Current issues of ACP Journal Club are published in Annals of Internal Medicine


Modifiable risk factors predicted the development of diabetic nephropathy

ACP J Club. 1997 Jul-Aug;127:17. doi:10.7326/ACPJC-1997-127-1-017

Source Citation

Gall MA, Hougaard P, Borch-Johnsen K, Parving HH. Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective, observational study. BMJ. 1997 Mar 15;314:783-8.



To determine the risk factors associated with the development of incipient and overt diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM) and normoalbuminuria.


Cohort study with a median follow-up of 5.8 years.


Diabetes clinic in Denmark.


176 patients who were < 66 years of age (median age 54 y, 70% men), had NIDDM and baseline normoalbuminuria (urinary albumin excretion [UAE] rate < 30 mg/24 h), completed the observation period from 1987 to death or January 1993, and had at least 1 recorded measure of UAE rate after baseline.

Assessment of risk factors

The following potential predictors of incipient or overt nephropathy were considered: sex, age, known duration of diabetes, body mass index, retinopathy, arterial blood pressure, baseline UAE rate, hemoglobin A1c (HbA1c) level, serum cholesterol concentration, coronary heart disease, and smoking history.

Main outcome measures

Development of incipient nephropathy (persistent microalbuminuria, UAE rate 30 to 299 mg/24 h for 2 of 3 consecutive 24-h collections) or overt nephropathy (persistent macroalbuminuria, UAE rate ≥ 300 mg/24 h for 2 of 3 consecutive 24-h collections).

Main results

36 patients (20%) developed incipient nephropathy, and 5 patients (3%) developed overt nephropathy. The 5-year cumulative incidence of incipient diabetic nephropathy was 23%. The following risk factors were associated with the development of incipient or overt diabetic nephropathy: a 10-fold increase in UAE rate (relative risk [RR] 11.1, 95% CI 3.4 to 35.9, P < 0.001), male sex (RR 2.6, CI 1.2 to 5.4, P < 0.02), presence of retinopathy (RR 2.4, CI 1.3 to 4.7, P < 0.01), increased cholesterol level (RR 1.4, CI 1.1 to 1.7, P < 0.01), elevated HbA1c level (RR 1.2, CI 1.0 to 1.4, P < 0.05), and greater age (RR 1.07, CI 1.02 to 1.12, P < 0.01). Duration of diabetes, obesity, arterial blood pressure, and smoking history were not associated with the development of increased UAE rate.


The development of incipient and overt diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus was associated with several modifiable risk factors. The strongest predictor was an increased urinary albumin excretion rate at baseline.

Source of funding: No external funding.

For article reprint: Dr. M.A. Gall, Steno Diabetes Center, DK 2820, Gentofte, Denmark. FAX 45-4443-8233.


The presence of microalbuminuria indicates nephropathy associated with NIDDM (1, 2). Increases in either micro- or macroalbuminuria serve as a surrogate marker for the worsening of NIDDM-associated nephropathy (1-3). The study by Gall and colleagues shows that an increase in albuminuria was the strongest modifiable risk factor for development of incipient and overt diabetic nephropathy. The average duration for patients to progress from normoalbuminuria to overt albuminuria, however, is between 5 and 8 years.

The study also supports previous observations that hyperlipidemia and poor glucose control are associated with increases in albuminuria (1-4). Thus, aggressive control of these risk factors and annual screening for microalbuminuria are recommended for all patients with diabetes (3). Spot urine collection for measurement of albumin-creatinine ratios is an accurate and simple method for screening and long-term follow-up of patients (3). Patients with a blood pressure of < 130/85 mm Hg who have microalbuminuria should have their blood glucose and cholesterol levels aggressively controlled and receive an angiotensin-converting enzyme inhibitor and low-sodium diet to maximize an antialbuminuric effect and, hence, slow progression of nephropathy.

George L. Bakris, MD
Rush University Hypertension CenterChicago, Illinois, USA

George L. Bakris, MD
Rush University Hypertension Center
Chicago, Illinois, USA


1. Bakris GL. Microalbuminuria: prognostic implications. Curr Opin Nephrol Hypertens. 1996;5:219-23.

2. Kikuchi M, Matsumoto T, Ohashi Y. Risk factors for development of proteinuria in NIDDM analyzed by Poisson regression. J Diabetes Complications. 1991;5:128-30.

3. Bennett PH, Haffner S, Kasiske BL, et al. Screening and management of microalbumi-nuria in patients with diabetes mellitus: recommendations to the Scientific Advisory Board of the National Kidney Foundation from an ad hoc committee of the Council on Diabetes Mellitus of the National Kidney Foundation. Am J Kidney Dis. 1995;25:107-12.

4. Suraniti S, Bled F, Girault A, Fressinaud P, Marre M. Serum lipids and urinary albumin excretion in non insulin-dependent diabetics. Mol Cell Biochem. 1992;109:197-200.