摘要:

We have previously reported that radiocontrast agents induce direct renal tubule cell toxicity in vitro. The observed toxic effects were markedly potentiated by concomitant hypoxia. In addition, we have reported that the ionic radiocontrast agent diatrizoic acid is more toxic than the nonionic radiocontrast agent iopamidol in this system. Using suspensions enriched in rabbit renal proximal tubule segments, we compared the direct toxicities of the ionic dimeric ioxaglic acid to the nonionic monomeric compound iopamidol. Toxicity was assessed by comparing tubule potassium and calcium content, ATP levels, and respiratory rates after exposure to clinically achievable concentrations of radiocontrast agents. Ioxaglate (25 mM) produced significant declines in tubule cation content and respiratory rate with 30 min of hypoxia followed by 60 min of reoxygenation compared to molar-equivalent concentrations of iopamidol under similar conditions. Meglumine, a cationic compound frequently present in ionic contrast agent solutions, and ioxaglate tubule toxicity was additive. Iopamidol and ioxaglate exhibited similar tubule cell toxicity when comparison was based on iodine content. These experimental results suggest that the intrinsic nephrotoxic potential of ioxaglic acid is greater than that of iopamidol on a molar basis, but that the nephrotoxic potential of the two radiocontrast agents is similar when comparison is based upon iodine content.

ISSN:0886-022X    

DOI:10.3109/08860229009087121

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The proximal convoluted tubule (PCT) is the major target for injury in gentamicin nephrotoxicity but the necrosis is often patchy and focal. The PCT is structurally, functionally, and metabolically heterogeneous, and the possibility of differential vulnerability to gentamicin-induced necrosis based on this heterogeneity has not been examined. A quantitative analysis comparing the extent of necrosis in the initial portion of the PCT (S1) to that in the more distal PCT (S2) and comparing necrosis in the PCT of superficial nephrons to that in juxtamedullary nephrons was done in rats after eight daily intraperitoneal doses of 100 mg gentamicin/kg rat weight. The results indicate that the PCT of superficial nephrons are more susceptible to necrosis than the PCT of juxtamedullary nephrons and that the initial S1 segment even in the superficial nephrons is remarkably resistant to injury. These findings suggest that some aspects of the functional or metabolic heterogeneity within the PCT may be related to either differential rates of uptake of the drug or to differences in intrinsic susceptibility to its toxic effects.

ISSN:0886-022X    

DOI:10.3109/08860229009087122

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Thirteen patients found to be hypertensive following renal transplantation were treated with either a calcium channel blocker or other antihypertensive therapy for control of blood pressure. Immunosuppression was either with cyclosporine and prednisone alone or with cyclosporine, azathioprine, and prednisone. Patients had weekly or biweekly cyclosporine whole-blood levels measured by radioimmunoassay drawn approximately 12 h after their last dose. Patients treated with cyclosporine and prednisone alone had their cyclosporine dosage adjusted to maintain their cyclosporine level between 400 and 900 ng/mL between 1 and 6 months following transplantation. Patients treated with cyclosporine, azathioprine, and prednisone had their cyclosporine level adjusted to be between 100 and 400 ng/mL during this same time period. Cyclosporine levels were significantly higher in verapamil-treated patients and significantly lower in nifedipine-treated patients as compared to controls. The dose of cyclosporine administered was significantly lower in the verapamil-treated patients and higher in the nifedipine-treated patients than controls. Normalizing the whole-blood cyclosporine level for the dose of cyclosporine, and verapamil-treated patients had a significantly greater, and the nifedipine-treated patients a significantly lower value than control patients. These data suggest the verapamil treatment results in significantly higher levels of cyclosporine whereas nifedipine therapy may actually result in lower cyclosporine levels for a given dose of cyclosporine than seen in patients not exposed to these drugs.

ISSN:0886-022X    

DOI:10.3109/08860229009087123

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

High-dose folinic acid with 5-fluorouracil (5-FU) is a novel combination chemotherapy used in the treatment of metastatic gastrointestinal cancer. One of the mechanisms of action of 5-FU is its conversion into fluorodeoxyuridylate (FdUMP), which inhibits thymidilate synthetase (TS). The rate of inhibition of TS is augmented by increasing concentrations of folinic acid. On the other hand, it is well known that treatment of animals with high doses of folinic acid results in acute renal failure due to tubular obstruction. In order to find out whether there are similar findings in the clinical setting, we investigated 8 patients (pts.) with metastatic gastrointestinal cancer who were treated with this chemotherapy. We used the following parameters: 1. excretion of four urinary enzymes (LDH, LAP, GGT, NAG); 2. creatinine clearance on days 1 and 5. Therapy consisted of folinic acid 200 mg/m2i.v. on days 1-5 and 5-fluorouracil 400 mg/m2on days 1-5. Each treatment cycle was repeated on day 28. We found a constant decrease in the excretion of all 4 enzymes from normal to subnormal values which was statistically significant (p<. 05) during the two treatment cycles. Creatinine clearance decreased about 50% in three patients from normal initial values. In conclusion, during therapy with high-dose folinic acid and 5-fluorouracil we found signs of tubular damage which are similar to those found in folate nephropathy.

ISSN:0886-022X    

DOI:10.3109/08860229009087124

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

We report a case of increasing hyperlactatemia in the course of repeated treatment by machine hemofiltration (MHF) using a lactate-bujfered replacement solution. The hyperlactatemia was associated with a reduction in mean arterial pressure, and in the majority of treatments a metabolic acidosis developed. Hyperlactatemia due to exogenous lactate may not be as benign as previously discussed.

ISSN:0886-022X    

DOI:10.3109/08860229009087125

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The prevalence of aortic valve and mitral valve or mitral annular calcification by echocardiography was studied in 66 dialysis patients and correlated with results of 24-h ambulatory and resting ECG data and 12-month survival. The well-known association of mitral valve or mitral annular calcification with cardiac conduction defects was confirmed. Those patients with mitral valve or mitral annular calcification demonstrated a higher prevalence of first-degree atrioventricular block and bundle branch block. Despite advanced age and these conduction defects, those patients with mitral valvular calcification did not show decreased survival at 12 months.

ISSN:0886-022X    

DOI:10.3109/08860229009087126

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The intraocular pressures of 16 patients with end stage renal failure treated with high-flux dialysis were measured before and during a high-flux dialysis treatment. The patients were selected so as not to have glaucoma or history of glaucoma. Intraocular pressures did not change significantly in any patients during or following a high-flux hemodialysis treatment. These data suggest that high-flux hemodialysis does not result in increases in intraocular pressure nor does it precipitate acute glaucoma in well-dialyzed patients undergoing intermittent in-center hemodialysis.

ISSN:0886-022X    

DOI:10.3109/08860229009087127

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

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 followup 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<. 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-treatedpatients as compared with the patients not receiving calcium blockers. It is reasonable to conclude that the calcium channel blocker nisoldipine is able to decrease the slope of progression of I/serum creatinine significantly in the majority of patients. It is also reasonable to suppose that there is a definite correlation between the decrease in BP, especially the diastolic or the MAP, and the slope of progression. We hypothesize that the beneficial action of the calcium blocker was not through changes in the intraglomerular hemodynamics, but rather through 2 possible mechanismsm: (a) the decrease in systemic BP which is transmitted unhindered to the glomerular capillaries; (b) by preventing calcium deposition in the renal cortex.

ISSN:0886-022X    

DOI:10.3109/08860229009087128

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

ISSN:0886-022X    

DOI:10.3109/08860229009087129

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The pituitary, thyroid, and ovarian hormone levels were measured by enzyme and fluorescence polarization immunoassays in 18 women with successful renal transplants (recipients): 10 menstruating, mean age 34.7 years, mean time after transplantation (Tx) 112.00 months, mean SCr 130.60µmol/L; and 8 menopausal, mean age 52.7 years, mean time after Tx 61.00 months, and mean SCr 119.00µmol/L. Five women of the menstruating group conceived 7 times and gave birth to 4 healthy infants. The findings were compared to 30 age-matched healthy subjects (controls) and to 13 women under chronic hemodialysis (hemodialyzedpatients): 2 menstruating, 24 and 36 years old, and 11 menopausal, mean age 59.4 years. Serum prolactin (PRL) showed a highly significant increase in hemodialyzed patients (p<. 0001) compared to controls. In recipients, PRL levels were significantly lower than in hemodialyzed patients, but higher than in controls (p<. 0001). LH and FSH were elevated in menstruating hemodialyzed patients (p<. 0001, p<. 02, respectively) and significantly high in menopausal hemodialyzed patients (p<. 02, p<. 01, respectively). In menstruating recipients, LH was also highly elevated (p<. 001), while FSH showed no significant difference from controls. In menopausal recipients the increase of LH was less prominent (p<. 02) but FSH was highly increased (p<. 001). T3, T4, and FTI were absolutely normal in recipients, while they were significantly lower than normal (p<. 0001) in hemodialyzed patients. Estradiol showed no significant difference in both groups of recipients, as well as in menopausal hemodialyzed patients. In conclusion, it seems that after successful renal Tx in females, thyroid function is absolutely restored, PEL secretion is almost normalized, gonadotropin secretion is ameliorated in menstruating women, and estradiol secretion is restored. Thus, the restoration of fertility in the menstruating group could be attributed to the normal gonadal and ameliorated gonadotropin secretion.

ISSN:0886-022X    

DOI:10.3109/08860229009087130

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor