Fluoride ion toxicity in rabbit kidney thick ascending limb cells.

BACKGROUND AND OBJECTIVE: Some halogenated agents, especially methoxyflurane, because of a higher level of fluoride production, induce a renal concentrating defect that could be related to an ascending limb impairment. We investigated the mechanisms of fluoride toxicity on an immortalized cell line. METHODS: Cells were cultured for 2, 6 or 24 h in the presence of fluoride. Toxicity evaluation was based on: cell numbers, protein content, leucine-incorporation, lactate dehydrogenase (LDH) and N-acetyl-beta-glucosaminidase (NAG) releases, Na-K-ATPase and Na-K-2Cl activities, electron microscope studies. Infrared analysis and fluoride microdetermination allowed crystal components. RESULTS: At 5 mmol after 24 h, fluoride decreased cell numbers (-14%, *P < 0.05), protein content (-16%*), leucine incorporation (-54%*), Na-K-2Cl activity (-84%*), increased LDH (+145%*) and NAG release (+190%*). Na-K-ATPase was more sensitive and impaired from 1 mmol for 24h and after 2 h at 5 mmol. Crystal formation in mitochondria occurred after 6 h at 5 mmol. Infra-red analysis and fluoride microdetermination established that crystals contained sodium, phosphate and fluoride. CONCLUSIONS: The results suggest that the Na-K-ATPase pump is a major target for fluoride toxicity in Henle's loop.

The chronic inhibition of angiotensin-converting enzyme impairs postoperative renal function.

UNLABELLED: Postoperative renal impairment can increase postoperative mortality and morbidity. We sought to identify preoperative risk factors responsible for postoperative renal impairment in patients undergoing aortic surgery. This prospective study included 249 patients admitted for aortic surgery. Preoperative and postoperative glomerular filtration rates (GFRs) were assessed with pre- and postoperative creatinine clearance measurements. Postoperative renal impairment was defined as a 20% decrease in GFR between Day 0 (before surgery) and Day 7 +/-1 day (after surgery). Preoperative and intraoperative variables considered as potentially responsible for postoperative renal impairment were tested. Chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs) was the only factor significantly associated with postoperative renal impairment (odds ratio [95% confidence interval] = 2.01 [1.05-3.83]). Chronic preoperative ACEI treatment is significantly associated with postoperative renal impairment. Inhibition of renal compensatory mechanisms caused by renin angiotensin system blockade might be responsible for the observed decrease in renal function in patients chronically treated with ACEIs undergoing aortic surgery. However, age and preoperative renal dysfunction were not associated with a postoperative decrease in GFR, but they were associated with a postoperative creatinine clearance <60 mL/min. IMPLICATIONS: The aim of this study was to identify preoperative risk factors responsible for postoperative renal impairment in vascular surgery. Chronic angiotensin-converting enzyme inhibitor treatment was the only factor significantly associated with postoperative renal impairment. Inhibition of renal compensatory mechanisms caused by renin angiotensin system blockade might be responsible for the observed decreased renal function.

Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients.

BACKGROUND: Hydroxyethylstarch used as a plasma-volume expander in brain-dead kidney donors has been suggested to induce osmotic-nephrosis-like lesions. We have studied its effect on kidney-transplant function. METHODS: 52 patients who had received hydroxyethylstarch of iodinated contrast-media before brain death were excluded. 69 other brain-dead patients were prospectively included over 18 months and randomised into two groups. In the hydroxyethylstarch-gelatin group, patients received hydroxyethylstarch up to 33 mL/kg for colloid plasma-volume expansion, and afterwards received modified fluid gelatin. In the gelatin-only group, patients received only modified fluid gelatin as colloid plasma-volume expander. Multiple organs were procured in 29 cases, which included the kidneys in 27 cases (hydroxyethylstarch-gelatin 15, gelatin-only 12). FINDINGS: There were no significant differences in the characteristics of patients between the two groups of kidney donors or of recipients (except for a small imbalance in sex in the recipients). During the first 8 days after transplantation, nine of 27 (33%) patients required extrarenal haemodialysis or haemodiafiltration in the hydroxyethylstarch-gelatin group compared with one of 20 (5%) in the gelatin-only group (p = 0.029). Serum creatinine concentrations were significantly lower in the gelatin-only group than in the other group (p = 0.009). 10 days after transplantation, mean (SD) serum creatinine was, respectively, 145 (70) and 312 (259) mumol/L. INTERPRETATION: These data suggest that hydroxyethylstarch used as a plasma-volume expander in brain-dead donors impairs immediate renal function in kidney-transplant recipients.

Fluoride ion toxicity in human kidney collecting duct cells.

BACKGROUND: Several halogenated anesthetics induce a urinary concentrating defect, partly related to fluoride ion toxicity in collecting duct cells. The aim of this study was to investigate the effects of fluoride ion in human kidney cells. METHODS: Immortalized human collecting duct cells were used. In a first set of experiments, the toxicity threshold concentration was determined by exposing cell cultures for 24 h to increasing concentrations of fluoride ion in the medium: 0, 1, 5, and 10 mM. The second set of experiments was a time- effect study in which cells were exposed to 5 mM fluoride for 2, 6, and 24 h. Assessment of toxicity was based on several endpoints: cell number, protein content, (3)H-leucine incorporation in newly synthesized proteins, extracellularly released lactate dehydrogenase, Na-K-ATPase pump activity, and electron microscope studies. RESULTS: After 24 h of exposure, fluoride ion decreased cell number (-23%, P<0.05), total protein content (-30%, P<0.05) and increased lactate dehydrogenase release (+236%, P<0.05) at a threshold concentration of 5mM. Fluoride ion also inhibited Na-K- ATPase activity at 5 mM (-58%, P<0.05). Major morphologic alterations of mitochondria, including crystal formation, were detected from 1 mM fluoride concentration. Time-effect studies showed that, after only 6 h of exposure at 5 mM, fluoride decreased cell number (-13%, P<0.05), (3)H-leucine incorporation (-48%, P<0.05), and Na-K-ATPase activity (- 20%, P<0.05) and increased lactate dehydrogenase release (+145%, P<0.05). Crystal deposits in mitochondria again were a more sensitive marker of cell injury, detectable after only 2 h of exposure. CONCLUSIONS: these results suggest that the mitochondrion is a target of fluoride toxicity in human collecting duct cells, and its alteration is partly responsible for the sodium and water disturbances observed in patients.