Questioning a Paradigm

Mostly I post my personal musings on science, healthcare, and other nonsense that catches my eye. Today I am going to post about a medical study that was just published in the July 2 issue of New England Journal of Medicine.

The first author is Michael Mauer, a pediatric nephrologist at the University of Minnesota and my research mentor during my fellowship (consider this my disclaimer of potential bias). The study examines changes in kidney function and structure over 5 years in patients with type 1 diabetes, the type most common in young children. This study examined primary prevention of diabetic kidney disease; patients without albuminuria (thought to be the earliest manifestation of the problem) or hypertension (high blood pressure), and with normal kidney function (glomerular filtration rate) were assigned to receive enalapril (which inhibits angiotensin converting enzyme), losartan (which blocks the angiotensin II receptor), or placebo. They not only examined all of these functional studies before and after 5 years of treatment, but also performed kidney biopsies with morphometric studies for the lesions seen in diabetic nephropathy (primarily expansion of the mesangium of the glomerulus).

Drugs that block the renin-angiotensin system, like enalapril and losartan, have been shown to benefit patients with advanced kidney disease from diabetes (shown in photo) and other causes. They also seem to benefit patients with early type 2 diabetes (the type seen more commonly in adults and associated with obesity). It has been hoped that they would prevent kidney disease entirely, although smaller, shorter studies have failed to demonstrate this phenomenon. Thus, the hope that this study would answer the question: should all patients with type 1 diabetes be put on these drugs at the time of diagnosis of diabetes?

The answer seems to be no for now. Neither drug showed a clear benefit over placebo in any parameter measured. The study is not perfect; a number of questions arise with careful reading of the article and the supplementary material. Like most studies, the results will breed discussion, more questions, and more experiments.

Probably the most important point I can make here is that

paradigms are meant to be shifted.

We cannot prove anything merely by arguing its logic or making observations from other situations. Logic and other situations suggest that these drugs would work!

 We must do the appropriate experiment if we really want to answer the question.

Diabetes is the most common cause of kidney failure in the United States, although most patients have type 2 diabetes. Drugs like enalapril and losartan still play an important role in the management of this disorder, especially in patients with type 2 disease and more advanced kidney problems. For now, though, we will not be starting these drugs along with insulin in newly diagnosed type 1 patients. And we must keep looking for treatments and cures.

Click below to link to the abstract: