B LAZARUS1, A LU1, M TEE1
1Monash Health, Clayton, Australia
A 26-year-old primiparous female was referred at 20 weeks gestation with a thrombotic microangiopathy (TMA) of unclear cause in the setting of poorly controlled type 1 diabetes mellitus. She reported fatigue and mild pedal oedema, but was otherwise asymptomatic and normotensive. Routine investigations demonstrated a microangiopathic haemolytic anemia (haemoglobin [Hb] 70 g/L, moderate schistocytes, haptoglobin <0.06 g/L, LDH 747 U/L) and new thrombocytopenia (platelets 98×10^9/L from 273×10^9/L in early pregnancy). Her renal function was preserved (serum creatinine [sCr] 50 micromol/L, urea 6.6 mmol/L), but there was microscopic hematuria (370 x10^6 cells/L) with glomerular morphology, and heavy proteinuria (urine protein:creatinine ratio 0.5g/mmol) in the setting of baseline macroalbuminuria (pre-pregnancy urine albumin:creatinine ratio 132mg/mmol). Foetal morphology and Doppler studies were normal. Thrombotic thrombocytopenic purpura was excluded (ADAMTS13 activity 95%). Regular blood transfusions were required to maintain a Hb > 80 g/L. Renal function worsened slightly (sCr 85umol/L, urea 14mmol/L) over a period of two weeks, and kidney biopsy demonstrated moderately advanced diabetic nephropathy and TMA without glomerular endotheliosis. Genetic testing for a panel of atypical haemolytic uraemic syndrome (aHUS) genes returned a heterozygous mutation of unknown significance in exon 2 of the CFI gene (c.292A>G, p.Thr98Ala). Eculizumab was commenced for presumed aHUS, however there was minimal improvement in platelet count, renal function and blood transfusion frequency. Over the subsequent 5 weeks she developed hypertension, hyperreflexia, and increased proteinuria. Caesarean section was successfully performed at 27+4 weeks for pre-eclampsia. Within 48 hours her platelet count normalised, haemolysis substantially improved and renal function stabilized (sCr 96 micromol/L, eGFR 71 ml/min), however hypertension persisted. We discuss our approach to distinguishing the cause of TMA in this challenging case.
Ben is a renal registrar at Monash Health.