Value of carnitine palmitoyltransferase 1α expression for the assessment of the degree of renal fibrosis and the progression of chronic kidney disease / 中华肾脏病杂志

ABSTRACT

Objective:To study the relationship between the expression of carnitine palmitoyltransferase 1α (CPT1α) and progression of renal interstitial fibrosis and chronic kidney disease (CKD), and to evaluate the value of CPT1α as a biomarker in pathological diagnosis of renal interstitial fibrosis and CKD.Methods:As a retrospective cohort study, information of CKD patients dignosed with tubulointerstitial fibrosis by renal biopsy and receiving follow-up from March 1, 2010 to July 30, 2017 in the Second Affiliated Hospital of Nanjing Medical University were collected. Renal tissues were stained by immunohistochemistry to detect the expression of CPT1α protein and then divided into three groups according to the quartile of proportion of CPT1α positive staining cells, including group Q1(>67.89%), group Q2(49.84%-67.89%) and group Q3(<49.84%). The degree of renal interstitial fibrosis was measured by Masson staining and lipid deposition was represented by Bodipy staining. Messenger RNA of CPT1α and collagen as well as other extracellular matrix genes were detected by real time-PCR. Relationships between proportion of CPT1α positive staining cells and renal interstitial fibrosis and renal function were analyzed by linear regression analysis. The relationship between CPT1α positive cell number ratio and renal function progression was measured by Pearson correlation analysis and generalized linear model. The effect of lipid-lowering medicine on renal function of CKD patients was analyzed by paired comparative analysis.Results:Ninety patients with CKD were included in this study. Renal interstitial fibrosis and lipid droplets deposition area increased in Q2/Q3 group compared with Q1 group by Masson and Bodipy staining (all P<0.05). Messenger RNA level of extracellular matrix-related proteins increased in Q2/Q3 group by real time-PCR than those of Q1 group (all P<0.05). Linear regression analysis showed that fibrosis area was negatively correlated with the proportion of CPT1α positive staining cells ( r=-0.309, P<0.01). The baseline expression of CPT1α in renal issues was negatively related with serum creatinine (Scr) ( r=-2.801, P<0.001), positively related with estimated glomerular filtration rate (eGFR) ( r=1.240, P<0.001). After a medium follow-up of 3.47 years, CPT1α positive cell number ratio was positively correlated with eGFR change rate by Pearson analysis ( r=0.220, P=0.038). Paired stratified analysis showed that taking lipid-lowering medicines attenuated the decrease of eGFR in Q2 group and Q3 group but not in Q1 group (both P<0.05). Conclusions:The decline of CPT1α in renal tissues of CKD patients is associated with the increase of Scr, the decrease of eGFR and renal interstitial fibrosis. CPT1α is a promising molecular marker to evaluate the degree of renal fibrosis and the progression of CKD.