Physician's Weekly Article - Screening & Treating Diabetic Nephropathy

       Improving glycemic control, aggressive antihypertensive treatment, and the use of ACE inhibitors or ARBs can slow rates of progression of diabetic nephropathy.

      Diabetic nephropathy occurs in an estimated 20% to 40% of patients with diabetes. “Nephropathy is a major cause of sickness and death in people with diabetes,” says George L. Bakris, MD. “The condition often leads to the need for dialysis or kidney transplantation in patients with diabetes.” Although there are no early symptoms in the initial stages of diabetic nephropathy, several nonspecific signs and symptoms manifest later in the disease, including fatigue, a foamy appearance of the urine, headache, nausea, and edema.

      The Importance of Regular Screenings

      Diabetic nephropathy is commonly accompanied by other complications, especially hypertension, retinopathy, and cardiovascular disease. According to recommendations from the American Diabetes Association (ADA), vigilant screening is paramount (Table 1). Patients with type 1 diabetes who have had the disease for 5 years or more are recommended to undergo annual testing to assess urine albumin excretion and kidney function. For those with type 2 diabetes, this testing should be done annually once patients are diagnosed. “Patients with microalbuminuria who progress to macroalbuminuria are most likely to develop end-stage renal disease [ESRD], so regular screenings are important,” says Dr. Bakris. “The presence of microalbuminuria alone doesn’t mean nephropathy is present, especially in the absence of hypertension. Conversely, increasing levels of microalbuminuria are a marker of diabetic nephropathy.” The ADA also recommends measuring serum creatinine levels at least once a year in all adults with diabetes to estimate the glomerular filtration rate (GFR), and stage level of chronic kidney disease (CKD), if present (Table 1).

      Efforts should also be made to optimally control glucose and blood pressure levels to reduce the risk or slow the progression of nephropathy, says Dr. Bakris. “Intensive diabetes management aimed at achieving A1C levels of less than 7% has been shown to delay the onset of microalbuminuria and the progression of micro- to macroalbuminuria in diabetes. Other investigations have provided strong evidence that lowering blood pressure to levels well below 140/90 mm Hg can also reduce nephropathy risks.”

      Medications Can Have A Strong Impact

      According to the ADA’s 2008 Standards of Medical Care, two classes of medications—ACE inhibitors and angiotensin receptor blockers (ARBs)—have been effective in treating patients with micro- and macroalbuminuria. Data have demonstrated that lowering systolic blood pressure levels with ACE inhibitors appears to be more beneficial than other antihypertensive drug classes in delaying diabetic nephropathy progression in type 1 diabetes (Table 2). They can also slow the decline in GFR in patients with microalbuminuria if blood pressure is lowered to such levels. In patients with type 2 diabetes, hypertension, and normal albuminuria levels, ACE inhibitors help delay progression of microalbuminuria. ACE inhibitors have also been shown to reduce major cardiovascular disease outcomes in patients with diabetes, further supporting their use.

      In clinical studies, ARBs have been shown to reduce the rate of progression from micro- to macroalbuminuria and ESRD in type 2 diabetes. “It’s important for physicians to start ACE inhibitor or ARB regimens at doses that have been shown to be beneficial in clinical trials,” Dr. Bakris explains. “Unfortunately, some providers are starting these regimens at sub-therapeutic doses. Additionally, these drug therapies should not be stopped when creatinine levels increase. Data have demonstrated that these regimens should be continued if creatinine levels increase by 30% to 40% and hyperkalemia is well managed because these patients stand to benefit the most.” Other drugs (eg, diuretics, calcium channel blockers, and ß-blockers) should be used as additional therapy to further lower blood pressure in patients already treated with ACE inhibitors or ARBs, or as alternate therapy in rare cases where patients cannot tolerate these drug classes, according to the ADA.

      Considering a Referral

      Continued surveillance of diabetic nephropathy is important to help assess responses to therapy and disease progression, but some cases may be more challenging than others. Dr. Bakris says that physicians should consider referring patients to experts whenever they are uncertain about the etiology of kidney disease or if they are having difficulty managing patients or if patients have advanced kidney disease. “Physicians should refer patients to nephrologists when estimated GFRs are at or below 45 ml/min per 1.73 m2. This can help reduce costs, improve quality of care, and keep patients off dialysis longer. At the very least, doctors should still educate their patients about the progressive nature of nephropathy and inform them that preserving their renal function aggressively can significantly improve their outcomes.”

      George L. Bakris, MD, has indicated to Physician’s Weekly that he has served as a consultant, been on the speaker’s bureau, or been on an advisory board for Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb/Sanofi-Aventis, Forest, GlaxoSmithKline, Merck, Novartis, Walgreens, Gilead, and Daiichi Sankyo. He has also received grants from the NIH, GlaxoSmithKline, and Forest.