Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients.
OBJECTIVE
Urinary liver-type fatty acid-binding protein (u-LFABP) is a marker of tubulointerstitial inflammation and has been shown to be increased in patients with type 1 diabetes and is further increased in patients who progress to micro- and macroalbuminuria. Our aim was to evaluate u-LFABP as a predictor of progression to micro- and macroalbuminuria in type 1 diabetes.


METHODS
From an inception cohort of 277 patients, u-LFABP, adjusted for urinary creatinine (enzyme-linked immunosorbent assay), was measured in 24-h urine samples from 165 normoalbuminuric patients 9.6 +/- 3.5 (mean +/-SD) years after onset of type 1 diabetes. The outcome measured was development of persistent micro- or macroalbuminuria or death.


RESULTS
Patients were followed for a median of 18 (range 1-19) years; 39 progressed to microalbuminuria, 8 of those progressed further to macroalbuminuria, and 24 died. In a Cox regression model, baseline log u-LFABP levels predicted the development of microalbuminuria, adjusted for known risk factors (sex, age, A1C, systolic and diastolic blood pressure, albumin excretion rate, serum creatinine, and smoking) (hazard ratio [HR] 2.3 [95% CI 1.1-4.6]) and log u-LFABP predicted mortality (adjusted HR 3.0 [1.3-7.0]). u-LFABP (above versus below the median) predicted the development of macroalbuminuria (adjusted HR 2.6 [1.2-5.4]). As a continuous variable, u-LFABP tended to predict macroalbuminuria (HR 1.9, P = 0.2), but numbers were small.


CONCLUSIONS
High levels of the tubular inflammation marker u-LFABP predict the initiation and progression to diabetic nephropathy and all-cause mortality, independent of urinary albumin excretion rate and other established risk factors.
Nielsen
Stine Elkjaer
SE
Steno Diabetes Center, Gentofte, Denmark. sene@steno.dk
Sugaya
Takeshi
T
Hovind
Peter
P
Baba
Tsuneharu
T
Parving
Hans-Henrik
HH
Rossing
Peter
P
D000328:Adult; D000419:Albuminuria / Q000175:diagnosis / Q000209:etiology; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000652:urine*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors
D050556:Fatty Acid-Binding Proteins; D003404:Creatinine