Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Chronic Cardiorenal Failure is Correlated with Endogenous Erythropoietin Levels and Decreases in Response to Low-Dose Erythropoietin Treatment

Abstract

Background: Neutrophil-gelatinase associated lipocalin (NGAL), a tubular injury marker, is associated with iron metabolism in hemodialysis patients. We investigated whether serum NGAL levels reflect iron metabolism in combined chronic heart failure and chronic kidney disease (CHF/CKD) and whether treatment with low-dose erythropoietin stimulating agent (ESA) modulates NGAL levels. Methods: In the EPOCARES trial (ClinTrialsNCT00356733) serum NGAL, hepcidin-25, transferrin saturation (TSAT), reticulocyte hemoglobin content (Ret-He) and endogenous erythropoietin (EPO) levels were measured. Results: Baseline serum NGAL levels correlated with cystatin C (r=0.767, p<0.001) and baseline EPO levels (r=-0.395, p=0.003). There was no correlation with baseline TSAT, Ret-He, and hepcidin-25 levels. After two weeks, NGAL levels decreased in the ESA-group (p=0.02), while there was no change in the no-ESA group (p=0.62). The magnitude in NGAL decrease in the ESA-group correlated with baseline EPO levels (r=0.431, p=0.01). Conclusions: In contrast to in HD patients, in combined CKD/ CHF, serum NGAL levels did not correlate with iron metabolism, hence NGAL might reflect tubular damage in these patients. NGAL levels inversely correlated with baseline EPO levels and decreased in response to short-term ESA treatment, which might reflect an effect of ESA on tubular damage. These findings need to be confirmed and alternative explanations should be evaluated.

Citrate Attenuates Adenine-Induced Chronic Renal Failure in Rats by Modulating the Th17/Treg Cell Balance

“…increase in patients with chronic renal failure [29]. Our study found the content of NGAL was significantly increased in model group and decreased with citrate treatment.…”

Citrate attenuates vascular calcification in chronic renal failure rats

“…NAGL, a tubular injury marker, is normally considered a sensitive marker of acute renal failure . It has been reported that NGAL is significantly increased in patients with CRF . Our results demonstrated the content of NGAL was significantly increased in the model group and reduced with citrate treatment.…”

Erythropoietin response to anaemia in heart failure

“…Sixteen of these articles presented data for two or more independent groups, each of which was evaluated as an individual study. 18,[21][22][23][24][26][27][28][29][30]32,34,[36][37][38][39] Table 1 shows the main baseline characteristics of the resulting 41 studies, comprising a total of 3137 stable heart failure patients, mean age ranging from 52 years to 80 years. The majority of the studies included females and males, approximately one-third of total patients being females.…”

“…First, the synthesis of Epo may be modulated by circadian rhythms. Nonetheless, blood sampling was performed in the early morning in the studies describing the time of blood withdrawal [23][24][25][26]30,32,33,35,36 and previous investigations describe minimal or no diurnal fluctuation of circulating Epo levels in adults. 71,72 Finally, the presence of publication bias in the MD in O/P Epo ratio was not discarded, although the methodological quality of the included studies was determined as moderate-to-high, indicating a generally low bias risk.…”

“…16,17 Abnormalities in Epo relative to Hb generally indicate either defective Epo production or resistance in the bone marrow, respectively distinguished by decreases or increases in the observed/predicted (O/P) Epo ratio. 16,17 In this respect, although numerous investigations have assessed Epo and Hb levels in patients with heart failure, 17–39 few studies have arithmetically related Epo to Hb, reporting varied O/P Epo ratios in the presence of anaemia. 17,19,25,32,36,38 It is possible that the small sample size and pathophysiological heterogeneity of heart failure as well as distinct methodology may limit the synthesis of previous studies.…”