Early post-transplant urinary IP-10 expression after kidney transplantation is predictive of short- and long-term graft function

Abstract

The early identification of renal transplant recipients at enhanced risk of developing acute and subclinical rejection would allow individualized adjustment of immunosuppression before functional graft injury occurs and would exclude these patients from drug-weaning studies. Protein and reverse transcriptase-polymerase chain reaction-based analyses of candidate markers in urine open the opportunity to closely monitor kidney-transplanted patients non-invasively. The chemokine interferon-inducible protein 10 (IP-10; CXCL10) might be an interesting candidate to uncover ongoing immune processes within the graft. Urine samples from kidney-transplanted recipients were retrospectively analyzed for IP-10 mRNA and protein expression. IP-10 levels were correlated with the incidence of acute rejection episodes proven by histology and long-term graft function assessed by the glomerular filtration rate 6 months post transplantation. IP-10 expression in urine identified patients with ongoing acute rejection episodes several days before a biopsy was indicated by rising serum creatinine levels. Most importantly, elevated levels of urinary IP-10 protein within the first four postoperative weeks were predictive of graft function at 6 months even in the absence of acute rejection. These data reveal a correlation between elevated IP-10 expression in urine at early time points post-transplantation and intragraft immune activation that leads to acute rejection and compromised long-term graft function.

Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody–Mediated Kidney Allograft Rejection

“…Protein markers have also been assessed for their ability to predict both clinical [3][4][5][6][7] and subclinical TCMR. 4,[8][9][10][11] C-X-C motif chemokine 9 (CXCL9) and CXCL10 are IFNg-dependent, C-X-C motif chemokine receptor 3-binding chemokines that are secreted by infiltrating inflammatory cells and renal tubular and mesangial cells. Schaub et al 10 first reported the association of CXCL9 and CXCL10, normalized to urine creatinine, with tubulitis.…”

Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The BAL Anz Trial

“…Although its utility has not been examined in dialysis patients, higher levels of urinary IP-10 have been associated with greater decline in renal function in patients with diabetic nephropathy (41). Moreover, higher early post-transplant IP-10 concentrations in urine have been associated with worse short-and long-term graft function after renal transplantation (42).…”

Urinary MicroRNA as Biomarker in Renal Transplantation

“…before elevation of serum creatinine) 6. Also, urinary CXCL‐10 mRNA has been shown to be elevated up to 6 to 7 days prior to an acute rejection episode 7. In a recent prospective multicenter study, urinary mRNA of CXCL‐9 (as well as urinary CXCL‐9 protein) was shown to be predictive for the presence of acute rejection 8.…”