Acute kidney injury (AKI) is a common complication among hospitalized patients, particularly in the Intensive Care Unit (ICU) setting, and it portends an ominous outcome. In fact, the incidence of AKI in critically ill patients varies from 35 to 70%, and it is associated with increased in-hospital mortality (10 to 60%) [1–4].

Although AKI is a common complication in the hospital and has an immediate impact on morbidity, mortality, and resource utilization, its detrimental effect appears to persist also after recovery, since AKI has shown to increase long-term mortality [5–7]. Understanding the impact of AKI on long-term outcomes will have a marked impact on treatment and risk stratification during hospitalization and will assist with guiding follow-up care after discharge.

Sepsis is a well-known risk factor for the development of AKI and nearly half of all patients with AKI have sepsis [8, 9]. Furthermore, AKI is associated with increased short-term mortality among septic patients [8–14]. Despite the detrimental effect of AKI on short-term outcome, to our knowledge, there is no study evaluating the influence of AKI on long-term mortality of hospital surviving septic patients.

In the present study, we sought to evaluate the impact of AKI on long-term mortality in a cohort of patients with sepsis.

This is a retrospective study that evaluated the influence of AKI during previous ICU admission on long-term mortality of hospital surviving septic patients admitted to the Infectious Disease Intensive Care Unit of our hospital between July 2002 and June 2007. This unit is the reference medical infectious disease unit for adult patients with infectious diseases who need intensive care, providing medical assistance to an area (Lisbon to south of Portugal) with almost 3000000 inhabitants.

Since this was a retrospective and observational study that did not evaluate a specific therapeutic or prophylactic intervention the institutional ethical approval was not required according to our institution's guidelines.

It has been shown that patients who survive AKI have a greater rate of long-term mortality and other adverse outcomes than patients who survive hospitalization without AKI, in varied settings, such as community/hospitalized patients, hospitalized patients, ICU patients, cardiac surgery, patients undergoing aortic stent placement or percutaneous coronary intervention, liver transplant and lung transplant [19].

Sepsis is a well-known risk factor for the development of AKI and nearly half of all patients with AKI have sepsis [8, 9]. Furthermore, AKI is associated with short-term mortality among septic patients [8–14]. Despite the detrimental effect of AKI on short-term outcome, to our knowledge, the influence of AKI on long-term mortality of septic patients has not yet been assessed.

We conducted a retrospective study of a cohort of 234 hospital surviving septic patients, in order to determine the impact of AKI during ICU admission on 2-year mortality. We found that AKI had a negative impact on 2-year mortality of patients with sepsis. As compared with patients without acute renal impairment, patients with AKI had an increased probability of death of 25.3%, which corresponded to a 3.2-fold risk of death. These findings expand on results from previous studies that showed the increased risk of short-term death associated with AKI in septic patients [8–14].

The mechanism by which AKI contributes to decreased long-term survival is not completely understood. After an episode of AKI, it is likely that there is failure to resolve renal structure and function adequately [20–22]. Acute kidney injury itself may increase the risk of subsequent events and decrease kidney reserve leading to an increased risk of chronic kidney disease. In fact, despite we do not have serial values of blood pressure, serum creatinine and proteinuria, it has been shown that chronic kidney disease with subsequent hypertension, proteinuria and increased cardiovascular disease has been appointed as a possible cause of poor long-term outcome among AKI patients [23]. Moreover, volume overload, coagulation abnormalities, an increased incidence of sepsis with multi-organ failure, and cytokine or immune-mediated major organ dysfunction are other possible explanations for poor survival among AKI patients [24, 25].

In the present study, mortality did not differ among AKI patients with and without complete renal function recovery. These results should be interpreted with extreme caution, since the number of patients may be insufficient to detect a difference on outcome. However, the similar outcome between AKI patients who did or not recover renal function could also be explained by the permanent injury to other vital organs caused by AKI, thus affecting future survival, despite the reversible nature of clinical AKI in which serum creatinine level returns to baseline after the episode [24–26]. Therefore, our results could also suggest that despite patients with septic AKI are prone to recover renal function [9, 14], they should be closely monitored after discharge.

Our study has several limitations. First, the single-centre nature of the study largely limits its generalizability, and its retrospective design with a relatively small cohort of patients did not allow the evaluation of other confounders with prognostic importance. Second, baseline serum creatinine was available only in 68.8% of patients, while in the remaining cases (31.2%) it was estimated by the Modification of Diet in Renal Disease equation, as it has been recommended and previously applied [1, 15]. Regarding this, it should be stressed that the use of Modification of Diet in Renal Disease equation to estimate baseline serum creatinine, despite performing reasonable well when basal glomerular filtration rate is normal or near normal, could overestimate the incidence of AKI in chronic kidney disease patients [27]. Third, the evolution for chronic kidney disease and end-stage renal disease after AKI, as well as the causes of death were unattainable. Fourth, outcome data were available only in 77% of patients. Regarding this issue, it is important to mention that hospital survivors lost to follow-up and with known follow-up were similar in terms of age, gender, race, medical history, illness severity, baseline renal function, proportion of patients with AKI, proportion of AKI patients in the different RIFLE categories or undergoing renal replacement therapy, percentage of patients with septic shock or need for mechanical ventilation, and length of hospitalization. Taking into consideration the similar characteristics of hospital survivors lost to follow-up and with known follow-up, we think that it is not expectable that substantially different results would be achieved if the outcome data of all surviving patients was available. In fact, our results are in line with those focusing on the effect of AKI on long-term outcome in other settings [19], and likely, AKI can also exert a negative influence on long-term outcome of patients with sepsis. Finally, the number of patients in the different AKI categories was too small to determine the role of severity of AKI on long-term outcome.

Despite the aforementioned constraints, our study has the main virtue of being, to our knowledge, the first study reporting the negative impact of AKI on long-term mortality of patients with sepsis, a specific setting where AKI is pathophysiological and clinically distinct from AKI of other etiologies [9, 28]. The appropriate management of the patients with sepsis through early goal-directed resuscitation, early administration of broad-spectrum antibiotic therapy, therapy with vasopressor agents (when fluid challenge fails to restore adequate blood pressure and organ perfusion), use of recombinant activated protein C (in patients with severe sepsis and high risk for death), use of low-tidal volume ventilation and blood glucose control is essential to prevent or limit AKI severity and, as such, could improve the long-term outcome of septic patients after hospital discharge [29].

Our results suggest that AKI negatively influences long-term mortality of patients with sepsis. Despite septic patients who develop AKI and survive their acute episode have greater likelihood for renal function recovery the negative impact of AKI on long-term mortality deserves an additional effort to closely monitor them after hospital discharge.