Detection of endotoxiuria in polycystic kidney disease patients by the use of the Limulus amebocyte lysate assay.

Urinary tract infections (UTI) due to gram-negative bacteria are a serious complication in patients with polycystic kidney disease (PKD). Endotoxin, a component of the cell wall of gram-negative bacteria, has been reported to be pro-cystogenic in experimental animals. Because endotoxin levels in urines (endotoxiuria) from PKD patients have not been reported, the Limulus amebocyte lysate (LAL) assay, which detects picogram quantities of endotoxin, was used to probe for this cyst-promoting chemical. Fifteen PKD patients (seven females, eight males), asymptomatic for UTI, were tested and compared with 10 female and 10 male controls. All urines were assessed for (1) evidence of aerobic bacteria by routine quantitative cultures, (2) bacteria and pyuria by microscopic examination of gram-stained urine, and (3) bacterial endotoxin by the LAL assay. LAL tests were positive in 73% (11/15) of PKD patients, but only 25% (5/20) of controls (P = 0.0058). There was no significant difference in test positivity between PKD females (71%) and males (75%). There was no correlation of age, degree of renal dysfunction, or urine osmolality with endotoxiuria. Routine quantitative cultures were negative for gram-negative bacteria in PKD patients and all controls (except one female), as were microscopic findings for intact bacteria and pyuria. Thus endotoxiuria, in the absence of classical signs, symptoms, and microbiological findings of UTI, raises the possibility that endotoxin is available intrarenally to promote cystogenesis even before a potential susceptibility of PKD patients to classical UTI is manifested. Sources of urinary endotoxin observed in PKD patients, such as cryptic intrarenal sites or leakage from the gastrointestinal (GI) tract, remain to be defined.