Kidney nephropathy

Animal data suggest that renal and liver effects may occur in humans exposed to high doses of hexachloroethane. Kidney and liver effects are not specific to hexachloroethane. Lesions of the kidney (nephropathy, linear mineralization, and hyperplasia) were reported at 10 mg/kg/day or greater in male rats (NTP 1989). Urinalysis also revealed granular and cellular casts in rats exposed to hexachloroethane (47 mg/kg/day or greater) for 13 weeks (NTP 1989). Because other compounds cause similar effects and because some of these effects are unique to male rats, they are not valuable as biomarkers for human hexachloroethane exposure. 

In a follow-up study in mice, exposure to DEA, via drinking water or by topical application, caused dose-dependent toxic effects in the liver (hepatocellular cytological alterations and necrosis), kidney (nephropathy and tubular epithelial necrosis in males), heart (cardiac myoqn e degeneration), and skin (site of application ulceration, inflammation, hyperkeratosis, and acanthosis). Doses ranged from 630 to 10,000 ppm in the drinking water and from 80 to 12 50 mg/kg in the topical application study. 

Nephritis. Inflammation of the kidney. Nephropathy. Disease of the kidneys. Nephrotoxic. Toxic or destructive to kidney cells. 

There is no y-GT activity in muscle, bone and erythrocytes. Despite high y-GT activity in kidneys, nephropathies do not result in y-GT elevations. During pregnancy, y-GT activity is normal or the serum values may show a declining tendency from the second trimester onwards. In the liver, y-GT is found in the membranes of hepatocytes and bile duct epithelia. The periphery of the liver lobule has the highest y-GT activity. Gamma-GT passes from the liver into the bile and is then excreted partly by the kidneys in the urine, (s. tabs. 5.4, 5.5)... 

The hypertension of salt-resistant persons is often treated with drugs that inhibit angiotensin converting enzyme (ACE). When left untreated, hypertension can provoke damage to kidneys (nephropathy) (Chowdhury etal., 1996). 

Uncontrolled or poorly controlled plasma glucose levels will result in the development and progression of microvascular and macrovascular diabetic complications that involve the eyes (retinopathy), kidneys (nephropathy), nerves (neuropathy), heart, and blood vessels (9). 

Perazella, M. A. 1996. Lead and the Kidney Nephropathy, Hypertension, and Gout. Connecticut Medicine 60 521-526. 

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Chymostatin-sensitive Il-generating enzyme Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction Trial Collaborative Study Captopril Trial ( The Effect of Angiotensin-Converting Enzyme Inhibition on Diabetic Nephropathy ) calcium channel blocking agents Candesartan in Heart Failure Assessment of Reduction in Morbidity and Mortality Trial congestive heart failure, but the latest recommendations use HF for heart failure chronic kidney disease cardiac output... 

Fenoldopam does not decrease the incidence of contrast nephropathy.40 Due to its hypotensive effect, it may worsen kidney function. 

Chronic kidney disease (CKD), also known as chronic renal insufficiency, progressive kidney disease, or nephropathy, is defined as the presence of kidney damage or decreased... 

ESRD secondary to PCKD and failed previous transplant. One prior renal transplant that occurred in 1995 (received kidney from husband), which failed secondary to chronic allograft nephropathy in 2004 (presumably from multiple rejection episodes within the first few years after transplant). For the previous transplant, the patient was maintained on cyclosporine, mycophenolate, and prednisone. 

Uric acid excretion is reduced in patients with chronic kidney disease, putting them at risk for hyperuricemia. In patients with persistently acidic urine and hyperuricemia, uric acid nephrolithiasis can occur in up to 25% of patients in severe cases, uric acid stones can cause nephropathy and renal failure. Extreme hyperuricemia can occur because of rapid tumor cell destruction in patients undergoing chemotherapy for certain types of cancer (see Chap. 85). 

Afzali B, Taylor AL, Goldsmith DJ. What we CAN do about chronic allograft nephropathy role of immunosuppressive modulations. Kidney Int 2005 68 2429-2443. 

The lead-induced nephropathy observed in humans and rodents shows a comparable early pathology (Goyer 1993). However, in rodents, proximal tubular cell injury induced by lead can progress to adenocarcinomas of the kidney (see Section 2.2.3.8). The observation of lead-induced kidney tumors in rats may not be relevant to humans. Conclusive evidence for lead-induced renal cancers (or any other type of cancer) in humans is lacking, even in populations in which chronic lead nephropathy is evident. 

Ochratoxin A (OTA) is a my cotoxin produced by some species of Penicillium and Aspergillus. It is nephrotoxic to all animal species tested and the causal agent of mycotoxic porcine nephropathy (Krogh, 1978). It was previously associated with the human renal disorder, Balcan endemic nephropathy (BEN), and tumours of the urinary tract (Pfohl-Leszkowicz et al., 2002). Recently, another endemic kidney disease (Tunisian chronic interstitial nephropathy, CIN) was linked to OTA-contaminated food (Creppy, 1999 Wafa et al.,... 

Wafa H, Abid-Essafi S, Abdellatif A, Noureddine G, Abdelfettah Z, Farielle E, Creppy E E and Hassen B (2004), Karyomegaly of tubular kidney cells in human chronic interstitial nephropathy in Tunisia respective role of Ochratoxin A and possible genetic predisposition , Human Experimen. Toxicol., 23, 339-346. 

The answer is c. (Hardman, pp 649—650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypo xanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

Risk factors for ARF include advanced age, acute infection, preexisting chronic respiratory or cardiovascular disease, dehydration, and chronic kidney disease (CKD). Decreased renal perfusion secondary to abdominal or coronary bypass surgery, acute blood loss in trauma, and uric acid nephropathy also increase risk. 

These signs of nephropathy were present in all of the males at the 62 mg/kg/day dose and 70% of the males at the 15 mg/kg/day dose. Kidney weights were significantly increased for the 62 mg/kg/day dose group. Renal effects were also present in female rats, but they were less severe than the effects seen in males and occurred at higher doses. A dose of 62 mg/kg/day in the diet for 16 weeks was associated with atrophy and degeneration of the tubules in 60% of the females (Gorzinski et al. 1985). 

Chronic exposure of both rats and mice resulted in tubular nephropathy in both males and females. In rats, lesions were present in 45-66% of the males when they were sacrificed at 110 weeks after receiving 212 and 423 mg/kg/day hexachloroethane for 66 weeks of a 78-week exposure period (NTP 1977 Weisburger 1977). The renal lesions were characterized by hyperchromic regenerative epithelium, necrosis, interstitial nephritis, fibrosis, focal pyelonephritis, tubular ectasis, and hyaline casts. Lesions were also present in females but had a lower incidence (18% and 59%) for the two dose groups. Two-year exposures of male rats to much lower doses (10 and 20 mg/kg/day) resulted in similar effects on the kidneys (NTP 1989). Minimal to mild nephropathy was present in females for doses of 80 and 160 mg/kg/day. Over 90% of the male and female mice exposed to 590 and 1,179 mg/kg/day hexachloroethane for 78 weeks displayed tubular nephropathy when sacrificed at 90 weeks (NTP 1977 Weisburger 1977). Regenerative tubular epithelium was visible and degeneration of the tubular epithelium occurred at the junction of the cortex and the medulla. Hyaline casts were present in the tubules, and fibrosis, calcium deposition, and inflammatory cells were noted in the kidney tissues. 

Male rats are sensitive to renal tubular nephropathy after exposure to hexachloroethane. The lesions observed are characteristic of hyaline droplet nephropathy. They are most likely the result of hexachloroethane or one of its metabolites binding to the excretory protein 2p-globulin, altering its kidney transport, and leading to the formation of hyaline droplets. This protein is synthesized by male rats and accounts for 26% of their urinary protein excretion (Olson et al. 1990). It is not excreted in female rats except in minimal quantities. Since some effects are also seen in kidneys of female rats and in male and female mice that do not synthesize 2p-globulin, hexachloroethane must also have milder adverse effects on the kidney through a different mechanism. 

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. 

The mechanism of renal toxicity is not clear. Because the spectrum of kidney lesions observed in male rats (Gorzinski et al. 1985 NTP 1989) resembled those for 2p-globulin nephropathy, hexachloroethane-induced kidney lesions may, in part, be due to hexachloroethane binding to this protein. On the other hand, renal toxicity was observed in female rats and did not present the same sequence of lesions. This suggests the effects in males may not be totally due to 2p-globulin. Specific methods to minimize renal toxicity, based on mechanism of action, cannot be proposed at this time. 

Chronic-Duration Exposure and Cancer. No studies were located in humans following chrome-duration exposure to hexachloroethane for any exposure route. No chronic animal studies were conducted using the inhalation route of exposure. In oral studies with rats, the kidney was identified as a primary target organ in males and females (NTP 1989). The kidney damage in male rats was the result of hyaline droplet nephropathy and, accordingly, was not suitable as the basis for an oral MRL. In contrast to acute- and intermediate-duration oral exposure, liver toxicity was not evident in rats following chronic oral exposure. There were no studies of chronic dermal exposure to hexachloroethane. 

BorghoffSJ. 1993. 2u-Globulin-mediated male rat nephropathy and kidney cancer relevance to human risk assessment. Chemical Industry Institute of Technology (CUT) Activities 1-8. 

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