Emöke Dimény

Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study.

Objective. There have been no endpoint studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance < 30 ml/min). Material and methods. The study subjects comprised 143 patients who were randomized either to placebo (controls; n=73; mean age 69.5 years) or to treatment with atorvastatin (n=70; mean age 67.9 years). The patients included were either non-dialysis (n=33), haemodialysis (n=97) or peritoneal dialysis (n=13) patients. Analysis focused on the primary endpoints of all-cause mortality, non-lethal acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Statistical analysis for endpoint data was mainly by intention-to-treat. Results. Primary endpoints occurred in 74% of the subjects. There was no difference in outcome between the control and atorvastatin groups. The 5-year endpoint-free survival rate from study entry was ≈20%. Atorvastatin was withdrawn in ≈20% of patients due to unacceptable side-effects. In the atorvastatin group, low-density lipoprotein (LDL) cholesterol was reduced by 35% at 1 month and then sustained. The controls showed a progressive reduction in LDL cholesterol until 36 months. Conclusions. Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival. In contrast to other patient groups, patients with severe chronic kidney disease, especially those on dialysis, seem to derive limited benefit from this lower dose of atorvastatin.

Safety and efficacy of atorvastatin in patients with severe renal dysfunction

Objective. To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. Material and methods. This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. Results. The follow-up period was a mean of 20±14.4 months (range 1–36 months) for those on atorvastatin versus 22±12.7 months (range 0.5–36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; −23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; −35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1–30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. Conclusion. Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Increased immunoreactivity of transforming growth factor-β in human kidney transplants

Transforming growth factor-beta (TGF-beta) has been known to be involved in the pathogenesis of various kidney diseases. TGF-beta is also a potent immunosuppressor that has been shown to be induced after allogeneic transplantation. We have studied the distribution of immunoreactive TGF-beta proteins in different compartments of 21 allogeneic transplanted kidneys that had been rejected through acute (eight interstitial or six vascular) and chronic (seven vascular) processes. This distribution was compared with that in seven non-rejected transplanted and five non-transplanted kidneys with intact morphology. There were no obvious differences between the three groups of rejected grafts and the transplanted non-rejected group for the expression of TGF-beta s. A major difference was seen between transplanted kidneys, which exhibited clearly positive TGF-beta and LTBP1 (latent TGF-beta binding protein) immunoreactivities, and the non-transplanted kidneys. The non-transplanted kidneys showed only very weak or no immunoreactivity for these proteins. The morphologically intact non-rejected grafts showed a significantly increased immunoreactivity compared with the non-transplanted kidneys. When the transplanted kidneys were classified into two groups (i.e. with or without diabetes mellitus) and compared with regard to the expression of all TGF-beta s, no difference was found. Thus, transplantation was the most important predictor for expression of TGF-beta s and LTBP1, and the largest expression increase in the allografts occurred in the interstitium, followed by the glomeruli and blood vessels. Tubuli and lymphocyte aggregates stained only faintly. The results imply that TGF-beta is induced rapidly after kidney transplantation. This induction can suppress immunoreactivation, but concomitantly promotes changes such as arteriosclerosis and fibrosis associated with rejection.

Serum Levels of Antibodies Against Oxidised LDL in Kidney Graft Recipients

Background/Aims: Lipid abnormalities present in the post-transplant period may contribute to the development and progression of complications leading to graft and patient loss. In the present study serum levels of antibodies against oxidised LDL (Ab-oxLDL) in kidney graft recipients were investigated along with their possible relation to the development of complications in the post-transplant period, and to the outcome of kidney transplantation. Methods: Serum levels of Ab-oxLDL and lipid pattern were evaluated in 92 kidney graft recipients before and at 3, 6, 12, and 24 months after kidney transplantation, as well as in 90 healthy blood donors (control group). Results: Kidney graft recipients had higher frequency of low levels of Ab-oxLDL as compared with the control group. A decrease in Ab-oxLDL levels was observed at 6 months post-transplant. Patients with early graft loss due to acute rejection had lower pre-transplant Ab-oxLDL levels (p < 0.05) as compared to patients with graft survival >3 months. Conclusions: It is suggested that decreased Ab-oxLDL levels found in kidney graft recipients may reflect impaired response to the products of lipid oxidation or increased consumption of Ab-oxLDL, and are associated with graft loss due to acute rejection.