Diabetic nephropathy is currently the leading cause of CKD. It is also one of the most significant long-term complications in terms of morbidity and mortality for individual patients with diabetes 
. It is well known that severe tubulointerstitial damage is associated with a faster decline in eGFR in CKD patients 
. In this study, we used two renal tubular injury biomarkers, NGAL and L-FABP, in addition to albuminuria, to predict the GFR decline rate in type 2 diabetic patients. Our results showed that the serum L-FABP level was significantly associated with eGFR, using regression analysis in the cross-sectional study. However, only the urine albumin excretion rate was significantly associated with eGFR and the eGFR decline rate in type 2 diabetic patients.
Tubulointerstitial and glomerular injuries have important roles in the pathogenesis of diabetic nephropathy 
. Several recent studies demonstrated that urinary tubular damage markers, such as KIM-1, NGAL and L-FABP, may have the potential to be clinical markers for identifying the development or progression of diabetic nephropathy 
. It was also reported that urine NGAL was significantly elevated in type 1 diabetic patients with or without albuminuria, and that urine NGAL increased significantly with increasing albuminuria 
. However, some studies have shown conflicting results. A study with type 2 diabetic patients showed that the urinary tubular markers, NGAL and L-FABP, were not significantly increased in the normoalbuminuria and microalbuminuria groups, compared to the normal control group 
. Another study with type 1 diabetic patients revealed that urine NGAL and L-FABP levels were not related to the decline in GFR, after adjustment for known promoters of progression 
. A matched case-control study for predicting incident CKD stage 3 also showed that adjustment for urinary creatinine and albumin concentration attenuated this association between NGAL and incident CKD stage 
. Our study included 140 diabetic patients with varying degrees of diabetic nephropathy; however, most of them had mild diabetic nephropathy (albuminuria <300 mg/day; eGFR >60). We observed that albuminuria increased and eGFR decreased in our study subjects as the study progressed. However, except serum NGAL, the urine NGAL and serum/urine L-FABP levels did not change significantly throughout the course of the study. The results of multivariate analysis also showed that NGAL and L-FABP lacked clinical value in predicting the GFR decline rate in type 2 diabetic patients.
Albuminuria is a clinical biomarker for glomerular injury. According to the staging, initial changes in diabetic nephropathy include glomerular hyperfiltration. The phase following hyperfiltration is associated with subtle morphological changes, including thickening of the glomerular basement membrane, glomerular hypertrophy, mesangial expansion, and modest expansion of the tubulointerstitium. In the microalbuminuric phase, significant glomerular injury is often noted. In advanced diabetic nephropathy, nodular glomerulosclerosis is the most prominent pathological presentation 
. Tubulointerstitial injury in the kidney is considered as a final common pathways to end-stage renal failure 
. Tubular cell proliferation and tubular hypertrophy are main presentations in the early diabetic nephropathy 
. Tubulointerstitial fibrosis is the late pathological presentation of chronic kidney disease. It is known that the rate of deterioration of renal function correlates best with the degree of tubulointerstitial fibrosis in diabetic nephropathy. These studies suggest that although in the majority of patients the primary event is a condition manifest by glomerular changes resulting in proteinuria, the long-term outcome is determined by tubulointerstitial fibrosis 
. In our study, most study subjects had early-stage diabetic nephropathy in the study beginning. We speculated that relatively less severe tubulointerstitial injury in our patients with early diabetic nephropathy might lead to the failure of the tubular injury markers, NGAL and L-FABP, to early predict the GFR deline in diabetic patients. This might also explain why only albuminuria was significantly correlated with the GFR decline rate in our study.
The results of this study are subject to some limitations. First, the sample number and unhomogenized characteristics of the study subjects might confound the study results. Second, this was a longitudinal observational study. The lack of a control group or effective intervention for comparison might limit the power of the study. Despite these limitations, the results of the cross-sectional analysis with baseline data were compatible with the longitudinal analysis results.
In conclusion, the results of this study suggest that tubular markers, such as NGAL and L-FABP, may not be predictive factors associated with GFR decline in type 2 diabetic patients. In addition, the urine albumin excretion rate was an independent factor associated with GFR decline rate in type 2 diabetic patients.