Early prediction of kidney graft function may assist clinical management, and for this, reliable non-invasive biomarkers are needed. We evaluated endotrophin (ETP), a novel non-invasive biomarker of collagen type VI formation, as a prognostic marker in kidney transplant recipients. ETP levels were measured with the PRO-C6 ELISA in the plasma (P-ETP) of 218 and urine (U-ETP/Cr) of 172 kidney transplant recipients, one (D1) and five (D5) days, as well as three (M3) and twelve (M12) months, after transplantation. P-ETP and U-ETP/Cr at D1 (P-ETP AUC = 0.86, p < 0.0001; U-ETP/Cr AUC = 0.70, p = 0.0002) were independent markers of delayed graft function (DGF) and P-ETP at D1 had an odds ratio of 6.3 (p < 0.0001) for DGF when adjusted for plasma creatinine. The results for P-ETP at D1 were confirmed in a validation cohort of 146 transplant recipients (AUC = 0.92, p < 0.0001). U-ETP/Cr at M3 was negatively associated with kidney graft function at M12 (p = 0.007). This study suggests that ETP at D1 can identify patients at risk of delayed graft function and that U-ETP/Cr at M3 can predict the future status of the allograft. Thus, measuring collagen type VI formation could aid in predicting graft function in kidney transplant recipients.

In chronic kidney disease (CKD), oxidative stress and inflammation contribute to disease progression and CKD-related morbidity. The nuclear factor erythroid 2-related factor 2 (Nrf2) system plays a central role in the cellular response to oxidative and inflammatory stress. In this brief report, we describe our investigation into whether alterations in the gene expression of key Nrf2 pathway components contribute to the endogenous activation of the Nrf2 system previously reported in less advanced CKD. To this end, we quantified the gene expression of Nrf2, its regulatory protein Kelch-like ECH-associated protein 1 (KEAP1), and the Nrf2 downstream target NAD(P)H:quinone oxidoreductase 1 (NQO1) in monocytes from patients in different stages of CKD. We observed significantly elevated NQO1 gene expression in CKD stage G3b compared to CKD stages G1-3a (p < 0.05), G4 (p < 0.01), and G5 (p < 0.001). In contrast, the gene expression levels of Nrf2 and KEAP1 did not differ significantly between CKD stages. These findings suggest that endogenous activation of the Nrf2 system in moderate CKD predominantly reflects functional activation, likely at the protein level, rather than changes in the gene expression of Nrf2 or KEAP1.

Matrix metalloproteinase type 9 (MMP-9), which cleaves collagen type IV in basal membranes, has been associated with the progression of chronic kidney disease. The objective of the present study was to evaluate the characteristics of donors, recipients, induction therapies, and allograft function on MMP-9 transcripts from mononuclear cells in kidney transplant recipients. Transcripts were determined in peripheral blood mononuclear cells from 67 incident renal transplant recipients eight days post-transplant using quantitative real-time PCR and quantified using the ΔΔCq method. Median MMP-9 transcripts were 6.1 (IQR, 1.5 to 66.5, N = 4) in AB0-incompatible donor transplants; 3.2 (IQR, 2.0 to 16.9, N = 17) in living donor transplants; and 4.2 (IQR, 2.3 to 9.2, N = 46) in deceased donor transplants (p = 0.8). Importantly, renal transplant recipients who were treated with thymoglobulin had significantly higher median MMP-9 transcripts compared to all other induction therapies (14.5; IQR, 2.8 to 31.9, N = 10; vs. 3.5, IQR, 2.2 to 8.8, N = 57; p = 0.01). Median MMP-9 transcript levels were similar in recipients with delayed allograft function and immediate allograft function (8.86; IQR, 5.29 to 11.57, N = 7; vs. 3.4; IQR, 2.35 to 9.49, N = 60; p = 0.245). Induction therapy with thymoglobulin causes significantly higher MMP-9 transcripts in peripheral blood mononuclear cells, probably indicating an increased inflammatory response.

1. Calcific uremic arteriolopathy (CUA), also termed calciphylaxis in chronic kidney disease (CKD) or nephrogenic calciphylaxis, is an infrequent condition that can develop in patients with kidney ...

Background: Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), regulate the extracellular matrix. This study examined messenger RNA transcripts of TIMP2 before and after kidney transplantation. Methods: Transcripts were measured in peripheral blood mononuclear cells from 105 kidney transplant recipients, including AB0-incompatible, AB0-compatible, and deceased donor transplantation patients. Quantitative real-time polymerase chain reaction was utilized. Results: Kidney transplant recipients (72 male; 33 female) were a median of 55 (44–63) years old. The median (interquartile range) of pretransplant TIMP2 transcripts was 0.68 (0.50–0.87) in kidney transplant recipients. In total, 9 out of 72 patients (13%) showed delayed graft function, i.e., need for dialysis within 1 week after transplantation. Preoperative TIMP2 transcripts were significantly lower in kidney transplant recipients who experienced delayed graft function compared to patients with immediate graft function (0.40 (0.32–0.62) vs. 0.68 (0.56–0.87); p = 0.01). There was no association between TIMP2 transcripts and age or gender. TIMP2 median transcripts were 0.73 (0.58–0.88) on the first postoperative day. TIMP2 transcripts were similar on the first postoperative day in patients with delayed graft function and immediate graft function. Conclusions: Preoperative TIMP2 transcripts were lower in patients with delayed allograft function. Future investigations are needed to establish the role of TIMP2 transcripts in transplant pathophysiology.