The third and fourth doses of eculizumab were given 1 and 2 weeks after transplantation, and then dosing was transitioned to every other week, with laboratory studies immediately before dosing

The third and fourth doses of eculizumab were given 1 and 2 weeks after transplantation, and then dosing was transitioned to every other week, with laboratory studies immediately before dosing. the door to this type of definitive care for this devastating disease. Introduction Atypical hemolytic uremic syndrome (aHUS) is a disease of the microvasculature classically characterized by the triad of hemolytic anemia, thrombocytopenia, and acute kidney injury (1C3). It disproportionately affects children, with more than half progressing to ESRD (4). A mortality rate of 10% to 15% has been reported during acute episodes. The likelihood of recurrence of aHUS after (-)-Epicatechin renal transplantation can make the decision to transplant particularly difficult, especially in aHUS patients who suffer multisystem dysfunction during renal exacerbations or at the time of native or transplant kidney loss (5C10). For many aHUS patients, lifelong dialysis has been prescribed as the treatment of choice for ESRD. aHUS is usually caused by uncontrolled activation of the alternative pathway (AP) of the complement system, with more than 120 reported loss-of-function mutations in the AP regulatory proteins complement factor H (CFH), complement factor I (CFI), and membrane-cofactor protein (4,9C13). Gain-of-function mutations in complement factor B (and the complement factor H-related (and (gene for membrane-cofactor protein), gene that encodes a fusion protein comprised of the first 18 short consensus repeats of CFH and the last 2 short consensus repeats of (21). This hybrid gene encodes a protein product identical to a functionally significant CFH mutant (c.3572C T, S1191L and c.3590T C, V1197A) that has been previously described in association with aHUS. Pretransplant Risk-Benefit Considerations The patient’s clinical history and her genotype results suggested a substantial risk for recurrence of her native disease should a kidney transplant be attempted. (-)-Epicatechin The patient’s life was not immediately in danger; however, she had a significant long-term risk for cardiac disease and a shortened life span if she remained on dialysis. The possibility of a combined deceased-donor liver-kidney transplant was considered, but given the significant morbidity and mortality reported with the procedure when first attempted for factor HCassociated aHUS, this was not pursued further. It was felt that this long-term risk of dialysis and the emerging evidence of the effectiveness of eculizumab represented an opportunity to utilize an alternative approach for this patient. With a transplant there were several potential risks: aHUS recurrence, contamination due to complement blockade (along with usual transplant immune suppression), the development of antibodies to the biologic agent eculizumab, and the long-term interpersonal and financial burden of being maintained indefinitely on a frequently delivered intravenous medication. The decision to proceed with kidney transplant was Ace made only after the family had been instructed on each of these risks and had decided along with their medical team that transplantation was the preferred option. Preparation for Transplantation A living nonrelated renal donor was identified after 15 months of chronic hemodialysis. Insurance approval for eculizumab preconditioning and subsequent therapy was obtained, and members of the Rare Renal Disease Clinic approved the patient for transplantation. She was immunized against meningococcus 6 months before transplant; however, no meningococcal vaccine response was noted with titer assessment. Before transplantation, the patient was re-immunized and placed on ciprofloxacin for (-)-Epicatechin meningococcal prophylaxis. All routine childhood (-)-Epicatechin immunizations were current per the American Academy of Pediatrics recommendations. Transplantation and Subsequent Course The patient received her usual thrice-weekly dialysis before renal transplantation. She underwent her second renal transplant 1 month before her 13th birthday using the protocol outlined in Table 1. One week before transplantation, PE with 1.5 volumes of albumin was performed and one dose of eculizumab (900 mg) was given immediately thereafter. The day before transplant, before hemodialysis, the patient received (-)-Epicatechin a second PE (1.5 volumes of fresh frozen plasma) and was admitted in preparation for surgery. A second dose of eculizumab (900 mg) was given the evening before surgery. Table 1. Protocol for the prophylactic use of eculizumab for renal transplant in aHUS Pretransplant evaluation????Donor evaluation for pathogenic aHUS mutations.????Immunize against meningococcus (as well as hemophilus and pneumococci if not current).????Verify titer if on dialysis or if immune suppressed at the time of vaccinationconsider re-immunization and antibacterial prophylaxis as necessary.Zero minus 1 week (before transplant)????Measure C3, C4, AH50, CH50, C5 functional level,.