Angiotensin-II receptor antagonist losartan reduces microalbuminuria in hypertensive renal transplant recipients

In recent years, it has been demonstrated that losartan lowers macroproteinuria in diabetic or non-diabetic renal transplant recipients (RTx) similar to angiotensin converting enzyme (ACE) inhibitors. Microalbuminuria (MAU) may reflect subclinical hyperfiltration damage of the glomerulus. It could be a marker of kidney dysfunction in renal transplantation. The aim of the study was to assess the efficacy of losartan in hypertensive RTx with MAU. This study was conducted in 17 (M/F: 4/13) stable RTx. No change was made in the medical treatment of the patients. All cases received 50 mg/day losartan therapy for 12 wk. Renal functions and MAU were determined 12 and 6 wk and just before the treatment as well as sixth and twelfth week of the treatment in all patients. Losartan satisfactorily lowered systemic blood pressure. A significant reduction in MAU was observed from 103 +/- 53 microg/min at the beginning to 59 +/- 25 microg/min in the sixth week and 47 +/- 24 microg/min in the twelfth week (p=0.0007 and 0.0005, respectively). From the sixth week of the treatment, the therapy significantly decreased hemoglobin, hematocrit and erythrocyte levels but did not change mean leukocyte and platelet counts, urea, creatinine levels and creatinine clearances. No serious side-effect was observed during the study. In conclusion, we found that losartan decreased MAU in hypertensive RTx. For that reason, it might be considered as the first choise antihypertensive agent for the renoprotection in selected patients.     

Apolipoprotein a polymorphism predicts lipoprotein a concentration in renal transplant recipients

Increased serum lipoprotein(a) is an independent risk factor for atherosclerosis in renal transplant recipients. Higher levels may be due to genetic factors, for example, apolipoprotein A isoforms and/or environmental states such as drugs and diets. We evaluated 75 renal transplant recipients including 30 men and 45 women of overall mean age of 30 ± 7 years and transplantation duration of 57 ± 10 months as well as 30 healthy controls for apolipoprotein A isoforms, lipoprotein(a) concentrations, serum triglycerides, serum cholesterol, serum creatinine, and serum homocysteine concentrations. High- and low-molecular-weight apolipoprotein A isoforms (>35 and <35 kringle 4) were observed in 71% and 29% of renal transplant recipients and 83% and 17% of controls. Average lipoprotein(a) concentration ratios between high- and low-molecular-weight apolipoprotein A isoenzymes were significantly greater in renal transplant recipients than in controls. Lipoprotein A and cholesterol concentrations that did not correlate with each other were not higher among the eight renal transplant recipients with creatinine levels greater than 1.8 mg/dL. Absolute levels in renal transplant recipients with failed grafts also were not different regarding the various apolipoprotein A phenotypes. Homocysteine levels were significantly higher with high-molecular-weight apolipoprotein A isoenzymes. A relationship existed between lipoprotein(a) and triglycerides, but not cholesterol: higher triglyceride levels were associated more with high-molecular-weight isoforms of apolipoprotein A (P = .027). Lipoprotein(a) concentrations are higher in low-molecular-weight isoforms of apolipoprotein but triglyceride levels and homocysteine concentrations are higher among the high-molecular-weight isoforms of apolipoprotein A. This finding could be used as a guideline to select the most appropriate drug for different apolipoprotein A isoforms.     

肾移植受者环孢素A治疗窗浓度的临床研究

为了探讨肾移植后患者全血ＣｓＡ谷浓度（ＴＬ）与临床的关系，寻求适合国人肾移植受者ＣｓＡ理想治疗窗浓度范围。应用ＦＰＩＡ法特异性单克隆试剂盒测定口服ＣｓＡ１２小时后全血谷浓度。结果表明，肾移植后在应用标准三联免疫抑制治疗中，ＣｓＡ理想治疗窗浓度范围应为：术后第１个月全血ＣｓＡＴＬ为３５０～４５０μｇ／Ｌ；第２个月为２５０～３５０μｇ／Ｌ；第３个月为２５０～３００μｇ／Ｌ；第４个月以后ＣｓＡＴＬ应维持在１５０～２５０μｇ／Ｌ范围内。此浓度范围既能达到满意的免疫抑制效果，又能减少ＣｓＡ的肝、肾毒性作用及排斥反应。因此，可视为国人肾移植受者ＣｓＡ的理想治疗窗浓度范围。     

Anemia due to losartan in hypertensive renal transplant recipients without posttransplant erythrocytosis

Losartan is a safe, effective long-term treatment for hypertension or posttransplant erythrocytosis (PTE) in renal transplant recipients. There were only a few studies in patients without PTE and their results were different. Starting from week 6 and continuing to the week 12 we observed a decrease in hemoglobin (Hb) and hematocrit (Hct) levels in patients without PTE. Anemia developed in 42.8% of the patients, and Hb levels increased after the withdrawal of losartan treatment. There was a significant decrease in Hct levels beginning from week 3 when compared with the control group. Our study suggests that losartan therapy can decrease Hb beyond its antihypertensive efficacy. Based on the capacity of losartan to decrease Hb and Hct, this drug should be carefully used in patients with preexistent anemia or low Hb levels.     

大黄制剂对肾移植受者环孢素血药浓度的影响分析

目的研究肾移植受者服用大黄制剂对环孢素血药浓度的影响。方法 2008年1月至2012年12月,湖州市第一人民医院10例肾移植受者术后采用环孢素＋吗替麦考酚酯/硫唑嘌呤＋泼尼松三联免疫抑制方案,环孢素用量为5~7 mg·kg-1·d-1,受者术后2~5年因便秘同时服用大黄苏打片（每片含大黄0.15 g,碳酸氢钠0.15 g）,3片/次,3次/d。服用当天及15 d监测受者环孢素血药浓度谷值（C0）、2h后血药浓度峰值（C2）以及肝肾功能,停药15d复查环孢素C0和C2。结果服用大黄苏打片15 d受者环孢素C0、C2均高于服用当天检测值,差异均有统计学意义（t=11.754和12.822,P均〈0.05）。停用大黄苏打片15 d复查环孢素C0、C2均低于服用15 d时检测值,差异均有统计学意义（t=10.020和13.596,P均〈0.05）;与服用当天检测值比较,差异均无统计学差异（t=1.375和0.251,P均〉0.05）。服用大黄苏打片15 d,受者肝肾功能指标与服用当天比较差异均无统计学差异（P均〉0.05）。结论肾移植术后服用环孢素的受者在长期使用含有大黄制剂的药物时,应注意监测环孢素血药浓度,必要时适当调整环孢素用量。     

Long-term follow-up of renal transplant recipients treated with losartan for post-transplant erythrosis

Post-transplant erythrosis (PTE) develops in 9 %–22 % of all renal transplant recipients. Defined as a persistently elevated hematocrit (> 0.51), it occurs most commonly during the first 2 years post-transplantation in hypertensive males with excellent allograft function. Several studies have focused on a major role for angiotensin II in PTE pathogenesis, and some case reports have suggested that losartan is an effective treatment for PTE. Nevertheless, its long-term safety and efficiency have not been reported in renal transplant recipients suffering from PTE. We describe four patients successfully treated with losartan for PTE. Hematocrit remained normal for 21, 18, 15, and 15 months, respectively, after the beginning of losartan therapy. Mean erythropoietin concentration was not modified by treatment (17 ± 3.7 mU/ml vs 17 ± 3.8 mU/ml) and serum creatinine concentration remained stable. We conclude that losartan is a safe and effective long-term treatment for PTE. Received: 18 December 1997 Received after revision: 6 March 1998 Accepted: 16 March 1998     

黄连素对肾移植患者环孢素A血浓度的影响

目的　研究黄连素对环孢素A（CsA）血浓度的影响。方法　将50例同种异体肾移植术后的患者随机分为2组。1组为黄连素组,30例;另1组为对照组,20例。用黄连素前测定所有受者的CsA血浓度谷值。黄连素用量为0.2g,每日3次,7d后复测所有受者的CsA血浓度值,同时测定肝、肾功能,观察期间免疫抑制剂用量不变,不用其它影响CsA血浓度的药物。结果　服用黄连素后CsA血浓度与服黄连素前相比显著升高,P＜0.001。结论　黄连素可提高CsA血浓度,与CsA联合应用可减少CsA用量。     

吗替麦考酚酯与麦考酚钠肠溶片对肾移植受体血药浓度的影响

目的  探讨吗替麦考酚酯（MMF）与麦考酚钠肠溶片（EC-MPS）在同等生物效应剂量下对肾移植受体麦考酚酸（MPA）血药浓度和不良反应的影响。方法  回顾性分析106例活体供肾移植受体的临床资料。按肾移植术后服用不同药物分为两组,MMF组（M1组,62例）和EC-MPS组（M2组,44例）。两组受体的免疫抑制方案分别为M1组用他克莫司（FK506）+MMF+泼尼松,M2组用FK506+EC-MPS+泼尼松。分析两组受体服药后1、2、3周和1、2、3个月MPA血药浓度的变化情况、不良反应发生情况及服用药物所花费用。结果  采取同等生物效应给药,服药后第1、2、3周,第1、2、3个月时M1组MPA血药谷浓度比M2组低,各个时间点两组间比较,差异均有统计学意义（均为P < 0.05）。与M1组比较,M2组术后不良反应的发生率较低且症状较轻。采用同等生物学效应给药,M1组服用MMF所花费用1 710元/月,M2组服用EC-MPS所花费用2 736元/月,但M1组因治疗药物不良反应所产生费用远高于M2组。结论  同等的生物效应剂量下服用EC-MPS的患者相对服用MMF的患者能维持更高的MPA血药浓度并且不良反应更少。     

Effect of risedronate on bone in renal transplant recipients

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.     

Randomized placebo-controlled study on the effects of losartan and carvedilol on albuminuria in renal transplant recipients

BACKGROUND: The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. To shed more light on this issue, we performed a double-blind, placebo-controlled, crossover study to evaluate the influence of the AT-1 angiotensin II receptor blocker, losartan, on the surrogate marker of kidney injury, albuminuria, in patients after renal transplantation. The safety of this therapy was also evaluated. METHODS: Fourteen of 16 patients (nine male, five female), age 45.36 +/- 3.04 years, 65.5 +/- 10.0 months after kidney transplantation, with hypertension and stable serum creatinine 123 +/- 4 micromol/L without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with losartan 50-100 mg and one with carvedilol 12.5-25 mg) in random order, allowing an 8-week placebo washout between treatments. The target office trough blood pressure was below 130/85 mmHg. RESULTS: The ambulatory blood pressure did not differ in the treatment periods. Losartan significantly reduced albuminuria relative to placebo and carvedilol (27.62+/-17.58 vs. 49.55 +/- 25.33 v. 44.77 +/- 21.9 mg/g creatinine; P < 0.01). A significant but not clinically relevant decrease in hemoglobin level after losartan was observed (losartan: 129 +/- 3.1 g/l, placebo: 134.2 +/- 3.2, carvedilol: 137.1 +/- 3.7; P < 0.001). Serum potassium, creatinine, creatinine clearance, and trough blood cyclosporine levels were unaffected. CONCLUSION: Losartan decreases microalbuminuria in renal transplant recipients with clinically minimal side effects.     

Dengue in renal transplant patients: a retrospective analysis

We reviewed the impact of dengue in 27 renal transplant recipients (9 females and 18 males) at a mean of 63 (6-287) months after transplantation. Their mean age was 37+/-14 years and all were first transplantations (21 live donors, 6 deceased donors). Twenty-six were dengue fever cases and one had dengue hemorrhagic fever. Symptoms were: fever (100%), muscular pain (90%), malaise (75%), and headache (68%). Eight (29%) patients were admitted to hospital with one death. All other cases had full recovery. Mean serum creatinine before dengue was 1.4+/-0.6 mg/dL, increased to a mean peak of 1.9+/-1.2 mg/dL (P<0.001), and returned to baseline after recovery (1.6+/-0.82 mg/dL, P=NS). After a mean follow-up of 39+/-18 months, four patients lost their grafts due to chronic allograft nephropathy and four died, due to infectious causes not related to dengue. The first episode of dengue in transplanted patients resembled a flu-like syndrome, as in the general population. It did not cause long-term damage to either the patient or the graft.     

Effect of apolipoprotein polymorphisms in renal transplant recipients

Cardiovascular disease (CVD) is the main cause of mortality among long-term renal transplant recipients (RTR). On the other hand, allograft chronic nephropathy is the primary cause of graft loss among long-term RTR. Hyperlipidemia is a predisposing factor for both conditions. Polymorphisms of the apolipoproteins modulate lipid metabolism. The aim of the study was to evaluate the effect of apo A-I, apo A-IV and apo C-III genotypes on the long-term results of renal transplantation. Clinical assessment (renal allograft and patient survival) and genotyping for apo A-I (+83C/T), apo C-III (Sst I), and apo A-IV (Thr347Ser and Gln360His) polymorphisms were evaluated in 516 kidney transplant patients and correlated with the clinical evolution over 12 months. The distribution of the apo A-I (+83C/T) polymorphisms was: CC 91.9%, CT 7.9%, and TT 0.2%. The apo C-III genotype showed: S1S1 84.4%, S1S2 15.2%, and S2S2 0.4%. The apo A-IV (Pvu II) polymorphism was: GG 82%, GT 18%, and 0% TT. Finally, the frequency of apo A-IV (Hinf I) polymorphism was: AA 69%, AT 27%, and TT 4%. The frequency of polymorphisms was similar between men and women. In conclusion, there was no significant influence of apolipoprotein polymorphisms on renal and patient survival.     

氯沙坦对肾移植术后受者血红蛋白的影响及其使用的安全性

Objective To evaluate the influence of losartan on levels of hemoglobin (Hb) in patients after renal transplantation. The safety of losartan in these patients was also evaluated. Methods Sixty-six hypertensive patients after renal transplantation with stable allograft function and serum creatinine levels below 176. 8 μmol/L (2 mg/dl) were divided into treatment group (n = 34) treated with losartan at a dose of 50 mg/d, and control group (n = 32) not treated with losartan. Each participant was followed up for 6 months, and differences in Hb, whole blood CsA trough concentration, blood pressure (BP), serum creatinine (Cr) and GFR were compared at baseline, and at the month 1, 2, 3 and 6. Results Serum Cr in treatment group showed a slight, hut significant increase at the month 1 (P<0.05 vs baseline), then gradually returned to the baseline until the month 6. Relatively, the estimated glomerular filtration rate (GFR) in treatment group was decreased slightly and temporarily. The Fib level in treatment group kept on dropping in the first two months (P <0.01 vs baseline), then remaining stable since the month 3. An uptrend of Hb was seen in the control group hut there was no statistically significant difference. For patients with Hb≥160 g/L, a progressive decrease in Hb was observed after losartan treatment (P<0.01 vs baseline), while a slight, non-significant decrease in the controls. For patients with Hb <160 μmol/L, Hb in treatment group was decreased in the first two months (P<0.01 vs baseline at the month 2), then gradually increased to baseline from the month 3 to 6. A progressive increase in Hb was seen in control group (P < 0.05 vs baseline). Conclusion Losartan can effectively and safely relieve and prevent posttransplantation erythrocytosis following renal transplantation.     

氯沙坦对肾移植术后受者血红蛋白的影响及其使用的安全性

目的 观察氯沙坦对肾移植术后受者血红蛋白的影响,探讨其使用的安全性.方法 选取肾移植术后超过3个月,移植肾功能稳定,有高血压的受者66例.随机将受者分为两组.实验组:34例,加用氯沙坦或使用氯沙坦替换原有的降压药物;对照组32例,不使用氯沙坦.分组后对受者进行6个月的观察,分别测定0(基础值)、1、2、3及6个月共5个时间点受者的血红蛋白、血肌酐、肾小球滤过率(GFR)及血压等指标,并观察各指标的变化趋势.结果 实验组受者在使用氯沙坦1～2个月时的血红蛋白水平较基础值显著下降(P<0.05),2～6个月时趋于稳定;对照组受者的血红蛋白水平较基础值轻度上升(P>0.05).实验组中伴有高血红蛋白血症(PTE)的受者使用氯沙坦1～3个月时血红蛋白水平呈持续下降趋势(P<0.05),3～6个月时趋于稳定;对照组中伴有PTE的受者血红蛋白水平较基础值轻度下降(P>0.05).实验组中不伴有PTE的受者血红蛋白水平呈先下降后回升趋势;对照组中不伴有PTE的受者血红蛋白水平较基础值显著升高(P<0.05).实验组受者使用氯沙坦1个月时血肌酐水平呈升高趋势,2～6个月时逐渐恢复到基础值;对照组受者血肌酐水平无显著变化(P>0.05).实验组受者的GFR轻度下降后逐渐恢复到基础值;对照组受者的GFR呈逐渐上升趋势.实验组受者的血压呈明显下降趋势(P<0.05);对照组受者的血压较基础值无显著变化.结论 肾移植术后使用氯沙坦能降低受者的高血红蛋白水平,对PTE有一定的治疗和预防作用,并且不会影响受者的移植肾功能.对于肾移植术后有高血压且发生高血红蛋白血症的受者,使用氯沙坦是安全的.     

氯沙坦对肾移植术后受者血红蛋白的影响及其使用的安全性

Objective To evaluate the influence of losartan on levels of hemoglobin (Hb) in patients after renal transplantation. The safety of losartan in these patients was also evaluated. Methods Sixty-six hypertensive patients after renal transplantation with stable allograft function and serum creatinine levels below 176. 8 μmol/L (2 mg/dl) were divided into treatment group (n = 34) treated with losartan at a dose of 50 mg/d, and control group (n = 32) not treated with losartan. Each participant was followed up for 6 months, and differences in Hb, whole blood CsA trough concentration, blood pressure (BP), serum creatinine (Cr) and GFR were compared at baseline, and at the month 1, 2, 3 and 6. Results Serum Cr in treatment group showed a slight, hut significant increase at the month 1 (P<0.05 vs baseline), then gradually returned to the baseline until the month 6. Relatively, the estimated glomerular filtration rate (GFR) in treatment group was decreased slightly and temporarily. The Fib level in treatment group kept on dropping in the first two months (P <0.01 vs baseline), then remaining stable since the month 3. An uptrend of Hb was seen in the control group hut there was no statistically significant difference. For patients with Hb≥160 g/L, a progressive decrease in Hb was observed after losartan treatment (P<0.01 vs baseline), while a slight, non-significant decrease in the controls. For patients with Hb <160 μmol/L, Hb in treatment group was decreased in the first two months (P<0.01 vs baseline at the month 2), then gradually increased to baseline from the month 3 to 6. A progressive increase in Hb was seen in control group (P < 0.05 vs baseline). Conclusion Losartan can effectively and safely relieve and prevent posttransplantation erythrocytosis following renal transplantation.     

氯沙坦对肾移植术后受者血红蛋白的影响及其使用的安全性

Objective To evaluate the influence of losartan on levels of hemoglobin (Hb) in patients after renal transplantation. The safety of losartan in these patients was also evaluated. Methods Sixty-six hypertensive patients after renal transplantation with stable allograft function and serum creatinine levels below 176. 8 μmol/L (2 mg/dl) were divided into treatment group (n = 34) treated with losartan at a dose of 50 mg/d, and control group (n = 32) not treated with losartan. Each participant was followed up for 6 months, and differences in Hb, whole blood CsA trough concentration, blood pressure (BP), serum creatinine (Cr) and GFR were compared at baseline, and at the month 1, 2, 3 and 6. Results Serum Cr in treatment group showed a slight, hut significant increase at the month 1 (P<0.05 vs baseline), then gradually returned to the baseline until the month 6. Relatively, the estimated glomerular filtration rate (GFR) in treatment group was decreased slightly and temporarily. The Fib level in treatment group kept on dropping in the first two months (P <0.01 vs baseline), then remaining stable since the month 3. An uptrend of Hb was seen in the control group hut there was no statistically significant difference. For patients with Hb≥160 g/L, a progressive decrease in Hb was observed after losartan treatment (P<0.01 vs baseline), while a slight, non-significant decrease in the controls. For patients with Hb <160 μmol/L, Hb in treatment group was decreased in the first two months (P<0.01 vs baseline at the month 2), then gradually increased to baseline from the month 3 to 6. A progressive increase in Hb was seen in control group (P < 0.05 vs baseline). Conclusion Losartan can effectively and safely relieve and prevent posttransplantation erythrocytosis following renal transplantation.     

氯沙坦对肾移植术后受者血红蛋白的影响及其使用的安全性

Objective To evaluate the influence of losartan on levels of hemoglobin (Hb) in patients after renal transplantation. The safety of losartan in these patients was also evaluated. Methods Sixty-six hypertensive patients after renal transplantation with stable allograft function and serum creatinine levels below 176. 8 μmol/L (2 mg/dl) were divided into treatment group (n = 34) treated with losartan at a dose of 50 mg/d, and control group (n = 32) not treated with losartan. Each participant was followed up for 6 months, and differences in Hb, whole blood CsA trough concentration, blood pressure (BP), serum creatinine (Cr) and GFR were compared at baseline, and at the month 1, 2, 3 and 6. Results Serum Cr in treatment group showed a slight, hut significant increase at the month 1 (P<0.05 vs baseline), then gradually returned to the baseline until the month 6. Relatively, the estimated glomerular filtration rate (GFR) in treatment group was decreased slightly and temporarily. The Fib level in treatment group kept on dropping in the first two months (P <0.01 vs baseline), then remaining stable since the month 3. An uptrend of Hb was seen in the control group hut there was no statistically significant difference. For patients with Hb≥160 g/L, a progressive decrease in Hb was observed after losartan treatment (P<0.01 vs baseline), while a slight, non-significant decrease in the controls. For patients with Hb <160 μmol/L, Hb in treatment group was decreased in the first two months (P<0.01 vs baseline at the month 2), then gradually increased to baseline from the month 3 to 6. A progressive increase in Hb was seen in control group (P < 0.05 vs baseline). Conclusion Losartan can effectively and safely relieve and prevent posttransplantation erythrocytosis following renal transplantation.     

氯沙坦对肾移植术后受者血红蛋白的影响及其使用的安全性

Objective To evaluate the influence of losartan on levels of hemoglobin (Hb) in patients after renal transplantation. The safety of losartan in these patients was also evaluated. Methods Sixty-six hypertensive patients after renal transplantation with stable allograft function and serum creatinine levels below 176. 8 μmol/L (2 mg/dl) were divided into treatment group (n = 34) treated with losartan at a dose of 50 mg/d, and control group (n = 32) not treated with losartan. Each participant was followed up for 6 months, and differences in Hb, whole blood CsA trough concentration, blood pressure (BP), serum creatinine (Cr) and GFR were compared at baseline, and at the month 1, 2, 3 and 6. Results Serum Cr in treatment group showed a slight, hut significant increase at the month 1 (P<0.05 vs baseline), then gradually returned to the baseline until the month 6. Relatively, the estimated glomerular filtration rate (GFR) in treatment group was decreased slightly and temporarily. The Fib level in treatment group kept on dropping in the first two months (P <0.01 vs baseline), then remaining stable since the month 3. An uptrend of Hb was seen in the control group hut there was no statistically significant difference. For patients with Hb≥160 g/L, a progressive decrease in Hb was observed after losartan treatment (P<0.01 vs baseline), while a slight, non-significant decrease in the controls. For patients with Hb <160 μmol/L, Hb in treatment group was decreased in the first two months (P<0.01 vs baseline at the month 2), then gradually increased to baseline from the month 3 to 6. A progressive increase in Hb was seen in control group (P < 0.05 vs baseline). Conclusion Losartan can effectively and safely relieve and prevent posttransplantation erythrocytosis following renal transplantation.