During the past several decades, there has been a tremendous increase in end-stage renal disease (ESRD) in patients with diabetes, especially those with type 2 diabetes. Between 1982 and 1992, for example, individuals with diabetes as the cause of their ESRD rose from 27 to 36%.¹ This trend is not changing as we enter the new millennium, despite improvements in screening and treatment.

Although the reason for this is debatable, the most likely etiology is simply that we are successful in helping our patients live longer. Better treatment of hypertension and hypercholesterolemia and a decrease in smoking prevalence have resulted in less cardiovascular mortality. Furthermore, improved treatments of acute myocardial infarction in patients with type 2 diabetes are also improving survival. Our patients are now living longer and thus have more time to develop ESRD.²

Despite the widespread use of renal replacement therapy in the United States, overall our patients do poorly. For example, one report of 84 consecutive patients with type 2 diabetes and ESRD found that 32% of the population died after a follow-up of only 211 days.³ Also concerning was the fact that iatrogenic nephrotoxic agents accounted for renal impairment in nearly 30% of patients. Furthermore, 80% of these patients with chronic renal insufficiency required emergency dialysis due to late referrals to the nephrology service.³

These types of reports are often criticized as not being applicable to other institutions or practice groups. My suspicion is that these data do actually reflect our individual community practices.

In this issue of Clinical Diabetes, Dr. Timothy C. Evans and Dr. Peter Capell review essential information about diabetic nephropathy for primary care providers (p. 7). They address details about epidemiology, pathogenesis, screening, and treatment in a simple and concise manner.

It seems paradoxical that, as our knowledge about treating this dreaded complication improves, we are losing our battle against ESRD. Why the discrepancy? This is a complex question, but the most visible data suggest that we do a poor job of screening for micro-albuminuria, let alone gross proteinuria.⁴

One needs to be cautious when interpreting these types of data, because surveys of physicians about their practice patterns may not be consistent with actual chart reviews. For example, one chart review reported that only 5% of primary care physicians screened for microalbuminuria, with 42% of subjects receiving a urinalysis to screen for gross proteinuria.⁵ A more recent chart audit concluded that there was better compliance for nephropathy screening, with 84­91% of patients being screened for gross proteinuria.⁶ However, even with this degree of screening, only 50% of patients with gross proteinuria had quantification of their protein excretion, and only 23­38% of patients with proteinuria were treated with an angiotensin-converting enzyme (ACE) inhibitor. There was no mention of microalbuminuria screening for patients without proteinuria, and other recent surveys have not shown improvements in microalbuminuria screening.⁷

Finally, in a survey including more than 3,400 people with diabetes, only 27% of patients received any type of renal testing in a 1-year period.⁸ The investigators captured their data from mailed surveys and chart audits, and for the latter included any type of renal test, including a serum creatinine or urinalysis for other diagnostic testing (such as urinary tract infection). Therefore, the results of this survey overestimated the true screening of the population.

Another controversial question often arises: Because there is a treatment for microalbuminuria, why not simply treat all patients with diabetes with an ACE inhibitor regardless of their hypertensive and albuminuric status?

Unfortunately, there are no randomized, controlled trials to suggest that this is the best, safest, and most cost-effective therapy. However, a decision analysis model recently reported that treating all patients with type 2 diabetes with an ACE inhibitor would slow progression to ESRD at a relatively low cost.⁹

Screening for microalbuminuria is more cost-effective, but it is not more effective, due to our abysmal adherence to screening recommendations. Should we discard the current recommendations of the American Diabetes Association given our poor compliance? I am finding this argument increasingly compelling, especially considering that the Heart Outcomes Prevention Evaluation trial reported that the ACE inhibitor ramipril (Altace) compared to placebo resulted in fewer cardiac outcomes and less microalbuminuria in subjects with and without diabetes.¹⁰

It has also been argued that, for patients with type 1 diabetes and a strong family history of diabetic nephropathy, it would be reasonable to initiate an ACE inhibitor.¹¹ An even stronger case to start treatment would be for patients with a strong family history of diabetic nephropathy and extremely high levels of HbA_1c. As is the case in type 2 diabetes, we do not have the classic randomized, controlled trial for this dilemma in people with type 1 diabetes. When I see someone with type 1 diabetes and an HbA_1c level chronically above 9% with siblings or parents who have developed ESRD, I am tempted to begin a low dose of an ACE inhibitor even without hypertension or microalbuminuria.

This is an exciting time for physicians treating patients with a risk of diabetic nephropathy or those with early renal disease. We do not actually know the natural history of this deadly disease anymore. Anecdotally, we are now seeing patients with little or no evidence of albuminuria who were started on their ACE inhibitors in the early 1980s, when the first agents were introduced. These, of course, are individuals who were screened for nephropathy before we had proven treatments other than the treatment of hypertension.

Now that we know we can change the natural history of diabetic nephropathy, we have a public health problem that can only be improved if the providers caring for these patients screen and treat their patients for this disease on a regular basis. The increase in the prevalence of ESRD in the United States from diabetes seems disgraceful to me.