Diabetic Kidney Disease

Diabetes is a worldwide epidemic that has led to a rise in increased diabetic disease. The increased prevalence of diabetes has also led to an increase in the number of macro and micro vascular complications in diabetes such as coronary heart disease, stroke, visual impairment, diabetic kidney disease and end stage renal disease. Diabetes remains the most common reason for progressing to end stage renal disease. Diabetic nephropathy is defined as diabetes with albuminuria impaired Glomerular filtration rate or both and is the single strongest predictor of mortality in patients with diabetes. 

Today diabetic kidney disease encompasses not only diabetic nephropathy but also Atheroembolic disease, ischemic nephropathy, and interstitial fibrosis that occur as a direct result of diabetes. Multiple trials showed that improved glycemic control in Type 1 and Type 2 diabetic patients reduced microalbuminuria, macroalbuminuria and progression to diabetic kidney disease and end stage renal disease.

What are the stages of Diabetic Kidney Diseases?

Diabetic nephropathy is categorized into stages based on the values of urinary albumin excretion, microalbuminuria and macroalbuminuria. Micro albuminuria cut off value is 20 – 199 mg/min and macroalbuminuria cut off value is more than 200 mg/min. Although microalbuminuria has been considered a risk factor for macroalbuminuria, but all patients progressed this stage and some may even regress to normoalbuminuria.

What are the common symptoms in patients with diabetic nephropathy?

In early stages of diabetic nephropathy, you may not notice any signs or symptoms. In later stages, the signs and symptoms include

  • Worsening blood pressure control
  • Protein in the urine
  • Swelling of feet, ankles, hands or eyes
  • Increased need to urinate
  • Confusion or difficulty in concentrating
  • Shortness of breath
  • Loss of appetite
  • Nausea and vomiting
  • Persistent itching
  • Fatigue 

What are the histopathological changes commonly seen in diabetic kidney disease

The mesangial expansion caused by increased matrix secretion and cell enlargement is the first change seen. A thickened basement membrane and podocytes effacement follows this. Vessels can undergo arterial hyalinosis of the afferent and efferent arterioles which leads to Glomerular hyperfilteration. Diabetic glomerulosclerosis are usually seen later in the disease. Structurally the podocytes suffer hypertrophy and then undergo foot process effacement which leads to increased albumin excretion. 

What are the risk factors for developing diabetic kidney diseases?

Diabetic nephropathy develops in almost 40% of patients with diabetes. When high blood glucose levels are maintained for long periods of time, longer duration of diabetes is a key factor here. Epidemiological and familial studies showed that genetic susceptibility contributes to diabetic nephropathy in both Type 1 and Type 2 patients. Other potential factors include sustained hyperglycemia or blood sugars or hypertension, or Glomerular filtration, hyperfliteration, Dyslipidemia, smoking, high protein urea levels, dietary such as amount of source of protein and fat in the diet consumed, etc.  

  • Genetic susceptibility
  • Longer duration of diabetes
  • Sustained high blood sugars
  • Hypertension
  • Dyslipidemia
  • Smoking
  • High proteinuria
  • High protein and high fat diet

Screening for diabetic nephropathy

Screening should be initiated at the time of diagnosis in Type 2 diabetic patients since 7% of them already have macroalbuminuria at that time. For Type 1 diabetic patients, screening has been recommended at 5 years after diagnosis. Puberty is an independent risk factor for macroalbuminuria. Screening must be repeated annually for both Type 1 and Type 2 patients. The first step in screening and diagnosis of diabetic nephropathy is to measure albumin in a spot urine sample collected either as the first urine in the morning or at random during a medical visit. This method is accurate, easy to perform and recommended by Medical Diabetic Association. 

Screening should not be performed in presence of conditions that increase urinary albumin at excretion such as urinary tract infections, Hematuria, acute febrile illness, rigorous exercise, uncontrolled hypertension or hyperglycemia and heart failure etc. 

There are some patients who have decreased Glomerular filtration rate in the presence of normal urinary albumin excretion. These GFR and urinary albumin excretion should be routinely measured for screening of diabetic nephropathy. Apart from this routine evaluation of blood urea nitrogen, serum creatinine and uric acid is also essential. An abdominal ultra sound scan also is very useful in diagnosing all the changes in the kidney and also obstructive changes if any in the kidney.

Tests to be done

  • Spot urine sample to measure albumin levels
  • GFR and UAE (Urinary Albumin Excretion)
  • Blood Urea Nitrogen Levels
  • S. Creatinine Levels
  • S. Uric Acid Levels
  • Abdominal Ultra Sound Scans

 Prevention and Treatment of diabetic kidney disease

The basis for prevention of diabetic kidney disease is the treatment of its known risk factors such as

  • Hypertension
  • Diabetes
  • Dyslipidemia
  • Smoking

This includes intensive blood sugar glucose control and maintaining HbAic below 6% showed significant reduction in micro and macroalbuminuria and thereby less risk of progression of diabetic kidney disease. Control of hypertension reduced risk of cardiac and renal events in diabetic patients. ACE inhibitors and ARB’s significantly diminished risk of diabetic kidney disease. 

The goal of treatment is prevention of progression from microalbuminuria to macroalbuminuria, the decline of renal functions in patients with macroalbuminuria and occurrence of cardio vascular events. Dietary intervention, Dyslipidemia control, Anemia correction, Low dose Aspirin usage, weight reduction etc also plays an important role in preventing progression to diabetic nephropathy. 

Diabetic Kidney Disease remains the main cause of end stage kidney failure in the world. The only accepted medical treatment for DKD is RAS inhibition. Newer agents such as SGLT2 inhibitors are novel promising therapies.  Despite all this, many patients still progress to Renal failure. In such cases and in End Stage Renal Disease, Hospitalized management , Renal Dialysis and ultimately Renal Transplantation is the only choice.