Early diagnostics of acute kidney injury (AKI) associated with hematopoietic stem cell transplantation (HSCT)
Kirill A. Smirnov, Vladimir A. Dobronravov, Boris V. Afanasiev, Olga V. Galkina, Irina M. Zubina, Evdokia O. Bogdanova
The First St. Petersburg I. Pavlov State Medical University, St. Petersburg, Russia
The patients undergoing hematopoietic stem cell transplantation (HCT) are at a high risk of acute kidney injury (AKI), which is further associated with significantly prolonged hospital stay, higher mortality and costs. A conventional diagnostics of AKI is based on functional parameters: >1,5-fold increase of serum creatinine, as a marker of glomerular filtration rate (GFR), and the rate of diuresis decline (AKIN classification – Acute Kidney Injury Network). However, the use of these criteria in clinical practice does not solve the problem of early diagnostics, as it reflects the development of advanced AKI lesions. Early stages of AKI (with potentially reversible structural alterations) are associated with up-regulation of biomarker (BMKI) molecules synthesized by resident and immune cells, which takes place during the first hours following the damage. The aim of our study was to determine diagnostic value of some biomarkers for early AKI detection in patients following hematopoietic stem cell transplantation (HSCT), as compared to routine methods.
The study involved 30 patients who underwent allogeneic HSCT. The AKIN criteria were limited to serum creatinine monitoring, since common HSCT treatment protocols require intensive hydration, maintaining the diuresis rates at 3-4 L. The urine samples were taken 7 days prior to HSCT (week 0), in the 1st, 2nd ,3rd, and 4th weeks post-transplant. Concentrations of the biomarker molecules (calbindin, clusterin, IL-18, KIM-1, GST-n, MCP-1) were measured in the samples.
Diagnostics according to the AKIN criteria yielded the following results: proportion of AKI (AKIN) cases in the 1st and 2nd weeks after HSCT was 7%, by the 3rd week, 17%; in the 4th week, 54% (p<0,05). Prevalence of cases with, at least, one increased BMKI was 79% in the 1st week, and 85% in the 2nd week, further remaining approximately at the same level. A proportion of cases with simultaneous elevation of several biomarkers was increased from 6% (pre-transplant) to 23% (week 1), 27% (week 2), 31% (week 3), and up to 38% 4 weeks after HSCT. In the 4th week, only 6% of cases did not show any increase of the BMKI, while the cumulative proportion of cases without clinical AKI (AKIN) comprised 40%. AKI (AKIN) is clearly related to the number of simultaneously elevated BMKI. The proportion of AKI cases (AKIN) with increase in 1 biomarker was 5%, with >4 biomarkers, 29%. ROC analysis showed that the number of elevated biomarkers has sufficient sensitivity, with regard to prediction of a clinical AKI (AKIN). SAUC= 0,69 (p=0,006).
1) Prevalence of increased biomarker concentrations following HSCT-related kidney damage is extremely high (93%).
2) Rising concentrations of the biomarkers precede clinical AKI (AKIN) manifestations.
3) The studied biomarkers exhibit a high predictive value, in terms of AKI (AKIN) development. The study was sponsored by the Committee on Science and Higher Education of the St. Petersburg Government.
Hematopoietic stem cell transplantation, biomarkers of acute kidney injury, predictive value