Nephrosis

Administration of trimethadione (Tridione) may result in hematologic changes, such as pancytopenia (decrease in all the cellular components of the blood), leukopenia, aplastic anemia, and thrombocytopenia Also reported are various types of skin rashes, diplopia (double vision), vomiting, changes in blood pressure, CNS depression, photosensitivity, and fatal nephrosis. Because these dm have been associated with serious adverse reactions and fetal malformations, they should be used only when other less toxic dm are not effective in controlling seizures. The oxazolidinediones may precipitate a tonic-clonic seizure... 

Renal Effects. Acute nephrosis has been reported in humans after acute, lethal intoxication (Fazekas 1971) by methyl parathion (Wofatox). This may be a secondary effect of hypoxia related to the neurologic effects of methyl parathion on vascular smooth muscle and on the electrical conduction system of the heart. It could also be related to therapeutic efforts. 

K. H. and Hultqulst, A. "Alpha-Fetoprotein In Antenatal Diagnosis of Congenital Nephrosis". Lancet, (1975), 1, 432-433. 

Hepatic Renal 1000 500 (toxic nephrosis 20% of males and 17% of females, cytomegaly) ... 

Osbome-Mendel rats appeared to be the most sensitive to the renal effeets of trichloroethylene. At a dose of 500 mg/kg/day, toxic nephrosis occurred in 78% of male and 60% of female Osbome-Mendel rats, 37% of male and 45% female ACI rats, 36% of male and 63% of female Marshall rats, and 20% of male and 17% female August rats. Another chronic study revealed renal tubular nucleocytosis in 50% of male rats exposed to 250 mg/kg/day trichloroethylene for 52 weeks by oil gavage (Maltoni et al. 1986). Further explanation of these studies is in Section 2.2.2.8. 

The liver is an organ that shows variable effects from trichloroethylene among species, and this can probably be attributed to interspecies differences in metabolism (see Section 2.4.2.1). Specifically, the apparent difference in susceptibility to trichloroethylene-induced hepatocellular carcinoma between humans and rodents may be due to metabolic differences (see Section 2.4.2.3). Kidney effects are also variable among species. Humans and mice are less sensitive than rats. In rats exposed chronically to trichloroethylene, toxic nephrosis characterized as cytomegaly has been reported (NTP 1988). The kidney effects in rats do not seem to be related to an increase in alpha-2 -globulin (Goldsworthy et al. 1988). Effects on the nervous system appear to be widespread among species, presumably due to interactions between trichloroethylene and neuronal membranes. 

Anti-nephritis activity and anti-nephrosis activity Hypoglycemic activity Cholesterol decreasing effect... 

Creatinine clearance < 60 mL/min/1.73 m2 (stages III-V chronic kidney disease), diabetes mellitus (with renal insufficiency), hypertension, chronic heart failure, cirrhosis, nephrosis, age >75 yr, cholesterol emboli syndrome, multiple myeloma (questionable)... 

NS (occup) Increase in death due to cerebrovascular disease, nephritis, and/or nephrosis NS Fanning 1988 Malcolm and Barnett 1982 Michaels et al. 1991... 

Treatment. Since the 1950s, the treatment of Wilson s disease has relied on chelating agents [25]. Early attempts to use BAL or EDTA for this purpose were unsuccessful, but penicillamine, triethylene tetramine dihydrochloride (trientine), and tetrathiomolybdate, all in combination with a low-copper diet, have proved to be effective, and result in the urinary excretion of large amounts of copper. The use of penicillamine is complicated by the fact that it may induce a transient worsening of neurologic function due to rapid mobilization of copper, and also has other side-effects, such as the development of nephrosis. Tetrathiomolybdate is an effective alternative with fewer side-effects [26]. In cases in which the dose was rapidly escalated, however, bone marrow suppression or liver function abnormalities have been described. 

Causes of nonosmotic release of arginine vasopressin, commonly known as antidiuretic hormone, include hypovolemia decreased effective circulating volume as seen in patients with congestive heart failure nephrosis cirrhosis and syndrome of inappropriate antidiuretic hormone (SIADH) release. 

Male New Zealand rabbits displayed nephrosis of the convoluted tubules and nephrocalcinosis when given doses of 320 and 1,000 mg/kg/day hexachloroethane in methyl cellulose solution for 12 days (Weeks et al. 1979). Kidney weights were increased significantly for the 1,000 mg/kg/day dose. There were no observed effects on the kidney with a dose of 100 mg/kg/day. 

Mild to moderate nephropathy in female rats exposed to 80 or 160 mg/kg/day for 2 years, a high incidence of nephropathy in mice exposed to 590 or 1,179 mg/kg/day for 78 weeks, and nephrosis in rabbits exposed to 320 or 1,000 mg/kg/day for 12 days, indicate that hexachloroethane has an effect on the kidney that is independent of 2p-globulin (NTP 1977, 1989 Weeks et al. 1979). Thus, the public health risk for renal effects should be considered when evaluating the possible effects of human exposure to hexachloroethane at hazardous waste sites. 

In 1948 Dent (D2) described the so-called nephrosis peptide. He observed the presence of this peptide in the deproteinized urine of two patients with nephrosis. However, he could not find this peptide in the... 

E4. Ellis, H., Wilson, C., and Muirbead, A., Evidence of tbe presence of a pitressin-like substance in the tissue fluids in nephrosis. Acta Paediat. 45, 77-84 (1956). 

The antagonistic properties of FR 900452 have also been examined in a model of endotoxin shock, the haemodynamic and haematological manifestations of this condition closely resembling the changes induced by PAF. FR 900452 (10 mg/kg, i.v.) almost completely prevents PAF (1 /ig/kg, i.v.)-induced thrombocytopenia and leukocytopenia in rabbits [295]. It also significantly inhibits endotoxin (E. coli LPS, 30 /ig/kg, i.v.)-induced thrombocytopenia but not leukocytopenia. The same dose of FR 900452 also causes the decreased arterial blood pressure to return to normal in the endotoxin-induced rat hypotension model, an effect also reported for other PAF inhibitors [121, 274], Finally, FR 900452 has been tested for its therapeutic effect on rat nephrosis induced by aminonucleoside (puromycin, 100 mg/kg, i.p.). At 100 mg/kg twice a day orally for 6 days, the agent significantly reduces urinary protein loss in nephrotic rats [298]. 

Parsy et al. (P6) observed abnormal metabolites of apo-B100-containing lipoproteins, linking these metabolites to accumulation of triglyceride-rich particles containing Lp(a). The excellent correlations found between Lp(a) concentrations and VLDL cholesterol and triglycerides support the hypothesis of a close link between Lp(a) and triglyceride-rich lipoproteins in nephrosis (S42). 

This point of view overlooks the fact that every well and normal individual is potentially an ill individual, and the roots of disease may be present in his make-up years before there is any overt disease. A dozen young men used as normal controls may each have metabolic peculiarities that point toward a different metabolic derangement gout, multiple sclerosis, diabetes, anemia, atherosclerosis, hypertension, nephrosis, hypothyroidism, rheumatoid arthritis, rheumatic heart disease, liver cirrhosis, and myasthenia gravis, for example, and yet at the time of their use as controls these young men may show no symptoms of the disease which is to appear later in life. It seems far from safe to assume that because an individual on clinical examination seems well, all of his blood values, for example, are normal and meaningless so far as disease susceptibilities are concerned. 

Although we have discussed briefly the implications of biochemical individuality for alcoholism, for gout, and for arthritis, these are merely examples. A host of other diseases need to be attacked with the same point of view and hold the same promise of success. These include multiple sclerosis, muscular dystrophy, myasthenia gravis, atherosclerosis, essential hypertension, ulcers, diabetes, epilepsy, rheumatic heart disease, nephrosis, liver cirrhosis, congenital heart disease (as well as a host of other malformations which probably involve nutritional deficiencies during fetal life) and even infective diseases such as tuberculosis or poliomyelitis. 

Renal Effects. The kidney also is sensitive to bromomethane. Anuria and proteinuria are common signs of renal injury in acutely exposed humans (O Neal 1987 Prain and Smith 1952 Viner 1945), but dose-response data are not available. In animals, nephrosis has been noted in rats and mice exposed to 160 ppm for 2-6 weeks (Eustis et al. 1988). 

Toxicoses from pine needles have been reported in field cases, but are rare and have only occurred in pregnant cattle. No toxicity other than abortion in cattle has been demonstrated from ICA or ICA derivatives. However, the abietane-type resin acids in ponderosa pine needles (concentrated in new growth pine tips) have been shown to be toxic, but not abortifacient at high doses, when administered orally to cattle, goats, and hamsters. Pathological evaluations of intoxicated animals includes nephrosis, edema of the CNS, myonecrosis, and gastroenteritis (Stegelmeier et al., 1996). While abietane-type resin acids may contribute to the occasional toxicoses reported in the field, they do not contribute to the abortions. Most cow losses in the field are associated with difficult parturition or post abortion toxemia due to retained fetal membranes. 

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