Impaired angiotensin II type 1 receptor signaling contributes to sepsis-induced acute kidney injury

Leisman, Daniel E.; Fernandes, Tiago; Bijol, Vanesa; Abraham, Mabel; Lehman, Jake R.; Taylor, Matthew D.; Capone, Christine; Yaipan, Omar Y.; Bellomo, Rinaldo; Deutschman, Clifford S.

doi:10.1016/j.kint.2020.07.047

Cited by 41 publications

(46 citation statements)

References 53 publications

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“…Conditions associated with endothelial dysfunction, such as septic shock or cardiopulmonary bypass, can reduce ACE activity, decrease angiotensin II, and increase renin levels ( 5 , 6 ). Decreased expression of AT1R was also reported in sepsis-associated AKI ( 7 ). This hypothesis is supported by several findings in Küllmar and colleagues, including higher and more prolonged vasopressor requirements, high Δ-renin levels, and higher renin over aldosterone ratio in patients with AKI.…”

mentioning

confidence: 68%

The Yin and Yang of the Renin–Angiotensin–Aldosterone System in Acute Kidney Injury

Legrand¹,

Bokoch

2021

Am J Respir Crit Care Med

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mentioning

confidence: 68%

The Yin and Yang of the Renin–Angiotensin–Aldosterone System in Acute Kidney Injury

Legrand¹,

Bokoch

2021

Am J Respir Crit Care Med

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“…Similar to our findings, renin was significantly associated with mortality in the ATHOS-3 study [ 23 ]. This concept of deficient angiotensin II signaling has been further suggested in recent reports of sepsis-associated AKI [ 24 ]. Based on these conflicting reports of RAS over-activation throughout the traditional RAS axis [ 15 ], as well as those reviewed here suggesting incomplete activation in the traditional RAS axis, this may be an indication that different RAS endotypes exist in critical illness.…”

Section: Discussionmentioning

confidence: 91%

Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study

Flannery

Ortiz-Soriano

et al. 2021

Crit Care

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Background Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. Methods Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5–7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline. Results Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without. Conclusions In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.

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“…Therefore, we investigated the gene expression of AGTR1 in MP-PRECs from four different donors and established the absence of expression in MP-PRECs (data not shown). This, together with the fact that Leisman et al (55) recently showed that AGTR1 expression is mostly located at the site of mesangial and vascular smooth muscle cells, suggests that the endothelium does not express AGTR1 in the kidney.…”

Section: Discussionmentioning

confidence: 95%

Machine-perfused donor kidneys as a source of human renal endothelial cells

Lammerts

Lagendijk

Tiller

et al. 2021

American Journal of Physiology-Renal Physiology

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Renal endothelial cells (ECs) play crucial roles in vasorelaxation, ultrafiltration, and selective transport of electrolytes and water, but also in leakage of the glomerular filtration barrier and inflammatory processes like complement activation and leukocyte recruitment. In addition, they are target cells for both cellular and antibody mediated rejection in the transplanted kidney. In order to study the molecular and cellular processes underlying EC behavior in renal disease, well characterized primary renal ECs are indispensible. In this report we describe a straightforward procedure to isolate ECs from the perfusion fluid of human donor kidneys by a combination of negative selection of monocytes/macrophages, positive selection by CD31 Dynabeads and propagation in endothelial specific culture medium. Thus, we isolated and propagated renal ECs from 102 donor kidneys, representative of all blood groups and major HLA class I and II antigens. Obtained ECs were positive for CD31 and von Willebrand Factor, expressed other endothelial markers such as CD34, VEGFR-2, TIE2, and PV-1 to a variable extent, and were negative for monocyte marker CD14 and lymphatic endothelial marker podoplanin. HLA class II was either constitutively expressed or could be induced by IFN-γ. Furthermore, we showed the diagnostic value of this renal endothelial biobank in renal endothelial specific cross matching tests for HLA antibodies.

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Impaired angiotensin II type 1 receptor signaling contributes to sepsis-induced acute kidney injury

Cited by 41 publications

References 53 publications

The Yin and Yang of the Renin–Angiotensin–Aldosterone System in Acute Kidney Injury

The Yin and Yang of the Renin–Angiotensin–Aldosterone System in Acute Kidney Injury

Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study

Machine-perfused donor kidneys as a source of human renal endothelial cells

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