Hope on the Horizon for Patients with Nephropathy

Diabetic nephropathy, including proteinuria, hypertension, and impaired glomerular filtration, is the leading cause of chronic kidney disease around the world.

Studies have shown between 30% and 40% of all Americans who have end-stage renal disease (ESRD) are diabetic. Medical insight and advances have increased the likelihood of glycemic and hypertension control and reduced microvascular complications for patients with type 1 diabetes (T1D) mellitus.

Despite these improvements in medical technology, diabetic nephropathy remains unpredictable and life-threatening. Available therapeutic strategies can sometimes slow diabetic neuropathy, but they are not preventive. Identifying high-risk patients at an early stage could help clinicians take appropriate steps to reduce risk.

A review article in the August 2014 issue of Current Opinion in Endocrinology, Diabetes, and Obesity summarizes what is known about diabetic nephropathy, beginning with the progressive pathology that develops over time. The authors noted that early progressive renal decline, which is an annual estimated glomerular filrtation rate (GFR) decline greater than 3.3% or 3 mL/min/1.73m², appears to predict progression to impaired renal function and eventual ESRD more accurately than microalbuminuria. However, the reason why early progressive renal decline develops is not clear.

Researchers have identified several new targets, including serum uric acid, insulin sensitivity, vasopressin, and sodium-glucose cotransporter-2 inhibition, that might prevent diabetic neuropathy if manipulated.

Better methods of measuring GFR are needed, and some investigational approaches are also promising, according to the authors. Urinary proteomic techniques are being explored, and capitalize on the fact that many urinary proteomic markers of diabetic neuropathy remain stable long enough to perform reliable polypeptide analysis. This approach would be practical in both real-world and noninvasive settings.

Research has indicated that lowering serum uric acid levels may prevent diabetic nephropathy development, and studies of uric acid lowering therapies are underway in patients with T1D.

Researchers are looking at long-term use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors to determine if their actions, including reducing hemoglobin A1c and attenuating renal hyperfiltration, will protect against renal decline.