THE OUTCOME OF ACUTE KIDNEY DISEASE IN CRITICALLY ILL ADULT PATIENTS: A PROSPECTIVE OBSERVATIONAL STUDY

The term acute kidney disease (AKD) was introduced by the Acute Disease Quality Initiative 16 workgroup in 2017, and it is believed to differ from acute kidney injury (AKI) in terms of pathophysiology, reversibility and/or progression to chronicity. A proportion of critically ill adults develop AKD during stay in the intensive care unit (ICU), with unclear evidence as to the clinical course and renal outcomes at and after ICU discharge. The present study aimed to evaluate major adverse kidney events (MAKE) at 90 days, in addition to validated kidney injury biomarkers in critically ill adults diagnosed de-novo with AKD during ICU stay.

After ethical approval, and registration (ClinicalTrials.gov Identifier: NCT03597854), this single-center, prospective study was carried out in a 20-bedded ICU of a tertiary care, public-sector, academic hospital between Jun 2018 and October 2019. All adult (age>18 years) ICU patients, who had baseline eGFR > 60 ml/min/1.73m2 prior to ICU admission and had an eGFR < 60 ml/min/1.73m2 during ICU stay, for a duration of > 7 days, were defined as having AKD and were considered for inclusion. Patients with unknown baseline serum creatinine, known chronic kidney disease, post-renal transplant status and pregnant patients were excluded. Patients whose serum creatinine recovered or patients who died within 7 days after the diagnosis of AKI were excluded. Clinical characteristics were recorded after obtaining written informed consent. Blood (ng/mL) and urine samples (ng/mg of Ucr: urinary creatinine) were collected for analyzing creatinine and neutrophil-gelatinase-associated-lipocalin (NGAL), kidney-injury molecule-1 (KIM-1) on day 7 (designated as day of onset of AKD) and ICU discharge. MAKE 90 was defined as occurrence of any one of the following outcomes: death from any cause < 90 days, dependence on renal replacement therapies or doubling of serum creatinine.

During study period, 520 adult patients were admitted; of them, 401 were excluded (235 had no AKI; 96 had AKI, but died within 7 days of AKI, 58 had pre-existing renal disease; 12 were pregnant).  A total of 119 patients were included in the present study, median age of 38 years (29-52), 68.9% were male, predominantly (82.4%) with medical illness preceding ICU admission. Up to 85% and 82% of these patients were on mechanical ventilatory and vasopressor support respectively. Mortality in the study cohort in ICU was 42.9% (n=51). MAKE 90 outcome occurred in 43.7 % (n=52) of the study population. Among patients with MAKE 90 outcome, plasma NGAL: 4538 (3896-4736) versus 3979 (2146-4654); p=0.05, urine NGAL: 1451 (1128-1925) versus 1124 (1004-1411); p= 0.02, plasma KIM1 levels : 499 (148-1089) versus 240 (55.6-326); p=0.03, were significantly higher on day of AKD onset (day7), while plasma NGAL: 4536 (3456-4878) versus 1604 (1110-2075) ; p=0.02, and plasma KIM:1756 (486-826) versus 159 (117-200) ;p=0.02, were significantly higher at ICU discharge compared to patients who did not achieve MAKE 90 outcome. Also, plasma and urinary biomarkers at day 90 (n=25) (all in patients with serum creatinine resolution), remained well above accepted cut-off values for plasma NGAL, urine NGAL and plasma KIM-1 among 44%, 64% and 96% of study participants, respectively. 

Table 1: Baseline characteristics of the study participants(n=119)

Abbreviations used: APACHE: acute physiology and chronic health evaluation; SOFA: sequential organ failure score ; AKI: acute kidney injury; ICU: intensive care unit

Table 2: Outcome parameters of the study participants (n=119)

Abbreviations used: LOS_ICU: length of stay intensive care unit; LOS_hosp: Length of stay hospital; AKD: acute kidney disease; RRT: renal replacement therapy

Table 3: Biomarker levels in study participants at the diagnosis of AKD, ICU discharge in survivors and 90day post AKI diagnosis. (#: lost to follow up: 43)

Abbreviations used: P-NGAL: Plasma-Neutrophil-Gelatinase-Associated-Lipocalin (NGAL), P-KIM-1: plasma kidney-injury molecule-1 (KIM-1); U-NGAL: Urine- Neutrophil-Gelatinase-Associated-Lipocalin (NGAL),U-KIM-1: Urine kidney-injury molecule-1 (KIM-1); AKD: acute kidney disease; AKI: acute kidney injury.  

Table 4: Comparison of plasma and urinary biomarkers in patients with and without MAKE 90 outcome

Abbreviations used: Abbreviations used: P-NGAL: Plasma-Neutrophil-Gelatinase-Associated-Lipocalin (NGAL), P-KIM-1: plasma kidney-injury molecule-1 (KIM-1); U-NGAL: Urine- Neutrophil-Gelatinase-Associated-Lipocalin (NGAL),U-KIM-1: Urine kidney-injury molecule-1 (KIM-1); AKD: acute kidney disease; AKI: acute kidney injury.  

Figure 1: Progression of biomarkers in patients with AKD at different time points.

Among critically ill adults with AKD, the present study showed mortality of 42.9% with development of MAKE 90 outcome in 43.7%. Plasma and urinary NGAL and KIM-1 at day 7 were significantly higher in those who had MAKE 90 outcome than those without. Plasma and urinary biomarkers at day 90 (n=25), in patients with serum creatinine resolution, remained well above accepted cut-off values for plasma NGAL, urine NGAL and plasma KIM-1 among 44%, 64% and 96% of study participants, respectively.