Wenhan Peng

Urinary fractalkine is a marker of acute rejection

Chemokines and their receptors play an important role in the development of allograft rejection through directing mononuclear cell invasion of the graft. To study whether chemokine assays in the urine could prove to be predictive of acute rejection, we measured the urinary excretion of several chemokines, including fractalkine, chemokine monokine induced by interferon-gamma, interferon-gamma-inducible protein 10, macrophage inflammatory protein-3 alpha, granzyme B, and perforin in 215 allograft recipients and in 80 healthy control subjects. The 67 patients with acute rejection had significantly higher levels of all urinary chemokines compared to the healthy controls or patients having chronic allograft nephropathy but with stable renal function. Only changes in urinary fractalkine differentiated patients with acute rejection from those with acute tubular necrosis. The 7 patients who lost their grafts had greater urinary fractalkine, interferon-gamma, and macrophage inflammatory protein-3 alpha concentrations than those patients with reversible acute rejection. The area under the receiver operating characteristic curve for fractalkine was the best indicator among all of the markers differentiating 39 patients diagnosed with steroid-resistant from the 28 patients with steroid-sensitive acute rejection and in predicting graft loss. Our study shows that measuring urinary fractalkine levels is a noninvasive approach for detecting acute rejection where high levels were associated with steroid-resistance and poor outcome.

Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases

X. Yu, F. Han, J. Wu, Q. He, W. Peng, Y. Wang, H. Huang, H. Li, R. Wang, J. Chen. Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases.
Transpl Infect Dis 2011: 13: 385–391. All rights reserved

Acute renal allograft rejection is associated with increased levels of vascular endothelial growth factor in the urine

Aim:  The purpose of this study was to assess whether measurement of urinary vascular endothelial growth factor (VEGF) could be adopted as a new non‐invasive diagnostic tool for acute rejection following renal transplantation.

Non-invasive Detection of Acute Renal Allograft Rejection by Measurement of Vascular Endothelial Growth Factor in Urine

Urinary vascular endothelial growth factor (VEGF) was determined by enzyme-linked immunosorbent assay in 199 renal allograft recipients and 80 healthy controls. Urinary VEGF level did not change significantly during the first 8 weeks after transplantation in 119 patients with stable renal function and there were no abnormal histological findings (No-AR). In 67 patients with acute rejection, urinary VEGF was significantly higher (28.57 ± 6.21 pg/μmol creatinine) than in the No-AR patients (3.05 ± 0.45 pg/μmol creatinine) and healthy controls (2.87 ± 0.35 pg/μmol creatinine). At a cut-off point of 3.26 pg/μmol creatinine, sensitivity and specificity for diagnosis of acute rejection were 86.6 and 71.4%, respectively. The 13 patients with subclinical rejection excreted urinary VEGF (16.14 ± 4.09 pg/μmol creatinine) at a significantly higher level than No-AR patients (3.05 ± 0.45 pg/μmol creatinine). At a cut-off point of 4.69 pg/μmol creatinine, sensitivity and specificity for diagnosis of subclinical rejection were 84.6 and 79.8%, respectively. In conclusion, monitoring VEGF in urine might offer a new non-invasive way to detect acute and subclinical rejection in renal transplant recipients.

Feasibility of diagnosing renal allograft dysfunction by oligonucleotide array: Gene expression profile correlates with histopathology

BACKGROUND Effective non-invasive monitoring method to tell histopathology is a big challenge in renal transplantation. METHODS We used 70-mer long oligonucleotide array with 449 immune related genes to determine gene expression profiles of peripheral blood mononuclear cells (PBMCs) under different immune status including stable renal function (TX), acute tubular necrosis (ATN), biopsy conformed acute rejection (AR), clinical rejection with pathology of borderline changes (BL), clinical rejection without biopsy proven/presumed rejection (PR) and renal dysfunction without rejection (NR). RESULTS Distinct molecular expression signatures in each group were found to correlate with histopathology. And we concluded that B cell chemokine CXCL13 and mast cell may play a role in renal allograft rejection through significant difference analysis and functional pathway analysis. CONCLUSIONS It provides a potential non-invasive method for monitoring renal allograft function and immune status of renal transplant recipients.

Interleukin‐2 receptor antagonist compared with antithymocyte globulin induction therapy in kidney transplantation from donors after cardiac death

The aim of this study was to compare the efficacy and safety of induction therapy using the interleukin‐2 receptor antagonist (IL‐2RA) with antithymocyte globulin (ATG) under a tacrolimus‐based immunosuppression regimen in kidney transplantation from donors after cardiac death.

Simple Cysts in Donor Kidney Contribute to Reduced Allograft Function

Background: Simple renal cysts may be an early marker of renal disease. We investigated whether simple cysts in donor kidney are associated with the decline of allograft function in living donor kidney transplantation. Methods: We retrospectively reviewed records of donors and recipients from 716 living donor kidney transplants performed between April 2007 and April 2015 in our hospital. Ninety-one donors with renal cysts and 64 recipients with cysts in donor kidney were noted. We compared these 64 cases to 128 no cyst-bearing controls matched for the donor gender, recipient gender, donor baseline serum creatinine (sCr), donor/recipient body surface area ratio, donor age, recipient age and the date of kidney transplantation in turn. Results: The presence of cysts was interrelated with age, gender and renal function independently in donors. Pathological findings of time-zero biopsy revealed that donor kidney harboring cysts existed more glomerular sclerosis compared with no cyst-bearing controls (p = 0.040). The estimating glomerular filtration rate levels of recipients were 80.82 ± 26.61 vs. 88.21 ± 23.12, 66.95 ± 17.42 vs. 72.15 ± 16.42 and 60.92 ± 22.17 vs. 68.72 ± 14.43 ml/min· 1.73 m2 in cyst-bearing and no cyst-bearing group on day 7, month 6 and year 5, respectively, after surgery (p < 0.05). The mean sCr were 112.14 ± 48.32 vs. 98.75 ± 29.71 and 126.28 ± 42.32 vs. 115.05 ± 26.35 μmol/l on the 7th day and a half year after transplant, respectively (p < 0.05). The 2 groups did not significantly differ in terms of the other characteristics. Conclusion: Simple cysts in donor kidney can influence the early and long-term allograft function. In living donor transplantation, kidney presenting cysts should be considered carefully at the time of donor selection.

Limited Sampling Strategy for Mycophenolic Acid in Chinese Kidney Transplant Recipients Receiving Enteric-Coated Mycophenolate Sodium and Tacrolimus During the Early Posttransplantation Phase.

Background: Mycophenolic acid (MPA), a potent immunosuppressant, is widely used in solid organ transplantations. This study aimed to investigate the pharmacokinetics of enteric-coated mycophenolate sodium (EC-MPS) in Chinese adult renal allograft recipients and to generate optimal model equations for estimation of the MPA area under the concentration–time curve from 0 to 12 hours (AUC0–12 h), using a limited sampling strategy (LSS). Methods: Serial blood samples were collected over 12 hours from 38 recipients of a primary living-related donor kidney graft treated with EC-MPS, tacrolimus, and corticosteroid. MPA concentrations were evaluated using an enzyme-multiplied immunoassay technique. The LSSs were developed and validated by multiple regression analysis using a 2-group method (test group, n = 19; validation group, n = 19). Results: The best algorithms obtained from the test group were the following: 15.09 + 1.05 × C1.5 + 1.8 × C4 + 4.18 × C6 (for 3 time points, r2 = 0.902) and 10.44 + 0.7 × C1 + 1.22 × C2 + 1.75 × C4 + 4.36 × C6 (for 4 time points, r2 = 0.941). When these algorithms were tested in the validation group, there were no significant differences in prediction errors. Conclusions: LSSs using time points of 1.5, 4, and 6 hours or 1, 2, 4, and 6 hours after dose provide effective and reliable estimations of the MPA AUC0–12 h in Chinese renal allograft recipients treated concomitantly with EC-MPS and tacrolimus during the early posttransplantation phase.

Dynamics of early post-operative plasma ddcfDNA levels in kidney transplantation: a single-center pilot study

Donor‐derived cell‐free DNA (ddcfDNA) is reported to be a promising noninvasive biomarker for acute rejection in organ transplant. However, studies on monitoring ddcfDNA dynamics during the early periods after organ transplantation are scarce. Our study assessed the dynamic variation in ddcfDNA in early period with various types and status of kidney transplantation. Target region capture sequencing used identifies ddcfDNA level in 21 kidney transplant recipients. Median ddcfDNA level was 20.69% at the initial time post‐transplant, and decreased to 5.22% on the first day and stayed at the stable level after the second day. The ddcfDNA level in DCD (deceased donors) group (44.99%) was significantly higher than that in LDRT (living donor) group (10.24%) at initial time, P < 0.01. DdcfDNA level in DGF (delayed graft function) recipients was lower (23.96%) than that in non‐DGF (47.74%) at the initial time, P = 0.89 (19.34% in DGF and 4.46% in non‐DGF on the first day, P = 0.17). DdcfDNA level at initial time significantly correlated with serum creatinine (r2 = 0.219, P = 0.032) and warm ischemia time (r2 = 0.204, P = 0.040). Plasma ddcfDNA level decreased rapidly follow an L‐shaped curve post‐transplant, and level in DGF declined slower than non‐DGF. The rebound of ddcfDNA level may indicate the occurrence of acute rejection.

The Effect of Histological CD20-Positive B Cell Infiltration in Acute Cellular Rejection on Kidney Transplant Allograft Survival

Background. It is controversial whether lymphocyte infiltration exhibited in biopsy specimens is associated with transplant outcomes. This study focused on the effect of CD20-positive B cell infiltration in biopsy specimens from allografts with acute cellular rejection (ACR) in a Chinese population. Methods. Altogether, 216 patients transplanted from Sep. 2001 to Dec. 2014 with biopsy-proved ACR (Banff I or Banff II) were included in the analysis. Biopsies were immunostained for CD20 and C4d. Baseline information, serum creatinine and GFR before and after treatment, steroid resistance, response to treatment, graft loss, and survival were analyzed. Results. Eighty-three patients were classified into CD20-negative group, and 133 patients were classified into CD20-positive group. Significantly more CD20-negative patients (49/83, 59.0%) received steroid plus antibody therapy compared with the CD20-positive group (52/133, 39.1%) (P = 0.004). The response to treatment for ACR did not differ between these two groups. The CD20-positive group had less graft loss (18.8% versus 32.5%, P = 0.022) and a better graft survival rate. Further exploration of the infiltration degree suggested that it tended to be positively related to graft survival, but this did not reach statistical significance. Conclusion. CD20-positive B cell infiltration in renal allograft biopsies with ACR is associated with less steroid resistance and better graft survival. The presence of CD20-positive B cells is protective for renal allografts.