[Clinicopathologic features and prognosis of patients with IgA nephropathy superimposed on transplant glomerulopathy].

Objective: To observe the clinicopathologic features and prognostic of patients with IgA nephropathy (IgAN) superimposed on transplant glomerulopathy (TG+ IgAN). Methods: Electronic medical records of Jinling Hospital were searched for TG+ IgAN patients that was diagnosed during January 2004 to December 2016. Clinicopathologic features and prognoses information were retrieved and analyzed. The primary outcome was initiation of replacement therapy or an eGFR declined to<15 ml·min(-1)·(1.73m(2))(-1). Results: A total of 49 patients with pathologically confirmed TG+ IgAN were enrolled in this study. The median time from renal transplantation to allograft biopsy was 85 months. There were 131 patients with TG in the control group. There was no statistical difference in the age, gender, and immunosuppressive regimen during renal biopsy in the two groups. In TG+ IgAN patients, the median serum creatinine level was 175 µmol/L, the median urinary protein was 1.45 g/24 h, and 16.3% of the patients had nephrotic range proteinuria, the incidence of microscopic hematuria was 40.8%, and the average hemoglobin was 105 g/L. In terms of pathology, the degree of glomerular mesangial matrix hyperplasia in the TG+ IgAN group was significantly heavier compared with TG group (P=0.004), and the degree of hyaline degeneration of the small arteries was lighter (P=0.043). There was no significant difference in interstitial inflammation (i), tubulitis (t), glomerulitis (g), peritubular capillaritis (ptc) and intimal arteritis (v). Calculated by Kaplan-Meier method, the median survival time of 49 patients with TG+ IgAN was 36.9 months, and there was no difference in survival rate of allografts compared with TG group. Conclusions: Compared with TG patients without IgA, TG+ IgAN patients had higher incidence of microscopic hematuria, more severe glomerular mesangial matrix hyperplasia, and no significant differences in other clinicopathological features. The prognosis of TG+ IgAN patients was not significantly different from those without IgAN.

Retrospective evaluation of the effect of mycophenolate mofetil dosage on survival of kidney grafts based on biopsy results.

INTRODUCTION: Plasma concentration monitoring is commonly used to adjust immunosuppressant dosage in transplant recipients, but adjustment is often based on clinical experience rather than rigorous quantitative indicators. METHODS: We examined the effect of mycophenolate mofetil (MMF) dosage on graft survival by pathologic and immunologic analysis of 88 kidney recipients who were given a postoperative immunosuppressive regimen of tacrolimus (FK506), MMF, and corticosteroids. Patients were given a conventional dosage (≥1.5 g/d; n = 40) or a reduced dosage (n = 48) of MMF owing to postoperative adverse side effects. RESULTS: The reduced-dose group included patients given low doses (≤1.0 g/d; n = 27), ultra-low doses (≤0.5 g/d; n = 15), and those who discontinued MMF (n = 6). The dose reduction group had increased acute rejection, chronic rejection, and graft dysfunction, poorer pathologic scores, and increased cell infiltration of graft tissue (CD4, CD8, CD68, and CD138 positivity) and expression of interleukin-2R and HLA-DR. Finally, hazard analysis indicated that patients given low doses and ultra-low doses of MMF had poorer long-term kidney grafts survival (hazard ratios of 1.52 and 1.78, respectively). CONCLUSIONS: These results indicate the importance of using an appropriate dosage of MMF in kidney transplant recipients.

Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

Effect of CYP3A5 genotype on renal allograft recipients treated with tacrolimus.

OBJECTIVE: Tacrolimus concentrations are associated with CYP3A5 genotype. The purpose of this study was to evaluate the outcomes and drug concentrations/doses among a posttransplant population with various CYP3A5 genotypes within 12 months. METHODS: Sixty seven kidney recipients receiving immunosuppression with tacrolimus + mycophenolate mofetil + prednisolone were grouped according to their CYP3A5 genotypes (*1/*1; *1/*3; *3/*3). The initial dose of tacrolimus (0.15 mg/kg/d) was adjusted according to achieve a target therapeutic window. All patients underwent a protocol biopsy at 1 month posttransplantation. We assayed serum creatinine and tacrolimus blood trough concentrations to calculate the concentration per dosage during follow-up. We also investigated the incidence of acute rejection episodes and the nephrotoxicity of tacrolimus according to the renal biopsy. RESULTS: There was no significant difference among serum creatinine concentrations. Tracrolimus blood concentrations showed a significant difference at day 7 and 1 month with no significant difference at 3, 6, or 12 months among the three groups. The CYP3A5*3/*3 group showed the largest concentration per dosage (C/D) and CYP3A5*1/*1, the smallest C/D. There was a significant difference among the three groups. The occurrence of an acute rejection episode within 3 months showed a significant difference among the three groups but not from 3 to 12 months after transplantation. Nephrotoxicity was greatest among the CYP3A5*3/*3 group. CONCLUSION: CYP3A5 influenced the blood concentrations of tacrolimus. Our study suggested to choose the initial dosage according to the CYP3A5 genotype to obtain a better outcome and reduce the incidences of acute rejection episodes and nephrotoxicity.

Prognostic effect of lymphocyte subgroup CD4+ and CD8+ cells in peripheral blood in renal transplant patients with cytomegalovirus viremia.

OBJECTIVE: Our aim was to evaluate the prognostic effect of peripheral blood lymphocyte subgroup CD4+ and CD8+ cells on renal transplant patients with cytomegalovirus (CMV) viremia. MATERIALS AND METHODS: Using 41 renal transplant patients with CMV-PCR(+) in peripheral blood and stable values of serum creatinine (SCr), we evaluated the changes in lymphocyte subgroup CD4+ and CD8+ cells with onset of antiviral therapy with gancyclovir for treatment of pneumonia. We compared patients with or without pneumonia. RESULTS: The lower the peripheral blood lymphocyte subgroup CD4+ and CD8+ cell numbers, the higher the incidence of CMV pneumonia. The numbers of CD4+ and CD8+ cells at 1 month posttransplantation and at the time of CMV-PCR(+) detection were significantly lower than those before transplantation in the CMV pneumonia group (P < .01) and also in the nonpneumonia group. CONCLUSIONS: The decrease in peripheral blood lymphocyte subgroup CD4+ and CD8+ cells after renal transplantation in patients with CMV viremia showed prognostic value for pneumonia. Increased CD4+ and CD8+ cells in peripheral blood combined with preemptive therapy may reduce the incidence of pneumonia among patients with CMV viremia.

Therapeutic effect of Tripterygium wilfordii on proteinuria associated with sirolimus in renal transplant recipients.

Sirolimus (SRL) is a potent immunosuppressive drug used to prevent acute allograft rejection after renal transplantation. Nevertheless, the occurrence of proteinuria has recently been recognized among patients on SRL-based therapy. The aim of this study was to investigate the therapeutic effects of Tripterygium wilfordii Hook F. (T II) on proteinuria associated with SRL in renal transplant recipients. According to accepting T II, 36 recipients were divided into 2 groups: T II group (n = 21) and valsartan group (n = 15). The T II group was administered 1 mg/kg/d, and the valsartan group, 80 mg twice per day for 12 months. Efficiency was then evaluated. Complete remission: proteinuria decreased by >50%; partial remission: proteinuria decreased by 20% to 50%; ineffective: proteinuria decreased by <20%. Upon 12-month follow-up, the total effective rates in the T II group and the valsartan group were 95.2% and 86.7% (P < .05), respectively. Twenty of 21 patients with proteinuria in the T II group were negative at 3-month follow-up with disappearance of edema. There were some adverse events that had greater incidence rates in the valsartan group compared with the T II group, such as hyperkalemia (26.7% vs 4.8%). We concluded that the application of T II markedly reduced proteinuria associated with SRL in renal transplant patients.

Peak effect in the critical current of type II superconductors with strong magnetic vortex pinning.

We perform 2D Langevin simulations studying the peak effect (PE) of the critical current taking into account the temperature dependence of the competing forces. We observe and report that the PE results from the competition of vortex-vortex interactions and vortex-pin interactions which have different temperature dependencies. The simulations reveal that the PE can take place only for certain pinning strengths, densities of pinning centers, and driving forces, which is in good agreement with experiments. No apparent vortex order-disorder transition is observed across the PE regime. In addition, the PE is a dynamical phenomenon, and thermal fluctuations can speed up the process for the formation of the PE.

A single-dose daclizumab induction protocol in renal allograft recipients: a Chinese single center experience.

This study prospectively compared immunoprophylaxis with a single dose of daclizumab versus no induction in kidney transplant recipients treated with a cyclosporine, mycophenolate mofetil, and prednisone-based immunosuppression regimen seeking to observe the impact of a single-dose regimen for prevention of acute rejection among Chinese renal allograft recipients. A total of 118 renal transplant recipients were randomized into a daclizumab induction therapy group (daclizumab group, n = 58) and a no induction group (control group, n = 60). The daclizumab group received a single-dose (1 mg/kg of ideal body weight by intravenous infusion) 2 hours before the operation. There was no induction therapy in the control group. There was no significant difference in the baseline parameters at randomization between the two groups. The mean time to the first episode of acute rejection was 41.2 +/- 3.2 days for the daclizumab group versus 11.2 +/- 4.6 days for the control group. The number of first biopsy-confirmed acute rejection episodes during the 6-months after transplantation was significantly different in the daclizumab (7,12.1%) versus the control group (14,23.3%; P < .001). At the end of 12 months, patient and graft survivals were 100% in the groups with or without daclizumab. We noted that the incidence of infection, including serious infection was similar, in the daclizumab group to that in the control group, 17.2% and 20.0%, respectively. This study showed that a single-dose of daclizumab effectively prevented acute rejection in Chinese renal allograft recipients.

Conversion from cyclosporine to tacrolimus for chronic allograft nephropathy.

We investigate the effect of conversion from a cyclosporine (CsA) based-regimen to a tacrolimus (FK506)-based regimen with respect to graft renal function induced by chronic allograft nephropathy (CAN). Thirty-one patients with a histological diagnosis of CAN were included after other causes of chronic graft dysfunction had been excluded. Conversion to FK506 was undertaken at an initial dose of 0.15 mg/kg/d, which was subsequently adjusted to maintain FK506 whole blood trough levels between 5 and 10 mug/L. The rate of decline of renal function before and after the FK506 conversion was represented by regression lines (slope) of the reciprocal of serum creatinine versus time. To evaluate the effect of conversion on allograft function, we gathered data on serum lipids, blood glucose, proteinuria, and hypertension. When postconversion slopes were compared to preconversion slopes for each patient, 20 patients (64.5%) showed positive regression lines and four patients (12.9%), less negative. Seven patients (22.6%) displayed an increased rate of decline in renal function with regression lines becoming more negative. FK506 was associated with a significant decrease in lipid levels, proteinuria, and hypertension. No patient returned to dialysis at the end of the 36-month follow-up. Conversion from a CsA-based regimen to a tacrolimus-based regimen was an effective alterative for salvage of patients with abnormal graft renal function induced by CAN.

Immunoregulation of thymosin alpha 1 treatment of cytomegalovirus infection accompanied with acute respiratory distress syndrome after renal transplantation.

We are the first to report the use of thymosin alpha1 to treat cytomegalovirus infection accompanied with acute respiratory distress syndrome after renal transplantation. The patients were divided into the thymosin alpha1 group (Zadaxin group, n = 32) and the control group (n = 14). All patients received the same rescue therapy protocol. Suitable antiviral (ganciclovir, 5 mg/kg every 12 hours, intravenously), antibacterial, or antifungal treatment was given if needed. In addition, patients in the Zadaxin group received thymosin alpha1, (1.6 mg) subcutaneously every other day or every day. The rescue success rate was significantly higher in the Zadaxin than in the control group (78.1% vs 50.0%) while the death rate was greatly reduced (21.9% vs 50%). In the Zadaxin group, the CD4(+) lymphocyte level was significantly increased on day 14; so was the ratio of CD4(+) and CD8(+) T-lymphocyte subsets. In the survival group, CD4(+) and CD8(+) lymphocyte cell counts were significantly increased on days 7, 14, and 21 compared with admission. This study suggested that thymosin alpha1 significantly promoted CD4(+) and CD8(+) lymphocytes, repairing cellular immunity and successfully reinforcing resistance to cytomegalovirus disease.

Rescue therapy by immunoadsorption in combination with tacrolimus and mycophenolate mofetil for C4d-positive acute humoral renal allograft rejection.

The aim of this study was to investigate the efficacy of immunoadsorption (IA) in combination with tacrolimus (TAC; 0.14 to 0.16 mg/kg/d) and mycophenolate mofetil (MMF; 1.5 to 2.0 g/d) rescue therapy for C4d-positive acute humoral rejection in nine cadaveric renal allograft recipients. Initial Panel reactive antibody (PRA-I and PRA-II levels were as high as 28.8% +/- 16.2% and 15.3% +/- 8.9%, IA therapy significantly decreased PRA-I and PRA-II levels to 5.9% +/- 2.9% and 2.2% +/- 0.6%, respectively. Total serum immunoglobulin levels were markedly decreased. Repeated allograft renal biopsy in nine patients revealed remission of acute humoral rejection (AHR), and the deposition of C4d disappeared and reduced. With a mean follow-up of 29.4 +/- 5.4 months, patient and allograft survivals were 100%, and renal function remained stable with a mean serum creatinine of 1.1 +/- 0.3 mg/dL. Our findings suggested that a therapeutic approach combining IA and TAC and MMF rescue improved the outcomes of AHR.

Clinical trial of Tripterygium Wilfordii Hook F. in human kidney transplantation in China.

OBJECTIVE: In this study, the effects of Triptergium Wilfordii Hook F.(T II) were assessed on human kidney allograft rejection and long-term survival. METHODS: This study compared treatment with T II(T II group, n=121) to that without T II(control group, n=102) among adult first cadaveric renal transplant recipients. The T II cohort of 121 recipients were divided into a regular dosage group (n=82) and a double dosage group (n=39). No antibody induction was administered to any patient. RESULTS: Biopsy-proven early acute allograft rejection occurred in 4.1% of patients in the T II group versus 24.5% of patients in the control group. No rejection or repeated rejections occurred in the double dosage group at 3 months after transplantation. Acute rejection episodes were milder in the T II than the control group. The incidence of CD25+ cells>10/ mm3 in the allografts at 3 months after transplantation was lower in the T II group than the control group, 15% and 50%, respectively. All patients tolerated T II well over the 5 years of this study. The 5-year graft survival censored for death with function was 96.7% in the T II group and 80.4% in the control group. CONCLUSION: T II was effective to prevent renal allograft rejection and increase long-term renal allograft survival among adult cadaveric renal transplant recipients.

C4d-positive acute humoral renal allograft rejection: rescue therapy by immunoadsorption in combination with tacrolimus and mycophenolate mofetil.

OBJECTIVE: We investigated the efficacy of immunoadsorption (IA) in combination with tacrolimus (FK506) and mycophenolate mofetil (MMF) rescue therapy for C4d-positive acute humoral rejection (AHR) of renal transplants. METHODS: Six of 185 cadaveric renal allograft recipients developed AHR at a mean of 4.8 +/- 0.8 days after the operation. C4d deposits were observed in peritubular capillaries (PTC) with accumulation of granulocytes. IA with staphylococcal protein A and FK506-MMF combination therapy were administered. RESULTS: After treatment with IA for 6.3 +/- 1.03 sessions combined with FK506 (0.14 to 0.16 mg.kg(-1).d(-1)) and MMF (1.5 g/d) therapy, renal function recovered in all the patients. The mean duration of treatment to a serum creatinine decrease was 14 +/- 2.9 days. The pre-IA panel reactive antibody reactivity (PRA) peaked at 50.2% +/- 6.1%, and was significantly reduced to 8.3% +/- 2.9% after IA. In four of six patients repeat allograft biopsy revealed a remission of AHR. With a mean follow-up of 18.8 +/- 5.46 months, patient and allograft survival are 100% and renal function remains stable with a mean serum creatinine of 1.2 +/- 0.22 mg/dL. CONCLUSION: The optimal treatment for alloantibody-mediated AHR remains uncertain. Our findings suggest that a therapeutic approach combining IA and FK506-MMF rescue improves the outcome of AHR.

[Effects of baoshen pill in treating chronic renal failure with long-term hemodialysis].

A clinical trial, to evaluate the effects of Baoshen Pill (Rheum palmatum extract, RPE) on hemodialytic patients was conducted. 42 cases with terminal stage of renal failure (Scr < 10 ml/min) on HD were divided at random into RPE treated group and control group. The results showed there were no statistically significant differences between two groups for Scr or BUN. Serum levels of TC, LDL-c, apo B and apo B/apo A1 dropped down and HDL-c, apo A1, albumin, pro-albumin and fibrinectin increased during the follow-up period (P < 0.05) in the treated patients. It is considered that the mechanisms of RPE in preventing chronic renal failure were not the action of whole body. Improving serum levels of albumin, lipoprotein, apolipoproteins might play important role in treatment.

[Clinical studies of recombinant human erythropoietin in patients on long-term dialysis].

Recombinant human erythropoietin (r-HuEPO) was administered in 68 dialyzed patients (32 on acetate hemodialysis, 24 bicarbonate hemodialysis and 12 on hemo-filtration). The mean initial Hb 52.7 +/- 8.0g/L, Ht 19.4 +/- 2.2%, serum ferritin > 100ng/L. Each patients received r-HuEPO intravenously, at the dose of 300U/Kg/w for 6.2 +/- 4.3 months. Target range: Hb 100-120g/L, Ht 30-35%. After r-HuEPO treatment, blood transfusion was not needed for any of the patients, anemia was ameliorated with increase of Hb and Ht levels. It was found that the minimum effective dose of the r-HrEPO was 150-300U/Kg/w. We conclude that r-HuEPO is effective as treatment for the anemia of dialyzed patients. However, hypertension, clotted dialyzers and dialysis access thromboses were been developed in some patients after correction of anemia. There is now a general consensus that these side effects may be minimized if r-HuEPO is initially given in small doses with increments to avoid a too rapid correction of the anemia.