Background: Late graft loss from interstitial fibrosis – tubular atrophy (IF/TA) continues to be the “Achilles' heel” of kidney transplantation (KT). Long-term calcineurin inhibitors (CNIs) exposure is the most closely factor related to the development of IF/TA. Thus, we aimed to investigate roles of urinary neutrophil gelatinase-associated lipocalin (uNGAL) combined with cytokines and microalbuminuria as predictors for IF/TA.

Methods: We performed a prospective cohort study with matched-pair kidney allograft tissue analyses of 51 KT recipients in early post-transplantation. Urine of the KT recipients with the tacrolimus (TAC) dose adjustments was collected at the day before the dose adjustment (day-1) and at 3 days after the dose alteration (day+3). Of these, KT recipients were divided into 2 groups based on the alteration of trough tacrolimus level ([Delta] C₀TAC); group 1 (n=24): negative delta C₀TAC (-ve [Delta]TAC) [C₀TAC at day+3 was lower than at day-1] and group 2 (n=27): positive delta C₀TAC (+ve [Delta]TAC) [C₀TAC at day+3 was higher or equal to day-1]. Urine creatinine (uCr), urine microalbumin, 24-h urine protein, and urine cytokines (IL-18, IL-6, TNF-α), in parallel with serum creatinine (sCr) and TAC levels were measured.

Results: Over a median follow-up of 2.7 years, there were no statistical significant change of sCr and uNGAL before TAC adjustment (day-1) in comparison with 3 day after (day+3) in both groups. However, the difference of the value between day+3 and day-1 of uNGAL/uCr were significant higher in group 2 (p<0.0001). Urinary IL-18 and IL-6 but not TNF-α, also increased in day+3 compare with day-1 (p<0.001 both) in group 2. Univariate survival analysis demonstrated that microalbumin-to-creatinine ratio and 24-h urine protein were associated with the composite end point (unadjusted analysis: protein-to-creatinine: hazard ratio [HR], 1.62; 95% confidence interval [95% CI], 1.36 to 1.93; p<0.001; 24-h urine protein: HR, 1.18; 95% CI, 0.99 to 1.41; p=0.06).

Conclusions: The alteration in uNGAL/uCr but not sCr could demonstrate the subtle kidney injury following TAC dose adjustment and long-term effect on IF/TA.

CITATION INFORMATION: Chancharoenthana W, Leelahavanichkul A, Wattanatorn S, Issara-Amphorn J, Avihingsanon Y, Praditpornsilpa K, Townamchai N. Changes in Urinary Neutrophil Gelatinase Associated Lipocalin Combined with Urine Cytokines and Microalbuminuria as Predictors for Interstitial Fibrosis and Tubular Atrophy in Kidney Transplantation: A Matched-Pair Tissue Cohort Study. Am J Transplant. 2017;17 (suppl 3).

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