Uncontrolled or poorly controlled diabetes affects the kidneys and leads to a condition called diabetic nephropathy, which is a leading cause of chronic renal failure in many countries, and Malaysia is no exception.

DIABETES is a condition where blood sugar is raised (hyperglycaemia) due to defects of insulin secretion (type 1), insulin action (type 2), or a combination of the two. Diabetics suffer from abnormalities of carbohydrate, fat and protein metabolism.

According to the National Health and Morbidity Survey (NHMS) III in 2006, the overall prevalence of diabetes (known and newly diagnosed) was 11.6%. The prevalence increases with increasing age, viz: the prevalence was 2% in those aged 18 to 19 years and between 20.8% and 26.2% in those aged 50 to 64 years.

There was an increase in the national prevalence of known and newly diagnosed diabetics from 8.3% in NHMS II in 1996 to 14.9% in NHMS III in 2006 in those aged 30 years and above. The prevalence of newly diagnosed diabetics increased from 2.5% in 1996 (NHMS II) to 5.5% in 2006 (NHMS III).

Uncontrolled or poorly controlled diabetes affect the kidneys and leads to the condition called diabetic nephro-pathy, which is a leading cause of chronic renal failure in many countries, and Malaysia is no exception. This condition also leads to significant long-term morbidity and mortality.

The condition is characterised by protein in the urine (albuminuria) on two or more occasions three to six months apart, decline in the kidneys’ glomerular filtration rate (GFR), and raised blood pressure.

The exact cause of diabetic nephropathy is unknown. It is believed that uncontrolled high blood sugar leads to kidney damage, especially when there is also high blood pressure (hypertension). As not all diabetics develop this condition, it is believed that the individual’s genetic or family history may play a role as well.

When the blood sugar is too high, it damages the filtering units of the kidneys (nephron) and the blood vessels within (glomerulus). These structures thicken and form scar tissue. In the course of time, more and more of these structures are damaged and destroyed, resulting in the leakage of protein into the urine (albuminuria).

The peak incidence of diabetic nephropathy in diabetics is in their second decade of the condition. It is uncommon for it to develop in patients who have had diabetes for less than 10 years.

The likelihood of diabetic nephropathy is increased in those with risk factors, i.e. poor control of blood sugar, poor control of blood pressure, family history of kidney disease or hypertension, type I diabetes before the age of 30 years, and smokers.

Complications

Diabetic nephropathy will lead to complications if its onset is not delayed or prevented by early treatment. The complications include severe hypertension, electrolyte disturbances, anaemia, infections, rapidly worsening chronic renal failure, and complications of dialysis and transplantation.

Diabetic nephropathy is often associated with other complications of diabetes.

Diabetic eye disease (retinopathy) is present in almost all type 1 diabetics with nephropathy. However, only about half of type 1 diabetics with proteinuria have retinopathy. As such, investigations would be carried out for non-diabetic causes of nephropathy if there is no retinopathy. Severe retinopathy resulting in blindness is markedly increased in diabetics with nephropathy.

Cardiovascular disease i.e. coronary heart disease, stroke, hypertension and peripheral vascular disease are also increased in diabetics with nephropathy.

Patients with advanced nephropathy are usually affected by disease of the peripheral nerves (neuropathy). This results in the development of foot ulcers, probably due to a combination of arterial and nerve disease. The foot ulcers are often associated with infection leading to an increased likelihood of amputation.

The nerves of the autonomic nervous system can also be affected. Sometimes there are no symptoms, but at other times, there are serious symptoms like sweating, impotence and fainting due to postural hypotension.

Clinical features

There are no symptoms in the early stages of diabetic nephropathy. The symptoms develop late and include fatigue, generalised itchiness, headache, nausea, vomiting, poor appetite, swelling of the legs, swelling around the eyes in the morning, weight gain and urine that foams or froths.

The physical findings are that of long-standing diabetes. The features of associated complications e.g. hypertension, coronary artery disease, stroke, peripheral vascular disease, retinopathy, peripheral neuropathy may also be present.

Diabetic nephropathy is usually diagnosed after finding small amounts of protein on routine urine examination (microalbuminuria). This may occur about five to 10 years prior to other symptoms. If a microalbuminuria test is positive i.e. albumin excretion of more than 20 micrograms per minute, it often means that there is early damage of the kidney by diabetes. The damage at the early stage is potentially reversible. As the test may be positive because of other reasons, it is usually repeated for confirmatory purposes.

Additional laboratory tests may be done. They include serum creatinine, blood urea, electrolytes, 24-hour urinary proteins and urine protein electrophoresis.

Imaging studies like renal ultrasound may be done to measure the size of the kidneys and to rule out obstruction.

A renal biopsy is not usually done unless there are doubts about the diagnosis, if other kidney disease is suspected, or if there are atypical features present. The renal biopsy will confirm the diagnosis.

However, the diagnosis of diabetic nephropathy is usually made without a biopsy if the following criteria are present i.e.

  • Persistent albuminuria;
  • Diabetic retinopathy; and
  • No other kidney or urinary tract disease is present.

Management

The goals of management are to prevent the nephropathy from worsening and to prevent the complications of diabetes from developing.

Keeping the blood pressure below 130/80mm Hg is an effective way of slowing damage to the kidneys. The angiotensin-converting enzyme (ACE) inhibitors and angio-tensin receptor blockers (ARBs) are the preferred medicines for treating hypertension in diabetics and those with signs of kidney disease. Careful blood pressure control is crucial in preventing the progression of diabetic nephropathy and other complications.

Ensuring that the blood sugar levels are at near normal levels will slow down the kidney damage, especially in the early stages of the nephropathy. This may require a combination of diet and medicines. The doses of the latter may need adjustment periodically.

The United Kingdom Prospective Diabetes Study (UKPDS) concluded that although intensive blood glucose control increased treatment costs, it substantially reduced the cost of complications and increased the time the patients were free of complications.

It is crucial that there is also control of blood lipid levels, maintenance of a healthy weight, and participation in regular exercise.

Urinary tract and other infections are common and will be treated with the appropriate antibiotics.

Doctors may recommend limiting dietary protein intake if the kidney function is poor as there are reports of a beneficial effect on renal function from such limitation. When the nephropathy is advanced, there is usually a need for phosphorus and potassium restriction too.

Once chronic renal failure develops, dialysis would be necessary. A kidney transplant may be considered at this stage. However, the very limited availability of donors poses a tremendous challenge to patients and their attending doctors.

Surgical measures are not usually required in diabetic nephropathy. They are usually limited to the management of associated complications like foot ulcers or peripheral vascular disease, establishing access for dialysis and renal transplantation.

Prevention

Appropriate patient information, patient compliance to management prescriptions and regular follow-up clinic or hospital visits are essential to the prevention and early recognition and management of diabetic nephropathy.

The management objectives are:

  • Optimal blood glucose control;
  • Control of hypertension; and
  • Avoidance of medicines that can damage the kidneys, e.g. commonly used non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen, naproxen and antibiotics like the aminoglycosides.

There is ample evidence that the early and optimal management of diabetes will delay or prevent the onset of diabetic nephropathy.

It is prudent to remember that microalbuminuria is an independent predictor of cardiovascular morbidity in diabetics. Deaths from any cause in diabetics are also increased if there is microalbuminuria and macroalbuminuria. Even in the non-diabetic population, microalbuminuria is a predictor of coronary and peripheral vascular disease and death from cardiovascular disease.

It would be in the interest of all diabetics to always remember the axiom “prevention is better than cure”.

Source: Dr Milton Lum