Clinical Inquiries

Does microalbuminuria screening in diabetes prevent complications?

Hale WA, Nashelsky J, Wilson SA. J Fam Pract 2003 Mar;52(3):229-31

Evidence-based Answer

Screening diabetic patients for microalbuminuria identifies those who may benefit from treatments that delay progression to renal failure (strength of recommendation: B, based on extrapolation from Level 1 treatment studies of patients with microalbuminuria).

No research has determined the best method for screening for microalbuminuria, or whether screening in primary care populations will produce better long-term outcomes. No studies have examined the role of microalbuminuria screening after angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) have been instituted for other indications.

Evidence-based Summary

Patients with diabetes mellitus have a 20% to 40% lifetime risk for development of nephropathy, and microalbuminuria is the earliest easily detectable marker of renal damage. 1 Improved control of blood sugar 2,3 and blood pressure 4 decreases but does not completely prevent development of microalbuminuria and progression to overt kidney failure. ACE inhibitors and ARBs have been shown to diminish this progression even in the absence of hypertension (the latter in type 2 diabetes only) (Table).

No prospective randomized trials of screening have been reported. There is uncertainty about what method of screening is most effective and practical in primary care settings. 10 Expert opinion recommends diagnosing microalbuminuria after 2 positive test results, 1 but whether repeated tests improve diagnostic accuracy is still controversial. 10

A large randomized controlled trial showing better long-term renal and vascular disease outcomes would be needed to give screening for microalbuminuria a strength of recommendation of A. Recruiting patients for such a study, and interpreting its results, would be difficult: many subjects would have other indications, such as hypertension or congestive heart failure, warranting use of potentially renoprotective medications.

Clinical Commentary

Blood pressure control and ACE inhibition improve mortality and morbidity for patients with diabetes mellitus type 2. Therefore, maximize ACE inhibitor or ARB doses, as tolerated, and aim for a blood pressure of 110–120/70–80 mm Hg (130/85 mm Hg is the maximum).

Using this plan, I do not routinely screen for microalbuminuria—which is, at best, a surrogate marker for nephropathy and poor blood pressure control—unless I believe it will work as an educational and motivational tool for patients who are less committed to self-care.

If serum creatinine becomes elevated, a 24-hour urine collection to examine volume, creatinine clearance, and protein can be used to help develop a negotiated care plan with the patient, which may or may not include referral. Until there is different evidence about screening and treatment options for microalbuminuria, I see no need to screen when the above plan is in effect.

Recommendations from Others

The American Diabetes Association recommends annual screening for microalbuminuria—after 5 years of established type 1 disease, and at time of diagnosis for type 2 diabetes without macroalbuminuria. Initial screening can use 1 of 3 methods: measurement of the albumin-to-creatinine ratio in a random, spot collection; 24-hour collection with creatinine, allowing the simultaneous measurement of creatinine clearance; timed (eg, 4-hour or overnight) collection. At least 2 of 3 tests measured within a 6-month period should show elevated levels before a patient is said to have microalbuminuria. 1

Figures

Reno- and cardioprotective efficacy of treatments for diabetic patients with microalbuminuria
DM type Medication NNT Time (years) To prevent endpoint
1 ACE inhibitor (Captopril) 7.9* 2 Clinical proteinuria 5
2 ACE inhibitor (Enalapril) 6.3* 5 Macroalbuminuria 6
2 ACE inhibitor (Enalapril) 2.4* 7 Significant proteinuria 7
2 ARB (Losartan) 3.6 3.4 End-stage renal disease 8
2 ACE inhibitor (Ramipril) 4 4.5 Cardiovascular disease 9 †
*Normotensive subjects
†Myocardial infarction, revascularization procedure, stroke, cardiovascular death, congestive heart failure requiring hospitalization, overt nephropathy, renal dialysis, or laser treatment for retinopathy
DM, diabetes mellitus; NNT, number needed to treat; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker

References

  1. No author listed. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002. Volume 25. Page(s): S33-S49.
  2. No author listed. Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications Trial (DCCT) Research Group. Kidney Int. 1995. Volume 47. Page(s): 1703-1720.
  3. No author listed. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study Group. Lancet. 1998. Volume 352. Page(s): 837-853.
  4. No author listed. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 UK Prospective Diabetes Study Group. BMJ. 1998. Volume 317. Page(s): 703-713.
  5. Laffel LM, McGill JB, Gans DJnull The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. Am J Med. 1995. Volume 99. Page(s): 497-504.
  6. Ahmad J, Siddiqui MA, Ahmad Hnull Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Diabetes Care. 1997. Volume 20. Page(s): 1576-1581.
  7. Ravid M, Lang R, Rachmani R, Lishner Mnull Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. A 7-year follow-up study. Arch Intern Med. 1996. Volume 156. Page(s): 286-289.
  8. Brenner BM, Cooper ME, de Zeeuw Det al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001. Volume 345. Page(s): 861-869.
  9. No author listed. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE study. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Lancet. 2000. Volume 355. Page(s): 253-259.
  10. Scheid DC, McCarthy LH, Lawler FH, Hamm RM, Reilly KEHnull Screening for microalbuminuria to prevent nephropathy in patients with diabetes. A systematic review of the evidence. J Fam Pract. 2001. Volume 50. Page(s): 661-s668.