Abstract:

IGFBP7*TIMP2 as an Early Predictor of Acute Kidney Injury after Lung Transplantation

Background:

Acute kidney injury (AKI) is a common postoperative complication occurring in up to 65% of lung transplant recipients. Postoperative AKI is associated with significantly increased morbidity and in-hospital mortality. AKI may also progress to chronic kidney disease, which can result in end stage renal failure requiring dialysis and possible kidney transplantation. Currently, AKI is diagnosed and staged using the Kidney Disease Improving Global Outcomes (KDIGO) criteria; these criteria define AKI based on serum creatinine (a product of muscle breakdown) concentrations or a sustained decrease in urine output. However, serum creatinine increase is often delayed, resulting in late diagnosis of AKI by which point there may already be significant kidney damage.

 Insulin growth factor binding product 7 (IGFBP7) and tissue inhibitor of metalloproteinases 2 (TIMP2) are cell-cycle arrest biomarkers that have been associated with early prediction of AKI in other surgical patient populations. To date, an association between AKI and IGFBP7*TIMP2 concentrations has not been investigated in lung transplant recipients.

Purpose: We hypothesized that post-reperfusion urinary concentrations of IGFBP7*TIMP2 would be associated with AKI risk and development in lung transplant recipients.

Methods:

We tested 187 recipients enrolled in the 5-center Lung Transplant Outcomes Group Acute Kidney Injury (LTOG-AKI) prospective cohort study. All patients were consented prior to enrollment. Urine samples were collected from patients prior to transplant and at 6 and 24 hours post reperfusion. Samples were analyzed using commercially available SimpleStep Abcam and R&D Quantikine ELISA kits to measure the urinary concentrations of IGFBP7 and TIMP2, respectively. Patients were characterized as having no AKI, mild AKI (Stage I), or moderate to severe AKI (Stage II or III) using the KDIGO creatinine criteria. Multivariate ordinal regression analysis was performed to investigate the association between IGFBP7*TIMP2 concentrations and AKI development post-transplantation.

Results: Postoperative AKI was diagnosed in 50.27% of patients in this study. Of patients who developed AKI, 24.06% of patients developed AKI Stage I and 26.2% of patients developed AKI Stage II or III. Overall, in-hospital mortality was 2.15% for patients without AKI, 2.22% for patients with AKI Stage I, and 18.75% for patients with AKI Stage II or III. There was no statistically significant difference in postoperative urinary concentrations of IGFBP7 & TIMP2 between patients who developed AKI and those who did not.

Conclusions: We found no association between post-reperfusion urinary concentrations of IGFBP7*TIMP2 and postoperative AKI development in lung transplant recipients. Further studies utilizing a larger cohort of lung transplant recipients could be conducted to validate these results.