Theophylline intoxication: clinical features and pharmacokinetics during treatment with charcoal hemoperfusion.

We describe a 50-year-old depressive patient with severe theophylline toxicity that occurred as a result of attempted suicide. Her theophylline levels peaked at 148 mg/l. She was promptly treated with charcoal hemoperfusion, and responded well. We describe the pharmacokinetics of theophylline removal via hemoperfusion, and review the literature.

Protein turnover in the hypertrophying kidney.

To establish whether altered proteolysis contributes to the increase in protein content in hypertrophying kidneys, we studied protein turnover in proximal renal tubules isolated from rats with three forms of renal hypertrophy, diabetes mellitus (DM), ammonium chloride-induced acidosis and compensatory renal growth (CRG). We found that in DM and in chronic acidosis the normal balance in protein turnover is altered due to attenuated proteolysis and accelerated protein synthesis. Together this favors an increase in kidney protein content. In contrast, in CRG, the increase in protein content is entirely due to increased protein synthesis. Thus, the changes in protein turnover leading to the net gain in kidney protein content in renal hypertrophy depends on the cause of hypertrophy.

[Hypercalcemia following rhabdomyolysis-induced acute renal failure].

Hypercalcemia is an uncommon clinical feature during recovery from acute renal failure. Moderate hypercalcemia developed during recovery of kidney function in a 24-year-old man with acute renal failure following polytrauma-induced rhabdomyolysis (myoglobinuria). He presented with multiple hematomas of the back, chest, abdomen and upper and lower limbs. He was asymptomatic during the hypercalcemic phase, when Ca reached 13.2 mg and PTH levels (immunoradiometric assay) were low, 8.7 muug/ml (normal 10-65).

Renal tubular cell protein breakdown in uninephrectomized and ammonium chloride-loaded rats.

Kidney enlargement after unilateral nephrectomy or the induction of a systemic acidosis with ammonium chloride is associated with an increase in kidney protein content. This reflects an imbalance between protein breakdown and protein synthesis. Because it has been shown in diabetic nephromegaly that depressed protein breakdown contributes to the increase in kidney protein content, this study examined whether altered protein breakdown is common to all forms of renal hypertrophy. Accordingly, protein turnover was measured in isolated proximal tubules from kidney in rats undergoing renal enlargement after uninephrectomy or chronic ammonium chloride-induced acidosis. In both conditions, kidney protein content and protein synthesis ([14C]valine incorporation) increased significantly. Fractional protein degradation was depressed in renal tubules isolated from the acidotic rats and was accompanied by a decrease in proximal tubule cathepsin B and combined B and L activities. These changes are comparable to earlier observations with the diabetic kidney. In contrast, after unilateral nephrectomy, protein breakdown is not reduced, and it can reasonably be concluded that, in this condition, protein gain reflects increased protein synthesis alone. It was concluded that the pattern of protein turnover leading to protein accretion in renal hypertrophy varies according to the initial stimulus for renal growth.

Tubular cell protein degradation in early diabetic renal hypertrophy.

Renal hypertrophy in diabetes is accompanied by an increase in kidney protein content, which reflects an imbalance between protein synthesis and degradation. This study determines whether altered cellular protein degradation contributes to the imbalance. Diabetes was induced in rats with streptozotocin (55 mg/kg/ip). After 2 or 4 days of diabetes, kidney weight and protein content were measured. Over the 4 days, despite a loss in body weight, kidney wet weight increased by 35% and protein content by 37% in the diabetic rats. Treatment with insulin prevented this increase. Long-lived protein degradation was measured in isolated proximal tubules prelabeled with (14C)valine in vivo. Two days after streptozotocin, protein degradation was depressed by 19% (P < 0.05) and by the fourth day by 27% compared with that in nondiabetic controls (2.6% +/- 0.2 versus 1.9 +/- 0.1% degraded/h; P < 0.01). This was accompanied by a similar diabetes-induced decrease in proximal tubule cathepsin B and L activity. Accordingly, this study provides direct evidence that, in diabetes, tubular cell protein breakdown is depressed and suggests that altered lysosomal cathepsin activity may contribute to this effect. Depressed proteolysis likely contributes to the increase in kidney protein content and hence to diabetic renal hypertrophy.

Effect of nisoldipine on ambulatory blood pressure under 24-hour noninvasive monitoring.

The antihypertensive effect of nisoldipine on ambulatory blood pressure was investigated using continuous noninvasive monitoring in 12 patients with moderate essential hypertension. Treatment with nisoldipine 5 mg twice a day for 2 weeks resulted in a decrease in the average of each patient's mean arterial pressure for the whole day from 110.3 +/- 6.8 to 103.2 +/- 8.8 mm Hg (P = 0.0007). This decrease in mean arterial pressure was due to a decrease in both systolic and diastolic pressures. The reduction in blood pressure was most marked at the time of the originally high blood pressure readings. Comparisons of consecutive means of 2-hourly mean arterial pressure readings showed a statistically significant effect from 6:00 AM to midnight. Blood pressures between midnight and 6:00 AM were similarly low, before and during nisoldipine therapy. There was no change in heart rate. Untoward symptoms were reported with similar frequency, and of similar severity, both before and during therapy. Nisoldipine 5 mg twice a day is an effective antihypertensive agent, reducing moderately elevated blood pressure in ambulatory, working patients with essential hypertension. At the dosage used, it had no demonstrable effect on heart rate and minimal, if any, side effects.

Calcium channel blocker nisoldipine in chronic renal failure.

Patients with a stable progression of chronic renal failure with a creatinine clearance of 15-45 mL/min were randomly assigned to two groups of antihypertensive therapy: 1--nisoldipine as the only antihypertensive agent and 2--antihypertensive drugs without calcium channel blockers and a placebo tablet instead of nisoldipine. The patients were already on a low-protein diet and some form of antihypertensive therapy but without calcium channel blockers. There were 18 patients in the placebo group and 20 patients in the nisoldipine group. The follow-up period averaged 23.7 +/- 10.6 (SD) months in the placebo group and 23 +/- 11.3 months in the nisoldipine group. The slopes of the reciprocal of serum creatinine were calculated for the period prior to and following our intervention. The number of patients whose slopes improved following intervention was 6/18 in the placebo group and 15/20 in the nisoldipine group (p less than .02). The patients whose slopes improved had a significant fall in systolic and diastolic BP, as well as in the MAP. Those whose slopes did not improve had a significant decrease in systolic BP, but no change in diastolic BP and no significant difference in the MAP. When all 38 patients are analyzed together, regardless of their grouping, the correlation between the difference percent in the slope, and the difference percent in the MAP, was significant. Furthermore, punch biopsies of the skin showed a markedly different calcium content in the two groups, which was significantly less in the nisoldipine-treated patients as compared with the patients not receiving calcium blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

The control of hypertension and its effect on renal function in rat remnant kidney.

Blood pressure control and its influence on the rat remnant kidney function were studied. The deterioration in kidney function was followed for up to 20 weeks at 4-weekly intervals in four groups of 5/6th nephrectomised rats. The groups studied were: (1) Control, untreated (C), given normal rat chow containing 21% protein; (2) nisoldipine (a dihydropyridine calcium channel blocker) treated (N), given nisoldipine freshly mixed daily in normal chow (0.3-0.6 mg/kg body weight); (3) dihydralazine-treated (H), fed normal chow and given dihydralazine added daily to the drinking water, about 15-25 mg/kg body weight daily; and (4) low-protein (6%) diet (LP), isocaloric and having the same sodium content as the normal chow. Proteinuria, serum creatinine, blood urea, histological damage as seen by light microscopy, and cumulative survival were taken to assess the severity of the chronic renal failure. All three therapeutic regimens attenuated significantly the rise in blood pressure which developed within less than 4 weeks in the rats with the remnant kidney. At the 16th week, means +/- standard deviations were, in group C, 237 +/- 20 mmHg; group N, 147 +/- 20 mmHg; group H, 164 +/- 23 mmHg; and group LP 149 +/- 16. Systolic blood pressure at the 8th week had a significant correlation with the serum creatinine of the 12th and of the 16th weeks. There was a strong correlation between blood pressure and the serum creatinine at the 16th week. This indicates that a time lag is necessary for the hypertension to have an effect on kidney function. Proteinuria, serum creatinine and blood urea were much higher in the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the calcium channel blocker nisoldipine on the progression of chronic renal failure in man.

Patients with stable renal insufficiency were randomized into two groups: (1) patients given the channel blocker nisoldipine (n = 17) and (2) placebo-treated patients (n = 17) also taking their regular antihypertensive therapy which did not include calcium blockers. Patients were already on low protein diet with a protein intake of 0.80 +/- 0.2 in the nisoldipine group versus 0.85 +/- 0.25 g/kg body weight in the placebo-treated group. The monthly progression of their renal failure was assessed by the reciprocal of serum creatinine versus time in months. After a mean follow-up of 17.4 +/- 8.2 (range 6-30) months, the nisoldipine-treated group had a significant decrease in their slope of progression, whereas the placebo-treated patients, after 16.94 +/- 7.2 (range 6-30) months of follow-up, had no significant change in their slope. The protein intake during follow-up was similar, being 0.85 +/- 0.2 g/kg actual body weight in the nisoldipine-treated group and 0.88 +/- 0.26 g/kg in the placebo group. The changes in slope did not correlate with the changes in blood pressure.