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AB0018 Tubulointerstitial injury in lupus nephritis and gene expresion of KIM-1
  1. L. Mas1,
  2. M. Hayes Salinas2,
  3. S. Retamozo2,
  4. V. Saurit2,
  5. F. Caeiro2,
  6. A. Diller3,
  7. J. De la Fuente4,
  8. P. Trujillo Salazar4,
  9. A. Alvarellos2,
  10. T. Alvarellos1
  1. 1Molecular Biology Lab
  2. 2Rheumatology Division
  3. 3Pathology Division
  4. 4Nephrology Division, Hospital Privado, Cordoba, Cordoba, Argentina

Abstract

Background The extent of tubular lesions and recruitment of inflammatory cells is belived to be and important predictor of renal function in immune- mediated glomerulonephritis (1) such as Lupus Nephritis (LN). The response of the renal tubules to proteinuria is implicated in progression of renal disease (2). Kidney Injury Molecule 1 (KIM-1), a recently discovered transmembrane tubular protein, is markedly induced in acute kidney injury and chronic kidney disease. KIM-1 is an ideal biomarker because is not expressed in normal kidney but specifically expressed in injured proximal tubular cells and such expression persist until the damage cells recovered (3).

Objectives The role of KIM-1 in LN remains elusive. In this study, we examined the correlation between gene expression of KIM-1 in the urinary sediment and biopsy of patients (P) with NL diagnosis, and the relationship between KIM-1 expression and urine Protein/Creatinine ratio (P/C).

Methods Twenty two kidney biopsies and 28 urine samples from 20 P with LN (17 F/3 M, age 33,55±12,28; Range: 15-72) were evaluated. Kidney biopsies were classified according to ISN/RPS scoring system (4). Urine samples from LN patients were divided as P/C <1 (Group I, N=12) and P/C >1 (Group II, N=16), and urine samples from healthy individuals (Group III, N=17) were analized as control. Levels of gene expression of KIM-1 were evaluated using Quantitative Real Time PCR (QPCR). All amplifications were carried out in duplicate and threshold cycle (Ct) scores were averaged for calculations of relative expression values. The Ct scores were normalized against Ct scores by subtracting the corresponding β2Microglobuline (β2M) control, or DCt=Ct,gene- Ct,B2M. A Spearman’s rank-order correlations (r) was used to test associations between gene expression levels in biopsy and urine pairs samples. To test for differential gene expression between groups a variance analysis (ANOVA) was performed.

Results We observed a significant correlation between biopsy and urine, Spearman r=0,6838 (p=0.0005). There were a statistically significant difference in the expression of KIM-1 between groups (p=0,0110). After ANOVA test, we observed that the levels of mRNA of KIM-1 in Group II were higher than those from Group I and there were higher than Group III.

Conclusions There was no expression of KIM-1 in normal urine. In LN, urinary KIM-1 gene expression is closely related to tissue KIM-1 and correlates with the severity of tubular interstitial injury.

Quantitation of urinary KIM-1 is likely to be a nobel noninvasive and sensitive method for the evaluation of kidney injury in P with LN.

  1. Zheng L, et al. Journal of Histochemistry and Cytochemistry. 56(5): 517-529, 2008.

  2. Hill G, et al. Kidney International. 60: 1893-1903, 2001.

  3. Hou W, et al. Transplantation Reviews. 24:143-146, 2010.

  4. Weening JJ, et al. Kidney International. 65 (2): 521-530, 2004.

Disclosure of Interest None Declared

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