Tubular atrophy

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). 

Rats fed 62 mg/kg/day for 16 weeks exhibited no overt toxicity. Kidney effects characterized by increased kidney weights and microscopic changes (tubular atrophy, degeneration, hypertrophy and/or dilation) were observed in males at 15 and 62 mg/kg/day in females tubular atrophy and degeneration of the kidneys were observed only at the highest dose. Both sexes also had increased liver weights at 62 mg/kg/day. ... 

Aerosol - Doses administered to mice between 35 and 150 mg/kg/day resulted in significant seminiferous tubule atrophy, decreased sperm concentrations, and increased numbers of sperm with abnormal morphology. Partial recovery of sperm production was apparent 3 to 6 months following dose cessation. Testicular lesions (tubular atrophy) in adult rats at oral dose levels as low as 16 mg/kg/day was shown. 

F tubular atrophy, glomeruli with fibrous infiltration)... 

New Zealand white rabbits administered doses of 0.3 and 0.9 mg/kg/day as triphenyl tin hydroxide by gavage during the period of organogenesis failed to gain weight at the same rate as the controls or the animals given 0.1 mg/kg/day. Food consumption was also reduced (Rodwell 1987). Male rats fed this same compound at closes of 0.3 mg/kg/day and above displayed a dose- related increase in Leydig cell hyperplasia (p<0.0005) and tubular atrophy (p=0.004) of the testes (Tennekes et al. 

Several adulterants added to nonherbal supplements, vitamins, and herbal medicine preparations can cause renal dysfunction and renal failure. Aristolochic acid is used as a herbal remedy for weight loss and has been reported to cause Chinese herb nephropathy characterized by extensive interstitial fibrosis with tubular atrophy and loss. Herbal medicine preparations produced in South Asia contain potentially harmful levels of lead, mercury, and/or arsenic which can lead to renal toxicity. 

In summary, the following effects were noted in males but not in a dose related maimer (1) renal cytoplasmic vacuolahon, anisokaryosis, nuclear vesiculation, nuclear pyknosis, tubular dilatation, tubular atrophy, and reticulin sclerosis were observed at 0.05 mg U/kg/day and above (all dose levels) (2) nuclear hyperchromicity was observed at 0.20 mg U/kg/day and above and (3) apical displacement of nuclei, protein casts, and collagen sclerosis were observed at low and high doses, but not at some intermediate doses. 

A 58-year-old woman developed acute renal insufficiency soon after a 7-day course of cefdinir 300 mg/day for acute bronchitis. Renal histology showed tubular atrophy and interstitial fibrosis accompanied by moderate lymphocyte infiltration. A lymphocyte stimulation test with cefdinir was positive. Serum creatinine concentrations continued to rise even after withdrawal of cefdinir, but steroid therapy normalized renal function. 

During treatment with extremely high doses of factor IX concentrate, to induce immune tolerance, nephrotic sjm-drome has been described (6,7). Withdrawal or dosage reduction is of crucial importance for the resolution of nephrosis (6). Renal biopsy in one of these patients showed peripheral capUlary wall thickening and deposits throughout the basement membrane (7). In addition minimal interstitial fibrosis and tubular atrophy were present. There were no deposits of factor IX in the glomeruli, which the authors attributed to absence of free factor IX epitope in the tissue (7). 

Limitations of the technique include 1) The induction of hydronephrosis may alter vasoreactivity 2) tubular atrophy eliminates tubular influences on the microcirculation such as those observed in the tubu-loglomerular feedback phenomenon and 3) intrinsic vascular resistances are higher and blood flows lower in hydronephrotic compared to normal kidneys. 

Landing BFI, Ang SM, Flerta N, Larson EF, Turner M. Labeled lectin studies of renal tubular dysgenesis and renal tubular atrophy of postnatal renal ischemia and end-stage kidney disease. Pediatr Pathol 1994 14 87-99. 

Figure 3. Sequential renal biopsies, separated by 10 years, in a patient with hypokalemia related to chronic diuretic abuse. Initial biopsy (on the left) shows proximal tubular cell vacuolization and mild interstitial inflammation. The subsequen t examination (on the right) demonstrates marked interstitial fibrosis, tubular atrophy and dropout.

TUbular d gen ratlon/slngla Cell necrosis PCT, cortex O TUbular degeneration, outer medulla Tubular atrophy, cortex... 

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