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Aims: Cyclosporine A (CsA) has represented a fundamental therapeutic weapon in immunosupression for the past three decades. However, its clinical use is not devoid of side effects, among which hypertension and vascular injury represent a major drawback. Endothelial cells are able to generate reactive oxygen and nitrogen species upon exposure to CsA, including formation of peroxynitrite. This may result in endothelial cell toxicity and increased tyrosine nitration. We have now studied the subcellular origin of superoxide formation in endothelial cells treated with CsA and the biochemical consequences for the function of mitochondrial enzymes. [ABSTRACT FROM PUBLISHER]

Background. Successful kidney transplantation is believed to reverse secondary hyperparathyroidism, but persistent disease has emerged in a significant number of allograft recipients. Parathyroid hormone (PTH) is not only involved in the aetiology of calcium/phosphate abnormalities and osteitis fibrosa, but it is also a permissive factor in the occurrence of hypertension, cardiovascular damage and dyslipidaemia. In experimental renal failure, abrogation of hyperparathyroidism by administration of a calcimimetic or parathyroidectomy (PTX) attenuates progression of renal failure. To evaluate the impact of PTX on blood pressure (BP), renal graft function and serum lipids, we performed a retrospective case-controlled study in renal graft recipients.Methods. Charts of 1647 kidney allograft recipients, transplanted between 1989 and 2004, were reviewed. Thirty-two patients with a functioning graft and a history of a successful PTX performed at least 9 months after transplantation were identified. Biochemical and clinical data available 6 months pre- and post-PTX were registered. Changes in BP, renal function and serum lipids were assessed. The data were compared with those obtained in a similar time frame in a control group closely matched for date of transplantation.Results. Systolic BP (149.9 vs 141.7?mmHg), diastolic BP (85.6 vs 81.9?mmHg), pulse pressure (64.3 vs 58.8?mmHg), total cholesterol concentration (221.4 vs 211.1?mg/dl) and low-density lipoprotein cholesterol concentration (123.9 vs 106.7?mg/dl) improved significantly after successful PTX. Serum creatinine, conversely, significantly increased after PTX (1.75 vs 2.13?mg/dl, P<0.0001). No significant changes were observed in the control group in the same time period.Conclusion. In patients with a functioning renal graft, BP and dyslipidaemia improve, whereas serum creatinine worsens following successful PTX. Our data are in agreement with a stimulatory effect of PTH on plasma renin activity and an inhibitory effect on lipase activity, as previously demonstrated by others. To what extent the increased serum creatinine following PTX reflects a true deterioration of the glomerular filtration rate and/or is the consequence of vitamin D-induced reduction of the renal tubular secretion of creatinine needs to be elucidated by further research. [ABSTRACT FROM AUTHOR]

Background: Several alterations in growth hormone (GH) secretion have been reported in patients with chronic renal insufficiency. However, cholinergic modulation of somatotopic cell function has not been fully clarified in uraemic patients. To gain further insight into the disrupted mechanism of GH regulation in chronic renal failure, we investigated whether the blockade of cholinergic muscarinic receptor with pirenzepine could modify the response of GH to its physiological releasing hormone. [ABSTRACT FROM PUBLISHER]

Background.An abnormally high mortality from atherosclerotic cardiovascular (CV) accidents has long been reported in patients on maintenance haemodialysis (HD). However, incidence of atherosclerotic CV accidents had not been so far assessed in predialysis patients. In order to evaluate the respective influence of uraemia and the dialysis procedure, we compared incidence of atherosclerotic accidents before and after initiation of HD in a large population of patients. [ABSTRACT FROM PUBLISHER]

Background: Diabetic nephropathy (DN) is a common cause of chronic renal failure (CRF). Patients with DN have abnormal lipoprotein metabolism that can be influenced by both the impairment of renal function and the metabolic control of diabetes. The aim of the study was to explore the specific composition lipoprotein abnormalities in patients with insulin-dependent DN in comparison with diabetic patients without nephropathy and non-diabetic CRF patients. [ABSTRACT FROM PUBLISHER]

Background and methods To characterize the abnormalities of lipoprotein composition in patients with chronic renal failure (CRF), the lipid and apolipoprotein (apo) concentrations and composition of major lipoprotein density classes were determined in 20 subjects with moderate to advanced renal failure (GFR 5–59 ml/min) and nine controls. Patients were divided into 14 normotriglyceridaemic (NTG) subjects with triglyceride (TG) levels ≤1.7 mmol/1 (150 mg/dl) and six hypertriglyceridaemic (HTG) subjects with TG ≥1.7 mmol/1. Lipoproteins were isolated by preparative ultracentrifugation: very low density (VLDL), intermediate density (IDL), low density (LDL) and high density (HDL) lipoproteins. Results Although all density classes were characterized by abnormal concentration and composition of some lipid and apo constituents, the most profound changes occurred in IDL and HDL. Cholesterol levels were elevated in VLDL and IDL with little change in LDL and reduced in HDL. TG levels were increased in all density classes. ApoB levels were increased in VLDL, IDL and LDL of all CRF patients reaching the significance levels in VLDL and IDL of HTG (P<0.01) In IDL, the levels of apoC-peptides and apoE were increased (P<0.01). ApoC-peptides and apo E were also elevated in VLDL of NTG and HTG, but their increase was only significant in HTG (P<0.01). In LDL, the concentration of apoC-II and apoC-III was significantly increased (P<0.05). However, in HDL there was significant (P<0.01) reduction of apoA-I, apoA-II and apoC-peptides in both patient groups. The major compositional change was a significant increase in the relative contents of apoC-II and apoC-III in VLDL, IDL and LDL (P<0.01). Conclusions Results indicate that the characteristic feature of dyslipoproteinemia in CRF is the accumulation of partially delipidized TG-rich apoB-containing lipoproteins enriched in apoC-peptides and distributed characteristically in the IDL density-range irrespective of fasting TG concentrations. Increased levels of these ‘remnant lipoproteins’ and reduced levels of HDL may represent risk factors for atherogenesis and progressive renal disease. [ABSTRACT FROM PUBLISHER]

Secondary hyperparathyroidism (SHPT) is a common occurrence in patients with chronic renal failure and is characterized by excessive serum parathyroid hormone (PTH) levels, parathyroid hyperplasia and imbalances in calcium and phosphorus metabolism. PTH acts as a uraemic toxin and it may be responsible for the following long-term consequences: renal osteodystrophy; non-skeletal abnormalities, including severe vascular and heart valve calcification; alterations in cardiovascular structure and function; immune dysfunction; and renal anaemia. The risk of developing SHPT is not the same for all uraemic patients. Black patients appear to have a higher risk of developing SHPT than Caucasian patients, and patients with diabetes have a lower risk than non-diabetic patients. Current treatments include dietary phosphate restriction, oral phosphate binders, vitamin D and its analogues, and, in severe cases, parathyroidectomy. These treatments do not provide optimal treatment for many patients, and compounds that directly inhibit PTH secretion may prove a major step forward in the treatment of SHPT. [ABSTRACT FROM PUBLISHER]