About one in three diabetics dependent on insulin eventually develop kidney failure, requiring dialysis or a kidney transplant to survive. Hope that these problems can be delayed, and perhaps even prevented, comes from the latest research into a new class of drugs called Ace inhibitors.
Ace inhibitors, which owe their discovery to research on the venom of a South American snake, are likely to prove as significant to modern medicine as the Nobel Prize-winning discovery of beta blockers. They are already used to treat high blood pressure and heart failure and may prove to have a role in brain problems such as Alzheimer’s disease.
However broad their eventual application, much current interest is focused on the potential of Ace inhibitors to decrease the long-term kidney damage caused by diabetes.
As well as having kidney problems, diabetics are about twice as likely as non-diabetics to have high blood pressure. (For this reason, all diabetics should have their blood pressure checked regularly.)
Adult-onset diabetics tend to have high blood pressure at the time their diabetes is diagnosed. But diabetics dependent on insulin develop the condition in the course of their disease — at roughly the same time as kidney damage becomes apparent.
This close association is certainly no accident. It was once thought that the kidney problems caused raised blood pressure. But many doctors now argue that the reverse is true. This is an important change in thinking because while we have no established way of reversing kidney damage, we have well-tried means of reducing blood pressure.
Losing weight, cutting down on salt and taking exercise are important ways of doing this without resorting to drugs. But full control of high blood pressure usually requires pharmacological intervention.
Hans-Henrik Parving, in Denmark, was one of the first doctors to urge aggressive treatment of high blood pressure in diabetics with established kidney disease. He showed convincingly that effective control of hypertension slowed the decline in kidney function.
Before treatment, his patients were on course for dialysis or kidney transplants within seven years. At the present rate of deterioration, it looks as if their kidneys will hold out for at least three times that long.
One of the main signs of kidney damage is fining protein in the urine. Its presence shows the kidneys are “leaky” (allowing large molecules through) and are not working so effectively as excretors of waste.
The problem can be detected by dipping a protein-sensitive strip in the urine. Using more sophisticated instruments, it is possible to detect far lower levels of protein — a condition called microalbuminuria. In itself, microalbuminuria is not harmful. But it is certainly a marker of early kidney damage.
Doctors had established that reducing high blood pressure helped patients with obvious kidney damage. The next question was whether they should give drugs to diabetics with normal blood pressure and only slight signs of kidney damage in the hope of catching the condition early, and perhaps of preventing it.
Certain scientists, among them Barry Brenner from Harvard Medical School, believe pressure within the filtering units (or glomeruli) of the kidney may be damagingly high even when blood pressure in the rest of circulation is normal.
This is where the Ace inhibitors become important — they may cut pressure in the glomeruli. Much work supporting this idea has come from animal experiments. But hopeful evidence in patients is beginning to emerge. Apparently, Ace inhibitors do reduce the amount of protein in the urine at doses which do not lower the normal blood pressure.
Dr Parving has demonstrated this in a small group of patients in Denmark. Research from Michel Marre in Paris, who has also used an Ace inhibitor in diabetic patients with microalbuminuria but normal blood pressure, shows the same effect.
If these results are confirmed, doctors may begin to prescribe Ace inhibitors to diabetics with normal blood pressure but early signs of kidney problems. The final issue would then be whether all diabetics should be treated with an Ace inhibitor despite a normal blood pressure and no evidence of early kidney disease, in hope of preventing its development.
As well as their potential in reducing the complications of diabetes, Ace inhibitors may have a role in brain disease. One of the most surprising findings to emerge from a meeting on Ace inhibitors was that memory deficits in rats could be reversed by an Ace inhibitor.
Researchers are impressed by the similarities between models of memory deficits in animals and Alzheimer’s disease in man.