Diabetic Nephropathy Diagnosis and Treatment Update

The annual costs (direct and indirect) related to diabetic nephropathy in the United States total $174 billion. Axel Pflueger, M.D., Ph.D. of the Division of Nephrology and Hypertension at Mayo Clinic in Minnesota, says, "Patients with diabetes are the fastest-growing group of renal dialysis and transplant recipients. Diabetic nephropathy is associated with a high cardiovascular mortality rate. About 40 percent of patients with diabetes will have diabetic nephropathy if they do not die prematurely of cardiovascular disease. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide. The growth in the number of patients with ESRD, however, exceeds the kidney donor pool. Screening for diabetic nephropathy is imperative and should be started early."

The cumulative incidence of increased urinary albumin excretion is 50 percent over a lifetime of diabetes mellitus (both type 1 and type 2). Dr. Pflueger explains that the course of urinary albumin excretion follows one of three paths:

• It returns to normal in one-third of cases
• Its increased level persists in one-third
• It progresses to frank proteinuria in one-third.

Almost all patients with diabetes who have nephrotic-range proteinuria (>3 g protein/24 hr) will eventually have ESRD if they do not die prematurely of cardiovascular disease. Diabetic nephropathy has several phenotypes, and many diabetic patients present with a decreased glomerular filtration rate and minimal or absent albuminuria, in contrast to the classic presentation of diabetic nephropathy. The five stages of diabetic nephropathy are:

The five stages of diabetic nephropathy

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Dr. Pflueger emphasizes that studies show that intensified therapy for diabetic nephropathy decreases progression and cardiovascular death. The primary intervention is treatment with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, or both, with proteinuria treatment goals of less than 17 mg/g creatinine in men and less than 25 mg/g creatinine in women. The renal function goal is to limit the glomerular filtration rate decline to less than 2 mL/min per year.

Adjunctive cardiorenal protective therapy is also key to successful outcomes. Dr. Pflueger highlights:

• The target for hypertension management should be blood pressure less than 130/80 mm Hg
• Dietary protein should be restricted to 0.6 to 0.8 g/kg per day; dietary salt should be restricted to less than 2 g per day
• Glycemic control should be optimized, with a target hemoglobin A1_c value of 7.0% or less
• Anemia should be corrected, with a target hemoglobin concentration of 11 to 12 g/dL
• If the concentration of calcium-to-phosphate product is increased, it should be corrected
• The target value for low-density lipoprotein cholesterol should be less than 100 mg/dL
• Antiplatelet therapy with aspirin is indicated, and smoking cessation is mandatory
• Body weight goal should be at the calculated ideal body weight
• Patients should be advised to avoid nonsteroidal anti-inflammatory drugs and other potential nephrotoxic substances, and medication use should be reviewed for dosing appropriate to kidney function
• Preventive-prophylactive measures for the prevention of acute kidney injury, such as contrast medium–induced acute kidney injury, should be implemented
• The importance of regular cardiovascular exercise should be emphasized, with a target of 45 minutes' duration four or five times weekly

Future pharmacologic therapeutic options may include pyridoxamine dihydrochloride, 25-hydroxyvitamin D, statins, aliskiren, AST-120, protein kinase C inhibitors (e.g., ruboxistaurin), pirfenidone, connective tissue growth factor inhibitor FG-3019, and lactobacillus. Trials are ongoing, however, and most of these agents are not yet available for evidence-based therapy.