Sequence of Progression of Albuminuria and Decreased GFR in Persons With Type 1 Diabetes: A Cohort Study

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.

Index Words: Natural history, decreased glomerular filtration rate, albuminuria, type 1 diabetes, age at onset