR Trial 2019): [7]

  • "Rituximab: 1 g IV on days 1 and 15 (single course). Repeat at 6 months if no response."
  • "Outcome: 60% complete remission vs. 20% with ciclosporin."
  • "Advantage: Better long-term remission, less toxicity than cyclophosphamide."

  Alternative (Ponticelli Regimen):

  • "Alternating monthly cycles of:"
    • Months 1, 3, 5: Methylprednisolone IV 1 g × 3 days, then oral prednisolone 0.4 mg/kg/day.
    • Months 2, 4, 6: Cyclophosphamide 2 mg/kg/day PO OR Chlorambucil 0.15 mg/kg/day.
  • "Remission: 60-70% at 12 months. Risk: Infection, malignancy."

Monitoring: Anti-PLA2R titre correlates with disease activity; falling titre predicts remission.

5. Focal Segmental Glomerulosclerosis (FSGS)

Primary FSGS:

• First-Line: Prednisolone 1 mg/kg/day (max 80 mg) for 16 weeks (extended trial). Taper if remission achieved.
• Remission: 30-50% (lower than minimal change disease). May take 16 weeks (vs. 8 weeks in MCD). [26]

Steroid-Resistant FSGS:

• Calcineurin inhibitors: Ciclosporin or tacrolimus.
• Mycophenolate mofetil: Alternative (less effective).
• Prognosis: Steroid-resistant FSGS has 50-60% risk of ESRD at 10 years.

Secondary FSGS (HIV, obesity, reflux nephropathy):

• Treat underlying cause.
• ACEi/ARB to reduce proteinuria.

6. Rapidly Progressive Glomerulonephritis (RPGN)

Type I (Anti-GBM Disease):

Induction:

• Plasmapheresis: Daily exchanges (60 mL/kg per session) for 10-14 days. Remove circulating anti-GBM antibodies.
• Cyclophosphamide: 2-3 mg/kg/day PO OR 15 mg/kg IV pulse monthly.
• Methylprednisolone: IV 500 mg-1 g × 3 days, then prednisolone 1 mg/kg/day, taper.
• Duration: Continue until anti-GBM antibodies undetectable (usually 3-6 months).

Prognosis:

• With plasmapheresis + immunosuppression: 50-60% renal survival (if creatinine less than 500 µmol/L at presentation).
• Without plasmapheresis: > 80% progress to ESRD. [20]
• If dialysis-dependent at presentation: less than 10% renal recovery.

Type III (Pauci-Immune/ANCA-Associated):

Induction (PEXIVAS Trial 2020): [27]

• Rituximab: 375 mg/m² IV weekly × 4 doses (or 1 g on days 1 and 15).
  • "OR Cyclophosphamide: 15 mg/kg IV every 2 weeks × 3 doses, then every 3 weeks (total 6 doses). Oral cyclophosphamide 2 mg/kg/day is alternative."
• Glucocorticoids:
  • "Standard dose: Methylprednisolone IV 500 mg-1 g × 3 days, then prednisolone 1 mg/kg/day, taper to 5 mg by 6 months."
  • "Reduced dose (PEXIVAS): Lower cumulative dose (no IV pulses); equivalent efficacy with fewer infections."
• Plasmapheresis: PEXIVAS trial showed NO benefit in ESRD/mortality. Not routinely recommended unless severe pulmonary hemorrhage.

Maintenance:

• Rituximab: 500 mg IV every 6 months for 18-24 months.
  • "OR Azathioprine: 2 mg/kg/day (older regimen; rituximab superior in MAINRITSAN trial). [28]"
• Low-dose prednisolone: 5-10 mg/day for 12-18 months.

Prognosis:

• With treatment: 80-90% remission; 50% relapse at 5 years (higher with c-ANCA/PR3).
• Without treatment: > 80% ESRD within 2 years.

Type II (Immune Complex RPGN):

• Treat underlying cause:
  • "Lupus nephritis Class III/IV: See below."
  • "Post-infectious: Supportive, antibiotics."
  • "IgA nephropathy with crescents: Steroids + cyclophosphamide (as above)."

7. Lupus Nephritis (Class III/IV)

Induction (EULAR/ERA-EDTA 2019): [29]

• Mycophenolate mofetil (MMF): 2-3 g/day PO in divided doses × 6 months.
  • "OR Cyclophosphamide: Euro-Lupus regimen (500 mg IV every 2 weeks × 6 doses) preferred over NIH high-dose regimen (lower toxicity, equivalent efficacy)."
• Glucocorticoids: Methylprednisolone IV 500 mg × 3 days, then prednisolone 0.5-1 mg/kg/day, taper to less than 7.5 mg by 6 months.

Maintenance:

• Mycophenolate mofetil: 1-2 g/day (preferred) OR Azathioprine 2 mg/kg/day.
• Hydroxychloroquine: 200-400 mg/day (all SLE patients; reduces flares).
• Duration: Minimum 3 years; lifelong if relapse history.

Prognosis:

• 10-year renal survival: 80-90% with treatment.
• Relapse rate: 30-50% at 10 years.

Supportive Pharmacotherapy

Blood Pressure & Proteinuria Reduction:

• ACE Inhibitors: Ramipril 2.5-10 mg OD, enalapril 5-20 mg OD.
  • "OR ARBs: Losartan 25-100 mg OD, irbesartan 150-300 mg OD."
• Target BP: less than 130/80 mmHg (KDIGO 2021). less than 120/75 if proteinuria > 1 g/day. [1]
• Proteinuria reduction: 30-50% with RAAS blockade. Slows CKD progression.
• Monitoring: Creatinine, potassium (risk of hyperkalemia, AKI).

SGLT2 Inhibitors:

• Dapagliflozin 10 mg OD, empagliflozin 10 mg OD.
• Indication: CKD with eGFR ≥20 mL/min, proteinuria (with or without diabetes).
• Benefit: Reduces proteinuria, slows eGFR decline, cardiovascular protection (DAPA-CKD trial). [30]

Diuretics:

• Loop diuretics: Furosemide 40-120 mg OD (edema, fluid overload).
• Thiazides: Ineffective if eGFR less than 30 mL/min.

Anticoagulation (Nephrotic Syndrome):

• Indication: Albumin less than 20 g/L (high thrombotic risk).
• Options: Prophylactic LMWH (enoxaparin 40 mg SC OD) OR warfarin (target INR 2-3).
• Duration: While albumin less than 20 g/L.

Statins:

• Indication: Nephrotic syndrome, CKD (cardiovascular risk reduction).
• Drug: Atorvastatin 20-80 mg OD.

Infection Prophylaxis (Immunosuppressed Patients):

• Pneumocystis jirovecii prophylaxis: Co-trimoxazole 480 mg OD (if on cyclophosphamide, rituximab, high-dose steroids).
• Vaccinations: Pneumococcal (PCV13 + PPSV23), influenza (annual), avoid live vaccines if immunosuppressed.

Renal Replacement Therapy

Indications for Dialysis:

• Severe uremia (pericarditis, encephalopathy, neuropathy).
• Refractory fluid overload (pulmonary edema).
• Severe metabolic acidosis (pH less than 7.1).
• Hyperkalemia (> 6.5 mmol/L, ECG changes).
• eGFR less than 10 mL/min with symptoms.

Modalities:

• Hemodialysis: Thrice-weekly; acute setting.
• Peritoneal dialysis: Continuous ambulatory (CAPD); suitable for stable patients.

Kidney Transplantation:

• Eligibility: ESRD secondary to GN.
• Recurrence risk: Varies by GN type (FSGS 30-50%, IgA nephropathy 30-40%, membranous 10-30%, anti-GBM less than 5%).
• Outcomes: 5-year graft survival 70-80%.

9. Complications

Acute Complications

Acute Kidney Injury:

• Rapidly declining GFR → uremia, oliguria.
• Management: Optimize hemodynamics, avoid nephrotoxins, consider dialysis.

Pulmonary Edema:

• Fluid overload (nephritic syndrome, ESRD).
• Management: IV furosemide (80-250 mg), oxygen, sit upright, consider dialysis (ultrafiltration).

Hypertensive Emergency:

• Severe hypertension (> 180/120 mmHg) with end-organ damage (encephalopathy, pulmonary edema, AKI).
• Management: IV labetalol, nicardipine, nitroprusside. Target 10-20% BP reduction in first hour (avoid precipitous drops → ischemia).

Thromboembolism (Nephrotic Syndrome):

• Incidence: 10-40% (DVT, PE, renal vein thrombosis). [12]
• Mechanism: Loss of antithrombin III, protein C/S, increased fibrinogen, platelet hyperactivity.
• Renal vein thrombosis: Acute flank pain, worsening proteinuria, hematuria. Diagnose with Doppler US/CT.
• Management: Anticoagulation (LMWH, warfarin). Prophylaxis if albumin less than 20 g/L.

Infection (Nephrotic Syndrome):

• Loss of IgG, complement factors → increased susceptibility.
• Common infections: Spontaneous bacterial peritonitis (S. pneumoniae, E. coli), cellulitis, pneumonia.
• Management: Prompt antibiotics, prophylactic pneumococcal vaccination.

Acute Tubular Necrosis (ATN):

• Superimposed on GN (hypotension, nephrotoxins).
• Diagnosis: Muddy brown casts, FENa > 2%.

Chronic Complications

GN-Specific Complication Rates

IgA Nephropathy:

• 15-20% progress to ESRD at 10 years; 30-40% at 20 years. [16]
• Worse prognosis: Crescents, proteinuria > 1 g/day, hypertension, eGFR less than 30 at presentation.

FSGS:

• 50-60% progress to ESRD within 10 years (primary FSGS).
• Steroid-resistant: 70-80% ESRD.

Membranous Nephropathy:

• Rule of thirds: 1/3 spontaneous remission, 1/3 stable, 1/3 progress to ESRD. [19]
• Worse prognosis: Male sex, older age, proteinuria > 8 g/day, hypertension, impaired renal function at diagnosis.

RPGN:

• Without treatment: 80-90% progress to ESRD within 6-12 months.
• With treatment: 50% ESRD at 5 years (pauci-immune), 20-30% (anti-GBM if treated early). [9]

10. Prognosis & Outcomes

Prognosis by GN Type

Predictors of Poor Outcome (All GN)

Clinical:

• Elevated creatinine at presentation (eGFR less than 30 mL/min).
• Severe proteinuria (> 3.5 g/day, nephrotic range).
• Hypertension (uncontrolled).
• Older age (> 60 years).

Histological:

• Crescents: > 50% glomeruli with crescents (RPGN).
• Glomerulosclerosis: > 25% globally sclerosed glomeruli.
• Interstitial fibrosis/tubular atrophy: > 25% (irreversible).
• Arteriosclerosis: Vascular disease.

Immunological:

• Persistent ANCA or anti-GBM positivity (active disease).
• Persistent low complement (SLE, ongoing immune complex deposition).
• High anti-PLA2R titre in membranous GN.

Treatment Response:

• Steroid resistance: Particularly in FSGS, minimal change disease.
• Incomplete remission: Persistent proteinuria > 1 g/day despite treatment.
• Relapse: Frequent relapses predict long-term CKD progression.

Long-Term Monitoring

All patients with GN:

• Creatinine/eGFR: 3-6 monthly (stable CKD), more frequent if deteriorating.
• Urinalysis + PCR: 3-6 monthly (monitor proteinuria).
• Blood pressure: Every visit.
• Surveillance for relapse: Clinical (edema, hematuria), serological (ANCA, anti-dsDNA, complement).

Post-immunosuppression:

• Monitor for infection, malignancy (skin cancer surveillance if cyclophosphamide).
• Bone health: DEXA scan if prolonged steroids, bisphosphonates if osteoporosis.

11. Prevention & Screening

Primary Prevention

Modifiable Risk Factors:

• Infection control: Prompt treatment of streptococcal infections (pharyngitis, impetigo) → prevents post-streptococcal GN.
• Vaccination: Hepatitis B vaccine (prevents HBV-associated membranous GN).
• Avoid nephrotoxins: NSAIDs (minimal change, membranous GN), heroin (FSGS).

Population Screening: Not recommended for asymptomatic individuals.

High-Risk Groups (Screening Recommended):

• SLE patients: Annual urinalysis + PCR (detect lupus nephritis early).
• ANCA-positive patients: Monitor creatinine, urinalysis for GN development.
• Family history of IgA nephropathy: Urinalysis if hematuria episodes.

Secondary Prevention (Prevent Progression)

Optimize RAAS Blockade:

• ACEi/ARB to target proteinuria less than 0.5 g/day.
• SGLT2 inhibitor (added benefit in CKD with proteinuria).

Blood Pressure Control:

• Target less than 130/80 mmHg (KDIGO 2021); less than 120/75 if proteinuria > 1 g/day.

Lifestyle:

• Sodium restriction (less than 2 g/day).
• Smoking cessation (reduces CKD progression).
• Weight loss (obesity-related FSGS).
• Avoid NSAIDs, nephrotoxic drugs.

Treat Underlying Causes:

• Control SLE activity (lupus nephritis).
• Antiretroviral therapy (HIV-associated nephropathy).
• Antiviral therapy for hepatitis B/C.

12. Key Guidelines

KDIGO 2021 Clinical Practice Guideline for Management of Glomerular Diseases: [1]

• Comprehensive GN management (all subtypes).
• Recommendations: ACEi/ARB for proteinuria, BP target less than 130/80, immunosuppression protocols.

KDIGO 2012 Glomerulonephritis Guideline: [31]

• Specific recommendations for IgA nephropathy, FSGS, membranous GN, lupus nephritis, ANCA vasculitis.

EULAR/ERA-EDTA 2019 Lupus Nephritis Guideline: [29]

• Mycophenolate preferred over cyclophosphamide for induction (Class III/IV).
• Maintenance: MMF preferred over azathioprine.

British Society for Rheumatology (BSR) 2020 ANCA-Associated Vasculitis Guideline:

• Rituximab preferred over cyclophosphamide for induction.
• Reduced-dose glucocorticoid regimen (lower infection risk).

13. Exam-Focused Content

Common Viva Questions

Q1: "Differentiate nephritic from nephrotic syndrome."

Model Answer: "Nephritic syndrome is characterized by glomerular inflammation presenting with hematuria (particularly dysmorphic RBCs and red cell casts), hypertension, oliguria, edema, and mild proteinuria typically less than 3 grams per day. It results from inflammatory glomerular injury causing reduced GFR and salt-water retention. Examples include post-streptococcal GN, IgA nephropathy, and RPGN.

Nephrotic syndrome presents with heavy proteinuria exceeding 3.5 grams per day, hypoalbuminemia below 30 g/L, edema, and hyperlipidemia. This results from loss of glomerular charge selectivity allowing massive albumin leak. Examples include minimal change disease, membranous GN, and FSGS. Complications include thromboembolism due to loss of anticoagulant proteins, and infection from loss of immunoglobulins."

Q2: "What is the diagnostic significance of red cell casts?"

Model Answer: "Red cell casts are pathognomonic for glomerulonephritis. They form when red blood cells traverse inflamed renal tubules and become embedded in Tamm-Horsfall protein matrix. Their presence has diagnostic specificity exceeding 95% for GN and mandates further investigation including serological workup and often renal biopsy. They must be distinguished from non-dysmorphic hematuria from lower urinary tract bleeding which does not produce casts."

Q3: "Outline your management approach to rapidly progressive glomerulonephritis."

Model Answer: "RPGN is a nephrological emergency defined by rapid decline in GFR—typically a 50% increase in creatinine within 3 months. My approach would be:

First, immediate investigations: Urinalysis with microscopy for RBC casts, urgent renal function, ANCA, anti-GBM antibodies, complement levels, ANA, and urgent renal ultrasound to confirm two kidneys and exclude obstruction.

Second, arrange urgent renal biopsy within 24-48 hours to determine the type: Type I (anti-GBM with linear IgG), Type II (immune complex with granular pattern), or Type III (pauci-immune ANCA-associated).

Third, initiate empirical immunosuppression if high clinical suspicion: IV methylprednisolone 500 mg to 1 gram for 3 days.

Fourth, type-specific treatment: For anti-GBM disease, urgent daily plasmapheresis plus cyclophosphamide and steroids. For ANCA vasculitis, rituximab or cyclophosphamide plus glucocorticoids; plasmapheresis is no longer routinely recommended per the PEXIVAS trial. For immune complex type, treat the underlying cause such as lupus nephritis with mycophenolate and steroids.

Without treatment, 80-90% progress to irreversible ESRD within 6 months."

Q4: "Describe the immunofluorescence patterns in glomerulonephritis and their significance."

Model Answer: "Immunofluorescence is critical for GN diagnosis and identifies three main patterns:

Linear IgG deposition along the glomerular basement membrane is pathognomonic for anti-GBM disease. This represents autoantibodies against the alpha-3 chain of type IV collagen.

Granular or 'starry sky' pattern with IgG, IgA, IgM, or C3 indicates immune complex-mediated disease. The specific immunoglobulin helps narrow the differential: predominant IgA in mesangium is diagnostic of IgA nephropathy; IgG and C3 suggest post-infectious GN, lupus, or membranous nephropathy depending on deposit location.

Pauci-immune pattern with minimal or absent immunoglobulin deposition characterizes ANCA-associated vasculitis. Despite florid inflammation and crescents on light microscopy, immunofluorescence is negative or shows only trace C3.

The immunofluorescence pattern combined with electron microscopy showing deposit location—subepithelial, subendothelial, or mesangial—allows definitive diagnosis."

High-Yield Clinical Pearls

Pearl 1: Complement Patterns

• Low C3 + Low C4 = SLE, cryoglobulinemia (classical pathway).
• Low C3, Normal C4 = Post-streptococcal GN, MPGN (alternative pathway).
• Normal C3 + C4 = ANCA vasculitis, anti-GBM, IgA nephropathy, minimal change, FSGS, membranous.

Pearl 2: Timing of Hematuria Post-Infection

• IgA Nephropathy (Synpharyngitic): Macroscopic hematuria within 1-2 days of URTI. Concurrent with infection.
• Post-Streptococcal GN: 2-3 weeks latency after pharyngitis/impetigo. Delayed immune response.

Pearl 3: Thrombosis Risk in Nephrotic Syndrome

• Risk highest when albumin less than 20 g/L (10-40% VTE risk).
• Consider prophylactic anticoagulation.
• Renal vein thrombosis: Acute flank pain, worsening proteinuria, hematuria.

Pearl 4: When NOT to Biopsy

• Small kidneys (less than 8 cm): Advanced CKD, low diagnostic yield, high complication risk.
• Uncontrolled hypertension (BP > 160/100): Risk of bleeding.
• Single kidney: Relative contraindication.

Pearl 5: Steroid Responsiveness

• Minimal change disease: 80-90% respond within 8-12 weeks (if no response by 16 weeks, consider FSGS).
• FSGS: 30-50% respond; may take 16 weeks (extended trial needed).
• Steroid resistance in presumed MCD → repeat biopsy (may be FSGS).

Pearl 6: RPGN Types Mnemonic

• Type I: "I" = Immunoglobulin (anti-GBM, linear IgG).
• Type II: "II" = Immune complexes (granular).
• Type III: "III" = Invisible (pauci-immune, ANCA).

Common Exam Mistakes

❌ Mistake 1: Diagnosing GN without confirming dysmorphic RBCs or RBC casts. ✅ Correction: Always perform urine microscopy; non-dysmorphic hematuria suggests urological cause.

❌ Mistake 2: Delaying renal biopsy in RPGN. ✅ Correction: RPGN requires urgent biopsy within 24-48 hours; delay worsens prognosis.

❌ Mistake 3: Using plasmapheresis routinely in ANCA vasculitis. ✅ Correction: PEXIVAS trial (2020) showed no benefit; reserve for severe pulmonary hemorrhage only.

❌ Mistake 4: Stopping ACEi if creatinine rises 20-30% after initiation. ✅ Correction: Rise up to 30% is acceptable (indicates effective RAAS blockade); stop only if > 30% rise or hyperkalemia.

❌ Mistake 5: Treating post-streptococcal GN with immunosuppression. ✅ Correction: Self-limiting; supportive care only (BP control, diuretics). Antibiotics treat infection, not GN.

Model OSCE Scenario Answer

Station: "This 35-year-old man presents with 1 week of cola-colored urine, ankle swelling, and headache. BP 165/105 mmHg. Urinalysis shows blood +++, protein ++. How would you investigate?"

Model Answer: "This presentation suggests acute glomerulonephritis given the macroscopic hematuria, proteinuria, hypertension, and edema. My investigation approach would be:

Bedside: I would perform urine microscopy looking specifically for dysmorphic red blood cells and red cell casts which are pathognomonic for GN. I would check vital signs including repeat blood pressure and assess volume status.

Bloods: Renal function (U&E, creatinine, eGFR) to assess for acute kidney injury. Full blood count for anemia or thrombocytopenia. Complement levels C3 and C4—low C3 with normal C4 suggests post-streptococcal GN or IgA nephropathy; low C3 and C4 suggests SLE. Immunology including ANCA for vasculitis, anti-GBM antibodies for Goodpasture syndrome, ANA and anti-dsDNA for lupus, and ASO titre for recent streptococcal infection. I would also check albumin and lipids as nephrotic-range proteinuria can occur in mixed presentations.

Urine: Quantify proteinuria with protein-creatinine ratio or 24-hour urine collection to determine if nephritic (less than 3.5 grams) or nephrotic range.

Imaging: Renal ultrasound to assess kidney size, echogenicity, exclude obstruction, and confirm two kidneys prior to potential biopsy.

Further management: If rapidly progressive features develop—rising creatinine, oliguria—I would arrange urgent renal biopsy within 24-48 hours and consider empirical immunosuppression. If stable, I would await serological results to guide biopsy decision and manage blood pressure with ACE inhibitor, fluid overload with diuretics, and sodium restriction while monitoring renal function closely."

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Medical Disclaimer: This content is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should be based on current guidelines, local protocols, and individual patient factors.