RESUMEN
Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody-targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size.
Asunto(s)
Síndrome Hemolítico Urémico Atípico/inmunología , Autoanticuerpos/sangre , Fallo Renal Crónico/inmunología , Trasplante de Riñón , Adolescente , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/sangre , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/terapia , Niño , Preescolar , Factor H de Complemento/inmunología , Proteínas del Sistema Complemento/análisis , Proteínas del Sistema Complemento/genética , Femenino , Humanos , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/métodos , Lactante , Irlanda , Fallo Renal Crónico/sangre , Fallo Renal Crónico/genética , Fallo Renal Crónico/terapia , Masculino , Intercambio Plasmático , Recurrencia , Diálisis Renal , Estudios Retrospectivos , Reino UnidoRESUMEN
AIM: Perfusion Index (PI) is a quantifiable measurement of peripheral perfusion and may be a useful adjunct to the assessment of circulatory status in the newborn. (i) To assess reproducibility of PI and (ii) To determine whether there is a difference between simultaneously obtained limb measurements of PI in newborns <32 weeks GA in the transitional period. METHODS: Perfusion Index was measured in newborns <32 weeks during the first 48 h of life. To examine reproducibility, the pulse oximetry probe was replaced on the same limb consecutively by the same operator. Upper and lower limbs were then simultaneously evaluated over a 5-min period. Heart rate, blood pressure, birth weight, ventilation requirement, inotrope use, lactate, PCO2 and CRIB-II score were also recorded. RESULTS: Thirty infants were assessed. Intraclass correlation coefficient for reproducibility in the same limb was high (r value = 0.982 p < 0.001). Measurements obtained in the right upper limb were consistently higher than either lower limb. The median (IQR) PI for the entire cohort was 0.70 (0.29-1.35). No correlation existed between gestational age, birth weight, CRIB scores, systolic and diastolic blood pressure, mean blood pressure and median PI values. CONCLUSION: Perfusion Index measurement is reproducible, and values are highest in the right upper limb. Wide differences between right upper and lower limb readings are most likely related to transitional circulatory changes.
