Eculizumab Modifies Outcomes in Adults with Atypical Hemolytic Uremic Syndrome with Acute Kidney Injury.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. METHODS: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. RESULTS: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. CONCLUSION: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.

Trasplante renal procedente de donante vivo HLA incompatible: Eficacia y pronóstico en 32 pacientes tras desensibilización / Kidney transplantation from HLA-incompatible live donors: Efficiency and outcome of 32 patients after desensitisation

La desensibilización es un método empleado en trasplante renal para tratar de trasplantar a pacientes que presentan una prueba cruzada positiva frente a su donante. El objetivo del estudio es mostrar los resultados de nuestro hospital en pacientes trasplantados renales con donantes vivos HLA incompatibles, tras un protocolo de desensibilización. Estudiamos a 32 pacientes de 46±14 años que presentaban una intensidad media de fluorescencia (MFI) frente a HLA de clase I de 7.979±4.089 y de 6.825±4.182 para MFI frente a clase II y relative intensity scale(RIS) de 8,9±7,6. La prueba cruzada fue positiva por citotoxicidad dependiente del complemento (CDC) en 18 pacientes, citometría de flujo (CF) en 7 y anticuerpos donante específicos (ADE) en 7. El protocolo empleado fue: rituximab, plasmaféresis/inmunoadsorción, inmunoglobulinas, tacrolimus, derivados ácido micofenólico y prednisona. Tras 8±3 sesiones de plasmaféresis/inmunoadsorción se trasplantó a 23 pacientes (71,9%) y resultó ineficaz en 9. Existían diferencias basales en MFI clase I (p<0,001), RIS (p=0,008) y cross-match por CDC, ADE o CF (p=0,05). El MFI de clase I y el RIS resultaron predictores de eficacia en curvas COR. Tras un seguimiento de 43±30 meses, 13 pacientes (56%) presentaron sangrado postoperatorio, 3 (13%) función retrasada injerto, 4 (17,4%) rechazo agudo, 6 (26%) viremia CMV y uno (4%) viremia BK. Al 5.° año, la supervivencia del paciente fue del 90% y la supervivencia renal del 86%. En ese mismo año, la creatinina fue de 1,5±0,4 y la proteinuria de 0,5±0,7. Conclusiones: El trasplante renal de donante vivo HLA incompatible tras la desensibilización fue posible en el 71,9% de los pacientes. MFI de clase I y RIS predicen ineficacia de la desensibilización. La supervivencia renal (86% al 5.° año) es aceptable con baja incidencia de rechazo agudo (17,4%), aunque con una mayor tendencia al sangrado postoperatorio (AU)

Desensitisation is a procedure undergone by the recipient of a kidney transplant from a donor who is cross-match positive. The aim of this study was to present the outcomes from our hospital of kidney transplant recipients from HLA-incompatible live donors after desensitisation. We studied 32 patients aged 46±14 years with a mean fluorescence intensity (MFI) versus class I HLA of 7979±4089 and 6825±4182 MFI versus class II and relative intensity scale (RIS) of 8.9±7.6. The complement-dependent cytotoxicity (CDC) cross-matching test was positive in 18 patients, flow cytometry was positive in 7 patients and donor-specific antibodies (DEA) were detected in 7. The protocol used was rituximab, plasmapheresis/immunoadsorption, immunoglobulins, tacrolimus, mycophenolic acid derivatives and prednisone. After 8±3 sessions of plasmapheresis/immunoadsorption, 23 patients were trasplanted (71.9%) and desensitisation was ineffective in 9. There were baseline differences in MFI class I (P<.001), RIS (P=.008), and CDC cross-matching, DSA and flow cytometry (P=.05). MFI class I and RIS were predictors of inefficiency in ROC curves. After follow-up of 43±30 months, 13 patients (56%) presented postoperative bleeding, 3 (13%) delayed graft function, 4 (17.4%) acute rejection, 6 (26%) CMV viraemia and 1 (4%) BK viraemia. Five-year patient survival was 90%, with 86% allograft survival. Five-year creatinine was 1.5±0.4 and proteinuria was 0.5±0.7. Conclusions: Kidney transplantation from HLA-incompatible live donors after desensitisation was possible in 71.9% of patients. MFI class I and RIS predict the inefficiency of desensitisation. Five-year allograft survival (86%) was acceptable with a low incidence of acute rejection (17.4%), although with a greater trend towards postoperative bleeding (AU)

Kidney transplantation from HLA-incompatible live donors: Efficiency and outcome of 32 patients after desensitisation. / Trasplante renal procedente de donante vivo HLA incompatible: Eficacia y pronóstico en 32 pacientes tras desensibilización.

Desensitisation is a procedure undergone by the recipient of a kidney transplant from a donor who is cross-match positive. The aim of this study was to present the outcomes from our hospital of kidney transplant recipients from HLA-incompatible live donors after desensitisation. We studied 32 patients aged 46±14 years with a mean fluorescence intensity (MFI) versus class I HLA of 7979±4089 and 6825±4182 MFI versus class II and relative intensity scale (RIS) of 8.9±7.6. The complement-dependent cytotoxicity (CDC) cross-matching test was positive in 18 patients, flow cytometry was positive in 7 patients and donor-specific antibodies (DEA) were detected in 7. The protocol used was rituximab, plasmapheresis/immunoadsorption, immunoglobulins, tacrolimus, mycophenolic acid derivatives and prednisone. After 8±3 sessions of plasmapheresis/immunoadsorption, 23 patients were trasplanted (71.9%) and desensitisation was ineffective in 9. There were baseline differences in MFI class I (P<.001), RIS (P=.008), and CDC cross-matching, DSA and flow cytometry (P=.05). MFI class I and RIS were predictors of inefficiency in ROC curves. After follow-up of 43±30 months, 13 patients (56%) presented postoperative bleeding, 3 (13%) delayed graft function, 4 (17.4%) acute rejection, 6 (26%) CMV viraemia and 1 (4%) BK viraemia. Five-year patient survival was 90%, with 86% allograft survival. Five-year creatinine was 1.5±0.4 and proteinuria was 0.5±0.7. CONCLUSIONS: Kidney transplantation from HLA-incompatible live donors after desensitisation was possible in 71.9% of patients. MFI class I and RIS predict the inefficiency of desensitisation. Five-year allograft survival (86%) was acceptable with a low incidence of acute rejection (17.4%), although with a greater trend towards postoperative bleeding.