Functional-morphologic correlations in assessing renal toxicity

Evaluation of the correlation of functional and morphologic assessments of renal toxicity are obviously important to the toxicologic pathologist. All clinical assessments of the nephrotoxicity of drugs are based on renal function tests while preclinical assessments involve functional and/or morphologic assessments in laboratory animals. However, there are considerable concerns about the sensitivity of the tests available to monitor renal function. In an attempt to assess the relative sensitivity of functional and morphologic indicators of nephrotoxicity, three data bases were examined for their ability to rank the nephrotoxicity of the three most widely used aminoglycosides. The functional data base was comprised of reported comparative clinical trial data and the morphologic data base was composed of preclinical studies available in the literature which used morphology as the basis of comparison. A third data base involved biochemical or mechanistic comparisons of aminoglycosides and represented data that was not based on clinical function test results or morphologic analysis. When these three data bases were compared, it was obvious that clinical function tests could not discriminate between the nephrotoxic liability of the three aminoglycosides. The preclinical renal morphology data base and the biochemical mechanistic data base both clearly discriminated the drugs one from another and ranked the three aminoglycosides in the same order. Several conclusions were suggested by these results. Comparisons of the nephrotoxic potentials of drugs in patients utilizing available renal function tests may be inconclusive primarily because clinical renal function tests are insensitive. Comparisons of the nephrotoxic liabilities of drugs in laboratory animals utilizing morphologic assessments of renal tissue damage may be the best comparison available.(ABSTRACT TRUNCATED AT 250 WORDS)