marinobufagenin and Albuminuria

Marinobufagenin (MBG) is an endogenous cardiotonic steroid (CTS) that inhibits the Na+/K+-ATPase. Human MBG is significantly increased in end-stage renal disease and immunization against MBG attenuates cardiovascular fibrosis in a rat model of uremic cardiomyopathy. Mineralocorticoid antagonists (MRA) block MBG binding sites and decrease proteinuria in chronic kidney disease (CKD) patients. We therefore aimed to investigate the association of MBG and albuminuria, as a marker of renal damage, as well as MBG and decline of glomerular filtration rate (GFR).. The Graz endocrine causes of hypertension (GECOH) study is a single center study of adults routinely referred for screening of endocrine hypertension. Plasma MBG was measured by an enzyme-linked immunoassay, and in a post-hoc analysis, follow-up creatinine levels were obtained. Patients with proteinuria >3.5g/day at baseline were excluded from further evaluation.. We measured MBG concentrations in 40 hypertensive subjects and excluded one patient due to pre-existing proteinuria. Plasma MBG was significantly correlated with albuminuria (Spearman ρ = .357; p = .028) and proteinuria (ρ = .336; p = .039). In linear regression analysis, the association remained significant after adjustment for age, sex, and BMI (β = .306; p = .036), and for mean systolic blood pressure (β = .352; p = .034). In follow-up analyses (N = 30), MBG was significantly associated with decline in GFR after adjustment for time-to-follow-up (β = -.374; p = .042).. The findings suggest that MBG plasma concentrations were associated with albuminuria as well as decline in kidney function. Whether MBG predicts hard renal endpoints warrants further investigations.

Topics: Adult; Aged; Albuminuria; Animals; Biomarkers; Bufanolides; Cardiotonic Agents; Enzyme Inhibitors; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension; Male; Middle Aged; Proteinuria; Rats; Renal Insufficiency, Chronic

In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.07%)-, intermediate (0.51%)-, or high (3.0%)-sodium diets during pregnancy and lactation. The offspring were weaned at 4 wk and subsequently kept on a 0.51% sodium diet. The kidney structure was assessed at postnatal weeks 1 and 12 and the expression of proteins of interest at term and at week 1. Blood pressure was measured in male offspring by telemetry from postnatal month 2 to postnatal month 9. The numbers of glomeruli at weeks 1 and 12 were significantly lower and, in males, telemetrically measured mean arterial blood pressure after month 5 was higher in offspring of dams on a high- or low- compared with intermediate-sodium diet. A high-salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both sprouty-1 and glial cell-derived neutrophic factor in the offspring's kidney. The expression of FGF-10 was lower in offspring of dams on a low-sodium diet, and the expression of Pax-2 and FGF-2 was lower in offspring of dams on a high-sodium diet. Both excessively high and excessively low sodium intakes during pregnancy modify protein expression in offspring kidneys and reduce the final number of glomeruli, predisposing the risk of hypertension later in life.

Topics: Albuminuria; Amniotic Fluid; Animals; Animals, Newborn; Blood Pressure; Body Weight; Bufanolides; Female; Humans; Intercellular Signaling Peptides and Proteins; Kidney Glomerulus; Litter Size; Male; Maternal Exposure; Organ Size; Pregnancy; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Sodium Chloride, Dietary; Sodium-Potassium-Exchanging ATPase; Transcription Factors