Glomerulonephritis Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mr Robert Chen is a 58-year-old man of Chinese-Australian background, a former painter, who presents with a 3-week history of progressive malaise, arthralgia, nasal crusting, and epistaxis, culminating in a 4-day history of haemoptysis, dyspnoea, and oliguria. He has a 40-pack-year smoking history and no significant past medical history. [1]

On examination he is tachypnoeic (RR 24) with oxygen saturation of 90% on room air, hypertensive (BP 156/92), and has bilateral basal crackles. There are palpable purpuric lesions on his lower limbs and a left foot drop consistent with mononeuritis multiplex. [1]

His investigations show a creatinine of 385 micromol/L, rising from a baseline of 95 over three months. His urinalysis shows blood 3+, protein 2+, with dysmorphic red cells and red cell casts on microscopy. His C3 and C4 are both normal. ANCA is strongly positive with MPO specificity. Anti-GBM antibody is negative. ANA is negative. His chest CT shows diffuse alveolar infiltrates consistent with pulmonary haemorrhage, and his renal biopsy shows pauci-immune necrotising and crescentic glomerulonephritis with crescents in 55% of glomeruli. [1]

His main problems are:

1. Pulmonary-renal syndrome from MPO-ANCA-associated vasculitis (microscopic polyangiitis) — pulmonary haemorrhage and crescentic pauci-immune GN
2. Acute kidney injury, KDIGO stage 3 (creatinine 4 times baseline)
3. Vasculitic mononeuritis multiplex (left foot drop)
4. Cutaneous vasculitis
5. Anaemia and systemic inflammation
6. Smoking and solvent exposure (occupational risk factors for AAV) [1]

This is a medical emergency. My immediate priority is to secure his airway and breathing, then begin urgent induction immunosuppression with methylprednisolone pulses and rituximab, with multidisciplinary involvement from nephrology, respiratory, and ICU." [1]

Examiner probing questions and model answers

Q1: "Why have you diagnosed microscopic polyangiitis rather than GPA?" [1]

"Both are ANCA-associated vasculitides, but the clinical pattern distinguishes them. Mr Chen has MPO-ANCA positivity, diffuse pulmonary haemorrhage (capillaritis), mononeuritis multiplex, and cutaneous purpura — all consistent with MPA. He has no granulomatous features of GPA — specifically, no destructive upper respiratory tract disease such as saddle nose deformity, subglottic stenosis, or erosive sinusitis, and his chest CT shows diffuse alveolar haemorrhage rather than cavitating nodules or granulomatous masses. PR3-ANCA is typical of GPA; MPO-ANCA is typical of MPA. While nasal crusting can occur in both, the absence of granulomatous ENT destruction, the MPO positivity, and the capillaritic lung pattern favour MPA. The distinction matters less for immediate treatment — both are treated identically with rituximab or cyclophosphamide and corticosteroids — but it matters for prognosis: MPA relapses less frequently than PR3-positive GPA." [1]

Q2: "Walk me through your decision on plasma exchange in this patient." [1]

"This is one of the most contested decisions in nephrology. The evidence has evolved significantly. MEPEX, published in JASN in 2007, randomised 137 patients with severe renal AAV (creatinine above 500) to plasma exchange versus methylprednisolone pulses. Plasma exchange reduced ESKD at 12 months from 43% to 19%. This established plasma exchange in clinical practice for severe renal AAV. [1]

However, PEXIVAS, published in NEJM in 2020, randomised 704 patients — the largest trial ever in AAV — and found that plasma exchange did NOT reduce the composite of death or ESKD (28% versus 31%, hazard ratio 0.86, P = 0.27). This has substantially reduced the routine use of plasma exchange. [1]

For Mr Chen specifically: his creatinine is 385, below the MEPEX threshold of 500, so the renal benefit evidence is weaker. However, he has life-threatening pulmonary haemorrhage. While PEXIVAS included pulmonary haemorrhage patients and found no overall benefit, many vasculitis centres still use plasma exchange for severe pulmonary haemorrhage on the rationale that rapid removal of circulating ANCA and inflammatory mediators may help control alveolar bleeding. KDIGO 2024 retains plasma exchange as a consideration for life-threatening pulmonary haemorrhage. [1]

My decision: I would discuss in the vasculitis MDT. Given the severity and immediacy of his pulmonary haemorrhage, I would favour a short course of plasma exchange — seven daily or alternate-day exchanges of one plasma volume with 5% albumin replacement — alongside rituximab and corticosteroids. If he were anti-GBM positive or double-positive, plasma exchange would be mandatory regardless." [1]

Q3: "What dose of rituximab would you give, and how does it compare to cyclophosphamide?" [1]

"I would give rituximab 375 mg per square metre IV weekly for four weeks, or the alternative regimen of 1 gram IV on days 1 and 15. Both are established by the RAVE and RITUXVAS trials. RAVE, published in NEJM in 2010, randomised 197 patients to rituximab versus cyclophosphamide for induction. Rituximab was noninferior — 64% achieved remission at 6 months versus 53% with cyclophosphamide — and in the pre-specified subgroup of relapsing disease, rituximab was superior (67% versus 42%). [1]

RITUXVAS, published alongside RAVE in 2010, studied 44 patients with newly diagnosed renal AAV and showed that rituximab plus two pulses of cyclophosphamide was equivalent to standard cyclophosphamide (76% versus 82% sustained remission). [1]

I prefer rituximab for Mr Chen because it avoids cyclophosphamide toxicity — haemorrhagic cystitis, infertility, secondary malignancy, and cumulative bone marrow suppression. He can also be maintained with rituximab after induction, simplifying his long-term regimen. Cyclophosphamide remains an option if rituximab is contraindicated or unavailable — IV pulses of 15 mg per kilogram every 2 to 3 weeks for 3 to 6 months." [1]

Q4: "His crescents are in 55% of glomeruli. What is his renal prognosis?" [1]

"Crescents are the histological hallmark of severe, rapidly progressive glomerular injury. They indicate rupture of the glomerular capillary wall with fibrin, macrophage, and epithelial cell proliferation into Bowman's space. The percentage of glomeruli with crescents correlates with prognosis. With crescents in 55% of his glomeruli, Mr Chen has severe disease. [1]

His renal prognosis is guarded. In ANCA vasculitis with crescents in over 50% of glomeruli and a presenting creatinine in the 350 to 500 range, approximately 30 to 50% of patients progress to ESKD within the first year despite treatment, and those who recover often have residual CKD. The key determinants of renal recovery are the presenting creatinine (lower is better), the percentage of normal glomeruli on biopsy (more is better), and the degree of tubulointerstitial fibrosis (which indicates irreversible scarring). [1]

If he progresses to dialysis dependence despite treatment, he has a 60 to 70% chance of remaining dialysis-dependent at 3 months, and most of those will not recover. For those who do recover, lifelong monitoring for CKD progression and disease relapse is essential. Transplantation is possible after 6 to 12 months of sustained remission — ANCA vasculitis recurs in approximately 15 to 20% of grafts, but graft loss from recurrence is uncommon." [1]

Q5: "He is about to start rituximab and high-dose steroids. What prophylaxis do you prescribe?" [1]

"First, Pneumocystis jirovecii pneumonia prophylaxis — this is essential. PJP is a leading cause of death in immunosuppressed vasculitis patients, particularly with the combination of high-dose corticosteroids and B-cell depletion. I prescribe trimethoprim-sulfamethoxazole 800/160 mg three times weekly for the duration of prednisone above 20 mg daily and until CD19 B-cell counts have recovered after rituximab (typically 6 to 12 months). For sulfa allergy, dapsone or atovaquone are alternatives. [1]

Second, gastric protection with a proton pump inhibitor during high-dose corticosteroid therapy. [1]

Third, bone protection — calcium and vitamin D supplementation, plus a DEXA scan to guide bisphosphonate use. He has smoking and likely glucocorticoid-related osteoporosis risk. [1]

Fourth, vaccination status should be reviewed and updated BEFORE rituximab suppresses vaccine responses — pneumococcal (Prevenar 13 then Pneumovax 23, 8 weeks apart), seasonal influenza, hepatitis B, and COVID-19 boosters. Live vaccines (such as zoster live) must be given before immunosuppression or avoided. [1]

Fifth, I would screen for latent infections before starting immunosuppression — TB (Quantiferon or Mantoux), hepatitis B and C (already negative here), HIV, and in a painter with potential soil exposure, consider Strongyloides serology (Strongyloides hyperinfection is a catastrophic complication of corticosteroid therapy in endemic or occupation-exposed patients)." [1]

Q6: "Tell me about the PEXIVAS trial and how it changed your steroid prescribing." [1]

"PEXIVAS, published in NEJM in 2020, was a 2-by-2 factorial trial of plasma exchange and glucocorticoid dosing in 704 patients with severe AAV. While the plasma exchange arm was neutral, the glucocorticoid arm was practice-changing. [1]

The trial compared a reduced-dose oral glucocorticoid regimen with a standard-dose regimen. The reduced-dose group received less cumulative steroid (the protocol reduced the dose faster and to a lower maintenance level). The reduced-dose regimen was noninferior to the standard dose for the composite of death or ESKD, AND it was associated with significantly fewer serious infections within the first year. [1]

This has changed my practice. Instead of the traditional prednisone 1 mg per kg per day for a month then slow taper, I now use a PEXIVAS-style reduced-dose approach: methylprednisolone pulses (500 to 1000 mg for 1 to 3 days), then oral prednisone starting around 0.5 to 0.75 mg per kg, tapering to below 10 mg by 3 months. This preserves the early anti-inflammatory effect while minimising the cumulative infection risk. For Mr Chen, this means I will taper his prednisone aggressively once his pulmonary haemorrhage and renal inflammation are controlled." [1]

Q7: "What is his long-term follow-up plan?" [1]

"After induction remission — typically 3 to 6 months — I transition to maintenance. For MPO-positive AAV, azathioprine (1 to 2 mg per kg per day) or rituximab (1 gram x2 every 4 to 6 months) are first-line. Given his mononeuritis and pulmonary involvement, I would favour rituximab maintenance for at least 18 to 24 months, as it has superior relapse prevention in the MAINRITSAN trials. [1]

Monitoring is lifelong. Monthly clinical review for the first year (BVAS, weight, blood pressure, respiratory symptoms, neurological examination), blood tests (creatinine, CRP, ANCA titre, FBC for cytopenia, immunoglobulins after rituximab), and urinalysis (proteinuria, haematuria). A rising ANCA titre or recurrent haematuria may herald relapse and warrants expedited review. [1]

I would counsel him on the relapse symptoms to watch for — recurrent haemoptysis, arthralgia, purpura, nasal symptoms, neurological changes — and ensure he has a direct contact for the vasculitis service. I would strongly advise smoking cessation, as smoking increases the risk of pulmonary haemorrhage and cardiovascular disease. I would involve occupational health to assess ongoing solvent exposure. [1]

Long-term, he is at increased cardiovascular risk from both CKD and chronic inflammation — I would optimise his cardiovascular risk factors aggressively. If he progresses to ESKD, I would plan for transplantation after sustained remission, and involve the transplant team early." [1]

Short Case Discussion

Scenario: "Examine this patient's hands and general appearance, then present your findings"

Candidate presentation (model): [1]

"On general inspection, the patient is a middle-aged woman with a cushingoid appearance — moon facies, central obesity, and thin skin with easy bruising, consistent with chronic corticosteroid therapy for what is likely a systemic disease. [1]

Examining the hands: the peripheral fingers show palpable purpura over the fingertips and nailfold infarcts. There is scarring from previous splinter haemorrhages. The palmar surfaces show no active lesions but there is old scarring from cutaneous vasculitis. There is evidence of vasculitic ulceration at the tip of the right index finger. The joints show no active synovitis but there is mild swan-neck deformity of the left second and third fingers suggesting old inflammatory arthropathy. The palms show mild palmar erythema. [1]

There is a functioning arteriovenous fistula at the left wrist, indicating the patient is on haemodialysis. [1]

In summary, these findings are consistent with a systemic vasculitis on immunosuppressive therapy complicated by end-stage kidney disease. The combination of nailfold infarcts, palpable purpura, cushingoid features, and dialysis fistula suggests long-standing ANCA-associated vasculitis or another systemic vasculitis with renal failure." [1]

Examiner: "What is the significance of the nailfold infarcts?" [1]

"Nailfold infarcts, also called splinter haemorrhages when they are linear, indicate small-vessel vasculitis or embolic disease. In the context of a systemic vasculitis such as ANCA-associated vasculitis, they reflect digital arteritis and microinfarction. They are one of the cutaneous manifestations of small-vessel vasculitis, alongside palpable purpura (the hallmark of leukocytoclastic vasculitis on the lower limbs), livedo reticularis, and digital ulcers. [1]

The differential for nailfold infarcts includes endocarditis (check for fever, murmur, other embolic phenomena), cholesterol emboli (after vascular procedures), antiphospholipid syndrome, and trauma. In this patient, the combination with palpable purpura and dialysis fistula strongly suggests systemic vasculitis." [1]

Examiner: "What other systems would you examine, and what would you look for?" [1]

"I would complete a systematic examination looking for evidence of multisystem vasculitis and its complications: [1]

Cardiovascular: blood pressure (hypertension from renal disease), heart sounds (functional murmurs from anaemia, pericardial rub from uraemic or vasculitic pericarditis), signs of heart failure from volume overload. Respiratory: chest auscultation for crackles (pulmonary oedema from volume overload, or residual fibrosis or scarring from previous pulmonary haemorrhage), and signs of pleural effusion. Abdomen: ballotable kidneys (enlarged in vasculitis or infiltrative disease, small and contracted in end-stage kidney disease), hepato-splenomegaly (associated autoimmune disease), ascites (from nephrotic syndrome or volume overload), and the presence of a Tenckhoff catheter or transplant. Neurological: mononeuritis multiplex (wrist drop, foot drop, sensory loss in a peripheral nerve distribution) — this is a hallmark of vasculitic neuropathy. I would test for power, sensation, and reflexes in a peripheral nerve distribution. Skin: a full search for purpura, ulcers, livedo, and nodules. [1]

The goal is to define the extent of organ involvement, the activity of disease (active purpura versus old scarring), and the complications of treatment and CKD." [1]

Examiner: "What is the significance of the mononeuritis multiplex in vasculitis?" [1]

"Mononeuritis multiplex — simultaneous or sequential infarction of two or more peripheral nerves — is one of the most specific clinical signs of systemic vasculitis. It occurs when vasa nervorum (the small arteries supplying peripheral nerves) become inflamed and occluded, causing nerve infarction. [1]

The classic pattern is asymmetric, affecting the peroneal nerve (foot drop), the ulnar nerve (wrist drop and claw hand), the median nerve, or the radial nerve. It can also affect cranial nerves. The diagnosis is clinical, confirmed by nerve conduction studies showing axonal neuropathy in a peripheral nerve pattern, and sometimes by nerve biopsy showing vasculitis of the vasa nervorum. [1]

In ANCA-associated vasculitis, mononeuritis multiplex indicates active, organ-threatening disease and is an indication for urgent induction immunosuppression. Recovery is often incomplete — axonal regeneration is slow (1 mm per day), and severe infarction may leave permanent deficit." [1]