IgA nephropathy and IgA vasculitis nephritis: Viva

Branch 1: Diagnosis and the defining features

The candidate should recognise that this boy has IgA nephropathy and state the defining feature: dominant mesangial IgA deposition on immunofluorescence. The clinical clue is the synpharyngitic timing of the macroscopic haematuria, appearing within one to two days of the sore throat, which is the single most discriminating bedside feature. A strong candidate should emphasise that the normal C3 and C4 exclude post-infectious glomerulonephritis, which has a one to two week latency and a low C3, and exclude lupus and membranoproliferative disease for the same reason. [1]

If the examiner presses on pathogenesis, the candidate should explain the multi-hit hypothesis: production of galactose-deficient IgA1, formation of antiglycan autoantibodies against it, generation of circulating immune complexes, and mesangial deposition with complement activation. The candidate should note that this is the same mechanism shared by IgA vasculitis nephritis, which is why the renal lesions are histologically identical. [1]

Branch 2: Classification and risk stratification

If asked how the disease is classified, the candidate should state the Oxford MEST-C score: M for mesangial hypercellularity, E for endocapillary hypercellularity, S for segmental sclerosis, T for tubular atrophy or interstitial fibrosis, and C for crescents. The candidate should emphasise that the T score is the strongest predictor of long-term progression, that the C score was added in the 2016 update after a multicentre study confirmed the independent prognostic value of crescents, and that the International IgA Nephropathy Prediction Tool integrates these with proteinuria, blood pressure, and estimated GFR to estimate the five-year risk of losing half of kidney function. [2]

Branch 3: The treatment ladder

If asked about management, the candidate should start with optimal supportive care as the foundation for every patient: an ACE inhibitor or angiotensin receptor blocker titrated to drive proteinuria under 1 g per day, blood pressure at the age-appropriate target, sodium restriction, weight management, and smoking avoidance, continued lifelong. The candidate should then describe the disease-specific therapies for the high-risk minority with persistent proteinuria over 0.75 to 1 g per day despite optimised supportive care. [1]

The candidate should know that corticosteroids reduce progression but that the TESTING trial showed the full-dose regimen (prednisolone 0.8 to 1 mg per kg per day) caused serious infections including fatal infection, so a reduced-dose regimen with tuberculosis screening and vaccination is now preferred. The candidate should mention targeted-release budesonide 16 mg per day as the steroid-sparing mucosal option shown to reduce proteinuria in the NefIgArd trial. [3]

For the rapidly progressive crescentic phenotype, with crescents in over 50 percent of glomeruli and a falling estimated GFR, the candidate should state that this is a medical emergency requiring urgent high-dose corticosteroids and cyclophosphamide, sometimes with plasma exchange. The candidate should close by emphasising the commitment to lifelong annual blood pressure and urinalysis, because the renal consequences can emerge decades later, and that recurrence after renal transplantation is the most common form of recurrent glomerulonephritis in a graft. [1]

Branch 4: The systemic scenario and IgA vasculitis nephritis

If the examiner changes the scenario to a young child with a palpable purpuric rash over the lower limbs and buttocks, arthritis, and abdominal pain, the candidate should shift to IgA vasculitis. The candidate should state that it is the most common childhood vasculitis, peaking at age four to six years, and is classified by the EULAR, PRINTO and PRES Ankara 2008 criteria, which require palpable purpura plus at least one of diffuse abdominal pain, arthritis, renal involvement, or IgA deposition on biopsy. [1]

The candidate should describe how the renal involvement is assessed and managed. Renal involvement develops in approximately 20 to 50 percent of children, almost always within four weeks of the rash. Mild isolated haematuria is managed conservatively, an ACE inhibitor is used for proteinuria, and corticosteroids plus immunosuppression are reserved for severe crescentic or nephrotic disease. The candidate should note the surgical pitfall: severe abdominal pain with currant-jelly stool is intussusception until proven otherwise. A strong candidate should close by emphasising that the renal lesion is histologically identical to IgA nephropathy because both share the galactose-deficient IgA1 mechanism, and that all survivors need lifelong nephrology follow-up. [1]