IgA nephropathy and IgA vasculitis nephritis: Case

This boy has IgA nephropathy. The diagnosis rests on the synpharyngitic timing of the macroscopic haematuria, the normal C3 and C4 which exclude post-infectious glomerulonephritis, and the biopsy showing dominant mesangial IgA deposition with IgG and C3. The Oxford score of M1 E1 S0 T1 C0 places him at moderate risk of progression, driven mainly by the T1 component and his proteinuria of 0.9 g per day, which sits just below the 1 g per day threshold that defines the high-risk category. [1]

Clinical findings

The defining clue is the temporal relationship between the haematuria and the sore throat. In IgA nephropathy the macroscopic haematuria is synpharyngitic, appearing within one to two days of the mucosal infection, whereas post-infectious glomerulonephritis waits one to two weeks and is accompanied by a low C3 and an elevated ASO. This boy's haematuria began on the same morning as the sore throat, his C3 and C4 are normal, and his ASO is not elevated, which together point firmly to IgA nephropathy and away from post-infectious disease. [1]

The proteinuria of 0.9 g per day is the most important prognostic variable, because sustained proteinuria over 1 g per day is the single strongest predictor of progression to end-stage kidney disease. His blood pressure at the 95th centile adds a second adverse marker. The Oxford score of M1 E1 S0 T1 C0 confirms the moderate risk: the T1 component reflects early tubulointerstitial scarring, which is the strongest histological predictor of long-term progression. The E1 component marks active, potentially steroid-responsive endocapillary inflammation. [2]

Investigations and diagnosis

The diagnosis is IgA nephropathy, confirmed by renal biopsy. The biopsy shows mesangial proliferation on light microscopy, dominant mesangial IgA deposition with IgG and C3 on immunofluorescence, and mesangial electron-dense deposits on electron microscopy, which is the characteristic triad. The Oxford MEST-C score is M1 E1 S0 T1 C0, and the International IgA Nephropathy Prediction Tool combines this with his proteinuria, blood pressure, and estimated GFR to estimate his five-year risk of losing half of kidney function, which frames the conversation about disease-specific therapy. [2]

The differential diagnosis was considered and excluded. Post-infectious glomerulonephritis was excluded by the synpharyngitic timing, the normal C3, and the absent ASO rise. Lupus nephritis was excluded by the negative ANA and the normal C4. ANCA-associated vasculitis was excluded by the negative ANCA. Thin basement membrane nephropathy causes persistent isolated microscopic haematuria rather than an acute macroscopic episode, and Alport syndrome was excluded by the absence of a family history of renal failure or deafness. [1]

Management and outcome

Management began with optimal supportive care as the foundation for every patient with IgA nephropathy. He was started on an ACE inhibitor, enalapril, titrated to drive proteinuria under 1 g per day while maintaining blood pressure at the age-appropriate target. An ACE inhibitor lowers intraglomerular pressure, reduces proteinuria, and slows progression independent of its blood-pressure effect. He was counselled on sodium restriction, weight management, and the absolute importance of not smoking. [1]

After six months of optimised supportive care his proteinuria had settled to 0.4 g per day and his blood pressure was at the 50th centile, so he did not meet the threshold for disease-specific therapy. Had his proteinuria remained over 0.75 to 1 g per day despite optimised supportive care, the treatment ladder would have moved to disease-specific therapy. Corticosteroids reduce progression, but the TESTING trial showed that 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 would have been preferred. Targeted-release budesonide 16 mg per day for nine months is the steroid-sparing mucosal option shown to reduce proteinuria. [3]

The family was counselled that IgA nephropathy is a chronic, slowly progressive disease, that approximately 20 to 40 percent of patients progress to end-stage kidney disease over 20 to 30 years, and that the strongest predictors are sustained proteinuria over 1 g per day, hypertension, reduced estimated GFR at diagnosis, and adverse Oxford T and C scores. He was committed to lifelong annual blood pressure and urinalysis, because the renal consequences can emerge decades after an apparently benign presentation. [1]

The counterfactual: if this had been IgA vasculitis nephritis

If this boy had instead presented at age five with a palpable purpuric rash over the shins and buttocks, swollen tender ankles, and colicky abdominal pain, the diagnosis would have been IgA vasculitis with nephritis. The renal lesion would have been histologically identical to his IgA nephropathy, because both share the galactose-deficient IgA1 mechanism. The diagnosis would have been clinical, using 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 management would have addressed the extra-renal features first. Severe abdominal pain would have been treated with systemic corticosteroids, prednisolone 1 to 2 mg per kg per day up to a maximum of 60 to 80 mg, and intussusception excluded if the pain was severe. Renal involvement would have been managed with an ACE inhibitor for proteinuria, with corticosteroids plus immunosuppression reserved for severe crescentic or nephrotic disease. As in the index case, all survivors would have been committed to lifelong annual blood pressure and urinalysis. This counterfactual illustrates the central teaching point: IgA nephropathy and IgA vasculitis nephritis are one mechanism in two costumes, separated by where the IgA immune complexes deposit. [1]