What is diabetic nephropathy?
Diabetic nephropathy is a complication seen in longstanding diabetes mellitus (sugar diabetes) where progressing impairment of kidney function leads to end-stage renal disease (ESRD). It affects both type 1 and type 2 diabetes patients and is the most common kidney condition requiring dialysis.
Diabetic nephropathy tends to develop in diabetic patients usually 15 to 25 years after the initial diagnosis of diabetes mellitus. It is more likely to occur in patients with poorly managed diabetes mellitus and results from the microvascular complications to the capillaries in the renal glomeruli (kidney’s filtering apparatus). Diabetic nephropathy is also referred to as Kimmelstiel-Wilson syndrome, after the two physicians who first reported it.
Signs and Symptoms of Diabetic Nephropathy
In the early stages of diabetic nephropathy, patients are asymptomatic (no symptoms evident). It is only towards the late stages that the predominant features of renal failure becomes evident. This includes :
- generalized edema (swelling of the body due to fluid retention)
- facial puffiness especially in the morning
- swelling of the legs that progressively worsens during the course of the day
- weight gain due to edema (water retention)
- foamy urine due to proteinuria
- nausea and/or vomiting
- loss of appetite
- Long standing uncontrolled diabetes is the single most important risk factor in the development of diabetic nephropathy.
- Cigarette smoking
- Concurrent diseases like hypertension and hyperlipidemia
- Family history of diabetic nephropathy
Complications of Diabetic Nephropathy
Diabetic nephropathy can lead to renal failure and severe hypertension. Hypoglycemia can develop in renal failure patients due to reduced renal excretion of insulin. Therefore, the insulin dosage may need to be reduced in diabetic nephropathy patients after renal failure has developed. At this stage, there is also an increased risk of complications in procedures like dialysis and transplantation.
Infections are common in diabetic patients. Increased potassium levels (hyperkalemia) can develop in renal failure patients. The hyperkalemia may worsen in hypertensive patients using ACE inhibitors and angiotensin II receptor blockers.
Stages of Diabetic Nephropathy
The development of diabetic nephropathy in type 1 diabetic patients is well understood but less so in type 2 diabetes. The progression of the disease is described in 5 stages in type 1 diabetes. The disease course can be highly variable, especially in type 2 diabetics. Some type 2 diabetics may remain stable with moderate proteinuria for several years while some patients advance across stages very quickly. Monitoring serum creatinine regularly can help in assessing disease progression and also the success of the treatment.
In the early stages of diabetes there is renal hypertrophy (enlargement) and increased renal blood flow resulting in increased glomerular filtration rate (GFR). Increased blood glucose levels are believed to be responsible for this change and intensive blood sugar control can reduce the features of this stage.
Glomerular lesions (like thickened glomerular basement membranes and arteriosclerosis) start appearing after 3-5 years of diagnosis of type 1 diabetes. The changes lead to the increased glomerular permeability resulting in albumin excretion of 30 to 300 mg/day in urine (microalbuminuria).
There is progression in glomerular damage (glomerulosclerosis) and increased albuminuria with more than 300 mg/day of albumin excreted in the urine. Systemic hypertension develops in more than 50% of the patients during this stage. Other renal function tests remain normal in this stage. This stage usually takes about 15 years after the diagnosis of type 1 diabetes.
There is further increase in the glomerular damage (increased glomerulosclerosis and occasional Kimmelstiel-Wilson nodular lesions) and albuminuria. There is progressive decrease in the renal function with blood urea and serum creatinine showing a gradual increase. GFR shows progressive decline of 10 mL/min per year. Most of the patients would have developed hypertension by this stage.
The progression of renal damage (extensive glomerulosclerosis and numerous Kimmelstiel-Wilson nodular lesions) to end stage renal disease (ESRD) is clinically marked by the appearance of massive proteinuria, low blood albumin levels and generalized edema (nephrotic syndrome). ESRD develops in most patients after about 10 years following the starting of rise in the serum creatinine concentration. At this stage the GFR would have fallen to 10 mL/min and dialysis or renal transplantation is needed for survival.
Diagnosis of Diabetic Nephropathy
- The earliest detectable laboratory abnormality is microalbuminuria.
- There is progressive increase in the 24 hour proteinuria with disease progression. Poorly controlled diabetes will also show a positive urine glucose test.
- Blood urea nitrogen (BUN) and serum creatinine can increase in the later stages of disease and these tests are done regularly to monitor the disease progression.
- Renal biopsy can confirm the diagnosis but is not needed in most patients as the diagnosis can be made with clinical correlation with the above tests.
Treatment of Diabetic Nephropathy
The management of diabetic nephropathy depends primarily on the stage of disease. Strict blood glucose control is the most important step in delaying the onset and progression of nephropathy. It has been found to be effective in reducing the microalbuminuria and proteinuria.
Control of hypertension is very important in delaying progression of nephropathy. Angiotensin-converting enzyme (ACE) inhibitors (like ramipril) and angiotensin II receptor blockers (like losartan) and preferred drugs in controlling blood pressure in diabetics and have been found to delay progression of proteinuria and the falling GFR.
Systolic blood pressure should be maintained near 120 mm Hg while diastolic blood pressure between 70-80 mm Hg. Beta blockers (like bisoprolol) and calcium channel blockers (like amlodipine) are alternative second line options.
In later stages aggressive measures in controlling blood pressure and strict blood glucose control remains the mainstay in slowing disease progression. In addition dietary control of protein and fat intake and cholesterol lowering treatment can help in the delay of disease progression.
Once the end-stage renal disease has developed renal replacement therapy is the only option available. Renal replacement may be done with regular dialysis (hemodialysis or peritoneal dialysis) or renal transplantation.
Combined kidney-pancreas transplantation is an option in type 1 diabetic patients. Despite dialysis and transplantation in diabetic nephropathy patients have a higher risk of mortality than non-diabetic nephropathy patients.
Urinary tract infections are common in diabetic patients and appropriate antibiotic therapy should be initiated promptly.