Factors influencing plasma lipid profiles including lipoprotein (a) concentrations in renal transplant recipients

Fasting plasma cholesterol, triglycerides, high-density lipoprotein (HDL) and apoprotein (apo) B were elevated in 214 nondiabetic renal transplant recipients renal transplant recipients when compared to a reference group. Apo (a) was slightly but not significantly lower in transplant recipients (median 118 mg/dl, range 16–1680 vs 130 mg/dl, 10–1176) and this difference could be predicted from Lp (a) isoform analysis. Cholesterol, triglyceride, apo B and apo (a) concentrations correlated negatively with creatinine clearance but none of these parameters showed a significant association with proteinuria. Patients treated with steroids had higher plasma HDL concentrations than those receiving cyclosporin monothetapy (P<0.01). The use of diuretics was associated with raised triglycerides (P<0.001) and cholesterol (P<0.01) and with reduced HDL (P<0.01) whilst patients receiving -blockers had significantly higher triglycerides (P<0.01) and lower HDL levels (P<0.02). In multiple regression analysis, age (P<0.01), creatinine clearance (P<0.05) and diuretic therapy (P<0.005) were independent risk factors for increased cholesterol whilst apo (a) levels correlated negatively with creatinine clearance (P<0.005). These results suggest that impaired renal function, steroids and non-immunosuppressive drugs contribute to lipid abnormalites in renal transplant recipients.     

Clinical evaluation of rosuvastatin in heart transplant patients with hypercholesterolemia and therapeutic failure of other statin regimens: short‐term and long‐term efficacy and safety results

We conducted an observational study of 30 heart transplant recipients with serum low‐density lipoprotein cholesterol (LDL‐c) >100 mg/dl despite previous statin therapy, who were treated with rosuvastatin 10 mg daily (5 mg in case of renal dysfunction). Serum lipids, creatine phosphokinase (CPK), bilirubin, and hepatic enzymes were prospectively measured 2, 4, and 12 weeks after the initiation of the drug. Clinical outcomes of patients who continued on long‐term rosuvastatin therapy beyond this 12‐week period were reviewed in February 2015. Over the 12‐week period following rosuvastatin initiation, serum levels of total cholesterol (TC) and LDL‐c and the ratio TC/high‐density lipoprotein cholesterol (HDL‐c) decreased steadily (P < 0.001). Average absolute reductions of these three parameters were –48.7 mg/dl, –46.6 mg/dl, and –0.9, respectively. Seventeen (57%) achieved a serum LDL‐c < 100 mg/dl. No significant changes from baseline were observed in serum levels of triglycerides, HDL‐c, hepatic enzymes, bilirubin, or CPK. Twenty‐seven (90%) patients continued on long‐term therapy with rosuvastatin over a median period of 3.6 years, with no further significant variation in lipid profile. The drug was suspended due to liver toxicity in 1 (3.3%) patient and due to muscle toxicity in 2 (6.7%) patients. All adverse reactions resolved rapidly after rosuvastatin withdrawal. Our study supports rosuvastatin as a reasonable alternative for heart transplant recipients with hypercholesterolemia and therapeutic failure of other statin regimens.     

Short-term effect of atorvastatin in hypercholesterolaemic renal-transplant patients unresponsive to other statins.

BACKGROUND: Atherosclerosis associated with hyperlipidaemia is a major cause of morbidity and mortality after renal transplantation. Atorvastatin is a new HMG-CoA reductase inhibitor that has shown a favourable profile of lipid reduction when compared with other statins. The aim of the study was to assess the efficacy and safety of atorvastatin in hypercholesterolaemic renal transplant patients who had previously been on statins with little or no effect. METHODS: Atorvastatin, 10 mg/day, was administered to 10 renal transplant recipients with persistent hypercholesterolaemia (total cholesterol >240 mg/dl) for a period of 3 months. All of them had already been on statins for at least 3 months. RESULTS: Atorvastatin exerted a satisfactory lipid-lowering effect in seven of 10 patients. On average, serum total cholesterol (311+/-36.2 vs 253+/-48.8 mg/dl; P:<0.05) and serum LDL cholesterol (184+/-30.9 vs 136+/-22.9 mg/dl; P:<0.05) significantly decreased after atorvastatin therapy, whereas serum HDL cholesterol (86+/-14.6 vs 84+/-22.1 mg/dl) remained unchanged. In five subjects with a baseline serum triglyceride level above 150 mg/dl, a marked reduction in triglycerides was also observed (261+/-80.3 vs 193+/-53.3 mg/dl; P:<0.05). Lp(a) did not significantly change (13+/-16.3 vs 15+/-23.9 mg/dl, P:=NS). Serum creatinine, transaminases, creatinine phosphokinase (55+/-21.3 vs 56+/-29.4 IU/l) and fasting cyclosporin A levels were unaffected. The drug was generally well tolerated and neither myositis nor rhabdomyolysis was reported. CONCLUSION: Short-term therapy with the new HMG-CoA reductase inhibitor, atorvastatin, appears to be effective in lowering atherogenic lipids in renal transplant patients who had had little or no response to other statins.     

Persistent post-transplant polyuria managed by bilateral native-kidney laparoscopic nephrectomy

Polyuria is not considered an absolute indication for pre-transplant nephrectomy; however, it may complicate post-transplantation fluid management. Bilateral native-kidney laparoscopic nephrectomy was performed at our centre in two patients (four kidneys) 1 month after they had received a living related-donor renal transplant. The indication for nephrectomy was severe post-transplant polyuria secondary to the patient’s underlying disease: juvenile nephronophthisis. Both patients had a persistent post-transplant daily urine output of 7–8 l/day and continued to have a variable serum creatinine level, dependent on intravenous hydration, more then 3 weeks after transplantation. Bilateral laparoscopic native-kidney nephrectomy in children has previously been reported. However, to the best of our knowledge, laparoscopic nephrectomy has not been described after kidney transplantation and certainly not in the immediate post-transplantation period. The procedure was well tolerated and did not affect renal graft function. In fact, following the procedure, serum creatinine levels stabilized, while daily fluid requirements decreased to 2.5–3.5 l/day in both patients. We concluded that bilateral native-kidney nephrectomy can be safely performed in paediatric renal transplant recipients in the immediate post-transplantation period. This new approach may allow preemptive transplantation and avoid the need for a transition period on dialysis in patients for whom pre-transplant nephrectomy is not absolutely indicated.     

Lipid Profile Before and After Renal Transplantation—A Longitudinal Study

Background. The data on lipid profile in renal transplant recipients from the Indian subcontinent is scant. Methods.?Lipid profile was studied in 30 consecutive patients of end stage renal disease before renal transplantation (0 month) and prospectively posttransplantation at 1, 3, and 6 months. The results were compared with 30, age and sex matched, healthy controls. All the patients received triple immunosuppression (prednisolone, azathioprine and cyclosporine). Results.?Pretransplantation, the hypertriglyceridemia and hypercholesterolemia was present in 20% and 7% of the patients and the difference (elevation) in the mean values of various lipid fractions was not significant compared to healthy controls except a fall in HDL (p<.01). After renal transplantation, there was a significant elevation in the mean values of total cholesterol, triglycerides, VLDL, and LDL cholesterol at 1, 3, and 6 months. HDL cholesterol levels remained significantly lower as compared to healthy controls. Although, the mean values of serum triglycerides and cholesterol were significantly higher in diabetic end stage renal disease compared to nondiabetic ESRD, however there was insignificant difference in the lipid profile amongst diabetic and nondiabetic renal allograft recipients. Conclusion.?Our data shows distinct elevation in the lipids and lipoproteins after renal transplantation and immunosuppressive drugs seem to be the culprit.     

Is low pre-transplant parathyroid hormone a risk marker for cardiovascular disease in long-term follow-up of renal transplant recipients?

Background

Secondary hyperparathyroidism and altered levels of parathyroid hormone (PTH) are associated with vascular events in chronic kidney disease. After renal transplantation, this association is not clear. Pre-transplant parathyroidectomy (PTX) is common, but post-transplant data are scarce. We aimed to study the effect of PTH at the time of transplantation on risk of post-transplant vascular events in renal transplant recipients with and without pre-transplant PTX.

Methods

258 patients from two Swedish transplant units were followed for 6 years. Separate analyses were made for patients with or without pre-transplant PTX. Patients with no pre-transplant PTX were stratified by quartiles of PTH at time of transplantation and patients with pre-transplant PTX were stratified by above and below median levels of PTH at time of transplantation. Hazard ratios for vascular events, mortality, and graft failure were calculated in adjusted Cox regression models.

Results

In patients with no pre-transplant PTX, the lowest quartile of PTH at transplantation had a higher risk of cardiovascular events compared to quartile 3 with an adjusted hazard ratio (95% CI) of 2.63 (1.04–6.67). In patients with pre-transplant PTX, the group below median of PTH had a higher risk of cardiovascular events with an adjusted hazard ratio (95% CI) of 18.15 (1.62–203.82) compared to patients above median of PTH.

Conclusion

Low levels of parathyroid hormone before transplantation were associated with increased risk of post-transplant vascular events both in patients with and without pre-transplant parathyroidectomy. Any conclusions on causal or direct effect of PTH on outcome cannot be drawn from this observational study.

     

Obesity following kidney transplantation and steroid avoidance immunosuppression

Abstract:  Obesity is an important co-morbidity within end-stage renal disease (ESRD) and renal transplant populations. Previous studies have suggested that chronic corticosteroids result in increased body weight post-transplant. With the recent adoption of steroid-sparing immunosuppressive strategies, we evaluated the effect of these strategies on body mass index (BMI) after renal transplantation. We examined 95 renal transplant recipients enrolled in National Institutes of Health clinical transplant trials over the past three yr who received either lymphocyte depletion-based steroid sparing or traditional immunosuppressive therapy that included steroids for maintenance immunosuppression. Recipients were overweight prior to transplant and no significant differences existed in pre-transplant BMI among treatment groups. Regardless of therapy, BMI increased post-transplant in all recipients. The BMI increase consisted of an average weight gain of 5.01 ± 7.12 kg (mean, SD) post-transplant. Additionally, in a number of recipients placed on maintenance steroids, subsequent withdrawal at a mean of 100 d post-transplant had no impact on weight gain. Thus, body weight and BMI increase following kidney transplantation, even in the absence of steroids. Thus, patients gain weight after renal transplantation regardless of the treatment strategy. Steroid avoidance alone does not reduce risk factors associated with obesity in our patient population.     

Metabolic cardiovascular syndrome after renal transplantation.

BACKGROUND: Cardiovascular disease (CVD) is the major cause of death in renal transplant recipients. Traditional risk factors like hypertension, dyslipidaemia and diabetes mellitus are common, but cannot completely account for the high prevalence of CVD in this population. The aim of the present study was to assess whether post-transplant glucose intolerance, defined as post-transplant diabetes mellitus, impaired glucose tolerance, or impaired fasting glucose, is associated with metabolic disturbances known to increase risk of cardiovascular disease, similar to what has been observed in the general population. METHODS: One hundred and seventy-three consecutive patients were prospectively examined 10 weeks after transplantation. An oral glucose tolerance test was completed in 167 patients. Questionnaires, medical records, and the results of various blood tests were used to evaluate a number of known cardiovascular risk factors in all patients. RESULTS: Glucose intolerance was present in about one-half the recipients and was associated with age, a positive family history of ischaemic heart disease, acute rejection, higher levels of serum triglycerides, apolipoprotein B and 2-h insulin, and lower levels of serum HDL cholesterol. After adjustment for age and sex, lower HDL cholesterol (P=0.005), higher serum triglycerides (P<0.001), apolipoprotein B (P=0.039) and 2-h insulin (P<0.001) were still associated with post-transplant glucose intolerance. CONCLUSIONS: Ten weeks after renal transplantation glucose intolerance is associated with a clustering of cardiovascular risk factors and metabolic abnormalities, consistent with a post-transplant metabolic cardiovascular syndrome.     

Tacrolimus-based triple-drug immunosuppression minimizes serum lipid elevations in pediatric cardiac transplant recipients.

BACKGROUND: Immunosuppression with corticosteroids and cyclosporine has been associated with hyperlipidemia, a risk factor for post-transplant coronary artery disease. The recent development of tacrolimus has created an alternative to cyclosporine-based triple drug immunotherapy. One potential benefit that has been reported in patients receiving tacrolimus is a minimization of elevation of both total and LDL cholesterol, compared to those increases observed in patients receiving cyclosporine-based immunosuppression. It is unclear in previous studies whether this beneficial effect is related to tacrolimus directly or to its corticosteroid sparing potential. To study this relationship, we compared lipid profiles from pediatric cardiac transplant recipients treated with corticosteroids, and either cyclosporine or tacrolimus. METHODS: The study group consisted of 23 patients (mean age = 12.3 years) with pre-transplant and serial post-transplant determinations of total cholesterol, LDL, HDL, and triglycerides. Patients were separated into 4 study groups, defined by immunosuppressive regimen (cyclosporine vs. tacrolimus) and prednisone dose (>0.10 mg/kg/day vs. < or =0.10 mg/kg/day). RESULTS: Patients who received cyclosporine and higher doses of prednisone experienced a mean 74 mg/dl increase from baseline in total cholesterol (p = .0001). None of the other 3 treatment groups demonstrated a statistically significant elevation. Similar trends were observed in LDL and triglyceride alterations between the 4 study groups. Interestingly, patients treated with tacrolimus and higher doses of prednisone demonstrated a significant rise in HDL from baseline (p = .0001), although those who received cyclosporine and higher dose prednisone failed to exhibit this rise. CONCLUSION: The minimal degree of lipid alteration seen in patients receiving tacrolimus and higher doses of prednisone indicates that this effect was not solely based upon the steroid-sparing properties of tacrolimus therapy. The data also suggests a possible synergistic effect between cyclosporine and higher doses of prednisone on hyperlipidemia. Therefore, in pediatric patients requiring higher corticosteroid doses late after transplantation, use of tacrolimus rather than cyclosporine may lead to more favorable lipid profiles and help minimize the risk of post-transplant coronary arteriopathy.     

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

Effect of lipid disorders on arteriosclerosis in renal transplant recipients

Background-Aim

After a patient successfully receives a renal transplant, an increase in total serum cholesterol and triglycerides, a decrease in high density cholesterol, and normal level in low density cholesterol may be noted. Coronary artery disease is one of the main causes of morbidity and mortality in renal recipients. This study was performed in order to determine the lipid profile of patients with chronic kidney disease that received a renal transplant, and correlate the effect of the lipid profile with atherogenesis.

Patients-Methods

The study included 30 patients, of whom 21 were male and 9 female, with a mean age of 48.43 years. The lipid status of all patients was measured one month prior to transplantation and at distinct time intervals (1, 3, 6, 12 months) after transplantation. Echocardiographic (triplex) evaluation was performed in all renal recipients before transplantation and 12 months post surgery. Twenty-nine patients received a renal graft from cadaveric patients while one received a renal graft from a living relative donor. It was the first transplantation for all patients after being on the transplant waiting list for a mean 4.2 years.

Results

Measurements of the lipid profile of these patients revealed statistically significant changes after renal transplantation. Moderate atheromatous lesions were found in 50% of patients before transplantation. One year after transplantation, 18% of patients revealed no atheromatous lesions, 54% had mild atheromatous lesions and 28% had severe atheromatous lesions. Total serum cholesterol levels had statistically significant changes (P<0.001), and the grade of stenosis of carotids was also affected (p=0.0013).

Conclusion

Our results suggest that changes in the lipid status in renal transplant patients are strongly correlated with atherogenesis in carotids and, in consequence, an increased cardiovascular risk for these patients. Long-term follow-up of renal recipients can be of significant use in monitoring cardiovascular disease.     

Role of dietary intervention on metabolic abnormalities and nutritional status after renal transplantation.

BACKGROUND: In these last years, several traditional risk factors for cardiovascular disease, like obesity, dyslipidaemia, hypertension and post-transplant diabetes mellitus have been also identified as important non-immunological risk factors leading to the development of chronic allograft nephropathy, the first cause of graft loss in transplanted patients. The aim of the present study was to determine the effects of a 12-month dietary regimen on the nutritional status and metabolic outcome of renal transplant recipients in the first post-transplant year. METHODS: Forty-six cadaver-donor renal transplant recipients (mean age 40.8 +/- 10.1-years), enrolled during the first post-transplant year (4.8 +/- 3.3 months) and followed prospectively for a 12 month period. Biochemical and nutritional markers, anthropometric measurements, body composition (by conventional bioelectrical impedance analysis) and dietary records (using a detailed food-frequency questionnaire) at baseline and after 12 months. RESULTS: Compliance to the diet was related to sex (male better than female) and was associated with weight loss primarily due to a decrease in fat mass, with decrease in total cholesterol and glucose plasma levels and with a concomitant rise in serum albumin. CONCLUSION: After renal transplantation, health benefits of proper metabolic balance that include reduced body fat, weight loss, lower cholesterol and triglycerides levels and an improvement, fasting glucose levels can be obtained when dietary intervention occurred.     

Improved attainment of NKF classified lipid target levels after conversion from cyclosporine to tacrolimus in renal graft recipients

In an open, prospective, multicenter study, stable renal graft recipients were converted to tacrolimus because of cyclosporine-related side effects. Seventy-five patients were switched primarily because of hyperlipidemia. After the switch to tacrolimus, mean total cholesterol was reduced by 15% at month 6. One hundred seventy-seven additional patients were switched primarily for other indications: hypertrichosis, gingival hyperplasia, and arterial hypertension, and these symptoms also improved after the switch. In this analysis, serum lipid levels were categorized according to a modified standard classification of lipid parameters for renal transplant patients (published by the NKF Work Group). The aim was to estimate the proportion of patients reaching normal lipid levels after the conversion to tacrolimus therapy. In patients with primary indication hyperlipidemia, the proportion with normal cholesterol levels increased significantly from 5.6% at baseline to 37.5% at month 6 (P < .05). For LDL cholesterol, the increase was from 54.1% at baseline to 64.9% at month 6, and for triglycerides the improvement was from 25.4% to 33.8%. HDL cholesterol levels remained stable. Similar changes of lipid parameters were also observed in the subgroups of patients converted to tacrolimus primarily because of other indications. After conversion from cyclosporine to tacrolimus, a significantly higher proportion of stable renal graft recipients reached normal total cholesterol levels. For LDL cholesterol and triglycerides, a trend for normalization was observed. Thus, the improvement of serum lipid levels resulted for many patients in a change to a better level class and improved or normalized their cardiovascular risk parameters.     

Prevalence and determinants of anemia in the immediate postkidney transplant period

At the time of renal transplantation, erythropoiesis-stimulating agents and iron supplementation are routinely discontinued in the prospect of recovery of renal function. This recovery, however, is often delayed and suboptimal. In addition, blood loss because of frequent diagnostic phlebotomies may be substantial. Renal transplant recipients may thus be considered at high risk of anemia in the immediate post-transplant period. We performed a single-center observational study, including 391 recipients of a single kidney. Hemoglobin levels and parameters of iron metabolism were monitored during the immediate post-transplant period, i.e., the first 3 months after transplantation. Hemoglobin levels decreased by 3.8 ± 1.5 g/dl to reach a nadir of 9.1 ± 1.2 g/dl at day 7. Transient severe anemia was observed in 91.3% of the patients. Donor age, gender, renal diagnosis of polycystic disease, pretransplant hemoglobin and ferritin level, estimated glomerular filtration rate at month 3, and duration of initial hospitalization were observed to be independently associated with the hemoglobin level at month 3. Transient severe anemia is an almost universal observation in incident renal transplant recipients. Poor graft function, high donor age, and low iron stores are independently associated with low hemoglobin levels at month 3.     

The effect of fluvastatin of hyperlipidemia in renal transplant recipients: A prospective,placebo- controlled study

Posttransplant hyperlipidemia is a common complication which may affect long term cardiovascular mortality. In this prospective, placebo-controlled study, 19 renal transplant recipients (11 male 8 female, mean age 31.2 ± 8.4 years) with good allograft function (serum creatinine <2 mg/dl) more than 6 months after transplantation were included. All the patients had hyperlipidemia (serum cholesterol >230 mg/dl and/or LDL-cholesterol >130 mg/dl) despite dietary interventions. The patients were treated with a triple immunosuppressive regimen. After a 8-week period of placebo plus diet regimen, the patients were put on fluvastatin plus diet for another 8 weeks. The patients were followed for its effect on lipid parameters and side effects. After convertion to fluvastatin, serum cholesterol (263.0 ± 31.6 vs 223.2 ± 31.6 mg/dl, p = 0.001), LDL-cholesterol (174.4 ± 28.3 vs 136.4 ± 28.5 mg/dl, p = 0.002), Apolipoprotein (Apo) A₁ (131.1 ± 16.9 vs 114.7 ± 18.4 mg/dl, p = 0.001) and Apo B (109.0 ± 29.8 vs 97.3 ± 31.5 mg/dl, p = 0.02) levels decreased significantly. Serum levels of triglycerides, VLDL-cholesterol and HDL-cholesterol levels did not vary under fluvastatin. Serum lipoprotein (a) levels were also unchanged during the whole study period (24.9 ± 19.4 vs 23.1 ± 19.8 mg/dl, p > 0.05). We concluded that fluvastatin effectively decreased atherogenic lipoproteins such as serum cholesterol, LDL-cholesterol, Apo B in posttransplant hyperlipidemia, however fluvastatin had no effect on another independent risk factor of atherogenesis, serum lipoprotein (a) levels. This revised version was published online in June 2006 with corrections to the Cover Date.     

Hypercholesterolemia is common after pediatric heart transplantation: initial experience with pravastatin.

BACKGROUND: Coronary allograft vasculopathy (CAV) is a progressive complication after cardiac transplantation and limits survival. Hyperlipidemia is a known risk factor for CAV, and pravastatin is effective in decreasing cholesterol levels in adults after transplantation. However, few data exist regarding lipid profiles and statin use after pediatric heart transplantation. We evaluated the prevalence of hyperlipidemia in pediatric heart transplant recipients and assessed the efficacy and safety of pravastatin therapy. METHODS: We performed a retrospective chart review of lipid profiles > or =1 year after surgery in 50 pediatric cardiac transplant recipients to assess the incidence of hyperlipidemia. Twenty of these patients received pravastatin for hypercholesterolemia. Their primary immunosuppression therapy was cyclosporine/prednisone plus either azathioprine or mycophenolate mofetil. We reviewed serial lipid profiles, creatinine phosphokinase, and liver enzymes. RESULTS: Overall, 36% of the patients (n = 50) had total cholesterol (TC) concentrations > 200 mg/dl and 52% had low-density lipoprotein (LDL) >110 mg/dL beyond 1 year after transplantation. Of the 20 treated with pravastatin, TC (236 +/- 51 vs 174 +/- 33 mg/dl) and LDL levels (151 +/- 32 vs 99 +/- 21 mg/dl) decreased significantly with therapy (p <.0001). We found no symptoms; however, 1 patient had increased creatinine phosphokinase. Liver enzyme concentrations remained normal in all. CONCLUSIONS: Hypercholesterolemia is prevalent in pediatric cardiac transplant recipients. Pravastatin therapy is effective in decreasing TC and LDL levels, seems to be safe, and is tolerated well. Further studies are necessary to determine whether pravastatin treatment is beneficial in decreasing CAV.     

肾移植术后血脂的变化对移植肾功能的影响

目的:探讨肾移植患者血脂代谢情况及其对移植肾功能的影响。方法:检测89例肾移植患者肾移植前、后的血脂水平,并与移植后1年内发生急性排斥反应及移植后1年时发生慢性移植肾功能不全的患者进行血清肌酐水平相关性分析。结果:与正常对照组比较,肾移植前、后的血清总胆固醇、低密度脂蛋白胆固醇的水平显著升高(P<0.01),甘油三酯、高密度脂蛋白胆固醇、极低密度脂蛋白胆固醇水平无显著差异。血载脂蛋白A1水平显著低于正常对照组(P<0.01)。移植前、后上述血脂水平无显著差异。移植前高胆固醇血症与急性排斥反应的发生存在相关性,高胆固醇血症对慢性移植肾功能不全患者血清肌酐水平升高存在影响。结论:肾移植患者血脂代谢紊乱明显不同于正常人群,高脂血症对急性排斥反应及慢性移植肾功能不全的发生具有不良影响。     

Pre-transplant Th1 and post-transplant Th2 cytokine patterns are associated with early acute rejection in renal transplant recipients

In this retrospective study, we tried to define pre- and post-transplant immunological parameters that identify patients at risk for early acute rejection. Lymphocyte subpopulations and plasma levels of cytokines and neopterin were determined pre- and post-transplant in 32 renal transplant recipients with biopsy-proven early acute graft rejection. Recipients without early acute rejection served as controls. High pre-transplant interferon-gamma (IFN-gamma) plasma levels (p = 0.006), consistently high levels of neopterin early post-transplant (p = 0.008), a post-transplant switch from a Th1 to a Th2 cytokine pattern with decreasing IFN-gamma (p = 0.02), low CD8+ lymphocyte counts (p = 0.006) and consistently high CD19+ B lymphocyte counts were associated with acute rejection. Our data suggest that patients with a pre-transplant Th1 and an early post-transplant Th2 cytokine pattern are pre-disposed for early acute rejection.     

Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients

Abstract. To determine the impact of long-term immunosuppression on serum lipids in stable renal graft recipients we measured serum lipids and apolipoprotein B concentrations in 20 patients receiving therapy with cyclosporin (CsA) and low-dose prednisolone (CsA/P) and in 18 patients on therapy with azathioprine and maintenance steroids (Aza/P). The patients were matched for age, body mass index, primary renal disease and dose of prednisolone, but not for the duration in transplantation and serum creatinine concentration. Triglyceride concentrations were significantly higher in the CsA/P group than in Aza/P-treated patients: 2.62 ± 0.35 vs 1.62 ± 0.23 mmol/l ( P < 0.05). Similarly, total cholesterol (C) levels were significantly more elevated in the CsA/P recipients than in the other group: 7.4410.32 vs 5.84 ± 0.25 (F<0.02). CsA/P patients had higher serum levels of LDL-C (4.79 ± 0.20 vs 3.43 ± 0.19 mmol/l ( P < 0.001) and apolipoprotein B concentrations (191 ± 13 vs 128 ± 9 mg/dl; P < 0.001). CsA/P and Aza/P recipients had similar concentrations of HDL-C (1.73 ± 0.13 vs 1.52 ± 0.09 mmol/l; NS). We conclude that in stable renal graft recipients with good transplant function long-term immunosuppression with CsA/P is associated with a more atherogenic lipid status than therapy with Aza/P.     

Correlation of C0 and C2 levels with lipid profiles in adolescent renal transplant recipients in the early and late posttransplant periods

Hyperlipidemia is a frequent complication after renal transplantation. Cyclosporine therapy is an important cause of hyperlipidemia. It is still controversial whether C0 or C2 is the most effective way to monitor blood cyclosporine concentrations to guide dosages. We sought to evaluate the relationship of C0 or C2 to serum lipid levels in the early and late posttransplant periods among adolescent renal transplant recipients. The posttransplantation charts of 26 adolescent renal transplant recipients were evaluated retrospectively. Serum C0 and C2 levels and serum lipid (triglyceride and total cholesterol) levels were analyzed both in the early (first 6 months) and the late (thereafter) posttransplant periods. Hypertriglyceridemia and hypercholesterolemia were defined as levels above the 95th percentile adjusted for age and gender. To evaluate the influence of C0 and C2 levels on serum lipids, we excluded one patient with familial hyperlipidemia. In addition, serum lipid levels of the remaining 25 patients were excluded in acute rejection periods and when the serum creatinine levels were above 2.5 mg/dL, representing chronic allograft nephropathy. Concurrently recorded serum C0 and C2 levels were present for only 21 patients. Overall, we evaluated the records of 245 visits for these 21 patients. The incidence of hyperlipidemia decreased in the late posttransplant period, being significant for hypercholesterolemia. C2 had strong negative correlation with serum lipids; it was significant for total cholesterol in the early posttransplant period (r=-0.542, P=.005), but weaker in the late posttransplant and whole posttransplant periods. Thus correlation of C2 with serum lipids showed differences during posttransplant follow-up. C0, on the other hand, was positively correlated with total cholesterol levels in all periods, being significant for the whole posttransplant period (r=0.293, P=.000) and for the late posttransplant period (r=0.196, P=.025). Although not statistically significant, C0 levels were higher among hypertriglyceridemic or hypercholesterolemic episodes both in the early and the late posttransplant periods. When only the C0 levels of all 25 patients were analyzed (789 visits), C0 and serum cholesterol levels were positively correlated both in the early and the late posttransplant periods (P=.013, r=0.198 and P=.000, r=0.177, respectively). We concluded that C0 has a more predictable correlation with serum cholesterol levels after renal transplantation in adolescent patients.