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Objective: To assess the knowledge and practice patterns of primary care physicians relating to the detection and treatment of diabetic nephropathy and to compare these findings with current standards of care., Design: National survey., Participants: 1,000 randomly selected physicians., Setting: Primary care., Intervention: Mailed questionnaire consisting of a six-page "Diabetes Survey.", Results: Among the 1,000 primary care physicians, 950 were considered eligible for the survey. Sufficiently completed surveys were returned by 216 physicians, yielding an adjusted response rate of 22%. In general, patients with type 1 diabetes were monitored more intensively than those with type 2 diabetes. Primary care physicians were more likely to monitor patients for overt proteinuria (86%) than microalbuminuria (58%). Of the physicians who claimed to monitor patients for microalbuminuria, 39% chose inappropriate methods for detection, which lowers the percentage of physicians who correctly monitored for microalbuminuria to 37%. More than 95% of the respondents were aware of the benefits of angiotensin-converting enzyme inhibitors (ACEIs) in delaying the progression of diabetic nephropathy. Patients with proteinuria (86%) were more likely to be treated with an ACEI than were patients with microalbuminuria (79%). If a patient presented with proteinuria but without hypertension, the use of ACEIs fell to 75%. Rates of referral to a nephrologist were low at early stages of the disease (3% to 11%) and remained relatively low (28%) at later stages, even when serum creatinine was greater than 3 mg/dL., Conclusion: Further efforts directed toward education of primary care physicians about diabetic nephropathy have the potential to improve the care of patients with this disorder. These findings demonstrate a unique opportunity for pharmacists to become educators to physicians in their community.

The pathophysiology and natural history of diabetic nephropathy are described, and recent developments in its prevention and treatment are discussed. Diabetic nephropathy can occur in both insulin-dependent and non-insulin-dependent diabetics. It is characterized by arterial hypertension, proteinuria, and progressive loss of renal function. Although the exact mechanism has not been fully elucidated, hyperglycemia with altered intraglomerular hemodynamics is an important contributor to the initiation and progression of the disease. Concurrent hypertension aggravates progression of the disease. Currently accepted strategies to slow the progression of diabetic renal disease have focused on antihypertensive therapy, strict glucose control, and restriction of dietary proteins. Recent publications support the hypothesis that angiotensin-converting-enzyme inhibitors have a unique ability, independent of their antihypertensive effect, to slow the progression of diabetic nephropathy. Investigational agents (e.g., aminoguanidine) may prove helpful in the management of the condition. Information about the prevention of diabetic nephropathy has grown significantly in the past few years.

Aminoguanidine is an investigational agent that may slow or prevent many diabetes-related complications. Since the elimination of aminoguanidine is dependent on renal function, its pharmacokinetics was investigated in eight chronic renal failure patients maintained on hemodialysis. Each patient received 300 mg of aminoguanidine hydrochloride during both an interdialytic and an intradialytic period. During the interdialytic period, the maximum aminoguanidine concentration (Cmax) and time to reach Cmax was 4.5 micrograms/mL and 1.5 hours, respectively. The terminal elimination half-life in these patients was prolonged (37.9 hours). The renal clearance was 2.1 mL/min. Only 8.7% of the administered dose was recovered unchanged in the urine, which is markedly reduced from what is recovered in urine in subjects with normal renal function. There was a positive correlation between the renal clearance of aminoguanidine and the patients' residual renal function (P < 0.05). During hemodialysis, the half-life of aminoguanidine was shortened to 3.9 hours. The hemodialysis clearance of aminoguanidine was 203.6 mL/min. After cessation of hemodialysis, a significant rebound in plasma aminoguanidine concentrations (mean, 39%) was observed. Thus, the dose of aminoguanidine hydrochloride will need to be significantly reduced in patients with end-stage renal disease. Given the interdialytic and intradialytic pharmacokinetics of aminoguanidine, three times weekly dosing after each hemodialysis session is suggested.