|Peterson, Stephen - Steve|
|Dombrink Kurtzman, Mary Ann|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/6/1998
Publication Date: N/A
Citation: Interpretive Summary:
Technical Abstract: PKD is the most common monogenetic disease in man. This fatal and incurable disease afflicts one in every 400-1000 humans, 12-15 million individuals worldwide. Kidney failure will occur in half of the PKD population by age 50; annual treatment costs for PKD exceed $1 billion in the USA. Although PKD has been viewed as a classical genetic disease, Werder et al have reported that germ-free conditions blocked cyst formation and increased survivorship in genetically cystic mice and endotoxin promoted cystogenesis in a germ-free, chemically-induced rat model of PKD (Gardner et al.). We set out to survey for the presence of fungal components in a small number of human PKD kidney tissues and cyst fluids. PKD kidneys were obtained at nephrectomy and handled by sterile technique. Using universal fungal primers, ITS1 (Internal Transcribed Spacer region; forward primer) and NL4 (Nuclear Large subunit; reverse primer), amplicons of the predicted molecular weight were obtained by polymerase chain reaction methods from 3 of 3 PKD kidneys, but not from normal human kidney. The finding of fungal DNA is consistent with the presence of fungal colonization or infection. Standard microbiological methods did not yield fungal growths from human PKD cyst fluids. However, a new species of Penicillium was cultured from two separate PKD patient kidneys during the propagation of epithelial cells isolated from dissected cyst walls. Based on these and other findings of microbial components, we have proposed that PKD is best viewed as an emerging infectious disease and/or microbial toxicosis in a genetically vulnerable human population. This hypothesis of potential fungal influences in PKD overlaps a growing awareness of sphingolipid biology in PKD and as a target of microbial toxins.