Living donor liver transplant recipients achieve relatively higher immunosuppressant blood levels than cadaveric recipients

Two recent brief reports suggest that recipients of living donor liver transplants achieve higher levels of immunosuppressive agents than cadaveric (CAD) liver transplant recipients administered the same dose. These results could have important implications regarding the dosing of immunosuppressives in living donor liver transplant recipients. We report our findings relative to immunosuppressive doses and levels in a cohort of 46 living donor liver transplant recipients. Immunosuppressive blood levels and doses were recorded weeks 1, 2, 3, and 4 and months 2, 3, 4, 5, and 6 for 46 living donor liver transplant recipients and 66 matched CAD liver transplant recipients who underwent transplantation between August 1997 and May 2001. The ratio of level to dose also was recorded at each interval. The mean overall cyclosporine A dose was similar in living donor liver transplant recipients (323 mg/d) compared with CAD recipients (344 mg/d; P = not significant [NS]). The mean overall tacrolimus dose was 15% lower in patients who underwent living donor liver transplantation (LDLT; 5.7 mg/d) than CAD transplantation (6.7 mg/d), although statistical significance was not achieved (P = .08). The mean overall cyclosporine A level was 18% higher in those undergoing LDLT (275 ng/mL) than CAD transplantation (234 ng/mL; P = .015). The mean overall tacrolimus level was the same in living donor liver transplant recipients (10.8 ng/mL) and CAD recipients (10.2 ng/mL; P = NS). The overall cyclosporine A level-dose ratio was 26% higher for those undergoing LDLT (0.83) than CAD transplantation (0.66; P = .01). The overall tacrolimus level-dose ratio was 26% higher for those undergoing LDLT (1.82) than CAD transplantation (1.44; P = .01). In conclusion, (1) living donor liver transplant recipients achieve higher blood levels of tacrolimus and cyclosporine A for a given dose compared with CAD recipients, and (2) this difference is observed up to 6 months after transplantation, when hepatic regeneration is completed. (Liver Transpl 2002;8:212-218.)     

Prednisone metabolism in recipients of kidney or liver transplants and in lung recipients receiving ketoconazole

BACKGROUND: Actual prednisone exposure in low-dose prednisone regimens, in part determined by cytochrome P450 metabolism, has been shown to be important for allograft survival. METHODS: Prednisolone (the principal active metabolite of prednisone) metabolism was determined in eight nontransplant patients and in transplant recipients receiving oral prednisone maintenance therapy (20 kidney and 6 liver recipients receiving cyclosporine [CsA] and eight lung recipients receiving ketoconazole and CsA or tacrolimus [FK506]). RESULTS: Prednisolone area under the curve (AUC)-dose-normalized (PNAUCn) to 1 mg/kg was 8,288+/-1,513 ng.hr/mL in kidney recipients, versus 4,826+/-999 ng/mL per hr in healthy subjects (P<0.001); it was also increased in liver recipients versus healthy subjects (11,456+/-1,214 ng.hr/mL, P<0.001). Liver recipients also metabolized prednisolone more slowly than kidney recipients (P<0.001). PNAUCn in lung recipients was similar in kidney recipients despite the effect of ketoconazole to slow CsA metabolism. In kidney transplant recipients, the rate of CsA metabolism was correlated with the rate of prednisolone metabolism (r=0.54, P=.026). Basal cortisol levels in all transplant recipients were lower than in healthy subjects, suggesting more prednisolone exposure in transplant patients. CONCLUSIONS: Prednisolone metabolism is slower in solid-organ transplant recipients than in healthy subjects. The slower metabolism of prednisolone, particularly in liver recipients, may help explain the immunologic effectiveness of low-dose prednisone regimens in these patients.     

肝移植术后多重耐药菌感染危险因素的单中心临床研究

目的  分析肝移植术后发生多重耐药菌（MDRO）感染的危险因素。方法  回顾性分析77例肝移植受者的临床资料,根据是否发生MDRO感染分为非MDRO感染组（51例）及MDRO感染组（26例）。总结肝移植受者术后MDRO的感染率和菌株分布情况;分析肝移植受者术后发生MDRO感染的危险因素;比较两组受者的预后情况。结果  肝移植术后MDRO感染率为34%（26/77）,主要为耐碳青霉烯类MDRO感染,主要感染部位为肺部、腹腔和切口。单因素分析提示术后气管插管≥48 h、重症监护室（ICU）入住时间≥72 h、住院时间≥30 d、再次手术、持续性肾脏替代治疗（CRRT）和他克莫司（Tac）血药浓度≥15 ng/mL是肝移植术后发生MDRO感染的危险因素。Cox回归分析提示术后气管插管≥48 h、再次手术、CRRT和Tac血药浓度≥15 ng/mL是肝移植术后发生MDRO感染的独立危险因素。MDRO感染组病死率高于非MDRO感染组[31%（8/26）比10%（5/51）,P=0.01]。结论  术后气管插管≥48 h、再次手术、CRRT和Tac血药浓度≥15 ng/mL会增加肝移植术后MDRO感染的风险,影响受者的预后。     

稳定期肾移植受者将他克莫司普通剂型转换为缓释剂型对移植肾功能的影响

目的观察稳定期肾移植受者由普通剂型他克莫司(Tac)转换为缓释剂型Tac后对移植肾功能的影响。方法回顾性分析山西省第二人民医院2011年12月至2019年6月由普通剂型Tac转换为缓释剂型Tac的83例稳定期肾移植受者,随访12~36个月,同时匹配83例继续服用普通剂型Tac的稳定期肾移植受者作为对照组。观察稳定期肾移植受者由普通剂型Tac转换为缓释剂型Tac后肾功能、谷值浓度个体内变异度(IPV)及依从性的变化、排斥反应的发生率及移植肾和移植受者的存活率。结果普通剂型Tac转换为缓释剂型Tac时间为移植后(42.76±30.50)个月,转换后24个月血清肌酐(SCr)明显低于转换前(P=0.013),估算肾小球滤过率(eGFR)明显高于转换前(P=0.005)。试验组较对照组在转换后36个月SCr明显降低(P=0.017),eGFR明显增高(P=0.038)。试验组转换前免疫抑制剂治疗障碍量表(ITBS)得分为(20.23±2.89)分,转换后为(17.63±3.08)分(P=0.000);Tac每日剂量转换前是(2.09±0.84)mg,转换后为(2.10±0.83)mg;Tac谷值浓度转换前为(7.22±2.84)ng/mL,转换后显著降低,人/肾均健康存活。结论稳定期肾移植受者由普通剂型Tac转换为缓释剂型Tac肾功能保持稳定且较普通剂型Tac相对更好,依从性明显改善,谷值浓度个体内变异度明显降低,长期服用的临床疗效和安全性良好。     

High serum soluble CD30 does not predict acute rejection in liver transplant patients

Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.     

肾移植对慢性肾功能不全尿毒症期患者睾丸体积及生育力指数的影响

目的 探讨肾移植对男性慢性肾功能不全尿毒症期患者睾丸体积及生育力指数的影响.方法 解放军第117医院肾移植中心30例慢性肾功能不全尿毒症期患者于肾移植术前以及术后1个月、3个月和1年应用彩超进行睾丸体积监测,并与20名正常男性的睾丸体积比较.另检测40例尿毒症期和40例肾移植受者的精液,并根据公式[精子密度(×106/mL)×精子活动力×精子正常形态率]计算出生育力指数.结果 慢性肾功能不全尿毒症期患者的睾丸体积术前左侧为(6.82±1.49)mL, 右侧为(7.46±1.89)mL;肾移植术后1个月、3个月和1年左侧分别为(8.25±1.67)mL、(9.31±1.56) mL和(9.80±1.51)mL,右侧分别为(9.18±1.76) mL、(10.41±1.43) mL和(11.09±1.45)mL,肾移植受者术后1个月、3个月和1年的睾丸体积均大于尿毒症期患者,差异有显著性意义(均P<0.01).正常对照组生育力指数为13.03(14.26),肾移植受者的生育力指数为7.19(10.18), 而尿毒症期患者的生育力指数仅为0.23(0.76).尿毒症期患者的生育力指数比肾移植受者和正常对照组均小,差异有显著性意义(均P<0.01). 结论 慢性肾功能不全尿毒症期患者睾丸体积缩小,生育力指数下降, 而成功的肾移植可以明显改善尿毒症期患者的睾丸体积及生育力指数.     

Hepcidin, an acute-phase protein and a marker of inflammation in kidney transplant recipients with and without coronary artery disease

BACKGROUND: In kidney transplant recipients, endothelial dysfunction and atherosclerosis are almost universal, as are cardiovascular complications. Inflammatory markers have been shown to play a role in the pathogenesis and progression of atherosclerosis, regarded as a chronic inflammatory condition. Iron metabolism is disturbed in chronic inflammatory diseases such as atherosclerosis. Hepcidin, the liver-expressed antimicrobial peptide, LEAP-1, is an acute-phase reactant produced in the liver that displays intrinsic antimicrobial activity. Cross-sectional study was performed to assess possible relations between hepcidin and inflammatory markers in kidney transplant recipients with versus without coronary artery disease (CAD). METHODS: Iron status, complete blood count, creatinine, albumin, and lipids were estimated using standard laboratory methods. Glomerular filtration rate (GFR) was calculated using the MDRD formula. Hepcidin, high-sensitivity C-reactive protein (CRP), IL-6, TNFalpha, and soluble receptor of transferrin were measured using commercially available kits. RESULTS: Kidney transplant recipients with CAD were older, and showed higher hepcidin, hsCRP, IL-6, TNFalpha, sTFR, ferritin, and lower cholesterol levels than did patients without CAD. Univariate analysis of values in kidney transplant recipients showed hepcidin to correlate significantly with total protein, ferritin, time after transplantation, creatinine, eGFR (simplified MDRD), cholesterol, neutrophil count, hsCRP, and IL-6. There were tendencies to correlate with TNFalpha. Multiple regression analysis showed that hepcidin was independently related to GFR, cholesterol, and hsCRP. CONCLUSIONS: Elevated hepcidin values in kidney allograft recipients may be due not only to impaired renal function, but also to a low-grade inflammatory state, as reflected by hepcidin correlations with hsCRP, IL-6, and ferritin.     

Do pretransplant C-peptide levels influence outcomes in simultaneous kidney-pancreas transplantation?

OBJECTIVE: To analyze outcomes in simultaneous kidney-pancreas transplantation (SKPT) recipients who retain C-peptide production at the time of SKPT. METHODS: This retrospective analysis of SKPTs from January 2002 through January 2007 compared outcomes between patients with absent or low C-peptide levels (<2.0 ng/mL, group A) with those having levels > or =2.0 ng/mL (group B). RESULTS: Among 74 SKPTs, 67 were in group A and seven in group B (mean C-peptide level 5.7 ng/mL). During transplantation, group B subjects were older (mean age 51 vs 41 years, P = .006); showed a later age of onset of diabetes (median 35 vs 13 years, P = .0001); weighed more (median 77 vs 66 kg, P = .24); had a greater proportion of African-Americans (57% vs 13%, P = .004); and had a longer pretransplant duration of dialysis (median 40 vs 14 months, P = .14). With similar median follow-up of 40 months, death-censored kidney (95% group A vs 100% group B, P = NS) and pancreas (87% group A vs 100% group B, P = NS) graft survival rates were similar, but patient survival (94% group A vs 71% group B, P = .03) was greater in group A. At 1-year follow-up, there were no significant differences in rejection episodes, surgical complications, infections, readmissions, hemoglobin A1C or C-peptide levels, serum creatinine, or MDRD GFR levels. CONCLUSIONS: Diabetic patients with measurable C-peptide levels before transplant were older, overweight, more frequently African-American and had a later age of onset of diabetes, longer duration of pretransplant dialysis, and reduced patient survival compared to insulinopenic patients undergoing SKPT. The other outcomes were similar.     

男性肝移植受者血清性激素水平及性功能的研究

目的 探讨男性肝移植受者术后血清性激素恢复过程及性生活质量.方法 采集69例原发病为良性肝病的已婚男性肝脏移植受者移植前后1～6个月血清标本,采用放射免疫法分析测定血清睾酮、雌二醇,采用酶联免疫吸附法性激素结合球蛋白的浓度,选择同期本院健康已婚体检男性23例为健康对照组.随访研究组69例肝移植术后存活半年以上的24～45岁患者的性功能状态.结果 患者肝移植术前血清雌二醇和性激素结合球蛋白明显高于健康对照组(雌二醇:87.56±31.21 vs.26.00±9.12,u=9.30,P＜0.0001,性激素结合球蛋白:134.50±30.68 vs.51.04±12.05,u=12.69,P＜O.0001)；睾酮明显低于健康对照组(睾酮:2.02±1.28 vs.4.82±1.48,u=-8.73,P＜0.0001)；与患者术前终末期肝病模型评分(model for end-stage liver disease,MELD)相关(分别r =0.80,r=-0.77,r =0.72,均P＜0.0001),术后2周时血清雌二醇与健康对照组相比差异无统计学意义,术后1个月时血清睾酮和性激素结合球蛋白与健康对照组相比差异无统计学意义.结论 男性肝移植术后1个月内血清雌二醇、血清睾酮和性激素结合球蛋白水平恢复正常,术后半年时性功能得到明显改善.     

Function of the ovaries in female kidney transplant recipients

OBJECTIVES: One of the effects of an improved general health state after successful kidney transplantation in women of reproductive age is recurrence of regular menstrual function. MATERIALS AND METHODS: Sixty-three ovarian cycles in female kidney transplant recipient, aged from 18 to 44 years, at 1.5 to 15 years after transplantation, were compared with 50 cycles of healthy women. We monitored the menstrual cycle duration as well as follicle stimulation hormone (FSH), leutinizing hormone (LH), estradiol, progesterone, prolactin, creatinine, and testosterone serum concentrations as well as hematocrit and obtained sonographic observations of ovarian follicle growth and ovulation. RESULTS: Of the recipients, 68.1% had regular menstrual cycles. Ovulatory cycles were observed in 45% of patients. Estradiol concentration established in the first phase of the cycle was significantly higher among the transplanted group (mean value 226.86 +/- 97.45 pg/mL vs 140.00 +/- 61.00 in the controls). A significantly lower level of progesterone (15.05 +/- 17.34 ng/mL vs 30.79 +/- 18.48 ng/mL in the controls) and of testosterone were observed in kidney recipients. Other hormonal parameters did not differ significantly between the groups. CONCLUSIONS: Similar serum FSH, LH, and prolactin concentrations as well as increased levels of estrogens were observed in kidney transplant recipients compared with healthy nonrecipients. The rate of ovulatory cycles in regularly menstruated kidney graft recipients was similar to that of healthy women. Stabilization of graft function resulted in restoration of normal ovarian hormone metabolism and ovulatory cycles in female kidney transplanted recipients.     

Association Between Mannose-Binding Lectin Levels and Graft Survival in Kidney Transplantation

The mannose-binding lectin (MBL) pathway of complement is activated by pattern recognition. Genetic MBL variants are frequent and associated with low MBL serum levels. Higher MBL levels may be associated with more complement-mediated damage resulting in inferior graft survival. Pre-transplant serum samples from 266 consecutive deceased donor kidney transplant recipients were analyzed for MBL concentration by ELISA. Subsequently the cohort was analyzed for transplant-related outcome. There was no significant difference in incidence of delayed graft function in recipients with a low MBL level (< or =400 ng/mL) compared to those with a higher MBL level (>400 ng/mL) (37.1 vs. 34.9%). At 10 years, death-censored graft survival was 89.9% in patients with an MBL level below 400 ng/mL compared with 78.8% at a higher MBL level (p < 0.02). Multivariate analysis including traditional risk factors for graft loss showed an independent risk of 2.7 (95% CI 1.2-6.3) for death-censored graft loss if pre-transplant MBL levels were above 400 ng/mL. This difference was almost entirely explained by rejection-associated graft loss (2.4 vs. 12.4%, p < 0.01). Higher MBL levels seem to be associated with a more severe form of rejection leading to treatment failure and graft loss. If these data can be confirmed, pre-transplant MBL levels may provide additional information for risk stratification prior to kidney transplantation.     

Changes in serum LECT 2 levels during the early period of liver regeneration after adult living related donor liver transplantation

We investigated changes in serum leukocyte cell-derived chemotaxin2 (LECT2) levels between donors and recipients in the early period during liver regeneration following adult living related donor liver transplantation (LRDLT). Five recipients (three women, two men; 37.0 +/- 15.8 years old), all of whom had end-stage liver failure, underwent LRDLT from healthy five donors (two women, three men; 41.6 +/- 14.3 years old) between June 2000 and February 2001. FK506 and methylprednisolone were used as immunosuppressants for recipients. Serum LECT2 levels decreased immediately after both the hepatectomy in all donors and the implantation of liver graft in all recipients. Donors showed a nadir at 3 to 12 hours, increasing at 24 to 48 hours. The nadir in recipients occurred several hours after the donors. The serum LECT2 levels of donors were significantly higher than those of recipients on day 5 (9.5 +/- 5.9 ng/mL vs 3.1 +/- 2.2 ng/mL, P = .04) and on day 7 (9.3 +/- 3.8 ng/mL vs 3.5 +/- 1.1 ng/mL, P = .04). Serum GPT and GOT levels were inversely proportionate to the serum LECT2 levels. The present studies suggest that LECT2 participates in liver regeneration and injury following hepatectomy.     

Renal Allograft Survival in Transplant Recipients with Focal Segmental Glomerulosclerosis

Previous literature suggests that the recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is more common in recipients who have received an HLA-identical living-related (LRD) transplant. To address the question if FSGS patients can safely receive a 6-antigen match LRD kidney transplant, we analyzed death-censored renal allograft survival data of FSGS patients from the United States Renal Data System database (USRDS). Using the USRDS and the U.S. Scientific Renal Transplant Registry between the years 1988-97, we found 19259 adult primary renal transplant recipients, of which 2414 patients had FSGS as their primary diagnosis as compared to 16845 patients who had other types of glomerulonephritis (GN). A Cox proportional hazard model was used to estimate death-censored graft survival among FSGS patients with a zero mismatch LRD kidney transplant. The model included a triple interaction term comparing FSGS vs. GN vs. living donation (LD) vs. cadaveric donation (CAD) vs. zero mismatch (six antigen or HLA-identical) vs. mismatch. Annually adjusted death censored graft loss rates per 1000 patients (ADGL) were calculated. Focal segmental glomerulosclerosis patients receiving a zero mismatch LRD kidney transplant had the lowest ADGL rate, losing 10.5 grafts per 1000 patients per year. Not significantly different but higher (14.3) was the ADGL rate for LD, zero mismatch GN recipients. The ADGL rate was significantly higher in FSGS recipients who received a LD, mismatched transplant (36.5). Focal segmental glomerulosclerosis patients who received a CAD, zero mismatched graft (44.1), or CAD, mismatched graft (63.2), had significantly higher ADGL rates. Zero mismatch LRD kidney transplants are not a risk factor for graft loss in FSGS patients but are associated with significantly better death-censored graft survival as compared to CAD 6-antigen match or mismatched donations.     

Maturation of dose-corrected tacrolimus predose trough levels in pediatric kidney allograft recipients

BACKGROUND: In contrast to adult kidney recipients, in whom the long-term evolution and clinical determinants of tacrolimus pharmacokinetics are well studied, less is known about the long-term evolution of tacrolimus pharmacokinetics in pediatric kidney transplant recipients. METHODS: One-hundred and five pediatric recipients of a kidney allograft, all treated with a corticosteroid-free immunosuppressive protocol, were included. The evolution of tacrolimus doses and predose trough (C0) levels was recorded at 3, 6, 9, 12, 18, and 24 months after transplantation, as well as all C0 levels obtained in the first 2 years after transplantation. The evolution and clinical determinants of tacrolimus exposure parameters were analyzed. RESULTS: Dose-corrected tacrolimus C0 levels (C0/dose/kg) increased in the first 2 years after kidney transplantation in pediatric recipients (P=0.001). This decrease in dose requirement by time was only significant in children older than 5 years at the time of transplantation (P=0.38, 0.03, and 0.001 for age groups <5, 5-12, and >12 years, respectively). In addition, the younger patients had significantly higher dose requirements (dose/kg) compared with older recipients (P=0.0002). CONCLUSION: Pediatric kidney transplant recipients exhibit maturation of dose-corrected tacrolimus predose trough levels with time after transplantation. This cannot be explained by differences in corticosteroid use, because all patients were treated with a corticosteroid-free protocol. The higher dose requirements for younger recipients and the absence of tacrolimus maturation in the youngest recipients suggest that age-dependent changes in tacrolimus intestinal first-pass effect, metabolism, or distribution play a role. Whether age-specific tacrolimus dosing algorithms will improve outcome needs further study.     

Cholecalciferol supplements improve vitamin D deficiency in renal transplant recipients

Most renal transplant recipients display vitamin D deficiency or insufficiency. The KDIGO guidelines suggest that this deficit should be treated as in the general population. Since there are few studies about the effects of cholecalciferol in de novo renal transplant recipients, we sought to assess these effects in long-term kidney graft recipients. Among 37 renal transplant recipients (19 males, 18 females) at a mean of 105 ± 82 months posttransplantation, vitamin D insufficiency or deficiency was treated with cholecalciferol (400-800 IU/d) plus calcium supplements (600-1200 mg/d of elemental calcium). These subjects were compared with 37 untreated recipients for a period between 6 and 12 months. At baseline, there were no differences between the groups in age at transplantation, sex, length of follow-up after grafting, function measured by estimated glomerular filtration rate (44.4 ± 16.8 treated vs 42.0 ± 15.0 mL/min/1.73 m² untreated; P = .527); iPTH (157 ± 103 treated vs 176 ± 118 pg/mL untreated; P = .461); 25OHD (14.7 ± 4.7 treated vs 15.7 ± 9.7 ng/mL untreated; P = .584); or 1.25OHD (34.1 ± 26.0 treated vs 34.0 ± 13.0 pg/mL untreated; P = .950). When compared with baseline values, iPTH (157 ± 103 vs 144 ± 89 pg/mL; P = .11) and 1.25OHD levels at 6 months (34.1 ± 26.0 vs 35.9 ± 26.3 pg/mL; P = .282) showed no change but 25OHD levels (14.7 ± 4.7 vs 22.6 ± 7.4 ng/mL; P = .000) and phosphate tubular reabsorption (64% ± 17% baseline vs 69% ± 14% at 6 months; P = .030) were increased in the treated patients. There were no differences in the parameters studied in untreated patients. Among the 27 recipients followed at 12 months, iPTH was decreased compared with baseline values (157 ± 103 vs 124 ± 62 pg/mL; P = .024) and 25OHD remained stable with respect to the values at 6 months (21.1 ± 5.3 ng/mL). No adverse effects of cholecalciferol were observed such as those to increase urinary calcium excretion. Low doses of cholecalciferol improved vitamin D status and decreased iPTH levels at 12 months. Higher doses than those used in our study are needed to increase serum 25OHD concentrations above 30 ng/mL.     

C2 is an age-independent parameter for optimal cyclosporine exposure in long-term kidney transplant recipients

The argument for therapeutic drug monitoring (TDM) of cyclosporine (Cya) has been discussed for the last two decades. So far, a generalized consensus has been reached for TDM of Cya microemulsion in adult transplant recipients, being Cya blood levels obtained 2 hours after the administration (C2), the most reliable in reflecting the overall Cya exposure. However, clear guidelines are not available for the pediatric population because of the distinct metabolism of the drug in this patient population. Therefore, adult data do not necessarily apply to children. In this retrospective analysis, the authors sought to define a universal parameter for pharmacokinetic clinical monitoring of Cya in long-term kidney transplant recipients, regardless of their age. Lower C2 levels were observed in all patients, adult and pediatric, who eventually developed chronic allograft dysfunction (CRAD) compared with patients who maintained stable kidney function throughout the entire follow-up (pediatric CRAD, 933 +/- 455 ng/mL; vs Stable, 1236 +/- 347 ng/mL, P = .0001; and adult CRAD, 781 +/- 518 ng/mL; vs Stable, 1088 +/- 452 ng/mL, P = .009). On the other hand, the risk of Cya underexposure was not highlighted by trough level monitoring (C0) because all patients have been maintained steadily on therapeutical C0 levels for the entire follow-up. In conclusion, for Cya maintenance therapy, C2 appears to be a superior strategy to C0 monitoring in both adult and pediatric kidney transplant recipients.     

他克莫司与肾移植术后糖尿病相关性的单中心研究

目的  探讨移植后糖尿病（PTDM）的主要危险因素,分析他克莫司与肾移植PTDM发生的相关性。方法  收集123例肾移植受者的临床资料,分为PTDM组（19例）和非PTDM组（104例）。分析两组受者的临床资料,采用二元logistic回归分析PTDM的危险因素。将24只小鼠分为对照组（生理盐水）,他克莫司低剂量组（0.1 mg/kg）、中剂量组（0.75 mg/kg）和高剂量组（1.5 mg/kg）,每组各6只,分别每日注射2次。分析他克莫司对小鼠血糖代谢的影响。结果  肾移植术后1年内PTDM发生率为15.4%（19/123）。受者年龄≥48岁、移植术后3个月他克莫司谷浓度≥9 ng/mL是肾移植术后发生PTDM的危险因素（均为P < 0.05）。低剂量组、中剂量组和高剂量组小鼠给药后的空腹血糖水平低于给药前（均为P < 0.05）,但不具有剂量依赖性（P=0.750）。低剂量组、中剂量组和高剂量组小鼠给药后餐后血糖水平高于给药前（均为P < 0.05）,且呈现他克莫司剂量依赖性（P=0.012）。结论  他克莫司与肾移植术后PTDM发生密切相关,受者年龄≥48岁、移植术后3个月他克莫司谷浓度≥9 ng/mL是PTDM发生的独立危险因素。他克莫司以剂量依赖性的方式影响小鼠餐后血糖水平。     

Cholesterol absorption and synthesis in pediatric kidney, liver, and heart transplant recipients

BACKGROUND: Hypercholesterolemia after organ transplantation is common. Previously, we observed higher serum total cholesterol (TC) concentrations in our pediatric kidney than liver or heart transplant recipients. To find an explanation to the observed difference, our kidney recipients' cholesterol synthesis and absorption efficiency was compared to those of liver and heart recipients. METHODS: Serum noncholesterol sterol ratios (10 x mmol to the mol of TC, surrogate estimates of hepatic cholesterol synthesis and intestinal absorption) were studied in 50 pediatric kidney, 25 liver and 12 heart transplant recipients without diabetes or cholestasis, and in 29 controls. RESULTS: The kidney recipients had lower Delta-cholesterol (P=0.031), similar lathosterol and higher desmosterol ratios (markers of cholesterol synthesis) (P=0.020), and similar campesterol and sitosterol ratios (markers of cholesterol absorption) when compared to the controls. The liver recipients had lower campesterol ratios than the kidney recipients and controls (P=0.002). Glomerular filtration rates were not associated with the ratios of noncholesterol sterols. Multivariate analysis showed markers of cholesterol synthesis to be lower and absorption to be higher in the kidney than the liver or the heart transplant recipients. Weight-adjusted dosages of immunosuppressive agents were associated with some ratios of noncholesterol sterols and cholestanol though these varied between the transplant recipient groups. CONCLUSIONS: Serum TC concentration in kidney recipients was not significantly associated with absorption efficiency or synthesis of cholesterol, though kidney transplantation was associated with low synthesis and high absorption efficiency of cholesterol. Immunosuppressive therapy with cyclosporine and methylprednisolone may modulate absorption efficiency and synthesis of cholesterol.     

肝癌肝移植术后应用亚砷酸化疗的临床效果观察

目的 探讨超出米兰标准的肝癌病人肝移植术后应用亚砷酸全身化疗对肿瘤复发的意义.方法 对23例超出米兰标准的肝癌病人肝移植术后采用亚砷酸化疗:静脉滴注10 mg/d,连续使用7 d后间隔7 d,重复4次为1疗程.以上病人接受1～4个疗程治疗.观察化疗病人的生存情况、肿瘤复发情况以及化疗副作用,并与同期16例未使用化疗的肝癌肝移植病人相比较.结果 经过3～32个月随访,共有30例病人出现肝癌复发,化疗组16例,非化疗组14例,复发部位最常见于肺部、移植肝及骨骼.化疗组与非化疗组肿瘤复发率无明显差异,出现肝癌复发的时间分别为移植术后(14.5±7.5)个月和(10.2±4.6)个月,化疗组复发时间明显延迟(P=0.026);6个月、1年生存率分别为91.3%、87.0%和93.7%、87.5%,两组间无明显差异,化疗组2年生存率明显高于非化疗组(73.9% vs 50.0%,P=0.037);6个月无瘤生存率无明显差别(87.0% vs 81.2%)、1、2年无瘤生存率化疗组明显高于非化疗组(82.6% vs 50.0%,P=0.030;65.2% vs 43.7%,P=0.023).亚砷酸使用过程中未发现严重副作用.结论 静脉使用亚砷酸化疗在超出米兰标准的肝癌肝移植病人中可以延迟肿瘤复发,改善病人长期存活情况.     

Intraoperative blood flow measurements in organ allografts can predict postoperative function

A reliable method to recognize the extent of ischemia/reperfusion injury in transplantation is needed in order to tailor the immunosuppressive scheme to the needs of a damaged organ. This study sought to assess the correlation between the total and the parenchymal blood flow into a transplanted kidney (n = 71) or liver (n = 15) shortly after revascularization with the early function of the organ after transplantation. The total blood flow in the renal artery in kidney recipients or in the hepatic artery and portal vein in liver recipients was measured by an electromagnetic flowmeter. The parenchymal blood flow (in several parts of the transplanted organ) was assessed using a laser-Doppler flowmeter. Two measurements were always taken after revascularization (5 to 60 minutes apart). Vascular resistance (VR) as calculated by the difference between the mean arterial pressure (MAP) and the central venous pressure (CVP) was correlated with immediate kidney or liver function parameters. Neither total renal blood flow (RBF) nor VR was different between the immediate function (IF) and delayed graft function (DGF) groups of kidney transplant patients. However, the cortical (parenchymal) blood flow was significantly greater in the IF than the DGF group at 5 minutes: 29.98 +/- 6.13 mL/min/100 g vs 23.56 +/- 6.46 mL/min/100 g (P < .001). The difference was even more significant at 35 minutes: 33.94 +/- 7.47 mL/min/100 g vs 15.47 +/- 3.34 mL/min/100 g (P < .0001). Among liver transplant patients, the results suggested a correlation between hepatic arterial blood flow and early graft viability and function. The most reliable predictor of early graft function was the portal blood flow, which correlated with the volume of secreted bile as well as the bilirubin, and transaminase levels and coagulation profile. Further studies must confirm the value of measurements of total and parenchymal blood flow in organ transplant recipients.