Accelerated renal fibrosis in cardiorenal syndrome is associated with long-term increase in urine neutrophil gelatinase-associated lipocalin levels.
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.
Laboratory of Cardiovascular Research, Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
Michal
M
Entin-Meer
Jeremy
J
Ben-Shoshan
Sofia
S
Maysel-Auslender
Ran
R
Levy
Pavel
P
Goryainov
Idit
I
Schwartz
Iris
I
Barshack
Camila
C
Avivi
Rinat
R
Sharir
Gad
G
Keren
D000209:Acute-Phase Proteins / Q000652:urine*; D000818:Animals; D015415:Biomarkers / Q000652:urine; D059347:Cardio-Renal Syndrome / Q000453:epidemiology / Q000473:pathology / Q000652:urine*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000453:epidemiology / Q000473:pathology / Q000652:urine; D007668:Kidney / Q000502:physiology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology / Q000473:pathology / Q000652:urine*; D009392:Nephrectomy; D011518:Proto-Oncogene Proteins / Q000652:urine*; D051381:Rats; D011917:Rats, Inbred Lew; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000473:pathology / Q000652:urine*; D012307:Risk Factors; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology / Q000473:pathology / Q000652:urine
D000209:Acute-Phase Proteins; D015415:Biomarkers; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins