Insulin and mineralocorticoids influence on extrarenal potassium metabolism in chronic hemodialysis patients.

Insulin-mineral corticoids effects on extrarenal K+ metabolism in dialysis patients. During the inter-dialytic interval in dialyzed patients, hydrogen and potassium ions are regulated by extrarenal mechanisms. We studied the hormonal and acidotic effects on the extrarenal potassium metabolism, in selected, anuric and stable, hemodialysis patients. Fifteen patients, were grouped according to the mean mid-week pre-dialysis K+ over the past 12 months: > 6.0 mEq/L (G1, n=5), = 5.1-6.0 mEq/L (G2, n=5), < or = 5.0 mEq/L (G3, n=5). After a mid-week hemodialysis session and 12 h fasting, they received 1 g/Kg glucose p.os (A). Insulin, aldosterone, renin, pH, HCO3-, glucose, body weight, blood pressure and heart rate were measured before and 60' after the meal. We recorded the same parameters, except insulin, in 15 patients, similarly grouped, before hemodialysis (T0) and on 3 consecutive off dialysis days (T1-T3); G1 received fluorohydrocortisone (FHC) 0.1 mg-0.3 mg/day, according to body weight and G3 spironolactone (SLT) 200 mg per day. G2 were controls (B). (A) A significant rise in glycemia (81 +/- 23 to 157 +/- 52 mg/dL, P<0.001) and insulin (11.8 +/- 6.2 to 46.8 +/- 19.5 microU/mL, P<0.001), with a drop in K+ (5.1 +/- 0.6 to 4.8 +/- 0.7 mEq/L, P=0.001) and aldosterone (453 +/- 373 to 383 +/- 364 pg/mL, P<0.01), were noted at T60 vs. T0, in all groups. Insulin levels correlated negatively (r=-0.54, P<0.04) to serum K+ at T60, in all patients. (B) No major pH, HCO3 and aldosterone changes were observed in the 3 groups. Despite that, K+ dropped in G1 by FHC (6.7 +/- 0.9 to 5.9 +/- 0.6 mEq/L, P<0.05), rose in G3 by SLT (4.4 +/- 0.4 to 5.4 +/- 0.3 mEq/L, P<0.05) and remained unchanged in controls (5.8 +/- 0.2 to 5.8 +/- 0.6 mEq/L), (T0 vs T3 pre-dialysis values). Glucose significantly lowered K+ by promoting adequate insulin secretion. Drugs affecting aldosterone action significantly influenced potassium metabolism. Acid-base balance was not important in K+ handling in steady state anuric dialysis patients.

Potential effect of metabolic acidosis on beta 2-microglobulin generation: in vivo and in vitro studies.

Beta 2-microglobulin (beta 2M) is responsible for dialysis-associated amyloidosis. Level of beta 2M in plasma increase during chronic renal failure; however, retention does not appear to be the sole mechanism responsible. The effect of metabolic acidosis on beta 2M production was examined. Thirty-six patients with stable chronic renal insufficiency, 12 uremic patients before their first dialysis, 8 hemodialysis patients who were assigned to acetate or bicarbonate dialysate and then crossed over to the alternative regimen, and 6 normal subjects given NH4Cl to initiate metabolic acidosis were studied. In vitro studies in the human myeloid cell line U 937 were also performed. beta 2M protein was measured with ELISA, beta 2M mRNA was measured with reverse transcription polymerase chain reaction, and the U 937 cells were studied at two pH levels with FACScan flow cytometry. The cells were exposed in vitro up to 60 min in a buffered incubation medium to either pH 5.10 or pH 7.34. An inverse correlation was found between beta 2M and bicarbonate concentrations in plasma in the stable chronic renal failure patients (r = -0.54; P < 0.05) and in the uremic patients before their first dialysis (r = -0.72; P < 0.05). In hemodialysis patients, blood pH and plasma bicarbonate values were lower (P < 0.05) and beta 2M concentrations in plasma were higher (P < 0.05) with acetate than with bicarbonate dialysate. In normal men, NH4Cl resulted in an increase (P < 0.05) in beta 2M mRNA expression in lymphocytes by an average factor of 1.5 (range, 1.1 to 1.8). In U 937 cells, the cell surface expression of beta 2M and HLA Class I heavy chain assembled with beta 2M decreased at low pH compared with normal pH. Concomitantly, an increase in beta 2M release into the supernatant was observed, possibly as the result of beta 2M dissociation from cell surface HLA Class I complex. The results suggest that metabolic acidosis may enhance cellular beta 2M generation and release.