Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05907434 |
| Other study ID # |
127_2022 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2022 |
| Est. completion date |
June 30, 2024 |
Study information
| Verified date |
June 2023 |
| Source |
Policlinico Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Renal failure is a common complication of lung transplant (LUTX). Early diagnosis of acute
kidney injury (AKI) in this cohort is of utmost importance, since AKI after LUTX is
associated with worsened short and long-term outcomes. To now, early biomarkers of renal
failure based on the measurement of cell-cycle arrest proteins have never been tested in this
population.
Description:
Bilateral lung transplantation (LUTX) is a surgical procedure offered to patients suffering
from chronic respiratory failure. LUTX provides a survival benefit to selected patients but
is associated with several short-term and long-term non-pulmonary complications. Acute kidney
failure (AKI) is frequent and associated with short-term and long-term morbidity and
increased mortality. Indeed, AKI occurs in up to two-thirds of transplanted patients, with
5-13% needing renal replacement therapy (RRT), and associated with mortality ranging from 13
to 50%.
Several risk factors may favor postoperative AKI in patients undergoing LUTX: preoperative
(e.g., the patients' preoperative renal function and comorbidities) , intraoperative (i.e.,
hypoxia, hypotension, massive blood components' transfusions, use of intraoperative
extracorporeal membrane oxygenation - ECMO) and postoperative (i.e., use of nephrotoxic
agents as tacrolimus and antibiotics).
In patients treated with LUTX, postoperative AKI increases ICU and hospital length of stay
and is associated with worsened survival10. At the same time, postoperative AKI is associated
with an increase in end-stage renal failure and consequent chronic renal failure11 with
potential needs of chronic RRT. Finally, AKI may determine primary graft disfunction with
direct and indirect mechanisms (i.e., inability to reach therapeutic targets of
anti-rejection drugs).
According to the most recent guidelines (i.e., the Kidney Improving Global Outcomes (KDIGO)
criteria), patients are classified as suppering postoperative AKI stage 1, stage 2, and stage
3 are diagnosed whether serum creatinine increases 1.5-1.9 times, 2-2.9 times, and >3 times
from the preoperative, respectively. However, these traditional indicators of kidney function
have limitations related to early and accurate identification of AKI. Furthermore, sCr has
limitations in the specific context of LUTX, both regarding baseline patients' clinical
characteristics and surgical. On the one hand, patients enlisted for LUTX are usually
undernourished, have reduced muscle mass, reduced protein and creatine intake, which severely
limit the sensibility and sensitivity of sCr changes for AKI diagnosis. On the other hand,
the need for massive fluid and blood products during LUTX resulting in fluid overload can
mask the increase in sCr, delaying the diagnosis of AKI. In addition, early detection of AKI
using sCr concentrations is limited by the fact that sCr concentrations increase when renal
function has already deteriorated15.
Thus, novel markers capable of early and effective diagnosis of AKI in this patient
population are a major clinical interest and may allow to carry out risk-mitigating clinical
approaches (e.g., volume optimization, avoid nephrotoxic agents).
Cell Cycle arrest proteins have been suggested as early indicators of AKI. In particular,
urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor
binding protein-7 (IGFBP-7) are biomarkers of the renal tubular cell cycle arrest at the
early phase of AKI. The product of the urinary concentrations of TIMP-2 and IGFBP-7 (urinary
[TIMP- 2] × [IGFBP-7]) is a promising biomarker for early prediction of AKI in various
clinical settings such as out-of-hospital cardiac arrest, in critically ill patients, and
following major surgery or emergency department admission .
It is possible to envision the employment of the urinary [TIMP- 2] × [IGFBP-7] index as early
indicators of renal failure in patients undergoing LUTX. Thus, with this prospective
observational study, the aim of the study is to test the sensitivity and specificity of this
index in detecting early AKI in patients undergone LUTX.
Hypothesis/objectives of the study:
In patients undergoing LUTX, the urinary biomarker [TIMP-2] × [IGFBP-7] measured on the first
postoperative day after LUTX was evaluated as a reliable early predictive index of
postoperative AKI compared to standard KIDGO criteria.
