Association between graft function and urine CXCL 10 and acylcarnitines levels in kidney transplant recipients

Kidney transplantation is an outstanding treatment that provides long-term survival and quality life for patients with chronic kidney disease. Despite modern immunosuppressive therapies, allograft rejection is one of the major causes of graft damage and loss. Therefore, early diagnosis and treatment of graft dysfunction is very important in renal transplant recipients. Although kidney biopsy is the gold standard diagnostic method in the diagnosis of allograft rejection, it cannot be performed frequently because it is an invasive procedure. Because of economical, practical and ubiquitous test, monitoring of serum creatinine is routinely performed in transplant recipients. But, there are limiting factors in which serum creatinine levels vary between individuals and are insufficient in diagnosis. Therefore, in kidney transplant recipients, the searches go on for a new, reliable biomarkers that can be used in the evaluation of graft function and in the diagnosis of allograft rejection. In our study, we performed urine CXCL 10 and metabolome (amino acids, free/acyl carnitines) analysis for graft function evaluation after transplantation. Our study included 67 kidney transplant recipients from living donors (23 female, 44 male; mean age±SD: 40,49±13,22 year). Renal biopsies were performed in patients with suspected graft dysfunction in accordance with clinical and laboratory evaluations (urine protein >3,5 g, serum creatinine level above 25% of the patient's basal level). According to pathology reports, patients were divided into two groups: chronic allograft dysfunction (CAD) (n=18) and antibody mediated allograft rejection (AMR (n=16)). The control group consisted of stable renal transplant recipients (n=33). Creatinine, protein, CXCL10, metabolome analysis in urine samples of all patients; creatinine and cystatin C analysis in serum samples were performed. Urine CXCL 10 levels were measured by ELİSA (Enzyme-Linked Immunosorbent Assay) method and metabolome analysis were performed by MS/MS (Tandem mass spectrometry) method. Creatinine (urine and serum) and protein (urine) levels were measured by colorimetric and spectrophotometric method; serum cystatin C levels were measured by nephelometric method. Patients' glomerular filtration rate (GFR) were calculated using creatinine-based MDRD (modification of diet in renal disease), C-G (Cockgrouft-Gault), CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration); cystatin-based CKD-EPI; creatinine and cystatin C-based CKD-EPI formulas. The performance of serum cystatin C and cystatin C based GFR to evaluate of graft functions in all groups; was higher than serum creatinine and creatinine based GFR results. A significant strong correlation was observed between creatinine based GFHCKD-EPİ and GFHMDRD (r=0,997). Urine leucine+isoleucine/creatinine, citrulline/creatinine, C0, C0/creatinine, C2, C2/creatinine, C3/creatinine levels were significantly higher; C10:1 and C14:2 levels were significantly lower in CAD and AMR groups compared to the control group (p <0,017). Urine CXCL 10/creatinine ratio were significantly higher in the AMR group than control and CAD groups (p values were 0,007 and 0,001; respectively). There was no statistically significant difference between CAD and control groups, levels of urine CXCL 10. The area under the ROC curve (AUC) (95% CI) for predicting AMR was 0,748 for urine C0/creatinine ratio; 0,744 for urine C0 levels; 0,741 for urine leucine+isoleucine/creatinine ratio. The area under the ROC curve for predicting CAD was 0,835 for urine leucine+isoleucine/creatinine ratio; 0,790 for C0/creatinine ratio; 0,769 for urine C2/creatinine ratio. The area under the ROC curve of CXCL 10/creatinine ratio for predicting AMR was 0,805. In conclusion, the results of our study showed that urine CXCL 10 and metabolome analysis were important to determinate graft function and predict allograft rejection episodes and chronic graft injury in renal transplant recipients. Keywords: Kidney transplantation, graft function, CXCL 10, metabolome.