Diabetic Nephropathy

What is diabetic nephropathy?

Diabetic nephropathy also called Kimmelstiel-Wilson disease; Diabetic glomerulosclerosis; is a progressive kidney disease that occurs as result of long term uncontrolled diabetes mellitus. It is a complication of diabetes Mellitus with a significant mortality and morbidity rate.

Causes

Several factors play part in development of diabetes Nephropathy.

• Uncontrolled high blood sugar
• High blood pressure
• Afro-Americans (13%), Hispanic (9.5%) and people with an Indian origin are said to be in higher risk of developing the condition than others.  
• Genetics

Does everyone with diabetes develop this?

No. Most people with diabetes do not develop this condition. People with type one diabetes are said to be at a higher risk of developing the disease than those with Type two diabetes.

What Happens in Diabetes Nephropathy?

In this condition, abnormality is found in the kidney. That is why it is called diabetes nephropathy. Kidneys are the organs, which filters blood and remove the waste products and other substances which are present in excess amounts from the body. This process occurs in millions of small units called the nephrones. Each nephrone has a part called the glomerulus. The glomerulus is composed of a tuft of tiny capillaries, which brings in blood and another membrane called the Bowman’s capsule. Both membranes of capillaries and the Bowman’s capsule have tiny holes, so they can act as a filter.  Most of the blood constituents with small molecular weight are filtered in to the glomerular filtrate. But, the bigger molecules like plasma proteins like albumin are not filtered. 

In uncontrolled Diabetes Mellitus, there is persistently high blood sugar. These high concentrations of blood sugar damage the above mentioned filtering membrane causing them to thickened (glomerulosclerosis). The pores in those membranes become lager. As a result the bigger molecules like plasma proteins like albumin leeks in to the membrane. So, finally albumin is found in the urine. Initially as the damage is little, only small amount of albumin is found. Therefore, it is called microalbuminuria. 

How to find out whether you have Diabetes Nephropathy? What are the Symptoms and signs?

• The initial abnormality found is microalbuminuria, which will not usually be detected unless you specially looked for it. People with type 1 diabetes are said develop microalbuminuria typically after 5 years. At this stage there are no symptoms. Therefore the patient feels fine. It is very important to detect the disease at this stage, because the kidney damage might be reversible. Microalbuminuria will present in urine for 5-10 years before the major symptoms of the disease start to show. The glomerular damage is not reversible once the renal damage has progressed to a level that a lot of albumin is found in urine. Therefore, doing urine analysis in diabetes patients is very important. 

• As the damage progresses high level of protein is found in urine even by a normal urine analysis. The patient himself may be able to detect high level of protein in urine.  This is indicated by presence of froth in urine and its foamy appearance.

• As the body continues to loose protein, the blood albumin levels gradually falls. Albumin plays a major role in keeping water getting out of blood vessels in to the surrounding tissues. As the albumin concentration goes down, more water gets off from the vascular compartment. This ultimately leads to swelling off the body. The swelling will first appear around in the mornings. Later as the disease progressed the swelling will start appearing in the legs and the feet. 

• High blood pressure
• High cholesterol and triglyceride levels
• Leg cramps
• Nocturia – passing urine several times at night
• Less need for antidiabetic treatment

Rests of the symptoms are very non specific and could be due to any other illness. They are,

• Fatigue
• Frequent hiccups
• Gastrointestinal symptoms like nauseas and vomiting
• Poor appetite
• General ill feeling

How is it confirmed?

The following parameters are considered when diagnosing the disease.

• Presence of macroalbuminuria – 300 mg of albumin present in urine passed within 24 hours.
• Presence of abnormal renal function tests – serum creatinine

                                                                          Calculated creatinine clearance
                                                                          Abnormal glomerular filtration rate

•   Presence of diabetes retinopathy
• Renal biopsy can confirm the diagnosis, but it is not always necessary if the history and clinical findings points towards the disease.

              - early stages shows mesangial expansion and glomerular basement membrane thickening.

              - Later stages - nodular glomerulosclerosis, also referred to as Kimmelstiel-Wilson disease.

                                                                  

How the Condition is managed? What are the Treatments?

Treatment of this condition is pointed towards the slowing down of kidney damage and controlling the associated problems. In this case, controlling the blood pressure plays a major role. It helps both in slowing the renal damage as well as reducing the cardiovascular damage (e.g.: strokes) seen in diabetes patients. Currently it is recommended to maintain blood pressure less than 130/80 mmHg. Following drugs are used to meet this goal.

• ACE Inhibitors – Causes renal vasodilatation and thereby increases renal blood flow.
• Diuretics also play a major role.

• Angiotensin receptor blockers – but the combination therapy has shown to worsen the outcome.

Tight control of blood glucose level – This has lead to a significant reduction in the progression of the disease.

Diet control to reduce blood glucose level

Avoid renal toxins – NSAIDs, Cyclooxygenase 2 inhibitors, radio contrast media