Vol. 16 •Issue 7
• Page 61
The Road to Renal Failure
An Overview of Diabetic Nephropathy
by Elizabeth Burris McCrary, NP
Diabetic nephropathy is a progressive disease that affects approximately 20% to 30% of patients with diabetes.1It is characterized by proteinuria and renal failure. Diabetic nephropathy is responsible for 40% of new cases of end-stage renal failure, and it is the leading cause of renal failure in the United States.2Early recognition of diabetic nephropathy in the primary care setting, along with subsequent intervention and management, are crucial to slowing its progression.1
Pathophysiology and Risk Factors
The pathophysiology of diabetic nephropathy involves structural and functional changes in the kidney as a result of metabolic and hemodynamic processes. These changes include glomerular basement membrane thickening, mesangial expansion, increased glomerular permeability and decreased glomerular filtration rate (GFR).3Hypertension and poor glycemic control are two of the most important modifiable risk factors for diabetic nephropathy.4Prolonged periods of poor glycemic control are often present in patients who develop diabetic nephropathy, and hypertension often correlates with the deterioration in renal function.
Genetics may play a role in the development of diabetic nephropathy.5Ethnicity apparently influences its development as well: Blacks, Mexican Americans and Pima Indians are at increased risk for diabetic nephropathy compared with other ethnic groups.6
Elevated plasma triglycerides and reduced high-density lipoproteins are also associated with diabetic nephropathy. Microalbuminuria, dietary protein and fat intake, circulating amounts of plasma proteins, and the presence of diabetic retinopathy are additional risk factors associated with the condition.5Other risk factors include cigarette smoking, obesity and anemia.7
Clinical Assessment
In the primary care setting, patients with diabetes should receive routine assessments designed to prevent complications including diabetic nephropathy. At each visit, review medical history and perform a focused physical examination.
This physical exam should include weight, blood pressure, a fundoscopic examination, evaluation of peripheral pulses and carotid bruits, and a cardiac examination.8Because the signs of diabetic nephropathy are not obvious, all patients with diabetes should be assessed for risk factors and predictors of the disease.9Patients with diabetic nephropathy are at an increased risk for cardiovascular disease; therefore, they should be evaluated often for heart disease.4
Diabetic nephropathy typically evolves in stages, which are determined by the amount of urinary albumin excretion (UAE).3(See table.) Methods for measuring UAE include 24-hour urine collection, random spot collection and timed urine collection. Random spot collection, which usually measures albumin to creatinine ratio, is the method recommended by the American Diabetes Association (ADA).10
Macroalbuminuria in overt diabetic nephropathy can be detected with the standard urine dipstick test. But microalbuminuria cannot be detected with urine dipstick and must be measured with more sensitive tests. The diagnosis of microalbuminuria is made based on elevated UAE results in two of three screenings taken over 3 to 6 months.1
Screening
Microalbuminuria is often the first manifestation of diabetic nephropathy.3Therefore, it is critical to routinely screen all patients with diabetes for microalbuminuria. For patients with type 1 diabetes, screening should begin after puberty or 5 years after diabetes is diagnosed. Patients with type 2 diabetes should be screened at the time of diabetes diagnosis, because the disease has probably been present for several years. After the initial screening, test for microalbuminuria annually.11Increasing values of microalbuminuria may indicate the progression of renal disease.
Serum creatinine is helpful in screening for renal disease and monitoring the progression of diabetic nephropathy. Serum creatinine estimates the GFR and should be measured annually in patients without known kidney disease and every 6 months in patients with identified kidney disease.1Further testing that may be beneficial in assessing diabetic nephropathy includes serum electrolytes, complete blood count, microscopic urinalysis, lipid profile, hemoglobin A1c HbA1c and renal ultrasound.8
Management
Management interventions for diabetic nephropathy aim to prevent the development or slow the progression of the condition. Control of risk factors (e.g., hyperglycemia and hypertension) and the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may assist in preventing the progression of diabetic nephropathy.12
When microalbuminuria is detected in a patient with diabetes, aggressive measures are necessary to improve prognosis.5Elevated blood glucose levels and an increase in systemic blood pressure may contribute to the increase in albumin permeability. Therefore, early interventions to decrease blood pressure and control blood glucose levels may reverse microalbuminuria and are critical in preventing the progression of nephropathy.13
Glycemic Control
Extensive research has shown that intensive glycemic control can delay the onset and slow the progression of diabetic nephropathy.14,15Although glycemic goals should be individualized, the ADA recommends general goals of HbA1cless than 7%, preprandial glucose of 90 mg/dL to 130 mg/dL, and postprandial glucose less than 180 mg/dL.10 ntensive glycemic treatments should be implemented to achieve these goals.
All patients with type 1 diabetes and many patients with type 2 diabetes use insulin to control glycemia. Certain oral antihyperglycemic medications may be beneficial in type 2 diabetes, as long as they are initiated early in the disease process.4Specifically, the thiazolidinediones (rosiglitazone [Avandia] and pioglitazone [Actos]) may provide advanced renoprotective effects due to their peroxisome proliferator-activated, receptor-gamma agonist effects.16But insulin secretagogues and sulfonylureas are not generally beneficial for patients with advanced diabetes because they have little endogenous insulin.4Metformin (Glucophage) and drugs in the sulfonylurea class should be used with caution in patients with renal insufficiency because they are excreted via the kidneys.1
Blood Pressure Control
The blood pressure goal for patients with diabetes should be 130/80 mm Hg or less. Reducing blood pressure in the diabetes patient who has a normal albumin level reduces the risk for microalbuminuria as well as cardiovascular events. The treatment of hypertension in patients with microalbuminuria decreases the rate of progression to macroalbuminuria.4Once macroalbuminuria, or overt diabetic nephropathy, has been reached, the progression cannot be stopped. But it can be delayed. Hypertension is the most influential factor during this stage, and it must be controlled to slow kidney failure.11
Controlling hypertension in the patient with diabetes often requires multiple agents.1 ue to their renoprotective effects, the initial drugs of choice for hypertensive patients with diabetes are ACE inhibitors or ARBs.17If blood pressure goals are not achieved with one of these agents, other classes of antihypertensive agents (e.g., thiazide diuretics, nondihydropyridine calcium channel blockers or beta blockers) may be added to the treatment regimen.1
ACE Inhibitors or ARBs
ACE inhibitors or ARBs should be initiated as soon as microalbuminuria is confirmed, regardless of blood pressure reading. ACE inhibitors such as captopril (Capoten) and ARBs such as losartan (Cozaar) have renoprotective effects independent of lowering blood pressure and delay the progression of renal disease.1These agents inhibit the renin-angiotensin-aldosterone system, delaying the decrease in GFR, the increase of albuminuria and the occurrence of end-stage renal disease. ACE inhibitors prevent the conversion of angiotensin I to angiotensin II and prevent vasoactive substances such as bradykinin from breaking down.13,18ARBs block the angiotensin II receptors, preventing angiotensin II action.13If microalbuminuria persists after the use of a combination of ACE inhibitors or ARBs and other antihypertensive agents, combination therapy with an ACE inhibitor and an ARB may be beneficial.1
Dyslipidemia
The ADA recommendations for lipid goals in patients with diabetes are low-density lipoprotein less than 100 mg/dL (less than 70 mg/dL for patients with overt cardiovascular disease), triglycerides less than 150 mg/dL and high-density lipoprotein greater than 40 mg/dL in men and greater than 50 mg/dL in women. To assist in meeting these goals, emphasize the need for physical activity and a diet low in saturated fat, trans fat and cholesterol — along with weight loss if needed.10Antilipemic agents (statins) are effective in reducing lipid levels and may slow GFR decline and reduce proteinuria.4
Managing Other Risk Factors
Because patients with microalbuminuria have an increased risk for cardiovascular disease, the management of diabetic nephropathy should also incorporate reduction in all cardiovascular risk factors.5Encourage lifestyle modifications including weight loss, smoking cessation, exercise and reduced intake of alcohol and sodium.1This will assist in controlling blood glucose levels, blood pressure and dyslipidemia, as well as cardiovascular disease and diabetes complications.12Restriction of dietary protein to less than 0.8 g/kg/day may help delay GFR decline in patients with macroalbuminuria.10
Patient Education
Regularly scheduled follow-up office visits are crucial to the successful management of diabetic nephropathy.8Thorough ongoing patient education is necessary to prevent the progression of diabetic nephropathy and to accomplish set goals.8,19
Stress the importance of frequent self-monitoring of blood glucose; self-monitoring is integral to glycemic control.10Carbohydrate intake should come from foods such as whole grains, fruits, vegetables and low-fat milk.12Patients with diabetes should also participate in aerobic activity 3 to 5 days per week for 30 to 45 minutes each day.10
Special Considerations
As renal function declines, the pharmacokinetics of drugs in the patient's regimen may change. This may require dosage adjustments, including reduced insulin dosages to avoid hypoglycemia.3
Patients with diabetic nephropathy must also avoid nephrotoxic drugs, such as NSAIDs and aminoglycosides.8,19Patients with renal impairment should avoid procedures that require radiocontrast because it increases renal failure risk.3
Outcome Evaluation and Referral Plan
In patients with diabetic nephropathy, outcomes can be evaluated and monitored by accurately assessing microalbuminuria at regular intervals, measuring blood pressure at each office visit, measuring HbA1clevels every 3 to 6 months, and measuring lipid levels at least annually.
Therapeutic outcomes often require multidisciplinary interventions. Registered dietitians, social workers, podiatrists, endocrinologists and diabetes educators are often involved in the care of patients with diabetic nephropathy. Every patient with diabetes should be screened annually for retinopathy by an ophthalmologist.19Strongly encourage smoking cessation in any patient who smokes, and prescribe the appropriate tools.6
Nephrologists should become involved when microalbuminuria develops, serum creatinine levels begin to elevate, GFR begins progressively declining, blood pressure is uncontrollable, hyperkalemia is present, or in any situation requiring additional expertise.3,20,21
Symptoms such as rapid progression of renal failure or massive proteinuria may suggest that the patient has a condition other than diabetic nephropathy. These symptoms indicate the need for an immediate nephrology referral.1
Putting It Into Practice
As the number of U.S. residents with diabetes continues to rise, nurse practitioners in primary care settings will have greater responsibility for managing and educating these patients.
It is imperative for nurse practitioners to identify patients with diabetes early in the disease process to prevent complications, including diabetic nephropathy. Hyperglycemia and hypertension are two of the most influential risk factors for diabetic nephropathy. Aggressive treatment and strict control of these risk factors, plus the use of ACE inhibitors or ARBs, can prevent or delay the progression of renal damage.11
References
1. Woodbridge M, Holman JR. Diabetic nephropathy: early clues, effective management. Consultant. 2006;46(7):809-818.
2. American Diabetes Association. Diabetic nephropathy. Diabetes Care. 2003;26(Suppl 1):S94-S98.
3. Rabkin R. Diabetic nephropathy. Clin Cornerstone. 2003;5(2):1-11.
4. Gross JL, et al. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care. 2005;28(1):164-176.
5. Foggensteiner L, et al. Management of diabetic nephropathy. J R Soc Med. 2001;94(5):210-217.
6. Winters SA, Jernigan V. Vascular disease risk markers in diabetes: monitoring and intervention. Nurse Pract. 2000;25(6 Pt 1):40-67.
7. Sasso FC, et al. Cardiovascular risk factors and disease management in type 2 diabetic patients with diabetic nephropathy. Diabetes Care. 2006;29(3):498-503.
8. Soman SS, Soman AS. Diabetic nephropathy. eMedicine. Available at: http://www.emedicine.com/med/TOPIC549.HTM. Accessed April 10, 2007.
9. Klein R, et al. Microvascular complications. In: Mazze RS, et al, eds. Staged Diabetes Management: A Systematic Approach. Minneapolis, Minn.: International Diabetes Center; 2000:229-236.
10. American Diabetes Association. Standards of medical care in diabetes — 2006. Diabetes Care. 2006;29(Suppl 1):S4-S42.
11. Evans JC, Capell P. Diabetic nephropathy. Clinical Diabetes. 2000;18(1):7-17.
12. Bowes M, et al. Prevention Strategies in Family Practice. AAFP Video CME Series. Leawood, Kan.: American Academy of Family Physicians; 2003.
13. Vivian EM, Rubinstein GB. Pharmacologic management of diabetic nephropathy. Clin Ther. 2002;24(11):1741-1756.
14. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977-986.
15. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837-853.
16. Hall PM. Prevention of progression of diabetic nephropathy. Diabetes Spectr. 2006;19:18-24.
17. Holcomb SS. Treating hypertension in diabetes patients. Nurse Pract. 2004;29(9):13-15.
18. Barnett A. Prevention of loss of renal function over time in patients with diabetic nephropathy. Am J Med. 2006;119(5 Suppl 1):405-407.
19. Russell TA. Diabetic nephropathy in patients with type 1 diabetes mellitus. Nephrol Nurs J. 2006;33(1):15-28.
20. Augustine J, Vidt DG. Diabetic nephropathy. Available at: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/nephrology/diabeticnephropathy/diabeticnephropathy.htm. Accessed April 10, 2008.
21. Loon NR. Diabetic kidney disease: preventing dialysis and transplantation. Clinical Diabetes. 2003;21:55-62.
Elizabeth Burris McCrary is a family nurse practitioner at Lawrence County Family Practice Clinic in Monticello, Miss.
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