Jianyong Wu

The significance of BOLD MRI in differentiation between renal transplant rejection and acute tubular necrosis

BACKGROUND Blood oxygen level-dependent MRI (BOLD MRI) can be used to assess intra-renal oxygen bioavailability by measuring the R2(*) level, which reflects tissue deoxyhaemoglobin levels. This study was designed to identify the significance of BOLD MRI in differentiation of acute rejection (AR) and acute tubular necrosis (ATN) in patients within 6 months after kidney transplantation. METHODS Eighty-two patients with normal graft function and 28 patients with biopsy-proven AR (n = 21) or ATN (n = 7) were enrolled. Patients with normal functioning allograft underwent BOLD MRI within 2 to 3 weeks post-transplantation, while patients with AR and ATN underwent BOLD MRI within 6 days before or after kidney transplant biopsy. Cortical R2(*) (CR2(*)) and medullary R2(*) (MR2(*)) levels were measured. RESULTS The mean CR2(*) level was significantly higher in the ATN group (15.25 +/- 1.03/s) compared to the normal group (13.35 +/- 2.31/s, P = 0.028) and AR group (12.02 +/- 1.72/s, P = 0.001). There was a significant difference also between the AR group and normal group on CR2(*) levels (P = 0.013). The mean MR2(*) level was significantly lower in the AR group (14.02 +/- 2.68/s) compared to the normal group (16.66 +/- 2.82/s, P < 0.001) and ATN group (19.47 +/- 1.62/s, P < 0.001). There was also a significant difference between the ATN group and normal group on MR2(*) levels (P = 0.011). There were no correlations between characteristics such as patient age, post-operation time, post-biopsy time, Scr level, HB level, urine output volume, MAP level, CNI trough concentration and R2(*) levels, except between MAP level and CR2(*) level (P = 0.029). CONCLUSIONS BOLD MRI could be a valuable method to discriminate between AR and ATN by measuring tissue oxygen bioavailability in early kidney allograft dysfunction.

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.

Kidney Transplantation from Hepatitis B Surface Antigen Positive Donors into Hepatitis B Surface Antibody Positive Recipients: A Prospective Nonrandomized Controlled Study from a Single Center

The number of patients on renal transplant waiting list is increasing rapidly in many countries, exacerbating the shortage of organs. We conducted a study to evaluate the safety and efficacy of deceased‐donor kidney transplantation from hepatitis B surface antigen (HBsAg)‐positive (+) donors into hepatitis B surface antibody (anti‐HBs)‐positive (+) recipients. Sixty‐five patients received grafts from HBsAg(+) donors, and 308 subjects received grafts from HBsAg‐negative(−) donors. Posttransplantation, recipients with HBsAg(−) grafts or HBsAg(+) grafts received 400 U of hepatitis B immunoglobulin once and twice, respectively. The seven recipients who received grafts from hepatitis B virus (HBV) DNA(+) donors were treated with hepatitis B immunoglobulin 400 U weekly for 3 months and lamivudine 100 mg daily for 6 months. All patients were monitored for liver function and hepatitis B viral status. The follow‐up period was 38.7 ± 15.4 months. Although two recipients developed de novo HBV infection, neither patient developed severe liver dysfunction nor died. The incidence of liver injury (39/65 vs. 207/308, chi‐square test, p > 0.05) and survival (log‐rank test, p > 0.05) did not differ between the groups. We conclude that anti‐HBs(+) recipients receiving HBsAg(+) grafts did as well as those receiving HBsAg(−) grafts.

Peritoneal dialysis-associated nontuberculous mycobacterium peritonitis: a systematic review of reported cases

BACKGROUND Peritonitis caused by nontuberculous mycobacterium (NTM) is an important complication in peritoneal dialysis (PD) patients. METHODS Cases of PD complicated by NTM peritonitis reported in the English language literature were identified in the PubMed database. The characteristics of these cases were reviewed. RESULTS In 41 articles, we identified 57 cases of PD-associated NTM peritonitis in patients ranging from 5 to 82 years. The prevalent clinical findings of these cases were fever, abdominal pain, cloudy fluid and an elevated leukocyte count in peritoneal fluid. These findings were non-specific and could not be differentiated from symptoms caused by Mycobacterium tuberculosis or other bacteria. The majority of these cases received empirical antibacterial therapy before diagnosis of NTM peritonitis. Isolates in more than half of the peritonitis cases were the rapidly growing Mycobacterium, Mycobacterium fortuitum (38.6%) and Mycobacterium chelonae (14.0%). In most cases, PD catheters were removed and experience with non-removal was limited. CONCLUSION Diagnosis of NTM infection should be considered in PD patients with peritonitis that are culture negative or refractory to empirical antibiotic therapy.

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

Angiotensin (1 7) prevent heart dysfunction and left ventricular remodeling caused by renal dysfunction in 5/6 nephrectomy mice

The renin–angiotensin system (RAS) plays a critical role in chronic renal failure associated with heart failure. In the past few years, angiotensin (Ang) (1–7) have been reported to counteract the effects of angiotensin II (Ang II) and were even considered as a new therapeutical target in RAS. The purposes of this study were to examine whether the Ang (1–7) improves the heart function and remodeling of the left ventricle (LV) in mice with 5/6 nephrectomy (NC). We used a 5/6 nephrectomy to induce significant renal dysfunction in wildtype mice (WT). Twelve weeks after NC, WT showed high blood pressure, significant left-ventricular dilation and dysfunction, which were accompanied by cardiomyocyte hypertrophy, diffuse interstitial fibrosis and oxidative damage of cardiomyocytes. Exogenous Ang (1–7) injection improved the heart function and remodeling of LV in mice with 5/6 NC accompanied by a reduction in cardiac interstitial fibrosis, inflammatory cytokine expression and oxidative damage levels of cardiomyocytes, decrease in the profibrotic signaling molecule transforming growth factor (TGF)-β and increase in the collagen degradation signaling molecule matrix metalloproteinase (MMP)-2, -9. However, these beneficial effects did not occur in hydralazine-treated mice. These findings suggest that (1) Exogenous Ang (1–7) injection improve the heart function and remodeling of LV in mice with 5/6 NC. (2) These beneficial effects are independent of its anti-blood pressure effect.

Slope of changes in renal function in the first year post-transplantation and one-yr estimated glomerular filtration rate together predict long-term renal allograft survival.

Wu J, Li H, Huang H, Wang R, Wang Y, He Q, Chen J. Slope of changes in renal function in the first year post‐transplantation and one‐yr estimated glomerular filtration rate together predict long‐term renal allograft survival. 
Clin Transplant 2010: 24: 862–868.

A pilot study of GC/MS-based serum metabolic profiling of acute rejection in renal transplantation.

AIMS Acute allograft rejection is one of the important complications after renal transplantation, and it is a deleterious factor for long-term graft survival. Rejection is a complex pathophysiologic process, which has been explained by transcriptome and proteome in RNA transcripts and proteins level respectively. How are serum metabolite levels in response to acute rejection? Can metabolite levels in serum be used to diagnose and explain acute renal allograft rejection? METHODS Gas chromatograph-mass spectrometry (GC-MS) was used to analyze serum metabolome in 22 recipients of acute rejection and 15 stable renal transplant recipients. RESULTS 46 endogenous metabolites included amino acid, fatty acid, carbohydrate and other intermediate metabolites were identified in 37 recipients. Principal component analysis based on these metabolites discriminated acute rejection group from stable recipients. Among these metabolites, the levels of 17 metabolites were significant higher in rejection group than those in stable group. These included amino acid (phenylalanine, serine, glycine, threonine, valine), carbohydrate (galactose oxime, glycose, fructose), carboxylic acid, lipids and other metabolite such as lactate, urea and myo-inositol. The levels of 5 metabolites of alanine, lysine, leucine, aminomalonic acid and tetradecanoic acid were low in rejection group compared to stable group. The prediction accuracy of acute rejection was 77.3% and stable function was 100% by supervised clustering based on these 22 metabolites. CONCLUSIONS This study demonstrated that metabolic profile was changed in response to rejection process and renal function can be reflected by serum metabolite levels. This study showed potential capability to diagnose acute rejection by metabolome analysis.

C4d deposition in allograft renal biopsies is an independent risk factor for graft failure.

Aim:  Association between C4d deposition and renal allograft survival is still uncertain. We retrospectively evaluated the clinical outcome of C4d deposition in allograft renal biopsies.

Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection

Abstract Background: Endothelial cell antigens are important targets in acute rejection (AR). Our goal was to measure the serum concentrations of pre-transplant anti-endothelial cell antibody (AECA) in panel reactive antibody (PRA) negative recipients and its impact on AR within 6 months following renal transplantation. Methods: We retrospectively examined pre-transplant sera from 392 patients using cellular enzyme linked immunosorbent assay (ELISA) with substrate from a permanent endothelial cell line EAhy926. Equal volumes of serum from 40 healthy volunteers were mixed and used as the negative control. Results: The positive rate of AECA was 15.8%. There were no significant differences with respect to age, gender, original disease, dialysis history, immune suppressive regimen, cytomegalovirus (CMV) antigen positive rate, complement dependent cytotoxicity (CDC) level and soluble CD30 (sCD30) levels between the AECA positive group and AECA negative group. AR rate in the AECA positive group was higher than that in the AECA negative group (35.5% vs. 22.4%, p=0.023). The AECA positive patients had significantly higher rates of acute grade II T-cell mediated rejection (TMR) and acute antibody mediated rejection (AMR) compared with AECA negative patients. The concentrations of sCD30, and AECA were independent risk factors for AR within 6 months; the odds ratios were 7.005 and 2.469, respectively. Conclusions: Positive AECA was an independent risk factor for AR and appeared to correlate with relatively severe rejection subtypes. Clin Chem Lab Med 2009;47:1265–9.