Nephropathy, chronic

Acute exposure to unleaded gasoline and a variety of light hydrocarbons present in gasoline produces a nephropathy in male rats characterized by (1) an excessive accumulation of protein (hyaline droplets) in epithelial cells of proximal tubule, (2) accumulation of casts at the corticomedullary junction, and (3) evidence of mild tubular regeneration. This nephropathy only occurs in male rats female rats and mice do not show any renal pathology. A number of chemicals present in unleaded petrol when tested alone have been shown to produce nephropathy and, in particular 2,2,4-trimethylpentane and decalin have been used as model compounds. Certain other industrial chemicals (1,4-dichlorobenzene and isophorone), natural products (o-limonene), and pharmaceuticals (levamisole) also produce this male-rat-specific nephropathy. Chronic exposure of male rats to unleaded petrol, 1,4-dichlorobenzene, isophorone, or o-limonene ultimately leads to the induction of a low incidence of renal adenomas and carcinomas. 

Hypertensive crises, renovascuiar hypertension, neonatai and chiidhood hypertension, stroke prevention, migraine prophyiaxis, nondiabetic nephropathy, chronic kidney disease, diagnosis of scieroderma renai crisis, and Bartter s syndrome (32,33)... 

The alimentary symptoms may be overshadowed by neuromuscular dysfunction, accompanied by signs of motor weakness that may progress to paralysis of the exterior muscles or the wrist (wrist drop), and less often, of the ankles (foot drop). Encephalopathy, the most serious result of lead poisoning, frequendy occurs in children as a result of pica, ie, ingestion of inorganic lead compounds in paint chips this rarely occurs in adults. Nephropathy has also been associated with chronic lead poisoning (147). The toxic effects of lead may be most pronounced on the developing fetus. Consequendy, women must be particulady cautious of lead exposure (148). The U.S. Center for Disease Control recommends a blood level of less than 10 p.m per 100 mL for children. 

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). 

Encephalopathic signs and Chronic nephropathy Colic, other overt ... 

Diabetes continues to be a major cause of excessive morbidity, severe disability and premature death in Western populations. In developed countries, the cost of diabetes to society may be estimated to be as high as 5% of the total health costs, much of which relates to the chronic vascular complications of this disorder (Williams, 1991). The vascular lesion in diabetes consists of (1) microangiopathy, distinguished by thickening of capillary basement membranes resulting in increased vascular permeability, which is clinically manifested as diabetic retinopathy (Fig. 12.1a) and/or nephropathy (Fig. 12.1b), and (2) macroangiopathy (Fig. 12.2),... 

Diabetic or HIV nephropathy, analgesic abuse nephropathy, cyclosporine nephropathy, and chronic interstitial nephritis... 

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... 

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. 

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

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. 

Ruster M, Sperschneider H, Funfstuck R, Stein G, Grone HJ. Differential expression of beta-chemokines MCP-1 and RANTES and their receptors CCR1, CCR2, CCR5 in acute rejection and chronic allograft nephropathy of human renal allografts. Clin Nephrol 2004 61 30-39. 

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

In a study of 102 cases of occupational lead poisoning, 17 cases of clinically verified chronic nephropathy were found (Lilis et al. 1968). Endogenous creatinine clearance was <80 pg/dL. The mean PbB level for the entire study population was 80 pg/dL (range, 42-141 pg/dL). Nephropathy was more common among those exposed to lead for more than 10 years than among those exposed for less than 10 years. 

Taken together, these studies provide some evidence for the association of chronic nephropathy in occupationally exposed workers with PbB levels ranging from 60 to >100 pg/dL. It should be noted, however, that PbB levels measured at the time of renal function testing may not fully reflect the exposure history that contributed to the development of chronic nephropathy in lead workers. 

A study of 55 adolescents who had been treated for lead intoxication in early childhood (11-17 years earlier) revealed no evidence of chronic nephropathy, as evidenced by endogenous creatinine clearance, BUN, serum uric acid, and routine urinalysis (Chisolm et al. 1976). PbB levels during the acute poisoning episode ranged from 100 to 650 pg/dL all patients received immediate chelation therapy. At the time of the study, their PbB levels had decreased to less than 40 pg/dL. 

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. 

Lilis R. 1981. Long-term occupational lead exposure, chronic nephropathy, and renal cancer A case report. Am J Ind Med 2 293-297. 

Lilis R, Gavrilescu N, Nestorescu B, el al. 1968. Nephropathy in chronic lead poisoning. BrJIndMed 25 196-202. 

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. 

In acute uric acid nephropathy, acute renal failure occurs as a result of blockage of urine flow secondary to massive precipitation of uric acid crystals in the collecting ducts and ureters. This syndrome is a well-recognized complication in patients with myeloproliferative or lymphopro-liferative disorders and results from massive malignant cell turnover, particularly after initiation of chemotherapy. Chronic urate nephropathy is caused by the long-term deposition of urate crystals in the renal parenchyma. 

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. 

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. 

Acute-, intermediate-, and chronic-duration oral exposures of male rats to doses of 10 mg/kg/day or greater were associated with renal tubular nephropathy (Gorzinski et al. 1985 NTP 1977, 1989 Weeks et al. 1979). Affected animals displayed tubular necrosis, hyaline droplets in tubular epithelial cells, regenerative tubular epithelium, interstitial nephritis, and fibrosis. The severity of the renal lesions varied with the dose and the duration of exposure. 

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. 

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