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 culture of hMIC was based on the primary culture of human renal medullary explants, selective detachment of interstitial cells and selective overgrowth of these cells in a serum-rich medium after dilution cloning. The homogenous population of cells obtained exhibited the characteristic morphological and functional characteristics of Type I interstitial cells, viz. stellate-shaped cells demonstrating numerous lipid droplets, abundant endoplasmic reticulum and mitochondria, fine filaments underlying the cell membrane and the production of extracellular matrix. Cytotoxicity studies using hMIC and known papillotoxins clearly demonstrated a reduction in cell viability that varied with bath exposure time and type of agent tested. While only phenylbutazone and mefenamic acid produced significant cytotoxicity after a 24 h incubation period, cell viability assessed using the MTT assay was only profoundly 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 potential of hMIC for investigating and defining the early cellular events in the pathogenesis of analgesic nephropathy.