Innovative therapies and a better understanding of the underlying mechanisms of diabetic kidney disease (DKD) are slowing its progression, according to a new Endocrine Society scientific statement on diabetic microvascular complications. The statement also describes the slow progress in finding genetic markers for diabetic kidney disease and says that the cause of disease is misdiagnosed for many patients.
“Vascular complications are the major cause of morbidity and mortality in diabetic patients,” according to “Diabetic Microvascular Disease: An Endocrine Society Scientific Statement.” The kidney, eye, and peripheral nervous system form the triad of “classical diabetes microvascular target tissues. Microvascular renal disease is … a major contributor to the development of end-stage kidney disease (ESKD) in the developed world.”
The best practices in therapy are not a surprise. “The latest research shows that maintaining tight control over blood sugar levels and blood pressure can help to reduce the risk of complications such as diabetic nephropathy,” said Eugene J. Barrett, MD, PhD, of the University of Virginia, who chaired the task force that developed the statement.
“Therapies to prevent or slow the development of DKD are multifactorial and include lowering blood sugar levels with medications, diet, and exercise, as well as treating hypertension and hyperlipidemia,” the statement says.
There are several medications that slow the progression of DKD, but they do not halt it, said Barry I. Freedman, MD, professor of internal medicine and chief of nephrology at Wake Forest School of Medicine, the lead author on the renal section of the statement.
Agents that block the renin-angiotensin aldosterone system (RAAS), such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are effective at slowing the progression of DKD in patients with high levels of proteinuria. New glucose-lowering agents, including sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-peptide 1 (GLP-1) agonists, provide hope for slowing progression of established DKD or preventing its development.
The statement reviews the various pathways to microvascular damage (see sidebar) and notes that some of the effectiveness of medications may stem from disrupting these pathways. For example, ACE inhibitors may contribute not only by lowering systemic blood pressure, but could also decrease glomerular capillary pressure by inhibiting the kidney’s production of angiotensin II. Angiotensin II may lead to kidney damage through the induction of local factors, including extracellular matrix protein synthesis via transforming growth factor-b and inflammatory cytokines.