Faculty Bibliography

Microorganisms may have a role in the pathogenesis and prevention of kidney stones. The subjects of this review include nanobacteria, Oxalobacter formigenes, and lactic acid bacteria. Not reviewed here is the well-described role of infections of the urinary tract with Proteus species and other urease-producing organisms associated with struvite stone formation. Nanobacteria have been proposed to be very small (0.08-0.5 nm), ubiquitous organisms that could play a role in stone formation. The theory is that nanobacteria can nucleate carbonate apatite on their surfaces and thereby provide the nidus for stone formation. However, their existence remains uncertain and many investigators are openly skeptical. Recent investigations suggest that they are artifacts, and not actually living organisms, but their proponents continue to study them. O. formigenes is an obligate anaerobe which may be important in the prevention of stone formation. Its sole substrate for generation of ATP is oxalate. It may thereby metabolize its human host's dietary oxalate and diminish intestinal absorption and subsequent urinary excretion of oxalate. There is evidence that the organism's absence, perhaps sometimes due to courses of antibiotics, may be a cause of hyperoxaluria and stone formation. In early investigations, patients not colonized with the organism can be recolonized. Urinary oxalate can be diminished by accompanying an oxalate-containing meal with the organism. One study demonstrated that a preparation of lactic acid bacteria successfully reduced urinary oxalate excretion in 6 patients with calcium oxalate stones and hyperoxaluria. The mechanism of this effect is uncertain since these bacteria lacked the gene possessed by O. formigenes which codes for that organism's oxalate uptake mechanism. The author is currently completing a small randomized controlled clinical trial with this preparation in calcium stone-forming patients with idiopathic hyperoxaluria

Fourteen hemodialysis patients were selected to receive once every other week darbepoetin alfa in substitution for weekly subcutaneously administered epoetin alfa. All patients included in the analysis were male veterans over the age of 18 on established and unchanging doses of subcutaneous erythropoietin alfa and on hemodialysis for at least 3 months. All patients had sufficient iron stores, defined as serum ferritin concentrations of greater than 100 mcg/L. Patients were converted to darbepoetin alfa using the manufacturer's conversion chart. Doses of darbepoetin alfa were adjusted to maintain a hemoglobin concentration greater than 11 to 12 g/dL and a hematocrit greater than 33% to 36%. Patients were followed for 4 months and evaluated for efficacy. Hemoglobin, hematocrit, and serum ferritin levels were measured at baseline and repeated every month. Among the 12 patients completing the study, 12 dose increases of darbepoetin alfa were needed. Switching these 12 patients from erythropoietin alfa to darbepoetin alfa was projected to increase acquisition cost by more than $36,000, assuming that these patients remained on their current doses of darbepoetin alfa for 1 year. The authors concluded that darbepoetin alfa should not be used in patients with anemia caused by chronic renal failure who require hemodialysis until further studies support this use

The Homocysteine Study (HOST) Veterans Affairs Cooperative Studies Program No. 453, is a prospective, randomized, two arm, double blind study of patients with end stage renal disease (ESRD) or advanced chronic kidney disease (ACKD, defined as an estimated creatinine clearance of 30 ml/min or less). Its primary objective is to determine whether administration of high doses of three vitamins, folic acid, vitamin B6 and vitamin B12, to lower the high plasma homocysteine levels, will reduce all cause mortality. The secondary objectives are to examine whether the treatment lowers the incidence of myocardial infarction, stroke, amputation of a lower extremity, a composite of death and the foregoing three events, the plasma homocysteine level, and, in ESRD patients undergoing hemodialysis, thrombosis of the vascular access. A unique feature of this trial is that after initial evaluation at enrollment and one return visit the follow up is exclusively by phone (or, if necessary, by mail). The subject is contacted every three months throughout the duration of the study from a central location. The study drug is shipped to the patient from a central location rather supplied locally. In a two year enrollment period, 2006 patients are to be enrolled. The duration of the observation period is four to six years. Data will be stored and analyzed at a coordinating center. The study design has the power to detect a reduction in all cause mortality rate of 17%. Issues related to the unique features of the design of this study are discussed