Effects of Bailing capsules for renal transplant recipients: a retrospective clinical study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The administration of immunosuppressive agents is always an important factor affecting the long-term survival of organ transplantation recipients. The best therapeutic regimen which either decreases the side effects of immune inhibitors or enhances the immunosuppressive efficacy is the goal of transplantation surgeons continue to search. This study investigated the effects of Bailing (Cordyceps sinensis) capsules on renal function and other systems of the body after renal transplantation.</p><p><b>METHODS</b>Clinical data of 80 renal transplant recipients who were administered Bailing capsules and 100 renal transplant recipients in the control group were retrospectively analyzed to compare the incidences of graft rejection and infection after transplantation. The results of routine blood and urine tests, liver and kidney functions, uric acid (UA), 24-hour urine protein (24 h-Upro), as well as 1- and 5-year patient renal allograft survival rates were compared between the two groups.</p><p><b>RESULTS</b>The follow-up was 3 - 5 years. The two groups were not shown to have statistically significant differences in age, gender, cold ischemia time, donor-recipient human leukocyte antigen typing, panel reactive antibodies, lymphocytotoxicity tests, and the application of immunosuppressive agents at the baseline. The two groups were also not significantly different in the incidence of acute injection after transplantation, recovery of renal function, and blood glucose level. The Bailing group was significantly lower than the control in the incidence of infection, serum aspartate aminotransferase/alanine aminotransferase, total bilirubin, UA, and 24-hour Upro, but significantly higher than the control group in peripheral red blood cell count and white blood cell count (P < 0.05). One-year and 5-year patient survival rates were 98.7% and 98.0%, respectively in the Bailing group, 95.0% and 93.0%, respectively, in the control group. One-year and 5-year renal allograft survival rates were 97.5% and 95.0%, respectively, in the Bailing group, and 92.5% and 84.0%, respectively, in the control group. The comparison of patient and renal allograft survival rates between the two groups using Kaplan-Meier survival curves and log-rank test showed that only the differences in renal allograft survival rates were statistically significant (Log-rank: 5 years: patient survival P = 0.420; renal allograft survival P = 0.049).</p><p><b>CONCLUSION</b>Bailing capsules were effective in preventing allograft rejection, protecting liver and kidney functions, stimulating hematopoiesis, and reducing the incidence of infection and thus are ideal immunoregulators.</p>

A retrospective comparison of the efficacy and safety in kidney transplant recipients with basiliximab and anti-thymocyte globulin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Induction therapy are utilized to achieve an adequate immunosuppression at the time of transplantation. The use of basiliximab or anti-thymocyte globulin (ATG) for induction therapy has significantly reduced the incidence of acute rejection episodes post-transplantation. The purpose of this study was to compare the efficacy and safety of the basiliximab in patients with immuno-induction therapy after kidney transplantation with the ATG.</p><p><b>METHODS</b>A retrospective analysis was carried out in kidney transplant recipients including 146 patients with the basiliximab and 116 cases with the ATG and the acute rejection, graft function, infective complications and 1-year and 5-year actuarial patient and graft survival after renal transplantation were compared between the two treatment groups.</p><p><b>RESULTS</b>There were no statistically significant difference between groups regarding age, sex, cold ischemic time, warm ischemic time, human leukocyte antigen (HLA) matching type between the donor and recipient, lymphotoxin test and the use of immunosuppressive agents. There was no statistical significance regarding the incidence of the acute rejection (9.59% vs. 8.62%, P = 0.481) and delayed graft function (10.27% vs. 9.48%, P = 0.501) between groups. There were significantly lower lung infection incidence (5.48% vs. 12.93%, P = 0.029) in the basiliximab-treated group in comparison with the ATG-treated group. One-year patient and graft survival rates were 98%, 97% for the basiliximab-treated group, and 95%, 73% for the ATG-treated group, respectively. Five-year patient and graft survival rates were 92%, 86% for the basiliximab-treated group and 93%, 72% for the ATG-treated group, respectively. Log rank test showed statistically significant difference with P = 0.038 for patients and P = 0.033 for grafts, respectively. There were significantly lower the incidence of granulocytopenia (8.22% vs. 17.24%, P = 0.022) and thrombocytopenia (4.11% vs. 19.83%, P = 0.000) after transplantation in the basiliximab-treated group in comparison with the ATG-treated group. There was no statistical significance regarding the incidence of the heart dysfunction after transplantation between the two groups (6.16% vs. 6.90%, P = 0.502).</p><p><b>CONCLUSION</b>The immuno-induction therapy with the basiliximab in kidney transplant recipients is efficient and safe with less complication compared with the ATG.</p>

Pharmacokinetics of enteric-coated mycophenolate sodium in Chinese renal transplantation recipients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mycophenolic acid (MPA) as an anti-proliferative immune-suppressive agent is used in the majority of immunosuppressive regimens in solid organ transplantation. This study aimed to investigate the pharmacokinetic (PK) characteristics of enteric-coated mycophenolate sodium (EC-MPS) and area under the curve (AUC) from 0 to 12 hours with limited sampling strategies (LSSs) in Chinese renal transplant recipients.</p><p><b>METHODS</b>This study was conducted in 10 Chinese renal transplant patients receiving living donor and treated with EC-MPS, cyclosporine, and corticosteroids. MPA concentrations were measured by enzyme multiplied immunoassay technique (EMIT). Whole 12-hour PK profiles were obtained on Day 4 after operation. LSSs with jackknife technique, multiple stepwise regression analysis, and Bland-Altman analysis were developed to estimate MPA AUC.</p><p><b>RESULTS</b>The mean maximum plasma concentration, the mean time for it to reach peak (T(max)), and the mean MPA AUC were (11.38 ± 2.49) mg/L, (4.85 ± 3.32) hours, and (63.19 ± 13.54) mg×h×L(-1), respectively. Among the 10 profiles, MPA AUC of four patients was significantly higher than that of the other six patients, and the corresponding T(max) was significantly longer than that of the other six patients. No patient exhibited a second peak caused by enterohepatic recirculation. The best models were as follows: 27.46 + 0.94C(3) + 3.24C(8) + 2.81C(10) (r(2) = 0.972), which was used to predict AUC of fast metabolizer with a mean prediction error (MPE) of -0.21% and a mean absolute prediction error (MAE) of 2.59%; 36.65 + 3.08C(8) + 5.30C(10) - 4.04C(12) (r(2) = 0.992), which was used to predict AUC of slow metabolizer with a MPE of 0.58% and a MAE of 1.95%.</p><p><b>CONCLUSIONS</b>The PKs of EC-MPS had a high variability among Chinese renal transplant recipients. The preliminary PK data indicated the existence of slow and fast metabolizer. These findings may be associated with the enterohepatic recirculation.</p>

Forkhead box protein 3 mRNA expression in the peripheral blood of kidney-transplant recipients with acute rejection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Regulatory T cells (Tregs) are immunologically and clinically interesting not least because of the important role they play in allograft rejection. Likewise, expression of the transcription factor forkhead box protein 3 (FOXP3), detected in transplant biopsies, is also of interest because of its role in the development of regulatory T cells. In this study, we investigated the relationship between FoxP3 mRNA expression and acute organ rejection in kidney-transplant recipients.</p><p><b>METHODS</b>In this prospective study, FoxP3 mRNA expression levels in peripheral blood samples from 10 recipients of living relative-donor kidney transplants were measured before transplantation as well as at the 14th and 90th days post-transplantation. In addition, 46 first-time kidney-transplant recipients participated in a cross-sectional study, with 28 patients classified as having acute organ rejection; whilst the remaining 18 patients had functionally stable allografts. FoxP3 mRNA expression levels in peripheral blood samples were compared between these two different groups.</p><p><b>RESULTS</b>Before transplantation mean FoxP3 mRNA levels vs. GADPH mRNA levels (lg(FoxP3 mRNA/GADPH mRNA)) in the 10 recipients were 1.11 ± 0.67. The mean FoxP3 mRNA expression levels measured at 14th and 90th days post-transplantation were significantly higher than before transplantation (1.69 ± 0.38, P = 0.03; 1.44 ± 0.21, P = 0.04, respectively). Additionally, the mean FoxP3 mRNA levels vs. GADPH mRNA expression levels (lg(FoxP3 mRNA/GADPH mRNA)) were significantly higher in recipients suffering acute rejection compared with those with stable allografts (1.77 ± 0.61 and 1.43 ± 0.27, respectively, P = 0.03).</p><p><b>CONCLUSIONS</b>After kidney transplantation, FoxP3 mRNA levels were found to increase in the peripheral blood of all recipients. Considerably higher FoxP3 mRNA levels were observed in recipients suffering acute rejection. These results suggest that FoxP3 mRNA levels in peripheral blood samples can be used as a diagnostic tool for identifying acute rejection.</p>

Expression characteristics of major histocompatibility complex class I-related chain A antibodies and immunoadsorption effect in sensitized recipients of kidney transplantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sensitized recipients have a high risk of immunological graft loss due to hyperacute rejection and/or accelerated acute rejection. The presence of major histocompatibility complex class I-related chain A (MICA) antibodies has also been described associated with an increased rate of kidney-allograft rejection. The aim of this study was to describe the expression of MICA antibodies in sensitized recipients of renal transplantation and evaluate its influence on the kidney transplantation recipients.</p><p><b>METHODS</b>A total of 29 sensitized recipients were included in this study. All patients received the MICA antibodies detection before and after protein A immunoadsorption. Panel reactive antibody (PRA), HLA-matches, acute rejection and postoperative one to four-week serum creatinine level were also collected and analyzed, respectively. No prisoners were used in this study.</p><p><b>RESULTS</b>Eight patients (27.6%) in all 29 sensitized recipients expressed the MICA antibodies but did not show higher acute rejection rate than the non-expressed patients (3/8, 37.5% vs. 8/21, 38.1%; P = 1.000). Recipients with PRA > 40% showed higher expression levels of MICA antibodies than the recipients with PRA < 40% (7/16, 43.8% vs. 1/13, 8.3%; P = 0.044). HLA mismatch did not have any effect on the expression of MICA antibodies (P = 1.000). MICA antibodies positive group had higher serum creatinine level than the control in postoperative one week ((135.4 ± 21.4) µmol/L vs. (108.6 ± 31.6) µmol/L, P = 0.036), but no significant difference in postoperative four weeks ((89.0 ± 17.1) µmol/L vs. (77.1 ± 15.9) µmol/L, P = 0.089). MICA antibodies decreased significantly after protein A immunoadsorption.</p><p><b>CONCLUSIONS</b>MICA antibodies increase in the sensitized recipients, which have significant effects on the function of allograft in early postoperative period. Protein A immunoadsorption can decrease MICA antibodies effectively in sensitized recipients.</p>

Rituximab induction therapy in highly sensitized kidney transplant recipients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients.</p><p><b>METHODS</b>Seven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21-47 years). The duration of hemodialysis was 3-12 months, with a mean duration of 11 months. For 4 patients, this was the second transplant; the previous graft survival time was 2-11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25-37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg × kg(-1) × d(-1)) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m(2)) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery. Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored.</p><p><b>RESULTS</b>No patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post-surgery. Diagnosis of acute rejections was based on the clinical assessments and pathological biopsy results. According to the Banff 07 classification of renal allograft pathology, one of the patients was Ia and the other was IIa; the C4d staining was negative in both patients. One patient received methylprednisolone plus cyclophosphamide and the other received antithymocyte globulin (ATG) therapy, both leading to successful reversion of the acute rejection. All patients were discharged postoperatively and all had normal renal function during the 7th to 12th month follow-up. Pulmonary infection occurred in 1 patient 4 months after surgery and was successfully cured.</p><p><b>CONCLUSION</b>Rituximab induction therapy can reduce the occurrence of postoperative humoral rejection in highly sensitized renal transplant recipients, suggesting that kidney transplantation may be safe and effective for these patients.</p>

Factors affecting the long-term renal allograft survival / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In the past decades, the one-year graft survival of cadaveric renal allografts has been markedly improved, but their long-term survival has not kept pace. The attrition rate of renal allografts surviving after one year remains almost unchanged. The causes for late graft loss are multiple. The aim of this study was to analyze the predictive factors that impact long-term survival of grafts after kidney transplantation.</p><p><b>METHODS</b>We retrospectively analyzed 524 kidney transplantation patients who were treated in our hospital between January 1991 and January 2000, including 254 patients who had lived more than 10 years with normal graft function (long survival group), and 270 cases whose renal graft had survived less than 10 years (control group). Specifically, we analyzed 10 factors that may potentially affect graft survival by both univariate and Logistic model multivariate analyses to pinpoint the independent risk factors.</p><p><b>RESULTS</b>Univariate analyses showed that no significant differences existed in the age or gender of recipients, dialysis time, lymphotoxin levels, or cold ischemia time between the two groups. However, the ratio of delayed graft function and acute rejection, and the uric acid levels of patients in the long survival group were significantly lower than those in the control group (P < 0.01). Furthermore, we found that the concentration of cyclosporin A at one year after transplantation and the histocompatibility antigen match of donor-recipients for patients within the long survival group were significantly higher than those in the control group (P < 0.01). Furthermore, multivariate analyses showed that these four factors were independent risk factors that impact patient survival.</p><p><b>CONCLUSIONS</b>The ratios of delayed graft function and acute rejection, the concentration of cyclosporin A at one year after transplantation, and serum uric acid levels are very important factors that affect the long-term survival of renal grafts.</p>

Multidetector row-CT in evaluation of living renal donors / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Multidetector-row CT (MDCT) has been evolving to the standard evaluating method of potential living donor in most centers, and can provide excellent details for selecting candidates and determining surgical technique. This study aimed to assess the value of MDCT in evaluation of the anatomy of living kidney donors and to reveal the prevalence of renal vascular variations in a Chinese population.</p><p><b>METHODS</b>One hundred and four potential donors underwent MDCT and the data sets were post-processed for reformatted images with various techniques, such as maximum intensity projection (MIP), a volume-rendering technique (VR), and multiplanar reformation (MPR). Donor nephrectomies were performed on 97 candidates after MDCT evaluation with the findings during surgery constituting the standard of reference. Resulting MDCT images were compared with actual anatomy found during surgery.</p><p><b>RESULTS</b>The MDCT images accurately displayed the anatomic structure of the main renal arteries and veins as well as the upper ureters, except in one case with horseshoe kidney. The prevalence of accessory arteries revealed in images was 27.2% (28/103) and early branching was found in 12.6% (13/103). Compared with findings during surgery, the detection of accessory arteries in MDCT images was 85.7% (6/7), and the detection of larger accessory arteries (> 1.5 mm in diameter) was 100%. Detection of early branching was 100%.</p><p><b>CONCLUSION</b>MDCT helps accurately evaluate the renal anatomy of potential donors thus facilitating the planning of surgery.</p>

Protein A immunoadsorption combined with rituximab in highly sensitized kidney transplant recipients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of protein A immunoadsorption combined with rituximab (RTX) in highly sensitized recipients of kidney transplants.</p><p><b>METHODS</b>Seven highly sensitized recipients of living-related renal transplants (4 men and 3 women, mean aged 42.5 years old (range 33 - 51)) were pretreated with this combination. Human leukocyte antigen (HLA) mismatch number was 2 - 5. Panel reactive antibody (PRA) of class I was high in 2 cases and that of class II was high in 1 case. All patients were pretreated with immunoadsorption 2 - 10 times. Immunoglobulin and PRA changes were monitored before and after absorption. The operation was conducted when PRA or immunoglobulin levels were at or below normal levels. Immunosuppressive drugs were provided 3 - 5 days before the operation, and one dose of RTX (375 mg/m(2)) was infused with polyclonal antibody on the day of operation. Postoperative creatinine (Cr), creatinine clearance rate (Ccr), PRA ratio, and immunoglobulin changes were monitored.</p><p><b>RESULTS</b>All 7 patients had good recovery without delayed graft function. Acute rejection occurred in 3 cases at postoperative days 8, 10, and 14, respectively. The Banff 07 biopsy grades were Ia in 1 case and IIa C4d0 in 2 cases. Successful reversion was achieved after giving methylprednisolone or antithymocyte immunoglobulin + cyclophosphamide. All patients were discharged with normal renal function, mean class I PRA was 14% and mean class II PRA was 35%. PRA was completely negative in 3 cases.</p><p><b>CONCLUSION</b>Protein A immunoadsorption combined with RTX can safely reduce the occurrence of humoral rejection in highly sensitized renal transplant recipients.</p>

Clinical observation of 153 cases of live donor kidney transplantation / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the outcomes of live donor renal transplantation.</p><p><b>METHODS</b>The clinical data of 153 patients who had undergone live donor kidney transplantation in our center from March 1999 to July 2008 were collected and retrospectively analyzed.</p><p><b>RESULTS</b>Delayed graft function (DGF) occurred in 8 patients, among whom 5 cases of DGF were successfully reversed by conservative treatment, 2 recipients died of refractory rejection and cardiac infraction, and 1 graft was resected because of severe infection. Eight recipients died of infection, cardiovascular events, and cerebral events soon after transplantation. All the 153 patients were followed up, and the 6-month, 1-year, 3-year, and 5-year survival number (and rates) were 139 (96.7% and 98.7%), 114 (94.7% and 98.7%), 62 (90.1% and 96.7%), and 36 (83.5% and 94.7%), respectively.</p><p><b>CONCLUSION</b>Live donor kidney transplantation plays an important role in the management of end stage renal disease, with satisfactory outcomes.</p>

Clinical analysis of urothelial carcinoma following renal transplantation / 中华泌尿外科杂志

Objective To analyze the clinical features of urothelial carcinoma in renal allograft re- cipients and to investigate its diagnosis and treatment.Methods A retrospective study was undertaken on 1293 renal allograft recipients in our center between 1998 and 2003.Of them ,21 cases(72.4% )had urothe- lial carcinoma(4 males and 17 females).All the cases had not had tumor before transplantation.In 17 cases the protopathy was chronic interstitial nephritis(CIN).The mean interval between tumorigenesis and trans- plantation was 26 months(range,6-62 months).Of the 21 cases,6 had bladder transitional cell carcinoma (TCC);6 had unilateral pelvic or ureter TCC;8 had unilateral pelvic or ureter and bladder TCC;1 had bilat- eral pelvic and ureter TCC.In 10 cases,the ipsilateral upper urinary tract of the graft was involved;and in 4 cases,the contralateral upper urinary tract was involved.Painless gross hematuria and iterative urinary tract infection were the cardinal symptoms.Surgical treatment was performed in 19 cases.Postoperatively,all the cases received immunosuppressants at one third reduction dose in combination with intravesical instillation chemotherapy.Results Two cases receiving palliative treatment died 5 and 8 months after diagnosis.The other 19 cases were followed for 2-5 years.Of them,13 cases had tumor recurrence.The recurrence sites were bladder and the contralateral upper urinary tract.All the cases had no acute rejection at reduced dose of immunosuppressants,and all had normal renal function except for 2 cases,who underwent removal of the graft and had dialysis again.Conclusions Renal allograft recipients whose protopathy is CIN and female recipients have the risk of urothelial carcinoma after renal transplantation.Urothelial carcinoma occurs more often in ipsilateral upper urinary tract of the graft than in contralateral upper urinary tract.Considering the high possibility of bilateral upper urinary tract involvement by TCC,prophylactic bilateral nephroureterectomy with bladder cuff excision should be considered in renal allograft recipients who have involvement of contra- lateral upper urinary tract of the graft.