scholarly journals Red blood cell antibody-induced anemia causes differential degrees of tissue hypoxia in kidney and brain

2018 ◽  
Vol 314 (4) ◽  
pp. R611-R622 ◽  
Author(s):  
Nikhil Mistry ◽  
C. David Mazer ◽  
John G. Sled ◽  
Alan H. Lazarus ◽  
Lindsay S. Cahill ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Blood Flow ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Tissue Hypoxia ◽  
Heme Oxygenase 1 ◽  
Cerebral Tissue

Moderate anemia is associated with increased mortality and morbidity, including acute kidney injury (AKI), in surgical patients. A red blood cell (RBC)-specific antibody model was utilized to determine whether moderate subacute anemia could result in tissue hypoxia as a potential mechanism of injury. Cardiovascular and hypoxic cellular responses were measured in transgenic mice capable of expressing hypoxia-inducible factor-1α (HIF-1α)/luciferase activity in vivo. Antibody-mediated anemia was associated with mild intravascular hemolysis (6 h) and splenic RBC sequestration ( day 4), resulting in a nadir hemoglobin concentration of 89 ± 13 g/l on day 4. At this time point, renal tissue oxygen tension (PtO2) was decreased in anemic mice relative to controls (13.1 ± 4.3 vs. 20.8 ± 3.7 mmHg, P < 0.001). Renal tissue hypoxia was associated with an increase in HIF/luciferase expression in vivo ( P = 0.04) and a 20-fold relative increase in renal erythropoietin mRNA transcription ( P < 0.001) but no increase in renal blood flow ( P = 0.67). By contrast, brain PtO2 was maintained in anemic mice relative to controls (22.7 ± 5.2 vs. 23.4 ± 9.8 mmHg, P = 0.59) in part because of an increase in internal carotid artery blood flow (80%, P < 0.001) and preserved cerebrovascular reactivity. Despite these adaptive changes, an increase in brain HIF-dependent mRNA levels was observed (erythropoietin: P < 0.001; heme oxygenase-1: P = 0.01), providing evidence for subtle cerebral tissue hypoxia in anemic mice. These data demonstrate that moderate subacute anemia causes significant renal tissue hypoxia, whereas adaptive cerebrovascular responses limit the degree of cerebral tissue hypoxia. Further studies are required to assess whether hypoxia is a mechanism for acute kidney injury associated with anemia.

In vivo microvascular structural and functional consequences of muscle length changes

1997 ◽  
Vol 272 (5) ◽  
pp. H2107-H2114 ◽  
Author(s):  
D. C. Poole ◽  
T. I. Musch ◽  
C. A. Kindig
Keyword(s):  
Blood Flow ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Oxygen Delivery ◽  
Sarcomere Length ◽  
Flow Dynamics ◽  
Capillary Diameter ◽  
Luminal Diameter ◽  
Length Changes

As muscles are stretched, blood flow and oxygen delivery are compromised, and consequently muscle function is impaired. We tested the hypothesis that the structural microvascular sequellae associated with muscle extension in vivo would impair capillary red blood cell hemodynamics. We developed an intravital spinotrapezius preparation that facilitated direct on-line measurement and alteration of sarcomere length simultaneously with determination of capillary geometry and red blood cell flow dynamics. The range of spinotrapezius sarcomere lengths achievable in vivo was 2.17 +/- 0.05 to 3.13 +/- 0.11 microns. Capillary tortuosity decreased systematically with increases of sarcomere length up to 2.6 microns, at which point most capillaries appeared to be highly oriented along the fiber longitudinal axis. Further increases in sarcomere length above this value reduced mean capillary diameter from 5.61 +/- 0.03 microns at 2.4-2.6 microns sarcomere length to 4.12 +/- 0.05 microns at 3.2-3.4 microns sarcomere length. Over the range of physiological sarcomere lengths, bulk blood flow (radioactive microspheres) decreased approximately 40% from 24.3 +/- 7.5 to 14.5 +/- 4.6 ml.100 g-1.min-1. The proportion of continuously perfused capillaries, i.e., those with continuous flow throughout the 60-s observation period, decreased from 95.9 +/- 0.6% at the shortest sarcomere lengths to 56.5 +/- 0.7% at the longest sarcomere lengths and was correlated significantly with the reduced capillary diameter (r = 0.711, P < 0.01; n = 18). We conclude that alterations in capillary geometry and luminal diameter consequent to increased muscle sarcomere length are associated with a reduction in mean capillary red blood cell velocity and a greater proportion of capillaries in which red blood cell flow is stopped or intermittent. Thus not only does muscle stretching reduce bulk blood (and oxygen) delivery, it also alters capillary red blood cell flow dynamics, which may further impair blood-tissue oxygen exchange.

Acute Kidney Injury During Warfarin Therapy Associated With Obstructive Tubular Red Blood Cell Casts: A Report of 9 Cases

2009 ◽  
Vol 54 (6) ◽  
pp. 1121-1126 ◽  
Author(s):  
Sergey V. Brodsky ◽  
Anjali Satoskar ◽  
Jun Chen ◽  
Gyongyi Nadasdy ◽  
Jeremiah W. Eagen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Warfarin Therapy ◽  
Kidney Injury

scholarly journals Double Whammy: Pigment Nephropathy and Warfarin-related Nephropathy As Aetiology for Acute Kidney Injury in a Patient With Mechanical Heart Valves

2019 ◽  
Vol 12 (1) ◽  
pp. 41-44 ◽  
Author(s):  
Arvind Conjeevaram ◽  
Priyangani Lohia ◽  
Ravishankar GS ◽  
Mahesha Vankalakunti
Keyword(s):  
Acute Kidney Injury ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Oral Anticoagulation ◽  
Heart Valves ◽  
Kidney Injury ◽  
Mechanical Heart Valves ◽  
Biopsy Diagnosis ◽  
Sheer Stress ◽  
Pigment Nephropathy

It is well known that patients with mechanical heart valves may develop sheer stress related hemolysis and consequent pigment related nephropathy. Warfarin Related Nephropathy (WRN) is a relatively new entity and defined as Acute Kidney Injury (AKI) in the setting of an INR of > 3.0 excluding other obvious etiologies. A biopsy diagnosis of WRN is conducted when red blood cell casts are noted filling and blocking the tubules; additionally, glomerular hemorrhage may be observed. We describe a patient with mechanical heart valves on oral anticoagulation who developed both pigment nephropathy and WRN causing AKI.

scholarly journals The Association between Red Blood Cell Distribution Width and Mortality in Critically Ill Patients with Acute Kidney Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Benji Wang ◽  
Huaya Lu ◽  
Yuqiang Gong ◽  
Binyu Ying ◽  
Bihuan Cheng
Keyword(s):  
Acute Kidney Injury ◽  
Blood Cell ◽  
Critically Ill ◽  
Red Blood Cell ◽  
Critically Ill Patients ◽  
Kidney Injury ◽  
Cell Distribution ◽  
Distribution Width ◽  
The Impact ◽  
Red Blood Cell Distribution

Background. Several investigators have sought risk factors for mortality in acute kidney injury (AKI). However, no epidemiological studies have investigated the impact of red blood cell distribution width (RDW) on prognosis for critically ill patients with AKI. The aim of this study was to investigate the association of RDW with mortality in these patients. Methods. We analyzed data from the MIMIC-III. RDW was measured upon ICU admission. The association between RDW and mortality of AKI was determined using a multivariate logistic regression and was expressed as the adjusted odds ratio with associated 95% confidence interval (CI). We also conducted subgroup analyses to determine the consistency of this association. Results. A total of 14,078 critically ill patients with AKI were eligible for this analysis. In multivariate analysis, adjusted for age and gender and compared with the reference group (RDW 11.1-13.4%) related to hospital mortality, the adjusted ORs (95% CIs) for RDW levels 13.5-14.3%, 14.4-15.6%, and 15.7-21.2% were 1.22 (1.05, 1.43), 1.56 (1.35, 1.81), and 2.66 (2.31, 3.06), respectively. After adjusting for confounding factors, with high RDW linked to an increase in mortality (RDW 15.7-21.2% versus 11.1-13.4%: OR, 1.57; 95% CI, 1.22 to 2.01; P trend <0.0001). A similar trend was observed for 30-day mortality. Conclusions. RDW appeared to be an independent prognostic marker in critically ill patients with AKI and higher RDW was associated with increased risk of mortality in these patients.

scholarly journals Identification of novel metabolomic biomarkers in an experimental model of septic acute kidney injury

2019 ◽  
Vol 316 (1) ◽  
pp. F54-F62 ◽  
Author(s):  
Jose L. Izquierdo-Garcia ◽  
Nicolás Nin ◽  
Pablo Cardinal-Fernandez ◽  
Yenny Rojas ◽  
Marta de Paula ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Experimental Model ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Principal Component ◽  
Renal Tissue ◽  
Serum Samples ◽  
Neutrophil Gelatinase Associated Lipocalin

The aim of this study is the identification of metabolomic biomarkers of sepsis and sepsis-induced acute kidney injury (AKI) in an experimental model. Pigs were anesthetized and monitored to measure mean arterial pressure (MAP), systemic blood flow (QT), mean pulmonary arterial pressure, renal artery blood flow (QRA), renal cortical blood flow (QRC), and urine output (UO). Sepsis was induced at t = 0 min by the administration of live Escherichia coli ( n = 6) or saline ( n = 8). At t = 300 min, animals were killed. Renal tissue, urine, and serum samples were analyzed by nuclear magnetic resonance (NMR) spectroscopy. Principal component analyses were performed on the processed NMR spectra to highlight kidney injury biomarkers. Sepsis was associated with decreased QT and MAP and decreased QRA, QRC, and UO. Creatinine serum concentration and neutrophil gelatinase-associated lipocalin (NGAL) serum and urine concentrations increased. NMR-based metabolomics analysis found metabolic differences between control and septic animals: 1) in kidney tissue, increased lactate and nicotinuric acid and decreased valine, aspartate, glucose, and threonine; 2) in urine, increased isovaleroglycine, aminoadipic acid, N-acetylglutamine, N-acetylaspartate, and ascorbic acid and decreased myoinositol and phenylacetylglycine; and 3) in serum, increased lactate, alanine, pyruvate, and glutamine and decreased valine, glucose, and betaine concentrations. The concentration of several metabolites altered in renal tissue and urine samples from septic animals showed a significant correlation with markers of AKI (i.e., creatinine and NGAL serum concentrations). NMR-based metabolomics is a potentially useful tool for biomarker identification of sepsis-induced AKI.

scholarly journals IGF-1 Deficiency Rescue and Intracellular Calcium Blockade Improves Survival and Corresponding Mechanisms in a Mouse Model of Acute Kidney Injury

2020 ◽  
Vol 21 (11) ◽  
pp. 4095
Author(s):  
Samiksha Wasnik ◽  
Xiaolei Tang ◽  
Hongzheng Bi ◽  
Amir Abdipour ◽  
Edmundo E. Carreon ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cell Injury ◽  
Combined Therapy ◽  
Kidney Injury ◽  
Cytosolic Calcium ◽  
Renal Tissue ◽  
Sublethal Dose ◽  
Gene Expression Response ◽  
Vascular Integrity

This study was undertaken to test two therapies for acute kidney injury (AKI) prevention, IGF-1, which is renal protective, and BTP-2, which is a calcium entry (SOCE) inhibitor. We utilized lipopolysaccharide (LPS) IP, as a systemic model of AKI and studied in five groups of animals. Three experiments showed that at 7 days: (1) LPS significantly reduced serum IGF-1 and intramuscular IGF-I in vivo gene therapy rescued this deficiency. (2) Next, at the 7-day time point, our combination therapy, compared to the untreated group, caused a significant increase in survival, which was noteworthy because all of the untreated animals died in 72 h. (3) The four pathways associated with inflammation, including (A) increase in cytosolic calcium, (B) elaboration of proinflammatory cytokines, (C) impairment of vascular integrity, and (D) cell injury, were adversely affected in renal tissue by LPS, using a sublethal dose of LPS. The expression of several genes was measured in each of the above pathways. The combined therapy of IGF-1 and BTP-2 caused a favorable gene expression response in all four pathways. Our current study was an AKI study, but these pathways are also involved in other types of severe inflammation, including sepsis, acute respiratory distress syndrome, and probably severe coronavirus infection.

scholarly journals Recent advances in renal hypoxia: insights from bench experiments and computer simulations

2016 ◽  
Vol 311 (1) ◽  
pp. F162-F165 ◽  
Author(s):  
Anita T. Layton
Keyword(s):  
Acute Kidney Injury ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Chronic Kidney Diseases ◽  
Hypoxic Injury ◽  
Complex Interactions ◽  
Recent Advances

The availability of oxygen in renal tissue is determined by the complex interactions among a host of processes, including renal blood flow, glomerular filtration, arterial-to-venous oxygen shunting, medullary architecture, Na+ transport, and oxygen consumption. When this delicate balance is disrupted, the kidney may become susceptible to hypoxic injury. Indeed, renal hypoxia has been implicated as one of the major causes of acute kidney injury and chronic kidney diseases. This review highlights recent advances in our understanding of renal hypoxia; some of these studies were published in response to a recent Call for Papers of this journal: Renal Hypoxia.

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