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1.
We sought to compare the treatment modalities of alendronate, alfacalcidol, and alendronate combined with alfacalcidol in renal transplant recipients with low bone mineral density. Sixty-four kidney graft recipients (22 women, 42 men) were recruited to this study. Of these 64 patients, 9 served as the control group with T scores more than -1. The remaining 55 patients randomly assigned to treatment had T scores less than -1 and were assigned to 3 groups: group 1 received alfacalcidol (0.5 microg/d); group 2, alendronate (10 mg/d); and group 3, alendronate (10 mg/d) + alfacalcidol (0.5 microg/d per os). Twenty-five patients were allocated to alfacalcidol, 13 patients to alendronate, and 17 patients to alendronate + alfacalcidol treatment. Bone mineral densities of the lumbar spine and femoral neck were measured before and 12 months after treatment. The groups were compared for risk factors of osteoporosis, biochemistry, and bone mineral density. Kruskal-Wallis, one-way ANOVA, and Student t tests were used. With the alendronate + alfacalcidol group, bone mineral density at the lumbar spine significantly increased by 7.9% (P = .006) with a significant improvement in T score (P = .003). Bone mineral density at the femoral neck significantly increased by 8% in the alendronate + alfacalcidol group (P = .01) with a significant improvement in T score (P = .02). The use of a combination of alendronate and alfacalcidol seemed to be safe and more effective than the separate use of the 2 agents to improve bone mass in renal transplant recipients.  相似文献   

2.
Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 +/- 0.08 and 6.1 +/- 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.  相似文献   

3.
BACKGROUND: Most hypertensive renal transplant recipients require two or more antihypertensive medications to achieve blood pressure control. However, which medications must be combined is still a matter of debate. METHODS: A prospective randomized open-label blinded evaluation trial comparing the six-month effects of the amlodipine-enalapril combination (n = 32) vs. enalapril alone (n = 33) and vs. amlodipine alone (n = 34) on arterial pressure, renal function, albuminuria and tolerability. RESULTS: At six months, diastolic arterial pressure was more adequately controlled (i.e., <90 mmHg) in the combination group than in the amlodipine and enalapril groups (100% vs. 82.4% and 84.8%, respectively, p = 0.038). The same trend was observed for systolic arterial pressure (65.6% vs. 58.8% and 51.5%, NS). The six-month change in albuminuria was similar in the combination group and in the enalapril group (-64.7% vs. -59.5%); however, patients in the combination group exhibited a greater reduction in albuminuria than in the amlodipine group (-64.7% vs. -29.0%, p = 0.002). As compared with baseline values, serum creatinine and potassium remained unchanged in the combination group, whereas they increased by 9 +/- 12 micromol/L (p = 0.01) and by 0.2 +/- 0.4 mmol/L (p < 0.01), respectively, in the enalapril group. The cyclosporine trough levels remained unchanged in the combination group, but increased in the amlodipine group. CONCLUSION: Angiotensin-converting enzyme inhibitor (ACEI)-calcium-channel blocker (CCB) combination controls arterial pressure more adequately than ACEI alone or CCB alone, reduces albuminuria and may prevent the ACEI-induced initial rise in serum creatinine.  相似文献   

4.
Horse antihuman thymocyte globulin (HAHTG) combined with prednisone and azathioprine (lmuran) was used as immunosuppressive therapy in a randomized controlled sutdy in 50 renal allograft recipients. Side effects of HAHTG administration given intravenously were mostly mild. In the treated group, four patients out of 26 died of infectious complications, whereas in the control group, three patients out of 24 died of infectious complications (chi2 = .01,P greater than .05). The graft survival at 18 months was ten of 24 in the control group and ten of 26 in the treated group (chi2 = 1.26, P greater than .05). Cumulative graft survival was 58.3% in the control group and 38.1% in the treated group at 18 months. However, if we consider the people who died with a functioning graft not as graft failure but as if they left the study, then the cumulative graft survival is 64.5% in the control group and 65.9% in the treated group. Thus, the mortality from infective causes and graft survival were not significantly different between the two groups. Hence, we draw the conclusion that use of HAHTG did not exert a beneficial effect on the ultimate outcome.  相似文献   

5.
BACKGROUND: Delayed graft function (DGF) is frequently observed in recipients of cadaveric renal transplants. Previous retrospective or nonrandomized studies have suggested that intraoperative administration of polyclonal antithymocyte preparations may reduce the incidence of DGF, possibly by decreasing ischemia-reperfusion injury. METHODS: We performed a prospective randomized study of Thymoglobulin induction therapy in adult cadaveric renal transplant recipients. Between January 2001 and January 2002, 58 adult cadaveric renal transplant recipients were randomized to receive intraoperative or postoperative Thymoglobulin induction therapy. Three to six doses of Thymoglobulin (1 mg/kg/dose) were administered during the first week posttransplant. Baseline immunosuppression consisted of tacrolimus (54 of 58) or cyclosporine A (4 of 58), steroids, and mycophenolate mofetil. DGF was defined by the requirement for hemodialysis within the first week posttransplant. RESULTS: There were no significant differences between the two groups in recipient demographics, donor age, cold ischemia time, or total number of doses of Thymoglobulin administered. Intraoperative Thymoglobulin administration was associated with significantly less DGF and a lower mean serum creatinine on postoperative days 10 and 14 (P<0.05). Posttransplant length of stay was also significantly shorter for the intraoperative Thymoglobulin patient group. The acute rejection rate was also lower in the intraoperative treatment group but this did not achieve statistical significance. There was no difference in the incidence of cytomegalovirus disease between the two groups. CONCLUSIONS: The results of this study indicate that intraoperative Thymoglobulin administration, in adult cadaveric renal transplant recipients, is associated with a significant decrease in DGF, better early allograft function in the first month posttransplant, and a decreased posttransplant hospital length of stay.  相似文献   

6.
This pilot trial was designed to assess the safety and efficacy of SRL in liver transplant recipients with renal dysfunction. Forty patients with renal dysfunction (24-hr CrCl 40-80 mL/min) were randomized to be withdrawn from the calcineurin inhibitor (CNI) and receive sirolimus (SRL) or to continue CNI (control arm). Improvement in 24-hour CrCl was seen in the SRL arm at 3 months (75 mL/min SRL vs. 56 mL/min control, P=0.012), whereas at 12 months there was a trend toward improvement in the SRL arm (72 mL/min SRL vs. 58 mL/min control, P=0.09). Two patients, one in each arm, developed steroid-sensitive rejection. Side effects of SRL were limited and included hyperlipidemia requiring treatment (15%), pruritis (5%), and mouth sores (25%). In this trial, SRL-based immunosuppression was a safe alternative to CNI. Although early improvements were observed, withdrawing CNI and replacing it with SRL did not result in a statistically significant improvement in renal function at 12 months of follow-up.  相似文献   

7.
BACKGROUND: To date, the clinical trials of tacrolimus (TAC) versus cyclosporine modified (CsA), have not defined which agent is more cost-effective for immunosuppression in renal transplant recipients especially in a quadruple immunosuppressive regimen. METHODS: The objective of this randomized, prospective study was to compare the clinical and economic outcomes of TAC versus CsA, in a regimen that consisted of Thymoglobulin induction, an antimetabolite, and prednisone. Between December 2000 and October 2002, 200 patients were enrolled and randomized in a 2:1 fashion (TAC n=134, CsA n=66). RESULTS: At 1 year, acute rejection (4% TAC vs. 6% CsA), patient survival (TAC 99% vs. CsA 100%), and graft survival (95% TAC versus 100% CsA, P=0.059) were similar. Serum creatinine levels were lower in the TAC group compared with the CsA group (1.3+/-0.3 vs. 1.6+/-0.7 mg/dL, P=0.03). The incidence of CMV infection was similar between the groups and two patients, both in the TAC arm, developed malignancy. Anti-hypertensive requirement (32% TAC vs. 32% CsA) and the incidence of posttransplant diabetes mellitus (4% TAC vs. 2% CsA) were similar. Pretransplant, fewer TAC patients received dyslipidemia treatment (40% TAC vs. 67% CsA, P=0.0005), while more CsA patients were able to discontinue these medications posttransplant (absolute change 25% TAC vs. 47% CsA). Total 12-month medication costs were similar (17,723 +/- 11,647 dollars TAC vs. 16,515 +/- 10,189 dollars CsA). CONCLUSIONS: When combined with Thymoglobulin induction, an antimetabolite, and corticosteroids, TAC and CsA are comparable in safety, efficacy, and cost in renal transplantation.  相似文献   

8.

Introduction

Renal transplant recipients (RTRs) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy, hypophosphatemia, and immunosuppression. This process occurs more frequently in the first year after renal transplantation (RTX), resulting in eventual bone loss and fractures. The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX.

Patients and Methods

We prospectively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16 ± 11.73 years, mean body mass index of 23.6 ± 3.73, and mean dialysis duration of 25.73 ± 17.67 months. We matched them based on age and sex: the alendronate-treated group received vitamin D (Vit D) during the study plus 30 mg alendronate weekly from 1 month after RTX. The control group only received Vit D. We measured serum calcium, phosphate, alkaline phosphatase, blood urea, creatinine, and intact parathyroid hormone (iPTH) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine, femur, and radius pretransplant baseline versus 3 and 6 months after RTX.

Results

At 6 month after RTX, the lumbar BMD in the alendronate group increased significantly from 0.819 ± 0.11 to 0.863 ± 0.14 (P < .01), while it decreased in the control group from 0.897 ± 0.17 to 0.817 ± 0.16 (P < .001). There was also a significant increase in radius BMD (P < .001) and a nonsignificant increase in femoral BMD in the alendronate versus a significant decrease of femoral and radius BMD (P < .001) in the control group at 6 months. Upon multivariate analysis, there was a significant correlation between alendronate and spine BMD (r = .45, P < .001) but no linear regression between age, sex, BMI, dialysis duration of or iPTH with femoral, spine, or radius BMD changes at month 6.

Conclusion

Low-dose alendronate was significantly useful to mitigate fast bone loss and increase BMD immediately after RTX.  相似文献   

9.
The ideal immunosuppressive treatment for African-American kidney transplant recipients has not been established. We performed a long-term prospective randomized trial comparing the results of tacrolimus (TAC) and cyclosporine (CSA) in the African-American population. Thirty-five African-American primary cadaveric renal transplant (CRT) recipients were enrolled in the study. Group I (n = 14) received TAC and group II (n = 21) received CSA; mean follow up was 78 months. We found no difference in patient/graft survival rates between the groups. Twelve patients in the CSA group were converted to TAC, mostly because of hypercholesterolemia or as a rescue for an acute rejection episode. Significant lower creatinine and cholesterol levels were seen at 1 year post-transplant, but this difference lost significance at 3 and 5 years, possibly because of conversion of most patients from CSA to TAC. In conclusion, African-American recipients of primary CRTs can achieve excellent long-term results with TAC-based immunosuppression.  相似文献   

10.
BACKGROUND: Between September 20, 1995 and September 20, 1997, 208 adult patients undergoing renal transplantation were randomized to receive tacrolimus/prednisone (n=106) or tacrolimus/prednisone/mycophenolate mofetil (n=102), with the goal of reducing the incidence of rejection. METHODS: The mean recipient age was 50.7+/-13.7 years. Sixty-three (30.3%) patients were 60 years of age or older at the time of transplantation. The mean donor age was 34.5+/-21.7 years. The mean cold ischemia time was 30.5+/-9.2 hr. The mean follow-up is 15+/-7 months. RESULTS: The overall 1-year actuarial patient survival was 94%; the overall 1-year actuarial graft survival was 87%. When the patient and graft survival data were stratified to recipients under the age of 60 who did not have delayed graft function, the overall 1-year actuarial patient survival was 97%, and the corresponding 1-year actuarial graft survival was 93%. There were no differences between the two groups. The overall incidence of rejection was 36%; in the double-therapy group, it was 44%, whereas in the triple therapy group, it was 27% (P=0.014). The mean serum creatinine was 1.6+/-0.8 mg/dl. A total of 36% of the successfully transplanted patients were taken off prednisone; 32% of the patients were taken off antihypertensive medications. The incidence of delayed graft function was 21%, the incidence of cytomegalovirus was 12.5%, and the initial and final incidences of posttransplant insulin-dependent diabetes mellitus were 7.0% and 2.9%; again, there was no difference between the two groups. CONCLUSIONS: This trial suggests that the combination of tacrolimus, steroids, and mycophenolate mofetil is associated with excellent patient and graft survival and a lower incidence of rejection than the combination of tacrolimus and steroids.  相似文献   

11.

Background

Avascular osteonecrosis (AVN) is a complication of renal transplantation. In this study, we present 12 cases of AVN associated with renal transplantation.

Methods

Renal transplant recipients (RTRs) with AVN (group I [GI]) were evaluated by using magnetic resonance imaging and blood urea nitrogen, creatinine, glucose, calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone, and urine analysis. We evaluated bone mineral density (BMD) of the femoral neck and lumbar vertebrae. All patients were treated with steroids, cyclosporine, or tacrolimus plus mycophenolate mofetil. Twenty-six RTRs (GII) without AVN were randomly selected as control subjects.

Results

The mean ages of GI and GII, were 33.81 ± 6.72 and 34.00 ± 7.65 years respectively (P > .05). The mean interval between transplantation and development of AVN was 12.08 ± 6.48 months. Although levels of blood urea nitrogen, creatinine, calcium, magnesium, and parathyroidhormone, as well as glucocorticoid doses in the first 12 months were similar in GI and GII, there were significant differences in serum alkaline phosphatase, hemoglobin levels, and white blood cell count between GI and GII (P < .05 for each). BMD T score <−1.5 was observed in 8/9 GI and 15/26 patients in GII. All of the patients with AVN except 1, were followed with conservative measures including calcium, magnesium, and vitamin D replacement therapies, bisphosphonate, and reduced or ceased glucocorticoid treatment. Although T scores of the femoral head were similar in GI and GII, the lumbar vertebral T score was significantly lower in GI than in GII (P < .052).

Conclusion

AVN developed within the first year after transplantation. Decreased lumbar vertebral BMD, which can be an indicator of glucocorticoid effect, accompanied AVN in nearly all patients. Despite the absence of renal dysfunction, increased bone destruction, anemia, and leucocytosis were coincidental or accompanying findings in our patients with AVN.  相似文献   

12.
13.
BACKGROUND: JC virus (JCV) viruria is more common than BK virus (BKV) viruria in healthy individuals but in kidney transplants (KT), polyomavirus nephropathy (PVAN) is primarily caused by BKV. Few cases of PVAN have been attributed to JCV. Systematic studies on JCV replication in KT are lacking. METHODS: Out of a cohort of KT patients screened with urine cytology, patients shedding decoy cells were studied (n=103). Molecular studies demonstrated BKV, JCV, or BKV+JCV shedding in 58 (56.3%), 28 (27.2%), and 17 (16.5%), respectively. Biopsy was performed when decoy cells persisted 2 months or serum creatinine increased >20%. RESULTS: BKV viruria was strongly associated with BKV viremia (93%), PVAN (48%, P=0.01) and graft loss (P=0.03). Higher BKV viremia correlated with graft dysfunction (P=0.01), more advanced histological pattern of PVAN (P<0.0001), and more infected cells in biopsy (P=0.0001). BKV viremia of > or =10,000 copies/mL was significantly associated with histologically confirmed PVAN (P=0.0001). Reduction of immunosuppression lead to disappearance of decoy cells in patients shedding BK (>93%). JCV viruria, was more often asymptomatic (P=0.002) and affected older patients (P=0.02). JCV PVAN was less common (21.4%) and was characterized by sparse cytopathic changes but significant inflammation and fibrosis. JCV viremia was rare (14.2%), transient, and low (mean 2.0E+03/mL). After reduction of immunosuppression decoy cells persisted in >50% of patients with JCV (P=0.0001), but no graft loss occurred. During the period of the current study, the incidence of BKV-PVAN was 5.5% and the incidence of JCV-PVAN was 0.9%. CONCLUSIONS: The data point to significant differences of BKV and JCV biology regarding replication and disease in KT patients, with important implications for screening and management.  相似文献   

14.
15.
16.
INTRODUCTION: Leptin plays an important role in regulating appetite and energy expenditure and also functions in the neuroendocrine, hematopoietic, and immune systems, among others. Leptin may be involved in modulating bone mineralization. The relationship between leptin and bone mineral density (BMD) is not clear. This study examined the relationship between BMD and serum leptin levels in renal transplant recipients. MATERIALS AND METHODS: Forty-one patients (28 men and 13 women; age 16 to 55 years) were grouped according to percentile of serum leptin level hypoleptinemic (<5th percentile, n = 14), normoleptinemic (between the 5th and 95th percentiles, n = 19), or hyperleptinemic (>95th percentile, n = 8). The patients also were grouped according to lumbar z score) and total femur z scores (>-2 vs <-2 for both). RESULTS: The groups with different leptin statuses were compared with respect to age, sex distribution, and body mass index. Mean lumbar z score and mean lumbar BMD were higher in the hyperleptinemic group than in the normo- and hypoleptinemic groups (P < .05 for all). Considering the 42 patients overall, those with lumbar z scores >-2 had higher mean serum leptin/BMI than those with lumbar z scores <-2 (0.55 +/- 0.65 vs 0.18 +/- 0.23, respectively, P < .05). Serum leptin/BMI ratio was correlated with lumbar z score (r = .38, P < .05) and lumbar BMD (r = .32, P < .05). CONCLUSION: In conclusion, the data indicate that elevated leptin level is associated with increased bone mass at lumbar sites in renal transplant recipients. This suggest that increased leptin has a bone-sparing effect, especially in the lumbar region, in this patient group.  相似文献   

17.
Hepatitis B may take a rapid and aggressive course in patients under immunosuppression. Nucleoside analogues have been shown to suppress viral replication effectively. To investigate the effect of famciclovir in immunosuppressed patients, 21 heart transplant recipients with chronic hepatitis B infection were included in a prospective study. PATIENTS AND METHODS: Patients have been treated with Famciclovir for a median of 14 months. Hepatitis B virus replication and biochemical parameters were regularly tested and liver biopsies were taken before treatment and after a median time of 7 months. HBV-polymerase was sequenced in all patients before therapy and in those patients who experienced virological breakthrough. RESULTS: Nineteen patients were treated for at least 6 months. Hepatitis B virus-DNA levels declined in all patients and became negative in 8 patients. Mean hepatitis B virus-DNA levels decreased from 199+/-269 to 34+/-53 pg/ml after 24 weeks (P=0.003). During treatment HBeAg became negative in five patients. Mean alanine aminotransferase decreased from 42+/-26 to 24+/-10 U/L (P=0.006). Histological analysis revealed improved inflammatory activity according to the Ishak-score in 11/16 (69%) patients. Total inflammatory activity scores decreased from 8 to 6 (median, NS), but interface hepatitis score (P=0.02) and lobular inflammation score (P=0.006) improved significantly. Median fibrosis scores fell from 5 to 3 (P=0.002). Three patients developed virological breakthrough on famciclovir after 7, 8, and 26 months of treatment showing HBV-polymerase amino acid changes L528 M, S567A, and I581K, respectively. CONCLUSIONS: Famciclovir improves not only biochemical and virological features but also hepatic inflammation and liver fibrosis in patients with chronic hepatitis B under heavy immunosuppression. Virological breakthrough may develop and requires close monitoring.  相似文献   

18.
目的研究更昔洛韦对肾移植术后巨细胞病毒(CMV)感染的预防作用。方法选取2004年行首次肾移植的55例患者,所有患者术后均常规应用环孢素A+霉酚酸酯+激素的免疫抑制方案。将患者随机分为2组,A组27例,从肾移植术后第2周起静脉滴注更昔洛韦5mg.kg-1.d-1,共30d,预防CMV感染;B组28例,没有针对CMV感染进行预防性用药。所有患者肾移植术后均随访6个月,检测其血清中CMV-IgG、CMV-IgM及CMV-DNA的表达,统计肾移植术后6个月时CMV感染率、CMV病的患病率、CMV感染时间、CMV病临床缓解时间、急性排斥反应发生率以及药物不良反应等项目。结果A、B两组患者的CMV感染率分别为37%和25%,CMV患病率分别为22.2%和14.3%,两组相比,差异无统计学意义。A组术后发现CMV感染时间较B组明显延迟(P<0.05),且发生CMV病后的临床缓解时间较B组显著缩短(P<0.05)。A、B两组急性排斥反应发生率分别为11.1%和21.4%,两组比较,差异无统计学意义。1例患者应用更昔洛韦后发生白细胞数减少,经集落刺激因子治疗后恢复。结论肾移植术后静脉滴注更昔洛韦对降低CMV感染率及发病率无明显作用,但可明显延迟肾移植术后CMV感染的发生时间,并显著缩短CMV发病后的临床症状缓解时间。提示肾移植术后CMV感染的预防性用药可能需要更长的时间。  相似文献   

19.
Hepatitis C virus (HCV)-induced cirrhosis is the commonest indication for orthotopic liver transplantation, but HCV recurrence is nearly universal and may worsen patient / graft outcomes. The frequency and severity of HCV recurrence has apparently increased in recent years, raising concern about a possible role for newer immunosuppression regimens in this increase, including potentially tacrolimus. We randomized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation. A pathologist blinded to treatment reviewed serial liver biopsies. Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus- and cyclosporine-treated patients were .38 and .54 (P = .19) and failure / death were .25 and .28, respectively (P = .789). Although cyclosporine-treated patients had significantly larger increases in median serum HCV RNA levels (months 1, 6, and 12), no significant differences were observed between the two treatment arms in histologically-diagnosed HCV recurrence / survival rates. In conclusion, choice of calcineurin inhibitors does not impact severity of recurrent HCV.  相似文献   

20.
Prevention of bone loss with alendronate in kidney transplant recipients   总被引:2,自引:0,他引:2  
Kovac D  Lindic J  Kandus A  Bren AF 《Transplantation》2000,70(10):1542-1543
  相似文献   

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