What are the 5 stages of diabetic nephropathy (and treatments)?

What are the 5 stages of diabetic nephropathy (and treatments)?

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

DN Stage 1. Hyperfiltration

Years from diagnosis – at onset
Urinary dipstick – negative
uACR (lab urine test) – normal, i.e. < 3 mg/mmol
GFR – increased (>150 ml/min)
BP – normal

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
Dipstick – negative
uACR – < 3 mg/mmol
GFR – normal (90-120 ml/min)
BP – normal

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 (low level of proteinuria)

Years from diagnosis – >5  years
Dipstick – N/positive
uACR – 3-30 mg/mmol
GFR – N or CKD1-2 (60-120 ml/min)
BP – normal or increased

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. Macroalbuminuria (high level of proteinuria) / overt nephropathy

Years from diagnosis – >10 years
Dipstick – positive
uACR – >30 mg/mmol (often >100 mg/mmol)
GFR – decreased (CKD3A-CKD4; i.e. 15-60 ml/min); creatinine normal to 150 (60-120 mcmol/L)
BP – 140/90 or higher

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. Many doctors would start these treatments at Stage 3 (or earlier), even if the blood pressure is normal.

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.

Summary

We have described what are the 5 stages of diabetic nephropathy (and treatments). It is very important to start treatment ASAP, preferably at Stage 2 (or before). We hope it has been helpful.

Other resource

What is diabetic nephropathy? (longer article)
5 stages of diabetic nephropathy
This is a review article: Selby, 2020.

 

Last Reviewed on 8 May 2024

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