in a previous issue of critical care , lai and colleagues describe a population - based cohort study evaluating the risk of severe sepsis following hospitalization associated with an episode of severe acute kidney injury ( aki ) requiring renal replacement therapy ( rrt ) . using a large administrative database over a 10-year period , patients with severe aki receiving rrt who survived to at least 90 days after hospital discharge were matched to those without severe aki and followed for approximately 4 years for the occurrence of severe sepsis . the adjusted risk of developing severe sepsis prompting hospitalization was approximately twofold higher among those having had severe aki compared with those not having had aki ( incidence rate of 6.84 vs. 2.32 per 100 person - years ) . importantly , even among survivors with severe aki who recovered kidney function to become dialysis independent , the adjusted risk of severe sepsis remained 50 to 70% higher compared with matched patients with no history of aki . aki remains a widespread complication of acute illness , occurring in one in five adults and one in three children in association with an acute hospitalization . trends from observational data provide compelling evidence that the incidence of aki continues to grow . while mortality has concomitantly decreased , more patients are ultimately suffering the long - term sequelae of aki . these sequelae include increased long - term risks of death , chronic kidney disease ( ckd ) , progression to end - stage kidney disease , reduced quality of life and excess resource utilization . prior data have shown that aki in critical illness most commonly occurs in association with sepsis and that its presence clearly worsens the risk of adverse outcomes . however , fewer studies have focused specifically on any increased risks imposed by aki for the downstream development of sepsis and consequent morbidity and mortality [ 7 - 11 ] . one of the earliest studies to show an increased risk of sepsis after aki was performed in a cohort of hospitalized patients suffering aki following radiocontrast procedures . among nonsurvivors similarly , nosocomial infections occur more commonly among critically ill patients with severe aki requiring rrt compared with matched controls . a recent cohort study noted that sepsis after any aki occurred in 40% of critically ill patients after a median 5 days . among critically ill patients with severe aki receiving rrt sepsis after aki portends a higher risk of rrt utilization and death and higher resource utilization . indeed , among nonsurvivors hospitalized with aki , sepsis was the most common attributable cause of death , occurring in 41% . these data clearly establish aki as an immediate and short - term risk factor for the development of nosocomial infections and sepsis . this specific short - term risk among critically ill patients would appear understandable ; however , the precise pathophysiologic mechanisms whereby aki increases susceptibility for sepsis remains incompletely understood . there is probably a complex interplay of modifying factors including premorbid conditions that are also associated with higher risk of infection , such as genetics ( for example , gene polymorphisms in inflammatory mediators ) , older age and comorbidities ( for example , ckd , cancers ) , as well as more proximate factors including acute immune dysregulation , acute organ dysfunction , and treatment - related risks ( for example , mechanical ventilation , hemodialysis catheter ) . the data described by lai and colleagues do not inform about the short - term risk of severe sepsis after aki . instead , their study specifically evaluated the longer - term risk of severe sepsis conditional on survival to 90 days after index hospitalization . while nonmodifiable risk factors such as genetics , age , comorbidity and ongoing treatment - related risks are probably still contributing factors , the biologic mechanisms whereby aki confers longer - term susceptibility to infection and sepsis are unknown . nonetheless , the aki and infection susceptibility association is plausible given that acute kidney insults are known to induce changes in gene regulation , oxidative stress , inflammation , leukocyte trafficking , and apoptosis and to incite systemic and distal organ injury . while the idea that aki independently confers increased risk of severe sepsis long after the occurrence of aki is conceptually appealing , there are some caveats to consider . the hypothesis posited by lai and colleagues is that aki confers a sustained susceptibility to the development of new infections or severe sepsis through persistent immune suppression or senescence . while the study did show an increased risk of severe sepsis for survivors who recovered from aki , the risk of severe sepsis among rrt - dependent survivors may largely be explained by rrt dependence itself . sepsis remains a leading cause of morbidity and mortality among end - stage kidney disease patients : the rate of sepsis for us chronic hemodialysis patients was recently reported to be 282 per 1,000 patient - years . similarly , persistent nondialysis - requiring ckd could serve to confound any association between aki and increased susceptibility to sepsis for those who recovered to become dialysis independent . maladaptive repair mechanisms after aki and incident ckd have been shown to modify the long - term risk of developing severe sepsis . the study by lai and colleagues has appropriately focused attention on the critical importance of long - term surveillance of survivors of aki and may ultimately generate a number of important additional avenues of inquiry . if the risk of downstream severe sepsis is increased among survivors of severe aki , can we identify those most susceptible and are such episodes amenable to preventative interventions ? first , additional mechanistic and clinical studies are needed to better define the nature , magnitude and duration of the risk of severe sepsis following aki , independent of the risks conferred by either ckd or end - stage kidney disease that requires ongoing rrt . aki : acute kidney injury ; ckd : chronic kidney disease ; rrt : renal replacement therapy . smb is supported by a canada research chair in critical care nephrology and clinical investigator award from alberta innovates  health solutions .
many prior studies have shown that , in critically ill patients , acute kidney injury ( aki ) commonly occurs in association with sepsis and its presence portends an increased likelihood of poor outcomes . 
 in contrast , few studies have focused specifically on the influence of aki on the long - term risk of developing sepsis . in a previous issue of critical care , a population - based cohort study by lai and colleagues reported a long - term increased risk of severe sepsis for patients surviving beyond 90 days following hospitalization with an episode of aki requiring renal replacement therapy . while the pathophysiologic mechanisms that underpin this finding remain to be elucidated and causality can not be proven , this study suggests that severe aki confers long - term susceptibility to infection and focuses further attention on the critical importance of long - term surveillance for survivors of severe aki . 
 further mechanistic and clinical studies are required to more precisely define the extent and duration of any increased risk of severe sepsis beyond which a need for ongoing renal replacement therapy following aki might be associated . 
 nonetheless , this novel study by lai and colleagues could lead to a number of important new avenues for clinical inquiry , such as whether it might be possible to identify those most susceptible to severe sepsis after aki and , ultimately , whether such episodes might be preventable .