Biomarkers in chronic kidney disease, from kidney function to kidney damage

Table 2 Novel biomarkers in chronic kidney disease

Biomarker source	Ref.	Population/type of study	Commentaries
u-LFABP Urinary	Nielsen et al[190]	227 newly diagnosed type 1 diabetic patients/longitudinal	Baseline u-LFABP levels predicted development of microalbuminuria (HR = 2.3, 95%CI: 1.1-4.6), and predicted mortality (HR = 3.0, 95%CI: 1.3-7.0)
NAG Urinary	Kern et al[191]	87 type 1 diabetics with microalbuminuria and 174 controls/longitudinal	Baseline NAG independently predicted microalbuminuria (OR = 1.86, P < 0.001) and macroalbuminuria (OR = 2.26, P < 0.001) but risk was attenuated in multivariate models
CTGF Urinary	Nguyen et al[192]	318 type 1 diabetic patients and 29 control subjects/cross sectional	U-CGTF was significantly higher in diabetic nephropathy than micro o normoalbuminuria. U-CGTF correlated with albuminuria and GFR
IL-18 Kidney tissue	Miyauchi et al[193]	12 type 2 diabetes with overt nephropathy and 7 patients with MCD/cross sectional	IL-18 expression in tubular cells was observed highly observed (83%) in patients with diabetes but only observed in 14.3% of MCD
ApoA-IV Plasma	Boes et al[194]	177 non-diabetic patients with mild to modetare renal CKD/longitudinal	Baseline ApoA-IV was a significant predictor of disease progression (HR = 1.062, 95%CI: 1.018-1.108) and patients with level above the median had significantly faster progression compared with patients with level below median (P < 0.0001)
CD14 mononuclear cells Urinary	Zhou et al[195]	16 patients with autosomal dominat polycystic kidney disease/longitudinal	Baseline urinary CD14 mononuclear cells correlated with 2 yr change in total kidney volume in males
NGAL	Bolignano et al[121]	33 patients with glomerulonephritis and proteinuria > 1 g per day/cross sectional	u-NGAL was higher in glomerulonephritis compared with controls and significantly correlated with serum creatinine and urinary protein excretion
Urinary	Smith et al[124]	158 patients with CKD stages 3 and 4/longitudinal	u-NCR was associated with a higher risk of death and initiation of renal replacement therapy
Urinary	Bolignano et al[125]	96 white patients with CKD/longitudinal	Baseline urinary and serum NGAL were predictors of CKD progression
Urinary/serum	Shen et al[119]	92 patients with chronic glomerulonephritis CKD stage 2-4, and 20 control subjects/longitudinal	s-NGAL levels were higher compared to controls and negatively correlated with the eGFR Patients with sNGAL level > 246 ng/mL had a poor 2 yr renal survival compared with the control group
Serum	Bhavsar et al[123]	286 participants from the ARIC and 143 matched controls/longitudinal	Higher quiartiles of NGAL (but no KIM-1) were associated with incident CKD
KIM-1 Serum	Krolewski et al[111]	107 diabetic type 1 with CKD 1-3 (AER > 500 mg/24 h)/longitudinal	Baseline plasma KIM-1 levels correlated with rate of eGFR decline KIM-1 levels (> 97 pg/mL) correlated with progression to ESRD
Urinary	Peters et al[109]	65 patients with Proteinuric IgAN and 65 control subjects/longitudinal	In patients with IgAN uKIM-1 excretion was significantly higher than controls uKIM-1 is independently predictor of ESRD
FGF-23	Nakano et al[134]	738 Japanese patients with CKD stages 1-5/longitudinal	Levels of FGF-23 associated with kidney function decline or initiation renal replacement therapy
Serum	Fliser et al[137]	227 non diabetic patients with CKD stages 1-4/longitudinal	FGF-23 was an independent predictor of CKD progression
	Lee et al[138]	380 patients with type 2 diabetes/longitudinal	Levels of FGF-23 was associated with increased risk of ESRD and was a significant risk factor for all cause mortality

u-LFABP: Liver-type fatty acid-binding protein; NAG: N-Acetyl-b-O-glucosaminidase; CTGF: Connective tissue growth factor; IL-18: Interleukin-18; ApoA-IV: Apolipoprotein A-IV; NGAL: Neutrophil gelatinase associated lipocalin; MCD: Minimal change disease; ARIC: Atherosclerosis Risk In communities; IgAN: IgA nephropathy; u-NCR: u-NGAL to creatinine ratio; eGFR: Estimated glomerular filtration rate; FGF-23: Fibroblast growth factor 23; CKD: Chronic kidney disease; KIM-1: Kidney injury molecule; AER: Albumin excretion rate; GFR: Glomerular filtration rate; U-CGTF: Urinary-connective tissue growth factor; u-NGAL: Urinary-NGAL; s-NGAL: Serum-NGAL; ESRD: End stage renal disease.