Molecule may protect against kidney damage

Kidney failure immediately after heart-bypass surgery hikes a patient’s risk of other complications and death. Scientists now report that people whose genes encode a protein called apolipoprotein E-IV (apoE-IV) are less likely to suffer such kidney failure than are patients who make another version of the protein.

Scientists are just beginning to understand the workings of apoE-IV and its counterparts, apoE-II and apoE-III. Every person makes one or two of the three subtypes. Most people produce apoE-III, and up to one-fourth, apoE-IV. The proteins play a role in immune reactions, activate certain enzymes, and usher fat particles to and from the liver during processing.

Scientists know that people with apoE-II, the least common form, have a heightened risk of chronic kidney failure. This condition takes years to develop into a full-blown kidney problem that requires dialysis. That link spurred Mark Stafford-Smith, an anesthesiologist at Duke University Medical Center in Durham, N.C., to investigate whether differences in apoE status might also influence the risk of abrupt kidney failure. The problem strikes about 8 percent of heart-bypass patients soon after surgery.

Stafford-Smith and his colleagues analyzed the concentrations of creatinine in blood taken from 414 nondiabetic and 150 diabetic heart-bypass patients before and after surgery.

Creatinine, a compound formed by muscle breakdown, is filtered out of the blood by the kidneys. Too much creatinine in blood signals that the kidneys are failing.

Nondiabetic patients with at least some apoE-II protein experienced a 34 percent jump in creatinine concentrations after bypass surgery, and those with only apoE-III saw a 27 percent rise. However, creatinine rose only 18 percent, on average, in people with apoE-IV or with a combination of apoE-III and apoE-IV, the researchers report in the August Anesthesiology.

Among the patients with diabetes, creatinine concentrations rose 30 percent in people with some apoE-II, 40 percent in those with only apoE-III, but only 23 percent in people with apoEIV, with or without apoE-III.

This study is the first to match apoE status with signs of sudden kidney trouble, Stafford-Smith says. While the observed blood-creatinine increases lie within the normal range, they represent a worrisome trend, he says.

Nearly all heart-bypass patients suffer minor kidney damage. Of bypass patients who develop abrupt kidney problems that require hospitalization but not dialysis, 20 percent die while still in the hospital. The other 80 percent—when compared with bypass patients without kidney problems—have more complications and are three times more likely to require a stay in an extended-care facility, Stafford-Smith says. Among the 1 to 2 percent of patients who need dialysis immediately after bypass surgery, most die in the hospital.

Thus, knowing people’s apoE status might help surgeons decide which patients are at greatest risk of kidney failure from heart surgery, he says.

How bypass surgery leads to kidney damage remains unclear. Some patients also suffer strokes or brain damage after the operation. In such cases, small particles, possibly dislodged in surgery, appear to clog brain capillaries.

Ironically, because apoE-IV has a poor record of clearing fat particles from the blood, some evidence suggests it could contribute to certain neurological problems. Moreover, apoE-IV appears to be a bad actor in Alzheimer’s disease, although the mechanism for that is unclear (SN: 5/18/96, p. 312).

The new study shows how a molecule “can pop up time and again playing what are perhaps opposite roles” in different diseases, says Lanny J. Haverkamp, a neuroscientist at Baylor College of Medicine in Houston.

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