Risk Of Subsequent Graft Failure Research Articles

Comparison of two RT-qPCR methods targeting BK polyomavirus microRNAs in kidney transplant recipients

BackgroundBK polyomavirus replication leads to progressive tubulointerstitial nephritis and ureteral stenosis, with a considerable risk of subsequent graft failure in kidney transplant recipients. Since specific antiviral therapies are lacking, new tools are required to enhance the biological monitoring of the infection. Viral microRNAs are promising new biomarkers, but the performance of RT-qPCR methods limits the clinical application and the validation of a standard method for quantification.MethodsWe compared TaqMan microRNA Assays and TaqMan Advanced miRNA Assays for bkv-miR-B1-3p and bkv-miR-B1-5p quantification in synthetic microRNA templates and in 44 urine samples belonging to 14 consecutive kidney transplant recipients with BK polyomavirus replication from Amiens University Medical Center in a 1-year span.ResultsCycle threshold values were constantly higher with TaqMan Advanced MicroRNA Assays. TaqMan microRNA Assays showed better performance in predicting the good prognosis of BK polyomavirus nephropathy.ConclusionOverall, TaqMan MicroRNA Assays appeared to be a more sensitive and accurate RT-qPCR method than TaqMan Advanced MicroRNA Assays to quantify bkv-miR-B1-3p and bkv-miR-B1-5p BKPyV miRNAs in patients’ urine samples.

Influence of Postoperative Intraocular Pressure on Graft Detachment After Descemet Membrane Endothelial Keratoplasty.

Descemet membrane endothelial keratoplasty (DMEK) seems to be the most promising technique for treating endothelium-related disorders of the cornea. However, graft detachment is a frequent complication. It often can be treated by rebubbling procedures. Unfortunately, this increases the risk of subsequent graft failure. It is therefore essential to define risk factors for graft detachment in DMEK. In this study, postoperative intraocular pressure (IOP) is investigated in this regard. In total, 1047 DMEK procedures in patients with Fuchs endothelial dystrophy or bullous keratopathy were reviewed. All rebubbling procedures were recorded as well as postoperative IOP values (first measure 2 hours postoperatively and highest and lowest value within 3 days after surgery), donor factors (donor age, organ culture time, and endothelial cell count), and whether DMEK surgery had been combined with cataract surgery (triple-DMEK). Incidence rates were estimated with the Kaplan-Meier method. Cox regression was used to assess statistical significance. The overall rebubbling rate was 24% after 8 weeks. Relative dips in IOP may be associated with a higher risk for graft detachment (hazards ratio = 0.41; P < 0.001). Graft detachment was neither significantly influenced by donor factors, first or maximum IOP, nor by simultaneous cataract surgery (triple-DMEK). Avoiding dips in IOP may reduce the risk for graft detachment after DMEK. To prevent lowering of IOP values in the early postsurgical period, it may be advisable to achieve tight surgical wounds at the end of DMEK surgery and optimal filling of the anterior chamber with air and optionally with gas.

Cumulative Exposure to Gamma Interferon-Dependent Chemokines CXCL9 and CXCL10 Correlates with Worse Outcome After Lung Transplant

Outcomes following lung transplant are suboptimal owing to chronic allograft failure termed bronchiolitis obliterans syndrome (BOS). Prior work in both mice and humans has shown that interferon gamma (IFNG)-induced chemokines, including CXCL9 and CXCL10, are elevated in patients with established BOS. We hypothesized that patients who ultimately developed BOS would have elevations in these chemokines before losing lung function. We utilized a high throughput multiplex enzyme-linked immunosorbent assay (ELISA) to measure biomarkers in bronchoalveolar lavage fluid (BALF). We modeled cumulative exposure to seven biomarkers (CXCL9, CXCL10, RANTES, IL1-RA, IL-17, MCP1 and IL-13) by calculating the 1-year area under the curve (AUC) for each biomarker in the BALF of 40 lung transplant patients who had at least four samples obtained in the first year posttransplant. Cumulative elevations in CXCL9 and CXCL10 were associated with a significant risk of subsequent graft failure after transplant (HR 9.37 and 5.52, respectively; p < 0.01 for both). Further these chemokines were also elevated in patients before the onset of BOS. CXCL9 and CXCL10 elevations were seen between 3 and 9 months before graft failure. Our data show that persistent presence of CXCL9 and CXCL10 portents worsening lung allograft function; measuring these IFNG-induced chemokines might prospectively identify patients at risk for BOS.

Pretransplantation Serum FT 3 Concentration in Kidney Recipients is Useful to Identify Higher Risk of Graft Failure

Background Free triiodothyronine (FT 3) is a marker of comorbidity in end-stage renal disease and in many acute and chronic diseases. The objective of the present study was to investigate the effects of pretransplantation FT 3 concentration on graft function. Materials and Methods Between 2003 and 2008, the study enrolled 86 patients who underwent renal transplantation. Twenty-six patients were women, and 60 were men, with overall mean (SD) age of 38 (10) years. In all patients, serum FT 3, free thyroxine, and thyroid-stimulating hormone concentrations were determined before transplantation. Demographic data and laboratory values were evaluated at 2 years posttransplantation. Results The overall graft survival rate at 2 years was 82.1%. Pretransplantation serum FT 3 concentration was inversely correlated with 2-year serum creatinine concentration ( r = −0.29; P = .01) and proteinuria ( r = −0.37; P < .00). Linear regression analysis demonstrated that serum FT 3 ( r 2 = 0.63; 95% confidence interval, 0.52–0.74; P = .00) was a statistically significant risk factor for increased serum creatinine concentration. No correlation was observed for thyroid-stimulating hormone or free thyroxine and posttransplantation data. Conclusion Patients with end-stage renal disease with low pretransplantation serum FT 3 concentration are at greater risk of subsequent graft failure. Measurement of pretransplantation serum FT 3 concentration could be a clinically useful method of identifying patients at increased risk of graft failure.

Evidence for Antibody-Mediated Injury as a Major Determinant of Late Kidney Allograft Failure

Late graft failure (LGF) is believed to be the consequence of immunologic and nonimmunologic insults leading to progressive deterioration in kidney function. We studied recipients with new onset late kidney graft dysfunction (n=173) to determine the importance of C4d staining and circulating donor-specific antibody (DSA) in subsequent LGF. One hundred seventy-three subjects transplanted before October 1, 2005 (mean time after transplant 7.3+/-6.0 years) had a baseline serum creatinine level of 1.4+/-0.3 mg/dL before January 1, 2006 and underwent biopsy for new onset graft dysfunction after that date (mean creatinine at biopsy 2.7+/-1.6 mg/dL). Statistical analysis was based on central DSA and blinded pathology determinations. Subjects were divided into four groups based on C4d and DSA: no C4d, no DSA (group A; n=74); only DSA (group B; n=31); only C4d (group C; n=28); and both C4d and DSA (group D; n=40). Among DSA+ recipients (groups B and D), group D had broader reactivity and a stronger DSA response. After 2 years, groups C and D (C4d+) were at significantly greater risk for LGF than groups A and B. Adjusting for inflammation (Banff i, t, g, and ptc scores) did not change the outcome. Local diagnosis of calcineurin inhibitor nephrotoxicity was spread across all four subgroups and did not impact risk of LGF. Evidence of antibody-mediated injury (DSA or C4d) is common (57%) in patients with new onset late kidney allograft dysfunction. The risk of subsequent graft failure is significantly worse in the presence of C4d+ staining.

Post-Transplant HLA class II Antibodies and High Soluble CD30 Levels are Independently Associated with Poor Kidney Graft Survival

HLA-specific antibodies (HSA) and soluble CD30 (sCD30) were measured in 208 renal transplant recipients with functioning grafts at least 1 year after transplantation (median 8.2 years) to investigate the predictive value of HSA and sCD30 on subsequent graft outcome. HSA (class I and class II) were detected by both ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up time of 3.5 years after antibody and sCD30 measurement. Recipients with post-transplant HLA class II antibodies had particularly poor graft outcome with a hazard ratio (HR) of 7.8 (p < 0.0001) when detected by ELISA, and a HR of 6.0 (p < 0.0001) when detected by Luminex. A high post-transplant sCD30 level >or=100 U/mL was associated with increased risk of subsequent graft failure (HR 2.7, p = 0.03). sCD30 and HSA had an independent and additive association with graft outcome. Recipients with HLA class II antibody and high sCD30 had the highest risk of subsequent graft failure (HR 43.4, p < 0.0001 and HR 18.1, p = 0.0008 for ELISA and Luminex, respectively). These data show that detection of HSA and serum sCD30 measured at least 1-year post-transplant provides valuable and predictive information regarding subsequent graft outcome.