MRCP Mastermind

28/08/2026

🧪 Immunohistological findings in major primary glomerulonephritides — MRCP high-yield

1. IgA nephropathy

IF: Mesangial IgA + C3 deposition

EM: Mesangial electron-dense deposits

📌 Key: Mesangial IgA

2. Post-streptococcal GN

IF: Granular IgG + C3 (“starry sky”)

EM: Subepithelial humps

📌 Key: Subepithelial humps

3. Membranous nephropathy

IF: Granular IgG + C3 along capillary loops/GBM

EM: Subepithelial deposits with foot-process effacement

📌 Primary disease: often IgG4 + anti-PLA2R

📌 Silver stain: Spike and dome

4. Minimal change disease

IF: Usually negative

EM: Diffuse foot-process effacement

📌 Key: Normal LM + negative IF + foot-process effacement

5. FSGS

IF: Usually negative; may show IgM/C3 trapping in sclerotic segments

EM: Foot-process effacement

📌 Key: Segmental sclerosis + podocyte injury

6. Membranoproliferative GN

IF: Depends on type:

Immune-complex: IgG + C3

Complement-mediated: predominantly C3

EM: Subendothelial ± mesangial deposits

📌 Key: MPGN pattern + double-contour GBM

7. Crescentic/rapidly progressive GN

Anti-GBM: Linear IgG ± C3 along GBM

Immune-complex: Granular deposits

Pauci-immune: Little or no immune deposition → typically ANCA-associated

📌 MRCP classic:
Linear = anti-GBM
Granular = immune complex
Pauci-immune = ANCA

🧠 One-line memory for exams

IgA → Mesangial IgA
PSGN → Granular IgG/C3 + subepithelial humps
Membranous → Granular IgG/C3 + subepithelial deposits
Minimal change → Negative IF + foot-process effacement
FSGS → IgM/C3 trapping + segmental sclerosis
MPGN → IgG/C3 or C3 + subendothelial deposits
Anti-GBM → Linear IgG
ANCA GN → Pauci-immune

25/08/2026

🩺 MRCP High-Yield: Membranous Nephropathy

🔹 A common cause of nephrotic syndrome in adults, particularly in examination settings.

🔹 Pathology: Subepithelial immune-complex deposition along the glomerular basement membrane, resulting in diffuse thickening of the glomerular capillary walls.

🔹 Key immunofluorescence finding: Granular deposition of IgG and C3 along the glomerular basement membrane.

🔹 Electron microscopy: Subepithelial deposits producing a characteristic “spike and dome” appearance on silver staining.

🔹 Major causes:
• Primary: Anti-PLA2R antibody-associated disease
• Secondary: Malignancy, hepatitis B or C, SLE, medications such as NSAIDs, and other autoimmune or infectious conditions

🔹 Clinical features:
• Nephrotic-range proteinuria
• Oedema
• Hypoalbuminaemia and hyperlipidaemia
• Microscopic haematuria may occur
• Increased risk of renal vein thrombosis and venous thromboembolism due to nephrotic syndrome

🔹 Diagnosis:
• Test for anti-PLA2R antibodies
• Perform a kidney biopsy when the diagnosis is uncertain, the presentation is atypical, or histological assessment is required for risk stratification
• If secondary disease is suspected, investigate for malignancy, infection and autoimmune disease

🔹 Management:
• ACE inhibitor or ARB to reduce proteinuria and control blood pressure
• Statin therapy when clinically indicated
• Dietary salt restriction and diuretics for oedema management
• Assess venous thromboembolism risk and consider prophylactic anticoagulation in selected patients
• In primary membranous nephropathy with a significant risk of progression, consider rituximab, cyclophosphamide with glucocorticoids, or calcineurin inhibitor-based therapy, according to risk profile and patient factors
• Treat the underlying cause in secondary membranous nephropathy

📌 MRCP Exam Pearls:
Nephrotic syndrome with positive anti-PLA2R antibodies should raise suspicion of primary membranous nephropathy.

“Spike and dome” appearance is characteristic of membranous nephropathy.

Subepithelial immune-complex deposits are characteristic of membranous nephropathy.

⚠️ Important: In adults with membranous nephropathy, always consider secondary causes, particularly malignancy, hepatitis B or C, SLE and medications.

25/08/2026

25/08/2026

🩺 MRCP High-Yield: Post-Streptococcal Glomerulonephritis (PSGN)

🔹 Cause: Immune-complex GN following Group A β-haemolytic Streptococcus infection

🔹 Timing:
• 1–3 weeks after streptococcal pharyngitis
• 3–6 weeks after skin infection

🔹 Classic presentation:
• Cola/tea-coloured urine
• Periorbital oedema
• Hypertension
• Oliguria ± acute kidney injury

🔹 Urinalysis:
• Haematuria + RBC casts
• Proteinuria, usually sub-nephrotic

🔹 Complement: Low C3 → usually returns to normal within 6–8 weeks

🔹 Evidence of recent streptococcal infection:
• ↑ A*O titre — more useful after pharyngitis
• ↑ anti-DNase B — particularly useful after skin infection

🔹 Biopsy (if required):
• LM → diffuse endocapillary proliferation
• IF → “starry sky” granular IgG, IgA, C3 deposits
• EM → subepithelial “humps”

🔹 Treatment: Mainly supportive → salt/fluid restriction, diuretics and BP control
• Treat any ongoing streptococcal infection with appropriate antibiotics
• Immunosuppression is not routinely indicated

📌 MRCP Pearl:
PSGN = nephritic syndrome + low C3 + 1–3 week latent period + subepithelial humps.

25/08/2026

🩺 MRCP High-Yield: IgA Nephropathy

🔹 Most common primary glomerulonephritis worldwide

🔹 Classic presentation: Recurrent visible haematuria occurring within 1–3 days of an upper respiratory infection → synpharyngitic haematuria

🔹 Other features: Microscopic haematuria, proteinuria, hypertension and variable renal dysfunction

🔹 Diagnosis: Kidney biopsy
→ Mesangial proliferation + IgA-dominant mesangial deposits on immunofluorescence

🔹 Important associations: IgA vasculitis, coeliac disease, chronic liver disease, HIV and inflammatory bowel disease

🔹 Treatment:
• Optimise BP and proteinuria → ACE inhibitor/ARB
• SGLT2 inhibitor in appropriate patients
• Selected high-risk patients may require targeted-release budesonide or other immunosuppressive strategies
• Avoid routine immunosuppression in patients at low risk of progression

🔹 Prognostic factors: Persistent proteinuria, hypertension, reduced eGFR and chronic histological changes

📌 MRCP Pearl:
IgA nephropathy = synpharyngitic haematuria
Post-streptococcal GN = haematuria typically 1–3 weeks after infection.

24/08/2026

💊 MRCP High-Yield: Aminoglycosides

🔹 Examples: Gentamicin, amikacin, tobramycin, streptomycin

🔹 Mechanism: Irreversibly bind 30S ribosome → inhibit protein synthesis → bactericidal

🔹 Coverage: Mainly aerobic Gram-negative bacilli, including Pseudomonas

🔹 No activity against anaerobes → require oxygen-dependent uptake into bacteria

🔹 Gram-positive organisms: Usually used in combination (e.g., gentamicin + a β-lactam) for synergistic effect against selected infections such as enterococcal endocarditis

🔹 Major adverse effects: Nephrotoxicity + ototoxicity

🔹 Important: Can cause neuromuscular blockade

🔹 PK pearl: Poor oral absorption → usually given IV/IM for systemic infection

🔹 Monitoring: Drug levels, renal function, and duration of therapy are important

🔹 MRCP pearl: Amikacin is generally more resistant to many aminoglycoside-inactivating enzymes than gentamicin/tobramycin.

📌 Remember: Aminoglycoside = 30S + aerobic Gram-negative + nephrotoxicity + ototoxicity.

23/08/2026

💊 MRCP High-Yield: LMWH

🔹 Examples: Enoxaparin, dalteparin, tinzaparin

🔹 Mechanism: Potentiates antithrombin III → mainly inhibits factor Xa (also IIa to a lesser extent)

🔹 Administration: Subcutaneous; predictable pharmacokinetics → usually no routine monitoring

🔹 Uses: DVT/PE treatment & prophylaxis, ACS, perioperative thromboprophylaxis, pregnancy

🔹 Major adverse effects: Bleeding, thrombocytopenia/HIT, osteoporosis with prolonged use

🔹 Renal impairment: Dose adjustment/caution required because LMWH is renally cleared

🔹 Antidote: Protamine → only partially reverses LMWH activity

🔹 Pregnancy: Preferred anticoagulant—does not cross the placenta

🔹 HIT: If suspected, stop all heparin products and use a non-heparin anticoagulant.

📌 MRCP pearl: LMWH → Factor Xa > IIa; SC administration; renal clearance; protamine only partially reverses.

Remember: LMWH = Xa inhibition + predictable dosing + pregnancy-friendly.

23/08/2026

💊 MRCP High-Yield: Warfarin

🔹 Mechanism: Inhibits vitamin K epoxide reductase (VKORC1) → ↓ factors II, VII, IX, X + proteins C & S

🔹 Monitoring: PT/INR
🎯 Most indications: INR 2.0–3.0
🎯 Mechanical mitral valve: usually higher target (often 2.5–3.5)

🔹 Onset: Delayed → initial fall in protein C can cause a transient hypercoagulable state → warfarin-induced skin necrosis

🔹 Pregnancy: Contraindicated in most pregnancies because of fetal toxicity/embryopathy and bleeding risk

🔹 Major interactions: Many drugs + vitamin K–containing foods can alter INR

🔹 Antidote: Vitamin K; severe/life-threatening bleeding → 4-factor PCC + IV vitamin K

🔹 MRCP pearl: Warfarin is preferred over DOACs in mechanical heart valves.

📌 Remember: Warfarin → VKORC1 → II, VII, IX, X ↓ → monitor INR.

23/08/2026

🧠 MRCP High-Yield: Sturge–Weber Syndrome

🔹 Cause: Sporadic GNAQ mutation → capillary–venous malformations

🔹 Classic triad:
• Port-wine stain — usually in V1 (ophthalmic) distribution
• Leptomeningeal angioma → seizures, stroke-like episodes, hemiparesis, developmental delay
• Glaucoma — due to abnormal ocular vascular development

🔹 Neurological hallmark: Seizures, often beginning in infancy

🔹 Imaging: Contrast-enhanced MRI → leptomeningeal enhancement; CT may show “tram-track” cortical calcifications

🔹 Eye: Glaucoma may occur ipsilateral to the port-wine stain

🔹 Important: No family history—typically sporadic

📌 MRCP pearl: Port-wine stain involving the ophthalmic (V1) territory → think Sturge–Weber and assess for neurological/ocular involvement.

Remember: Port-wine stain + seizures + glaucoma = Sturge–Weber syndrome.

03/02/2026