Statins inhibit NK cell cytotoxicity by membrane raft depletion rather than inhibition of isoprenylation.

To investigate the potential determinants of the pleiotropic effects of statins, we measured NK cell cytotoxicity in samples from normal subjects and patients, including patients receiving statin therapy. In a multivariate analysis, NK cell cytotoxicity was related to total plasma cholesterol concentration rather than statin use. In vitro, we investigated the role of lipid modification, specifically the effects on membrane rafts and raft-dependent signal transduction. We demonstrate that statins reduce NK cell cytotoxicity and that membrane cholesterol depletion by cyclodextrins has a similar effect. In contrast, isoprenyl transferase inhibitors had little or no effect on NK cell function. We hypothesise that the pleiotropic effects of statins reflect changes in membrane cholesterol and, specifically, the density of membrane rafts. Moreover, there is likely to be a relationship between membrane cholesterol, membrane rafts and cell function that may be involved in the pathogenesis of cardiovascular and metabolic diseases.

A rare cause of nephrotic syndrome in autosomal-dominant polycystic kidney disease.

We report the case of a 49-year-old lady who presented with hypertension, breathlessness and malaise. She was thrombocytopenic, with polycystic kidneys on imaging, and was found to have nephrotic syndrome. Serological results were consistent with systemic lupus erythematosus (SLE) and a renal biopsy confirmed WHO class V lupus nephritis. This is the first reported case of nephrotic syndrome due to lupus nephritis in a patient with autosomal dominant polycystic kidney disease (ADPKD) and underlines the importance of renal biopsy in patients with ADPKD and nephrotic range proteinuria.

The cholesterol paradox is flawed; cholesterol must be lowered in dialysis patients.

In the general population, elevated cholesterol is associated with cardiovascular disease and mortality and lowering cholesterol is associated with improved outcomes. This reflects the predominance of isolated atherosclerotic coronary disease in the general population. In patients with renal disease, however, the relationship between serum lipids and cardiovascular outcomes is much less clear and even reversed. In our opinion, the relationship between cholesterol and coronary disease is obscured by high levels of co-morbid disease, malnutrition, inflammation, atypical dyslipidemia and the fact that myocardial infarction is not the typical presentation of cardiovascular disease in patients with renal disease. Thus, cholesterol lowering will still be effective in patients with chronic kidney diseases.