Histopathological changes in septic acute kidney injury in critically ill children: a cohort of post-mortem renal biopsies

Rameshkumar, Ramachandran; Krishnamurthy, Sriram; Ganesh, Rajesh Nachiappa; Mahadevan, Subramanian; Parameswaran, Narayanan; Satheesh, Ponnarmeni; Jain, Puneet

doi:10.1007/s10157-016-1343-z

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…Other well-known contributors for AKI as invasive mechanical ventilation and hemodynamic instability could not be evaluated as they were common denominators in our population (7,(29)(30)(31). To be noticed, we found 91.8% of ATI, 49.4% being moderate to severe, similar to other COVID-19 studies with 70.6%-100%; contrary to this, in patients who are septic, some reports account for 20%-30% of ATI (32,33). In this sense, the coparticipation of cytokine storm, nephrotoxic medication, and, possibly, a deeper and more prolonged hypoxia contributing to hypoperfusion could explain the higher incidence of ATI, without taking into account any direct viral-contributing action so far.…”

Section: Discussionsupporting

confidence: 90%

“…Clinical data are provided in Supplemental Table 1. Median age was 57 (50-67) years, 59 (69%) were men, body mass index was 29 (26)(27)(28)(29)(30)(31)(32)(33)(34)(35) kg/m 2 , 43 (51%) had diabetes, and 39 (46%) had chronic hypertension. All patients required invasive mechanical ventilation, 70 (82%) received vasopressors, 83 (98%) were treated with anticoagulants (43% prophylactic and 53% therapeutic dose), 56 (66%) were treated with steroids, and 30 (35%) received at least one potential nephrotoxic medication.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

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Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19)

Rivero

Merino-López

Olmedo

et al. 2021

CJASN

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Background and objectivesAKI in coronavirus disease 2019 (COVID-19) is associated with higher morbidity and mortality. The objective of this study was to identify the kidney histopathologic characteristics of deceased patients with diagnosis of COVID-19 and evaluate the association between biopsy findings and clinical variables, including AKI severity.Design, setting, participants, & measurementsOur multicenter, observational study of deceased patients with COVID-19 in three third-level centers in Mexico City evaluated postmortem kidney biopsy by light and electron microscopy analysis in all cases. Descriptive and association statistics were performed between the clinical and histologic variables.ResultsA total of 85 patients were included. Median age was 57 (49–66) years, 69% were men, body mass index was 29 (26–35) kg/m2, 51% had history of diabetes, 46% had history of hypertension, 98% received anticoagulation, 66% were on steroids, and 35% received at least one potential nephrotoxic medication. Severe AKI was present in 54% of patients. Biopsy findings included FSGS in 29%, diabetic nephropathy in 27%, and arteriosclerosis in 81%. Acute tubular injury grades 2–3 were observed in 49%. Histopathologic characteristics were not associated with severe AKI; however, pigment casts on the biopsy were associated with significantly lower probability of kidney function recovery (odds ratio, 0.07; 95% confidence interval, 0.01 to 0.77). The use of aminoglycosides/colistin, levels of C-reactive protein and serum albumin, previous use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, antivirals, nonsteroid anti-inflammatory drugs, and anticoagulants were associated with specific histopathologic findings.ConclusionsA high prevalence of chronic comorbidities was found on kidney biopsies. Nonrecovery from severe AKI was associated with the presence of pigmented casts. Inflammatory markers and medications were associated with specific histopathologic findings in patients dying from COVID-19.

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Section: Discussionsupporting

confidence: 90%

Section: Clinical Characteristicsmentioning

confidence: 99%

Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19)

Rivero

Merino-López

Olmedo

et al. 2021

CJASN

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“…Surprisingly, we found no association between low levels of antithrombin and kidney failure or underlying kidney disease. Other studies in adults have clearly shown that antithrombin may help limit acute kidney injury ( Yin et al., 2017 ; Kong et al., 2017 ; Wang et al., 2015 ; Rameshkumar et al., 2017 ).…”

Section: Discussionmentioning

confidence: 97%

Antithrombin deficiency is associated with mortality and impaired organ function in septic pediatric patients: a retrospective study

Niederwanger

Hell

Hofer

et al. 2018

PeerJ

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BackgroundSepsis remains a major problem in intensive care medicine. It is often accompanied by coagulopathies, leading to thrombotic occlusion of small vessels with subsequent organ damage and even fatal multi-organ failure. Prediction of the clinical course and outcome—especially in the heterogeneous group of pediatric patients—is difficult. Antithrombin, as an endogenous anticoagulant enzyme with anti-inflammatory properties, plays a central role in controling coagulation and infections. We investigated the relationship between antithrombin levels and organ failure as well as mortality in pediatric patients with sepsis.MethodsData from 164 patients under the age of 18, diagnosed with sepsis, were retrospectively reviewed. Antithrombin levels were recorded three days before to three days after peak C-reactive protein to correlate antithrombin levels with inflammatory activity. Using the concept of developmental haemostasis, patients were divided into groups <1 yr and ≥1 yr of age.ResultsIn both age groups, survivors had significantly higher levels of antithrombin than did deceased patients. An optimal threshold level for antithrombin was calculated by ROC analysis for survival: 41.5% (<1 yr) and 67.5% (≥1 yr). The mortality rate above this level was 3.3% (<1 yr) and 9.5% (≥1 yr), and below this level 41.7% (<1 yr) and 32.2% (≥1 yr); OR 18.8 (1.74 to 1005.02), p = 0.0047, and OR 4.46 (1.54 to 14.89), p = 0.003. In children <1 yr with antithrombin levels <41.5% the rate of respiratory failure (66.7%) was significantly higher than in patients with antithrombin levels above this threshold level (23.3%), OR 6.23 (1.23 to 37.81), p = 0.0132. In children ≥1 yr, both liver failure (20.3% vs 1.6%, OR 15.55 (2.16 to 685.01), p = 0.0008) and a dysfunctional intestinal tract (16.9% vs 4.8%, OR 4.04 (0.97 to 24.08), p = 0.0395) occurred more frequently above the antithrombin threshold level of 67.5%.ConclusionIn pediatric septic patients, significantly increased mortality and levels of organ failure were found below an age-dependent antithrombin threshold level. Antithrombin could be useful as a prognostic marker for survival and occurrence of organ failure in pediatric sepsis.

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“…Previous studies have demonstrated the occurrence of both tubular necrosis and apoptosis in sepsis-induced AKI (21,22). The study of Takasu et al presented histological evidence for a low incidence of tubular necrosis in sepsis, with a rare instance of apoptosis in kidney tissue as detected by staining for cleaved cytokeratin-18 (23).…”

Section: Discussionmentioning

confidence: 99%

RIPK3 promotes sepsis-induced acute kidney injury via mitochondrial dysfunction

et al. 2018

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Sepsis causes acute kidney injury (AKI) in critically ill patients, although the pathophysiology remains unclear. The receptor-interacting protein kinase-3 (RIPK3), a cardinal regulator of necroptosis, has recently been implicated in the pathogenesis of human disease. In mice subjected to polymicrobial sepsis, we demonstrate that RIPK3 promotes sepsis-induced AKI. Utilizing genetic deletion and biochemical approaches in vitro and in vivo, we identify a potentially novel pathway by which RIPK3 aggravates kidney tubular injury independently of the classical mixed lineage kinase domain-like protein-dependent (MLKL-dependent) necroptosis pathway. In kidney tubular epithelial cells, we show that RIPK3 promotes oxidative stress and mitochondrial dysfunction involving upregulation of NADPH oxidase-4 (NOX4) and inhibition of mitochondrial complex I and -III, and that RIPK3 and NOX4 are critical for kidney tubular injury in vivo. Furthermore, we demonstrate that RIPK3 is required for increased mitochondrial translocation of NOX4 in response to proinflammatory stimuli, by a mechanism involving protein-protein interactions. Finally, we observed elevated urinary and plasma RIPK3 levels in human patients with sepsis-induced AKI, representing potential markers of this condition. In conclusion, we identify a pathway by which RIPK3 promotes kidney tubular injury via mitochondrial dysfunction, independently of MLKL, which may represent a promising therapeutic target in sepsis-induced AKI.

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Histopathological changes in septic acute kidney injury in critically ill children: a cohort of post-mortem renal biopsies

Abstract: The most common renal histopathological change in septic AKI in critically ill children was normal histology followed by ATN.

Cited by 9 publications

References 27 publications

Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19)

Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19)

Antithrombin deficiency is associated with mortality and impaired organ function in septic pediatric patients: a retrospective study

RIPK3 promotes sepsis-induced acute kidney injury via mitochondrial dysfunction

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