Molecular mechanisms of trauma-induced acute kidney injury: Inflammatory and metabolic insights from animal models

Burmeister, David M.; Gómez, Belinda I.; Dubick, Michael A.

doi:10.1016/j.bbadis.2017.04.011

Cited by 36 publications

(22 citation statements)

References 136 publications

(201 reference statements)

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“…AKI is also independently associated with increased mortality in thermal injury [ 5 – 7 ]. Associated problems of AKI include retention of blood urea nitrogen (BUN), volume overload, reduced antioxidant status, altered immunologic responses, and mitochondrial damage within the kidney [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Enteral resuscitation with oral rehydration solution to reduce acute kidney injury in burn victims: Evidence from a porcine model

et al. 2018

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Intravenous (IV) resuscitation of burn patients has greatly improved outcomes and become a cornerstone of modern burn care. However, the heavy fluids and vascular access required may not be feasible in austere environments, mass casualty, or delayed transport scenarios. Enteral resuscitation has been proposed for these situations; we sought to examine the effectiveness of this strategy on improving burn-induced kidney injury. Anesthetized Yorkshire swine sustaining 40% TBSA full-thickness contact burns were randomized to three groups (n = 6/group): fluid deprivation, ad libitum water access, or 70 mL/kg/d Oral Rehydration Salt solution (ORS). Urine and blood were collected at baseline (BL), 6, 12, 24, 32, and 48h post-burn, at which point tissue was harvested and CT angiography performed. Although fluid consumption by ad libitum and ORS groups were matched (132±54mL/kg versus 120±24mL/kg, respectively), ORS intake increased urine output compared with water and no water (47.3±9.0 mL/kg versus 16.1±2.5 mL/kg, and 24.5±1.7 mL/kg respectively). Plasma creatinine peaked 6h following burn (1.67±0.07mg/dL) in all animals, but at 48h was comparable to BL in animals receiving water (1.23±0.06mg/dL) and ORS (1.30±0.09mg/dL), but not fluid deprived animals (1.56±0.05mg/dL) (P<0.05). Circulating levels of blood urea nitrogen steadily increased, but also decreased by 48h in animals receiving enteral fluids (P<0.05). Water deprivation reduced renal artery diameter (-1.4±0.17mm), whereas resuscitation with water (-0.44±0.14 mm) or ORS maintained it (-0.63±0.20 mm;P< 0.02). Circulating cytokines IL-1β, IL-6, IFNγ, and GM-CSF were moderately elevated in the fluid-deprived group. Taken together, the data suggest that enteral resuscitation with ORS rescues kidney function following burn injury. Incorporating enteral fluids may improve outcomes in resource-poor environments and possibly reduce IV fluid requirements to prevent co-morbidities associated with over-resuscitation. Studies into different volumes/types of enteral fluids are warranted. While ORS has saved many lives in cholera-associated dehydration, it should be investigated further for use in burn patients.

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Section: Introductionmentioning

confidence: 99%

Enteral resuscitation with oral rehydration solution to reduce acute kidney injury in burn victims: Evidence from a porcine model

et al. 2018

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“…Separately, acute kidney injury (AKI) disrupts the kidneys' blood filtering function and increases mortality, hospital length of stay, and hospital costs ( 7 ). Molecular mechanisms driving AKI have also been informed by a variety of animal models from chemical induction to trauma ( 8 , 9 ). However, there remains a growing need to address the lack of effective treatments for AKI.…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Multipotent CD24+ Cells From the Renal Papilla of Swine

et al. 2018

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Over 100,000 patients in the United States are currently waiting for a kidney transplant. With just over 10,000 cadaveric kidneys transplanted annually, it is of the utmost importance to optimize kidney viability upon transplantation. One exciting avenue may be xenotransplantation, which has rejuvenated interest after advanced gene editing techniques have been successfully used in swine. Simultaneously, acute kidney injury (AKI) is associated with high morbidity and mortality and currently lacks effective treatment. Animal models have been used extensively to address both of these issues, with recent emphasis on renal progenitor cells (RPCs). Due to anatomical similarities to humans we aimed to examine progenitor cells from the renal papillae of swine kidneys. To do this, RPCs were dissected from the renal papillae of healthy swine. Cell surface marker expression, proliferation, and differentiation of the RPCs were tested in vitro. Additionally, a mixed lymphocyte reaction was performed to examine immunomodulatory properties. RPCs displayed spindle shaped morphology with limited self-renewing capacity. Isolated RPCs were positive for CD24 and CD133 at early passages, but lost expression with subsequent passaging. Similarly, RPCs displayed myogenic, osteogenic, and adipogenic differentiation capacities at passage 2, but largely lost this by passage 6. Lastly, direct contact of RPCs with human lymphocytes increased release of IL6 and IL8. Taken together, RPCs from the papilla of porcine kidneys display transient stem cell properties that are lost with passaging, and either represent multiple types of progenitor cells, or a multipotent progenitor population. In instances of ischemic insult, augmentation of/with RPCs may potentiate regenerative properties of the kidney. While the use of swine for transplantation and ischemia studies confers obvious advantages, the populations of different progenitor cell populations within pig kidneys warrants further investigation. Ultimately, while gene editing techniques enhance the potential for xenotransplantation of organs or cells, the ultimate success of this strategy may be determined by the (dis)similarities of RPCs from different species.

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“…(F) Dissection of the right kidney to expose cyst wall TA B L E 1 Serum Biochemistry Differences in Animals with and without Cysts. Serum was collected immediately after CT.Values of blood urea nitrogen, creatinine, albumin, total protein, glucose, and WBCs in the blood were not different between animals with cysts and those without (normal) and all values were within normal range (P ≥ 24).…”

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confidence: 99%

“…Yorkshire swine are often used for various research models including xenotransplantation, hemorrhage, and burn. At the United States Army Institute of Surgical Research, trauma studies often examine organ dysfunction (including acute kidney injury)24 and animals frequently undergo postmortem evaluation of organs following a research study. Anecdotally, renal cysts have been reported, with not much information on how they may affect kidney function.…”

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confidence: 99%

A 30% incidence of renal cysts with varying sizes and densities in biomedical research swine is not associated with renal dysfunction

Gómez

Little

Leon

et al. 2020

Anim Models and Exp Med

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Background: Renal cystic disease arising from various etiologies results in fluid-filled cavities within the kidneys. Moreover, preexisting renal dysfunction has been shown to exacerbate multiple pathologies. While swine bred for biomedical research are often clinically inspected for illness/parasites, more advanced diagnostics may aid in uncovering underlying renal abnormalities. Methods: Computed tomography was performed in 54 female prepubertal Yorkshire swine to characterize renal cysts; urine and blood chemistry, and histology of cysts were also performed. Results: Digital reconstruction of right and left kidneys demonstrated that roughly one-third of the animals (17/54; 31%) had one or more renal cyst. Circulating biomarkers of renal function were not different between animals that had cysts and those that did not. Alternatively, urinary glucose (P = .03) was higher and sodium (P = .07) tended to be lower in animals with cysts compared to animals without, with no differences in protein (P = .14) or potassium (P = .20). Aspiration of cystic fluid was feasible in two animals, which revealed that the cystic fluid urea nitrogen (97.6 ± 28.7 vs 911.3 ± 468.2 mg/dL), potassium (29.8 ± 14.4 vs 148.2 ± 24.85 mmol/L), uric acid (2.55 ± 1.35 vs 11.4 ± 5.65 mg/dL), and creatinine (60.34 ± 17.26 vs 268.99 ± 95.79 mg/dL) were much lower than in the urine. Histology demonstrated a cyst that markedly compresses the adjacent cortex and is lined by a single layer of flattened epithelium, bounded by fibrous connective tissue which extends into the parenchyma. There is tubular atrophy and loss in these areas. Conclusion: This study provides valuable insight for future studies focusing on kidney function in swine bred for biomedical research.

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Molecular mechanisms of trauma-induced acute kidney injury: Inflammatory and metabolic insights from animal models

Cited by 36 publications

References 136 publications

Enteral resuscitation with oral rehydration solution to reduce acute kidney injury in burn victims: Evidence from a porcine model

Enteral resuscitation with oral rehydration solution to reduce acute kidney injury in burn victims: Evidence from a porcine model

Isolation and Characterization of Multipotent CD24+ Cells From the Renal Papilla of Swine

A 30% incidence of renal cysts with varying sizes and densities in biomedical research swine is not associated with renal dysfunction

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