Kidneys renal function tests

No studies in animals were located which support the observation of renal effects in the Rosenman et al (1987) study. Studies in animals have focused only on the deposition of silver in the kidney following oral exposure (Olcott 1947 1948) and renal function tests were not conducted. 

Monitor electrolytes and renal function tests in symptomatic patients. Administer intravenous fluids to maintain urine output and to protect the kidneys from myoglobinuria. The prognosis is good if animals do not develop rhabdomyolysis or secondary infection. No chronic problems are expected from BZ itself (Holstege, 2006). 

Cyclophosphamide can also cause tubular necrosis in experimental animals [82]. No clinical nephrotoxicity has been described, even when carefully assessed in patients receiving high doses of cyclophosphamide [83, 84]. Although there are no detectable alterations of renal function tests, some subtle changes in tubular kidney physiology do occur. Bode and associates [85] studied the mechanism of water retention that occurs from cyclophosphamide. They determined that cyclophosphamide directly affected the tubules, causing increased water resorbtion and sodium loss. This water retention is self-limited and lasts only a day or two. It is not a major clinical problem. 

Kluwe, W. M. 1981. Renal function tests as indicators of kidney injury in subacute toxicity studies. Toxicology and Applied Pharmacology 57 414 24. 

U.S. military veterans with gout Pb exposure intensities unknown current PbB comparable in normal function and kidney disease EDTA Pb mobilization renal function tests 50% of gout patients had renal failure gout patients with kidney failure had almost twice the amount of chelatable Pb Batuman etal. (1981)... 

RISK FOR INEFFECTIVE TISSUE PERFUSION RENAL When the patient is taking a drag tiiat is potentially toxic to die kidneys, die nurse must carefully monitor fluid intake and output. In some instances, die nurse may need to perform hourly measurements of die urinary output. Periodic laboratory tests are usually ordered to monitor the patient s response to therapy and to detect toxic drag reactions. Seram creatinine levels and BUN levels are checked frequentiy during the course of therapy to monitor kidney function. If the BUN exceeds 40 mg dL or if the serum creatinine level exceeds 3 mg cIL, the primary health care provider may discontinue the drug therapy or reduce the dosage until renal function improves. 

Monitoring Perform periodic blood counts and liver and kidney function tests. Discontinue use if blood dyscrasias or signs of hepatic or renal disorders occur. Frequently measure arterial blood pressure during IV use. 

Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Creatinine clearance is a useful quantitative indicator of renal function. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. 

The best characterized multidrug transporter is P-gp which is a membrane protein encoded by the mdrl gene. The most intriguing feature of P-gp is its ability to interact with a large number of structurally and functionally different amphiphilic compounds. P-gp expression can be acquired during the course of treatment (e.g., in leukemias, lymphomas, ovarian carcinomas) or it is constitutive (e.g., in colorectal and renal cancers). In normal tissues of mammals P-gp is localized on the luminal surface of transporting epithelia in liver, kidney, small intestine, testes, and blood-brain barrier. 

Some studies of renal function in chromate production workers found negative or equivocal results. In a survey of a facility engaged in chromate production in Italy, where exposure concentrations were 0.01 mg chromium(VI)/m3, results of periodic urinalyses of workers who worked in the production of dichromate and chromium trioxide for at least 1 year were generally unremarkable, with the exception of one case of occasional albuminuria and a few cases of slight urobilinuria (Sassi 1956). As part of a mortality and morbidity study of workers engaged in the manufacture of chromium(VI) compounds (84%) and chromium(III) compounds (16%) derived from chromium(VI) in Japan, 94 workers who had been exposed for 1-28 years were given a complete series of kidney function tests (not further characterized) 3 years after exposure ended. All values were within normal limits (Satoh et al. 1981). 

Inulin is used in an important test for renal failure called the inulin clearance method (Gretz et al., 1993 Chiu, 1994). As inulin is neither secreted nor reabsorbed in the kidney, it can be administered by injection to measure glomerular filtration rate. The relative amounts of inulin in the plasma and urine give an indication of renal function. 

Initial evaluation of the effect of a chemical on renal function often is performed in intact, unanesthetized animals. An advantage of this type of study is that a great deal of information concerning overall renal function may be obtained relatively quickly using noninvasive methods. A major limitation of these noninvasive tests is lack of specificity These tests provide no information concerning an intrarenal site of toxicity, but rather assess overall kidney function. 

Fortunately, the kidney has a remarkable ability to compensate for the loss of renal functional mass. Within a short time after unilateral nephrectomy, the remaining kidney hypertrophies such that overall renal function appears normal by standard clinical tests. Compensation becomes a problem when evaluating the effects of nephrotoxicants specifically, changes in kidney function may not be detected until the ability of the kidney to compensate is exceeded. Then, within a short period of time, an animal might develop life-threatening renal failure. 

Qll Simple concentration and dilution tests can be used to check whether the regulatory mechanisms of the kidney are operating normally. There are also simple dipstick tests for the presence of protein and other abnormal constituents in urine the absence of these abnormal constituents is an indication that renal function has returned to normal. 

As renal function improves, the excretion of urea increases and the concentration of urea in blood declines. So a reduction in blood urea nitrogen (BUN) is also a useful sign of returning kidney function. More complex tests, such as creatinine clearance, would be needed to check whether the glomerular filtration rate (GFR) has returned to normal. 

Renal function is an indication of the physiological state of the kidney glomerular filtration rate (GFR) describes the flow rate of Altered fluid through the kidney, while creatinine clearance rate (Ccr) is the volume of blood plasma that is cleared of creatinine per unit time, and is a useful measure for approximating the GFR. Most clinical tests use the plasma concentrations of the waste substances of creatinine and urea, as well as electrolytes, to determine renal function. The nephron is the functional unit of the kidney (Figure 10.1) it consists of two parts ... 

B-10) Creatinine as a test of renal function. Creatinine, which is derived from creatine phosphate, normally is excreted almost totally by the kidney. Blood levels of serum creatinine, as well as urea, are useful indices of renal function, their elevation often being a sign of renal insufficiency. 

Mannitol Stimulation of osmotic diuresis is possible using mannitol (10-20% solution). (128) Mannitol is neither metabolized in the body nor reabsorbed by the tubules and is excreted almost totally through the kidney. Renal circulation and renal filtration are raised, and by reducing tubular absorption (= osmotic diuresis), water excretion is increased ( diuresis starter ). The saluretic effect is, however, relatively small. In the case of restricted renal function, application of mannitol is contraindicated. If necessary, the mannitol test (i.v. injection of 75 ml of a 20% solution) can be carried out beforehand. With enhanced diuresis of > 40 ml/hr, the kidneys still function adequately, so that it is possible to stimulate osmotic diuresis by means of a mannitol infusion. 

Pulmonary edema, renal failure, and liver injury should be managed symptomatically. However, based on toxicity similarities to trichloroethylene, data on plasma levels of following 1,2-dichloroeth-ylene overdose/exposure are not clinically very useful. Renal and liver function tests should be monitored in the presence of suspected kidney or liver injury. 

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