Proenkephalin and DKK-3 levels and kidney function in patients after hematopoietic stem cell transplantation
Aleksandra Kaszynska1, Malgorzata Kepska-Dzilinska1, Ewa Karakulska-Prystupiuk2, Agnieszka Tomaszewska2, Grzegorz Basak2, Marcin Zorawski3, Inga Drozak1, Zuzanna Jakubowska1, Jolanta Malyszko1.
1Nephrology, Dialysis and Transplantation, Medical University of Warsaw, Warsaw, Poland; 2Haematology, Transplantation and Internal Medicine, Medical University of Warsaw, Warsaw, Poland; 3Cardiology, Lipidology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
Introduction: Hematopoietic stem cell transplantation-HSCT could be complicated by acute kidney injury and chronic kidney disease. Proenkephalin (PENK) has been recently shown to reflect glomerular dysfunction and predict new-onset acute kidney injury and heart failure. Dickkopf-3 (DKK3) is a stress induced, renal tubular epithelial-derived, secreted glycoprotein involved in the development of interstitial fibrosis and has primarily been assessed as a marker of fibrosis in chronic kidney disease (CKD) and may also be able to predict those who develop acute kidney injury. While previous studies investigated PENK and DKK-3 utility as a biomarker in individuals with preserved renal function, urinary PENK and DKK-3 in patients after HSCT remains to be established.
Aim of the study: The aim of the study was to assess urinary PENK and DKK-3 concentration in patients at least 3 months after HSCT under ambulatory care of Hematology, Transplantation and Internal Medicine Department and to investigate their correlations with kidney function reflected as serum creatinine and eGFR.
Materials and Methods: We studied 80 prevalent patients after allogeneic HSCT (due to mainly hematological reasons i.e. acute leukemias and lymphomas) and 32 healthy volunteers to obtained normal ranges for biomarkers.
Urine proenkephalin and DKK-3 concentrations were assessed using commercially available a sandwich ELISA immunoassay. Demographic and clinical data were collected from patients’ records. XLSLAT 2022 and STATA software were used for statistical analyses.
Results: PENK and DKK-3 were significantly higher in patients after HSCT when compared to healthy volunteers. When we divided patients according to kidney function (below and over 60 ml./min/1.72m2), we found that concentration of PENK and DKK-3 were significantly higher in 23 patients with CKD stage 3 relative to patients with eGFR over 60 ml.min.1.72m2. In univariate correlations PENK was inversely related to eGFR (r=-0.21, p<0.05), while DKK-3 was not significantly related to either creatinine or eGFR.
Conclusion: Patients after allogeneic HSCT despite normal or near normal kidney function show evidence of kidney injury. However, further research is required to establish the clinical utility of the new biomarker.
[1] stem cell transplantation
[2] chronic kidney disease
[3] acute kidney injury
[4] biomarkers