microalbuminuria in diabetes mellitus

Last reviewed 10/2023

• microalbuminuria is defined as:
  • albumin:creatinine ratio >2.5mg/mmol (men) or >3.5mg/mmol (women) or albumin concentration >20mg/l
• microalbuminuria development precedes persistent albuminuria in type 1 and type 2 diabetics
• if there is a positive screening test for microalbuminuria in a diabetic then other causes of proteinuria in a diabetic should be considered
• antihypertensive therapy slows progression of microalbuminuria to albuminuria in both type of diabetes
• NICE guidance relating to renal disease in type II diabetes is linked below. This provides useful guidance for the management of type II diabetics with renal disease

Notes:

• Progression from microalbumiuria to macroalbuminuria, diabetic nephropathy and end-stage kidney disease
  • in type 1 diabetes, there is evidence that patients who have had diabetes for more than 15 years and screen positive for microalbuminuria, have a 30% risk of progression to overt albuminuria over a period of 10 year follow-up. If the screening is positive for microalbuminuria in a type 1 diabetic, then an ACE inhibitor should be used even if the patient is normotensive
  • both micro- and macroalbuminuria are stronger predictors of cardiovascular mortality than of end-stage renal failure.. only a minority of patients with microalbuminuria will progress to end-stage renal failure, because death from a cardiovascular cause commonly occurs before renal failure has developed...Control of blood pressure in patients with type 2 diabetes significantly reduces the progression of diabetic kidney disease (1)
  • in type 2 diabetes
    • a cohort study examined the risk of development of overt nephropathy in adults (defined in this study as an albumin excretion rate (AER) >200 µg/min in at least two consecutive overnight urine collections) in type 2 diabetic patients (2)
      • the study involved 1,253 type 2 diabetic patients recruited at baseline (1991-1992), 765 with normoalbuminuria (albumin excretion rate [AER] <20 microg/min) and 488 with microalbuminuria (AER 20-200 microg/min)
        • median follow-up was 5.33 years
        • at baseline examination, microalbuminuric subjects were treated more often with insulin and had higher values of HbA1c, triglycerides, fibrinogen, creatinine, and systolic and diastolic blood pressure than normoalbuminuric patients
        • 202 cases of overt nephropathy were identified of 5,452.7 person-years of observations, giving an incidence rate of 37.0/1,000 person-years (95% CI 32.3-42.6); of those, 84 were normoalbuminuric and 118 microalbuminuric at baseline, giving incidence rates per 1,000 of 25.8 (95% CI 20.9-32.0) and 53.6 (95% CI 44.7-64.2), respectively
      • in this study there was a 3.7% progress every year to overt nephropathy
        • the study authors concluded that microalbuminuria is associated with a 42% increased risk of progression to overt nephropathy. Other independent predictors are HbA(1c), HDL cholesterol, apolipoprotein B, and fibrinogen

      • a systematic review stated "..Intensive glucose control reduces the risk for microalbuminuria and macroalbuminuria, but evidence is lacking that intensive glycemic control reduces the risk for significant clinical renal outcomes, such as doubling of the serum creatinine level, ESRD, or death from renal disease during the years of follow-up of the trials..." (3)

        
        
        
  • risk of cardiovascular and renal events related to albuminuria and eGFR in type 2 diabetes
    • a study investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data (4)
      • during an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event
        • adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution
        • patients with both UACR >300 mg/g and eGFR <60 ml/min per 1.73 m(2) at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors
        • the study authors concluded that high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes
          
          
  • progression from microalbuminuria to macroalbuminuria in children with type 1 diabetes
    • a cohort study revealed that (4):
      • in childhood onset type 1 diabetes, the only modifiable predictors were poor glycaemic control for the development of microalbuminuria and poor control and microalbuminuria (both persistent and intermittent) for progression to macroalbuminuria
      • cumulative prevalence of microalbuminuria was 25.7% (95% confidence interval 21.3% to 30.1%) after 10 years of diabetes and 50.7% (40.5% to 60.9%) after 19 years of diabetes and 5182 patient years of follow-up
        • only modifiable adjusted predictor for microalbuminuria was high HbA1c concentrations (hazard ratio per 1% rise in HbA1c 1.39, 1.27 to 1.52)
        • blood pressure and history of smoking were not predictors
        • microalbuminuria was persistent in 48% of patients. Cumulative prevalence of progression from microalbuminuria to macroalbuminuria was 13.9% (12.9% to 14.9%); progression occurred at a mean age of 18.5 (5.8) years

Reference:

• (1) Drug and Therapeutics Bulletin 2005; 43:41-48.
• (2) Bruno G et al. Progression to overt nephropathy in type 2 diabetes: the Casale Monferrato Study. Diabetes Care. 2003 Jul;26(7):2150-5.
• (3) Coca SG et al. Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: systematic review and meta-analysis intensive glucose control in type 2 diabetes.Arch Intern Med. 2012 May 28;172(10):761-9.
• (4) Ninomiya T et al. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. Am Soc Nephrol. 2009 Aug;20(8):1813-21(4) Amin R et al. Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008 Mar 29;336(7646):697-70