Is the monocyte/lymphocyte ratio a predictor for graft survival in kidney transplant recipients?

ABSTRACT INTRODUCTION: Although significant advancements have been made in research on immunosuppression and tissue compatibility to improve graft survival and prevent acute rejection in the short term, there is still a need to enhance graft survival in the long term. The selection of therapeutic agents and dosage determination increasingly requires non-invasive, cost-effective, easily accessible, and specific biomarkers. In the quest for non-invasive biomarkers, immune markers involved in the pathophysiology of rejection have been prominently investigated OBJECTIVE: We aimed to contribute to the literature by investigating the potential of the monocyte-to-lymphocyte ratio (MLR), which is low-cost and assessable in routine tests, as a biomarker for graft survival and its ability to guide immunosuppressive therapy in this study MATERIALS AND METHODS: In this retrospective study, a total of 450 kidney transplant patients followed between 1996 and 2022 at the Department of Nephrology, Dokuz Eylül University Faculty of Medicine, were initially included. After excluding patients under 18 years old, those with a history of secondary transplantation, a cancer diagnosis, and individuals lost to follow-up, a total of 186 patients were considered for statistical analysis. Graft failure was defined as biopsy-proven rejection, stage 3-4 chronic kidney disease, or the initiation of any form of dialysis treatment. RESULTS: In this text, findings from a study are presented. The study included 450 kidney transplant patients followed at the Department of Nephrology, Dokuz Eylül University Faculty of Medicine, between 1996 and 2022, revealing significant insights into graft survival.Out of 186 kidney transplant patients observed over a median follow-up period of 75 (interquartile range: 49-110) months, graft failure was observed in 54 individuals, constituting 28.3% of the cohort.Patients experiencing graft failure were statistically significantly younger in terms of age compared to those who did not encounter graft failure (p<0.001). However, no significant difference was found concerning gender.Among primary diseases, patients experiencing graft failure had relatively lower rates of diabetes and polycystic kidney disease (p=0.017). While diabetes mellitus was more common in patients without graft failure, this difference was not statistically significant (p=0.13). There were no significant differences between the groups in terms of hypertension, incident diabetes mellitus, and the duration of hemodialysis prior to transplantation (p=0.57, p=0.07, p=0.14, respectively).Hemodialysis was the preferred dialysis modality for both groups during the pre-transplant period. The mean duration of dialysis was similar between the groups.The percentage of kidney transplants from living donors was higher in both groups, and HLA mismatch results were comparable.The most prominent induction therapy across the entire study population was Anti-Thymocyte Globulin (ATG). There was a significant difference observed in immunosuppressive regimens between the groups (p=0.001). The percentage of dual therapy including mycophenolate mofetil with steroids was notably higher in patients experiencing graft failure.Biopsy-proven acute rejection was observed in 50 patients with graft failure and 15 patients without graft failure (p<0.001).Throughout the follow-up period, one patient in the graft failure group developed BK nephropathy, while eight patients in the non-graft failure group had no documented nephropathy.No significant difference was found between the groups concerning CMV (Cytomegalovirus) infection.Over the follow-up period, a total of 74 patients deceased, 21 of whom were from the graft failure group, while 53 were from the non-graft failure group.The monocyte-to-lymphocyte ratio (MLR) was significantly higher in patients with graft failure during the first month after transplantation and gradually decreased until the 9th month. It exhibited fluctuations over five years and increased between 5 to 10 years (p=0.42).MLR values were statistically significantly higher in the graft failure group during the first 6 months but did not show a statistically significant difference between 6 months and 108 months. They remained elevated in the graft failure group (p values; p=0.01 for month 1, p=0.001 for month 3, p=0.018 for month 6, p>0.05 between months 9-98, p=0.01 for both month 108 and month 120). CONCLUSION: In the kidney transplant patient group, individuals with particularly higher MLR values during the first 6 months post-transplantation are at a greater risk of long-term graft loss. Therefore, detecting elevated MLR levels early in the course of transplantation may serve as a simple, easily accessible biomarker for long-term graft loss. KEYWORDS: Renal Transplantation, Rejection, Greft Failure, Monocyte/Lymphocyte Ratio