What is diabetic nephropathy?

What is diabetic nephropathy?

Diabetic nephropathy (DN) is a serious complication of diabetes that affects the kidneys. It is more commonly caused by Type 2 diabetes (DN2), rather than Type 1 (DN1).

In this article we will describe 10 facts about diabetic nephropathy.

1. Definition

Diabetic nephropathy is a progressive long-term kidney disease caused by diabetes, particularly in individuals with poorly controlled blood pressure (and, to an extent, blood sugar levels).

High blood pressure (and high blood sugar) harms the glomeruli (mini-filters) causing proteinuria (a protein leak in the urine), and eventually CKD.

DN is one of 3 ‘microvascular’ (small blood vessel) complications of DM – others are diabetic retinopathy (eyes) and diabetic neuropathy (nerves).

How long does it take for diabetes to cause kidney damage?

Clinically obvious kidney damage begins 2-5 years after diabetes starts (see point 6 below, on the 5 stages of DN). The more serious stages (DN Stage 4+) start at least 10 years after the start of diabetes.

Diabetic nephropathy is almost always associated with high blood pressure (hypertension). The combination of diabetes and high blood pressure accelerates kidney damage.

2. Pathology: glomerular disease

It is a glomerular disease, i.e. it primarily damages the glomeruli of the kidneys.

3. Leading cause of chronic kidney disease (CKD) and ESRF

It is the leading cause of end-stage renal failure (ESRF) worldwide – when the diagnosis is known*. Hence 20% of people on dialysis have DN.

4. Diagnosis

For most patients with DN, it is a ‘clinical diagnosis’, i.e. made by your GP (or nephrologist) based on a patient who has had DM (usually Type 2 diabetes) more than 10 years, with a characteristic pattern of kidney blood and urine tests, and a normal kidney ultrasound.

There are high levels of protein in the urine, especially as the disease becomes more severe. A renal biopsy is not normally done, unless there is doubt as to the diagnosis.

On examination there may be high blood pressure with signs of fluid overload, including ankle swelling.

5. Pathophysiology

The exact mechanisms underlying diabetic nephropathy are complex and involve various factors, including: inflammation, oxidative stress, and the accumulation of advanced glycation end products (AGEs).

DN is considered a ‘secondary glomerular disease’ meaning that the glomeruli are the main site of damage – and the disease is ‘secondary’ to diabetes; rather than starting in the glomeruli themselves  (like a glomerulonephritis, which is a ‘primary glomerular disease’). Other kidney diseases affect other parts of the kidney.

It is called a ‘microvascular’ type of complication, as it affects small blood vessels in the kidneys – in a similar way to diabetic eye and foot disease. Many patient with DN will therefore have eye and foot disease as well.

6. 5 Stages of diabetic nephropathy (with treatments, i.e. how to slow progression)

There are 5 stages of diabetic nephropathy. This is called the Mogensen classification of diabetic nephropathy.

DN Stage 1. Hyperfiltration

Years from diagnosis – at onset
Dipstick – negative
uACR – < 3 mg/mmol
GFR – inc (>150 ml/min)
BP – N

Treatment
There is no specific treatment for DN at this stage.

Stage 2. Normoalbuminuria  (normal levels of proteinuria = protein in the urine)

Years from diagnosis – 2-5 years
Urine dipstick – negative
uACR (urine lab test) – < 3 mg/mmol
GFR – N (60-120 ml/min)
BP – N

Treatment
There is no specific treatment for DN at this stage. But tight control of blood pressure and glucose (maintaining stable blood sugar levels) can help slow the progression of diabetic nephropathy at this stage – and is part of the prevention strategy.

Stage 3. Microalbuminuria (higher levels of proteinuria)

Years from diagnosis – 5-10 years
Dipstick – N/positive
uACR – 3-30 mg/mmol
GFR – N (60-120 ml/min)
BP – N/+

In the early stages, diabetic nephropathy often presents as microalbuminuria, which means there are small amounts of albumin (a protein) in the urine. This is an early sign of kidney damage and the patient will not notice any symptoms. This is why as soon as someone develops diabetes, they need regular testing of their urine for microalbuminuria.

Treatment
There continues to be no specific treatment for DN at this stage. But continued tight control of blood pressure, glucose (maintaining stable blood sugar levels) and urinary protein (combined) can help slow the progression of diabetic nephropathy at this stage as well.

Stage 4. Overt nephropathy/macroalbuminuria (higher levels of proteinuria)

Years from diagnosis – 10-25 years
Dipstick – positive
uACR – >30 mg/mmol (often >100 mg/mmol)
GFR – dec (15-60 ml/min)
BP +

As the disease progresses, microalbuminuria can advance to macroalbuminuria, where larger amounts of albumin are excreted in the urine. This indicates more severe kidney damage.

High levels of protein in the urine is a hallmark of advancing DN, and is a serious sign. The urine may become frothy when it develops. When the protein levels in the urine are high enough, and blood protein levels are low enough, it is called ‘nephrotic syndrome’.

Regarding GFR, patients are usually in CKD3B-4 at this stage.

Treatment
Medication such as angiotensin-converting enzyme inhibitors (ACE, e.g. Ramipril) or angiotensin receptor blockers (ARBs, e.g. Losartan); and/or SGLT2 inhibitors (e.g. Dapagliflozin) should be prescribed. These help to reduce the protein levels in the urine.

Over time, in some patients, the kidneys’ ability to filter waste and excess fluid from the blood deteriorates. This leads to a worsening renal function and CKD, and increased urinary protein levels; resulting in symptoms such as fatigue, ankle swelling, shortness of breath (ankle and pulmonary oedema). Diuretics (water tablets) may be required at this stage.

Stage 5. ESRF (CKD5, i.e. kidney failure)

Years from diagnosis – > 15 years
Dipstick – positive
uACR – >30 mg/mmol (often >100 mg/mmol)
GFR – dec  (<15 ml/min)
BP ++

Treatment
Despite all interventions, patients with severe DN will need to be prepared for dialysis; plus or minus a kidney or kidney-pancreas (type 1 DM only). The outlook on dialysis is not great, with an average survival of 3 years from the start of dialysis.

7. Treatment

Although there are no specific treatments for DN, tight control of blood pressure, glucose (maintaining stable blood sugar levels) and urinary protein (combined) can help slow the progression of diabetic nephropathy – and is part of the prevention strategy.

Treatments are outlined in the section above.

8. Dialysis and kidney transplantation

As described above, despite all interventions, patients with severe DN will need to be prepared for dialysis; plus or minus a kidney or kidney-pancreas (type 1 DM only). It is important that planning starts early – in early Stage 4 diabetic nephropathy – as GFR starts to fall under 60 ml/min.

9. Screening and monitoring

Regular screening for microalbuminuria and kidney function is essential for individuals with diabetes to detect kidney damage early. Monitoring kidney function involves measuring blood creatinine and glomerular filtration rate (eGFR).

10. Lifestyle factors

Lifestyle modifications, such as adopting a healthy diet, regular exercise, smoking cessation, and limiting alcohol consumption, can play a role in reducing the risk of diabetic nephropathy and its progression.

*Note. Actually the commonest cause is ‘unknown’, which is the ’cause’ in 30% of cases of ESRD.

Summary

We have described what is diabetic nephropathy. We hope it has been helpful.

Other resource

5 stages of diabetic nephropathy (shorter article)
There is more information on diabetic nephropathy written by the renal team at UHCW Coventry.
This is a review article: Selby, 2020.

Last Reviewed on 8 May 2024