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The urinary CXC chemokine ligand (CXCL)10 detects renal transplant inflammation noninvasively, but has limited sensitivity and specificity. In this study, we performed urinary proteomic analysis to identify novel biomarkers that may improve the diagnostic performance of urinary CXCL10 for detecting alloimmune inflammation in renal transplant patients.In preliminary studies, adult renal transplant patients with normal histology (n = 5), interstitial fibrosis and tubular atrophy (n = 6), subclinical (n = 6) and clinical rejection (n = 6), underwent in-depth urine protein compositional analysis with LC-MS/MS, and matrix metalloproteinase-7 (MMP7) were identified as a potential candidate for the diagnosis of renal allograft inflammation. Urine MMP7 performance was then studied in a larger, prospective adult renal transplant population (n = 148 urines from n = 133 patients) with matched surveillance/indication biopsies. The diagnostic performance of urinary MMP7 and CXCL10 in combination was next evaluated using concordance (C-) statistics, net reclassification improvement and integrated discrimination improvement indices, to determine whether it was better than CXCL10 alone.Urinary MMP7:creatinine (Cr) was lower in normal transplants compared to those with inflammation: glomerulonephritis (P = 0.009), viral nephropathies (P = 0.002), interstitial fibrosis and tubular atrophy and inflammation (P = 0.04), borderline (P = 0.08), subclinical (P = 0.01) and clinical rejection (P = 0.0006), and acute tubular necrosis (P0.0001). Urinary MMP7:Cr and CXCL10:Cr significantly distinguished noninflamed from inflamed biopsies (area under the curve, 0.74 and 0.70, respectively). The addition of urinary MMP7:Cr to CXCL10:Cr improved the diagnostic performance for subclinical and clinical inflammation/injury by integrated discrimination improvement (P = 0.002) and net reclassification improvement (P = 0.006) analyses.Urinary MMP7:Cr improves the overall diagnostic performance of urinary CXCL10:Cr for distinguishing normal histology from subclinical and clinical inflammation/injury, but not subclinical inflammation alone.

Background Soluble vascular cell adhesion molecule-1 (sVCAM-1) is a marker of endothelial injury and a potent predictor of cardiovascular mortality in patients with kidney failure on dialysis. The longitudinal effects of dialysis on endothelial dysfunction and in particular the effects of renal transplantation on markers of endothelial function including sVCAM-1 have not been well characterized. Methods We used the Transplant Manitoba registry and biobank to assemble a retrospective cohort of all patients receiving a first kidney transplant between January 1, 2000, and December 31, 2005 (n=186). One hundred seventy-four patients had at least two serum samples pretransplant and at least two samples posttransplant. In total, 1,004 serial samples (median 5/patient) were analyzed. Factors associated with sVCAM-1 were examined using mixed linear models. Results The sVCAM-1 levels increased progressively on dialysis (0.15 [0.10 to 0.20] ng/mL/day; P, Supplemental digital content is available in the article.

Reactivation of latent Mycobacterium tuberculosis infection is an important health concern for patients on hemodialysis because of their immunosuppressed state and in kidney transplant patients receiving immunosuppressive therapy to prevent organ rejection. There are several tests available to determine the presence of latent tuberculosis infection: the tuberculin skin test (TST), QuantiFERON-TB Gold (QFT-G), and T-SPOT.TB. The objective of this study is to evaluate the diagnostic accuracy of these tests in determining latent tuberculosis infection in the hemodialysis population.The study design was a systematic review. We selected studies with adequate information to ascertain test sensitivity or specificity of the TST, QFT-G, and TSPOT.TB with regards to determining latent tuberculosis infection in the hemodialysis population.One hundred two articles were selected for full review, and 17 were included in the meta-analysis. The TST had a pooled sensitivity of 31% (26%-36%, 95% confidence interval) and specificity of 63% (60%-65%) across eight studies. The QFT-G test had a pooled sensitivity of 53% (46%-59%) and specificity of 69% (65%-72%) across nine studies. The T-SPOT.TB test had a pooled sensitivity of 50% (42%-59%) and specificity of 67% (61%-73%) across three studies.The QFT-G and the T-SPOT.TB tests were more sensitive than the TST for diagnosis of latent tuberculosis infection in patients on hemodialysis while offering a comparable level of specificity. This systematic review calls into question the practice of using the TST to screen in this population, especially in patients considered for kidney transplantation.