Calcium-free hemodialysis for the management of hypercalcemia.

The drug therapies for hypercalcemia of malignancy have been known to be associated with either limited efficacy or cumulative toxicity in patients with advanced renal failure. To establish the guidelines for the use of dialysis and to determine its optimal prescription for hypercalcemia, calcium-free hemodialysis was performed in 6 hypercalcemic patients with renal failure not responding enough to forced saline diuresis. Calcium-free dialysate contained sodium 135, potassium 2.5, chloride 108, magnesium 0.75, bicarbonate 30 mmol/l. Mean hemodialysis time was 160 +/- 27 min and mean Kt/V urea was 0.75 +/- 0.2. Plasma calcium concentrations fell from a mean value of 2.92 +/- 0.21 mmol/l (range 2.55-3.25) to 2.58 +/- 0.16 mmol/l at 1 h of hemodialysis and to 2.16 +/- 0.33 mmol/l (range 1.63-2.53) following 2-3 h of hemodialysis. The ionized calcium (n = 4) decreased from 1.44 +/- 0.14 mmol/l to 0.99 +/- 0.2 mmol/l. No patient showed any hypocalcemic symptoms and signs during hemodialysis. The rate of decrease in plasma calcium did not appear to produce adverse effects in any of the patients. There was a significant positive correlation between the decrease in plasma calcium concentration and the Kt/V urea (y = 1.4x - 0.29, r = 0.92, p < 0.01). We conclude that calcium-free hemodialysis is indicated when the presence of severe renal failure prevents the administration of large volumes of intravenous fluids to hypercalcemic patients. The amount of dialysis (Kt/V urea) can be used to predict the decrease in plasma calcium concentration during calcium-free hemodialysis.

Verapamil attenuates calcium-induced mitochondrial swelling and respiratory dysfunction.

A protective effect of verapamil against hypoxic renal proximal tubule injury has been demonstrated in vitro. In contrast to other cytoprotective agents such as glycine or alanine, the protective effect of verapamil is associated with better maintenance of cellular ATP and potassium levels. These findings suggested a possible direct effect of verapamil on the mitochondria in addition to known effects of verapamil on membrane Ca channels. In the present study, the direct effects of verapamil on Ca-induced swelling, respiratory dysfunction, Ca uptake rate and phospholipase activity of renal cortical mitochondria were determined. Verapamil (100 microM) significantly inhibited Ca-induced mitochondrial swelling and partially prevented the associated reduction in respiratory control ratio (State 3/State 4: Ca + verapamil: 2.8 +/- 0.1 vs. Ca alone, 2.0 +/- 0.2; P < .01). A phospholipase A2 inhibitor, dibucaine (100 microM), significantly inhibited Ca-induced mitochondrial swelling and attenuated the decrease in respiratory control ratio (Ca + dibucaine: 2.9 +/- 0.1 vs. Ca alone, 2.0 +/- 0.2; P < .001). Neither agent, either alone or combined, completely prevented the respiratory dysfunction. Either verapamil or dibucaine attenuated the mitochondrial Ca uptake rate and reduced the rate of Ca-stimulated polyunsaturated free fatty acid accumulation; verapamil treatment also was associated with diminished net release of saturated and monounsaturated free fatty acids. These findings demonstrate that verapamil exerts a protective effect against Ca-induced mitochondrial damage which may be mediated in part by its effect to suppress mitochondrial Ca uptake and mitochondrial phospholipase activity.

Erythrocyte sodium transport in dialyzed uremic patients.

To investigate the status of the Na+ concentration and ionic fluxes in red cells of human subjects with dialyzed chronic uremia, the authors measured the Na(+)-K+ pump activity as well as Na(+)-K+ cotransport (CoT), Na(+)-Li+ countertransport (CTT) and Na+ passive permeability in erythrocytes from 37 normal subjects and 23 chronic uremic patients receiving maintenance hemodialysis. The mean intracellular Na+ concentration [Na+]i value in the pre-dialytic group was significantly lower than that in control subjects (p less than .0001), but tended to recover to the normal value of [Na+]i in the post-dialytic group. The mean intracellular K+ concentration value in the post-dialytic group was significantly higher than that of the control group (p less than .001), but not significantly different from that of the pre-dialytic group. It was found that the Na(+)-K+ pump activity of erythrocytes in the pre- and post-dialytic groups markedly decreased over that of the normal control group with statistical significance (p less than .0001, respectively). The Na(+)-K+ pump activity in the post-dialytic group, however, tended to recover, but not significantly. The rate constant for ouabain-sensitive Na+ efflux in the post-dialytic group was significantly decreased over that of the normal controls (p less than .05). The authors observed a significant decrease of the Na+ CoT value (p less than .001 respectively) and rate constant for Na+ CoT (p less than .05, respectively) in the patients with pre- and post-dialytic uremia vs. that of normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)