Frontiers in diabetic nephropathy: can we predict who will get sick?

O ver my practice lifetime, a subtle but persistent change has occurred in the profile of diseases that afflict patients. We no longer are faced with saving patients from acute, catastrophic illness but rather must palliate chronic disease. While the change in life expectancy for patients with AIDS most clearly documents this shift in illness acuity, a walk through the medical floors of any hospital illustrates that most patients suffer from chronic, debilitating, but preventable conditions. Data from the Centers for Disease Control document that chronic disease is onerous (http://www.cdc.gov/nccdphp/overview.htm). Seven of every 10 Americans who die each year, or more than 1.7 million people, die of a chronic disease. More than 90 million Americans live with chronic illnesses. Chronic diseases account for 70% of all deaths in the United States. The medical care costs of people with chronic diseases account for more than 75% of the nation’s $1.4 trillion medical care costs. Diabetes is the fifth leading cause of death according to the Centers for Disease Control data, and kidney disease is the ninth. For nephrologists, diabetic nephropathy is the intersection of these broad categories and the most obvious and compelling manifestation of the chronic disease epidemic. As is well known to the readership, diabetic nephropathy is the leading cause of progressive kidney disease and ESRD (Incidence and Prevalence, Renal Data Service [1]). Patients with diabetic ESRD now account for 53% of incident patients, up from 28% in 1980 and comprise 45% of the prevalent ESRD population, up from 18% in 1980. On average, approximately 30% of diabetics will develop nephropathy. This observation raises the fundamentally important question: “Can we identify who will get sick?” (and perhaps, “Who will stay well?”). Why is this issue important? We have identified a number of strategies that will slow progression of diabetic nephropathy, including assiduous BP (2,3) and glucose control (4–6), and the use of drugs that block the actions of angiotensin II (7,8). Implementation of these strategies remains suboptimal despite widespread educational efforts for physicians and patients. For example, in an analysis of medical records of 15,768 visits to 12 general internal medicine clinics, BP was controlled using criteria from the 6th Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) in only 36% of visits, and diabetic patients were significantly less likely than patients without diabetes to have their BP controlled to the JNC VI recommended level (9). After conclusion of the Diabetes Complication and Control Trial, glucose control worsened in subjects who had been enrolled in the intensively-treated cohort despite the demonstrated benefit of optimal blood glucose levels on diabetic microvascular complications (6). The discrepancies between excellent outcomes achieved in rigorous clinical trials and the results demonstrated in clinical practice suggests a failure in translation of the lessons we have learned; this is an area of intense interest for investigators focused on diabetes (10,11) and other chronic diseases. The nihilists among us suggest that community implementation of clinical trial protocols is impractical, or maybe even impossible. I would maintain that there is a critical need to devise strategies that accomplish this goal, including identifying patients at highest risk for developing chronic disease, such as diabetic nephropathy, for preventive and intensive interventions. The patients at highest risk for diabetic nephropathy may need to be in care delivery systems that have a clinical trial infrastructure, which educate patients and promote compliance with the treatment strategies known to be effective. Although the costs associated with realization of more effective health care delivery systems may be considerable, the substantial human and economic costs imposed by diabetic nephropathy on patients, their families, and health care systems should be reduced with a net economic (and human) benefit. Formal cost-effective analysis will be needed to prove this hypothesis (12). Even with Published online ahead of print. Publication date available at www.jasn.org.