Abstract
Kidney transplantation is the treatment of choice for patients with advanced chronic kidney disease (CKD) and end stage renal disease (ESRD). However, acute rejection (AR) is a common complication in kidney transplantation and is associated with reduced graft survival. Current diagnosis of AR relies mainly on clinical monitoring including serum creatinine, proteinuria, and confirmation by histopathologic assessment in the biopsy specimen of graft kidney. Although an early protocol biopsy is indispensable for depicting the severity of pathologic lesions in subclinical acute rejection (subAR), it is not acceptable in some cases and cannot be performed because of its invasive nature. Therefore, we examined the detection of noninvasive biomarkers that are closely related to the pathology of subAR in protocol biopsies three months after kidney transplantation. In this study, the urinary level of microtubule-associated protein 1 light chain 3 (LC3), monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and human epididymis secretory protein 4 (HE4) were measured three months after kidney transplantation. Urine samples of 80 patients undergoing kidney transplantation between August 2014 to September 2016, were prospectively collected after three months. SubAR was observed in 11 patients (13.8%) in protocol biopsy. The urinary levels of LC3, MCP-1, NGAL, and HE4 were significantly higher in patients with subAR than in those without, while those of L-FABP did not differ between the two groups. Multivariate regression models, receiver-operating characteristics (ROC), and areas under ROC curves (AUC) were used to identify predicted values of subAR. Urinary HE4 levels were able to better identify subAR (AUC = 0.808) than the other four urinary biomarkers. In conclusion, urinary HE4 is increased in kidney transplant recipients of subAR three months after kidney transplantation, suggesting that HE4 has the potential to be used as a novel clinical biomarker for predicting subAR.
Highlights
Steady advances in immunosuppression of kidney transplant recipients have resulted in a remarkable decrease in the risk of acute rejection, but long-term outcomes still remain suboptimal [1,2,3]
Various biomarkers for kidney damage have been recently identified such as microtubule-associated protein 1 light chain 3 (LC3), monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and human epididymis secretory protein 4 (HE4)
We examined whether the urinary levels of LC3, MCP-1, L-FABP, NGAL, and HE4 could predict or detect Subclinical acute rejection (subAR) three months after kidney transplantation
Summary
Steady advances in immunosuppression of kidney transplant recipients have resulted in a remarkable decrease in the risk of acute rejection, but long-term outcomes still remain suboptimal [1,2,3]. Studies of kidney transplant recipients have shown that subAR is associated with an increased risk of graft fibrosis [4,5] and graft loss [6,7,8]. Protocol renal biopsy is needed to monitor patients with stable renal function. Noninvasive biomarkers are needed to monitor patients who are stable following kidney transplantation. Various biomarkers for kidney damage have been recently identified such as microtubule-associated protein 1 light chain 3 (LC3), monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), and human epididymis secretory protein 4 (HE4). We examined whether the urinary levels of LC3, MCP-1, L-FABP, NGAL, and HE4 could predict or detect subAR three months after kidney transplantation
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