Abstract

Aim In renal transplant (tx) recipients, diagnosis of acute cellular rejection or allograft nephropathy is based on serum creatinine (Cr) level and invasive biopsies. However, serum Cr level usually increases with the onset of any type of allograft injury, and biopsies do not always indicate graft injury. On the other hand, urine is produced and excreted by the kidneys may have a potential to reflect renal allograft injury. We have investigated the presence of osteoprotegerin (OPG), monokine induced by interferon-γ (MIG) and interferon- γ induced protein of 10 kDa (IP-10) in the urine of renal tx patients with acute or chronic cellular or humoral rejection or nephrotoxicity. Methods 51 renal tx recipients who were biopsied for possible rejection were included. Donor-specific HLA-antibodies (DSA) and biomarkers were measured by solid phase immunoassays. Results All patients with clinical and biopsy proven cellular rejection had significantly elevated level of all three OPG, MIG and IP-10 chemokines. OPG alone was elevated in patients with humoral, glumerulonephropathy or tubular injury. Increase level of IP-10 appeared to be more specifically correlated with acute cellular rejection. No correlation was noted with humoral rejection, diagnosed by the presence of DSA and/or C4d staining. Interestingly, all three markers were in the normal range in four patients with serum Cr>2.4, but no indication of cellular rejection. The latter patient’s biopsies showed tubular injuries with no clear cut indication. Conclusions Discussion: This study shows that quantitation of chemokines biomarkers in the urine of renal allograft recipients may be an effective method for detection of cellular rejection. This non-invasive method may be used as an alternative method to reduce the need for invasive biopsies which may cause clinical complications such as bleeding or infection.

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