Diabetic Kidney Disease

Importance and Risk factors

The number of people suffering from diabetes mellitus is increasing all over the world. The impact of a growing number of diabetic patients is an increase in the incidence of diabetic kidney disease, one of the worst complications of diabetes that carries a high mortality.

What is diabetic kidney disease?

Persistent high blood sugar damages small blood vessels of the kidney in long-standing diabetes. This damage initially causes loss of protein in the urine. Subsequently it causes hypertension, swelling and symptoms of gradual damage to the kidney. Finally, progressive deterioration leads to severe kidney failure (ESKD). This diabetes induced kidney problem is known as diabetic kidney disease. Diabetic nephropathy is the medical term used for diabetic kidney disease.

Why is it important to learn about diabetic kidney disease?

• The incidence of diabetes is growing very fast throughout the world.
• Diabetic kidney disease (diabetic nephropathy) is the number one leading cause of chronic kidney disease.
• Diabetes mellitus is responsible for 40-45 % of newly diagnosed patients with end stage kidney disease (ESKD).
• Therapy of ESKD is costly and may be unaffordable for patients in developing countries.
• Early diagnosis and treatment can prevent diabetic kidney disease. In diabetics with established chronic kidney disease, meticulous therapy can postpone the need for dialysis and transplantation significantly.
• There is an increased risk of death from cardiovascular causes in patients with diabetic kidney disease.
• Early diagnosis of diabetic kidney disease is therefore essential in the care of the diabetic patient.

How many diabetics develop diabetic kidney disease?

There are two major types of diabetes mellitus, each with different risks of developing diabetic kidney disease.

Type 1 Diabetes (IDDM - Insulin Dependent Diabetes Mellitus):

Type 1 diabetes usually occurs at a young age and insulin is needed to control it. About 30 - 35% of Type 1 diabetics develop diabetic kidney disease.

Type 2 Diabetes (NIDDM - Non Insulin Dependent Diabetes Mellitus):

Type 2 diabetes usually occurs in adults and is controlled without insulin in most of the patients. About 10 - 40% of Type 2 diabetics develop diabetic kidney disease. Type 2 diabetes is the number one cause of chronic kidney disease, responsible for more than one of every three new cases.

Which diabetic patient will develop diabetic kidney disease?

It is difficult to predict which diabetic patient will develop diabetic kidney disease. But major risk factors for its development are:

• Type 1 diabetes with onset before 20 years of age
• Poorly controlled diabetes (higher HbA1c levels)
• Poorly controlled high blood pressure
• Family history of diabetes and chronic kidney disease

• Vision problem (diabetic retinopathy) or nerve damage (diabetic neuropathy) due to diabetes
• Presence of protein in urine, obesity, smoking and elevated serum lipids

When does diabetic kidney disease develop in a diabetic patient?

Diabetic kidney disease takes many years to develop, so it rarely occurs in the first 10 years of diabetes. Symptoms of diabetic kidney disease manifest 15 to 20 years after the onset of Type 1 diabetes. If a diabetic person does not develop diabetic kidney disease in the first 25 years, the risk of it ever developing decreases.

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.

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.

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.

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.

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.

Prevention and Treatment of Kidney Disease

How can diabetic kidney disease be prevented ?

Important tips to prevent diabetic kidney disease include:

• Follow up regularly with the doctor.
• Achieve the best control of blood sugar. Keep HbA1C levels less than 7%.
• Keep blood pressure below 130/80 mmHg. Antihypertensive drugs called angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) should be used to control hypertension and aid in the reduction of albuminuria.
• Restrict sugar and salt intake and eat a diet low in protein, cholesterol and fat.
• Check kidneys at least once a year by performing a urine test for albumin and blood test for creatinine (and eGFR).
• Other measures: Exercise regularly and maintain ideal weight. Avoid alcohol, smoking, tobacco products and indiscriminate use of painkillers.

Treatment of diabetic kidney disease

• Ensure proper control of diabetes.
• Meticulous control of blood pressure is the most important measure to protect the kidneys. Blood pressure should be measured regularly and maintained below 130/80 mmHg. Treatment of hypertension slows the progression of chronic kidney disease.
• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are antihypertensive drugs that have a special advantage for diabetic patients. These antihypertensive drugs have the additional benefit of slowing the progression of kidney disease. For maximum benefit and kidney protection, these drugs are administered at the earliest stage of diabetic kidney disease when microalbuminuria is present.
• To reduce facial or leg swelling, drugs which increase urine volume (diuretics) are given along with restriction of salt and fluid intake.
• Patients with kidney failure due to diabetic kidney disease are prone to hypoglycemia and therefore need modification in drug therapies for diabetes. Short acting insulin is preferred to control diabetes. Avoid long acting oral hypoglycemic agents. Metformin is usually avoided in patients with serum creatinine levels more than 1.5 mg/dl due to the risk of lactic acidosis.
• In diabetic kidney disease with high serum creatinine, all measures of treatment of chronic kidney disease (discussed in Chapter 12) should be followed.
• Evaluate and manage cardiovascular risk factors aggressively (smoking, raised lipids, high blood glucose and high blood pressure).
• Diabetic kidney disease with advanced renal failure requires dialysis or kidney transplant.

Diabetic patients with microalbuminuria should be referred to a kidney specialist. The patient with diabetic kidney disease should immediately consult a doctor in case of:

• Rapid unexplained weight gain, marked reduction in urine volume, worsening of facial and leg swelling or difficulty in breathing.
• Chest pain, worsening of pre-existing high blood pressure or very slow or fast heart rate.
• Severe weakness, loss of appetite or vomiting or paleness.
• Persistent fever, chills, pain or burning during urination, foul-smelling urine or blood in urine.
• Frequent hypoglycemia (low sugar level) or decreased requirement of insulin or anti-diabetic medications.
• Development of confusion, drowsiness or convulsion.