Cystatin C is correlated with mortality in patients with and without acute kidney injury

BACKGROUND: Recent research has shown cystatin C to predict mortality and cardiovascular morbidity independent of renal function. The aim of this study was to evaluate the prognostic value of cystatin C on mortality in adult general ICU patients with acute kidney injury (AKI). We later expanded the study and included patients without signs of AKI. METHODS: A total of 845 ICU patients were analysed for cystatin C and classified according to the RIFLE criteria. Of these, 271 patients with either creatinine >150 micromol/l, urea >25 or anuria/oliguria entered the AKI cohort. The remaining 562 patients entered the non-AKI cohort. Both cohorts were divided into quartiles according to cystatin C at entry. In the non-AKI cohort, we split the highest cystatin C quartile into two. The relationship between the different cystatin C quartiles and mortality in patients with and without AKI was estimated by hazard ratios (HR) derived from the Cox proportional hazards regression model. RESULTS: A relationship between cystatin C and mortality was found in patients with and without AKI, being stronger in patients without AKI. In AKI patients, the HR comparing cystatin C above and below the median more than doubled from the second year on compared to the first year follow-up. After exclusion of patients in the non-AKI cohort with 'potential AKI' (creatinine >100 micromol/l or urea > 20 mmol/l), the correlation between cystatin C levels and risk of death was strengthened. CONCLUSIONS: Cystatin C is correlated with mortality independently of renal function measured by creatinine in patients entering the general ICU

Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients

BACKGROUND: Breakdown of renal endothelial, tubular and glomerular matrix collagen plays a major role in acute kidney injury (AKI) development. Such collagen breakdown releases endostatin into the circulation. The aim of this study was to compare the AKI predictive value of plasma endostatin with two previously suggested biomarkers of AKI, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). METHODS: We studied 93 patients without kidney disease who had a first plasma sample obtained within 48 h of ICU admission. We identified risk factors for AKI within the population and designed a predictive model. The individual ability and net contribution of endostatin, cystatin C and NGAL to predict AKI were evaluated by the area under the receiver operating characteristics curve (AUC), likelihood-ratio test, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: In total, 21 (23 %) patients experienced AKI within 72 h. A three-parameter model (age, illness severity score and early oliguria) predicted AKI with an AUC of 0.759 (95 % CI 0.646-0.872). Adding endostatin to the predictive model significantly (P = 0.04) improved the AUC to 0.839 (95 % CI 0.752-0.925). In addition, endostatin significantly improved risk prediction using the likelihood-ratio test (P = 0.005), NRI analysis (0.27; P = 0.04) and IDI analysis (0.07; P = 0.04). In contrast, adding cystatin C or NGAL to the three-parameter model did not improve risk prediction in any of the four analyses. CONCLUSIONS: In this cohort of critically ill patients, plasma endostatin improved AKI prediction based on clinical risk factors, while cystatin C and NGAL did not

Creatinine- and Cystatin C-Based Incidence of Chronic Kidney Disease and Acute Kidney Disease in AKI Survivors

Background. Renal dysfunction after acute kidney injury (AKI) is common, potentially modifiable, but poorly understood. Acute kidney disease (AKD) describes renal dysfunction 7 to 90 days after AKI and is determined by percentage change in creatinine from baseline. Chronic kidney disease (CKD) is defined as the estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2 persisting for more than 90 days. We compared CKD incidence using both creatinine- and cystatin C-based GFR with AKD incidence at 90 days in AKI survivors. Methods. A prospective cohort study was conducted in a Swedish intensive care unit (ICU) between 2008 and 2010. We included AKI patients alive at 90 days. We excluded patients 100 years, death before follow-up, CKD prior to admission, and follow-up before 60 days or beyond 270 days. Creatinine and cystatin C were measured at 90 days and converted to eGFR (mL/min/1.73 m2). Results. We included 274 patients. At 90-day follow-up, the median creatinine eGFR (MDRD) was 81.6 (IQR 58.6–106.8) and median cystatin C eGFR was 51.5 (IQR 35.8–70.7). The incidence of CKD (eGFR < 60) was 25.8% based on creatinine but 63.7% using cystatin C estimates. AKD was present in 47 patients (18.9%). Age, discharge cystatin C, creatinine at discharge, and female gender predicted creatinine-defined CKD at follow-up. Age, discharge cystatin C, CRRT on ICU, and diabetes were associated with cystatin C-based CKD. Conclusions. In AKI survivors followed up at 3 months, CKD criteria were met in a quarter of patients using creatinine and in two-thirds using cystatin C eGFR. Less than one-fifth of patients fulfilled AKD criteria. The application of AKD criteria may underestimate renal dysfunction in AKI survivors

Evolution of chronic renal impairment and long-term mortality after de novo acute kidney injury in the critically ill; a Swedish multi-centre cohort study

Introduction: Acute Kidney Injury (AKI) is common in critical ill populations and its association with high short-term mortality is well established. However, long-term risks of death and renal dysfunction are poorly understood and few studies exclude patients with pre-existing renal disease, meaning outcome for de novo AKI has been difficult to elicit. We aimed to compare the long-term risk of Chronic Kidney Disease (CKD), End Stage Renal Disease (ESRD) and mortality in critically ill patients with and without severe de novo AKI. Method: This cohort study was conducted between 2005 and 2011 in Swedish intensive care units (ICU). Data from 130134 adult patients listed on the Swedish intensive care register-database was linked with other national registries. Patients with pre-existing CKD (4192) and ESRD (1389) were excluded, as were cases (26771) with incomplete data. Patients were classified according to AKI exposure during ICU admission. Outcome in the de novo AKI group was compared to the non-exposed (no-AKI) intensive care control group. Primary outcome was all-cause mortality. Follow-up ranged from one to seven years (median 2.1 years). Secondary outcomes were incidence of CKD and ESRD and median follow-up was 1.3 years. Results: Of 97 782 patients, 5273 (5.4%) had de novo AKI. These patients had significantly higher crude mortality at one (48.4% vs. 24.6%) and five years (61.8% vs. 39.1%) compared to the control group. The first 30% of deaths in AKI patients occurred within 11 days of ICU admission whilst the 30-centile in the no-AKI group died by 748 days. CKD was significantly more common in AKI survivors at one year (6.0% vs. 0.44%) than in no-AKI group (adjusted incidence rate ratio (IRR) 7.6). AKI patients also had significantly higher rates of ESRD at one (2.0% vs. 0.08%) and at five years (3.9% vs. 0.3%) than those in the comparison group (adjusted IRR 22.5). Conclusion: This large cohort study demonstrated that de novo AKI is associated with increased short and long-term risk of death. AKI is independently associated with increased risk of CKD and ESRD as compared to an ICU control population. Severe de novo AKI survivors should be routinely followed-up and their renal function monitored.Funding Agencies|Karolinska Institute; Stockholm County Council; Baxter Healthcare Corporation</p

Additional file 3: of Long-term mortality and risk factors for development of end-stage renal disease in critically ill patients with and without chronic kidney disease

Excluded cases. Details of excluded cases including table of demographic and outcome data. (DOCX 24 kb

Additional file 1: of Long-term mortality and risk factors for development of end-stage renal disease in critically ill patients with and without chronic kidney disease

Swedish health registers. Details of the Swedish National health registers. (DOCX 30 kb

MOESM1 of Plasma endostatin may improve acute kidney injury risk prediction in critically ill patients

Additional file 1: Tables S1–S5. Clinical model and biomarker performances for AKI prediction. Figures S1, S2. Cystain C and NGAL kinetics. Tables S6–S9 and Figures S3–S5. Sensitivity analyses excluding age from clinical model