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Preface and Contents

Diabetic Kidney Disease

When to suspect? and Diagnosis

When does one suspect diabetic kidney disease in a diabetic patient?

Diabetic kidney disease can be suspected in a diabetic patient in the presence of:

  • Foamy urine or the presence of albumin/protein in the urine (seen in early stage).
  • High blood pressure or worsening of pre-existing high blood pressure.
  • Swelling of the ankles, feet and face; reduced urine volume or weight gain (from accumulation of fluid).
  • Decreased requirement of insulin or anti-diabetic medications.
  • History of frequent hypoglycemia (low sugar level). Better control of diabetes with the dose of anti-diabetic medications with which diabetes was controlled poorly in the past.
  • Diabetes controlled without medicine. Many patients feel proud and happy with sugar control, thinking that diabetes has been cured, but the unfortunate and actual fact is that the person has worsening kidney failure. Anti-diabetic medications have a prolonged effect in patients with kidney failure.
  • Symptoms of chronic kidney disease (weakness, fatigue, loss of appetite, nausea, vomiting, itching, pallor and breathlessness), which develop in later stages.
  • Elevated values of creatinine and urea in blood tests.
Signs of harmful effects of diabetes on kidney are excess protein in urine, high blood pressure and swelling.

How is diabetic kidney disease diagnosed and which test detects it at the earliest?

The two most important tests used to diagnose diabetic kidney disease are the urine test for protein and the blood test for creatinine (and eGFR). The ideal test to detect diabetic kidney disease at the earliest is a test for microalbuminuria (see below). The next best diagnostic test is the urine test for albumin by standard urine dipstick test, which detects macroalbuminuria. Blood tests for creatinine (and eGFR) reflect kidney function with higher values of serum creatinine indicating more severe renal function and increasing in the later stage of diabetic kidney disease (usually after the development of macroalbuminuria).

What is microalbuminuria and macroalbuminuria?

Albuminuria means the presence of albumin (type of protein) in urine. Microalbuminuria, which indicates the presence of a small amount of protein in urine (urine albumin 30-300 mg/day), cannot be detected by a routine urinalysis. It can only be detected by special tests. Macroalbuminuria, which indicates the presence of a large amount of albumin in the urine (urine albumin > 300 mg/day), can be detected by routinely performed urine dipstick tests.

Warning: Frequent reduction of blood sugar or diabetes controlled without medication--suspect diabetic kidney disease.

Why is the urine test for microalbuminuria the most ideal test for the diagnosis of diabetic kidney disease?

Because the test for microalbuminuria can diagnose diabetic kidney disease at the earliest, it is the most ideal test for the diagnosis. Early diagnosis of diabetic kidney disease in this stage (known as high risk stage or incipient stage) is beneficial for patients because if detected early, diabetic kidney disease can be prevented and reversed with meticulous treatment.

The microalbuminuria test can detect diabetic nephropathy 5 years earlier than standard dipstick urine tests and several years before it becomes dangerous enough to cause symptoms or an elevated serum creatinine value. In addition to the risk to kidney, microalbuminuria independently predicts a high risk of developing cardiovascular complications in diabetic patients.

Early diagnostic ability of the microalbuminuria warns patients about developing the dreaded disease and provides doctors the opportunity to treat such patients more vigorously.

When and how often should a urine test for microalbuminuria be done in diabetics?

In Type 1 diabetes, the test for microalbuminuria should be done 5 years after the onset of diabetes and every year thereafter. In Type 2 diabetes, the test for microalbuminuria should be done at the time of diagnosis and every year thereafter.

Two most important diagnostic tests of diabetic kidney disease are urine test for protein and serum creatinine.

How is urine tested for microalbuminuria in diabetics?

For screening of diabetic kidney disease, random urine is tested first by standard urine dipstick test. If protein is absent in this test, a more precise urine test is performed to detect microalbuminuria. If urine albumin is present in routine test, there is no need to test for microalbuminuria. To diagnose diabetic nephropathy correctly, two out of three tests for microalbuminuria need to be positive within a three- to six-month period in the absence of a urinary tract infection.

Three most common methods used for the detection of microalbuminuria are:

Spot urine test: This test is performed using a reagent strip or tablet. It is a simple test which can be performed in an office practice and is less expensive. Because this test is less accurate, a positive test using a reagent strip or tablet should be confirmed by a urine albumin to creatinine ratio.

Albumin-to-creatinine ratio: Urinary albumin-to-creatinine ratio (ACR) is the most specific, reliable and accurate method of testing microalbuminuria. ACR estimates 24-hour urine albumin excretion. In an early morning urine sample, albumin-to-creatinine ratio (ACR) between 30-300 mg/g is diagnostic of microalbuminuria (normal value of ACR < 30 mg/g). Because of the problem of availability and cost, the number of diabetic patients in whom diagnosis of microalbuminuria is established by this method is limited in developing countries.

24-hour urine collection for microalbuminuria: Total urine albumin of 30 to 300 mg in a 24 hour urine collection suggests microalbuminuria. Although this is a standard method for the diagnosis of microalbuminuria, it is cumbersome and adds little to prediction or accuracy.

Urine test for microalbuminuria is the first and most accurate test for the diagnosis of diabetic kidney disease.

How does standard urine dipstick test help in the diagnosis of diabetic kidney disease?

The standard urine dipstick test (often reported as “trace” to 4+) is the most widely and routinely used method for detection of protein in urine. In patients with diabetes, the standard urine dipstick test is an easy and quick method to detect macroalbuminuria (urine albumin >300 mg/day). The presence of macroalbuminuria reflects stage 4 - overt diabetic kidney disease.

In the development of diabetic kidney disease, macroalbuminuria follows microalbuminuria (stage 3 - incipient diabetic kidney disease), but usually precedes more severe kidney damage, i.e. nephrotic syndrome, and the rise in serum creatinine due to chronic kidney disease. While the detection of microalbuminuria identifies the patients with diabetic kidney disease early, its cost and unavailability in developing countries limits its use. In such a scenario, the urine dipstick test to diagnose macroalbuminuria is the next best diagnostic option for diabetic kidney disease.

The urine dipstick test is a simple and cheap method and is readily available even in small centers. It is therefore an ideal and feasible option for the mass screening of diabetic kidney disease. Vigorous management even at this stage of diabetic kidney disease is rewarding and may delay the need for dialysis or kidney transplantation.

How is diabetic kidney disease diagnosed?
Ideal method:

Annual screening of diabetic patients by testing the urine for microalbuminuria and testing blood for creatinine (and eGFR).

Practical method:

Three monthly measurements of blood pressure and urine dipstick test; and annual blood test for creatinine (and eGFR) in all diabetic patients. This method of detection of diabetic kidney disease is easily affordable and possible even in small towns of developing countries.

Annual urine test for microalbuminuria is the best strategy for the early diagnosis of diabetic kidney disease.