Silver stain showing double-contouring in the glomerular basement membrane structure.
Trichome stain shows arteriolar occlusion, consistent with a thrombotic microangiopathy
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Electron micrograph showing subendothelial lucency and epithelial cell foot process effacement.
A 27-year-old woman was transferred for a higher level of care. She recently delivered a healthy child at 37 weeks by C-section after presenting to her obstetrician with blood pressure over 160/100 and over 3+ urine albumin on dipstick. She was given a preliminary diagnosis of preeclampsia. Shortly after presentation she developed elevated transaminases, thrombocytopenia to about 50,000, an elevated lactate dehydrogenase level greater than 900, and peripheral schistocytes. Her serum creatinine on presentation was over 4 mg/dL and promptly worsened. Urine protein totaled over 3 grams per day and urine sediment showed dysmorphic red blood cells. She was given doses of dexamethasone, started on plasmapheresis, and hemodialysis at the referring institution.
She had no prior medical history and limited prenatal care. She reported no preceding vomiting or diarrhea. Her family history was positive for a sister with kidney failure during pregnancy. An ADAMTS-13 level was sent. She required continued plasmapheresis to maintain platelet level and limit rises in LDH. She continued to require intermittent hemodialysis. A renal biopsy was eventually performed. Representative micrographs are shown below. A diagnosis of pregnancy associated/atypical hemolytic uremic syndrome (aHUS) was considered.
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This case was prepared by Kevin T. Harley, MD, Assistant Clinical Professor of Medicine, Division of Nephrology & Hypertension, University of California Irvine.
Fremeaux-Bacchi V, Fakhouri F, Garnier A, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013 Apr;8(4):554-62
Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81
Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009 Oct 22;361(17):1676-87
The renal biopsy showed evidence of glomerular ischemia with a number of glomeruli appearing shrunken with retraction from Bowman’s capsule. Mesangial cellularity was normal. Glomerular basement membranes appeared diffusely wrinkled with some double contouring. The interstitium did not show active infiltrate. A number of arterioles showed evidence of occlusion some with fibrin staining material. Immunofluorescence staining for IgG, C3, and C1q was negative to low intensity.
Atypical hemolytic uremic syndrome (aHUS) is a disorder related to over-activity and dysregulation of the alternate complement pathway. Other renal pathology related to dysfunction of this pathway include atypical post-infectious glomerulonephritis, dense deposit disease (MPGN type 2), and the so-called C3 glomerulopathies. About 20% of aHUS cases are diagnosed during pregnancy. At least 20% are also familial and the Complement Factor H mutations are the most common genetic mutation noted. Familial aHUS tends to have a worse renal prognosis compared to non-familial forms. The C5 inhibitor eculizimab is approved for treatment of aHUS and is given to stabilize the over-active alternate complement pathway.
Cases of aHUS may present in a similar way to TTP. Severe thrombocytopenia (platelets under 30k) is more likely to represent TTP than aHUS and more likely to respond to plasmapheresis. C3 nephritic factor is positive is most cases of dense deposit disease but not necessarily in aHUS.