POLYCYSTIC KIDNEY-DISEASE - AN UNRECOGNIZED EMERGING INFECTIOUS-DISEASE

Polycystic kidney disease (PKD) is one of the most common genetic dise ases in humans. We contend that it may be an emerging infectious disea se and/or microbial toxicosis in a vulnerable human subpopulation. Use of a differential activation protocol for the Limulus amebocyte lysat e (LAL) assay showed bacterial endotoxin and fungal (1-->3)-beta-D-glu cans in cyst fluids from human kidneys with PKD. Fatty acid analysis o f cyst fluid confirmed the presence of 3-hydroxy fatty acids character istic of endotoxin. Tissue and cyst fluid from three PKD patients were examined for fungal components. Serologic tests showed Fusarium, Aspe rgillus, and Candida antigens. IgE, but not IgG, reactive with Fusariu m and Candida were also detected in cyst fluid. Fungal DNA was detecte d in kidney tissue and cyst fluid from these th ree PKD patients, but not in healthy human kidney tissue. We examine the intertwined nature of the actions of endotoxin and fungal components, sphingolipid biolog y in PKD, the structure of PKD gene products, infections, and integrit y of gut function to establish a mechanistic hypothesis for microbial provocation of human cystic disease. Proof of this hypothesis will req uire identification of the microbes and microbial components involved and multifaceted studies of PKD cell biology.