stages of diabetic nephropathy

Last edited 06/2021 and last reviewed 10/2023

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.

 

STAGE Normal Micro Macro End Stage Renal Disease (ESRD)
albumin excretion (mg/l) <20 20-200 >200 >1000
blood pressure 120/75 130/85 145/95 160/100
GFR (ml/min) >110 >110 <100 <30

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)
    • ACR (albumin creatinine ratio) category ACR (mg/mmol)
      A1 <3
      A2 3-30*
      A3 >30**
      • * 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):

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: