Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: Acute kidney injury is a relatively frequent complication of allogenic hematopoietic stem cell transplant, resulting in increased risk of morbidity and mortality. Early diagnosis and management of acute kidney injury is of great importance for prevention of poor outcomes in these transplant recipients. MATERIALS AND METHODS: Fifty consecutive patients, hospitalized for allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation Unit of Gazi University Faculty of Medicine, were included in this prospective study. Serial measurements of serum creatinine and creatinine clearance were obtained before administration of conditioning regimen and at 0, 7, 14, 21, and 28 days after start of conditioning. Blood and urine samples were also obtained for the measurement of serum cystatin C and urine neutrophil gelatinase-associated lipocalin levels before conditioning and 24 hours before each serum creatinine measurement. RESULTS: During the median 25 days of follow-up, acute kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2, and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury Network classification. There were significant positive correlations between serum cystatin C levels and serum creatinine levels and negative correlations with creatinine clearance levels at each time point (P < .001), whereas no statistically significant associations were observed with urinary neutrophil gelatinase-associated lipocalin levels. Both univariate and multivariate Cox regression models showed a statistically significant association between serum cystatin C levels and development of acute kidney injury, whereas urine neutrophil gelatinase-associated lipocalin levels did not show any significant associations. CONCLUSIONS: Serum cystatin C levels might be a useful marker for early detection of acute kidney injury in adult allogenic hematopoietic stem cell transplant recipients. Close monitoring of kidney function by sensitive biomarkers might provide early recognition and timely management of acute kidney injury in high-risk patient populations.

Salt increases monocyte CCR2 expression and inflammatory responses in humans.

Inflammation may play a role in the link between high salt intake and its deleterious consequences. However, it is unknown whether salt can induce proinflammatory priming of monocytes and macrophages in humans. We investigated the effects of salt on monocytes and macrophages in vitro and in vivo by performing a randomized crossover trial in which 11 healthy human subjects adhered to a 2-week low-salt and high-salt diet. We demonstrate that salt increases monocyte expression of CCR2, a chemokine receptor that mediates monocyte infiltration in inflammatory diseases. In line with this, we show a salt-induced increase of plasma MCP-1, transendothelial migration of monocytes, and skin macrophage density after high-salt diet. Macrophages demonstrate signs of an increased proinflammatory phenotype after salt exposure, as represented by boosted LPS-induced cytokine secretion of IL-6, TNF, and IL-10 in vitro, and by increased HLA-DR expression and decreased CD206 expression on skin macrophages after high-salt diet. Taken together, our data open up the possibility for inflammatory monocyte and macrophage responses as potential contributors to the deleterious effects of high salt intake.

Hypothalamic Energy Regulatory Peptides in Chronic Kidney Disease.

Loss of appetite affects one-third of patients with CKD and is the leading cause of malnutrition in this population. Orexigenic Agouti-related peptide (AgRP) with neuropeptide-Y (NPY) and anorexigenic melanocyte-stimulating hormone-α (MSH-α) with cocaine- and amphetamine-regulated transcript (CART) are known to regulate appetite. In this study, we aimed to evaluate the levels of these peptides in CKD patients compared to healthy subjects and demonstrate the effects of dialysis treatment and erythropoiesis-stimulating agent (ESA) therapy. The cross-sectional study is composed of consecutive inclusion of 20 healthy individuals, 20 predialysis CKD patients, 20 HD, and 20 peritoneal dialysis (PD) patients. Exclusion criteria were an active infection, history of malignancy, hypo- or hyperthyroidism, and diabetes. Patients on dialysis had targeted Kt/Vs. Demographic features and BMIs of the four groups were similar. Levels of AgRP, NPY, AMSH, and CART were significantly different between groups. Nondialysis CKD patients had significantly lower hypothalamic hormones compared to healthy individuals, HD and PD patients (P = 0.02, P = 0.03, and P = 0.07 for AgRP; P = 0.02, P = 0.01, and P = 0.09 for NPY; P = 0.02, P = 0.02, and P = 0.03 for AMSH; P = 0.02, P = 0.005, and P = 0.030 for CART). Dialysis patients with or without ESA treatment had similar hormone levels (P = 0.13 for AgRP; P = 0.11 for NPY; P = 0.23 for AMSH, and P = 019 for CART). Predialysis CKD patients have lower orexigenic and presumably indirectly lower anorexigenic peptides compared to healthy subjects and dialysis patients. ESA treatment does not affect these hypothalamic peptides in dialysis patients.

Circulating gelatinases are not prognostic of treatment response and survival in locally advanced rectal cancer patients undergoing preoperative chemoradiotherapy.

PURPOSE: To investigate whether the serum levels of matrix metalloproteinases (MMPs) are predictive on treatment response and survival in locally advanced rectal cancer (LARC) patients undergoing preoperative chemoradiotherapy. PATIENTS AND METHODS: Serum MMP-2 and MMP-9 was analyzed by enzyme-linked immunosorbent assay and obtained before, midway, and 1-month after the end of preoperative radiotherapy treatment. The prognostic significance of serum MMP-2 and MMP-9 levels and their association with other pathological findings for LARC patients were evaluated. RESULTS: Serum levels of MMP-2 or MMP-9 were found to decrease with increasing clinical stage and negative correlation was statistically significant (P < 0.05). There was no statistically significant difference in tumor response and survival between the low and high MMP-2 and MMP-9 groups. MMP-2 and MMP-9 were not correlated with local-regional recurrence. CONCLUSIONS: We propose that serum levels of MMP-2 and MMP-9 are not predictive on treatment response and survival in LARC patients.

The role of inflammatory biomarkers in CHD-associated pulmonary hypertension in children.

OBJECTIVE: The present study aims to identify the role of inflammatory markers such as C-reactive protein, interleukin-6, and fractalkine in CHD-associated pulmonary hypertension in children. METHODS: This is a prospective review of 37 children with CHD-related pulmonary hypertension, 21 children with congenital heart defects, and 22 healthy children. RESULTS: Serum C-reactive protein and interleukin-6 levels were significantly higher in the children with CHD-related pulmonary hypertension (respectively, p=0.049 and 0.026). Serum C-reactive protein concentrations correlated negatively with ejection fraction (r=-0.609, p=0.001) and fractional shortening (r=-0.452, p=0.007) in the pulmonary hypertension group. Serum fractalkine concentrations correlated negatively with ejection fraction (r=-0.522, p=0.002) and fractional shortening (r=-0.395, p=0.021) in the children with pulmonary hypertension. Serum interleukin-6 concentrations also correlated negatively with Qs (r=-0.572, p=0.021), positively with Rs (r=0.774, p=0.001), and positively with pulmonary wedge pressure (r=0.796, p=0.006) in the pulmonary hypertension group. A cut-off value of 2.2 IU/L for C-reactive protein was able to predict pulmonary hypertension with 77.5% sensitivity and 77.5% specificity. When the cut-off point for interleukin-6 concentration was 57.5 pg/ml, pulmonary hypertension could be predicted with 80% sensitivity and 75% specificity. CONCLUSION: Inflammation is associated with the pathophysiology of pulmonary hypertension. The inflammatory markers C-reactive protein and interleukin-6 may have a role in the clinical evaluation of paediatric pulmonary hypertension related to CHDs.

Protective effect of adrenomedullin on contrast induced nephropathy in rats / Efecto protector de la adrenomedulina en la nefropatía inducida por contraste en ratas

Background and aims: Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. Methods: Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. Results: Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. Conclusion: This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue

Antecedentes y objetivos: La incidencia de la nefropatía inducida por contraste (NIC) está aumentando y la vasoconstricción renal y la hipoxia medular son mecanismos importantes. Los enfoques terapéuticos son muy limitados y existe un gran interés en avanzar en las estrategias preventivas. La adrenomedulina es un péptido relativamente nuevo con propiedades antioxidantes, vasoactivas y vasodilatadoras. Nuestro objetivo es investigar si la adrenomedulina puede jugar un papel preventivo frente al desarrollo de la NIC experimental. Métodos: Se distribuyeron ratas Wistar albinas (n = 24) de forma aleatoria en cuatro grupos de 6: control (C), adrenomedulina (A), medio de contraste (MC) y adrenomedulina más medio de contraste (AMC). Las ratas no ingirieron agua desde el día 1 al día 4 (durante 72 horas). Posteriormente, se les administraron las sustancias de forma intravenosa. Los grupos A y AMC recibieron una dosis de adrenomedulina de 12 µg/kg. Los grupos MC y AMC recibieron una única dosis de medio de contraste de alta osmolaridad: 10 ml/kg de diatrizoato (Urografin 76 %, Schering AG, Alemania). Los días 1 y 6 se tomaron muestras de sangre para realizar análisis de función renal y de marcadores inflamatorios, incluidos el TNF-α, IL-1β, IL-6 e IL-18. Tras el sacrificio, se examinaron las histologías renales con tinción hematoxilina-eosina. Resultados: En comparación con el grupo MC, los niveles de cistatina C sérica fueron significativamente inferiores en el grupo AMC (P < 0,05). Además, la tasa de excreción diaria de proteínas, los cambios absolutos en el gasto urinario diario y los valores de aclaramiento de la creatinina fueron significativamente inferiores en el grupo AMC que en el grupo MC (P < 0,05). En la evaluación histopatológica, en lo que respecta al grado de daño tubular y los valores de congestión medular, el grupo AMC presentaba niveles ligeramente mejores en comparación con el grupo MC. Sin embargo, según los marcadores inflamatorios, las diferencias no presentaron significación estadística. Conclusión: El estudio ha demostrado que la adrenomedulina resulta beneficiosa en los análisis de función renal deteriorada en un modelo experimental de NIC. Por lo tanto, la adrenomedulina puede ser un candidato para la profilaxis de la NIC. No obstante, se necesitan más estudios que arrojen luz sobre este tema

Protective effect of adrenomedullin on contrast induced nephropathy in rats.

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. METHODS: Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. RESULTS: Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. CONCLUSION: This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue.