IgA nephropathy and IgA vasculitis nephritis: SAQ

This boy has IgA nephropathy. The diagnosis rests on the synpharyngitic timing of the macroscopic haematuria (appearing on the same day as the sore throat), 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. [1]

Question 1 (10 marks)

Outline your management of this adolescent, including the role of supportive care, the indications for disease-specific therapy, and the prognosis you would discuss with the family. [2]

The foundation is optimal supportive care and it is the step most often under-prescribed. I would start an ACE inhibitor or an angiotensin receptor blocker, titrated to drive proteinuria under 1 g per day while maintaining blood pressure at or below the age-appropriate target. An ACE inhibitor lowers intraglomerular pressure, reduces proteinuria, and slows progression independent of its blood-pressure effect. I would reinforce sodium restriction, weight management, exercise, and smoking avoidance, and the regimen is continued lifelong. I would monitor the spot urine protein-to-creatinine ratio, blood pressure, and estimated GFR at regular intervals. [2]

Disease-specific therapy is considered for the high-risk minority: patients with persistent proteinuria over 0.75 to 1 g per day despite three to six months of optimised supportive care. This boy has only 1+ proteinuria on dipstick, so I would first quantify it with a spot protein-to-creatinine ratio and optimise the ACE inhibitor before deciding. If he remained in the high-risk category, I would use the International IgA Nephropathy Prediction Tool, which integrates proteinuria, blood pressure, estimated GFR, and the Oxford MEST-C score to estimate the five-year risk of losing half of kidney function, and I would discuss corticosteroids and targeted-release budesonide with the family. [3]

For corticosteroids, the TESTING trial established that steroids reduce progression but 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 preferred. Targeted-release budesonide 16 mg per day for nine months is the steroid-sparing mucosal option, shown to reduce proteinuria in the NefIgArd trial. [3]

The prognosis I would discuss is that of a chronic, slowly progressive disease. Approximately 20 to 40 percent of patients progress to end-stage kidney disease over 20 to 30 years, with the strongest predictors being sustained proteinuria over 1 g per day, hypertension, reduced estimated GFR at diagnosis, and adverse Oxford T and C scores. Children generally fare better than adults but carry the disease for more decades, so the cumulative risk is real. I would commit the family to lifelong annual blood pressure and urinalysis, because the renal consequences can emerge decades later. [2]

Question 2 (10 marks)

Two years later, a 6-year-old girl presents with palpable non-blanching purpura over her shins and buttocks, swollen tender ankles, and colicky abdominal pain. Urinalysis shows microscopic haematuria and proteinuria, and her C3 is normal. Describe how the diagnosis and management differ from the first case, and how you would assess and manage her renal involvement. [2]

This girl has IgA vasculitis, the most common childhood vasculitis, presenting with the classic tetrad of palpable purpura, arthritis, abdominal pain, and renal involvement. The diagnosis is 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. The renal lesion, IgA vasculitis nephritis, is histologically identical to the IgA nephropathy in the first case, driven by the same galactose-deficient IgA1 mechanism. The key differences from the first case are the younger age (peak four to six years), the systemic vasculitic features, and the absence of synpharyngitic macroscopic haematuria. [2]

The acute management addresses the extra-renal features. Severe abdominal pain is treated with systemic corticosteroids, prednisolone 1 to 2 mg per kg per day up to a maximum of 60 to 80 mg, which shortens the duration of abdominal symptoms. Arthritis is managed with simple analgesia and rest. I must exclude intussusception if the abdominal pain is severe or associated with currant-jelly stool, classically ileocolic, by urgent ultrasound looking for a target sign. Steroids given for abdominal or joint disease do not prevent IgA vasculitis nephritis, so I would not prescribe them for that purpose alone. [2]

For her renal involvement, I would quantify the proteinuria with a spot protein-to-creatinine ratio and monitor the renal function and blood pressure. Renal involvement develops in approximately 20 to 50 percent of children with IgA vasculitis, almost always within the first four weeks of the rash. For mild isolated haematuria, supportive care and close monitoring suffice. I would use an ACE inhibitor for proteinuria. Corticosteroids plus immunosuppression are reserved for severe crescentic or nephrotic disease, because the evidence that steroids prevent IgA vasculitis nephritis when given at rash onset is weak. [2]

The prognosis of IgA vasculitis nephritis in children is broadly favourable, with complete recovery in most. The minority with heavy proteinuria, nephrotic syndrome, or crescents in over 50 percent of glomeruli have a worse long-term renal outlook. I would commit her to lifelong annual blood pressure and urinalysis, because, as in the first case, the renal consequences of IgA disease can emerge years after an apparently benign episode. [2]