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Kidney tubules: intertubular, vascular, and glomerular cross-talk - PubMed

Review

Kidney tubules: intertubular, vascular, and glomerular cross-talk

David A Ferenbach et al. Curr Opin Nephrol Hypertens. 2016 May.

Abstract

Purpose of review: The kidney mediates the excretion or conservation of water and electrolytes in the face of changing fluid and salt intake and losses. To ultrafilter and reabsorb the exact quantities of free water and salts to maintain euvolemia a range of endocrine, paracrine, and hormonal signaling systems have evolved linking the tubules, capillaries, glomeruli, arterioles, and other intrinsic cells of the kidney. Our understanding of these systems remains incomplete.

Recent findings: Recent work has provided new insights into the workings of the communication pathways between tubular segments and the glomeruli and vasculature, with novel therapeutic agents in development. Particular progress has also been made in the visualization of tubuloglomerular feedback.

Summary: The review summarizes our current understanding of pathway functions in health and disease, as well as future therapeutic options to protect the healthy and injured kidney.

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Conflict of interest statement

Conflicts of interest

D.A.F. declares no conflicts of interest.

Figures

FIGURE 1
FIGURE 1

Sites of tubular nitric oxide generation, and its autocrine and paracrine effects. Nitric oxide is generated via endothelial (eNOS or NOS3), inducible (iNOS or NOS2), and neuronal (nNOS or NOS1) nitric oxide synthases throughout the tubule. It then exerts autocrine and paracrine effects on surrounding tubules, blood vessels, and glomeruli.

FIGURE 2
FIGURE 2

Distribution of dopamine producing cells and dopamine receptors within the tubular cells of the nephron. Dopamine is released from cells of the proximal convoluted tubule and exerts both paracrine effects and hormonal actions via interactions with different subtypes of dopamine receptors on different nephron segments and uptake by blood vessels.

FIGURE 3
FIGURE 3

Paracrine effects of the secretory phenotype seen in G2/M-arrested tubular epithelial cells. The proportion of tubular cells in the G2/M phase of the cell cycle increases in response to severe maladaptive or sustained renal injuries. These cells produce factors including connective tissue growth factor (CTGF) and TGF-β1. These exert paracrine effects on both neighboring tubular cells as well as interstitial and endothelial cells, and macrophage numbers and phenotypes. There is resultant deposition of collagen within the kidney, with the development of fibrosis. AKI, acute kidney injury; G2/M, Gap 2/mitosis (G2/M); TGF, transforming growth factor.

FIGURE 4
FIGURE 4

Tubuloglomerular feedback from the macula densa to the glomerulus. In response to altered distal flow and chloride delivery, cells of the macula densa initiate a signaling cascade, involving generation of molecules via cyclooxygenase 2, nitric oxide synthase, and ATP release (via metabolism to adenosine). These exert effects on extraglomerular mesangial cells and on the afferent arteriole – causing net constriction or dilatation and resultant changes in glomerular filtration rate.

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References

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