Acute kidney injury, outcome studies

Abstract

Acute kidney injury (AKI) is a complex syndrome for which no effective treatment exists, and our understanding of this condition is limited. If the acute kidney injury is severe enough to require renal replacement therapy, mortality rates at six months are around 60%. Yet, even this severe form of AKI is common affecting over 5% of all patients admitted to the intensive care unit.

The overall objective of this thesis was to study the association between acute kidney injury and short-term as well as long-term outcome. In total, we studied 3710 patients, in two single-centre and two multicenter studies. All four papers were restricted to adults only.

The first paper addresses the lack of transparency and comparability in AKI studies due to the absence of a uniform classification system and non-existence of consensus on when to measure mortality. We were able to demonstrate that the novel RIFLE criteria are useful not only because they enable a better description of the condition of severe AKI but because they predict mortality; patients with RIFLE class F, failure, had a relative risk of death of 3.4 (95% CI 1.2-9.3) as compared to RIFLE class R, risk. Moreover, a minimum two month follow-up was proposed as we found that this caught most of the severe AKI mortalities.

The second paper investigates the impact of choice of renal replacement therapy modality in the ICU. We evaluated outcomes both in terms of mortality and morbidity. 32 Swedish ICUs contributed data on 2,202 patients requiring continuous or intermittent renal replacement therapy (CRRT and IRRT, respectively). Within 90 days of initial dialysis, 1,100 patients had died. No association was found between dialysis modality and 90-day mortality. Among the 90-day survivors, the risk of end-stage renal disease (ESRD) requiring hemodialysis was considerably higher in patients treated with IRRT than in those treated with CRRT (adjusted odds ratio 2.60, 95% CI 1.5 4.3). However, the trend towards a higher risk of ESRD with IRRT decreased with increasing duration of follow-up. Among the 90-day survivors who did develop ESRD, the risk of death was markedly higher in patients treated with IRRT in the ICU than in those treated with CRRT (hazard ratio (HR) 2.3, 95% CI 1.3 4.1).

The third paper described the outcome of patients with manifest end-stage renal disease treated in the ICU with renal replacement therapy. Again, 32 Swedish ICUs contributed data on 245 patients. Diabetes and heart failure are significant risk factors for 90-day mortality, with an odds ratio (OR) of 1.9 and 2.0 respectively. The ICU ESRD cohort had increased long-term mortality as compared to non-ICU ESRD patients: relative risk of death 2.32 (95% CI 1.84-2.92). A comparison with the mortality rate in the general population yielded a standardized mortality ratio of 25 (95% CI: 19.6-31.4).

The fourth paper broadens the scope, and evaluates the prognostic value for cystatin C on mortality in adult general ICU patients with and without acute kidney injury. The relation between cystatin C and mortality was found to be dose dependent in patients with and without AKI. This relation was preserved even after adjusting for age, main ICU diagnoses and RIFLE. In AKI patients the HR comparing cystatin C above and below median more than doubled from the second year on compared to the first year follow-up. After exclusion of patients with potential AKI (creatinine > 100 μmol/l or urea > 20 mmol/l) in the non-AKI cohort the correlation of cystatin C levels and risk of death were strengthened.