Heme oxygenase (HO) catalyzes the degradation of heme to biliverdin, iron, and CO. The inducible isoform (HO-1) has been implicated as a modulator of the inflammatory response. HO-1 activity can be induced by hemin and inhibited with zinc protoporphyrin IX (ZnPP). Using these reagents, we assessed the possibility that HO-1 modulates the inflammatory response by altering the expression of endothelial cell adhesion molecules. Endotoxin (lipopolysaccharide, LPS)-induced expression of P- and E-selectin expression was quantified in different vascular beds of the rat using the dual radiolabeled monoclonal antibody technique. Pretreatment with hemin attenuated, whereas ZnPP treatment exacerbated, the increased selectin expression normally elicited by LPS. Biliverdin, at an equimolar dosage, was as effective as hemin in attenuating LPS-induced selectin expression in the lung, kidneys, liver, and intestines. These findings indicate that the anti-inflammatory properties of HO-1 may be related to an inhibitory action of P- and E-selectin expression in the vasculature. Biliverdin (or its metabolite, bilirubin), rather than CO, may account for this action of HO-1 on endothelial cell adhesion molecule expression.
Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease (ESKD) in the United States. Risk factor modification, such as tight control of blood glucose, management of hypertension and hyperlipidemia, and the use of renin–angiotensin–aldosterone system (RAAS) blockade have been proven to help delay the progression of DKD. In recent years, new therapeutics including sodium-glucose transport protein 2 (SGLT2) inhibitors, endothelin antagonists, glucagon like peptide-1 (GLP-1) agonists, and mineralocorticoid receptor antagonists (MRA), have provided additional treatment options for patients with DKD. This review discusses the various treatment options available to treat patients with diabetic kidney disease.
1 July 2021 in American Journal of Kidney Diseases
Octogenarians frequently require maintenance hemodialysis (HD) for treatment of stage renal disease ESRD. Although the Fistula First Initiative recommends creating an arteriovenous fistula as the preferred dialysis access method, vascular access selection should be based on life expectancy and functional status at treatment initiation. This is a retrospective analysis of 4-year outpatient data (January 1, 2004 through December 31, 2007) of incident octogenarian dialysis population in an academic institution. Thirty-nine of 268 patients were octogenarians with a mean (± SD) age of 83.4 ± 3.4 years, and 25 were men. Kaplan-Meier survival and Fisher's post hoc statistical analyses were performed. Thirty-seven octogenarian patients selected HD and two selected peritoneal dialysis. Among the 37 HD patients, 29 initiated dialysis with a tunneled cuffed catheter, 6 with an arteriovenous fistula, and 2 with an arteriovenous graft. Three patients regained renal function after an average 112 days and one was lost to follow-up. Of the 33 remaining on HD, 8 required nursing home admission and 25 were discharged home after initiating HD. Among these 33, 19 died and 14 remained on HD at the end of study period. Days on dialysis (mean ± SEM) before death in those discharged to a nursing facility versus home were 52.6 ± 14.7 versus 386.1 ± 90.7 (P < 0.05), respectively. Vascular access planning should include assessment of functional status and life expectancy in octogenarian HD patients.