Toll-like 4 Receptor (TLR4) Expression on Peripheral Blood Mononuclear Cells in Renal Transplant Recipients with Pre-transplant Chronic Interstitial Nephritis Indicates Patients at Risk of Graft Deterioration

Objective: To investigate the relationship between pre-transplant chronic interstitial nephritis (CIN), TLR4ex and transplanted kidney function.

Materials And Methods: TLR4ex was measured in peripheral blood mononuclear cells of 43 CIN kidney transplant recipients. We compared TLR4ex among 33 patients with pre-transplant chronic non-infectious interstitial nephritis (NIN) and 10 patients with pre-transplant chronic pyelonephritis (Py). At the beginning (Day-0) TLR4ex, as well as concentrations of cyclosporin A (CyA) and tacrolimus (TAC) were determined. Both CIN and NIN patients were divided according to the respective median of TLR4ex into groups of low-TLR4 expression (L-TLR4ex) and high-TLR4 expression (H-TLR4ex). Serum creatinine/glomerular filtration rate (sCr/EGFR) was assessed on Day-0 and after the follow-up (F-up). The magnitudes of sCr/EGFR change (ΔsCr/ΔEGFR) were evaluated. The treatment was maintained stable along the F-up period (median 11.9 months).

Results: Day-0: in CIN with L-TLR4ex TAC was lower but sCr/EGFR were not different from H-TLR4ex; in Py TLR4ex and TAC were lower than in NIN with no difference in sCR/eGFR. After F-up: in CIN with L-TLR4ex sCR/EGFR and ΔsCr/ΔEGFR were worse than in H-TLR4ex; in Py sCR/EGFR and ΔsCr/ΔEGFR were worse than in NIN. The regression analysis points out prospective impact of Py and TLR4ex on sCR/eGFR and ΔsCr/ΔeGFR.

Conclusion: In CIN, both TLR4ex and Tac appear to be a useful positive predictor of the effectiveness of immunosuppression. Chronic pyelonephritis indirectly promotes faster progression of chronic transplanted kidney disease.