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ADA Standards Highlight GFR Screening for Nephropathy

Oct 23, 2007

Creatinine screening needed in addition to albuminuria testing.

Traditionally, albuminuria screening has been the gold standard for assessing nephropathy risk in diabetes patients. But updated American Diabetes Association (ADA) treatment standards now call on physicians to also measure the estimated glomerular filtration rate (GFR)—a calculation that requires that they first determine patients’ serum creatinine level.
Screening for nephropathy risk is a mainstay of diabetes management, given that diabetes-related nephropathy is the leading cause of end-stage renal disease. Approximately 20–40% of people with diabetes will eventually develop diabetic nephropathy.1


Before ADA’s revision of the treatment standards, physicians traditionally only looked at rising creatinine levels after seeing an increase in urinary albumin excretion. But the new standards call on them to assess both simultaneously when screening their diabetes patients for signs of renal disease. The reason: Kidney damage—characterized by rising creatinine levels and hence falling GFR—can develop without a rise in albuminuria.

The GFR can be calculated using a kidney disease prediction formula based on data collected in the Modification in Diet and Renal Disease (MDRD) study. The National Kidney Foundation provides assistance with GFR calculation on its Web site (see "FYI").

A doubling of serum creatinine level indicates a halving of GFR; a threefold increase suggests a 75% loss of kidney function.
"It is now clear that stage 3 or higher chronic kidney disease [GFR <60 ml/min per 1.73 m2] occurs in the absence of urine albumin excretion in a substantial proportion of adults with diabetes," the standards state. "Screening this population for increased urine albumin excretion alone, therefore, will miss a considerable number of [chronic kidney disease] cases."

ADA’s treatment guidelines recommend prescribing angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor-blockers (ARBs) to treat both micro- and macroalbuminuria—defined as approximately 300 mg of albumin/24 hr, or 500 mg of total proteinuria/24 hr (macroalbuminuria is often called "dipstick-positive proteinuria," as that is about where protein shows on the urinary dipstick).

The guidelines note a lack of "adequate head-to-head comparisons" of ACE inhibitors and ARBs in nephropathy treatment with diabetes patients, but state there is clinical evidence to support the following statements:

  • In patients with type 1 diabetes, with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy.
  • In patients with type 2 diabetes, hypertension, and microalbuminuria, ACE inhibitors and ARBs have been shown to delay the progression to macroalbuminuria.
  • In patients with type 2 diabetes, hypertension, macroalbuminuria, and renal insufficiency (serum creatinine >1.5 mg/dl), ARBs have been shown to delay the progression of nephropathy.
  • If one class is not tolerated, the other should be substituted.

More specifically, good evidence exists for using ACE inhibitors and ARBs for slowing nephropathy progression in diabetes patients with frank proteinuria (>300 mg of albumin in the urine over 24 hours or >500 mg of total protein) with or without hypertension. In addition, evidence indicates these medications are useful for patients in the microalbuminuric range 30–300 mg of albumin in the urine, notes Robert Stanton, MD, chief of the Nephrology Section at Joslin Clinic in Boston, and an associate professor of medicine at Harvard University.

However, there is little to no evidence that diabetes patients who have no increased urine albumin levels derive any unique benefit from ACEs and ARBs, even if they have decreased GFR (also reflected as increased serum creatinine), says Stanton. Also, there is little to no evidence that diabetes patients with normal GFR and normal urine albumin levels gain any unique benefit from ACE inhibitors or ARBs, as compared with any other blood pressure medication, says Stanton. In fact, it can be controversial to prescribe these drugs purely for prophylaxis in type 2 diabetes patients who have normal blood pressure and no apparent evidence (yet) of microalbuminuria, notes Mark E. Molitch, MD, professor of medicine at North-western University Feinberg School of Medicine in Chicago.

If, however, a diabetes patient becomes hypertensive, "it might make sense to either start with an ACE or ARB, or use it in combination with another med, as in the future some benefit might be proven in these patients," says Stanton.

Indeed, when hypertension is present in diabetes patients, there should be no questions about use of ACE inhibitors or ARBs to control it because high blood pressure poses numerous health risks, including development or worsening of diabetic nephropathy, says Julia Vargas-Jerez, MD, of Naomi Berrie Diabetes Center at Columbia University Medical Center in New York City.

"Tight blood pressure control has been proven to reduce risk of diabetic nephropathy," says Vargas-Jerez. "Blood pressure goals for diabetes patients without complications are around 130/80 [mmHg]. For diabetes patients with complications, we want to aim for tighter control—around 120/70 [mmHg]."

It should be noted that ADA’s guidelines indicate that ACE inhibitors appear to reduce severe cardiovascular disease, providing a further reason to use ACE inhibitors preventatively in patients with diabetes and microalbuminuria.
Experts also note that diet and exercise play a key role in preventing nephropathy in at-risk patients.
Screening Recommendations

  • To reduce the risk and/or slow the progression of nephropathy, optimize glucose control.
  • To reduce the risk and/or slow the progression of nephropathy, optimize blood pressure control.
  • Perform an annual test for the presence of microalbuminuria in type 1 diabetic patients with diabetes duration of ≥5 years and in all type 2 diabetic patients, starting at diagnosis and during pregnancy.
  • Serum creatinine should be measured at least annually for the estimation of glomerular filtration rate (GFR) in all adults with diabetes regardless of the degree of urine albumin excretion. The serum creatinine alone should not be used as a measure of kidney function but instead used to estimate GFR and stage the level of chronic kidney disease (CKD).

Source: American Diabetes Association: Position Statement: Standards of Medical Care in Diabetes—2007. Diabetes Care 30 (Suppl.1):S1–S41, 2007.
Assistance calculating the glomerular filtration rate (GFR) is available on the National Kidney Foundation Web site at www.kidney.org/professionals/kdoqi/gfr_calculator.cfm.


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