Diabetic Nephropathy

Key Points

  • Diabetic nephropathy is the most common  cause of severe CKD in the UK
  • Definition = persistent albuminuria (ACR>2.5) on ≥ 2 separate occasions separated by >3 months
  • Typically coexists withretinopathy and neuropathy
Epidemiology
  • 20% of all ESRF patients are diabetic
    • Diabetes is the most common cause of ESRF
  • 20% of DMII patients will develop ESRF
Pathophysiology
  • Diabetic nephropathy describes kidney disease due to microvascular disease
    • Result in intrinsic kidney damage followed by GFR deterioration (i.e. CKD)
    • Exacerbated by hypertension which often coexists with diabetes
  • Natural history of progression (Mnemonic – Elevated Glomerulus Means Nephropathy)
  1. Renal hyper-perfusion due to high BP which results in :
    1. Initial GFR elevation due to hyperglycaemia
    2. Albuminuria (ACR >2.5)
    1. Glomerular hypertrophy
  • This stage is reversible with glycaemic control and HTN management – therefore screening is key
  1. Glomerular hyperfiltration follows on from the hyperperfusion
    • Hyperglycaemia causes  pathological changes via AGEs (Advanced Glycosylated End-products) that cause destruction in the glomerulus/tubules, leading to:
      • Mesangial expansion
      • GBM thickening
      • Glomerulosclerosisdue to intraglomerular HTN
  1. Proteinuria indicates progression of disease (ACR >25mg)
    • T
    • GFR may be raised or normal
  1. Stage 4 – Nephropathy (i.e. CKD develops)
    1. GFR decreases (as creatinine rises)
    2. Increased proteinuria develops (ACR >300mg can develop)
Aetiology
  • As with most conditions, risk factors are unmodifiable and modifiable
  • Unmodifiable:
    • Genetics
    • Increasing age
    • Increasing duration of diabetes (usually develops after ≥10 years with diabetes)
    • Ethnicity
  • Modifiable
    • Tightly linked with cardiovascular disease – both cause and effects it
      • Hypertension
      • Hyperlipidaemia
    • Low baseline albuminuria
    • Smoking
    • Presence of retinopathy/neuropathy

Clinical features
  • These generally stem from the complications of CKD, and so are the same for all CKD (for which I will do a separate set of notes)
Diagnosis and staging

As with all CKD, the two main factors to consider are:

  1. GFR – indicates the level of kidney damage
    • Can remain high in isolated kidney damage
    • If low, this indicates advanced disease (Nephropathy)
  2. Albuminuria/proteinuria – the amount of protein in the urine
    1. Urine dipstick gives a qualitative indication
    2. Urine ACR can also be assessed quantitatively using 2 tests:
      1. Urinalysis with first pass morning sample with specialised sticks
      2.  24hr test with albumin/creatinine can be used instead
  • A higher ACR indicates more kidney damage:
    • >2.5mg/mmol = albuminuria (>3.5 in males)
    • >25mg/mmol = proteinuria
    • >250mg/mmol = severe proteinuria

Management

Both prevention and management (of diagnosed nephropathy) have the same 3 main principles

  1. Treating hypertension is the mainstay- maintain a BP of <130/80mmHg in all diabetics 
    • ACE inhibitors are used in all diabetics for primary prevention (ARBs are used if ACEIs are not tolerated). These not only treat hypertension, but also reduce progression of albuminuria
  2. Glycaemic control
  3. Statins can help in patient

Referral criteria

  • Patients are referred to a nephrologist if:
    1. Urine ACR >70
    2. Suspecting other differentials of CKD (e.g. glomerulonephritis, CCF, etc).
      • These are indicated by sudden onset, rapid deterioration eGFR, and an absence of other diabetic complications (e.g. retinopathy)