The problem

One of the complications of diabetes - type 1 or type 2 - is kidney failure. In the case of type 2, it's called end-stage renal disease (ESRD), and it's increasing at an alarming rate - doubling, in fact, in the last 10 years. (This corresponds with the epidemic of type 2 diabetes now prevalent in the USA). As there's no parallel increase in the numbers of kidney donated for transplantation, most of the new cases have to go on to dialysis, indefinitely. All this emphasizes the need for steps to prevent ESRD, and this is the subject of 3 articles and a recent editorial in the New England Journal of Medicine.

What can be done

The first step is to be sure that blood sugar levels and high blood pressure are adequately controlled. Apart from adoption of a suitable lifestyle (no smoking, healthy diet, exercise), there are excellent medications that allow such control to be achieved.

One type of the commonly used high blood pressure medications has been found to slow the development of ESRD in type 1 diabetics. What's more, this effect is over-and-above the drug's effect on high blood pressure. These drugs belong to the angiotensin-converting-enzyme (ACE) inhibitors class. So far, there has not been evidence of their effectiveness in type 2 diabetics with early kidney disease.

Recently, a new class of blood pressure lowering drugs have been developed that are close relatives of the ACE inhibitors. The three studies just reported in the New England Journal of Medicine describe the use of two of these drugs - irbesartan and losartan - in patients with type 2 diabetes who were at risk of ESRD.

Angiotensin-receptor antagonist drug trials

In one of the studies, irbesartan was given to patients with type 2 diabetes and high blood pressure who had a slight amount of protein in their urine, but no other signs of kidney disease. The patients were kept on their usual medications during the study. Two dose levels (150 and 300 mg daily) of irbesartan were compared with a dummy tablet (placebo) over a 2-year period.

In this study, irbesartan reduced the number of patients who developed a critical amount of protein in the urine in the 2-year period, a greater benefit being shown with the higher dose. Blood pressures were not changed significantly by the medication. There were no serious side effects

The other studies were done in type 2 diabetics with more advanced kidney disease. In one, losartan (50 to 100 mg daily) was compared with a placebo, for an average of 3½ years. Losartan significantly reduced development of ESRD and hospital admissions for heart failure, but had no effect on the death rate.

The third study compared irbesartan (300 mg daily) with another high blood pressure drug (amlodipine, a calcium channel blocker) and placebo, over 2½ years. The same benefits were seen: a slowing of the development of ESRD, but again no reduction in mortality during the study period.

In all three studies, the benefits were clearly more pronounced than those that could be attributed to changes in blood pressure. On average, there was a delay in the onset of ESRD, and hence the need for dialysis (or a kidney transplant) for about 2 years.

Conclusions

Given their apparent usefulness in type 1 diabetics, one may ask why ACE inhibitors have not been studied in this sort of study. It must be realized that such studies, if they are to provide any conclusive results, are extremely expensive to carry out. Much of the money comes from pharmaceutical companies, and they are clearly more interested in evaluating newer drugs that are still under patent protection.

If, indeed, ACE inhibitors and angiotensin-receptor blockers are found to be equally effective in patients at risk of ESRD, the decision about which type to prescribe should be based on possible side effects and cost. ACE inhibitors produce a troublesome cough in 5-20% of patients, and this side effect is rarely reported with angiotensin-receptor blockers. On the other hand, ACE inhibitors are relatively cheap - so cheap, in fact, that one expert has recommended that all middle-aged type 2 diabetics should be prescribed an ACE inhibitor, regardless of whether they have any evidence of kidney disease.

In spite of these encouraging results with the angiotensin-receptor blockers, it must be remembered that the benefits achieved represent a postponement, but not total prevention, of ESRD. We still need more effective approaches - apart from the obvious ones (diet, exercise, blood pressure and diabetic medications) - to prevent type 2 diabetes in the first place.