Endotoxin and nanobacteria in polycystic kidney disease

Background. Microbes have been suspected as provocateurs of polycystic kidn ey disease (PKD), but attempts to isolate viable organisms have failed. Bac terial endotoxin is the most often reported microbial product found in PKD fluids. We assessed potential microbial origins of endotoxin in cyst fluids from 13 PKD patients and urines of PKD and control individuals. Methods. Fluids were probed for endotoxin and nanobacteria, a new bacterium , by the differential Limulus Amebocyte Lysate ass ay (dLAL), genus-specifi c antilipopolysaccharide (LPS) antibodies, monoclonal antibodies to nanobac teria, and hyperimmune serum to Bartonella henselae (HS-Bh). Selected speci mens were also assessed by transmission electron microscopy (TEM) and nanob acterial culture methods. Results. LPS or its antigenic metabolites were found in more than 75% of cy st fluids tested. Nanobacteria were cultured from 11 of 13 PKD kidneys, vis ualized in 8 of 8 kidneys by TEM, and immunodetected in all 13 PKD kidneys. By immunodetection, nanobacterial antigens were found in urine from 7 of 7 PKD males, 1 of 7 PKD females, 3 of 10 normal males, and 1 of 10 normal fe males. "Nanobacterium sanguineum" was dLAL positive and cross-reactive with antichlamydial LPS and HS-Bh. Some cyst fluids were also positive for LPS antigens from Escherichia coli, Bacteroides fragilis and/or Chlamydia, and HS-Bh, as were liver cyst fluids from one patient. Tetracycline and citrate inhibited nanobacterial growth in vitro. Conclusion. Nanobacteria or its antigens were present in PKD kidney, liver, and urine. The identification of candidate microbial pathogens is the firs t step in ascertaining their contribution, if any, to human disease.