At a Glance

Diabetic nephropathy is diagnosed when a patient with established diabetes mellitus has persistent proteinuria. If the glomerular filtration rate is reduced, serum creatinine can be elevated and the estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) can be reduced. Patients with type 1 diabetes should be screened for microalbuminuria beginning 5 years after diagnosis and yearly thereafter. Patients with type 2 diabetes should be screened for microalbuminuria at the time of diagnosis and yearly thereafter.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Initially perform a urine dipstick. If the dipstick is repeatedly positive for protein in a diabetic individual and other causes of proteinuria have been excluded, diabetic nephropathy is present. Very commonly, such patients suffer from hypertension. If the dipstick is negative, urinary albumin excretion can be assessed by:

• measuring the amount of albumin excreted in a 24-hour urine collection

• measuring the amount of albumin excreted in a timed urine collection that is less than 24 hours (with albumin excretion per minute reported)

• calculating the albumin to creatinine ratio (mcg to mg)

Small but pathological amounts of albumin in the urine can be referred to as "microalbuminuria" or "minimal albuminuria." To be clear, microalbuminuria refers to small amounts of albumin in the urine, and microalbumin is not a small albumin molecule. The dipstick is usually positive if "macroproteinuria" is present. Macroproteinuria can be referred to as "clinical albuminuria." When a 24-hour urine is collected, the completeness of collection can be estimated by measuring the creatinine excretion. Adults usually excrete 1 or more grams of creatinine per day. (Table 1)

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Other than measuring the creatinine to albumin ratio in a spot urine sample, the completeness of collection of the urine over the time interval of collection is very important. There are many causes of transient proteinuria when diabetic microalbuminuria should not be sought, such as: following exercise, during acute illness, or a febrile episode. Contamination of urine with blood can lead to misleading results. In the absence of diabetes, hypertension by itself can increase urinary albumin excretion.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The diagnosis of diabetic nephropathy requires that persistent proteinuria be documented. Therefore, however proteinuria is defined (e.g., by dipstick testing or by microalbumin measurement), proteinuria must be confirmed in two of two serial samples or in two of three serial samples over the course of 3-6 months. If proteinuria is not confirmed, the patient should be retested in 1 year. When diabetic nephropathy is diagnosed, a baseline measurement of the glomerular filtration rate should be undertaken by measuring the eGFR or by measuring the creatinine clearance in a 24-hour urine sample.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Angiotensin converting enzyme (ACE) inhibitors or angiotensive receptor blockers (ARBs) can reduce the magnitude of microalbuminuria.

References

Fioretto, P, Barzon, I, Mauer, M. "Is diabetic nephropathy reversible?". Diabetes Res Clin Pract. vol. 104. 2014. pp. 323-328.