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Etiology

Microalbuminuria predicted progression to diabetic nephropathy in type 1 diabetes mellitus

ACP J Club. 1994 July-Aug;121:25. doi:10.7326/ACPJC-1994-121-1-025


Source Citation

Almdal T, Nörgaard K, Feldt-Rasmussen B, Deckert T. The predictive value of microalbuminuria in IDDM. A five-year follow-up study. Diabetes Care. 1994 Feb;17:120-5.


Abstract

Objective

To determine the predictive value of microalbuminuria and urinary albumin excretion rate (UAE) as risk factors for diabetic nephropathy in patients with type 1 diabetes mellitus.

Design

Cohort analytic study constructed from records with 5-year follow-up.

Setting

Danish outpatient diabetes clinic.

Patients

From a consecutive sample of 679 patients with type 1 diabetes who were screened for microalbuminuria (UAE, 30 to 299 mg/24 h) in 1985, 155 (23%) were positive. 118 patients (76%) (mean age 35 y, 51% women) with microalbuminuria who still attended the clinic in 1990 and 1991 were matched for sex, age, and duration of diabetes to a control group of 112 patients with normal baseline UAE (< 30 mg/24 h) who also still attended the clinic in 1990 and1991.

Assessment of risk factors

Determination of 24-hour UAE 1 to 3 times per year, hemoglobin A1c(HbA1c) 2 to 4 times per year, blood pressure and direct ophthalmoscopy once per year, and smoking habits during the 5-year study period.

Main outcome measures

UAE rate, annual change in UAE rate, and development of diabetic nephropathy (defined as UAE > 300 mg/24 h).

Main results

Of the 118 patients who had microalbuminuria, 33% became normoalbuminuric (95% CI 24% to 42%), 48% remained microalbuminuric (CI 38% to 57%), and 19% developed diabetic nephropathy (CI 12% to 27%). Of the 112 control patients, 8% developed microalbuminuria and 2% developed diabetic nephropathy. The median baseline UAE in patients with microalbuminuria who became normoalbuminuric was lower than the UAE level in patients who remained microalbuminuric or who developed diabetic nephropathy (P < 0.02). Patients with microalbuminuria who developed diabetic nephropathy had a higher median baseline value of UAE than those remaining microalbuminuric (P < 0.02). Patients with microalbuminuria who developed diabetic nephropathy had higher HbA1c values than did patients who remained or became normoalbuminuric (P < 0.02). Of the 118 patients with baseline microalbuminuria, 36 (31%) were progressors (had a yearly relative increase in UAE of > 5%). Of the 112 patients with normoalbuminuria, 11 (10%) were progressors. Progressors had higher mean HbA1c values, blood pressure levels, and incidence of proliferative retinopathy than nonprogressors (P < 0.01).

Conclusion

Microalbuminuria predicted progression to diabetic nephropathy in carefully treated patients with type 1 diabetes mellitus over 5 years.

Source of funding: Not stated.

For article reprint: Dr. T. Deckert, Steno Diabetes Center, DK-2820 Gentofte, Denmark. FAX 415-3168-2322.


Commentary

When clinical diabetic nephropathy develops in type 1 diabetes, no known therapy prevents eventual renal failure. Treatments that reduce the risk for developing clinical nephropathy are burdensome and expensive, and it would be useful to identify patients destined to develop nephropathy for more selective use of these treatments.

Microalbuminuria was established as a strong predictor of clinical diabetic nephropathy in type 1 diabetes by 4 small cohort studies published in the early 1980s (1-4). Each used a different definition of microalbuminuria but, in each, almost all patients with microalbuminuria developed nephropathy within 6 to 14 years. By following a much larger, more recently treated cohort, Almdal and colleagues confirm the predictive value of microalbuminuria using the current definition. Only 19% of patients with a single abnormal UAE value, however, developed clinical nephropathy within 5 years of routine diabetic care, and 33% of patients who were microalbuminuric had normal UAE 5 years later. Although more patients may develop nephropathy in time, only 31% of patients who were microalbuminuric initially showed a progressive increase in UAE. As is often the case, the predictive value of this test turns out to be weaker than initial studies suggested. This is plausible given the many factors that transiently increase urine albumin, but confidence in this specific estimate of predictive value should be tempered by the high dropout rate (24%).

Microalbuminuria is a useful risk marker for clinical nephropathy at a stage when therapy can delay or prevent its onset. Annual measurement of UAE helps clinicians decide whether to recommend intensive insulin therapy, treatment of mild hypertension, or treatment of normotensive patients with angiotensin-converting enzyme inhibitors. Transient increases in UAE are common, however, and a single elevated value should not be given much weight.

William E. Clutter, MD
Washington University School of MedicineSt. Louis, Missouri, USA


References

1. Parving HH, Oxenbøll B, Svendsen PA, Christiansen JS, Andersen AR. Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. Acta Endocrinol. 1982;100:550-5.

2. Viberti GC, Hill RD, Jarrett RJ, et al. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet. 1982;1:1430-2.

3. Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984;311:89-93.

4. Mathiesen ER, Oxenbøll B, Johansen K, Svendsen PA, Deckert T. Incipient nephropathy in type 1 (insulin-dependent) diabetes.Diabetologia. 1984;26:406-10.