Reduction of left ventricular diameter and mass after surgical arteriovenous fistula closure in renal transplant recipients

BACKGROUND: Left ventricular hypertrophy and dilatation is a frequent finding in kidney transplant recipients, which may be favored by the persistent patency of arteriovenous fistula. The purpose of the current study was to prospectively investigate whether surgical closure of the fistula allows reduction of abnormalities of left ventricular morphology in stable renal transplant patients. Furthermore, we studied the ability of preoperative echocardiographic and noninvasive hemodynamic measurements, including the effects of a temporary occlusion of the fistula, to predict postoperative left ventricular diameter and mass reduction. METHODS: Seventeen kidney transplant recipients referred for surgical arteriovenous fistula closure were prospectively studied. Standard echocardiographic parameters, heart rate, and blood pressure were assessed preoperatively at baseline and during an acute pneumatic fistula occlusion. These measurements were repeated 3 to 10 weeks after surgical closure. Six kidney transplant recipients with patent arteriovenous fistulas referred for routine echocardiographic follow-up served as a control group. RESULTS: Surgical fistula closure decreased left ventricular end-diastolic diameter and mass indexes (29.9+/-2.4 to 27.4+/-2.1 mm/m2, P<0.001, and 141+/-37 to 132+/-39 g/m2, P<0.05, respectively), whereas no changes were seen in controls after a similar delay. Postoperative left ventricular end-diastolic diameter and mass reductions correlated best with the increases in total peripheral resistance (r=0.85, P<0.0001) and mean arterial blood pressure (r=0.64, P=0.006) during pneumatic occlusion, respectively. CONCLUSIONS: Surgical closure of arteriovenous fistula reduces left ventricular diameter and mass in kidney transplant recipients. Increases in blood pressure and total peripheral resistance induced by temporary fistula occlusion are the best predictors of these morphological changes.     

Carotid atheromatosis in nondiabetic renal transplant recipients: the role of prediabetic glucose homeostasis alterations

BACKGROUND: Prediabetic glucose homeostasis alterations are important cardiovascular risk factors but their role in renal transplant recipients (RTR) has not been established. METHODS: In 172 RTRs without pretransplant or de novo diabetes, we measured carotid intima media thickness (c-IMT) and performed an oral glucose tolerance test (OGTT). RESULTS: In multivariate analysis, age, hypertension and male sex were independently associated with a c-IMT in the third tertile. A significant interaction between gender and glucose homeostasis parameters was observed. Among male RTR, those with a c-IMT in the third tertile showed significantly higher plasma glucose and HbA1c levels (5+/-0.5% vs. 5.1+/-0.5% vs. 5.5+/-0.4%; P<0.01 tertile 3 vs. 2 or 1) than those in other tertiles. Insulin action parameters were not significantly different. The odds ratio of being in the higher c-IMT tertile was 2.9 (95% CI: 1.05-8.1) per each 1% increase of HbA1c. By contrast, glucose and HbA1c levels were not significantly different between c-IMT tertiles in female RTR. However, age-adjusted insulin levels after OGTT were higher (86+/-10 vs. 51.7+/-9.4; P=0.02) and the insulin sensitivity index lower (0.8+/-0.3 vs. 0.048+/-0.03; P=0.04) among females in the third tertile as compared to the first one. CONCLUSION: Prediabetic glucose homeostasis alterations in RTRs are related to carotid atherosclerosis, although there may be gender differences in the underlying alteration.     

Reduction of left ventricular mass by lisinopril and nifedipine in hypertensive renal transplant recipients: a prospective randomized double-blind study

BACKGROUND: Cardiovascular disease is the dominant cause of death in renal transplant recipients. Left ventricular hypertrophy (LVH) is a known risk factor. After renal transplantation, persistent hypertension is an important determinant for the further evolution of LVH. The aim of the present study was to compare the effect of an angiotensin converting enzyme (ACE) inhibitor (lisinopril) with a calcium channel blocker (CCB) (controlled release nifedipine) in treatment of posttransplant hypertension focusing on changes in LVH. METHODS: One hundred fifty-four renal transplant recipients presenting with hypertension (diastolic BP> or =95 mmHg) during the first 3 weeks after transplantation were randomized to receive double-blind 30 mg nifedipine or 10 mg lisinopril once daily. RESULTS: One hundred twenty-three patients completed 1 year of treatment. Good quality echocardiographic data were available in 116 recipients (62 nifedipine/54 lisinopril) 2 and 12 months posttransplant. Blood pressure was equally well controlled in the two groups throughout the study (mean systolic/diastolic+/-SD after 1 year: 140+/-16/87+/-8 mmHg with nifedipine and 136+/-17/85+/-8 mmHg with lisinopril). Left ventricular mass index was reduced by 15% (P<0.001) in both groups (from 153+/-43 to 131+/-38 g/m2 with nifedipine and from 142+/-35 to 121+/-34 g/m2 with lisinopril). There were no statistically significant differences between the two treatment groups at baseline or at follow-up. CONCLUSIONS: In hypertensive renal transplant recipients with well-controlled blood pressure, there is a regression of left ventricular mass after renal transplantation. The regression of left ventricular mass index is observed to a similar extent in patients treated with lisinopril or nifedipine.     

Sirolimus interferes with iron homeostasis in renal transplant recipients

BACKGROUND: Sirolimus is an immunosuppressive drug whose use is frequently associated with anemia. A pathogenic link between sirolimus-induced anemia and the appearance of an inflammatory state was recently suggested. Because inflammation-related anemia is characterized by a functional iron deficiency, we investigated whether sirolimus may influence iron homeostasis and serum levels of hepcidin, a key mediator of inflammation-related anemia. METHODS: To this purpose, 42 consecutive transplanted patients with biopsy-proven chronic allograft nephropathy were randomized (2:1 ratio) to receive either a 40% cyclosporine reduction (group A, 14 patients) or immediate cyclosporine withdrawal and sirolimus introduction (group B, 28 patients). Hemoglobin levels and iron status were evaluated 6 months before and after randomization. RESULTS: The two groups had similar hemoglobin levels and iron status at baseline. We did not observe any significant change in hemoglobin and iron status in group A patients after randomization. On the contrary, we observed a significant reduction of hemoglobin without any change of red blood cell count after sirolimus introduction, with a significant reduction of mean corpuscular volume and mean corpuscular hemoglobin. Serum iron and transferrin saturation (TSAT) levels were markedly reduced after the switch, while ferritin serum concentrations remained stable. Although sirolimus-induced anemia was recently suggested to resemble inflammation-related anemia, hepcidin serum levels were similar in the two groups after randomization. None of group A and eight of group B patients presented a TSAT <20 and were given iron supplementation after randomization, in all of them oral iron therapy did not influence either hemoglobin or serum iron levels. CONCLUSION: We demonstrated that sirolimus-induced anemia is independent of the drug antiproliferative effect and does not present the features of inflammation-related anemia. This event may be due to the direct influence of sirolimus on iron homeostasis.     

Treatment of hyperhomocysteinemia with folic acid reduces oxidative stress in renal transplant recipients

BACKGROUND: We conducted a prospective, uncontrolled, open study to assess the relationship between homocysteine (tHcy) and oxidative stress in chronic, stable, renal transplant recipients (RTR). METHODS: Included in the study were 17 chronic, stable RTR. All the patients received folic acid (5 mg/day). tHcy and total antioxidant capacity (TAOC) were measured before and at the end of the study period. RESULTS: Mean tHcy concentration was 26+/-10 micromol/L. tHcy significantly decreased during the study period (26+/-10 vs. 18+/-7 micromol/L; P<0.001). There was a significant inverse relationship between TAOC and tHcy (r= -0.33; P=0.01). TAOC significantly increased during the study period (1.49+/-0.23-1.78+/-0.6; P<0.001). There was an inverse relationship between the variation in tHcy and the variation in TAOC (r= -0.44; P=0.01). CONCLUSION: Our results demonstrate that hyperhomocysteinemia contributed to increased oxidative stress in RTR. tHcy-lowering treatment with folic acid may lower oxidative stress.     

Electrocardiographic left ventricular hypertrophy in renal transplant recipients: prognostic value and impact of blood pressure and anemia

Left ventricular hypertrophy (LVH) is an independent risk factor for death and cardiovascular disease in the general population and dialysis patients. However, the causes and consequences of LVH have not been well described in renal transplant recipients (RTR). A retrolective cohort study was conducted in 473 RTR who were alive and free of cardiac disease at 1 yr. LVH was defined using the Cornell electrocardiographic (EKG) criteria. A total of 416 patients had an interpretable first-year EKG (88%), and 284 had an interpretable fifth-year EKG (78% of 5-yr survivors). Baseline characteristics were similar in patients with and without EKG. Of 416 patients, 57 had LVH in the first year, whereas 38 of 284 patients had LVH in the fifth year, of which 18 cases were de novo. Baseline LVH was a risk factor for death (RR 1.9 [1.22, 3.22]) and congestive heart failure (CHF) (RR 2.27 [1.08, 4.81]) and was independent of other major prognostic variables. Persistent or de novo LVH in the fifth year predicted subsequent death (RR 2.15 [1.14,4.01]) and CHF (2.71 [1.17, 6.30]). Anemia and diastolic BP were independent risk factors for increasing Cornell voltage (a marker of LV mass) between first and fifth years. Systolic BP was the only predictor of de novo LVH at 5 yr. It seems that EKG LVH is a significant risk factor for death and CHF in RTR and that anemia and hypertension are risk factors for LV growth. Whether aggressive treatment of hypertension and anemia can improve outcomes merits further study.     

三维斑点追踪成像技术定量评价肾移植受者术后左心室整体应变

目的  探讨采用三维斑点追踪成像（3D-STI）技术定量评价肾移植受者术后3个月内左心室整体应变的应用价值。方法  选取34例肾移植受者,分别于术前、术后7 d、术后1个月、术后3个月收集受者的血压、血清肌酐和他克莫司血药浓度等资料,同时对受者行常规超声心动图和3D-STI检查,收集受者超声心动图检查参数[左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVESV）、左心室射血分数（LVEF）]和3D-STI检查参数[左心室整体纵向峰值应变（GPLS）、整体圆周峰值应变（GPCS）、整体径向峰值应变（GPRS）及整体面积峰值应变（GPAS）]。比较受者术前、术后7 d、术后1个月、术后3个月上述指标的变化,分析应用3D-STI技术定量评价肾移植受者术后3个月内左心室整体应变的变化特点及其应用价值。结果  肾移植受者术前至术后3个月内各时间点间LVEF和GPCS比较,差异均无统计学意义（均为P > 0.05）。术前至术后3个月内各时间点间LVEDV、LVESV、GPLS、GPAS和GPRS比较,差异均有统计学意义（均为P < 0.001）。GPLS、GPAS、GPRS在术后1个月内呈连续下降趋势,术后3个月有所上升但仍低于术前水平。结论  应用3D-STI技术能够敏感地发现肾移植受者术后LVEF未见明显改变时左心室整体应变的改变,与常规超声心动图比较,3D-STI可以更准确地评价肾移植受者术后左心室整体应变的变化特点。     

Random blood glucose measurements and survival in nondiabetic renal transplant recipients

New-onset diabetes after renal transplantation (PTDM), a common consequence of immunosuppression, is associated with reduced patient survival. However, we know little about the impact of less marked changes in glucose homeostasis. To investigate this problem, we used data on average random blood glucose values during the first, second, and third months posttransplantation, derived from a cohort of 1186 patients who received their first cadaveric or living-donor transplant between 1984 and 2002. We analyzed both patient and death-censored graft survivals, subgrouping recipients into those with end-stage renal failure due to diabetic nephropathy versus those with PTDM versus patients without diabetes. We confirmed that PTDM patients display reduced survival following transplantation, but a long-term survival similar to that of patients with diabetic nephropathy and end-stage renal disease. However, among patients without diabetes, random blood glucose was also a strong determinant of outcome, even when in the low normal range. In contrast, neither the presence of diabetes nor random glucose levels showed a significant impact on graft survival. PTDM is recognized to be an important, potentially modifiable, risk factor for cardiovascular disease in transplant recipients. Our data suggest that there is a gradation of increased risk associated with impaired glycemic control that affects patients who do not have diabetes. These data support the need for improved understanding of glycemic control in transplant recipients and for more detailed screening for impaired glucose tolerance in this population.     

Impaired glucose oxidation and glucose-induced thermogenesis in renal transplant recipients.

BACKGROUND: Renal transplant recipients often show various metabolic abnormalities including reduced glucose tolerance, impaired insulin sensitivity and altered lipid metabolism. However, the acute effects of carbohydrate ingestion on substrate utilization and energy expenditure have not been fully elucidated. METHODS: We evaluated: (i) basal energy expenditure (EE) and substrate utilization, (ii) metabolic fate of an oral glucose load, and (iii) substrate-induced thermogenesis in: (a) 15 non-diabetic renal transplant recipients (Tx) (BMI 25+/-1) on triple immunosuppressive therapy, (b) 11 patients with primary glomerulonephritis (BMI 25+/-1) (Cort) receiving prednisone treatment, and (c) 12 healthy subjects (BMI 26+/-1) (N). Continuous indirect calorimetry was performed in the basal post-absorptive state for 60 min and continued for an additional 180 min following an oral glucose load (75 g). RESULTS: In the basal state, EE was similar in the three study groups. It averaged 14.6+/-0.7, 15.7+/-1.3, and 14.1+/-0.8 cal/kg/min in Tx, Cort, and N respectively. Glucose oxidation was higher in N (1.3+/- 0.2 mg/kg/min) than in Tx (0.7+/-0.2) and Cort (1.0+/-0.2) (P<0.05 in N vs. Tx and vs. Cort), whereas lipid oxidation was lower in N (0.6+/-0.1 mg/kg/min) than in Tx (0.9+/-0.1) and Cort (0.9+/-0.05) (P<0.03 in N vs. Tx and vs. Cort). After glucose ingestion, total carbohydrate oxidation averaged 21.2+/-2, 31.0+/-3, and 29.6+/-3 g, which represented 28+/-3, 41+/-3 and 39+/-2% of the total glucose load in Tx, Cort and N respectively (P<0.01 Tx vs Cort and N). The cumulative increase of EE (180 min) was 9.7+/-2, 13.2+/-3 and 13+/-3 kcal in Tx, Cort, and N respectively. CONCLUSIONS: The present data show that in non-diabetic renal transplant recipients basal EE is normal. However, basal lipid oxidation is higher and glucose oxidation is lower than in healthy subjects. In addition, the oxidative disposal of a glucose load and substrate-induced thermogenesis are impaired.     

Echocardiographic evaluation of left ventricular filling pressure in heart transplant recipients

Objectives. Diastolic dysfunction is a major cause of morbidity in heart transplant recipients. A reliable, non-invasive marker of left ventricular (LV) filling pressure would simplify follow-up in these patients. We aimed to test the validity of echocardiographic indices of LV filling pressure in a contemporary population of heart transplant recipients. Design. Eighty-three patients were examined by right-sided heart catheterisation and echocardiography one year after heart transplantation. We explored the association between echocardiographic parameters of LV filling pressure and invasively measured pulmonary capillary wedge pressure (PCWP). Results. Peak early mitral flow velocity divided by septal early mitral relaxation velocity (E/e’_septal) was the echocardiographic parameter that best correlated with PCWP (r = 0.47; p < 0.001). At a cut-off value of 22, E/e’_septal could identify patients with a PCWP above 12 mm Hg with a sensitivity of 56% and a specificity of 95%. Conclusions. The E/e’ index was moderately associated with LV filling pressure in heart transplant recipients. Echocardiographic parameters of diastolic function should be interpreted with caution when estimating left ventricular filling pressures in this population.     

Correlation between oxidative stress and immunosuppressive therapy in renal transplant recipients with an uneventful postoperative course and stable renal function

Background Reactive oxygen species (ROS) are important mediators of cellular damage and lipid peroxidation is the most important expression of ROS-induced oxidative stress. Recent studies have suggested that increased plasma malondialdehyde (MDA) levels are a consequence of specific immunosuppressive therapies. This study aims at investigating the relation between oxidative stress and immunosuppressive therapies in renal transplant patients with stable renal function and uneventful postoperative course. Methods The study group included 26 renal patients. Two groups of renal transplant recipients, treated with a different combination of immunosuppressive agents were studied (Group A: CyA, MMF, Steroids and Basiliximab, Group B: Tacrolimus, MMF, Steroids and Daclizumab). All patients had an uneventful postoperative course. Plasma MDA levels were measured before transplantation, 1 and 6 months after. Plasma concentration of endogenous creatinine (Cr) was used as a measure of stable renal function. Results Levels of MDA were increased before the transplantation in all renal patients (MDA: 7.81 ± 4.81, normal levels: 2.23–4.08 nmol/ml, P < 0.05). Combined therapy with CyA was associated with high values of MDA at 6 months measurement after transplantation. However this tendency of increased MDA levels did not achieve a statistical significance (Group A: 6.97 vs. 9.06 nmol/ml, P>0.05). On the contrary, statistically significant diminution of MDA levels was observed in Group B patients (Tacrolimus–MMF–steroids) at 6 months measurement after transplantation. (Group B: 8.61 vs. 4.11 nmol/ml, P<0.02<0.05). Conclusions Immunosuppressive combined therapy with CyA was associated with the high values of MDA that were measured posttransplantly. Our study provides strong evidence that Tacrolimus is significantly associated with improved free radical metabolism.     

Urinary angiotensinogen level is increased in renal transplant recipients with masked hypertension and is correlated with left ventricular mass index and albuminuria in these patients

Activation of the local renin‐angiotensin system (RAS) is an independent risk factor for the development of proteinuria and left ventricular hypertrophy (LVH) more commonly seen in masked hypertensives. It has been reported that urinary angiotensinogen (UAGT) level provides a specific index of the intrarenal RAS status. The aim of this study was to evaluate the association between UAGT and left ventricular mass index (LVMI) and urinary albumin‐creatinine ratio (UACR) in renal transplant recipients (RTRs) with masked hypertension (HT). A total of 116 non‐diabetic‐treated hypertensive RTRs were included in this study. The patients were divided into two groups: masked hypertensives and controlled hypertensives. Forty‐two (36.2%) of RTRs had masked HT. Mean UACR and LVMI levels were higher in RTRs with masked HT than in RTRs with controlled HT (P < 0.001). UAGT level was also higher in masked hypertensives compared to controlled hypertensives (P < 0.001). Multivariable regression analysis showed that UAGT was positively correlated with UACR (β = 0.024, P = 0.001) and LVMI (β = 0.082, P = 0.001) in masked hypertensives. Consequently, masked HT was considerably frequent (36.2%) in treated hypertensive RTRs and high UAGT levels accompanied by high albuminuria and LVMI levels were seen in these patients. Overproduction of the UAGT may play a pivotal role in the development of LVH and proteinuria in masked hypertensives.     

Oxidative stress and coenzyme Q10 supplementation in renal transplant recipients

Recently some reports about the oxidative stress in renal transplant recipients have been published. The role of coenzyme Q10 (CoQ10) as radical scavanger is largely known. The aim of our study was to evaluate the protective role of CoQ10 in renal transplant recipients on lipid peroxidation and lipids parameters, as well as its influence on antioxidant enzymes, neutrophils chemiluminescence and urinary enzymes. The study was performed in 11 long term allograft recipients treated additionally with CoQ10 90 mg/day in three doses, 30 mg each for four weeks. The malonyldialdehyde (MDA) and 4-hydroxynonenal (4-HNE), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the basic parameters of lipid metabolism such as total cholesterol (TC), high and low density lipoproteins (HDL, LDL), triglycerides (TG), atherogenicity indicators [LDL/HDL; (TC-HDL)/HDL] were evaluated. The chemiluminescence of neutrophils (luminol, fLMP-method) were mesured and the activity of N-acetyl-beta-D-glucosaminidase (NAG), alanylaminopeptidase (AAP), elastase, alpha-1-antitrypsin. All parameters were estimated before and after CoQ10 treatment. Statistically significant changes were noticed with the LDL and atherogenicity indicators (p < 0.01) (decrease) as well as HDL level (p < 0.001) (increase). Also the significant decrease of fMLP stimulated PMNL chemiluminescence (p < 0.05) confirms the antioxidative properties of CoQ10. The significant increase of NAG activity (p < 0.05) can't be the result of nephrotoxic effect, because NAG-B is unchanged. Serum concentration of creatinine and cyclosporine A in renal allograft recipients was unchanged after CoQ10 treatment. The presented date shows that further study with CoQ10 treatment in renal transplant in larger numbers and over longer periods should be considered.     

Association between chronic periodontal disease and left ventricular hypertrophy in kidney transplant recipients

Periodontal disease (PD) may cause a systemic inflammatory reaction and contribute to left ventricular hypertrophy (LVH) in hypertensive subjects. This study aimed to assess whether chronic PD may contribute to LVH in patients after kidney transplantation. The study analyzed 99 patients divided according to Community Periodontal Index of Treatment Needs (CPITN) score into patients with advanced PD (CPITN 3-4) and patients without or with moderate periodontal lesions (CPITN 0-2). Patients with CPITN 3 to 4 were characterized by a significantly higher plasma high-sensitivity C-reactive protein (HS-CRP) concentration (6.2+/-2.2 vs. 1.7+/-0.3 mg/L, P<0.05) and left ventricular mass index (LVMI) (150+/-7 vs. 111+/-3 g/m, P<0.001) in comparison with patients with CPITN 0 to 2. In the multiple regression model, LVMI was dependent on CPITN (P<0.001), HS-CRP (P<0.05), serum cholesterol (P<0.05), and creatinine concentration (P<0.05). In conclusion, it appears that advanced PD in patients after kidney transplantation is associated with LVH.     

The influence of donor age on renal function in transplant recipients

To the extent that age-related declines in kidney function are caused by intrarenal alterations, donor age should affect glomerular filtration rate (GFR) after renal transplantation. Although some investigations have suggested that transplantation of aging kidneys may cause an increased incidence of primary allograft failure, the effects of donor age on GFR are unknown. In the present study, 201 patients who had allografts that survived for at least 24 months were investigated. The age range of the donors was 7 to 61 years. Multivariate regression analysis demonstrated that both donor and recipient age had significant, independent effects on creatinine clearance at 1 year, and at last follow-up, 5.0 +/- 1.9 years (mean +/- SD) after transplantation. The effect of donor age on renal function could not be attributed to differences in the number of rejection episodes, the frequency or duration of posttransplant acute tubular necrosis, age of the recipient, or other factors. Donor age had no effect on allograft survival, and did not affect the rate of decline in creatinine clearance between 1 year and last follow-up. Thus, these results suggest that donor age is associated with intrarenal alterations that lead to reductions in renal function after transplantation, but donor age may not affect long-term prognosis or allograft survival in the late posttransplant period.     

Homocysteine in renal transplant recipients: association with transplant duration and renal function

BACKGROUND: Hyperhomocystinemia is an established risk factor for cardiovascular events and has been identified as an important cause of morbidity and mortality in renal transplant recipients. This investigation was aimed to determine the effect of age and transplant duration on serum total homocysteine (tHcy) levels in renal transplant recipients. METHODS: We analyzed serum levels of tHcy, albumin, alkaline phosphatase, alanine transferase, bilirubin, calcium, corrected calcium, cholesterol, creatinine, folate, phosphate, potassium, sodium, triglycerides, urea and vitamin B12 in 88 transplant patients (ages, 14-67 years; transplant duration, 1-252 months) and 60 control subjects. RESULTS: Our results showed significant hyperhomocystinemia in transplant patients (19.92 +/- 0.72) as compared to controls (9.28 +/- 0.25), while male subjects in both groups had significantly higher tHcy than females. There was no correlation between patients' age and serum tHcy, whereas the time after transplantation was significantly correlated with tHcy (r=0.318, P<0.01). A significant correlation was observed between tHcy and serum urea, creatinine, vitamin B12 and potassium in renal transplant patients. CONCLUSION: This study clearly demonstrated significant hyperhomocystinemia and renal impairment in transplant recipients. A time-course increase in serum tHcy during posttransplant duration warrants long-term monitoring of patients for effective clinical management.     

Evolution pattern of auto-antibodies against oxidized low-density lipoproteins in renal transplant recipients

An increased degree of oxidative stress in renal transplant recipients and a possible role of ciclosporin A (Cs-A) immunosuppressive therapy in this process have already been described. However, prospective data using in vivo markers and the influence of Cs-A in the oxidizability of low-density lipoprotein (LDL) are scarce. We aimed at investigating in this prospective study the evolution pattern of auto-antibodies directed against malondialdehyde-modified LDL (MDA-LDL) and Cu2+-oxidized LDL in 28 stable renal transplant recipients on Cs-A immunosuppressive therapy before and after 3 successive years of renal transplantation. Also, the effect of enrichment of LDL with Cs-A on the susceptibility of LDL to in vitro oxidation was tested. The results showed a significant increase of both auto-antibody titres (MDA-LDL and Cu2+-oxidized LDL) after 1 year, and the values remained high during the 2nd and the 3rd year following transplantation. The yearly mean relative variations of auto-antibodies against MDA-LDL and Cu2+-oxidized LDL during the follow-up period were 133, 149, and 137%, and 111, 115, and 117%, respectively. A significant correlation was observed during the 1st year between Cs-A trough blood level and Cu2+-oxidized LDL auto-antibody: r = 0.04 (p = 0.046). Incorporation of Cs-A into LDL from healthy volunteers showed no changes during the lag phase in comparison with Cs-A-free LDL, indicating that Cs-A had no effect on in vitro LDL oxidizability. Our results suggest that Cs-A may be involved earlier in the LDL oxidation, but the mechanism by which it acts is still unclear.