Original Investigation
Pathogenesis and Treatment of Kidney Disease
Sequence of Progression of Albuminuria and Decreased GFR in Persons With Type 1 Diabetes: A Cohort Study

https://doi.org/10.1053/j.ajkd.2007.08.005Get rights and content

Background

The sensitivity of albuminuria in predicting loss of kidney function has been questioned. We determined the sequence of kidney disease stages (microalbuminuria, macroalbuminuria, low estimated glomerular filtration rate [eGFR], and end-stage renal disease [ESRD]) and characterized those without albuminuria before a low eGFR.

Study Design

The Pittsburgh Epidemiology of Diabetes Complications Study is a prospective cohort investigation of childhood-onset type 1 diabetes.

Setting & Participants

480 study participants with eGFR greater than 60 mL/min/1.73 m2 (mean age, 27 years; diabetes duration, 19 years at study entry) were prospectively followed up for 16 years.

Outcomes & Measurements

Low eGFR was defined as creatinine clearance less than 60 mL/min/1.73 m2 from timed urine collections; microalbuminuria, as albumin excretion rate between 20 to 200 μg/min (30 to 300 mg/24 h); macroalbuminuria, as albumin excretion rate greater than 200 μg/min (>300 mg/24 h); and ESRD, as dialysis or renal transplantation.

Results

The 33 of 480 individuals (7%) who developed ESRD had prior albuminuria. 71 of 480 (15%) individuals developed low eGFR. 66 of 71 (93%) had prior/concurrent albuminuria, and 5 of 71 (7%) did not. Incident low eGFR values in the 5 patients were: (1) 54, (2) 58, (3) 59, (4) 59.7, and (5) 59.8 mL/min/1.73 m2. 3 of 5 (60%; patients 1, 4, and 5) subsequently developed albuminuria. Final eGFRs in the 5 patients were: (1) 94, (2) 86, (3) 60, (4) 65, and (5) 54 mL/min/1.73 m2, respectively.

Limitations

GFR and insulin sensitivity were not measured, but estimated. Incident decreased eGFR in patients without preceding/concurrent albuminuria may be caused by misclassification or a temporary eGFR decrease.

Conclusions

Moderately decreased eGFR may occur rarely in patients with type 1 diabetes without preceding albuminuria.

Section snippets

Methods

Participants in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, a 16-year prospective investigation of patients with childhood-onset (age < 17 years) type 1 diabetes, who had normal eGFR (defined as 24-hour creatinine clearance >60 mL/min/1.73 m2 [>1.0 mL/s/1.73 m2] at baseline assessment; n = 480) were selected for study. These individuals had been given a diagnosis or been seen within 1 year of diagnosis at Children’s Hospital of Pittsburgh from 1950 to 1980 and were

Results

Characteristics of individuals with normal eGFR at time of first evaluation in the EDC Study are listed in Table 1, categorized by level of albuminuria. As expected, individuals with microalbuminuria or macroalbuminuria were older and had longer duration of diabetes and higher blood pressure and lipid and inflammatory marker levels, but lower eGDR. They were also more likely to have other diabetes complications at baseline. Similar results were obtained after age adjustment.

Discussion

Recently, the question was raised whether albuminuria regularly precedes the loss of GFR in patients with diabetic kidney disease.1, 2, 3 Thus, we assessed the sequence in which albuminuria, decreased GFR, and ESRD occurred in a cohort of childhood-onset type 1 diabetes. We found that all subjects who developed ESRD had prior albuminuria. Nonetheless, although the majority of individuals without albuminuria or low eGFR at study entry remained without these abnormalities (n = 182; 64%) or

Acknowledgements

We thank Dr Dorothy Becker for assistance with recruitment of the cohort and HbA1 measurements and all study participants for their invaluable contributions.

Support: This research was funded by National Institutes of Health grant DK34818.

Financial Disclosure: None.

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    Originally published online as doi:10.1053/j.ajkd.2007.08.005 on October 3, 2007.

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    Copyright © 2007 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.