Stages of diabetic nephropathy

Diabetic nephropathy can be classified into normal, microalbuminuria, macroproteinuria and endstage renal disease, according to the amount of albumin excreted. Albumin excretion should be measured on 3-4 samples before persistent microabuminuria is declared to be present as there is often a diurnal variation in excretion of upto 40%. It should also be noted that there is a relationship between the blood pressure and level of proteinuria.

Patients with microalbuminuria often have associated problems of hypertension, left ventricular hypertrophy and insulin resistance.

Patients that develop frank proteinuria are a group that have more problems and appear to have more aggressive disease and particularly have problems with macrovascular disease with an increased mortality.

NICE suggest (1):

• clinicians should use urine albumin:creatinine ratio (ACR) in preference to protein:creatinine ration (PCR) in order to detect proteinuria
  • ACR has greater sensitivity than protein:creatinine ratio (PCR) for low levels of proteinuria. For quantification and monitoring of proteinuria, PCR can be used as an alternative. ACR is the recommended method for people with diabetes
  • for the initial detection of proteinuria, if the ACR is between 3 mg/mmol and 70 mg/mmol, this should be confirmed by a subsequent early morning sample. If the initial ACR is 70 mg/mmol or more, a repeat sample need not be tested
  • regard a confirmed ACR of 3 mg/mmol or more as clinically important proteinuria
  • quantify urinary albumin or urinary protein loss for:
    • people with diabetes
    • people without diabetes with a GFR of less than 60 ml/min/1.73 m^2
• NICE suggested a classification of CKD incorporating GFR and ACR (1)

• * Relative to young adult level
• ** Including nephrotic syndrome (ACR usually >220 mg/mmol)

• CKD is classified according to estimated GFR (eGFR) and albumin:creatinine ratio (ACR), using 'G' to denote the GFR category (G1-G5, which have the same GFR thresholds as the CKD stages 1-5 recommended previously) and 'A' for the ACR category (A1-A3), for example:
  • a person with an eGFR of 25 ml/min/1.73 m2 and an ACR of 15 mg/mmol has CKD G4A2.
  • a person with an eGFR of 50 ml/min/1.73 m2 and an ACR of 35 mg/mmol has CKD G3aA3
  • an eGFR of less than 15 ml/min/1.73 m2 (GFR category G5) is referred to as kidney failure
  • it is noted that:
    • increased ACR is associated with increased risk of adverse outcomes
    • decreased GFR is associated with increased risk of adverse outcomes
    • increased ACR and decreased GFR in combination multiply the risk of adverse outcomes

This is summarised as (2):

Open Image in Modal

Abbreviations: ACR, albumin:creatinine ratio; CKD, chronic kidney disease

Notes:

• consider using eGFRcystatinC at initial diagnosis to confirm or rule out CKD in people with:
  • an eGFRcreatinine of 45-59 ml/min/1.73 m2, sustained for at least 90 days and
  • no proteinuria (albumin:creatinine ratio [ACR] less than 3 mg/mmol) or other marker of kidney disease
• do not diagnose CKD in people with:
  • an eGFRcreatinine of 45-59 ml/min/1.73 m2 and
  • an eGFRcystatinC of more than 60 ml/min/1.73 m2 and
  • no other marker of kidney disease
• use of renin-angiotensin system antagonist to people with CKD based on ACR:
  • angiotensin-converting enzyme inhibitors (ACE inhibitors)/ angiotensin-II receptor blockers (ARBs) should be offered to non-diabetic people with CKD:
    • diabetes and an ACR of 3 mg/mmol or more (ACR category A2 or A3)
    • hypertension and an ACR of 30 mg/mmol or more (ACR category A3)
    • an ACR of 70 mg/mmol or more (irrespective of hypertension or cardiovascular disease)

Reference:

• NICE (July 2014). Chronic Kidney Disease - Early identification and management of chronic kidney disease in adults in primary and secondary care
• The North West London Health and Care Partnership. North West London Diabetes Guidelines (Accessed 30/6/2020).