Introduction:
Patients with chronic kidney disease (CKD) frequently experience gastrointestinal symptoms, particularly those pertaining to the upper gastrointestinal tract, which includes nausea, vomiting, abdominal discomfort, indigestion, early satiety, postprandial fullness, and constipation. Increased stomach weight, parietal cell density, and enterochromaffin-like (ECL) cell density were linked to chronic renal failure (CRF) with hypergastrinemia. Acid secretion and stomach mucosal blood flow are increased in chronic renal failure.
Renal insufficiency significantly increases the mucosal hyperemic and stomach acid secretory responses to pentagastrin. In addition to progressive azotemia (increase, or accumulation, of blood creatinine, various secondary waste products in the body, and nitrogenous wastes (BUN; typically ranging from 7 to 21 mg/dL)), hypertension, and proteinuria, the patient has histological alterations such as focal glomerulosclerosis (scar tissue in the kidney filtration unit) in chronic renal failure. The use of nonsteroidal anti-inflammatory medicines (NSAIDs) and Helicobacter pylori infection are the two main causes of peptic ulcer disease (PUD). The reason for PUD in people with Crohn's disease (CRF) is not an increased NSAID exposure; rather, Helicobacter pylori infection of the stomach mucosa is thought to be more common in CKD patients.
How Kidney and Gastrin Metabolism Interrelated?
The body produces more than 50 to 80 millimoles of metabolic acid compared to metabolic alkali. Renal excretion is the main method by which the body eliminates these acids. Large numbers of functional nephrons are lost gradually and irreversibly, leading to chronic renal failure. An accumulation of weak acids that are not being eliminated by the kidneys occurs in bodily fluids when renal function significantly diminishes. Furthermore, as a result of the lowered glomerular filtration rate, less phosphate and NH4+ are excreted, which lowers the quantity of bicarbonate that is added back to the bodily fluids. Thus, severe metabolic acidosis may be linked to persistent renal failure.
It is hypothesized that a higher incidence of gastrointestinal diseases related to acidity is linked to chronic kidney disease because the symptoms of those illnesses might lead to reduced nutritional intake or a refusal to eat, which can result in malnutrition and a worse prognosis; those disorders may be of serious concern. Several authors discovered that CKD patients had lower stomach acid pH levels. Researchers found that some individuals had hypersecretion of stomach acid, and some had hyposecretion. The other researchers' findings are unequivocal. This study was conducted to observe the basal stomach acid state in patients with chronic renal failure and to link gastric acid status with the various stages of chronic kidney disease. The findings of this study may contribute to improving the prognosis of individuals with chronic renal failure by changing their treatment regimen.
What Is Gastrin?
A peptide hormone called gastrin is important in controlling blood pressure and salt homeostasis. Dopamine interacts either directly or indirectly with other hormones that regulate blood pressure, such as gastrin, and is also involved in the control of salt balance and blood pressure. The objective of this research was to investigate the processes behind the relationship between gastrin and dopamine. Specifically, the hypothesis that renal dopamine production is increased in response to gastrin produced in the kidneys to maintain normal blood pressure levels was examined. It is demonstrated that gastrin increases renal dopamine synthesis in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively) by enhancing cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane.
The removal of gastrin from the circulation is not much aided by glomerular filtration, and only a little quantity of gastrin is eliminated by the urine. The extra-renal tissue capillary networks have a significant function in the breakdown of some or all molecular gastrin forms. An additional conclusion is that patients experiencing renal failure may have hypergastrinemia due to a combination of factors including decreased kidney gastrin catabolism and increased gastrin synthesis, which is mostly associated with hypochlohydria and secondary hyperparathyroidism.
In patients suffering from renal failure, the mechanism of the feedback connection between HCl and gastrin is weaker due to inhibition of gastrin acid secretion. Additionally, there is a permanent stimulation of G-cells, which leads to the development of hyperplasia, increased secretory activity, and hypergastrinemia. Although parietal cells are still able to respond to the highest stimulation, they become less sensitive to a persistently elevated serum gastrin concentration. Large, mostly physiologically inactive (big big gastrin, component I) molecular forms of gastrin become more concentrated in patients with renal failure, particularly in those with severe hypergastrinemia.
How Does Renal Influence the Gastrin Metabolism?
- Renal Dopamine: The kidney's production of dopamine is crucial for controlling blood pressure, water and electrolyte balance, and both. Ion transporter, channel, and pump activity are directly and indirectly inhibited by endogenous renal dopamine, which acts in an autocrine or paracrine fashion and partially through the regulation of protein expression. Dopamine's physiological effects are brought about by the occupancy of certain receptors that are expressed throughout the renal and nephron vasculature. The uptake of the dopamine precursor l-3,4-dihydroxyphenylalanine (l-DOPA) by renal proximal tubule cells and the activity of l-aromatic amino acid decarboxylase (l-AADC), the enzyme that converts l-DOPA into dopamine in humans and rodents, are required for the renal production of dopamine.
- Gastrin and Dopamine: Gastrin can raise sodium excretion in the kidneys via binding to the cholecystokinin 2 (CCK2) receptor, which is produced by the stomach and duodenum's G-cells. Renal tubules absorb more gastrin than other gut hormones released in reaction to food consumption. Gastrin has a role in the regular control of blood pressure and renal salt management through its interaction with dopamine. In fact, normotensive rats—rats that do not spontaneously develop hypertension—synergistically enhance sodium excretion through D1-like receptors, such as the D1 dopamine receptor and CCK2 receptor. Protein kinase C (PKC) is stimulated by the CCK2 receptor; PKC and Akt/PKB contribute to the insulin-induced increase in l-DOPA uptake into RPT cells.
Conclusion:
In conclusion, gastrin increases the production of dopamine by stimulating the RPTC's absorption of l-DOPA through the CCK2 receptor. The activation of LAT-1 in the plasma membrane may be the mechanism by which gastrin stimulates the absorption of l-DOPA. Compared to salt-resistant BALB/c mice, salt-sensitive C57Bl/6J mice have reduced RPT absorption of l-DOPA. When gastrin expression is specifically reduced in the kidney, BALB/c mice have a drop in urine dopamine and an increase in blood pressure. These findings underscore the significance of gastrin in inducing renal dopamine production, thus opening up new avenues for the management and prevention of hypertension.
