CAPITULO 5: MARCO TEÓRICO
5.2 Diferentes informes de la competitividad de las naciones
What are the outcomes for patients with AKI? There is clear evidence that outcomes for AKI are poor. According to local data, only 56% of patients who experienced severe AKI in hospital survived to discharge; only 28% survived to 3 years post discharge.43Most studies of AKI in the intensive care unit
(ICU) report a mortality exceeding 50%. It is clear that ICU and in-hospital mortality increases alongside severity of AKI.1,4,46–56Despite the trend of lower mortality in recent years, AKI still remains an important negative prognostic factor, particularly in critically ill patients. Even small isolated increases in serum creatinine levels have an associated increase in short-term morbidity and mortality and in longer-term outcomes, including 1-year mortality;38,48,57–62this is even more the case when RRT is required.5,6,13,34,63
A study from the Medicare Sample Beneficiary Analytical File from 1992 to 2001 found that patients with AKI who required RRT had an in-hospital mortality rate of 32.9%, compared with 27.5% in patients with AKI not requiring RRT, and 4.6% in patients without AKI. Importantly, it found that the mortality rate was 32.6% in patients with AKI coded as a secondary diagnosis, and 15.2% in patients with AKI coded as a primary diagnosis.40This confirms what is already known: that isolated AKI without other organ
involvement has a better prognosis than AKI in the context of multiple organ failure.
Chronic kidney disease is an independent predictor of morbidity and mortality.64,65Hence we would
assume that AKI in CKD has a summative effect on outcome, giving rise to the question whether or not the outcome of AKI differs with the presence of background CKD. Studies actually demonstrate lower in-hospital mortality rates in patients with AKI with a background of CKD than in patients without a background of CKD.41,53,57,66–69This would seem counterintuitive. One explanation might be that patients with CKD require less of an insult to manifest clinically apparent AKI, and thus the severity of the AKI episode is less in these patients, resulting in better outcomes. In addition, patients experiencing‘silent and discrete’ AKI, which remains unrecognised and does not lead to admission, will not be captured by epidemiological studies. Only the more seriously ill patients with clinically apparent and recognised AKI will be included, leading to a bias in mortality statistics. Conversely, those with CKD may have more resilience to acute insults secondary to conditioning or priming, and tolerate AKI better. It is also possible that those with CKD receive better/different care from their non-CKD counterparts when AKI is identified, thus impacting outcomes. Finally, it been suggested that results may be confounded by malnutrition (lower serum creatinine values from low muscle mass).57
Even small isolated increases in serum creatinine levels have an associated increase in short-term morbidity and mortality and in longer-term outcomes, including 1-year mortality.1,2,4,47,58,59,70,71‘Silent and discrete’
episodes of AKI in the community, therefore, require further research directed at recognition and early indentification, as intervention in this group may have a significant effect on outcomes.
Another outcome of paramount interest is renal recovery. According to the annual report of the US Renal Disease Survey 2006,60approximately 6% of patients with AKI progressed to ESRD within 2 years, and
two-thirds of hospitalised patients who had AKI and progressed to ESRD had background CKD. CKD or comorbid conditions leading to CKD are risk factors that predict dialysis dependence following AKI.61,62
Wald et al.72looked at outcomes of chronic dialysis and death in AKI patients requiring in-hospital dialysis
who survived free of dialysis for at least 30 days after discharge, from a 10-year cohort of all adult patients in Ontario, Canada. Patients with AKI were three times more likely than those without AKI to require chronic dialysis.72Individuals with pre-existing CKD who had AKI requiring dialysis had a twofold higher risk of chronic
dialysis than patients with CKD without AKI requiring dialysis. Patients with AKI requiring dialysis without pre-existing CKD had a 15-fold higher risk of chronic dialysis than patients with CKD without AKI.72
Other observational and database studies demonstrate that AKI, with a background of CKD, leads to ESRD at a higher frequency than does AKI alone.12,40,46Ishani et al.12assessed, based on Medicare claims, a random
cohort of 233,803 hospitalised patients aged≥ 67 years on discharge and without previous ESRD or AKI. Patients with concomitant AKI and CKD were far more likely to develop ESRD, indicating a strong multiplicative effect of the interaction on ESRD development.12A population-based study by Ali et al.46compared patients
with ACKD and those with AKI alone. Patients with ACKD were older, with less chance of renal recovery.
Importantly, these studies all depend on the definitions of both CKD and AKI, which may not be accurate or comparable. For example, the definition of CKD is based on diagnostic coding or pre-operative GFR taken as a baseline function. These can introduce bias in AKI and CKD detection. Singh et al.73suggested
that differences could also reflect greater specificity of administrative codes for AKI among patients without CKD. This underlines the need for consensus on the definition of baseline function. The debate surrounding definition will be discussed in more detail later.
There is mounting evidence that AKI contributes significantly to CKD and CKD progression, leading to ESRD. Okusa et al.30(pathophysiological concepts from Sutton et al.28) suggest that, following AKI, there
are four possible outcomes: (1) full recovery; (2) incomplete recovery resulting in CKD; (3) exacerbation of pre-existing CKD accelerating progression to ESRD; and (4) non-recovery of function leading to ESRD. We suggest a fifth outcome: AKI does not necessarily have to be associated with progressive CKD; instead, incomplete recovery may occur, leading to step-down in GFR, which subsequently remains stable.
There is no doubt that mortality from AKI is high. In those who survive, there may be decline in function, in some cases leading to ESRD, either at the time of AKI or in the future.51,74–77Even in patients with complete recovery there is still reduced survival and increased incidence of CKD in the years following AKI.12,78Patients experiencing AKI are likely to also have risk factors for CKD. It may be that patients
without known background CKD who develop AKI already have unrecognised renal disease and reduced functional reserve, not yet manifested as CKD. These patients are programmed to develop future CKD, and the AKI episode simply speeds up the development of overt CKD. Ishani et al.,12based on Medicare
claims, reported that of patients with AKI and no background of CKD, 72.1% had CKD documented within 2 years of AKI. Triverio et al.79demonstrated that AKI progressed to CKD within 3 years in 50% of
patients without background CKD. Hsu et al.80suggested that the growth of ESRD incidence (in the USA)
could not be accounted for solely by the rise in CKD incidence. Growth in ESRD incidence may partly be attributable to AKI.
There are further studies suggesting that development of CKD and dialysis dependency follow AKI.1,2,7,9,67,81
Amdur et al.82tested the hypothesis that AKI, and specifically ATN, causes CKD. A total of 5404 out of
113,272 patients (US Department of Veterans Affairs database, 1999–2005) had diagnostic codes indicating AKI or ATN without background CKD. A diagnosis of ATN without background CKD was associated with a similar time to development of stage 4 CKD to that of a patient with early CKD. Twenty per cent of survivors of ATN rapidly progressed to CKD stage 4. Diagnostic codes of AKI and ATN were associated with a significant decline in function over time after hospital discharge. Survivors of AKI were more likely than controls to progress to late-stage CKD. The authors concluded that AKI might be an important cause of CKD.82
If AKI is a cause of CKD, it seems logical that AKI may exacerbate pre-existing CKD. There are, however, difficulties in testing this hypothesis. A large number of risk factors for AKI are the same as those for CKD. AKI also occurs more frequently in an older population with greater burden of comorbidity, in which there may be greater risk of CKD progression anyway. Many studies looking at outcome following AKI concentrate on survival and subsequent ESRD development; however, resultant CKD and CKD progression are less well reported. These studies again depend on the definitions used.
Could minor episodes of AKI in the community, which are not acknowledged to have occurred because renal function is either not tested or not properly assimilated, be contributing to development and/or progression of CKD? The effect of‘silent and discrete’ episodes of AKI in the community on CKD progression is presently unknown. There is growing evidence that‘multiple hits’ may well contribute to progression in susceptible individuals.
Following an episode of AKI, Kidney Disease: Improving Global Outcomes (KDIGO) guidelines83suggest
that we should evaluate patients within 3 months for resolution of AKI, and at 3 months or after for new onset or worsening of pre-existing CKD. They also suggest that if patients do not have CKD they should be considered at increased risk, on the assumption that one AKI episode demonstrates‘susceptibility’ and qualifies a high-risk population. Further research is warranted to inform the optimal follow-up period and to facilitate better understanding of the clinical consequences of AKI in patients with and without underlying CKD.83