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J H Dirks

Publications and source records attributed to J H Dirks.

At least 19 recordsLinked to original sources
PubMed1989

Effect of magnesium diet in gentamicin-induced acute renal failure in rats.

Clearance experiments were conducted with metabolic cages to determine the effect of dietary magnesium on gentamicin nephrotoxicity. Three groups of male Wistar rats were given low, medium- or high-magnesium diets. Following baseline clearances, gentamicin was administered by intramuscular injection (20 mg/kg). Additional clearances were performed 6 and 11 days after gentamicin administration. 24-hour clearances were also taken 8 days after gentamicin withdrawal. The present experiments demonstrated that high magnesium intake protected the kidney against injury induced by gentamicin. This reduction in nephrotoxicity was probably due to competition of binding between magnesium and gentamicin to the renal membrane. Histological examinations were also done in these animals. The results showed that the most severe changes were seen in rats receiving a low-magnesium diet. Rats given a high-magnesium diet showed the least toxic changes while rats receiving a medium-magnesium diet showed changes of intermediate severity. These observations complemented the results obtained from 24-hour clearances and indicate the protective effect of dietary magnesium on the development of acute renal failure following administration of gentamicin.

Acute Kidney Injury↗
PubMed1988

Renal magnesium wasting and hypocalciuria in chronic cis-platinum nephropathy in man.

1. The renal handling of calcium and magnesium was studied in six patients with persistent hypomagnesaemia after cis-platinum treatment for testicular tumours. 2. In comparison with normal subjects, the patients showed hypomagnesaemia (mean 0.54 mmol/l), which was associated with a normal urinary magnesium excretion (mean 4.83 mmol/24 h). Urinary calcium excretion was significantly lower in the patients than in the normal subjects (mean 2.05 vs 5.15 mmol/24 h, respectively; P less than 0.01), despite slightly higher total serum calcium levels (2.53 vs 2.38 mmol/l, respectively; P less than 0.05). During magnesium chloride infusion, when serum magnesium levels were comparable in patients and controls, urinary calcium excretion remained lower in the patients, indicating that hypomagnesaemia was not the cause of the hypocalciuria. 3. Dietary magnesium supplementation resulted in a significant increase in the serum magnesium levels in the patients, while dietary magnesium deprivation resulted in a comparable decrease in urinary magnesium excretion in patients and controls (to 1.46 and 2.00 mmol/day, respectively), although the serum magnesium level fell further (to 0.46 mmol/l) in the patients. 4. The dissociation of renal calcium and magnesium excretion appears to be part of the intrinsic tubular defect caused by cis-platinum. This dissociation of urinary calcium and magnesium excretion, which resembles that seen in Bartter's syndrome, may result from a lesion in the distal convoluted tubule.

Administration, Oral↗
PubMed1988

Cyclosporin-induced hypomagnesaemia and renal magnesium wasting in rats.

1. Twenty-four hour clearance studies were performed on three groups of rats to determine the hypomagnesaemic effect of cyclosporin. Group I rats served as controls, whereas group II rats received 10 mg of cyclosporin/kg and group III rats received 20 mg of cyclosporin/kg daily. 2. After 7 days of cyclosporin treatment, plasma magnesium concentration was 1.04 +/- 0.01 mmol/l in control rats compared with 0.85 +/- 0.01 mmol/l in group II and 0.81 +/- 0.02 mmol/l in group III. After 14 days of cyclosporin administration, group III rats developed severe hypomagnesaemia (0.67 +/- 0.01 mmol/l). This reduction in plasma magnesium was associated with an increase in the urinary excretion of magnesium. 3. This reduction in plasma magnesium and increment in magnesium excretion returned to normal 7 days after cessation of treatment. 4. Additional three-phase acute clearance experiments were performed on eight normal and 12 cyclosporin-treated rats (20 mg/kg). These animals were subjected to acute magnesium chloride infusion. After graded magnesium chloride infusion, despite a similar rise in plasma magnesium, the fractional magnesium excretion was significantly higher in the cyclosporin-treated animals. 5. Analysis of the fractional intestinal absorption of magnesium suggested that the development of hypomagnesaemia after cyclosporin treatment is due to magnesium loss by the kidney. Furthermore, this effect of cyclosporin on magnesium transport is only present during cyclosporin treatment and is reversible when treatment with cyclosporin is withdrawn.

Animals↗
PubMed1988

Effect of cisplatin on proximal straight tubule transport of divalent cations in the rabbit.

Clearance and in vitro microperfusion studies were performed in rabbits to determine the effect of cisplatin on proximal straight tubule transport of calcium and magnesium. Rabbits were injected with cisplatin (2.5 mg/kg i.p. once weekly) for 3 weeks, whereas control rabbits received normal saline solution which served as a diluent for cisplatin. In 5 rabbits, 24-hour clearance studies were performed with the aid of a metabolic cage. Following cisplatin treatment, fractional excretion of magnesium rose significantly (73.3 +/- 11.5 vs. 111.4 +/- 17.5%). Glomerular filtration rate fell with cisplatin treatment (4.05 +/- 0.76 vs. 2.81 +/- 28 ml/min). There was no difference in fractional excretion of calcium (26.3 +/- 9.5 vs. 22.7 +/- 3.2%). The cortical and juxtamedullary proximal straight tubules were perfused in vitro. Net volume absorption was the same in the control and cisplatin-treated rabbits. However, there was a significant reduction in JCa (cortical 0.57 +/- 0.10 vs. -0.10 +/- 0.12 pmol/min/mm; juxtamedullary 0.96 +/- 0.17 vs. 0.31 +/- 0.37 pmol/min/mm) and JMg (cortical 0.43 +/- 0.08 vs. -0.15 +/- 0.07 pmol/min/mm; juxtamedullary 0.40 +/- 0.27 vs. -0.30 +/- 0.28 pmol/min/mm). In contrast to chronic administration, acute addition of cisplatin into the bath had no effect on JCa and JMg in the cortical and juxtamedullary proximal straight tubules. These data indicate that chronic but not acute cisplatin treatment depresses the transport of calcium and magnesium in the cortical and juxtamedullary nephrons of the proximal straight tubule of the rabbit.

Animals↗
PubMed1988

Sodium thiosulfate prevents cisplatin-induced hypomagnesemia.

Clearance studies were performed in four groups of male Wistar rats to assess the protective effect of sodium thiosulfate on cisplatin-induced hypomagnesemia. In group I, sodium thiosulfate (400 mg/kg) was injected intraperitoneally once weekly for 3 consecutive weeks. In group II, only cisplatin (2.5 mg/kg) was administered. In group III, both cisplatin (2.5 mg/kg) and sodium thiosulfate (400 mg/kg) were injected via the intraperitoneal route. When both drugs were administered together, they were injected into different parts of the peritoneal cavity. In group IV cisplatin was administered intraperitoneally and sodium thiosulfate intravenously. Sodium thiosulfate prevented a rise in plasma creatinine. The overall glomerular filtration rates of groups III and IV were the same as in group I. Hypomagnesemia was noted in group II, whereas in groups I, III, and IV the plasma magnesium level remained unchanged. The fractional excretion of magnesium was also higher in group II than in groups I, III, and IV. These differences persisted for the duration of the study. These results suggest that concurrent injections of sodium thiosulfate intraperitoneally or intravenously prevented the hypomagnesemic and the nephrotoxic effects of cisplatin and can be of clinical significance.

Animals↗
PubMed1988

Is lymphocyte magnesium concentration a reflection of intracellular magnesium concentration?

Diuretics are known to cause magnesium depletion, and the aim of the present experiment is to establish the relationship between lymphocyte magnesium concentration and intracellular magnesium concentration during chronic diuretic therapy. Studies were conducted in male Wistar rats that were subjected to daily administration of furosemide (2 mg/kg/day IP) for 19 weeks. Clearance measurements were performed during the baseline week and subsequently during the third, seventh, eleventh, fifteenth, and nineteenth weeks in both furosemide-treated (n = 32) and control rats (n = 32). Lymphocyte magnesium concentration was also measured as a determinant of intracellular magnesium concentration. Magnesium concentrations in kidney, bone, skeletal, and heart muscle tissues were also quantitated at week 11 and at the end of the experiment. After 11 weeks of furosemide administration, furosemide-treated rats developed a lower plasma magnesium concentration (0.95 +/- 0.01 mmol/L) compared with that in the control group (0.99 +/- 0.01 mmol/L). This difference persisted from week 11 to week 19 of the experiment. Fractional excretion of magnesium was modestly elevated in the furosemide-treated group. After 7 weeks of furosemide treatment, lymphocyte magnesium concentration decreased significantly in furosemide-treated rats when compared with that in the control group (1.56 +/- 0.09 micrograms/mg protein vs 1.33 +/- 0.07 micrograms/mg protein). During week 19, the lymphocyte magnesium concentration had fallen to 0.75 +/- 0.04 micrograms/mg protein as compared with 1.45 +/- 0.08 micrograms/mg protein in the control rats. There is a significant correlation between lymphocyte magnesium concentration and plasma magnesium concentration. Our present results indicate that during long-term diuretic therapy, lymphocyte magnesium concentration mirrors the reduction in plasma magnesium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of parathyroid and antidiuretic hormone on water and calcium permeability in the rat collecting duct.

Because the rat papilla has parathyroid hormone (PTH)-sensitive adenylate cyclase and because of indirect evidence that PTH may alter collecting duct water and also calcium transport, the effects of PTH on rat papillary collecting duct water and calcium transport have been studied. PTH in concentrations of 50 and 500 ng/ml significantly increased diffusional water permeability by 20 and 38%, respectively, while 5,000 ng/ml had no additional effect. This permeability response was small when compared to a 78% increase in water permeability with a maximal (0.5 ng/ml) concentration of antidiuretic hormone (ADH). The normal increase in water permeability with ADH was depressed in the presence of PTH (500 ng/ml) but was overcome when the ADH concentration was increased from 0.5 to 5 ng/ml. Neither PTH nor ADH altered the permeability of the collecting duct to calcium which was low (0.19 +/- 0.03 micron/s). Increasing either the bath or perfusate calcium concentration from 1 to 5 mM did not alter calcium permeability. These studies suggest that PTH acts as a partial agonist to ADH within the papillary collecting duct and that PTH is unlikely to have a major role in collecting duct calcium transport.

Animals↗
PubMed1987

Effect of acidosis and alkalosis on divalent ion transport across the proximal straight tubule of the rabbit.

In vitro microperfusion experiments were performed on the cortical proximal straight tubule of the rabbit to examine the effect of acid base disturbances on calcium and magnesium transport by this segment of the nephron. During acidosis (pH 7.22 +/- 0.01) net calcium reabsorption was reduced, whereas during alkalosis (pH 7.82 +/- 0.02) net calcium reabsorption was increased. Our flux experiments with 45Ca indicate that the efflux of Ca from the lumen to the bath remained the same during acidosis; however, the back-flux (bath to lumen) of calcium increased. On the other hand, during alkalosis the efflux of calcium rose and the influx of calcium remained unchanged. These changes in fluxes during acid-base disturbances can be accounted for mainly by changes in ionized calcium as a result of pH changes. We failed to observe any effect of acid-base changes on net magnesium transport by the superficial proximal straight tubule.

Acidosis↗
PubMed1986

Effects of acid-base disturbances on renal handling of magnesium in the dog.

Clearance and micropuncture studies were performed in four groups of acutely thyroparathyroidectomized animals to study the effects of alkalosis and acidosis on the renal handling of magnesium. Our results indicate that chronic metabolic acidosis reduces, whereas acute metabolic alkalosis enhances, magnesium reabsorption. The site within the nephron where absorption of magnesium increases or decreases during acid-base disturbances was beyond the late proximal tubule. Tubular fluid bicarbonate was also measured in these experiments, and the results indicated that magnesium reabsorption in the distal tubule correlated to bicarbonate delivery. However, whether this was a direct or an indirect effect of bicarbonate on magnesium transport could not be delineated.

Absorption↗
PubMed1986

The physiology of renal magnesium handling.

Present evidence suggests that the renal handling of magnesium is normally a filtration-reabsorption process as evidence for secretion is unsubstantiated. Magnesium reabsorption has distinctive features when compared with that of sodium and calcium. The proximal tubule concentration of magnesium rises to levels about 1.5 times greater than the glomerular filtrate and only 20-30% of the filtered magnesium is reabsorbed in this segment. Although the fractional reabsorption of magnesium is only half that of sodium, it changes in parallel with that of sodium in response to changes in extracellular fluid volume. The major portion of filtered magnesium (some 65%) is reabsorbed in the loop of Henle and evidence indicates that the thick ascending limb is the principal segment involved in magnesium absorption. Recent observations suggests that magnesium reabsorption in the ascending limb may be voltage dependent and secondary to active sodium chloride reabsorption. The loop of Henle appears to be the major nephron site where magnesium reabsorption is regulated possibly by cAMP-mediated hormones including parathyroid hormones, calcitonin, glucagon and antidiuretic hormone. About 10% of the filtered magnesium is delivered into the distal nephron. The distal tubule reabsorbs only a small fraction of the filtered magnesium which may be regulated by the same cAMP-mediated hormones involved in control of magnesium in the loop.

Animals↗
PubMed1986

Long-term morphological and biochemical observations in cisplatin-induced hypomagnesemia in rats.

A model of cisplatin (cis-diamminedichloroplatinum II) induced hypomagnesemia with renal magnesium wasting was developed in rats. Following three weekly intraperitoneal injections of cisplatin (2.5 mg/kg body weight) hypomagnesemia was evident after the second injection of cisplatin and persisted for at least 24 weeks after the last injection. The plasma magnesium concentration was 0.69 +/- 0.01 mM in cisplatin-treated rats and 0.79 +/- 0.01 mM in control rats 24 h after the second injection (less than 0.01). Despite a lower plasma magnesium concentration in cisplatin-treated rats, the fractional urinary excretion of magnesium was similar in both groups, indicating inappropriate renal magnesium excretion in cisplatin-treated rats. Rat kidneys fixed in situ by arterial infusion were examined by light and electron microscopy at the following times: 24 h after the first and second injections and 48 h and 1, 4, 8, 16, and 24 weeks after the third injection. Focal necrosis of the proximal tubule cells in the outer stripe of the medulla (S3 segment) was noted 24 h after the second injection. Following this, there was dilatation of the S3 segment proximal tubules which were lined by variably flattened epithelial cells devoid of brush borders. Many of these cells had enlarged, hyperchromatic nuclei, and few mitoses were observed. These changes were most extensive at 4 weeks, diminished after this, but were still present focally at 24 weeks. In this model the cisplatin-induced hypomagnesemia persists long after discontinuation of therapy as in humans, and the S3 segment is the prime target of the cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Studies on the pathogenesis of cisplatin-induced hypomagnesemia in rats.

After three weekly intraperitoneal injections of cisplatin (2.5 mg/kg body wt), male Wistar rats developed chronic hypomagnesemia, which was evident from the second week and persisted throughout the 8-week experiments. Plasma magnesium concentration was 0.69 +/- 0.01 mM in cisplatin-treated rats compared to 0.80 +/- 0.02 mM in pair-fed control rats (P less than 0.01) in the eighth week of experimentation. Despite a similar dietary magnesium intake, urinary excretion of magnesium in cisplatin-treated rats was inappropriately high, relative to the lower plasma magnesium concentration, indicating the presence of renal magnesium wasting induced by cisplatin. During the 3 weeks of cisplatin injections, metabolic balance studies indicated abnormal renal excretion and a reduction in the fractional intestinal absorption of magnesium. A compensatory period of significantly greater retention of magnesium then occurred in cisplatin-treated rats beginning in the fourth week. Clearance and recollection micropuncture studies in a separate group of rats revealed normal magnesium and calcium transport in the superficial proximal and distal nephron. Following acute MgCl2 infusion, the urinary excretion of magnesium and calcium were significantly higher in cisplatin-treated rats than in control rats; however, micropuncture studies of superficial nephrons failed to demonstrate abnormal transport of these divalent cations. It is possible, therefore, that 7 weeks of cisplatin treatment led to tubular adaptation that might have obscured the defect in magnesium reabsorption. Morphological examination indicated that pathological changes were confined to the S3 segment of proximal corticomedullary nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Enhanced distal absorption of potassium by magnesium-deficient rats.

The effect of acute potassium infusion on renal tubular reabsorption of potassium by magnesium-deficient and pair-fed control rats has been studied by the recollection micropuncture method. During potassium chloride infusion, the amount of potassium remaining in the distal tubule is lower in magnesium-deficient than in pair-fed rats. This could be due to a reduction in potassium secretion or to an enhancement of potassium reabsorption. The present study demonstrates enhanced renal potassium retention in the magnesium-deficient rat, and is in contrast to previous reports of renal potassium wasting in this circumstance.

Absorption↗
PubMed1985

Effects of phosphate and calcium infusion on renal phosphate transport in the dog.

The effect of phosphate infusion on renal tubular handling of calcium and phosphate was examined in dogs which had been thyroparathyroidectomized (TPTX) immediately prior to the studies. Phosphate infusions in TPTX animals caused a small decrease in total and ultrafilterable plasma calcium, and decreased phosphate reabsorptive capacity in the proximal tubule and loop segment. Infusion of CaCl2 during phosphate loading to offset the fall in plasma calcium prevented the reduction in proximal phosphate reabsorptive capacity. However, between the proximal and distal sampling site, the reduction in phosphate reabsorptive capacity could not be prevented by CaCl2 administration. These data are consistent with the presence of two phosphate transport systems; one in the early proximal tubule, modulated by changes in plasma calcium level, and a second in the loop segment, which is independent of calcium. While the data suggest that the depression of proximal phosphate reabsorption during phosphate infusion may be secondary to the fall in plasma calcium concentration, they do not exclude a direct effect of infused phosphate on proximal phosphate reabsorption that may be antagonized by an opposing direct effect of the calcium infusion.

Animals↗
PubMed1985

Actions of parathyroid hormone are not impaired during chronic metabolic acidosis.

The effect of parathyroid hormone (PTH) on renal excretion of calcium, phosphate, and bicarbonate was studied in acutely thyroparathyroidectomized dogs with metabolic acidosis. Ammonium chloride 10 gm/day for 3 days was given to 15 dogs to induce chronic metabolic acidosis. Clearance results obtained from these experiments showed that infusion of Beckman 1-34 PTH into normal and acidotic dogs resulted in a marked increase in phosphate and bicarbonate excretion, accompanied by a small reduction in calcium excretion and a slight but significant increase in plasma ultrafilterable calcium. Complementing our clearance data, micropuncture results obtained from the proximal and distal tubules of these animals indicated an enhancement of calcium reabsorption in the distal tubule after administration of PTH. Phosphate reabsorption by the proximal and distal tubules was reduced after infusion of PTH in both normal and acidotic dogs. The fraction of bicarbonate reabsorbed in the proximal tubule was reduced after PTH infusion, but the fraction of bicarbonate reabsorbed in the distal tubule remained unchanged. These data suggest that the phosphaturic, the hypocalciuric, and the bicarbonaturic effects of PTH were not impaired during chronic metabolic acidosis.

Acidosis↗
PubMed1979

Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney.

Clearance and micropuncture studies have been performed in dogs to examine the effects of acute and chronic metabolic acidosis and acute alkalosis on tubular sodium and calcium transport. Acute metabolic acidosis, induced by the infusion of hydrochloric acid, decreased proximal fluid reabsorption and increased the fractional delivery of sodium and calcium to the distal tubule, but not to the final urine. In comparison with normal dogs, dogs with chronic metabolic acidosis (induced by feeding ammonium chloride) showed an increase in proximal fluid reabsorption and a dissociation of calcium from sodium reabsorption more distally, leading to an increased delivery of calcium relative to sodium at the distal tubule and in the final urine. The infusion of sodium bicarbonate to correct chronic metabolic acidosis, both in intact and thyroparathyroidectomized (TPTX) dogs, reduced proximal fluid reabsorption and caused a selective enhancement of calcium reabsorption relative to sodium in the more distal nephron, resulting in a reversal of the dissociation observed in acidosis, both at the distal tubule and in the final urine. By contrastin fusion of sodium chloride in parathyroid-intact acidotic dogs did not reduce proximal fluid reabsorption or enhance tubular calcium reabsorption. In nonacidotic dogs, both intact and TPTX, infusion of sodium bicarconate to induce acute alkalosis resulted in selhese data demonstrate the presence of a component of tubular calcium reabsorption situated beyond the proximal tubule, which is inhibited by chronic (but not acute) metabolic acidosis and enhanced by metabolic alkalosis (or bicarbonate infusion) independently of parathyroid hormone.

Acidosis↗