P0624INCREASED URINARY BIOMARKERS OF KIDNEY INJURY IN PATIENTS AFTER ALLOGENETICHEMATOPOETIC STEM CELL TRANSPLANTATION REFLECT KIDNEY DAMAGE EVEN IN NORMALN KIDNEY FUNCTION
Authors: Kepska Malgorzata , Chomicka Inga , Karakulska-Prystypiuk Ewa , Tomaszewska Agnieszka , Basak Grzegorz , Zorawski Marcin , Malyszko Jolanta 
Published: June 2020

Abstract

Background and Aims
Chronic kidney disease (CKD) and acute kidney injury (AKI) are common complications of hematopoietic stem cell transplantation (HSCT) associated with increased morbidity and mortality. On the other hand, presence of CKD is often used as an exclusion criterion when selecting patients who undergo HSCT, especially when fludarabine in conditioning or GVHD prophylaxis with a calcineurin inhibitor is contemplated. There is also no threshold (CKD stage, level of serum creatinine etc) below which patients should not undergo allogeneic HSCT. Kidney function in patients undergoing HSCT is frequently worsened by previous chemotherapy and exposure to a variety of nephrotoxic drugs. Several biomarkers were widely investigated for early diagnosis of acute kidney injury, including neutrophil gelatinase associated lipocalin (NGAL), urinary liver-type fatty acid-binding protein (uL-FABP) and others, however, in patients undergoing HSCT, the published literature is exceptionally scarce. A few studies with inconclusive results stress the knowledge gap and need for further research.
The aim of the study was to assess biomarkers of kidney injury in patients at least 3 months after HSCT (to avoid the effect of calcineurin inhibitors) under ambulatory care of Hematology, Oncology and Internal Medicine Department, University Teaching Hospital.

Method
We studied 80 prevalent patients after allogeneic HSCT and 32 healthy volunteers to obtained normal ranges for biomarkers. In this cross-sectional study following biomarkers of kidney injury in urine were evaluated: IGFBP-7/TIMP2 (insulin growth factor binding protein-7/, tissue inhibitor of metalloproteinases-2), netrin-1, semaphorin A2 using commercially available assays.

Results
All the biomarkers studied were significantly higher in patients after HSCT when compared to healthy volunteers (all p&lt;0.001). When we divided patients according to kidney function (below and over 60 ml./min/1.72m2), we found that only concentration of IGFBP-7 was significantly higher in 23 patients with CKD stage 3 (i.e. eGFR below 60ml.min/1.72m2) relative to patients with eGFR over 60 ml.min.1.72m2. All biomarkers in both subgroups of patients with eGFR below and over 60 ml./min/1.72m2 were significantly higher relative to healthy volunteers. In univariate correlations sempahorinA2 was related to netrin 1 (r=0.47, p&lt;0.001), IGFBP7 (r=0.35, p&lt;0.01), TIMP2 (r=0.32, p&lt;0.01), whereas IGFBP7 was positively related to serum creatinine (r=0.38, p&lt;0.001) and inversely to eGFR (r=-0.36, p&lt;0.001).

Conclusion
Concluding, patients after allogeneic HSCT despite normal or near normal kidney function show evidence of kidney injury, which might be due to comorbidities, previous chemotherapy, conditioning regimen,complement activation, calcineurin therapy after HSCT, other possible nephrotoxic drugs etc. Nephroprotective strategies are to be considered as chronic kidney disease is a risk factor for increased morbidity and mortality in this vulnerable population.