Kidney dysfunction

Subchronic Studies. Although short-term repeated exposure studies provide valuable information about toxicity over this time span, they may not be relevant for assessment of ha2ard over a longer time period. For example, the minimum and no-effects levels determined by short-term exposure may be significantly lower if exposure to the test material is extended over several months. Also, certain toxic effects may have a latency which does not allow their expression or detection over a short-term repeated-exposure period for example, kidney dysfunction or disturbances of the blood-forming tissues may not become apparent until subchronic exposure studies are undertaken. 

Lactic acidosis (buildup of lactic acid in the blood) may also occur with die administration of metformin. Although lactic acidosis is a rare adverse reaction, its occurrence is serious and can be fatal. Lactic acidosis occurs mainly in patients with kidney dysfunction. Symptoms of lactic acidosis include malaise (vague feeling of bodily discomfort), abdominal pain, rapid respirations, shortness of breath, and muscular pain. In some patients vitamin B12 levels are decreased. This can be reversed with vitamin B12 supplements or with discontinuation of the drug therapy. Because... 

Amphotericin B-induced ARF occurs in as many as 40% to 65% of patients treated with the conventional desoxycholate formulation.30 Nephrotoxicity is due to renal arterial vasoconstriction and distal renal tubule cell damage. Risk factors include high doses, treatment for at least 7 days, preexisting kidney dysfunction, and concomitant use of other nephrotoxic drugs.31 Three lipid-based formulations of amphotericin B have been developed in an attempt to decrease the incidence of ARF amphotericin B lipid complex, amphotericin colloidal dispersion, and liposomal amphotericin B. The range of... 

Certain subgroups of the population may be more susceptible to the toxic effects of lead exposure. These include crawling and house-bound children (<6 years old), pregnant women (and the fetus), the elderly, smokers, alcoholics, and people with genetic diseases affecting heme synthesis, nutritional deficiencies, and neurological or kidney dysfunction. This is not an exhaustive list and reflects only current data available, further research may identify additional susceptible subgroups. 

Prealbumin (trans- thyretin) 2-3 Binds triiodothyronine and to a lesser extent thyroxine carrier for retinolbinding protein Kidney dysfunction Cirrhosis, hepatitis, stress, inflammation, surgery, hyperthyroidism, cystic fibrosis, kidney dysfunction, zinc deficiency... 

Results of studies in humans and animals suggest that sperm abnormalities, evidence of DNA damage such as chromosomal anomalies, and tests for liver and kidney dysfunction may serve as biomarkers of the effects of 1,2-dibromoethane (Ellingham et al. 1986 Heinrichs 1983 NTP 1982,... 

A number of clinical tests are available to detect kidney damage. The clinician examining a patient or the toxicologist monitoring an animal toxicity stndy collects urine and blood samples. Indications of kidney damage (which, of course, for the human patient could be related to many factors other then chemical toxicity) include urinary excretion of excessive amonnts of proteins and glucose, and excessive levels in the blood of unexcreted waste products such as urea and creatine. A number of additional kidney function tests are available to help pin down the location of kidney dysfunction. 

Patients exhibit a broad spectrum of abnormalities, including liver and kidney dysfunction with hepatomegaly, high levels of copper and iron in the blood, severe neurologic defects, and skeletal malformations. 

Nickel that has been absorbed into the blood stream is primarily excreted in the urine. Therefore, individuals with kidney dysfunction are likely to be more sensitive to nickel. The increased sensitivity of persons with kidney disfunction is also suggested by increased serum concentrations of nickel in dialysis patients (Hopfer et al. 1989). Because diabetics often have kidney damage, and because of the hyperglycemic effects of nickel observed in animal studies, the sensitivity of diabetics to nickel is also likely to be increased. 

In humans, 2,4-D in large doses can cause coma and generalized muscle hypotonia. Rarely, muscle weakness and marked hypotonia may persist for several weeks. In laboratory animals, signs of liver and kidney dysfunction have also been reported with chlorphenoxy herbicides. Several epidemiologic studies performed by the US National Cancer Institute confirmed the causal link between 2,4-D and non-Hodgkin s lymphoma. Evidence for a causal link to soft tissue sarcoma, however, is considered equivocal. 

No evidence of liver or kidney dysfunction was found in 73 male workers employed for an average of 8.2 years (range, 0.5-23 years) in a plant in the Netherlands producing allyl chloride, 1,3-dichloropropene, epichlorohydrin and hexachlorocyclopentadiene. Mean allyl chloride concentrations ranged from 0.21 to 2.89 mg/mL the values for hexachlorocyclopentadiene ranged from 0.01 to 0.23 mg/mL Exposures to 1,3-dichloropropene and epichlorohydrin were well below the current maximmn allowable concentrations. The results of the liver and kidney function tests were compared with those of 35 men in the same plant who were not occupationally exposed to these chemicals (Boogaard et al., 1993). 

Type XI (Fanconi-Bickel) Glucose transporter (GLUT2) Liver Failure to thrive, enlarged liver, rickets, kidney dysfunction... 

Adverse Effects. Enfuvirtide must be administered by subcutaneous injection, and local pain and irritation occurs at the injection site in most patients. Other common side effects include peripheral neuropathy and immune complex reactions that can lead to serious problems including respiratory distress syndrome, kidney dysfunction, and possibly Guillain-Barre syndrome. 

Adverse Effects. The primary problem associated with cyclosporine is nephrotoxicity, which can range from mild, asymptomatic cases to severe kidney dysfunction, which requires discontinuation of the drug.33,46 Hypertension is also a common adverse effect, especially when cyclosporine is used for prolonged periods.58 Other problems include neurotoxicity, gingival hyperplasia, hair growth (hirsutism), and increased infections. These problems, however, tend to... 

R4. Raz, E., Brezis, M., Rosenmann, E., and Eilat, D., Anti-DNA antibodies bind directly to renal antigens and induce kidney dysfunction in the isolated perfused rat kidney. J. Immunol. 142, 3076-3082 (1989). 

For this collection of data, we selected patients with acute kidney dysfunction or acute renal failure who met the above criteria for exercise-induced acute renal failure (ALPE), and who also matched our description. We collected a total of 155 patients with ALPE. The first 118 patients [2,3,22,27,30,34,35,37-95, Yamagata (personal communication, 1986), Ishikawa (unpublished results, 1994), Kadowaki (personal communication, 1996)] included 20 who we encountered before December 2000, and the remaining 37 patients [36,96-126] included 2 who we encountered between January 2001 and December 2004. 

Treatment should be selected based on the grade of kidney dysfunction. In deciding on conservative therapy, hydration must be controlled. Hydration is normalized according to the presence or absence of overhydration and dehydration, although dehydration is rare. When oliguria, hyperpotassemia, and uremia are observed (21% of the patients), dialysis therapy should be considered according to the indication for dialysis therapy in acute tubular necrosis. 

Pharmacokinetics Bretylium is poorly absorbed from the gastrointestinal tract and therefore is usually administered parenter-ally. The drug is excreted unchanged in the urine, and dosage may have to be adjusted in patients with kidney dysfunctions. 

Therapeutic applications Cisplatin has found wide application in the treatment of solid tumors such as metastatic testicular carcinoma in combination with vinblastine (see p. 390) and bleomycin (see p. 386), ovarian carcinoma in combination with cyclophosphamide (see p. 388), or alone for bladder carcinoma. Carboplatin is employed when patients cannot be vigorously hydrated as is required for cisplatin treatment, or if they suffer from kidney dysfunction or are prone to neuro- or ototoxicity. 

Itai-itai disease was identified in residents of the Jinzu River Basin in Japan in the mid-1940s. A lead and zinc mine polluted the river with high levels of Cd. The river water was used in the irrigation of rice fields and for drinking water. People affected by the disease suffered severe kidney dysfunction and painful skeletal symptoms. In the worst cases, bones would break from slight pressure, even from simply coughing. It is important to note that the worst cases were presented in... 

Iron deficiency, pregnancy, hypoxia, chronic blood loss, estrogens Kidney dysfunction... 

C-8) (C-10) Tyrosinemia. There are enzyme defects at steps in the metabolism of tyrosine. These result in the accumulation of tyrosine and its metabolites in the urine and serum. Liver and kidney dysfunction, and mental retardation are common. The condition may be treated by lowering tyrosine and phenylalanine intake. Vitamin C may be helpful as it is a cofactor for hydroxyphenylpy-ruvate hydroxylase at this step. 

Adverse effects include CNS symptoms (reversible blurring of vision, diplopia, dizziness and ataxia) and depression of cardiac AV conduction. Alimentary symptoms, skin rashes, blood disorders and liver and kidney dysfunction also occur. Osteomalacia by enhanced metabolism of vitamin D (enzyme induction) occurs over years so also does folate deficiency. Enzyme induction reduces the efficacy of combined and progestogen-only contraceptives. Carbamazepine impairs cognitive function less than phenytoin. 

Platt, J.F., liUis, J.H., Rnbin, J.M., Merion, R.M., Lucey, M.R. Renal duplex Doppler ultrasonography a noninvasive predictor of kidney dysfunction and hepatorenal failure in liver disease. Hepatology 1994 20 362-369... 

Kidneys Dysfunction of the proximal tubule may occur as a late manifestation of Wilson s disease. Epithelial flattening, a loss of the brush-border membrane, mitochondrial anomalies and fatty cellular changes can be observed. These findings are, in turn, responsible for proteinuria with a predominance of hyperaminoaciduria (L. UzMAN et al., 1948). Enhanced calciuria and phosphat-uria may cause osteomalacia as well as hypoparathyroidism. (329, 344) Glucosuria and uricosuria, if present, are without clinical relevance. Due to decreased bicarbonate resorption, tubular acidosis may occur, with a tendency towards osteomalacia as well as the development of nephrocalcinosis and renal stones (in some 15% of cases). (344, 356, 392) The intensity of the copper deposits in the kidneys correlates closely with the cellular changes and functional disorders. The glomerular function is not compromised, with the result that substances normally excreted in the urine are not retained. 

Marked pitting with Mees lines (homogeneous transverse white lines in the nail plates) in the fingernails, a disorder that has not been previously reported, was attributed to ciclosporin-associated kidney dysfunction in a 41-year-old man who inadvertently took ciclosporin 300 mg/day for psoriasis (161). 

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