Renal atrophy

Lopez-Rodriguez, C. el al., 2004, Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression. Proc. Natl. Acad. Sci. U.S.A. 101(8) 2392-2397. 

In two cases long-term use of indinavir appeared to have been responsible for renal atrophy (23), and again one wonders whether crystals may have been present but radiologicaUy invisible. 

Hanabusa H, Tagami H, Hataya H. Renal atrophy associated with long-term treatment with indinavir. N Engl J... 

Indications Central yang insufficiency phlegm rheum disease. Chronic bronchitis, bronchial asthma, pulmonary emphysema, cardiac or nephrotic edema, valvular disease, Basedow s disease, Meniere s disease, neurosis, neurasthenia, hysteria, motion sickness, rheumatoid arthritis, chronic gastritis, chronic nephritis, renal atrophy, hypertension, sinusitis, rhinitis, anemia, conjunctivitis,chronic optic nerve disorders, optic nerve atrophy, and nebula... 

Interstitial nephritis has been described from renal biopsies in patients treated with indinavir [119-124], in some cases with eosinophiluria and crystals (assumed to be indinavir) associated with histiocytes and giant cells in the renal tubules. Some of these patients were asymptomatic, while other had urinary symptoms as described above and crystalluiia. Renal atrophy associated with long-term use of indinavir was described in two patients with hematuria, pymia, and reversible renal insufficiency [125]. 

Tamm Horsfall Sy (and TMHN, 6) Renal atrophy -Obstructive NP (5)... 

The amino acids L-leucine, T-phenylalanine, L-tyrosine, and L-tryptophan all taste bitter, whereas their D-enantiomers taste sweet (5) (see Amino ACIDS). D-Penicillamine [52-67-5] a chelating agent used to remove heavy metals from the body, is a relatively nontoxic dmg effective in the treatment of rheumatoid arthritis, but T.-penicillamine [1113-41 -3] produces optic atrophy and subsequent blindness (6). T.-Penicillamine is roughly eight times more mutagenic than its enantiomer. Such enantioselective mutagenicity is likely due to differences in renal metaboHsm (7). (R)-ThaHdomide (3) is a sedative—hypnotic (3)-thaHdomide (4) is a teratogen (8). 

Primary hyperparathyroidism occurs as a result of hyperplasia or the occurrence of adenoma. Secondary hyperparathyroidism may result from renal failure because of the associated phosphate retention, resistance to the metabolic actions of PTH, or impaired vitamin D metabolism. The last-mentioned factor is primarily responsible for the development of osteomalacia. Muscle symptoms are much more common in patients with osteomalacia than in primary hyperparathyroidism. Muscle biopsy has revealed disseminated atrophy, sometimes confined to type 2 fibers, but in other cases involving both fiber types. Clinical features of osteomalacic myopathy are proximal limb weakness and associated bone pain the condition responds well to treatment with vitamin D. 

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). 

Coenzyme Q10 (CoQlO) deficiency. This mitochondrial encephalomyopathy has three main clinical presentations. A predominantly myopathic form is characterized by the triad of exercise intolerance, recurrent myoglobinuria, and CNS involvement. A more frequent ataxic form is dominated by ataxia and cerebellar atrophy, variously associated with weakness, developmental delay, seizures, pyramidal signs, and peripheral neuropathy, often simulating spinocerebellar atrophy. A third presentation with fatal infantile encephalomyopathy and renal involvement, has been described in two families. The biochemical defect (or defects) presumably involve different steps in the biosynthesis of CoQlO, but are still unknown, as are the molecular defects. Diagnosis, however, is important because all patients - and especially those with the myopathic and infantile forms - benefit from CoQlO supplementation [13,14]. 

Adult males, age 16 weeks, fed pelleted commercial duck diet for 10 weeks diet formulated to contain 24% lead-contaminated sediment (3400 mg Pb/kg DW sediment = 816 mg Pb/kg DW total diet) 1 of 10 died vs. none in controls survivors had atrophied breast muscles, green staining of feathers around the vent, viscous bile green staining of the gizzard lining, and renal intranuclear inclusion bodies. Blood had 6.1 mg Pb/kg FW, liver had 2.8 mg Pb/kg FW, and feces had 1660 mg Pb/kg DW 61... 

Long-term lithium therapy is associated with a 10% to 20% risk of morphologic renal changes (e.g., glomerular sclerosis, tubular atrophy, and interstitial nephritis). 

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). 

EPA has derived a chronic oral RfD of 0.001 mg/kg/day for hexachloroethane (IRIS 1995). This value is based on a NOAEL of 1 mg/kg/day for atrophy and degeneration of the renal tubules in rats exposed for 16 weeks (Gorzinski et al. 1985). The NOAEL was divided by an uncertainty factor of 1,000 to account for interspecies extrapolation, human variability, and the use of a subchronic study. EPA places medium confidence in this RfD (IRIS 1995). 

Renal effects have been observed in both male and female rats in a chronic-duration oral study. Male Fischer 344 rats exposed to 1,4-dichlorobenzene at 150 and 300 mg/kg/day for 2 years exhibited nephropathy, epithelial hyperplasia of the renal pelvis, mineralization of the collecting tubules in the renal medulla, and focal hyperplasia of the tubular epithelium. Each of these effects was associated with hyalin droplet formation. There were also increased incidences of nephropathy in female Fischer 344 rats dosed with 1,4-dichlorobenzene at 300 and 600 mg/kg/day. Histopathologically, the nephropathy was characterized by degeneration and regeneration of the tubular epithelium, tubular dilatation with attenuation and atrophy of the epithelium, granular casts in the tubules of the outer stripe of the medulla, thickening of the basement membranes, and minimal accumulation of interstitial collagen (NTP 1987). 

Mice exposed continuously to 100 ppm or intermittently to 400 ppm for 11 days had histopathologic evidence of brain lesions characterized by degeneration and atrophy of the granular layer of the cerebellum. Daily exposure of mice to 1000 ppm for 2 years induced a functional limb muscle impairment and atrophy of the spleen. At 2400ppm administered daily, there were renal and hematopoietic effects and the mice were moribund by day 9. For rats exposed to 3 500 ppm 6 hours/day for up to 12 days, clinical signs included severe diarrhea, incoordination of the forelimbs, and, in a few animals, hind limb paralysis and convulsions. ... 

Administered by oral gavage to rats for 6 months, all three isomers produced splenic lesions. The meta and para isomers produced testicular atrophy, whereas o/t/ o-nitrotoluene caused renal lesions. ... 

Renal function impairment Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have occurred in patients on chronic lithium therapy. The relationship between such changes and renal function has not been established. 

Aristolochic acid All products containing aristolochic acid 04/16/2001 Aristolochic acid is associated with renal interstitial fibrosis with atrophy and loss of tubules, and the development of end-stage renal failure... 

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