4.6 Review

Molecular mechanisms of kidney crosstalk with distant organs

Related references

Note: Only part of the references are listed.
Article Urology & Nephrology

Myeloid CCR2 Promotes Atherosclerosis after AKI

Anne M. Huesing et al.

Summary: The risk of cardiovascular events increases after renal ischemia-reperfusion (IR) injury. Leukocytes play a crucial role in the growth and instability of atherosclerotic plaques. This study established a model of enhanced remote atherosclerosis after renal IR injury and investigated the underlying inflammatory mechanisms.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2022)

Article Urology & Nephrology

Hypomorphic expression of parathyroid Bmal1 disrupts the internal parathyroid circadian clock and increases parathyroid cell proliferation in response to uremia

Soren Egstrand et al.

Summary: This study revealed the rhythmic expression of parathyroid signature genes and the essential role of the circadian clock system in regulating parathyroid cell function. Knockdown of the core clock gene Bmal1 disrupted the parathyroid circadian clock rhythmicity and resulted in downregulation of genes involved in mitochondrial function and ATP synthesis. Furthermore, the knockdown mice showed an increased proliferative response in the parathyroid gland when combined with uremia.

KIDNEY INTERNATIONAL (2022)

Article Multidisciplinary Sciences

Identification of kidney injury-released circulating osteopontin as causal agent of respiratory failure

Fatima Zohra Khamissi et al.

Summary: This study identifies circulating osteopontin (OPN) released from kidney tubule cells as a novel mediator in acute kidney injury (AKI)-induced acute lung injury (ALI). OPN triggers lung endothelial leakage, inflammation, and respiratory failure. The study also demonstrates the elevated levels of OPN in AKI patients and its correlation with kidney injury.

SCIENCE ADVANCES (2022)

Article Medicine, Research & Experimental

Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease

Nkiruka Arinze et al.

Summary: Chronic kidney disease (CKD) is an independent risk factor for peripheral artery disease (PAD). The role of uremic solutes retained in CKD patients in PAD is not well understood. This study reveals that tryptophan-derived uremic solutes inhibit beta-catenin, a key regulator of angiogenesis, in several cell types including endothelial cells. These solutes downregulate beta-catenin through the aryl hydrocarbon receptor (AHR). CKD mouse models show reduced beta-catenin and blood vessel density in ischemic limbs, which correlates with increased levels of uremic solutes and AHR activity. In a cohort of PAD patients, higher plasma levels of tryptophan metabolites and increased AHR-inducing activity in endothelial cells are associated with an increased risk of adverse limb events. Targeting the tryptophan metabolite/AHR/beta-catenin axis may provide new therapeutic strategies for PAD in CKD patients.

JOURNAL OF CLINICAL INVESTIGATION (2022)

Article Cell Biology

Indoxyl sulfate impairs angiogenesis via chronic aryl hydrocarbon receptor activation

Zachary R. Salyers et al.

Summary: This study revealed that uremic metabolites negatively impact endothelial cell function by activating the aryl hydrocarbon receptor, leading to impaired angiogenesis. Therapeutic aryl hydrocarbon receptor antagonists may have potential for improving angiogenesis in the context of chronic kidney disease and cardiovascular disease.

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY (2021)

Article Urology & Nephrology

Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury

Sho Hasegawa et al.

Summary: The study found that activating Adrb2 signaling in macrophages induces the expression of Tim3, contributing to anti-inflammatory alterations. In vivo, treatment with salbutamol can block LPS-induced systemic inflammation and protect against renal IRI, with protection being reduced in macrophage-specific Adrb2 cKO mice.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)

Article Multidisciplinary Sciences

Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis

Yuya Yoshida et al.

Summary: Dysfunction of the circadian clock is linked to cardiovascular disease pathogenesis. Even in the presence of high blood pressure and elevated levels of angiotensin II, Clk/Clk mice with chronic kidney disease show reduced cardiac inflammation and fibrosis. The monocytic expression of GPR68, induced by altered CLOCK activation, exacerbates heart inflammation and fibrosis under CKD conditions.

NATURE COMMUNICATIONS (2021)

Article Urology & Nephrology

The circadian clock is disrupted in mice with adenine-induced tubulointerstitial nephropathy

Hiroaki Motohashi et al.

KIDNEY INTERNATIONAL (2020)

Article Urology & Nephrology

Intestinal microbiota control acute kidney injury severity by immune modulation

Jihyun Yang et al.

KIDNEY INTERNATIONAL (2020)