First published January 2006; Updated April 2021

Approximately 1.8 million people in the UK have been diagnosed with diabetes (which is about three per cent of the UK population) and as many as a million remain undiagnosed1. Ninety per cent of these patients have type 2 diabetes, the rate of which is predicted to double by 20102.

Microalbuminuria is defined as the presence of 20–200µg/min levels of albumin in the urine (30– 300mg/24 hours); it is a condition that represents the first sign of diabetic nephropathy and is an important indicator of increased cardiovascular (CV) risk3.

Roughly 50 per cent of patients with diabetes develop microalbuminuria (or incipient nephropathy)4, and about a third of these patients progress to proteinuria or macroalbuminuria5: (Urinary Albumin Excretion (UAE) >200µg/min). Almost all proteinuric diabetic patients develop End Stage Renal Disease (ESRD) or die prematurely from CV disease4.

Type 2 diabetic patients with hypertension are at particular risk of nephropathy. Diabetic nephropathy carries an alarming CV risk profile, one that increases progressively along the disease continuum6. In five years, 32 per cent of patients with type 2 diabetes and microalbuminuria are dead (53 per cent of these deaths are due to CV disease). It is therefore extremely important that the risk of microalbuminuria onset is reduced5.

Current recommendations

Currently general practice is already proficient in the management of diabetic patients with existing microalbuminuria and overt proteinuria. This has been aided by guidelines from the National Institute for Health and Clinical Excellence (NICE) and using published trial data. The 2004 NICE hypertension guideline states that Angiotensin Converting Enzyme (ACE) inhibitors should be used as a second-line therapy after diuretics in all hypertensive patients at risk of new onset diabetes7.

More pertinently, if hypertensive patients have type 2 diabetes they should be managed in accordance with the NICE management of type 2 diabetes (management of blood pressure and blood lipids) 2002 guideline3. This states that if a hypertensive patient already has type 2 diabetes with existing microalbuminuria or proteinuria, ACE inhibitors are the first line option with a Blood Pressure (BP) target of 135/75mmHg. Where ACE inhibitors are unsuitable or are contraindicated in people with microalbuminuria or proteinuria, then Angiotensin Receptor Blockers (ARBs) may be considered as alternative first-line therapy.

NICE also stated that if a hypertensive patient has type 2 diabetes without microalbuminuria or proteinuria, ACE inhibitors, ARBs, beta-blockers or thiazide diuretics are first-line treatments – with a BP target of 140/80mmHg. 

Recent evidence

A number of trials8-11 have shown that the progress of existing microalbuminuria and proteinuria can be slowed by the use of both ACE inhibitors and ARBs. A more recent study has compared the effects of an ACE inhibitor and a calcium channel blocker in preventing development of microalbuminuria. The BENEDICT12 study was a multicentred, randomised, double blind, parallel group study that involved 1,209 patients aged ≥40 years with type 2 diabetes and hypertension, normal UAE of <20µg/min and normal renal function (serum creatinine ≤1.5mg/dL) to one of four treatments (the ACE inhibitor trandolapril plus the calcium channel blocker verapamil, trandolapril alone, verapamil alone, or placebo)12. The primary end point was development of persistent microalbuminuria (defined as UAE 20-200µg/min at two consecutive clinic visits), assessed over a median of 3.6 years.

Trandolapril slowed the progression to microalbuminuria by 53 per cent compared to placebo (p=0.01), and this benefit exceeded expectations based on changes in BP alone. The addition of verapamil did not increase renoprotection, while verapamil alone had a similar effect to placebo on progression to microalbuminuria.

Other recommendations

The 2004 Quality and Outcomes Framework13 also recognises the significance of microalbuminuria in diabetic patients by providing a specific reward for recording and treating the condition in diabetic patients. A record of microalbuminuria in the past 15 months (exception reporting for proteinuria) can yield a maximum of three points against a 90 per cent register target. And treating patients with proteinuria or microalbuminuria with an ACE inhibitor or an ARB can gain a further three points against a 70 per cent register target.

Part two of the recently published National Service Framework for Renal Services also recommends surveillance, including testing of renal function, in patients with hypertension and diabetes (although the desirability of testing for microalbuminuria is not explicitly stated)14.

Screening

There are a variety of testing methods for microalbuminuria. The simplest and most convenient screening method is a random urine sample test of Albumin Creatinine Ratio (ACR)15.

A normal ACR is <2.5mg/mmol in men and <3.5mg/mmol in women, but microalbuminuria is any value above these up to 30mg/mmol. Above 30mg/mmol and it becomes overt proteinuria, which is readily identifiable by a standard urine dipstick test.

It is advised that early morning specimens are taken for microalbuminuria testing, in order to reduce the influence of diurnal variation in albumin excretion.

Conclusion

With the increasing prevalence of obesity and diabetes in the population, the problem of diabetic nephropathy is – if anything – going to worsen with time. Left unchecked, microalbuminuria represents the tip of a diabetic nephropathy iceberg with huge CV/renal morbidity and mortality connotations. By following guidelines and recent evidence, GPs can be at the frontline of preventing this condition.

Key points

  • Approximately 50 per cent of patients with diabetes develop microalbuminuria (or incipient nephropathy).
  • A third of these patients progress to proteinuria.
  • Almost all proteinuric diabetic patients develop ESRD or die prematurely from CV disease.
  • Current guidelines state that if a hypertensive patient has type 2 diabetes with existing microalbuminuria or proteinuria, ACE inhibitors should be the first line option.

References 

  1. Diabetes UK website. http://www. diabetes.org.uk/ (date last accessed: 13/12/05)
  2. Purcell H, Daly C. Reducing the cardiovascular risk in diabetes. The Practitioner 2005: 249 (1669): 233–4
  3. NICE. Inherited guideline H, 2002. Management of type 2 diabetes – management of blood pressure and blood lipids. http://www.nice.org. uk/page.aspx?o=38551 (date last accessed: 02/12/05)
  4. Alder Al, Stevens RJ, Manley SE, et al. Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney International International 2003;63: 225-32
  5. The Royal College of General Practitioners’ Effective Clinical Practice Unit. Guideline entitled: ‘Diabetic renal disease: prevention and early management’ 2002; 63: 225-32.
  6. de Zeeuw D. Albuminuria, not only a cardiovascular/renal risk marker, but also a target for for treatment? Kidney Int Suppl 2004; 92: s2-6
  7. NICE guidelines, August 2004: Hypertension – management of hypertension in adults in primary care. http://www.nice.org.uk/page. aspx?o=218469 (date last accessed: 02/12/05)
  8. Parving HH, Lehnert H, BrochnerMortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Eng J Med 2001: 345: 870-8
  9. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE study and MICRO-HOPE substudy. Lancet 2000;355: 253–9
  10. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effective of angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Eng J Med 2001; 345: 851–60
  11. Brenner BM, Cooper Me, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Eng J Med 2001; 345: 861–9
  12. Ruggenenti P, Fassi A, Ilieva A. The Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med N Engl J Med 2004;351:1941–51
  13. Department of Health. Annual QOF review process guidance. Quality and outcomes framework. http://www. dh.gov.uk/PolicyAndGuidance/ OrganisationPolicy/PrimaryCare/ PrimaryCareContracting/PrimaryCare ContractingArticle/fs/en?CONTENT_ =4082246&chk=1yjGCE (date last accessed: 21/12/05)
  14. The National Service Framework for Renal Services. February 2005. Part Two: Chronic Kidney Disease, Acute Renal Failure and End of Life Care. http://www.dh.gov.uk/assetRoot/04 /10/26/80/04102680.pdf (date last accessed: 02/12/05)
  15. Maxwell P. Managing diabetic nephropathy. The Practitioner 2005; 249 (1666): 9–10