Acute hemolytic anemia and acute kidney injury induced by non-high-dose ascorbic acid in a Child with glucose-6-phosphate dehydrogenase deficiency

A 77-year-old man was admitted with severe acute kidney injury and nephrotic syndrome. He was started on eltrombopag for chronic idiopathic thrombocytopenic purpura 6 weeks earlier. An ultrasound of the kidneys was normal and an auto-antibody screen was negative. The use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient’s development of acute renal failure and eltrombopag therapy. Literature review identified only one other case of nephrotic syndrome and acute kidney injury associated with eltrombopag therapy in which a kidney biopsy revealed focal segmental glomerulosclerosis. Due to the challenges faced during the prevailing SARS-CoV-2 pandemic and persistent low platelet counts a renal biopsy was not undertaken. On stopping eltrombopag, the patients renal function stabilised and he successfully went into remission following treatment with high dose corticosteroids and diuretics. This report of a serious case of reversible renal failure and nephrotic syndrome after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before its commencement for future use.

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A pharmacologically-based approach to high dose methotrexate administration to investigate nephrotoxicity and acute kidney injury biomarkers in children and adolescents with newly diagnosed osteosarcoma

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04248-8 ◽

2021 ◽

Author(s):

Elizabeth Fox ◽

Christine Busch ◽

Alexander DeBernardo ◽

Blair Segers ◽

Joseph Gottschalk ◽

...

Keyword(s):

Acute Kidney Injury ◽

Children And Adolescents ◽

Kidney Injury ◽

High Dose ◽

High Dose Methotrexate ◽

Newly Diagnosed ◽

Dose Methotrexate

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Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2104347118 ◽

2021 ◽

Vol 118 (37) ◽

pp. e2104347118

Author(s):

Ravi Shankar Keshari ◽

Narcis Ioan Popescu ◽

Robert Silasi ◽

Girija Regmi ◽

Cristina Lupu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hemolytic Anemia ◽

Complement Activation ◽

Inflammatory Responses ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Multiple Organ ◽

Immune Recognition ◽

Gram Positive ◽

Terminal Complement

Late-stage anthrax infections are characterized by dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to extreme bacteremia, sepsis, multiple organ failure, and, ultimately, death. Despite the bacterium being nonhemolytic, some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS) through unknown mechanisms. We recapitulated the pathology in baboons challenged with cell wall peptidoglycan (PGN), a polymeric, pathogen-associated molecular pattern responsible for the hemostatic dysregulation in anthrax sepsis. Similar to aHUS anthrax patients, PGN induces an initial hematocrit elevation followed by progressive hemolytic anemia and associated renal failure. Etiologically, PGN induces erythrolysis through direct excessive activation of all three complement pathways. Blunting terminal complement activation with a C5 neutralizing peptide prevented the progressive deposition of membrane attack complexes on red blood cells (RBC) and subsequent intravascular hemolysis, heme cytotoxicity, and acute kidney injury. Importantly, C5 neutralization did not prevent immune recognition of PGN and shifted the systemic inflammatory responses, consistent with improved survival in sepsis. Whereas PGN-induced hemostatic dysregulation was unchanged, C5 inhibition augmented fibrinolysis and improved the thromboischemic resolution. Overall, our study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and likely other gram-positive infections in which PGN is abundantly represented. Neutralization of terminal complement reactions reduces the hemolytic uremic pathology induced by PGN and could alleviate heme cytotoxicity and its associated kidney failure in gram-positive infections.

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Concentration of meropenem in patients with sepsis and acute kidney injury before and after initiation of continuous renal replacement therapy: a prospective observational trial

Pharmacological Reports ◽

10.1007/s43440-019-00056-3 ◽

2020 ◽

Vol 72 (1) ◽

pp. 147-155 ◽

Cited By ~ 1

Author(s):

Ilona Nowak-Kózka ◽

Kamil J. Polok ◽

Jacek Górka ◽

Jakub Fronczek ◽

Anna Gielicz ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Kidney Injury ◽

Regional Citrate Anticoagulation ◽

High Dose ◽

Prolonged Infusion ◽

Time Points ◽

Drug Concentrations ◽

Before And After

Abstract Background The effect of renal replacement therapy on drug concentrations in patients with sepsis has not been fully elucidated because the pharmacokinetic properties of many antimicrobials are influenced by both pathophysiological and treatment-related factors. The aim of this study was to determine meropenem concentrations in patients with sepsis before and after the initiation of continuous venovenous hemodialysis with regional citrate anticoagulation (RCA-CVVHD). Methods The study included 15 critically ill patients undergoing RCA-CVVHD due to sepsis-induced acute kidney injury. All participants received 2 g of meropenem every 8 h in a prolonged infusion lasting 3 h. Meropenem concentrations were measured in blood plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Blood samples were obtained at six-time points prior to and at six-time points after introducing RCA-CVVHD. Results The median APACHE IV and SOFA scores on admission were 118 points (interquartile range [IQR] 97–134 points) and 19.5 points (IQR 18–21 points), respectively. There were no significant differences in the plasma concentrations of meropenem measured directly before RCA-CVVHD and during the first 450 min of the procedure. The drug concentration reached its peak 2 h after initiating the infusion and then steadily declined. Conclusions The concentration of high-dose meropenem (2 g every 8 h) administered in a prolonged infusion was similar before and after the introduction of RCA-CVVHD in patients with sepsis who developed acute kidney injury.

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Acute kidney injury following prophylactic flucloxacillin and gentamicin in primary hip and knee arthroplasty

Clinical Kidney Journal ◽

10.1093/ckj/sfaa059 ◽

2020 ◽

Author(s):

Judi Graham ◽

Emma Borthwick ◽

Christopher Hill ◽

Janine Blaney ◽

Nicola Gallagher ◽

...

Keyword(s):

Acute Kidney Injury ◽

Knee Arthroplasty ◽

Prophylactic Antibiotic ◽

Kidney Injury ◽

Binary Logistic Regression ◽

Surgical Site Infections ◽

Ideal Body Weight ◽

High Dose ◽

Binary Logistic Regression Model ◽

Hip And Knee Arthroplasty

Abstract Background Following concerns regarding the emergence of Clostridium difficile infection in 2010, we changed antibiotic prophylaxis in patients undergoing primary hip and knee arthroplasty from cefuroxime to flucloxacillin and single-dose (SD) gentamicin. A subsequent perceived increase in the incidence of post-operative acute kidney injury (AKI) led us to evaluate the AKI incidence between different prophylactic antibiotic regimes used at our centre. Methods We examined the incidence of AKI as defined by Kidney Disease: Improving Global Outcomes criteria in 1588 patients undergoing primary hip or knee arthroplasty from January 2010 to January 2015. Patients received the following prophylactic antibiotic regimes: 8 g flucloxacillin in four divided doses and SD gentamicin 1.5 mg/kg ideal body weight (IBW; maximum dose 120 mg; n = 400), 8 g flucloxacillin alone in four divided doses (n = 400), SD cefuroxime (n = 400), triple-dose (TD) cefuroxime (n = 188) and teicoplanin with SD gentamicin 1.5 mg/kg IBW (n = 200). Results The incidence of AKI was as follows: flucloxacillin and gentamicin (13%); flucloxacillin alone (8.5%); SD cefuroxime (2%); TD cefuroxime (0.5%); and teicoplanin and gentamicin (3%). Of the six patients who developed Stage 3 AKI, all were in the flucloxacillin and gentamicin group. The odds ratio for the development of AKI derived from a binary logistic regression model was highest in the flucloxacillin and gentamicin group [7.79 (95% confidence interval 3.54–17.14), P < 0.0001]. Conclusions Our findings suggest that the use of prophylactic high-dose flucloxacillin and gentamicin should be used with caution in patients undergoing primary hip or knee arthroplasty without a clear advantage in reducing surgical site infections given the association with increased rates of AKI.

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