renal tubular injury

biomarker
lipid peroxidation
hypoxic tissue injury

sepsisnephrotoxins
cardiac surgery
acute tubular necrosis
apheresis

renal transplantation

microcirculation

predicting dialysis-free survival

ischemiaradiocontrast agents

hypertension

diabetes nephropathy

FOR EARLY DETECTION OF ISCHEMIC EVENTS ON ACUTE KIDNEY INJURYFOR DISEASE MANAGEMENT OF CHRONIC KIDNEY DISEASESRENISCHEM
L-FABP ELISA Kit
Urinary L-FABP ELISA kit

L-FABP BIOMARKER WEBSITE OPENED!

fabp websearch®

Mechanism of L-FABP excretionL-FABP urinary excretion within proximal tubule cytoplasm
Free Fatty Acids (FFAs) are bound to serum albumin filtered through glomeruli and reabsorbed into the proximal
tubule along with albumin. FFAs up-regulate of L-FABP gene expression. L-FABP, a carrier protein or 14kDa
expressed in the proximal tubule plays a role in the intracellular transport of FFAs to mitochondria and/orperoxisomes for metabolism.
Lipoperoxides are accumulated in proximal tubules during renal ischemia/reperfusion. L-FABP is excreted from theproximal tubules into urine by binding these cytotoxic lipids.
Reactive oxygen generated due to peritubularischemia/reperfusion injury change free fatty
acids to fatty acid peroxides(lipoperoxides),which are highly toxic to cells.
L-FABP binds with these lipoperoxides, and is
excreted outside of cells. Thus, it is thoughtthat L-FABP is “renoprotective”—it works toprotect the kidneys.

To urine
Renal tubule lumen

Cytoplasm ofproximal tubule

Reactive
oxygenOxidative
stress

Mitochondria

L-FABPAlbumin

LipoperoxideFree fatty acidLysosome
Tubulointerstitual sideIschemia-reperfusion injury

Clinical Evidence
Urinary L-FABP is a useful biomarker for early detection of Acute Kidney
Injury (AKI) and is a good predictor of the onset of AKI

21.5＊

＊

＊

3h6h＊

＊

18h24h＊,†10.5
0pre-post-Non- AKI group ( 37 patients )

800

＊,†
＊,†

600

＊

400
200

48h

＊ : P<0.05[vs.Non-AKI group]† : P<0.05[vs.pre-]AKI group ( 48 patients )Urinary L-FABP (μg / gCr)

A total of 85 patients who underwent cardiac
surgery were classified into AKI group andnon-AKI group according to AKIN criteria.
Serum creatinine and urinary L-FABP weremeasured both pre- and post- operation.

Serum creatinine (mg / dl)

The conventional diagnostic method for AKI, uses serum creatinine as an indicator of detected AKI development
24 hours after cardiac surgery. In contrast, urinary L-FABP showed a significant increase immediately after theoperation which demonstrated that urinary L-FABP can be used for earlier detection of AKI development.

＊＊＊＊0pre-post-3h

6h

18h

24h48hKatsuomi Matsui, et al. Circulation Journal.2012; 76: 213-220

Clinical Evidence
For early diagnosis of diabetic nephropathy
The level of urinary L-FABP increased significantly according to the severity of diabetic nephropathy. Urinary L-FABP
in the patients with normal albuminuria was significantly higher than in normal control subjects. Thus, urinary
L-FABP is a useful biomarker for early diagnosis of diabetic nephropathy.

Relationship between urinary L-FABP levels and progression of diabetic nephropathy
Urinary L-FABP was measured in 147 patients
who had diabetic nephropathy and wasdivided according to the disease stage. The
average value and standard variation of eachdisease stage were calculated and shownin the graph to the right, together with theurinary L-FABP value of healthy volunteers.

p<0.0001

Urinary L-FABP (μg / g · Cr)

p<0.0001

p<0.0001

864300250
200
1500NoCo rmalntrol

p<0.0001＊p<0.0005 vs any other stages＊

Non-Paired Test

100
5002

＊

p<0.0001

Noalbrmal
um
inu

＊

＊NoCo rmal
ntrol

Noalbrmal
um
inu

ria

n=79n=64Micalb rouminu

ria

n=30

Ma
alb cro
uminu

n=30

En
rend-staal gefailurriaen=23Stages of diabetic nephropathy

ria

Modified from Kamijyo-Ikemori.A.et al.Diabetes Care 34: 691-696,2011

Urinary L-FABP is useful to detect the risk of renal function deterioration
Renal function decreased significantly in the following 4 years in the group that showed abnormal values inboth urinary L-FABP and urinary albumin. Early stage risk of renal function deterioration resulting in diabetic
nephropathy can be detected with high accuracy by measuring urinary L-FABP, which reflects tubular function,
together with simultaneous measurement of urinary albumin, which is an indicator of glomerular injury.
90eGFR values

8070*: p=0.002 [vs The other 3 groups]

60*

L-FABP Abnl, Alb Abnl

A total of 86 cases with eGFR 60 were takenfrom the 147 diabetic patients and classified
into 4 groups according to urinary L-FABPlevels (Normal: 8.4μg/gCr or less) and urinary
albumin levels (Normal: under 30mg/gCr)collected during the first year following
diagnosis. The changes in eGFR were tracked
in the 4 groups.

L-FABP Abnl, Alb Normal

5040

L-FABP Normal, Alb Abnl

Abnl : L-FABP＞8.4μg/gCr, Alb≧30mg/gCr

L-FABP Normal, Alb Normal

Normal : L-FABP≦8.4μg/gCr, Alb＜30mg/gCr

012years

34(In-house data from Manufacturer)

For monitoring effectiveness of kidney disease treatment

Rate of change(%)■treatment before ■6 months treatment■12 months treatment

100160

80

15060

140

40130

201200110

Alb

L-FABP

Systolic blood pressure(mmHg)

Urinary albumin, urinary L-FABP, and systolic blood pressure after 6 months of treatment and 12 months treatment
were significantly decreased compared to the baseline values. Urinary L-FABP, similarly to urinary albumin is useful,for monitoring antihypertensive therapy for early-stage diabetic nephropathy.

Systolic blood pressure
Tsukasa Nakamura, et al.Diabetologia.2007 Feb;50(2):490-2

Patients who have microalbuminuria wererandomly assigned to receive ARB for 12months. Urinary albumin, urinary L-FABP, andsystolic blood pressure were then monitored toobserve the course of treatment.

RENISCHEM®
L-FABP ELISA TMB Kit, High Sensitivity Kit
Urinary L-FABP ELISA kit

Assay specifications
Size:
96 Wells
Intended User:
Lab professionals
Store Temperature: 2-8°C
Method:Enzyme-Linked-ImmunoSorbent Assay of 2-step
sandwich method
Sample:Human urine
Assay time:
120min.
Shelf life:
24 months (TMB)
Measurable range:

12 months (High Sensitivity)
1.5 – 200ng/mL (TMB)
0.3 – 60ng/mL (High Sensitivity)

Kit component
L-FABP Antibody CoatedMicroplate
Pretreatment Solution
Assay Buffer
The 2nd Ab-POD ConjugateSubstrate Solution
Wash Agent (x 40 concentrate)
Stop Solution
Standard Diluent (0ng/mL)
L-FABP Standard (400ng/mL)
Pretreatment Microplate
Plate Seal

96 Well x 1
12mL x 1
12mL x 1
12mL x 1
12mL x 1
50mL x 1
12mL x 1
2.5mL x 1
0.5mL x 1
96Well x 1x 2 sheets		

L-FABP-Related Articles
CKD[1] 		Urinary fatty acid–binding protein as a new clinical marker of the progression ofchronic renal disease. J Lab Clin Med. 143(1): 23-30, 2004.
[2]
Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as amarker for the monitoring of chronic kidney disease: A multicenter trial. J Lab Clin
Med. 145(3): 125-133, 2005.
[3]
Clinical significance of urinary liver-type fatty acid–binding protein in patients withdiabetic nephropathy. Diabetes Care. 28(8): 2038-2039, 2005.
[4]
Urinary liver-type fatty acid-binding protein: discrimination between IgA nephropathy
and thin basement membrane nephropathy. Am J Nephrol. 25(5): 447-450, 2005.
[5]
Urinary liver-type fatty acid-binding protein predicts progression to nephropathy intype 1 diabetic patients. Diabetes Care. 33(6): 1320-1324, 2010.
[6]
Urinary L-FABP and anaemia: distinct roles of urinary markers in type 2 diabetes. EurJ Clin Invest. 40(2): 95-102, 2010.
[7]
Clinical significance of urinary liver-type fatty acid-binding protein in diabetic
nephropathy of type 2 diabetic patients. Diabetes Care. 34(3): 691-696, 2011.
[8]
Predictive effects of urinary liver-type fatty acid-binding protein for deteriorating
renal function and incidence of cardiovascular disease in type 2 diabetic patients
without advanced nephropathy. Diabetes Care. 36(5): 1248-1253, 2013.
[9]
Urinary liver-type fatty acid-binding protein and progression of diabetic nephropathy
in type 1 diabetes. Diabetes Care. 36(7): 2077-2083, 2013.
[10] Clinical significance of urinary liver-type fatty acid-binding protein as a predictor of
ESRD and CVD in patients with CKD. Clin Exp Nephrol. 20(2): 195-203, 2016.

between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding
protein. Sci Rep. 6:33077. 2016.

Pharmacology
[22]
[23]

[24]
[25]

[26]
[27]
[28]

[29]
[30]

AKI[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]

[19]
[20]

[21]

Quantification of L-type fatty acid binding protein in the urine of preterm neonates.
Early Hum Dev. 81(7): 643-646, 2005.
Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol.
18(11): 2894-2902, 2007.
Liver fatty acid-binding protein as a biomarker of acute kidney injury after cardiac
surgery. Kidney Int. 73(4): 465-472, 2008.
Urinary liver-type fatty acid-binding protein in septic shock: effect of polymyxin
B-immobilized fiber hemoperfusion. Shock. 31(5): 454-459, 2009.
Evaluation of new acute kidney injury biomarkers in a mixed intensive care unit. Crit
Care Med. 39(11): 2464-2469, 2011.
Usefulness of urinary biomarkers in early detection of acute kidney injury after
cardiac surgery in adults. Circulation Journal. 76(1): 213-220, 2012.
Mild elevation of urinary biomarkers in prerenal acute kidney injury. Kidney Int.
82(10): 1114-1120, 2012.
Urinary liver-type fatty acid-binding protein linked with increased risk of acute kidney
injury after allogeneic stem cell transplantation. Biol Blood Marrow Transplant.
20(12): 2010-2014, 2014.
Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization
related to cardiovascular events. Int J Nephrol Renovasc Dis. 8: 91-99, 2015.
Clinical usefulness of urinary liver-type fatty-acid-binding protein as a perioperative
marker of acute kidney injury in patients undergoing endovascular or openabdominal aortic aneurysm repair. J Anesth, 30(1):89-99. 2015.
Impact of clinical context on acute kidney injury biomarker performances: differences[Contact][Manufacturer]Effect of pitavastatin on urinary liver-type fatty acid–binding protein levels in patientswith early diabetic nephropathy. Diabetes Care. 28(11): 2728-2732, 2005.
Angiotensin II receptor antagonist reduces urinary liver-type fatty acid-binding protein
levels in patients with diabetic nephropathy and chronic renal failure. Diabetologia.
50(2): 490-492, 2007.
Tubular and glomerular injury in diabetes and the impact of ACE inhibition. Diabetes
Care. 32(9): 1684-1688, 2009.
Effect of pioglitazone on urinary liver-type fatty acid-binding protein concentrations
in diabetes patients with microalbuminuria. Diabetes Metab Res Rev. 22(5): 385-389,
2006.
Renal L-type fatty acid-binding protein mediates the bezafibrate reduction of
cisplatin-induced acute kidney injury. Kidney Int. 73(12): 1374-1384, 2008.
Renoprotective effects of various angiotensin II receptor blockers in patients withearly-stage diabetic nephropathy. Kidney Blood Press Res. 33(3): 213-220, 2010.
Additive antioxidative effects of azelnidipine on angiotensin receptor blocker
olmesartan treatment for type 2 diabetic patients with albuminuria Hypertens Res
34: 935-941, 2011.
Renoprotective and antioxidant effects of cilnidipine in hypertensive patients.
Hypertens Res. 35(11): 1058-1062, 2012.
Renoprotective effect of the xanthine oxidoreductase inhibitor, Topiroxostat,onAdenine-Induced Renal Injury. Am J Physiol Renal Physiol, 310(11):F1366-1376,
2016.

Toxicology
[31]
[32]
[33]

[34]
[35]
[36]

[37]
[38]

Urinary excretion of liver-type fatty acid-binding protein in contrast medium-inducednephropathy. Am J Kidney Dis. 47(3): 439-444, 2006.
A role of liver fatty acid-binding protein in cisplatin-induced acute renal failure.
Kidney Int. 72(3): 348-358, 2007.
L-type fatty acid binding protein transgenic mouse as a novel tool to explore
cytotoxicity to renal proximal tubules. Drug Metab Pharmacokinet. 23(4): 271-278,
2008.
Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury inaristolochic acid nephrotoxicity. Am J Pathol. 178(3): 1021-1032, 2011.
Urinary liver-type fatty acid-binding protein level as a predictive biomarker ofcontrast-induced acute kidney injury. Eur J Clin Invest. 42(5): 557-563, 2012.
Remote ischemic pre-conditioning alleviates contrast-induced acute kidney injury inpatients with moderate chronic kidney disease. Circulation Journal. 77(12): 30373044, 2013.
Human liver-type fatty acid-binding protein protects against tubulointerstitial injury inaldosterone-induced renal injury. Am J Physiol Renal Physiol. 308(2): F114-121, 2014.
Response of urinary liver-type fatty acid-binding protein to contrast media
administration has a potential to predict one-year renal outcome in patients withischemic heart disease. Heart Vessels. 30(3): 296-303, 2015.

Address: Hamamatsucho Bldg., 1-1-1 Shibaura, Minato-ku, Tokyo 105-0023, JAPANURL: http://www.cmic-holdings.co.jp/e/index.shtml
E-mail: l-fabp@cmic.co.jp

R-16-01
2016-10