Accelerated renal fibrosis in cardiorenal syndrome is associated with long-term increase in urine neutrophil gelatinase-associated lipocalin levels

Michal Entin-Meer, Jeremy Ben-Shoshan, Sofia Maysel-Auslender, Ran Levy, Pavel Goryainov, Idit Schwartz, Iris Barshack, Camila Avivi, Rinat Sharir, Gad Keren

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Cardiac events are the main cause of death among patients with end-stage renal failure. Even a mild renal disease is currently considered a major risk factor for cardiovascular complications following myocardial infarction (MI). The aim of the present study was to detect histological, sera and urine characteristics of kidney injury in cardiorenal syndrome (CRS) compared to chronic kidney disease (CKD) with an intact cardiac function. Methods: We employed a rat model for CRS, in which an acute MI (AMI) was induced 4 weeks after establishment of subtotal nephrectomy. Four weeks later, left ventricular function was assessed by echocardiography and changes in renal performance were examined using histological and biochemical parameters. Results: Increased interstitial fibrosis as well as renal inflammation were observed in renal sections derived from CRS rats, compared to subtotal nephrectomy (CKD)-only animals. Moreover, we found that even though AMI on the background of CKD was not associated with a further decrease in creatinine clearance or a further increase in sera BUN levels compared to CKD only, a significant long-term elevation in urine neutrophil gelatinase-associated lipocalin (Ngal) levels was detectable post-MI induction. Conclusions: AMI in the CKD setting is associated with accelerated renal fibrosis and long-term elevated urine Ngal values, suggesting that cardiac dysfunction contributes to accelerated intrinsic kidney injury in CKD. The data indicate that elevated urine Ngal may potentially serve as an early non-invasive laboratory parameter for a left ventricular dysfunction-related renal injury.

Original languageEnglish
Pages (from-to)190-200
Number of pages11
JournalAmerican Journal of Nephrology
Volume36
Issue number2
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Cardiorenal syndrome
  • Chronic kidney disease
  • Fibrosis
  • Left ventricular dysfunction
  • Neutrophil gelatinase-associated lipocalin
  • Subtotal nephrectomy

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