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 five years in type 1.
Patients should be tested for proteinuria if they have any of the following risk factors:
- GFR ≤60 ml/min/1.73 m2.
- Cardiovascular disease.
- Structural renal tract disease, multiple renal calculi or prostatic hypertrophy.
- Multisystem diseases with potential kidney involvement, eg systemic lupus erythematosus.
- Family history of chronic kidney disease (CKD) stage 5 or hereditary kidney disease.
- On detection of haematuria.
Making the diagnosis
National Institute for Health and Clinical Excellence (NICE) guidance has recommended that an early morning urinary albumin:creatinine ratio (ACR) should be used in preference to other tests of proteinuria, because ACR offers greater sensitivity for the detection of lower, but clinically significant, levels of proteinuria. This is also a more convenient test than a 24-hour collection.
The upper limit of normal is regarded as a urine albumin:creatinine ratio of:
- 2.5 mg/mmol in men.
- 3.5 mg/mmol in women.
If the laboratory report uses different units, these approximate equivalents may be useful:
- ACR 30 mg/mmol = protein:creatinine ratio (PCR) 50 mg/mmol = urinary protein excretion 0.5 g/24 h.
- ACR 70 mg/mmol = PCR 100 mg/mmol = urinary protein excretion 1 g/24 h.
A positive result should be repeated once or twice in the subsequent month and, if it is borderline, a full 24-hour urine collection will give a more definitive result.
NB: false positive results can occur after heavy exercise or with urinary tract infection.
Chronic kidney disease (CKD)
In patients with significant proteinuria, important objectives of therapy to delay the progression of CKD are to optimise blood pressure control and reduce proteinuria. In patients classified as stages 1, 2 and 3A, cardiovascular risk factors should be managed in accordance with national guidelines, including management of hypertension. All patients should be offered angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).
Referral for specialist opinion should be considered in:
- Younger patients (less than 55 years).
- Those with evidence of progressive kidney disease (eGFR declining at more than 4 mls/min/year), after confirmation with a second blood test.
- Those with proteinuria (PCR greater than 100).
In patients with diabetes and an ACR ≥2.5 mg/mmol (men) or ≥3.5 mg/mmol (women), with or without hypertension, offer ACE inhibitors or ARBs. Maintain blood pressure below 130/80 mm Hg.
Suspect renal disease (other than diabetic nephropathy) and consider further investigation or referral when the albumin:creatinine ratio (ACR) is raised and any of the following apply:
- There is no significant or progressive retinopathy.
- Blood pressure is particularly high or resistant to treatment.
- The patient had a previously documented normal ACR and develops heavy proteinuria (ACR >100 mg/mmol).
- Significant haematuria is present.
- The GFR has worsened rapidly.
- The patient is systemically ill.
In patients who are hypertensive and have an ACR ≥30 mg/mmol, offer ACE inhibitors/ARBs to everyone first-line; otherwise, follow normal hypertension guidelines, eg calcium-channel blocker first-line if aged >55 years.
In patients who are neither diabetic nor hypertensive, but have an ACR ≥70 mg/mmol, offer ACE inhibitors/ARBs to reduce proteinuria and slow any progression.
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. The process can be reversed by controlling blood pressure, especially with ACE inhibitors. Glycaemic control is not quite so vital. Stopping smoking is imperative.
Intensive management of blood pressure and glycaemia in both type 1 and type 2 diabetes has been shown, in the Diabetes Chronic Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS), to improve outcome.
For the best outcome for heart and kidneys, a combination of blood pressure control and use of ACE inhibitors, statins and aspirin is required.
Further reading & references
- Type 2 diabetes: the management of type 2 diabetes (update), NICE Clinical Guideline (May 2008)
- Chronic kidney disease, NICE Clinical Guideline (September 2008)
- Hypertension: management of hypertension in adults in primary care, NICE Clinical guideline (June 2006)
- Allen KV, Walker JD; Microalbuminuria and mortality in long-duration type 1 diabetes. Diabetes Care. 2003 Aug;26(8):2389-91.
- No authors listed; Intensive diabetes management: implications of the DCCT and UKPDS. Diabetes Educ. 2002 Sep-Oct;28(5):735-40.
- 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.
|Original Author: Dr Hayley Willacy||Current Version: Dr Hayley Willacy||Peer Reviewer: Dr Adrian Bonsall|
|Last Checked: 19/08/2011||Document ID: 365 Version: 22||© EMIS|
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