Human renal medullary interstitial cells and analgesic nephropathy

The aim of this study was to investigate the effects of known papillotoxins using cultures of human renal interstital medullary cells (hRMIC). The cul ture of hMIC was based on the primary culture of human renal medullary expl ants, selective detachment of interstitial cells and selective overgrowth o f these calls in a serum-rich medium after dilution cloning. The homogenous population of cells obtained exhibited the characteristic morphological an d functional characteristics of Type I interstitial cells, viz. stellate-sh aped cells demonstrating numerous lipid droplets, abundant endoplasmic reti culum and mitochondria, fine filaments underlying the cell membrane and the production of extracellular matrix. Cytotoxicity studies using hMIC and kn own papillotoxins clearly demonstrated a reduction in cell viability that v aried with bath exposure time and type of agent tested While only phenylbut azone and mefenamic acid produced significant cytotoxicity after a 24 h inc ubation period, cell viability assessed using the MTT assay was only profou ndly reduced by aspirin and paracetamol following sub-chronic exposure for 7 days. The rank order of cytotoxicity observed in hMIC was phenylbutazone > mefenamic acid > aspirin > paracetamol. The results demonstrate the poten tial of hMIC for investigating and defining the early cellular events in th e pathogenesis of analgesic nephropathy.