Patient is a 13-year-old G1P0 female who developed severe acute kidney injury following delivery. Pregnancy was complicated by preeclampsion leading to induction of labor at 37 weeks gestation. At the time of delivery vs Prior to delivery, serum creatine was < 0.5 mg/dl and urinalysis was without proteinuria, although the patient reported headache and malaise. About 3 h post-delivery, she developed severe post-partum hemorrhage secondary to uterine atony, for which she required 3.6 l of blood products. Afterwards, she was noted to have severe hypertension, with blood pressure readings of > 160/90 mmHg. She developed oliguria not responsive to fluid resuscitation or diuretic therapy. Due to developing respiratory distress, she was transferred to the adult medical ICU (MICU) for further management.
MICU course
On arrival to the ICU, chest imaging showed new infiltrates and the patient was treated for hospital acquired pneumonia. Initial blood cultures grew coagulase negative staphylococcus, treated with vancomycin for 72 h. Her serum creatinine (Cr) on admission to the MICU was 2.24 mg/dL). Given this finding in conjunction with persistent oligo-anuria, a right internal jugular hemodialysis catheter was placed, and iHD was initiated on post-partum day three. Renal ultrasound at that time was normal.
Further lab evaluation revealed proteinuria (urine protein to creatinine ratio 19,000 mg/g), transaminitis (AST 37 unit/L, ALT 229 unit/L), worsening anemia (Hgb dropped from 10.5 to 7.1 g/dL), thrombocytopenia (101 K/mcl nadir, with a recent platelet transfusion given for HD catheter placement), and an elevated LDH (2679 units/L; normal < 325 units/L). She was diagnosed with Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP) syndrome. She remained persistently hypertensive requiring increasing doses of beta blockers. Due to persistent hypertension and worsening pulmonary edema, she was transferred from the adult hospital to the local pediatric hospital for further management on post-partum day 7.
Pediatric hospital course
On arrival, the patient had hypertension and respiratory failure requiring BiPAP. Due to fluid overload, she was started on aquapheresis for continuous ultrafiltration. Seven liters of volume was removed in the next 48 h, (Supplementary Fig. 1), with improvement in her blood pressure. Once stabilized, she underwent kidney biopsy on postpartum day 10, which revealed thrombotic microangiopathy (TMA), see Fig. 1. Histology showed thrombi and arteriolar hemorrhage in glomeruli, some with complete necrosis, and small arteries show fibrinoid necrosis and endothelial swelling, with no noted injury to the kidney tubules or interstitium. Additional workup demonstrated normal ADAMTS13 activity (67%) and normal complement evaluation, including sC5B9 (237 ng/mL; normal < 244 ng/mL), C3 (115mg/dL; normal 71–150 mg/dL), C4 (30.2 mg/dL; normal 15.7–47.0 mg/dL), and CH50 (272 units; normal 101–300 units) values, normal factor H and I levels, and absence of Factor H autoantibodies. Hemolysis labs showed elevated LDH at 1751 U/L and low haptoglobin at < 8 mg/dL (See Fig. 2). Shiga toxin testing was not performed due to absence of diarrhea. Liver enzymes were reassuring, with normal ALT at 14 unit/L. The patient was started on complement blockade with eculizumab immediately following the biopsy results (post-partum day 11) after receiving meningococcal immunization (see Supplementary Fig. 2). Penicillin prophylaxis was initiated and continued for duration of eculizumab therapy.
Due to improving volume status, respiratory status, and hematologic parameters, she was rapidly transitioned from continuous renal replacement therapy to iHD (see Supplementary Fig. 1). Soon after eculizumab initiation, her hemolysis improved (see Fig. 2). Her estimated dry weight was eventually established as 62.5 kg (see Supplementary Fig. 1). She received eculizumab 900 mg every 72 h for four doses. Eculizumab efficacy was evaluated by laboratory evaluation of CH50 (goal < 14 U), eculizumab drug levels (goal > 99 mcg/mL), sC5b9 (ng/ml), as well as markers as hemolysis (including hemoglobin and LDH, Fig. 2). On discharge, she was transitioned to maintenance eculizumab dosing of 1200 mg every week. She was undergoing dialysis 3 days per week and began to produce urine.
Patient follow up
Renal function and urine output continued to improve as an outpatient. CH50 levels and eculizumab levels remained therapeutic (eculizumab 277 mcg/mL, CH50 12 U, Supplementary Fig. 2). Eculizumab dosing frequency was able to be spaced, initially to every 2 weeks followed by every 4 weeks at 6 months after disease presentation, with stability in hemolysis labs (see Fig. 2). By 6 weeks following presentation, she was producing 2 l of urine per day and hemodialysis was discontinued. Her serum Cr stabilized at 1.3–1.5 mg/dL (see Supplementary Fig. 3) with an estimated glomerular filtration rate (GFR) of 53 ml/min/1.73m2 and all supplements/therapies for chronic kidney disease were discontinued. She remained only on anti-hypertensive therapy, including an ACE inhibitor for persistent proteinuria (which was initiated once the patient initiated a long-acting contraceptive agent). Her eculizumab was discontinued by 12 months, at which time her markers of hemolysis (LDH, haptoglobin) were normal, with stable platelets and hemoglobin (see Fig. 2). Complement genetic testing panel of 10 genes associated with aHUS (C3, CFB, CFH, CFHR1, CFHR3, CFHR5, CFI, DGKE, MCP, THBD) showed no variants of clinical significance.
