Acid-base balance: a quest for alkalinity data.
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Acid-Base Equilibrium↗
Biomedical subjects
C Chaimovitz
Publications and source records attributed to C Chaimovitz.
Extreme hypermagnesemia due to ingestion of Dead Sea water.
We describe 3 patients who developed extreme hypermagnesemia due to ingestion of water of the Dead Sea, which would have been fatal were it not for the protective effects of the accompanying hypercalcemia. We emphasize the clinical features of this condition and the importance and effectiveness of early hemodialysis as the main modality of treatment.
Aged↗
Aluminum-related osteomalacia: clinical and histological improvement following treatment with desferrioxamine (DFO).
Aluminum-related osteomalacia has been a topic of major interest for some time. Patients on dialysis who are affected exhibit reduced parathyroid function and osteomalacia associated with high levels of aluminum in the extracellular fluid and tissues. In bone, aluminum is found in the interface between mineralized and nonmineralized osteoid. In the present study we attempted treatment of the aluminum-related bone disease with DFO, a potent chelating agent. A thyroparathyroidectomized patient on hemodialysis with proven osteomalacia and aluminum deposits in bone received DFO 3 times/week for 1 year. Consequently, there was a marked improvement in his skeletal status, both clinically and histologically. This was associated with aluminum deposits within the mineralized component of bone as well as elevated parathyroid function measured in blood and bone. These findings suggest that calcification may occur despite the presence of aluminum in the mineralizing front. The main beneficial effect of DFO could be relief of the inhibitory action of aluminum on parathyroid cells and osteoblasts.
Adult↗
Enhancement of 24,25-dihydroxyvitamin D levels in patients treated with continuous ambulatory peritoneal dialysis.
We measured 24,25-dihydroxyvitamin D [24,25(OH)2D] levels in patients treated with chronic ambulatory peritoneal dialysis (CAPD), before and after receiving vitamin D2 or 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3). Vitamin D2 administration led to an increase in 25-hydroxyvitamin D (25-OH-D) and a concomitant rise in 24,25(OH)2D. No change was observed in 1,25-dihydroxyvitamin D [1,25(OH)2D]. Administration of 1 alpha-OH-D3 resulted in an increase in 1,25(OH)2D3, and a concomitant rise in 24,25(OH)2D, but no change in 25-OH-D3. Thus, 24,25(OH)2D levels may be increased in CAPD patients by raising 25-OH-D levels, or by raising 1,25(OH)2D3 levels. Since the latter enhances specifically the renal 24-hydroxylase enzyme, we conclude that this enzyme is present in CAPD patients with kidneys in situ, and may be stimulated by adequate 1,25(OH)2D3 levels. Thus, administration of 1 alpha-OH-D3 to CAPD patients with kidneys in situ seems to be sufficient to obtain normal levels of 1,25(OH)2D3 and 24,25(OH)2D3. However, anephric patients require vitamin D2 in addition as a source of 25-OH-D, the substrate for extrarenal production of 24,25(OH)2D.
Calcifediol↗
Effect of guanidino-propionic acid on lymphocyte proliferation.
The 'uremic toxin', guanidino propionic acid (GPA), which was detected in uremic serum in correlation with BUN level, modified the mitogenic response of normal lymphocytes to phytohemagglutinin (PHA). Mild modifications can be detected in the concentrations which are found in uremic patients. Other guanidino compounds which have been detected in uremic sera, such as guanidino succinic acid (GSA), guanidino butyric acid (GBA) and guanidino acetic acid (GAA), show similar inhibitory pathways. It is suggested that guanidino compounds contribute to the immunological disturbances in uremia. The complexity of their action on lymphocyte mitogenic response is probably the cause of the conflicting results which have been reported in the literature.
Cell Division↗
Verapamil improves defective duodenal calcium absorption in experimental chronic renal failure.
Experiments were carried out to establish whether abnormalities in cellular calcium metabolism in chronic renal failure contributed to the impaired production of 1,25-dihydroxy vitamin D3 [1,25(OH)2D3]. For this purpose the calcium influx blocker verapamil was administered chronically to 5/6 nephrectomized rats (SNX) and sham-operated rats (sham). SNX and sham-nontreated animals served as controls. Fractional duodenal calcium absorption was severely depressed in SNX rats, compared to sham group. Administration of verapamil to SNX rats caused an improvement in calcium absorption despite similar degrees of renal insufficiency as in the nontreated SNX animals. The effect of verapamil requires residual renal parenchyma, since it was not reproduced in bilaterally nephrectomized rats. 45Ca uptake by renal cortical slices obtained from SNX rats was significantly elevated, as compared to sham group, and was corrected in uremic rats treated with verapamil. Plasma concentrations of 25-hydroxy vitamin D3 (25-OH-D3) were similar in all experimental groups. The 1,25(OH)2D3 plasma level in SNX rats was similar to values obtained in the control group, with an almost 2-fold increase in verapamil-treated animals. Quin-2 measurements of cytoplasmic calcium concentration in cultured proximal tubular cells revealed that verapamil prevents calcium bursts provoked by anoxic insult, by parathyroid hormone and by alpha 1-adrenergic stimuli. We conclude that verapamil treatment of SNX rats improves the duodenal absorption of calcium via augmentation of 1,25(OH)2D3 production.(ABSTRACT TRUNCATED AT 250 WORDS)
Aminoquinolines↗
Calcium metabolism in uremic nephrocalcinosis: preventive effect of verapamil.
The aim of the present study was to examine calcium metabolism of the renal cortex in experimental chronic renal failure, together with morphologic criteria of nephrocalcinosis and to determine the effect of chronic verapamil administration on these parameters. In subtotally nephrectomized (SNX) rats 3 weeks after surgery, renal cortical calcium content increased more than two-fold. 45Ca incorporation into renal cortical slices in SNX revealed a 35% increase, associated with a 50% increase in a lanthanum-resistant fraction of 45Ca uptake. Radiocalcium wash-out curves in this group demonstrated abnormal retention of the isotope for up to 30 min of incubation. In contrast, radiocalcium incorporation and wash-out in SNX rats chronically treated with verapamil were similar to that obtained in the sham group. Verapamil administration significantly reduced, but did not normalize, renal cortical calcium content. Von Kossa staining demonstrated the deposition of calcium in the renal parenchyma of SNX rats. Ultrastructurally, it was accompanied by mitochondrial disorganization and calcification, as well as by the tubular basement membrane destruction and mineralization. These morphologic patterns of nephrocalcinosis were significantly ameliorated in SNX rats treated with verapamil. We conclude that chronic verapamil administration results in amelioration of uremic nephrocalcinosis.
Animals↗
Comparative study of costs and quality of life of chronic ambulatory peritoneal dialysis and hemodialysis patients in Israel.
The more widespread use of chronic ambulatory peritoneal dialysis (CAPD) as an alternative to hemodialysis (HD) has focused attention on costs and quality of life aspects of different dialysis modalities. Costs for hospital HD exceed $23,000 annually, while CAPD annual costs are near $10,500 and home HD about $9,000. There are additional initial costs incurred during the first year of treatment, which range from under $2,000 for hospital-based HD and CAPD to over $11,000 for home HD. Quality of life aspects were compared for CAPD and hospital HD patients. Forty-six CAPD patients and 208 hospital HD patients were interviewed regarding ability to work, performance of physical activity, quality of sleep and sexual activity. The two patient groups were similar demographically (age, sex, origin and level of education). There were no statistically significant differences between the two patient groups for each of the quality of life variables, although CAPD patients showed slightly better results.
Adolescent↗
X-ray microanalysis of uremic nephrocalcinosis: cellular distribution of calcium, aluminium and silicon in uremic nephrocalcinosis.
Nephrocalcinosis with a deposition of aluminum and silicon has been previously reported in uremic rats. To clarify the origin of these elements thin sections of renal cortex were examined by means of electron microscopy and energy dispersive x-ray microanalysis. Studies were performed on subtotally nephrectomized rats (SNX) and sham-operated control animals. Electron microscopy of proximal tubular epithelial cells in SNX rats unlike control rats revealed severe mitochondrial disorganization; irregularity of the tubular basement membrane which exhibited various inclusions; and lamellar bodies within the brush border membrane. On x-ray microanalysis disorganized mitochondria contained calcium and silicon, while secondary lysosomes displayed aluminum and silicon. The tubular basement membrane of SNX rats, as well as lamellar body-like inclusions within the brush border contained calcium, aluminum and silicon together. It is suggested that lysosomal and mitochondrial interaction in proximal tubular cells of uremic rats may contribute to the deposition of calcium together with aluminum and silicon in the renal parenchyma, resulting in nephrocalcinosis.
Aluminum↗
Verapamil improves defective intestinal calcium absorption in uremia.
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Animals↗
Vascular hypersensitivity to noradrenaline: a possible mechanism of hypertension in rats with chronic uraemia.
Studies were performed to evaluate the mechanism involved in the hypertension of moderate renal failure in partially (five-sixth) nephrectomized rats. Cardiac index (CI) was studied by means of the microsphere technique, and systemic vascular resistance (SVR) calculated from the mean arterial resistance MAP/CI, in four groups of experimental animals: (A) partially nephrectomized rats; (B) group A rats chronically treated with the calcium channel blocker verapamil; (C) sham-operated rats; (D) sham-operated rats treated with verapamil. The results demonstrate a significant increase in MAP in group A rats, which was due to a 72% increase in SVR as compared with groups C and D. In group B rats, MAP decreased significantly owing to a marked decrease in SVR (40%) as compared with group A. However, MAP remained higher in group B than in group C. The vascular responsiveness to noradrenaline was studied in group A, group C and group A rats after parathyroidectomy (group A1). An increased pressor responsiveness to noradrenaline was indicated by a shift of the noradrenaline dose-response curve to the left in group A rats as compared with group C rats. This change was corrected after partial nephrectomy. We conclude that hypertension in nephrectomized rats is due to an increase in SVR, and that an increased pressor responsiveness to catecholamines may play a role in this phenomenon. Furthermore, verapamil reduced the hypertension, and parathyroidectomy improved the abnormal sensitivity to noradrenaline in group A rats. These results raise the possibility that an abnormality in calcium metabolism, possibly due to secondary hyperparathyroidism, may be implicated in the hypertension of mildly uraemic rats.
Animals↗
Losses of 1,25- and 24,25-dihydroxycholecalciferol in the peritoneal fluid of patients treated with continuous ambulatory peritoneal dialysis.
We measured peritoneal losses of the active vitamin D metabolites 1,25(OH)2D3 and 24,25(OH)2D3 in patients receiving continuous ambulatory peritoneal dialysis (CAPD). The serum concentration of 24,25(OH)2D3 was considerably lower than in hemodialysis patients. The serum concentration of 1,25(OH)2D3 was undetectable and rose to levels similar to those in hemodialysis patients only after loading with much higher oral doses of 1-alpha-vitamin D3 than those received by hemodialysis patients. Losses of both metabolites in peritoneal fluid were considerable, averaging approximately 6-8% of the plasma pool per day. These losses lead to low serum levels of these active vitamin D metabolites in CAPD patients, which may be an important factor in exacerbating renal osteodystrophy. Our results indicate the need for increased replacement doses of vitamin D metabolites in CAPD patients.
24,25-Dihydroxyvitamin D 3↗
Quality of life of patients on chronic dialysis.
The quality of life of 106 patients on chronic dialysis in two medical centers in Israel was studied; 97 diabetic nonuremic patients served as a control group. Of the dialysis patients, 60% were between 30 and 59 years old and 81% had less than or equal to 12 years of formal education; 53% did not work, and 53% of the married patients were not sexually active. Only 22% could engage in usual physical activity. No significant difference was found between the patients of the two centers, despite demographic and geographic differences. Patients greater than or equal to 60 years old had a poorer quality of life compared with younger patients and with the parallel control group. The group of patients with greater than or equal to 12 years of formal education had five times more full-time workers than did those with less than or equal to 8 years education. We conclude that: 1) More dialysis patients are not restored to full normal function compared with the control group of nonuremic diabetics; and 2) In terms of patient rehabilitation, dialysis achieved better results with patients who had greater than or equal to 13 years of education, and patients greater than or equal to 60 years old had poorer results than did those who were younger.
Adult↗
[Hemodynamic changes in essential hypertension].
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Hemodynamics↗
[Continuous ambulatory peritoneal dialysis].
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Diabetes Mellitus↗
[Treatment of end-stage diabetic nephropathy].
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Diabetic Nephropathies↗
X-ray microanalysis of uremic nephrocalcinosis.
The nature of uremic nephrocalcinosis was studied by means of X-ray microanalysis in 5/6 nephrectomized rats. The data show that calcified deposits in the renal parenchyma of uremic rats contained substantial amounts of calcium, magnesium, aluminum and silicon. Since calcificates did not reveal a uniform composition they were arbitrarily divided into 3 categories: 'high-calcium' with Mg:Al:Si: Ca molar ratios 7:3:8:37; 'low-calcium' particles were characterized by Fe:Mg:Al:Ca:Si molar ratios 7:3:5:6:13; while 'intermediate-calcium' particles showed Al:Mg:Si:Ca molar ratios equivalent to 2:4:6:7. The variability of calcified deposits in the renal parenchyma of 5/6 nephrectomized rats might be due to different sources, different environmental conditions along the nephron and different stages of calcification process. It is suggested that aluminum and silicon content of deposits may be of value in further characterization of uremic nephrocalcinosis.
Aluminum↗