Background: Chronic kidney disease (CKD) is a potent risk factor for cardiovascular disease (CVD). CVD risk increases in a stepwise manner with increasing kidney impairment and is significantly reduced by kidney transplantation, suggesting a causal relationship. Dyslipidemia, a well recognised CVD risk factor, is highly prevalent in CKD. While dyslipidemia is a risk factor for CKD, kidney impairment can also induce a dyslipidemic state that may contribute to the excess burden of CVD in CKD. We utilised a multipronged approach to determine whether a causal relationship exists. Materials and Methods: Retrospective case-control analysis of 816 patients admitted to the Royal Hobart Hospital in 2008–2009 with different degrees of kidney impairment and retrospective before-after cohort analysis of 60 patients who received a transplanted kidney between 1999 and 2009. Results: Decreased estimated GFR (eGFR) was independently associated with decreased high density lipoprotein (HDL, p < 0.0001) and increased triglyceride concentrations (p < 0.01) in multivariate analysis. There was no significant relationship between eGFR and low density lipoprotein (LDL) or total cholesterol in multivariate analysis. Kidney transplantation increased HDL (p < 0.0001) and decreased triglyceride (p = 0.007) concentration, whereas there was no significant change in LDL and total cholesterol. These effects were dependent on maintenance of graft function, statin therapy (those who were on) if graft failure occurred then HDL again decreased and triglycerides increased. Conclusions: Kidney transplantation ameliorated alterations in plasma lipoprotein profile associated with kidney impairment, an effect that was dependent on the maintenance of graft function. These data suggest that kidney function is a determinant of HDL and triglyceride concentrations in patients with CKD.

No abstract

No abstract

Cyclodextrins (CDs) were discovered over a century ago for their ability to complex with several macromolecules and have found use in pharmaceutical industry to enhance solubility of drugs. Cationic CDs can bind nucleic acids (NA) and are being tested for delivery of NA to cells. Extracellular NAs can act as pro-inflammatory triggers and their inefficient clearance may activate Toll-like receptors (TLR) and contribute to autoimmune diseases such as lupus. We hypothesized that NA-binding CD (NABCD) may be used for scavenging extra-cellular NA to prevent pro-inflammatory responses. Here we investigated whether NABCD can modulate immune activation triggered by DNA or NA-TLR ligands. Indeed, in vitro assays using bone marrow derived macrophages (BMM) showed that NABCD induced a statistically significant inhibition of the expression of innate immune activation genes including Mx1, Prkr, Il1b and Tnfa when exposed to DNA or poly I:C. Treatment of C57BL/6 mice with TLR ligand polyI:C induced an acute pro-inflammatory response indicated by upregulation of interferon response genes and cytokine production. Treatment with NABCD not-only attenuated the innate-immune activation, but also modulated the adaptive immune response by significantly preventing a Th1 skewing of the immune response. The NABCD-treated mice also had higher numbers of IL-10 producing CD4 T-cells and more Foxp3+T-regulatory cells in the spleens as compared to mice treated only with polyI:C. Our data indicate a feasibility for the use of NABCD for modulating NA-induced proinflammatory responses and may find applications for treatment of autoimmune diseases such as lupus, where extra-cellular DNA plays a pathogenic role.