Nanobacteria strike the kidney again.
While scientists had already identified flawed genes at the heart of most cases of PKD, a research group now suggests that odd microbes, known as nanobacteria, play an equally important role in the disease's progression. Last year, Finnish investigators argued that many kidney stones result from unusually small bacteria that form calcium-rich shells around themselves (SN: 8/1/98, p. 75). These nanobacteria seem to live within kidneys or in the urine that the organs produce.
For the past decade, Marcia Miller-Hjelle of the University of Illinois College of Medicine at Peoria and her colleagues have investigated whether an infectious agent plays a role in PKD. Several clues motivated the hunt. First, the onset of PKD varies among people with identical gene mutations. While PKD can destroy kidneys in childhood, some people suffer no problems until decades later.
Second, when examining fluid within the cysts, the researchers found an immune-stimulating bacterial substance called endotoxin, which indicates that PKD kidneys were infected. Finally, studies have shown that mice with a form of PKD will survive longer if kept in a germfree environment.
Despite all this evidence, Miller-Hjelle and her colleagues were unable to isolate and cultivate any infectious microbe from the kidneys or cyst fluids of people with PKD. Then, they learned of nanobacteria, which don't grow in traditional culture media. Working with the Finnish scientists who discovered the microbes, the researchers found signs of nanobacteria in most people with PKD. For example, they cultured the microbes from 10 of 12 kidneys from PKD patients. Microscopy revealed nanobacteria in each of seven PKD kidneys, and cyst fluids contained proteins specific to nanobacteria.
While not dismissing the importance of gene mutations, the investigators speculate that nanobacteria and their endotoxin cause much of PKD's harm. The gene mutations may create kidneys that are especially vulnerable to damage, perhaps because the organs can't repair themselves easily.
"It's a combination of environment and genetics," suggests Illinois' J. Thomas Hjelle. The researchers now plan to grow PKD-prone mice in germfree conditions and infect them with nanobacteria.
"It's certainly feasible that the presence of an infectious microbe can accelerate or exacerbate the disease process," comments PKD investigator James P. Calvet of the University of Kansas Medical Center in Kansas City. Yet, there's strong evidence that many PKD cysts form extremely early in life, even during fetal development, he notes. Such cysts are difficult to explain as the result of an infection, says Calvet.