Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes
Elevated circulating adipocyte fatty acid-binding protein (AFABP) levels have been found to correlate with diabetic nephropathy staging in cross-sectional studies. However, it remains unclear whether these higher serum levels reflect a role of AFABP in the development of diabetic kidney disease (DKD), or simply result from its impaired renal clearance in DKD. Here we investigated prospectively the prognostic importance of serum AFABP level in the development of adverse renal outcomes in a large clinic-based cohort of participants with type 2 diabetes.
Baseline serum AFABP levels were measured in 5454 Chinese participants from the Hong Kong West Diabetes Registry. The association between circulating AFABP levels and incident adverse renal outcomes—defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy or kidney transplantation, or renal deaths—was evaluated using multivariable Cox regression analysis.
Over a median follow-up of 5 years, 754 of the 5454 participants developed incident adverse renal outcomes. Elevated circulating AFABP levels were independently associated with incident adverse renal outcomes (HR 1.43, 95% CI 1.31, 1.57, p < 0.001) after adjustments for conventional risk factors for DKD progression. Importantly, the prognostic role of serum AFABP was independent of the baseline albuminuria status or eGFR levels of the study participants.
Circulating AFABP levels were predictive of incident adverse renal outcomes, even in participants with relatively well-preserved kidney function at baseline, suggesting its potential to be a useful marker for early risk stratification in DKD.
KeywordsAdipocyte fatty acid-binding protein Microvascular complications Nephropathy Prediction model Type 2 diabetes mellitus
Adipocyte fatty acid-binding protein
Angiotensin II receptor blocker
Diabetic kidney disease
End-stage renal disease
High-sensitivity C-reactive protein
Integrated discrimination improvement
c-Jun NH2-terminal kinase
Kidney injury molecule-1
Net reclassification index
Tumour necrosis factor receptor
We thank RLC Wong (Department of Medicine, University of Hong Kong, Hong Kong) for her technical assistance in the measurements of serum AFABP and hsCRP levels. Some of the data were presented as an abstract at the International Diabetes Federation Western Pacific Region Congress (IDF-WPR) in 2014.
CHL contributed to analysis of the data and writing of the manuscript. CYYC, YCW, DTWL, MMAY, WSC and AX contributed to the interpretation of data and revising the manuscript. CHYF contributed to analysis of the data and writing of the manuscript. KSLL initiated and supervised the study, critically revised for important intellectual content and is the guarantor of this work, and as such has had full access to all study data and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors have approved the final version.
This work was supported by the Health and Medical Research Fund (reference 14150781).
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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