Transglutaminase inhibition reduces fibrosis and preserves function in experimental chronic kidney disease

Progressive tissue fibrosis is involved in debilitating diseases that affect organs including the lungs, liver, heart, skin, and kidneys. Recent evidence suggests that tissue transglutaminase, an enzyme that crosslinks proteins, may be involved in tissue fibrosis by crosslinking and stabilizing the extracellular matrix or by recruiting and activating the large latent transforming growth factor (TGF)-β1 complex. We treated rats that had undergone 5/6-nephrectomy with two different irreversible inhibitors of transglutaminase and found that both prevented a decline in kidney function and reduced the development of glomerulosclerosis and tubulointerstitial fibrosis by up to 77% and 92%, respectively. Treatment reduced the accumulation of collagen I and collagen III, with the primary mechanism of action being direct interference with the crosslinking of extracellular matrix rather than altered regulation of TGFβ1. We conclude that inhibition of transglutaminase offers a potential therapeutic option for chronic kidney disease and other conditions that result from tissue fibrosis. Copyright © 2007 by the American Society of Nephrology.

Top-down lipidomics of low density lipoprotein reveal altered lipid profiles in advanced chronic kidney disease

This study compared the molecular lipidomic profi le of LDL in patients with nondiabetic advanced renal disease and no evidence of CVD to that of age-matched controls, with the hypothesis that it would reveal proatherogenic lipid alterations. LDL was isolated from 10 normocholesterolemic patients with stage 4/5 renal disease and 10 controls, and lipids were analyzed by accurate mass LC/MS. Top-down lipidomics analysis and manual examination of the data identifi ed 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profi le in disease. The total lipid and cholesterol content was unchanged, but levels of triacylglycerides and N -acyltaurines were signifi cantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were signifi cantly decreased in chronic kidney disease (CKD) patients. Chemometric analysis of individual lipid species showed very good discrimination of control and disease sample despite the small cohorts and identifi ed individual unsaturated phospholipids and triglycerides mainly responsible for the discrimination. These fi ndings illustrate the point that although the clinical biochemistry parameters may not appear abnormal, there may be important underlying lipidomic changes that contribute to disease pathology. The lipidomic profi le of CKD LDL offers potential for new biomarkers and novel insights into lipid metabolism and cardiovascular risk in this disease. -Reis, A., A. Rudnitskaya, P. Chariyavilaskul, N. Dhaun, V. Melville, J. Goddard, D. J. Webb, A. R. Pitt, and C. M. Spickett. Topdown lipidomics of low density lipoprotein reveal altered lipid profi les in advanced chronic kidney disease. J. Lipid Res. 2015.

Looking to the future : Predicting renal replacement outcomes in a large community cohort with chronic kidney disease

Peer reviewed

Looking to the future : Predicting renal replacement outcomes in a large community cohort with chronic kidney disease

Peer reviewed

Looking to the future : Predicting renal replacement outcomes in a large community cohort with chronic kidney disease

Peer reviewed

The association between vitamin K2 intake and glucose homeostasis in individuals with and without chronic kidney disease

Thesis (Master's)--University of Washington, 2016-08

Long-term outcomes following “presumed” total parathyroidectomy for secondary hyperparathyroidism of chronic kidney disease

Aim. The most efficacious surgical treatment for renal hyperparathyroidism is still subject of research. Considering its low incidence rate of long-term relapse, “presumed” total parathyroidectomy without autotrasplantation (TP) may be indicated for secondary hyperparathyroidism (2HPT) in patients with chronic kidney disease (CKD), not eligible for kidney transplantation. The aim of this study was to analyse the TP long-term results in 2HPT haemodialysis (HD) patients. Method. Between January 2004 and October 2009, 25 2HPT HD patients, not eligible for kidney transplantation, underwent TP of at least four parathyroid glands. Clinical status and intact parathyroid hormone (iPTH) serum levels were assessed intraoperatively and during a 36-month follow-up. Results. TP improved the typical clinical symptoms and a significant reduction of iPTH serum levels was achieved in each patient. Aparathyroidism was never observed; in case of severe postoperative hypocalcemia, hypocalcemic seizures were never reported and the long-term recurrence rate was 8%. Only one patient received a kidney transplantation. Postoperative cardiovascular events (hypertension, peripheral artery disease, arrhythmia, coronary or cerebrovascular disease) were observed in 32% of cases and mortality rate was 16%. Conclusions. Considering its low long-term relapse rate and the absence of postoperative aparathyroidism, TP may still be considered the treatment of choice in patients with aggressive forms of 2HPT or of advanced dialytic vintage, with no access to renal transplantation. In case of postoperative hypoparathyroidism, hypocalcaemia can be effectively managed by medical treatment.

Meta-analysis of the influence of chronic kidney disease on the risk of thromboembolism among patients with nonvalvular atrial fibrillation

Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist. However, the extent to which CKD increases the risk of thromboembolism in patients with nonvalvular AF and the benefits of anticoagulation in this group remain unclear. We addressed the role of CKD in the prediction of thromboembolic events and the impact of anticoagulation using a meta-analysis method. Data sources included MEDLINE, EMBASE, and Cochrane (from inception to January 2014). Three independent reviewers selected studies. Descriptive and quantitative information was extracted from each selected study and a random-effects meta-analysis was performed. After screening 962 search results, 19 studies were considered eligible. Among patients with AF, the presence of CKD resulted in an increased risk of thromboembolism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.20 to 1.76, p = 0.0001), particularly in case of end-stage CKD (HR 1.83, 95% CI 1.56 to 2.14, p <0.00001). Warfarin decreased the incidence of thromboembolic events in patients with non-end-stage CKD (HR 0.39, 95% CI 0.18 to 0.86, p <0.00001). Recent data on novel oral anticoagulants suggested a higher efficacy of these agents compared with warfarin (HR 0.80, 95% CI 0.66 to 0.96, p = 0.02) and aspirin (HR 0.32, 95% CI 0.19 to 0.55, p <0.0001) in treating non-end-stage CKD. In conclusion, the presence of CKD in patients with AF is associated with an almost 50% increased thromboembolic risk, which can be effectively decreased with appropriate antithrombotic therapy. Further prospective studies are needed to better evaluate the interest of anticoagulation in patients with severe CKD.