Regulation of Renal Function by the Gastrointestinal Tract: Potential Role of Gut-Derived Peptides and Hormones

Abstract

The concept of a regulatory link between the gastrointestinal tract and kidneys is not new. The idea that dietary intake and composition can affect renal function is perhaps self-evident, but defining this relationship, especially in terms of sensors and effectors, is proving more difficult. That the gastrointestinal tract can exert some control over renal function was strengthened by the early observation that oral ingestion of a sodium chloride load has a greater natriuretic effect than when the same amount is given intravenously. This effect was subsequently shown to be independent of changes in aldosterone and atrial natriuretic peptide, although not necessarily angiotensin-II. However, the nature of any intestinal natriuretic peptide remains uncertain, despite suggestions that various gut-derived hormones, including guanylin and uroguanylin, may be involved. There is also an emerging concept of gastrointestinal taste and taste-like receptor mechanisms present throughout the gastrointestinal tract, which may govern the excretion of other key electrolytes, including potassium and phosphate. The evidence for gut sensors of nutrients such as proteins, amino acids, glucose, and acid is now becoming more established. Thus, we can anticipate the existence and eventual characterization of several gut ion sensors.

Gut sensing of dietary K+ intake increases renal K+ excretion

“…There are many gut peptides and hormones released in response to intake of dietary nutrients and ions that affect renal functions (19). In the present study, we examined whether there are hormones or kaliuretic substances released from the gut in response to dietary K ϩ .…”

“…There is ample evidence for interactions between the gastrointestinal tract and the kidney (19). There are many gut peptides and hormones released in response to intake of dietary nutrients and ions that affect renal functions (19).…”

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila

“…Abnormal fluid regulation has also been described in mice lacking VIP or PACAP (40,42,43), so it will be of interest to establish if PDF signaling has related in vivo roles in flies. The presence of VIP/PACAP immunoreactivity in neural fibers of the lower urinary tract of mammals suggests a local, transmitter-like action on the excretory muscle receptors (12), and VIP is generally believed to act as a local neurotransmitter rather than as a circulating hormone (44,45). However, systemic effects of gut-derived VIP cannot be ruled out.…”

“…The directionality of this endocrine signal from the gut to the renal system is unexpected and may be of relevance to mammals, where functional links between the digestive and excretory systems are well established with regard to absorption and secretion, and evidence suggests that communication between the two systems might facilitate their concerted action (44). An enterorenal axis, whereby unidentified gut-derived signals affect kidney function ;;MyoIA-GAL4/+ (red, n = 6) and PdfR…”

Gut hormones and gut microbiota: implications for kidney function and hypertension

“…37,44 Indeed, high intake and intestinal absorption of sodium contribute to development of hypertension. The sodium-proton exchanger subtype 3 (NHE3) is an important mediator of sodium absorption in the gut.…”