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Can Bacteria Be Trained to Do the Kidney's Work?

Eli A. Friedman, M.D.

In industrialized countries, peritoneal- and hemo-dialysis sustain the lives of more than a quarter of a million patients whose kidneys don't work effectively (renal insufficiency). The cost of this therapy, however, exceeds health care budgets in all developing countries. The majority living in poorer nations have no chance of effective treatment should their kidneys fail. Even in richer countries, concerned about rising health care costs, it may one day be difficult for everyone who needs it to receive dialysis. But there is hope. Two cutting-edge bionic approaches offer the possibility of a low-cost way of substituting for failing kidney function (uremia). For all those who cannot afford expensive dialysis to keep them alive, there is urgency in the quest for this alternative, minimal cost therapy.

The Bowel as a Substitute Kidney

One possibility involves construction of a bioartificial kidney in which filtering and secreting kidney functions are performed by culture-grown cells implanted in a hollow fiber or mesh matrix.(1) In the other approach, trained bacteria will break down nitrogenous wastes within the gut. These treatments are still in the experimental stages but show promise.

Historical Background

More than two thousand years ago, Hippocrates, the ancient Greek physician, vaguely described oral treatment for kidney disorders.(2) Use of bowel elimination as a means of managing kidney disease is recorded in Dioscorides' Materia Medica in 40 B.C. in which terra sigillata, a sacred earth found on the Greek island of Lemnos, is advocated for multiple disorders including diseases of the kidney.(3) By 100 A.D., Pliny prescribed this esteemed medicine as an oral sorbent against complaints of the spleen and kidneys, copious menstruation, poisons and wounds caused by serpents. Though terra sigillata is forgotten, other oral sorbents including charcoal,(4) oxidized starch,(5) locust bean gum (a mannose polymer derived from seeds of the ceratonia siliqua tree)(6) and microcrystalline carbon with an oxygen complex surface oxide(7) have each been reported in this century as beneficial in the uremic syndrome by promoting nitrogenous waste extraction.

Oral Sorbents

In 1976, W.J. Kolff, a distinguished researcher, pioneered the investigation of the usefulness of oral sorbents in uremia, exploring the effect of charcoal ingestion on nitrogenous waste serum levels.(8) He found that creatinine, uric acid and other nitrogenous human wastes can easily be removed with charcoal, although perhaps the charcoal removes too much. He also found that phosphates can easily be removed with aluminum preparations.

The real problem is the waste product, urea. Twenty grams of urea must be removed from a person's bloodstream every day in order to maintain the best possible metabolic balance. Scientists realized that limiting dietary protein might help minimize the nitrogenous waste burden, a step now incorporated in the management of kidney failure.(9) By using various polymers as capsules (microencapsulation) around particles of activated charcoal, the amount of charcoal needed to remove 400 mg of creatinine is reduced from 190 g to approximately 50g.(10)

Recently, AST-120, an oral sorbent synthesized in Japan, comprised of particles of porous carbon has attracted attention. Clinical trials (thus far limited to Japan) of AST-120, administered to 27 patients with renal insufficiency, prolonged the interval between hemodialysis treatments from a mean of 5.0 months in controls to a mean of 14.3 months, giving the patients an extra nine months free from dialysis.(11)

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