LAS VEGAS – Contrary to conventional wisdom, neither ACE inhibitors nor angiotensin receptor blockers have any role to play in primary prevention of diabetic kidney disease, according to Dr. Robert C. Stanton, chief of nephrology at the Harvard University’s Joslin Diabetes Center, Boston.
"I don’t see any unique indication for ACE inhibitors and ARBs for the primary prevention of kidney disease in diabetic patients, especially given that around 70% of diabetes patients will never develop kidney disease. They’re perfectly fine blood pressure pills. But as a magic kidney disease prevention drug, I don’t see any evidence for that. Of course, patients with proteinuria are another issue entirely. Those drugs absolutely are beneficial in that setting," he said at a meeting sponsored by the National Kidney Foundation.
Dr. Robert C. Stanton
When Dr. Stanton polled his audience electronically during the course of his talk, however, the majority of physicians indicated that they believe ACE inhibitors and ARBs are indeed useful for primary prevention of diabetic kidney disease. The evidence, Dr. Stanton emphasized, shows otherwise.
For example, a well-conducted, randomized, multicenter, placebo-controlled, 5-year clinical trial showed no benefit for enalapril or losartan in preventing kidney disease in patients with type 1 diabetes (N. Engl. J. Med. 2009;361:40-51). And three randomized controlled trials showed no primary preventive benefit for candesartan in more than 5,000 patients with type 1 or type 2 diabetes (Ann. Intern. Med. 2009;151:11-20).
Dr. Stanton noted that lots of other interventions have been proposed for the primary prevention of kidney disease in diabetes patients. Some are supported by solid evidence of benefit, others are not.
Here is his view of the preventive landscape:
• Intensive blood glucose control. "This is the easy one," he said. "A lot of us in the diabetes world feel that a hemoglobin A1c of 7% is the appropriate target for preventing many complications. It’s a reasonable target and should be achieved whether you’re talking about type 1 or type 2 patients."
The nephrologist noted that recent 25-year follow-up data from the landmark Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study showed that fully 18 years after the intervention ended, patients assigned to intensive blood glucose control still showed highly impressive 50% reductions in the cumulative incidence of both microalbuminuria and end-stage renal disease compared with patients placed on less intensive control (Diabetes Care 2014;37:24-30).
• Smoking cessation. Smoking has been linked to a several-fold increased risk of diabetic kidney disease. "I think of diabetes as an endothelial cell disease, and smoking is the greatest endothelial cell poison we’ve come up with. So stopping smoking is something well worth doing," Dr. Stanton said.
• Blood pressure control. No question exists regarding its renoprotective effect. But recent guidelines are dizzyingly all over the map in terms of target pressure recommendations.
"I’m getting a major headache reading these articles right now. I can show you the data. Good luck! I personally like a target of 130/80 mm Hg or less, particularly when it’s not that hard to get there. But I’d let you decide what particular target you favor," he said.
He prefers 130/80 mm Hg as a target blood pressure for primary prevention of diabetic kidney disease in large part because of a meta-analysis showing that it was associated with a 10% reduction in the risk of developing microalbuminuria and an 11% decrease in end-stage renal disease (PloS Med 2012;9(8):e1001293).
• Weight loss. The growing bariatric surgery literature supports weight loss as a primary preventive strategy.
• Protein intake. There is no role for a low-protein diet – say, less than 0.8 g/kg per day – for primary prevention of kidney disease in diabetes patients. And Dr. Stanton believes a high-protein diet in the range of more than 1.5 or 2 g/kg per day is best avoided in patients with diabetes, although he stressed that the evidence on this score remains sketchy.
Still, "I would not go on a body-building diet or an Atkins-type diet," he cautioned.
• Targeting glomerular hyperfiltration. Studies have shown conflicting results. "For me, there’s no clear role for targeting hyperfiltration," said Dr. Stanton, who cited a comprehensive review that he finds persuasive (Diabetologia 2010;53:2093-104).
The key to developing more effective primary prevention strategies, according to Dr. Stanton, will be first to establish markers that clearly identify the 30% or so of diabetes patients who will go on to develop renal disease, then test novel interventions specifically in that high-risk group.
Promising biomarkers include circulating tumor necrosis factor alpha receptor levels, von Willebrand factor, monocyte chemoattractant factor, asymmetrical dimethylarginine, interleukin-6 and -8, and Fas receptor.