Expression of PBMC TLR4 in Renal Graft Recipients Who Experienced Delayed Graft Function Reflects Dynamic Balance Between Blood and Tissue Compartments and Helps Select a Problematic Patient

Abstract

Both Toll-like receptor 4 (TLR4) and monocytes focus stimuli, causing them to contribute differently to chronic injury of a transplanted kidney.

Aim: The aim of our study was to determine if TLR4 monocyte is a diagnostic tool and possibly a target for therapeutic intervention.

Materials: We studied 143 kidney transplant (KT) patients (88 male, 55 female; 50.3 ± 12.8 years); median was 10.4 post KT, follow-up was 11.4 months, and 46 patients had delayed graft function (DGF+) history. Control group (38 healthy volunteers) had monocyte mRNA-TLR4 expression (TLR4ex). DGF+ were divided by median of TLR4ex (-0.1034) into 2 groups: low-TLR4 expression (L-TLR4ex) and high-TLR4 expression (H-TLR4ex).

Results: We showed that in comparison with DGF-, the DGF+ had much lower TLR4ex, and worse KT function both currently (TLR-day) (serum creatinine [sCr] P = .002; estimated glomerular filtration rate [eGFR] P = .001) and post follow-up (sCr P = .006; eGFR P = .005). The DGF+ with L/H-TLR4ex comparison showed no differences in TLR-day KT function but did show differences in post follow-up (sCr P = .01; eGFR P = .02; ΔeGFR% P = .001). Regression analysis showed an association between recipient age, tacrolimus concentration, and uremic milieu (ie, TLR-day sCr and GFR with TLR4ex). Reverse regression analysis indicated an association of TLR4ex (especially L/H-TLR4ex) with post follow-up parameters of KT function and numeric/qualitative measures of change.

Conclusion: DGF affects the fate of a graft. Within a several months after transplantation, TLR4ex of peripheral blood mononuclear cells declines in DGF patients. Low LR4ex in patients with DGF+ is associated with poor prognosis for the efficiency of the KT. In patients with DGF+, the proper selection of immunosuppression (tacrolimus dosing) is very important. Higher concentrations of tacrolimus may improve prognosis. The analysis of TLR4ex change may be a useful parameter for the real assessment of immunosuppression efficacy. It is important for transplanted organ function that peripheral blood mononuclear cells effectively leave circulation and remain in the graft.