Neutrophil gelatinase-associated lipocalin and acute kidney injury in endovascular aneurysm repair or open aortic repair: a pilot study

Introduction: Acute kidney injury (AKI) occurs frequently after abdominal aortic surgery and there is currently no effective marker able to detect early onset. The aim of this study is to evaluate the ability of neutrophil gelatinase-associated lipocalin (NGAL) to early identify the development of acute renal damage in patients undergoing endovascular aneurysm repair (EVAR) or open aortic repair (OAR). Materials and methods: Serial samples of blood and urine were obtained from 25 patients undergoing both EVAR and OAR. Seven male subjects with AKI and 18 subjects with no-AKI (17 males, 1 female) were included in the study. We determined concentrations of serum creatinine (sCr) and urinary, serum and whole blood NGAL (uNGAL, sNGAL, bNGAL) collected at baseline, and after 4 and 18 hours. AKI was defined according to the RIFLE criteria (risk, injury, failure, loss of kidney function, and end-stage kidney disease): increase by 50% in sCr or reduction of at least 25% of estimated glomerular filtration rate (eGFR) from baseline. Results: Seven patients developed AKI in the stage Risk. There was no significant difference in sNGAL concentrations in the AKI group as compared to no-AKI group. However, the uNGAL/uCreatinine ratio and bNGAL concentrations were significantly higher after 18 hours in the AKI group (no-AKI 1.69 (0.91 - 2.47) vs AKI 3.2 (2.08 - 5.92) ng/mg for uNGAL/uCreatinine ratio, P = 0.036; and no-AKI 83 (59 - 131) vs AKI 164 (126 – 263) ng/mL for bNGAL, P = 0.029). Conclusions: Our results suggest that uNGAL, sNGAL and bNGAL, after abdominal aortic surgery, are not suitable as early biomarkers of AKI

Sarcopenia in Chronic Kidney Disease: Focus on Advanced Glycation End Products as Mediators and Markers of Oxidative Stress

Sarcopenia is common in chronic kidney disease (CKD), and it is independently associated with morbidity and mortality. Advanced glycation end products (AGE) are mainly known as aging products. In CKD, AGE accumulate due to increased production and reduced kidney excretion. The imbalance between oxidant/antioxidant capacities in CKD patients is one of the main factors leading to AGE synthesis. AGE can, in turn, promote CKD progression and CKD-related complications by increasing reactive oxygen species generation, inducing inflammation, and promoting fibrosis. All these derangements can further increase AGE and uremic toxin accumulation and promote loss of muscle mass and function. Since the link between AGE and sarcopenia in CKD is far from being fully understood, we revised hereby the data supporting the potential contribution of AGE as mediators of oxidative stress in the pathogenesis of sarcopenia. Understanding how AGE and oxidative stress impact the onset of sarcopenia in CKD may help to identify new potential markers of disease progression and/or therapeutic targets

Role of the Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Prognostic Factor for Mortality in Hemodialysis and Peritoneal Dialysis Patients

End-stage renal disease patients on dialysis (CKD-G5D) have a high mortality rate due to cardiovascular diseases (CVD). In these patients, inflammation, oxidative stress, and uremia increase the production of glycation products (AGEs) which in turn accelerate CVD onset and progression. Recently, attention has been given to the soluble receptor for AGEs (sRAGE) as a marker of inflammation, oxidative stress, atherosclerosis, and heart failure in CKD-G5D. However, its association with patient outcomes is still under debate. Our aim is to explore whether sRAGE may be a predictor of mortality in CKD-G5D. We studied 123 CKD-G5D for 24 months. Of these patients, 56 were on hemodialysis (HD) and 67 on peritoneal dialysis (PD). Demographic, anthropometric, biochemical, and clinical data were recorded. sRAGE was quantified by enzyme-linked immunosorbent assay. sRAGE was a predictor of mortality at 2-year follow-up. Each increase of 100 pg/mL in sRAGE levels was associated with an approximately 7% increased risk of mortality. Furthermore, in the entire study group, as well as in PD and HD patient subgroups, sRAGE was positively correlated with brain natriuretic peptide (BNP) levels. Mortality rates as well as sRAGE levels in patients who died did not differ between PD and HD patients. In conclusion, the positive association observed with BNP levels suggests a role for sRAGE as a prognostic factor for mortality in CKD-G5D patients displaying an active process of cardiac remodeling

AGEs and sRAGE Variations at Different Timepoints in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) are affected by enhanced oxidative stress and chronic inflammation, and these factors may contribute to increase advanced glycation end-products (AGEs). In this study we quantified AGEs and soluble receptors for AGE (sRAGE) isoforms and evaluated the association between their variations and eGFR at baseline and after 12 months. We evaluated 64 patients. AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer, and sRAGE by ELISA. Median age was 81 years, male patients accounted for 70%, 63% were diabetic, and eGFR was 27 ± 10 mL/min/1.73 m2. At follow up, sRAGE isoforms underwent a significant decrement (1679 [1393;2038] vs. 1442 [1117;2102], p p = 0.004). Although AGEs and AGEs/sRAGE ratios were inversely related with eGFR, their basal values as well their variations did not show a significant association with eGFR changes. In a cohort of patients with a stable clinical condition at 1 year follow-up, AGEs/sRAGE was associated with renal function. The lack of association with eGFR suggests that other factors can influence its increase. In conclusion, AGEs/sRAGE can be an additional risk factor for CKD progression over a longer time, but its role as a prognostic tool needs further investigation

Association between Advanced Glycation End-Products and Sarcopenia in Patients with Chronic Kidney Disease

Background: In patients with chronic kidney disease (CKD), there is an overproduction and accumulation of advanced glycation end-products (AGEs). Since AGEs may have detrimental effects on muscular trophism and performance, we evaluated whether they may contribute to the onset of sarcopenia in CKD patients. Methods: We enrolled 117 patients. The AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer and soluble receptor for AGE (sRAGE) isoforms by ELISA. As for the sarcopenia definition, we used the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. Results: The average age was 80 ± 11 years, 70% were males, and the mean eGFR was 25 + 11 mL/min/1.73 m2. Sarcopenia was diagnosed in 26 patients (with a prevalence of 22%). The sarcopenic patients had higher levels of circulating AGEs (3405 ± 951 vs. 2912 ± 722 A.U., p = 0.005). AGEs were higher in subjects with a lower midarm muscle circumference (MAMC) (3322 ± 919 vs. 2883 ± 700 A.U., respectively; p = 0.005) and were directly correlated with the gait test time (r = 0.180, p = 0.049). The total sRAGE and its different isoforms (esRAGE and cRAGE) did not differ in patients with or without sarcopenia. Conclusions: In older CKD patients, AGEs, but not sRAGE, are associated with the presence of sarcopenia. Therefore, AGEs may contribute to the complex pathophysiology leading to the development of sarcopenia in CKD patients