The mechanism of increased renal susceptibility to toxic substances in the elderly. Part I. The role of increased vasoconstriction.

The mechanisms of increased susceptibility to nephrotoxins in aging are complex and incompletely understood. It is very important to try to increase our knowledge of them because adults become increasingly vulnerable to nephrotoxic substances, as they grow older. In addition, the percentage of elderly people will increase markedly in the near future, at least in the developed countries. Drugs such as diuretics, laxatives, NSAIDs, aminoglycosides and other nephrotoxic antibiotics, and converting enzyme inhibitors are used a lot by aging people and can produce severe renal problems. Beside drugs, the clinical use of radiocontrast agents also rises in older patients. It seems that the main mechanism of the increased renal susceptibility to toxic substances in the elderly is a disbalance between vasoconstrictor and vasodilator factors (in favor of vasoconstrictor ones). Increased propensity to vasoconstriction (to Ang II, ET and PAF), as well as increased levels of oxidatively modified biomolecules in the elderly, may enhance susceptibility of old kidney to toxic substances. In addition, all mechanisms that influence both mesangial and fibroblast cell proliferation and over-production of extracellular matrix might also be involved in the processes that make the old kidney prone to drug-induced chronic toxic injury.