|Dombrink Kurtzman, Mary Ann|
|Peterson, Stephen - Steve|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 9/11/1997
Publication Date: N/A
Citation: N/A Interpretive Summary:
Technical Abstract: Polycystic kidney disease may be an emerging infectious disease and/or microbial toxicosis in a vulnerable human subpopulation. Endotoxin was found in cyst fluid taken from the nephrectomized kidneys of 6 of 6 autosomal dominant (AD) PKD patients, and 1 of 2 autosomal recessive (AR) PKD patients. Fatty acid analysis of cyst fluid confirmed the presence of 3-hydroxy fatty acids characteristic of endotoxin. Fungal (1-3)-beta-D-glucans were found in cyst fluid from 2 of 6 ADPKD and 1 of 2 ARPKD kidneys. Tissue and cyst fluid from three ADPKD patients were examined for fungal components. Serological tests demonstrated Fusarium, Aspergillus, and Candida antigens. IgE reactive with Fusarium and Candida were also detected in cyst fluid. Fungal DNA was detected in kidney tissue and cyst fluid from patients, but not in healthy human kidney tissue. Because some of the fungi observed are known to produce toxins that influence sphingolipid biology and endotoxin can directly mimic some actions of ceramide, we measured sphingoid base levels in ADPKD and ARPKD tissue and cyst fluid. Free sphinganine, an important intermediate in the de novo synthesis of ceramide, was found in only 2 of 6 ADPKD kidneys, 0 of 4 dissected cyst walls, and 0 of 10 cultures of cyst wall cells. Free sphinganine was not found in ARPKD kidney tissue and cells in vitro. Normal human kidney tissue did contain free sphinganine. Only the "chocolate cyst fluids" from ADPKD kidneys contained free sphinganine. Thus, the presence of infection, microbial components, and anomalies in sphingolipid biology need to be considered as potential early and long term contributors to the pathophysiology of PKD.