Sepsis associated Acute Kidney Injury: incidence, risk factors and continuous renal replacement therapies

Abstract

A-AKI has a high incidence and mortality in critically ill septic patients. We hypothesized that current recommendations for sepsis management do not prevent SA-AKI incidence. Furthermore, the need for CRRT in septic shock patients with SA-AKI is very high. We hypothesized that CRRT timing in these patients should be based on urine output (UO). Finally, when CRRT is indicated, we hypothesized that CVVHD is superior to CVVH in terms of extracorporeal circuit patency and abscence of dialytrauma. In our first study the worsening of SA-AKI stage or the appearance of SA-AKI during the following 7 days (from sepsis onset) was clearly associated with a worst outcome in terms of survival (90-day survival). An important percentage of septic patients presented hypotension and this was clearly associated with SA-AKI incidence as well as the presence of an abdominal etiology which is a well-known risk factor for SA-AKI development. Although the accomplishment of the SSC tasks in our study population was globally low, contrary to other studies we did not observe a decrease of SA-AKI incidence in those patients who had high levels of accomplishment. When SSC tasks were separately analized, early antibiotic administration was not related with a lower incidence of SA-AKI either. In those patients who were hypotensive, EGDT measures achievement did not decrease SA-AKI incidence. In our second international observational study, we analyzed all those patients with SA-AKI whom required CRRT due to a septic shock condition within the first 24 h from CRRT initiation. A higher age, severity of illness, medical as opposed to surgical admission, a higher BUN at CRRT initiation, a decreased UO and SCr at CRRT initiation, and more days from hospital admission to CRRT initiation were all associated with worse survival. No association between SA-AKI stage at CRRT initiation and 90-day mortality was observed, the same as the majority of previous studies reported. Whether earlier strategies of CRRT initiation (known as “timing”) could have an impact in the outcome of patients with SA-AKI was evaluated in a subgroup of homogeneous patients with septic shock all of them presenting advanced SA-AKI stage 3 at ICU admission and initiated on CRRT within the first 5 days from ICU admission. UO and time from ICU to CRRT were compared as timing criteria and UO proved to be more useful when deciding CRRT initiation than a standard “clock time” from ICU admission variable. To demonstrate a higher EC patency with the use of CVVHD in SA-AKI patients we performed a third study comparing the use of CVVHD associated to an adsorption capacity membrane with the use of CVVH associated to the same membrane. Filters were changed at 24 h and 48 h in order to ensure de adsorption capacity. We observed a trend to a longer EC patency with the use of CVVHD although this was not translated in a decrease in the number of dialytrauma events. Cytokines concentrations were measured during the first 72 h and no differences were observed between both groups with the use of an adsorption capacity membrane. Based on all these previous findings we can conclude that SA-AKI incidence and mortality are high in critically ill patients with sepsis especially in those who present hypotension or septic shock. These last patients due to their severe condition often require CRRT which should be initiated only in advanced AKI stages with immediate initiation criteria together with the help of UO. Finally, CRRT in SA-AKI patients when necessary should be encouraged to a preferential use of CVVHD associated to adsorption capacity membranes which seem to improve EC patency with no clinical outcome differences when compared to CVVH.

A pesar de los avances en los campos del fracaso renal agudo (FRA) y la sepsis, la aparición de fracaso renal agudo de origen séptico (FRA-S) en el paciente crítico continúa asociándose a una elevada morbimortalidad. En la actualidad el tratamiento del FRA-S es de soporte y fundamentalmente dirigido al cumplimiento de las recomendaciones internacionales en el manejo del paciente séptico, minimizar la hipervolemia asociada a la disminución de la diuresis, y evitar el uso de nefrotóxicos. En estos pacientes críticos con FRA-S es habitual la necesidad de terapias de reemplazo renal (TRR) como tratamiento de soporte. El momento de inicio de las TRR y la modalidad empleada han generado en los últimos tiempos una importante discusión científica sin que por el momento se haya evidenciado ninguna mejoría pronóstica con el inicio precoz o con el uso de una modalidad determinada. Es por ello que el propósito de este trabajo durante estos años ha sido el de evaluar la incidencia real y mortalidad asociada que el FRA-S tiene en el paciente crítico con sepsis, la identificación de los factores de riesgo asociados a la aparición de FRA-S, el impacto que el cumplimiento de las medidas internacionales en la sepsis tiene sobre la incidencia de FRA-S, la identificación de las variables clínicas asociadas al pronóstico de los pacientes críticos con FRA-S que requieren TRR así como su posible utilidad para definir una estrategia de inicio precoz (con impacto pronóstico), y por último, a través un ensayo clínico piloto, evaluar en el mismo tipo de población (enfermos críticos con FRA-S) los beneficios del uso de una modalidad difusiva como la hemodiálisis venovenosa continua (HDVVC) en comparación con el uso de una modalidad convectiva como la hemofiltración venovenosa continua (HVVC), empleando la misma membrana con capacidad de adsorción en ambos grupos.