Acute kidney injury : a study of function markers

Acute Kidney Injury (AKI) is defined as a sudden decrease in the kidneys' ability to filtrate waste products and excrete excess water. Detecting AKI primarily relies on measuring the increased concentration of function markers (i.e., creatinine and cystatin C) and even measuring urine output. This thesis aimed to investigate the performance of kidney function markers in patients during critical illness. To study the variations of the function markers in an ICU population and to examine the performance of the most commonly used estimated glomerular filtration equations. In addition, to investigate the associations between creatinine and cystatin C and long-term mortality and to identify factors predictive of renal dysfunction after ICU discharge.

Both creatinine and cystatin C are within the normally acceptable limits of daily variation which means that changes in function markers between sampling-times during the day are likely to indicate a change in the biomarker levels due to the disease or treatment. Combination of both creatinine and cystatin C enables the best agreement between estimated and measured glomerular filtration rate. Levels of cystatin C after critical illness is strongly associated with 90-day and 1-year mortality in both AKI and non-AKI patients. Creatinine, on the other hand, has little value as a prognostic marker in the majority of patients. The incidence of CKD (eGFR<60) in ICU patients three months after AKI was 25.8% when using creatinine-based eGFR and 63.7% using cystatin C-based eGFR. Creatinine-defined CKD at follow-up was predicted by age, discharge cystatin C, discharge creatinine, and female sex. Cystatin C-defined CKD at follow-up was predicted by age, discharge cystatin C, CRRT in ICU, and diabetes.

List of scientific papers

I. Intra-day variability of cystatin C, creatinine and estimated GFR in intensive care patients. Ravn B, Larsson A, Martensson J, Martling CR, Bell M. Clin Chim Acta. 2016;460:1-4.
https://doi.org/10.1016/j.cca.2016.06.014

II. Superiority of Serum Cystatin C Over Creatinine in Prediction of Long-Term Prognosis at Discharge From ICU. Ravn B, Prowle JR, Martensson J, Martling CR, Bell M. Crit Care Med. 2017;45(9):e932-e40.
https://doi.org/10.1097/CCM.0000000000002537

III. Creatinine versus cystatin C based glomerular filtration rate in critically ill patients. Ravn B, Rimes-Stigare C, Bell M, Hansson M, Hansson L O, Martling CR, Larsson A, Mårtensson J. [Accepted]
https://doi.org/10.1016/j.jcrc.2019.04.007

IV. Creatinine- and Cystatin C-Based Incidence of Chronic Kidney Disease and Acute Kidney Disease in AKI Survivors. Rimes-Stigare C, Ravn B, Awad A, Torlén K, Martling C-R, Bottai M, Mårtensson J, Bell M. Critical Care Research and Practice. 2018;2018:1-8.
https://doi.org/10.1155/2018/7698090