Kidneys renal system study

MVA is now known to be metabolized by routes other than those which give rise to terpenoids and steroids. The breakdown occurs predominantly in the kidneys to give C2 units that can be utilized in fatty-acid synthesis. The sterol and the shunt pathways have been evaluated in nine different tissues of rat previous conclusions that the kidneys are the predominant site of both types of metabolism have been confirmed. MVA is known to accumulate, at a low level, in the blood, and these results suggest that impairment of renal clearance of serum MVA by either route may account for the hypercholesterolaemia associated with some kidney disorders. A study of the effects of possible antimetabolites of MVA (for example the 2,3-anhydro-compound) on the formation of cholesterol in cell-free systems from liver has been reported. ... 

Liano F, Junco E, Pascual J, Madero R, Verde E The spectrum of acute renal failure in the intensive care unit compared with that seen in other settings. The Madrid Acute Renal Failure Study Group. Kidney Int SuppI 66 S16-S24, 1998 Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 273 117-123, 1995... 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

The National Kidney Foundation (NKF) developed a classification system for CKD (Table 23-11.1 The staging system defines the stages of CKD based on GFR level, but also accounts for evidence of kidney damage in the absence of changes in GFR, as in stage 1 CKD. The GFR is calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) study equation ... 

Several animal studies were located using the oral route for intermediate-duration and based on a combination of these studies, adverse effects have been reported in many organ systems. Hepatic, renal, and hematologic (Bombard et al. 1988 Carlson 1977 Hollingsworth et al. 1956 NTP 1987) effects have been the most consistent observations. The MRL was based on a minimal LOAEL of 188 mg/kg/day based on increased liver weights in rats. Since kidney effects involve hyaline droplet nephropathy, the renal effects were not considered to be a suitable basis for the MRL. 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, dermal/ocular, or other effects in humans after dermal exposure to hexachlorobutadiene. Liver, kidney, and dermal/ocular effects were reported in animals. These effects are discussed below. All LOAEL values for systemic effects in rabbits after acute-duration exposure are recorded in Table 2-3. 

Cardiovascular Effects. Most studies of humans exposed to carbon tetrachloride by inhalation have not detected significant evidence of cardiovascular injury, even at exposure levels sufficient to markedly injure the liver and/or kidney. Changes in blood pressure, heart rate, or right- sided cardiac dilation have sometimes, but not always, been observed (Ashe and Sailer 1942 Guild et al. 1958 Kittleson and Borden 1956 Stewart et al. 1961 Umiker and Pearce 1953), and are probably secondary either to fluid and electrolyte retention resulting from renal toxicity, or to central nervous system effects on the heart or blood vessels. Carbon tetrachloride also may have the potential to induce cardiac arrhythmias by sensitizing the heart to epinephrine, as has been reported for various chlorinated hydrocarbon propellants (Reinhardt et al. 1971). 

The principal effects of carbon tetrachloride in humans are on the liver, the kidneys and the central nervous system. These effects are apparent following either oral or inhalation exposure, and limited data indicate they can occur after dermal exposure as well. All of the effects seen in humans except renal injury are demonstrable at roughly comparable exposure levels in animals, although there are some variations in susceptibility between species that are likely to be related to differences in metabolism. No studies were located regarding reproductive and developmental effects in humans after exposure to carbon tetrachloride. In rats, carbon tetrachloride was not shown to adversely affect reproduction or development. Studies with both mice and rats suggest that sufficiently high doses of carbon tetrachloride may increase the risk of liver tumors in exposed humans. 

Of 12 patients with ascites due to cirrhosis of the liver, who received subcutaneous octreotide 300 micrograms bd for 11 days, 11 had increased renal plasma flow and 10 had a reduced GFR (44). Creatinine concentrations did not change. The effects of octreotide on the kidneys have been variably reported in previous studies. In patients with cirrhosis the effects are likely to be affected by the activated renin-angiotensin-aldosterone system. 

The lowest LOAEL value (0.083 mg/kg/day) in healthy humans ingesting white phosphorus for an intermediate duration was identified in the Sontag (1938) study. Lower LOAEL values have been identified in children with rickets (Phemister 1918). Because these children had a pre-existing condition, these data were not considered reliable. Other systemic effects and neurological effects were observed at this dose. This study was not selected as the basis of an intermediate-duration oral MRL because it is a case report of a single child and no assessment of hepatic or renal toxicity (liver and kidneys are two primary targets of white phosphorus toxicity) was made. 

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