Clinical effectiveness

For the early diagnosis of renal disease accompanying tubular dysfunction

Key word:CKD (Chronic Kidney Disease)

Chronic Kidney Disease (CKD) and L-FABP

Urinary L-FABP is associated with the degree of tubulointerstitial injury in human kidney biopsy tissue[1] and is a marker reflecting tubular stress burden, and has been proven useful when predicting a kidney prognosis in clinical studies targeting chronic renal disease patients[2]. Urinary L-FABP has greater sensitivity than conventional, important urinary protein markers, and can determine patients whose renal disease will progress. Also, because urinary L-FABP increases as renal disease progresses and decreases with its remission, it is useful for the monitoring of renal disease.

A-1: Histological evaluation of renal tubulointerstitial lesions and urinary L-FABP

A-2: Diabetic nephropathy and MCNS kidney tissue (Masson trichrome stain and fat stain)

In diabetic nephropathy, stronger tubulointerstitial injury compared to MCNS was found, and adipose accumulation in renal tubules was confirmed.

(e) Diabetic Nephropathy (DN)
Masson trichrome stain, Fat stain

(f) Minimal Change Nephrotic Syndrome (MCNS)
Masson trichrome stain, Fat stain

(Partly modified from figure 1 and figure 2 of article [3])

FIGS. a,b e,f
Pathological tissue images (x100) of (a) Diabetic Nephropathy (DN) and (b) Minimal Change Nephrotic Syndrome (MCNS).

FIGS. c,d
(c) Tubulointerstitial injury score (%) for both disease groups and (d) urinary L-FABP (mean ± standard deviation, **p<0.01 vs. MCNS)(No significant differences seen in other urinary markers in both disease groups)

Subjects

8 cases exhibiting nephrotic syndrome and diagnosed with diabetic nephropathy from renal biopsy and clinical history and 12 Minimal Change Nephrotic Syndrome (MCNS) cases, in order to examine the correlation between histological tubulointerstitial injury in CKD (Chronic Kidney Disease) and urinary markers.

Method

Urine was collected from the above subjects at the time of hospitalization just before renal biopsy for 24 hours, and measured values for urinary protein, urinary albumin, urinary NAG, urinary L-FABP were compared with pathological histology evaluations across both groups.

Results

No significant difference was found in both groups for urinary protein, urinary albumin and urinary NAG, but significantly high values were shown for urinary L-FABP alone in the diabetic nephropathy cases, matching the result of histological tubulointerstitial injury evaluations (FIGS. c,d).

Because urinary L-FABP was able to detect the degree of nephrotic syndrome tubulointerstitial injury, which is something that cannot be determined with conventional urinary markers, the implication is that the appearance of urinary L-FABP is possibly tubular injury-specific in earlier stage diabetic nephropathy.

B: Comparison of blood L-FABP and urinary L-FAPB (kidney disease specificity of urinary L-FABP)

Comparison of (a) blood L-FABP and (b) urinary L-FABP in liver disease patients (71 casesdisease patients), CKD patients (73 casesCKD patients), and healthy subjects (71 caseshealthy subjects)
(Mean ± standard deviation,  vs. healthy subjects*p<0.05 vs. healthy subjects, vs. CKD patients$p<0.05 vs. CKD patients, vs. liver disease patients#p<0.05 vs. liver disease patients )

(Partly modified from figure 3 of article [4])

Subject

Because L-FABP is also expressed in the liver and intestinal tract, the possibility of blood L-FABP levels rising in cases of liver or intestinal disease is conceivable. There is a report of clinical analysis in such instances of whether urinary L-FABP is affected by blood L-FABP[4].

The results of blood and urinary L-FABP measurements for 71 liver disease patients with normal kidney function (disease patients), 73 CKD patients with normal liver function (CKD patients), and 71 healthy subjects (healthy subjects) are shown in the figure to the left.

In liver disease patients with normal kidney function, blood L-FABP showed significantly high values more than 7 times greater than that of healthy subjects, but it was confirmed that no significant difference in urinary L-FABP compared to healthy subjects exists. Meanwhile, in CKD patients with normal liver function, urinary L-FABP showed significantly high values compared to both healthy subjects and liver disease patients, while blood L-FABP showed a non-significant tendency to increase compared with healthy subjects. This is thought to be caused by a clearance decrease in CKD patients.

Results

In previous investigations, the implications have been that even in diseases that show high values for blood L-FABP, urinary L-FABP is not affected if kidney function is normal, with no differences according to gender or age.
Urinary L-FABP reacts subtly to tubular injury by means of a mechanism that is different from conventional NAG and α1M urinary marker, and can be considered to be a kidney disease-specific biomarker excreted from kidney tissue.

Reference

  • [1] Kamijo, A. et al., Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules. Am J Pathol. 165(4): 1243-1255, 2004. PubMed
  • [2] Kamijo, A. et al., Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: A multicenter trial. J Lab Clin Med. 145(3): 125-133, 2005. PubMed
  • [3] Sasaki, H. et al., Urinary fatty acids and liver-type fatty acid binding protein in diabetic nephropathy. Nephron Clin Pract. 112(3): c148-156, 2009. PubMed
  • [4] Kamijo, A. et al., Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. Mol Cell Biochem. 284(1-2): 175-182, 2006. PubMed

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How to use RENISCHEM® L-FABP POC kit

For nonclinical safety evaluation

Urinary L-FABP kits for Rat, Dog, Cat, Monkey and Pig are available for the purpose of monitoring drug nephrotoxicity and drug effectiveness.
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