Current applications of plasmapheresis in clinical toxicology.

The clinical applications of plasmapheresis are rapidly increasing in number and scope. This trend is also observed in the application of plasmapheresis as a method of detoxification in clinical toxicology. Because of a lack of large controlled series, the rationale for using plasmapheresis must be confirmed in each type of intoxication by evidence of effective clearance, as well as by high plasma protein binding and a low volume of distribution of the toxic substance. Plasmapheresis is used mostly to treat phalloid mushroom intoxications. In this potentially fatal intoxication, for which there is no antidote, plasmapheresis is at least as effective as haemoperfusion in reducing mortality from as high as 30-50% with conventional therapy to <20%. In our series of 28 patients treated with plasmapheresis, mortality was 17.8%. In our experience, plasmaphe-resis is also very effective in the treatment of life-threatening intoxications with tricyclic (amitriptyline) and 4-cyclic (maprotyline) antidepressants. We confirmed a 63% reduction in the plasma level of amitriptyline in one patient after single plasmapheresis. Other drugs such as L-thyroxine, verapamil, diltiazem and carbamazepime are also removed effectively by plasmapheresis, as are theophylline and heavy metals (mercury and vanadate). Phosphoroorganic substances are not removed effectively. We measured the plasma concentrations of dimethoate in two patients with this intoxication and did not find clinically significant clearance with plasmapheresis.

Balkan nephropathy: a disorder of renal embryogenesis?

There is evidence to suggest that a renal embryogenesis disorder, with an associated deficit of nephrons, may be the cause of nephropathy later in the lives of patients with Balkan endemic nephropathy (BEN). This evidence includes the renal dysplasia or hypoplasia observed in BEN patients, the high incidence of renal pelvic and renal artery aberrations, primitive glomeruli and obstructed tubules on kidney biopsy, and an adult Fanconi-type syndrome of generalized proximal tubular dysfunction with hyperchloremic acidosis, potassium wasting, preserved urinary acidification, tubular proteinuria, aminoaciduria, uricosuria, hypomagnesemia, sodium wasting and normotension, as well as evidence from epidemiological data. The disease has affected no more than 2 generations, most of whom were in their 50s during 1965-1970, when maximal numbers of patients were seen. We are now observing a decreasing prevalence of BEN in Bulgaria and, even though this may have resulted from some prophylactic measures, the disease disappears much as it had appeared, as an epidemic. We speculate that some environmental factor may have had an impact on embryogenesis and resulted in nephropathy in patients with BEN. This could have been famine during the devastating Balkan wars in the beginning of 20th century, but may also have been an infectious or environmental factor, limited to the affected areas around the Danube river, which acted only during a limited period of time.

Vasopeptidase inhibition affords greater renoprotection than angiotensin-converting enzyme inhibition alone.

The renoprotective efficacy of the vasopeptidase inhibitor omapatrilat (OMA) was compared with that of enalapril (ENA) in male Munich-Wistar rats subjected to 5/6 nephrectomy. ENA and OMA administered beginning on day 2 after surgery were equally effective in normalizing systolic BP (SBP) and preventing glomerulosclerosis (GS) for 12 wk. Micropuncture studies of rats performed using a similar treatment protocol demonstrated greater reduction of glomerular capillary hydraulic pressure with OMA than with ENA, at similar mean arterial pressures. To investigate whether these glomerular hemodynamic differences might be associated with differences in chronic renoprotective efficacy, additional rats were included in a protocol in which treatment was delayed until 4 wk after surgery (after the onset of hypertension and proteinuria) and continued for a longer period. Both treatments normalized SBP, but OMA resulted in more sustained reduction of proteinuria than did ENA. At week 20, OMA- and ENA-treated rats exhibited less GS than did untreated (control) rats at week 12, but only the difference in control versus OMA values was statistically significant [GS scores: control (12 wk), 36 +/- 4%; ENA (20 wk), 22 +/- 6%; OMA (20 wk), 14 +/- 2%]. The remaining ENA-treated rats were euthanized at 32 wk because of rapidly increasing proteinuria, whereas the remaining OMA-treated rats demonstrated a substantially slower increase in proteinuria until euthanasia at 50 wk. At this extremely late time point, OMA-treated rats exhibited GS scores similar to those of ENA-treated rats at 32 wk and control rats at 12 wk [GS scores: ENA (32 wk), 34 +/- 5%; OMA (50 wk), 38 +/- 8%]. It is concluded that, in this model, OMA affords greater long-term renoprotection than ENA when doses are adjusted to yield equivalent control of SBP.