Clinical Quiz 7
A Caucasian 13 and 9/12-year old female presented to a pediatric nephrology unit with moderate edema (periorbital and of the lower limbs), myalgia and headache. Physical examination revealed hypertension (130/80 mmHg). A full work-up showed nephrotic range proteinuria (2 g/24hr), microhematuria (107 RBC/field), slightly reduced renal function (GFR 85 ml/min/1.73 m2 by Schwartz formula). Normal serum complement (C3 and C4), serum albumin 2.3 g/dl, full blood count with slight anemia (10.1 g/dl), normal WBC and platelets.
Previous history was unremarkable and in particular negative for infections, UTIs, medications, episodes of foamy urine or of macrohematuria. Previous routine blood exams had showed normal renal function, normal urinalysis, persistent slight anemia on full blood count with a beta-thalassemic trait.
Family history was positive for thrombotic events in the mother, secondary to MTHFR homozygosis, type 2 diabetes in the paternal grandfather. No family history of renal disease.
The patient was treated symptomatically with fluid and salt restriction, amlodipine to control her blood pressure. A renal biopsy was performed.
Which of the below would you NOT include in your differential diagnosis?
- Minimal change disease
- Membranous nephropathy
- Thrombotic microangiopathy
- Post-infectious GN
- Immune-mediated glomerulonephritis
This is what the renal biopsy showed:
The renal biopsy images do NOT show:
- By light microscopy, diffuse endothelial hyperplasia and capillary wall thickening
- By light microscopy, fragmented red blood cells trapped in the capillaries’ wall.
- By light microscopy, a small arteriolar thrombus.
- By electron microscopy, foot process fusion and effacement
- By electron microscopy, amorphous material deposition in the subendothelial space and multilayering of the glomerular basal membrane.
Immunofluorescence was negative for C3, IgG, IgM, IgA, C1q, fibrinogen.
At this point, what would your diagnosis and therapeutic approach be?
- Atypical presentation of thrombotic microangiopathy – treat with supportive therapy, screen for genetic abnormalities of the alternative complement pathway, check periodically to anticipate an episode of hemolytic uremic syndrome
- Minimal change disease – treat with oral prednisone
- Membranous nephropathy – dose antiPLA2R antibodies and treat with immunosuppression
- C3 glomerulopathy – treat with supportive therapy and if necessary immunosuppression
- Immune-mediated glomerulopathy – treat with immunosuppression, screen for systemic lupus erythematosus