Histamine in the kidneys: what is its role in renal pathophysiology?

Abstract

Starting with a role for histamine role in renal haemodynamics, evidence has accumulated, over time, suggesting a wider range of actions on renal function and this has renewed interest in the pathophysiological role of histamine in the kidney. Here we provide an up-to-date review of this topic. As the kidney expresses enzymes that synthesize and metabolise histamine, along with its receptors, all the components for histaminergic transmission are present in this tissue. The distribution of histamine receptors matches a wide range of effects. We address the questions of the redundancy of H 1 and H 2 receptors in renal haemodynamics, the complementary role of H 1 and H 4 receptors in renal filtration and reabsorption, and the dichotomy between local and neuronal H 1 and H 3 receptors. Experimental models of renal disease raise the possibility of new therapeutic approaches based on histamine. The effects of histamine on renal function are not yet fully understood and their elucidation is still ongoing. LINKED ARTICLES: This article is part of a themed section on New Uses for 21st Century. To view the other articles in this section visit

Histamine provides an original vista on cardiorenal syndrome

“…HDC activity in the aorta and in the kidney as reported in diabetes, hypertension, and in response to high shear stress may be relevant to CRS (10,11). Histamine concentrations measured in the mouse kidney are well above circulating levels despite a scarcity of resident mast cells (11). Glomeruli produce large amounts of histamine, and HDC is expressed in proximal tubule cells of mice as well as in the human kidney.…”

“…Importantly, in the absence of specific granules for storage, other myeloid cells distinct from mature mast cells or basophils as well as nonmyeloid cells display a high HDC enzymatic activity and low intracellular levels of histamine, which may suggest secretion immediately after synthesis (9). HDC activity in the aorta and in the kidney as reported in diabetes, hypertension, and in response to high shear stress may be relevant to CRS (10,11). Histamine concentrations measured in the mouse kidney are well above circulating levels despite a scarcity of resident mast cells (11).…”

“…Glomeruli produce large amounts of histamine, and HDC is expressed in proximal tubule cells of mice as well as in the human kidney. Renal HDC activity is high in diabetic rats and is also markedly up-regulated in the mouse kidney during pregnancy (11).…”

Challenges in the development and exploitation of new therapeutic options targeting the histaminergic system

“…Histamine and the H 4 receptor are commonly elevated in inflamed tissue, diabetic organs and cancer cells, offering wide clinical possibilities. These include common skin disorders, atopic dermatitis and psoriasis (H 4 receptor; Schaper‐Gerhardt, Rossbach, et al, 2020), diabetic nephropathies (H 1 , H 4 receptors; Grange et al, 2020), cancers (H 4 receptor as a target and marker; Massari, Nicoud, & Medina, 2018), neuropsychiatric and neurocognitive diseases (Provensi, Costa, et al, 2020; Provensi, Passani, et al, 2020), tic disorders (Pittenger, 2020) and chronic pain (Obara, et al, 2020). Sprinkled amongst the review articles, there are a series of original research papers which further highlight the potential of targeting the peripheral H 4 receptor for dermal (anti‐pruritic and anti‐inflammatory; Mommert, et al, 2020; Schaper‐Gerhardt, Wohlert, et al, 2020) and vestibular (Petremann, et al, 2020) disorders.…”

“…As well as these advanced programmes, several other indications are discussed in this section. Renewed interest in the pathophysiological role of histamine and, in particular, the H 4 receptor in the kidney is developed in this section, with particular regard to diabetic nephropathy (Grange et al, 2020). The controversial role of the histaminergic system in different neoplasias including gastric, colorectal, oesophageal, oral, pancreatic, liver, lung, skin, blood and breast cancers is discussed in detail, with the H 4 receptor again rising up as the most convincing candidate for targeting (Massari, et al, 2018).…”