[Therapeutic effect of tonsillectomy on IgA nephropathy after kidney transplantation].

Objective: To observe the clinical effect of tonsillectomy on IgA nephropathy (IgAN) after renal transplantation. Methods: From March 2011 to July 2018, 201 kidney transplantation recipients who were diagnosed of IgAN by transplant renal biopsy in the Department of Organ Transplantation of the First Affiliated Hospital of Sun Yat-sen University were retrospectively reviewed, of which 18 patients underwent tonsillectomy after renal biopsy. The clinical data of the 18 patients were collected, patient and kidney survival time and function of the transplanted kidney were analyzed. Results: Of the 18 recipients, 13 were male and 5 were female, with an average age of (36.0±10.9) years. All 18 patients survived during follow-up. Two patients returned to dialysis treatment 10 months and 14 months after tonsillectomy, respectively. The creatinine was 94 (78, 133) µmol/L, 95 (74, 139) µmol/L, 106 (87, 158) µmol/L and 95(81, 147) µmol/L before tonsillectomy, 3 months, 1 year and 2 years after tonsillectomy, respectively (P=0.206). Urinary protein quantification was 0.31 (0.16, 1.38) g/24 h, 0.34 (0.10, 1.42) g/24 h, 0.33 (0.11, 0.56) g/24 h and 0.25 (0.10, 0.50) g/24 h at the same time points, respectively (P=0.104). The two patients who returned to dialysis were diagnosed of IgAN by transplant renal biopsy because of elevated creatinine, proteinuria and hematuria, 9 years and 4 years after kidney transplant respectively. Renal biopsy suggested that glomerular and segmental sclerosis were 7/24, 5/24 and 1/6, 2/6, respectively. Additionally, interstitial fibrosis and tubular atrophy (IF/TA) were both occupied 30% in the biopsies, and tonsillectomy was performed 461 days and 1 077 days after diagnosis of IgAN, respectively. Conclusions: Tonsillectomy can maintain the stability of renal function and prevent the aggravation of proteinuria in IgAN patients after renal transplantation. However, if pathology suggests obvious glomerulosclerosis or IF/TA, tonsillectomy may not be effective.

Calcineurin inhibitor conversion to rapamycin can improve graft function in living donor kidney transplantation with older donors.

BACKGROUND: Recipients of living donor kidney transplantations from older donors often experience a lower glomerular filtration rate (GFR) than those from young donors. Calcineurin inhibitors (CNI) may cause nephrotoxicity, especially in recipients of older donor organs. The aim of this study was to investigate whether CNI withdrawal and conversion to rapamycin improved graft function among transplantation recipients of living donor kidneys from older donors. METHODS: We collected 83 living donor kidney transplantations using donors aged >50 years from January 2004 to December 2009, including 25 who underwent conversion to rapamycin at the end of 3 months, while 58 cases were maintained on CNI. Baseline characteristics, complications, and graft functions were compared between the groups. RESULTS: Donor age, recipient age, body weight, human leukocyte antigen mismatch, delayed graft function, acute rejection rate, serum creatinine, and estimated GFR were comparable between the 2 groups at the end of 3 months. The 1-year serum creatinine were 111.8 ± 25.5 µmol/L in CNI withdrawal versus 132.5 ± 35.9 µmol/L in the CNI-maintained group (P = .013) with 1-year estimated GFR of 86.9 ± 8.2 mL/min versus 77.4 ± 7.2 mL/min and 3-year estimated GFR of 76.1 ± 7.8 mL/min versus 67.0 ± 6.4 mL/min, respectively (both P < .001). The rates of acute rejection were 24% versus 22.4%, and chronic rejection, 4.0% versus 10.3% respectively (P > .05). One CNI withdrawal patient (4.0%) lost the graft function while 4 (6.9%) did so in the CNI-maintained group (P > .05). Logistic multivariate regression showed that maintained CNI usage, acute rejection episodes, and female donors to male recipients were independent risk factors for abnormal 1-year serum creatinine levels (P < .05). CONCLUSION: CNI withdrawal with conversion to rapamycin improved graft function in living donor kidney transplantations from older donors.

Population pharmacokinetics of mycophenolic acid in senile Chinese kidney transplant recipients.

To explore the pharmacokinetic characteristics of mycophenolic acid (MPA) among elderly Chinese kidney transplant recipients, we enrolled 24 patients over 60 years old (65.6 +/- 3.6) as the (Gs) group and 24 patients of 39.6 +/- 14.3 years old as a control group (Ga). Venous blood samples were taken at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours after the morning dose of mycophenolate mofetil at 10 to 12 weeks posttransplant. Plasma MPA concentrations were measured by a validated high-performance liquid chromatography method. Within 6-month posttransplant follow-up, there had not been an acute rejection episode when five elderly and one other adult experienced severe adverse events (SAEs), such as pneumonia and leukocytopenia. MPA area under the curve (AUC) in Gs was significantly lower than that among Ga (P < .05), while there was no significant difference in predose, peak concentrations, or peak times (P > .05). The concentration-time curve of Gs showed a bipeak pattern in five patients (20.8%) during the early stage (2 to 4 hours postdose). AUC in the subgroup of Gs with SAEs (n = 5) was significantly higher than that of elderly subjects without SAEs (n = 19) (P = .042). When Gs were subdivided at a cutting AUC point of 25 mug/mL, the SAE incidence was significantly higher in the subgroup with a higher AUC than than those with the lower AUC (P = .047). Through multiple stepwise regression, we obtained a minimal model to estimate MPA AUC of elderly recipients: AUC = 3.0410 + 9.8588 x C(0) + 0.5963 x C(0.5) + 2.5612 x C(3) (R(2) = .893).

Characteristics of neoplasm occurrence and the therapeutic effect of sirolimus in South Chinese kidney transplant recipients.

Kidney transplantation (KTx) recipients are at a higher risk of oncogenesis when compared to the general population. Sirolimus (SRL), a potent immunosuppressant, has shown promising antineoplastic effects in vitro and in vivo. This study retrospectively analyzed the neoplasm occurrence and the efficiency of SRL on unresectable malignancies in South Chinese KTx recipients. Thirty-three (1.64%) of 2017 patients who received KTx from January 1984 to December 2004 developed neoplasms at 4 to 117 months posttransplant, mostly in digestive organs (33.3%), the hematologic system (15.2%), or the skin (12.1%). The most common type was liver cancer (24.2%), followed by skin cancer, lymphoma, and thyroid cancer (9.1%). The median survival times were 41.5 and 6.0 months for those who did (n = 10) receive radical surgery or did not (n = 23), respectively. The 20-month survival rates were 70.0% versus 13.0% (P < .01). For unresectable patients, the median survival time of those treated with SRL (n = 8) was 14.5 months compared to 3.0 months for those who did not (n = 15). The survival rates at 12(th) and 20(th) months were 75.0% and 37.5% in the SRL group and 6.7% and 0% in the non-SRL group (P < .05). In conclusion, when compared with Western studies, a lower incidence and unique location pattern (liver cancer-dominant) are characteristics of de novo posttransplant neoplasms in South Chinese KTx recipients. Early diagnosis and feasible radical surgery are favorable for prognosis, and SRL is a treatment of choice for KTx recipients with neoplasms.

Clinical pharmacokinetics of tacrolimus after the first oral administration in combination with mycophenolate mofetil and prednisone in Chinese renal transplant recipients.

INTRODUCTION: Data on tacrolimus pharmacokinetics in combination with mycophenolate mofetil and prednisone are scarce in Chinese renal transplantation recipients. The purpose of this study was to detect interpatient pharmacokinetic variability of tacrolimus and to assess the predictability of individual tacrolimus concentrations at various times for the area under the curve (AUC) seeking to find the best sampling time for an abbreviated AUC to predict the total body exposure of tacrolimus after the first oral dose in Chinese renal transplantation recipients. METHODS: Sixteen primary kidney transplant recipients were treated with methylprednisolone and antilymphocyte globulin for 3 days. The first tacrolimus oral dose (0.075 mg/kg) was given at day 3 posttransplant. Mycophenolate mofetil and prednisone were administered orally posttransplant. Blood samples were obtained at 0.5, 1.0, 1.5, 2.0, 3.0, 5.0, 8.0, and 12.0 hours after taking the first oral dose. Tacrolimus blood concentrations were measured by ELISA. Twelve-hour AUC (AUC12) for each patient was calculated using the linear trapezoid rule. Associations between the blood concentration at each sampling time point and the AUC12 were evaluated by Pearson correlation coefficients. Abbreviated sampling equations were derived by multiple, stepwise regression analyses performed using AUC12 as the dependent variables. The variance in the strength of association between predicted AUC (AUC(P)) and AUC12 was reflected by linear regression coefficients of multiple determinations. RESULTS: In 16 patients, AUC12 values were within the range of 44.40 ng x h/mL to 158.01 ng x h/mL (mean = 92.23 +/- 34.97 ng x h/mL). The area of the maximum AUC12 was almost fourfold higher than that of the minimum AUC12. C12 significantly correlated with AUC(12) after the first tarcrolimus oral dose (r = .846, P < .001). C5, C8, and C3 showed better correlations: r = .924, .924, and .911, respectively. From stepwise multiple regression, C5 seemed to be the best predictor of total body exposure to tacrolimus (r = .92, r2 = .85). Alternatively, the concentrations at 5 and 1.5 hours or 5, 1.5, and 3 hours as an abbreviated AUC were as good as a full pharmacokinetic study (r = .97, r2 = .94, and r = .99, r2 = .99, respectively). CONCLUSIONS: Tacrolimus AUC12 show remarkable interindividual variations after the first oral dose in combination with mycophenolate mofetil and prednisone in Chinese renal transplant recipients. Although C12 is a good predictor of efficacy, C5 might be the best predictor of the first AUC12. A two-point sampling method using C5 and C1.5 or three-point sampling method using C5, C1.5, and C3 might be the best abbreviated AUC for a cost-effective tacrolimus monitoring strategy.