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Microalbuminuria

Microalbuminuria is defined as excretion of between 30 and 300mg of albumin a day in the urine.

  • Less than 30 mg is insignificant.
  • Over 300 mg is albuminuria or macroalbuminuria.

Albumin levels below 300mg a day are not detectable by standard dipstick testing, so any positive result is more severe than "microalbuminuria".

Aetiology

Patients with type 2 Diabetes may have microalbuminuria at presentation as they may have had latent disease for years.
This is not usual in type 1 Diabetes. Hence it is recommended that annual screening for microalbuminuria should start at diagnosis in type 2 but only after 5 years in type 1.1

Risk Factors Diabetes and hypertension are both risk factors but together the risk is very high.
Other causes of albuminuria include:

All pass through a brief phase of microalbuminuria, but this is short and the diagnosis is usually made with a more substantial proteinuria.

Making the Diagnosis
  • An early morning urine specimen is more convenient than a 24 hours collection.
  • The upper limit of normal is regarded as a urine albumin:creatinine ration of 2.5mg/mmol in men and 3.5mg/mmol in women.
  • Some laboratories set a limit of 20mg albumin per litre.
  • A positive result should be repeated once or twice in the next month and if it is borderline a full 24 hours urine collection will give a more definitive result.
  • Levels below 300mg a day are not detectable by conventional dipstick testing but there are now some sticks for microalbuminuria available on the market.
  • False positive results can occur after heavy exercise or with UTI.
  • If a diabetic develops heavy proteinuria, especially in a fairly short space of time, then another cause should be sought.
  • The same is true if there is no retinopathy.
  • If blood creatinine rises above 150 μmol/l referral to a nephrologist is recommended.

Management in Diabetes Mellitus

The three pillars of management are:

  1. Control of blood pressure - BP should be reduced to 135/75.1
    • This may be quite difficult to achieve, especially in type 2 diabetics, and may require several drugs.
    • Use an ACE inhibitor as first line, checking U&E before and after commencing therapy.
    • ACE inhibitors have a specific beneficial action and can even reverse microalbuminuria in the absence of hypertension. 2
    • Angiotensin 2 antagonists (AT2) may be used if the patient does not tolerate an ACE and it can even be added to full dose of an ACE if microalbuminuria persists but potassium levels must be carefully monitored.3
    • Remember usual advice about salt, high alcohol intake and encouraging exercise.
    • The value of ACE inhibitors in both diabetic and non-diabetic cases with microalbuminuria was shown in the HOPE trial.4
  2. Control of glycaemia - Target HbA1C is 7.5% or less.
    Adjust drugs, insulin and diet accordingly.
  3. Stopping smoking - The presence of microalbuminuria is a further reason to exhort any diabetic who smokes to stop.5

Prognosis

In type 1 diabetes microalbuminuria is a prognostic indicator of renal failure but in type 2 diabetes it is a prognostic indicator of ischaemic heart disease.
Fundamentally it is the same process and pathology in both but type 2 diabetics have further advanced coronary atheroma at the time of diagnosis. It represents damage to the basement membrane allowing more protein to leak through the glomeruli than can be reabsorbed and this is indicative of all complications of Diabetes. The damaged basement membrane also predisposes to atheromatous plaque formation. Hence it may point to retinopathy, neuropathy and many other complications.
Microalbuminuria is a powerful predictor of increased mortality.6
The process can be reversed by controlling blood pressure, especially with ACE inhibitors. Glycaemic control is not quite so vital. Stopping smoking is imperative.

Prevention

Intensive management of blood pressure and glycaemia in both type 1 and type 2 diabetes has been shown in the DCCT and UKPDS to improve outcome 7
For the best outcome for heart and kidneys a combination of blood pressure control, use of ACE inhibitors, statins and aspirin are required.8

Document References
  1. NICE Guidelines; Management of type 2 diabetes - renal disease, prevention and early management (Guideline F), NICE (2002)
  2. Wade VL, Gleason BL; Dual blockade of the renin-angiotensin system in diabetic nephropathy.; Ann Pharmacother. 2004 Jul-Aug;38(7-8):1278-82. Epub 2004 Jun 8. [abstract]
  3. Chuahirun T, Simoni J, Hudson C, et al; Cigarette smoking exacerbates and its cessation ameliorates renal injury in type 2 diabetes.; Am J Med Sci. 2004 Feb;327(2):57-67. [abstract]
  4. Sleight P; The HOPE Study (Heart Outcomes Prevention Evaluation).; J Renin Angiotensin Aldosterone Syst. 2000 Mar;1(1):18-20. [abstract]
  5. Dykeman-Sharpe J; Proteinuria, a modifiable risk factor: angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs).; CANNT J. 2003 Oct-Dec;13(4):34-6; quiz 37-8. [abstract]
  6. Allen KV, Walker JD; Microalbuminuria and mortality in long-duration type 1 diabetes.; Diabetes Care. 2003 Aug;26(8):2389-91. [abstract]
  7. No authors listed; Intensive diabetes management: implications of the DCCT and UKPDS.; Diabetes Educ. 2002 Sep-Oct;28(5):735-40.
  8. Deferrari G, Ravera M, Berruti V, et al; Optimizing therapy in the diabetic patient with renal disease: antihypertensive treatment.; J Am Soc Nephrol. 2004 Jan;15 Suppl 1:S6-S11. [abstract]
Internet and Further Reading
  • NSF for Diabetes
Acknowledgements EMIS is grateful to Dr Hayley Willacy for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2007.
DocID: 365
Document Version: 20
DocRef: bgp2115
Last Updated: 25 Jan 2007
Review Date: 24 Jan 2009




















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