Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis

Abstract

Background: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca²⁺-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive.

Methods: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) and biopsy-proven acute tubular necrosis (ATN) and followed them up for more than three months. The subjects were divided into high- and low-renal-tubular-TRPA1-expression groups for the comparison of the total recovery of renal function and mortality within three months. The significance of TRPA1 in patient prognosis was evaluated using Kaplan-Meier curves and logistic regression analysis.

Results: Of the 46 adult AKI patients with ATN, 12 totally recovered renal function. The expression level of tubular TRPA1 was detected by quantitative analysis of the immunohistochemistry of biopsy specimens from ATN patients. The AKI patients with high tubular TRPA1 expression showed a high incidence of nontotal renal function recovery than those with low tubular TRPA1 expression (OR = 7.14; 95%CI 1.35-37.75; p = 0.02). High TRPA1 expression was independently associated with nontotal recovery of renal function (adjusted OR = 6.86; 95%CI 1.26-37.27; p = 0.03).

Conclusion: High tubular TRPA1 expression was associated with the nontotal recovery of renal function. Further mechanistic studies are warranted.

Keywords: TRPA1; acute kidney injury; acute tubular necrosis; recovery of renal function.

Figure 1

Flowchart presenting the selected biopsy-proven acute tubular necrosis (ATN) population.

Figure 2

Different staining of kidney tissues from patients with ATN and association of TRPA1 expression with oxidative stress or tubular injury score. (A) Representative images of immunohistochemical staining of TRPA1, 8-OHdG, and periodic acid-Schiff staining of kidney tissues from patients with ATN and normal controls; 8-OHdG, an oxidative stress marker (B) QISV of tubular 8-OHdG (C) Tubular injury score. ATN patients were stratified into high and low expression groups by the cutoff value of 0.194 for tubular TRPA1 QISV based on the ROC curve analysis. Data are expressed as mean ± SD. * p < 0.05; TRPA1—Transient receptor potential ankyrin 1; 8-OHdG—8-hydroxy-2’-deoxyguanosine; QISV—quantitative immunohistochemical staining value; ROC—receiver operating characteristic; SD—standard deviation.

Figure 3

Cumulative incidence of total recovery of renal function among the ATN patients with different expression levels of tubular TRPA1. Incidence rate of the events of total recovery of renal function was significantly higher in the low tubular TRPA1 expression group than in the high tubular TRPA1 expression group during the follow-up period (log-rank test; p = 0.02).

Figure 4

Cumulative incidence of mortality among the ATN patients with different expression levels of tubular TRPA1. Although ATN patients with high expression of tubular TRPA1 had a higher incidence of all-cause mortality than those with low expression of tubular TRPA1 during the follow-up period, the result was not statistically significant (log-rank test; p = 0.07). The severity of acute kidney injury may play a mediating role in all-cause mortality. Therefore, further research excluding the mediating factor is warranted.