BLOG: suPAR as a biomarker among patients undergoing allogeneic HCT
Click Here to Manage Email Alerts
Acute kidney injury is a frequent complication following hematopoietic cell transplantation.
Risk factors include allogeneic (vs. autologous) transplant, conditioning regimens, engraftment syndrome, graft-versus-host disease involving a kidney, exposure to drugs like calcineurin inhibitors for prevention or treatment of GVHD, and antibiotics for prophylaxis and treatment of infections.
Neutrophil gelatinase-associated lipocalin (NGAL) and creatinine are well established biomarkers of acute kidney injury (AKI) in the general population. Their role in AKI following HCT is not well known.
Soluble urokinase-type plasminogen activator receptor (suPAR) is a novel biomarker that has been studied in various clinical scenarios, including COVID-19-associated AKI, post-coronary angiography and cardiac surgery, critically ill patients and older patients presenting with AKI. However, its role as a biomarker in post-HCT AKI has not been established.
The Blood and Marrow Transplant Clinical Trials Network 1202 study assessed the clinical utility of suPAR for prediction and prognostication of post-HCT AKI requiring dialysis (AKI-D). The study also compared the performance of suPAR with creatinine and NGAL in this patient population.
Utilizing the BMT CTN 1202 cohort (NCT01879072), adults who developed AKI-D following HCT were included as AKI cases. Controls were selected from the patients who did not develop AKI during the 2 years of follow up. Controls were matched with cases based on age, sex and conditioning regimen.
Frozen serum samples collected prior to transplant and at days 7, 14, 21 and 28 following HCT were used for this study. Additional samples at day 42 and later — when available — also were analyzed. All serum samples were assayed for suPAR, NGAL and creatinine.
The association between these biomarkers, AKI-D and OS was analyzed.
The two groups (n=62 in each group) were similar in demographic variables. A significantly higher percentage of patients in the AKI group than controls were on a tacrolimus-based regimen for GVHD prophylaxis.
Median time from transplant to AKI-D was 2.6 months.
suPAR levels at Day 7 were higher among patients with AKI than controls compared to controls (median, 2.7 ng/mL vs. 2.1 ng/mL; P = .002).
In multivariate analysis, only the Day 7 suPAR level was associated with development of AKI-D (P = .009). Creatinine and NGAL were not associated with AKI-D. The area under the curve for the receiver operating characteristic curve for Day 7 suPAR levels was 0.7485.
OS was evaluated for both cases and controls based on a cut-off of 2.48 ng/mL for suPAR values. Levels greater than 2.48 ng/mL were associated with shorter OS for both cases and controls.
This study showed that suPAR may be an early marker of AKI, with Day 7 suPAR levels being prognostic for stage III AKI and OS after HCT.
These findings should be evaluated in future prospective studies to advance our current understanding of suPAR as a biomarker for AKI and OS among HCT recipients.
References:
- Azam TU, et al. J Am Soc Nephrol. 2020;doi:10.1681/ASN.2020060829.
- Hayek SS, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa1911481.
- Huang Y, et al. Clin Exp Nephrol. 2023;doi:10.1007/s10157-022-02300-2.
- Krishnappa V, et al. Int J Nephrol. 2016;doi:10.1155/2016/5163789.
- Lopes JA, et al. Bone Marrow Transplant. 2016;doi:10.1038/bmt.2015.357.
- Parikh CR, et al. Kidney Int. 2002;doi:10.1046/j.1523-1755.2002.00455.x.
- Walls AB, et al. Pharmaceuticals (Basel). 2021;doi:10.3390/ph14090843.
- Wen Y, et al. Crit Rev Clin Lab Sci. 2021;doi:10.1080/10408363.2021.1879000.
For more information:
Bhavna Bhasin-Chhabra, MD, can be reached at bhasin-chhabra.bhavna@mayo.edu.
Collapse
Read more about
Click Here to Manage Email Alerts