Letter:
To the Editor,
The journal’s article ”Urinary TIMP‐2 and IGFBP‐7 protein levels as
early predictors of acute kidney injury after cardiac surgery” piqued
our attention. 1 It highlights the early
identification of AKI after cardiac surgery based on a spike in urinary
TIMP-2 and IGFBP-7 protein levels and links this with urinary dilution
measurements. We agree that [TIMP2] [IGFBP7] can help determine
postoperative AKI risk. We believe a few ideas could improve the overall
quality based on our expertise in reviewing your paper.
Firstly, IGFBP-7 has a specificity of 90.7% and a sensitivity of 32.4%
in detecting early-stage oesophagal small cell carcinoma, excluding
patients with this disease from preoperative
evaluation.4 This shows that patients with ESCC may
provide misleadingly favourable AKI results following cardiac surgery.
Acute aggravation of Chronic Obstructive Pulmonary Disease is also
associated with an increase in IGFBP-7 levels; 14% of patients who
developed AKI after cardiac surgery have a history of COPD. Their
increase in IGFBP-7 may have been caused by Acute exacerbation of COPD
or pulmonary problems resulting from anaesthesia.2While identifying novel biomarkers for predicting AKI onset has been a
significant emphasis in recent years, less attention has been dedicated
to searching for valuable biomarkers predictive of AKI outcome,
including renal recovery and the requirement for renal replacement
therapy, and patient death.3 IGFBP7 and neutrophil gelatinase-associated
lipocalin (NGAL) were found as the most significant predictors of renal
recovery in a small cohort of critically sick adult patients using a
proteomic method; subsequent validation validated the prognostic utility
of IGFBP7 and NGAL in predicting death. The authors mentioned that 28%
of patients developed AKI after cardiac surgery associated with a rise
in urinary TIMP-2 and IGFBP-7 levels but did not mention KIM-1, a type I
transmembrane glycoprotein with two extracellular domains that separate
from the cell surface and enter the urine. KIM-1 expression is
negligible in normal kidneys but rapidly increases in AKI patients after
heart surgery. Urine KIM-1 is a simple, noninvasive, and specific
biomarker for AKI.3 The authors focused on intra- and
postoperative urine samples. AKI could also be anticipated
preoperatively before cardiac surgery by urine spermidine, a polyamine
with known antioxidant capabilities, which demonstrated the highest
ability to identify high-risk patients.3
The correlation between urinary albumin increases (up to 100-fold) and
TIMP2 and IGFBP7 excretion supports the hypothesis of enhanced
glomerular permeability to all three proteins followed by decreased
endocytic absorption by injured proximal tubules. These results show
urinary albumin assay should supplement clinical TIMP2/IGFBP7
evaluations. Exclusion criteria should include nephrotoxic medication
screening (ibuprofen, vancomycin, angiotensin-converting enzyme
inhibitors, gentamycin, etc.).4 Preoperative screening for tumour
markers like IGFBP-7 can prevent false-positive ESCC and colorectal
cancer outcomes. Even in preoperative samples, urinary markers like
spermidine show promise in screening high-risk outpatients for AKI.
Blacks tend to have AKI-related surgery. Hence blacks and whites should
be evaluated independently.5