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.     

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.     

Effect of a soy protein diet on serum lipids of renal transplant patients.

OBJECTIVE: The aim of the present study was to evaluate the effect of a soy-protein diet on plasma lipid levels of renal transplant recipients with moderate hypercholesterolemia. DESIGN: Dietary intervention case-control observational study. SETTING: Renal transplantation outpatient clinic. PATIENTS: Fifteen stable patients who had renal transplantation (serum creatinine < 2 mg/dL) with moderate hypercholesterolemia (low-density lipoprotein [LDL] cholesterol > 140 mg/dL). INTERVENTION: After a baseline dietary interview, dietary counseling was given individually with the goal of substituting 25 g of animal protein with 25 g of soy protein for a 5-week period, using commercially available soy foods, according to each patient's own preference.Main outcome measures Before and after the soy-diet period, plasma lipid profiles including total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1 and B were determined. Protein catabolic rate was assumed as a measure of dietary protein intake. RESULTS: Two patients dropped out. After the soy diet, total cholesterol (254 +/- 22 to 231 +/- 31 mg/dL, P <.05) and LDL cholesterol (165 +/- 20 versus 143 +/- 20 mg/dL, P <.01) decreased significantly. No significant changes were observed regarding HDL cholesterol and triglycerides. Dietary protein intake did not differ at baseline (73.2 +/- 22.9 g/day) and during the soy diet (72.6 +/- 15.6 g/day), when the reported actual soy protein intake resulted 26 +/- 8 g/day. CONCLUSIONS: This study shows that soy proteins given as part of the daily protein intake have beneficial effects on serum LDL cholesterol levels of renal transplant recipients with moderate hypercholesterolemia. Soy proteins could be of use in the nutritional management of renal transplant recipients.     

肾移植患者的血脂改变

目的 研究肾移植患者的血脂变化。方法 对上海市8家医院174例肾移植的资料进行调查分析。结果 与正常对照组相比，肾移植患者术前血胆固醇（Tch)、低密度脂蛋白胆固醇（LDL－ch)显著增高，血甘油三酯（TG）、高密度脂蛋白胆固醇（HDL－ch)、极低密度脂蛋白胆固醇（VLDL－ch)与正常对照组的差异无显著性；载脂蛋白Al(Apo A1)及卵磷脂胆固醇酰基转移酶（LCAT）均低于正常对照组，脂蛋白（a)[Lp(a)]的水平显著高于正常对照组；肾移植患者手术前后上述各指标的变化不显著。结论 肾移植患者脂质紊乱相当常见，应高度重视。     

The impact of functioning pancreas–kidney transplantation and pancreas alone transplantation on the lipid metabolism of statin‐naïve diabetic patients

Abstract: Objective: To compare the lipid profile (total cholesterol – TC, triglycerides – TG, high density lipoprotein cholesterol – HDL‐c, low density lipoprotein cholesterol – LDL‐c and non‐HDL cholesterol – NHDL‐c) of patients with functioning pancreas–kidney transplantation (PKT) or pancreas transplantation alone (PTA) after one (T1) and two yr (T2) following their pre‐transplantation data (T0). Methods: Fifty‐three type 1 diabetic patients underwent pancreas transplantation (42 PKT and 11 PTA) remaining euglycemic after transplantation were evaluated before and one and two yr after the procedures. They were using predominantly tacrolimus‐mycophenolate mofetil‐based immunosuppression and low glucocorticoid dose with systemic venous drainage of the pancreatic graft. None of them used hypolipidemic agents for economical reasons. Lipids were reported as means ± standard error of the mean. Data obtained in T0 were compared with T1 and T2 using ANOVA followed by Student’s t‐test. Results: TC, LDL‐c, NHDL‐c and TG were lower in T1 and T2 when compared with T0 (p < 0.05) in PKT, while no change was observed for HDL‐c (p > 0.05). PTA group showed no significant changes in lipids. Conclusion: In spite of the known side effects of tacrolimus‐based immunosuppression to lipids, our study with a statin‐naïve sample showed improvements (PKT) or stabilization (PTA) in the serum lipid profile after pancreas transplantation.     

Effects of immunosuppressive drugs on serum lipid levels in renal transplant recipients

BACKGROUND: Hyperlipidemia is an important metabolic disorder that is common among renal transplant recipients. This study investigated the possible effects of transplantation and immunosuppressive drugs on lipid profiles in this patient group. METHODS: We retrospectively evaluated the records of 179 patients who underwent renal transplantation between 1996 and 2000, recording lipid profile findings-total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), and triglyceride (TG)-before and at least 6 months after transplantation. We also recorded patient demographics, underlying renal disorder, and immunosuppressive drug regimens. RESULTS: Sixty-nine (38.5%) patients were women and 110 men (61.5%). The mean age (+/- SD) of the 179 recipients was 35.7 +/- 11.8 years (range, 11 to 62 years). The respective pre- versus posttransplantation lipid profile findings were: TC, 171.6 +/- 42.4 mg/dL versus 204.7 +/- 45.3 mg/dL, P < .001; LDLc, 114.5 +/- 34.5 mg/dL versus 142.2 +/- 39.7 mg/dL, P < .001; HDLc, 46.7 +/- 13.6 mg/dL versus 42.5 +/- 12.3 mg/dL, P = .001; TG, 142.9 +/- 55.7 mg/dL versus 178.8 +/- 71.8 mg/dL, P < .001. Increased lipid levels were found to be independent of patient age, sex, donor type, and immunosuppressive drug regimen. CONCLUSION: The results suggested that antihyperlipidemic drugs should be administered routinely to renal transplant recipients irrespective of the immunosuppressive drug regimen or graft source.     

Serum lipid pattern unifies following renal transplantation in children

Hyperlipidemia is a common problem in solid organ transplant recipients. In this study we evaluated the role of pre-transplant renal replacement therapy on early and late changes of serum lipid levels in children following renal transplantation. In 46 children with chronic renal failure (median age 10.3 years) and 12 children with heart failure (median age 5.0 years), cholesterol and triglycerides were measured before and during follow-up after transplantation. Children with renal failure had significantly higher serum lipids than controls (n=34, median age 9.2 years) and patients with heart failure. Pre transplantation, cholesterol and triglycerides were significantly lower in the hemodialysis than in the peritoneal dialysis population, whereas conservatively treated children had intermediate levels. After transplantation, serum cholesterol converged towards a mean level of 208 mg/dl and triglyceride levels converged towards a uniform level of 195 mg/dl at 9 months post transplant. The ratio of cholesterol/high-density lipoprotein significantly decreased from 4.7 to 3.8. The pattern of "post-transplant hyperlipidemia" was similar in both renal and cardiac allograft recipients. Hence, the early post-transplant changes of serum lipid pattern are markedly dependent on the mode of pre-transplant renal replacement therapy. Later, serum lipid levels were no longer influenced by prior renal replacement therapy and showed a new pattern of "post-transplant hyperlipidemia" in all children.     

Changed composition of high-density lipoprotein subclasses HDL2 and HDL3 after renal transplantation

The concentrations of cholesterol in the high density lipoprotein (HDL) fraction and the HDL2 and HDL3 subclasses were compared in 333 male renal transplant recipients, 36 male patients on maintenance hemodialysis, and 43 healthy men. The subclasses were separated by a precipitation method using polyethylene glycol 6000 and dextran sulphate. In hemodialyzed patients, total HDL cholesterol and both subclasses were reduced. In renal transplant recipients, both total HDL cholesterol and HDL2 were normal, whereas HDL3 remained reduced, analogous to hemodialyzed patients. It can be concluded that a successful renal transplantation has a beneficial effect on HDL metabolism and thus on the development of atherosclerosis.     

Lipid abnormalities in stable liver transplant recipients – effects of cyclosporin, tacrolimus, and steroids

Dyslipidemia is common after liver transplantation, but the underlying mechanisms are largely unknown. We studied the lipid profile of 27 liver transplant recipients randomized to receive either cyclosporin (CyA, n = 14) or tacrolimus (n = 13) and compared them with 20 healthy, matched controls. Before transplantation, patients presented low total and low-density lipoprotein (LDL) cholesterol (as compared to controls) that increased shortly, i. e., 3 months, after transplantation. Eighteen months post-transplantation, total and LDL cholesterol levels decreased to pretransplant values but tended to remain higher in CyA-treated patients. However, at that time, prednisone treatment was more prevalent among CyA-treated than tacrolimus-treated patients and fully accounted for the difference in cholesterol levels. Indeed, regardless of therapy, patients not receiving prednisone exhibited lower cholesterol levels than prednisone-treated patients and controls. We conclude that prednisone therapy, rather than CyA or tacrolimus immunosuppression, seems to be the major determinant of increased cholesterol levels. Received: 19 June 1997 Received after revision: 24 October 1997 Accepted: 10 November 1997     

Cell cholesterol transport to plasma in blood from patients with renal failure or a kidney transplant

Accumulation and distribution of cell cholesterol in plasmalipoproteins of incubated blood was examined in 36 patientswith chronic renal failure including 13 who were dialysis-independent,12 on haemodialysis, and 11 on continuous ambulatory peritonealdialysis (CAPD), 17 renal transplant recipients, and 8 healthycontrols. In addition, transport of cholesterol between redblood cells and high-density lipoprotein subfraction 3 (HDL₃isolated from a subgroup of patients with chronic renal failurewas determined. Significantly less cell cholesterol appearedin plasma (P<0.002) and HDL (P=0.03), the main recipientof cell cholesterol, in patients with chronic renal failurecompared with healthy subjects. Corresponding values in bloodfrom renal transplant recipients were similar to controls. Inpatients with chronic renal failure, plasma HDL₃ cholesterollevels (P<0.02), HDL₃ phospholipid content (P<0.01) andnet transport of red cell cholesterol to isolated HDL₃ (P<0.001)were significantly lower compared with controls. The data suggestthat in patients with chronic renal failure, low levels of plasmaHDL₃ of abnormal composition may restrict the incorporationof cell cholesterol into the antiatherogenic HDL fraction potentiallyleading to inefficient transport of cholesterol from peripheraltissues and the development of atherosclerosis. These abnormalitiesappear to be reversed by renal transplantation.     

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.     

Cardiovascular risk profile after conversion from cyclosporine A to tacrolimus in stable renal transplant recipients

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in renal recipients. In addition to steroids, cyclosporine A (CsA) has been implicated in contributing to increased cardiovascular risk. Conversion from CsA to tacrolimus (TAC) has been shown to improve hyperlipidemia and hypertension, but little is known about the differential effects of CsA versus TAC on other cardiovascular risk factors. We investigated overall cardiovascular risk profile after conversion from CsA to TAC. METHODS: This was an open-label, single-arm prospective study; 22 adult renal recipients who were receiving CsA-based immunosuppression with serum total cholesterol greater than 200 mg/dL more than 1 year after transplantation were enrolled. CsA was replaced by TAC. Blood pressure, fasting lipid profile, homocysteine, fibrinogen, C-reactive protein, hemoglobin A1c, and creatinine were measured at baseline and at 3 and 6 months after conversion. RESULTS: There was a significant improvement in fibrinogen (366 +/- 81 - 316 +/- 65 mg/dL, P <0.001), total cholesterol (250 +/- 50 - 207 +/- 29 mg/dL, P <0.001), and low-density lipoprotein cholesterol (155 +/- 43 - 121 +/- 24 mg/dL, P <0.001) after conversion. No new onset or worsening of diabetes mellitus was observed after conversion. There were no significant differences in HDL cholesterol, triglycerides, homocysteine, C-reactive protein, hemoglobin A1c levels, serum creatinine, mean blood pressure, and mean number of antihypertensive medications required before and after conversion. CONCLUSIONS: Our results indicate that conversion to low-dose TAC may be preferable over CsA for chronic maintenance immunosuppression because it improves the overall cardiovascular risk profile without any apparent adverse effects.     

Efficacy and safety of atorvastatin after pediatric heart transplantation.

BACKGROUND: Lipid abnormalities are prevalent after pediatric and adult heart transplantation. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are efficacious and safe and can lower the incidence of graft coronary artery disease after heart transplantation in adults. Given the high prevalence of lipid abnormalities and the increased recognition of graft coronary disease in children, we retrospectively investigated the efficacy and safety of atorvastatin among pediatric heart transplant recipients. METHODS: Thirty-eight patients were started on atorvastatin 48.2 +/- 54.4 months after transplantation. Atorvastatin dosage was 0.2 +/- 0.1 mg/kg per day. No patient had changes in drug dose unless there was evidence for rhabdomyolysis, myositis or an asymptomatic rise in creatine kinase above normal. Laboratory studies included total cholesterol, triglycerides; high, low and very low-density lipoproteins (HDL, LDL and VLDL, respectively); creatine kinase; creatine; and serum alanine transaminase. RESULTS: Significant declines in total cholesterol (20%), triglyceride (18%) and LDL (26%) were observed after starting atorvastatin therapy. There were no significant changes in HDL or VLDL compared with baseline. There were also no differences in alanine transaminase pre- vs post-atorvastatin therapy. Complications included muscle pain (n = 2) and asymptomatic elevations in creatine kinase (n = 2). Two of these 4 patients developed rhabdomyolysis. Excluding these 4 patients, creatine kinase did not rise compared with baseline. No patient developed alterations in renal function. CONCLUSIONS: Use of atorvastatin in pediatric heart transplant recipients is effective in lowering total cholesterol, triglyceride and LDL without altering HDL levels. Complications included rhabdomyolysis, seen in 5%. Baseline and routine screening of creatine kinase should be employed in all pediatric patients undergoing HMG-CoA reductase inhibitor therapy.     

Lipid and apolipoprotein profiles of uremic dyslipoproteinemia--relation to renal function and dialysis

To study the effect of renal function on the development of lipid and apolipoprotein abnormalities in human renal disease, we have investigated 75 patients at different stages of renal insufficiency. The patient population consisted of 19 patients with less advanced renal failure (CRF:1) characterized by a mean glomerular filtration rate (GFR) of 37.4 +/- 14 ml/min, 31 patients with advanced renal failure (CRF:2) having a mean GFR value of 7.9 +/- 7.3 ml/min and 25 patients on maintenance hemodialysis (CRF:HD). Patients in the CRF:1 group had normal plasma triglyceride (TG) and total cholesterol (TC) levels. In the CRF:2 and CRF:HD group, TG levels were increased two- to threefold, together with a moderate elevation of TC levels. All patient groups had elevated levels of VLDL cholesterol and slightly decreased levels of HDL cholesterol. The apolipoprotein profile of all patient groups was characterized by significantly reduced levels of apolipoprotein (Apo)A-I and ApoA-II and significantly increased levels of ApoC-III. CRF:2 and CRF:HD patients had also moderately elevated levels of ApoB, ApoC-I and ApoC-II. Levels of ApoE were only elevated in CRF:HD patients. All patients, regardless of TG levels, had significantly lower ApoA-I/ApoC-III ratios than controls. GFR was positively correlated with ApoA-I and inversely correlated with TC, TG and ApoC-III. CRF:HD patients had slightly higher ApoA-I and ApoA-II and lower ApoB levels compared to CRF:2 patients. Patients with vascular disease had higher TC, TG, ApoB, ApoC-II and ApoE than patients without vascular disease. These results demonstrate that the dyslipoproteinemia with CRF is already manifested at the early stages of disease through its abnormal apolipoprotein rather than lipid profile.     

Low-Density Lipoprotein Oxidizability and the Alteration of Its Fatty Acid Content in Renal Transplant Recipients Treated With Cyclosporine/Tacrolimus

Renal transplantation is widely used to treat patients with end-stage renal disease. Atherosclerosis is an important posttransplantation risk factor for renal transplant recipients. Subsequent to transplantation low-density lipoprotein (LDL) particles become susceptible to oxidative modification, which results in atherosclerosis. Therefore, the aim of our study was to investigate differences in the susceptibility of LDL particles to oxidation by analyzing LDL fatty acid levels among renal transplant recipients. The changes in lag phases and fatty acid levels of LDL were observed over 4 months among renal transplant recipients treated with Cyclosporine (CsA; n = 7) or Tacrolimus (FK-506; n = 9). We also analyzed cholesterol and triglyceride levels of patients and healthy controls. The lag phase at the 60th day after transplantation was significantly shorter than the results either before transplantation or among control subjects. In conclusion, a similar decrease in lag phase was observed in both above groups, but the FK-506-treated group showed a better lipid profile than the CsA-treated group.     

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.     

High-density lipoprotein cholesterol subfractions in chronic uremia

Cholesterol content in high-density lipoprotein (HDL) subfractions has been studied in 108 patients at different evolutive stages of chronic renal failure (CRF) under conservative treatment. Results have been compared with healthy control subjects, patients receiving hemodialysis, and renal graft recipients. Significant low levels of total HDL and HDL2 cholesterol are observed in men with CRF. The more severe the CRF, the more likely that total HDL and HDL2 cholesterol will be low. Moreover, a significant inverse correlation is found between HDL2 cholesterol and serum creatinine levels. In women, although a decrease in total and HDL2 subfraction is observed, no significant differences are found across the severity of CRF. Serum HDL2 cholesterol levels are decreased in men and women receiving hemodialysis, while raised total HDL and HDL2 cholesterol levels are observed in normally functioning renal grafts. These results indicate that according to the "HDL hypothesis," despite other associated risk factors, the high cardiovascular mortality rates noted mainly in men with CRF under conservative treatment and in patients receiving hemodialysis could be explained, at least in part, by the sustained and progressive decrease in total HDL and HDL2 values. From this point of view, our study suggests the need to promote early kidney transplantation.     

Effect of fluvastatin on acute renal allograft rejection: a randomized multicenter trial.

BACKGROUND: Statin therapy has been reported to reduce the acute rejection rate following renal transplantation in a pilot study. The present study is the first randomized, double-blind and adequately powered study to examine the effect of statins on acute rejection of renal allografts. METHODS: A total of 364 patients were randomly assigned to receive either fluvastatin 40 mg or placebo in combination with conventional cyclosporine-based immunosuppressive therapy. The primary end point was treated first acute rejection. Secondary end points included biopsy-proven rejection, histological severity of rejection, occurrence of steroid-resistant rejection, and serum creatinine at three months following transplantation. RESULTS: Fluvastatin was well tolerated; no patients developed myositis or rhabdomyolysis. There was no difference in the acute rejection rate [86 (47.3%) fluvastatin vs. 87 (47.8%) placebo] and no significant difference in the severity of rejection, steroid resistant rejection or mean serum creatinine at three months (160 micromol/L vs. 160 micromol/L). Total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglyceride levels increased following renal transplantation. With the exception of the increase in HDL-C, which was augmented, the increases in lipid parameters were significantly reduced by fluvastatin (total cholesterol +17.5% vs. 35.7%; LDL-C +6.3% vs. 46.7%; HDL-C +43.3% vs. 38.1%; triglyceride +52.2% vs 77.6%). CONCLUSIONS: Contrary to the reported effects of statins, fluvastatin had no effect on the incidence or severity of acute rejection following renal transplantation. There were no increases in adverse events. A significant and potentially beneficial alteration in the lipid profile was observed in the early post transplant period. We conclude that fluvastatin may be used safely to correct dyslipidemia in patients with end-stage renal failure through the peri-transplant period.     

Altered flow properties of blood and increased plasma fibrinogen in cyclosporin-treated renal allograft recipients.

BACKGROUND: Abnormalities in blood rheology may be factors contributing to cardiovascular complications and the progression of renal failure in kidney allograft recipients. The haemorheological variables haematocrit, fibrinogen, whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency and fluidity were measured in 27 cyclosporin A (CyA)-treated patients who had received a renal graft at least 6 months previously. Their creatinine clearance was in the range of 12-92 ml/min/1.73 m2 (mean 55+/-19). The values were compared with those obtained from a control group comprising 20 healthy subjects matched according to age, sex and smoking habits. RESULTS: The haematocrit, plasma fibrinogen, whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency, body mass index (BMI), mean arterial pressure (MAP) and serum triglycerides were increased in the transplanted patients, and the serum high density lipoprotein (HDL)-cholesterol and erythrocyte fluidity decreased. The haemorheological variables were used as dependent variables in a stepwise regression analysis with age, MAP, BMI, urinary albumin excretion rate, blood CyA concentration, creatinine clearance, and serum triglycerides, cholesterol and HDL-cholesterol as independent variables. Plasma fibrinogen was positively correlated with BMI and blood CyA. The whole blood viscosity was positively correlated with blood CyA and negatively with serum HDL-cholesterol. Only serum triglycerides remained correlated with erythrocyte aggregation tendency. CONCLUSIONS: All variables with a known impact on blood viscosity were altered in the present group of renal transplant recipients. Inappropriate regulation of erythrocyte formation, overweight, the use of CyA, high triglycerides and low HDL-cholesterol levels may be factors contributing to this. The importance of impaired flow properties of blood for the development of cardiovascular diseases and transplant glomerulosclerosis needs to be examined.     

Lipid and lipoprotein (a) concentrations in renal transplant patients.

Lipid and lipoprotein concentrations, including lipoprotein (a), were measured in 67 clinically stable renal allograft recipients and compared with age- and sex-matched controls. Median lipoprotein (a) concentrations were significantly elevated in the transplant group (P = 0.048), with the distribution of apoprotein (a) isoforms being similar between the two groups. The transplant group also demonstrated significant elevations in cholesterol (P less than 0.0001), triglycerides (P = 0.0007) and low-density lipoprotein cholesterol (P less than 0.0001). There was no significant difference in high-density lipoprotein cholesterol concentrations between the groups although there was the expected tendency for higher values in females. Lipoprotein abnormalities are common following renal transplantation and these patients also demonstrate elevated lipoprotein (a) values. This unique lipoprotein is known to be atherogenic and may contribute to the development of vascular disease, which is a common mode of death in these patients.