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Yasser M. Hafez

Yasser M. Hafez

Tanta University, Egypt

Title: NLRP3 inflammasome expression and urinary HSP72 in relation to biomarkers of inflammation and oxidative stress in diabetic nephropathy patients

Biography

Biography: Yasser M. Hafez

Abstract

Diabetic  nephropathy  (DN)  is  one  of  the  major  causes  of  end-stage  renal  disease.  Nod-like receptors  nucleotide-binding  domain  and  leucine-rich  repeat  pyrin-3  domain  (NLRP3) inflammasome  displays  a  considerable  role  in  the  chronic  inflammatory  state  observed  in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection the acute kidney injury.  The  aim  of  this  study  was  to  evaluate  NLRP3 relative  gene  expression, its correlation with inflammatory  and oxidative stress markers,  and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees  of  DN.  Forty-five type 2 diabetic patients were enrolled in this study:  15 normoalbuminuric; 15 microalbuminuric; 15 macroalbuminuric patients in addition to 15 healthy controls. Clinical examination and routine laboratory investigations were done.  NLRP3 mRNA expression was assessed by real time PCR. Serum 8-hydroxy-2’-deoxyguanosine (8-OHdG), IL-1β and uHSP72 levels were estimated by enzyme-linked immunosorbent assay.  Serum chitotriosidase  (CHIT1)  activity  was  examined.  Significant  higher  NLRP3  mRNA  expression, serum  8-OHdG,  IL-1β  and  uHSP72  levels,  in  addition  to  CHIT  1  activity were  documented  in the  macroalbuminuric  patient  group  as  compared  to  the  other  two  diabetic  and  control  groups. They  were  significantly  positively  correlated  and  to  urinary  albumin/creatinine  ratio,  serum creatinine  and  HA1c.  Multiple  linear  regression  analysis  using  UACR  as  dependent  variable, confirmed that uHSP72, and relative NLRP3 mRNA expression were the independent predictors of  DN  (β  were  0.432  and  0.448  respectively,  P<0.001).  Receiver  operating  characteristic analyses  revealed  that  both  NLRP3  mRNA  expression  and  uHSP72  levels  were  useful biomarkers  discriminating  DN  patients  from  T2DM  patients  (AUC  were  0.957  and  0.983 respectively) Conclusion: uHSP72 may be considered as a novel potential diagnostic biomarker for  the  early  detection  of  DN.  Moreover,  these  data  support  the  pivotal  role  of  NLRP3  in  the development and progression of DN.