scholarly journals Metabolic Acidosis in Patients with CKD: Epidemiology, Pathogenesis, and Treatment

2021 ◽  
pp. 1-16
Author(s):  
Marcin Adamczak ◽  
Stanisław Surma

<b><i>Background:</i></b> Metabolic acidosis in CKD is diagnosed in patients with plasma or venous blood bicarbonate concentration lower than 22 mmol/L. Metabolic acidosis occurs in about 20% of patients with CKD. Metabolic acidosis may lead to dysfunction of many systems and organs as well as CKD progression. Currently, sodium bicarbonate is mainly used for pharmacological treatment of metabolic acidosis in patients with CKD. Veverimer is a new drug dedicated to treatment of metabolic acidosis in patients with CKD. Orally given veverimer binds hydrogen ions in the intestines and subsequently is excreted from the body with feces. Clinical studies have shown that veverimer is effective in increasing serum bicarbonate concentrations in CKD patients with metabolic acidosis. Here, we present review of the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients. <b><i>Summary:</i></b> Metabolic acidosis is common in patients with CKD and contributes to CKD progression and many complications, which worsen the prognosis in these patients. Currently, sodium bicarbonate is mainly used in metabolic acidosis treatment. The role of the new drug veverimer in the metabolic acidosis therapy needs further studies. <b><i>Key Message:</i></b> The aim of this review article is to summarize the current knowledge concerning the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients.

1981 ◽  
Vol 55 (2) ◽  
pp. 95-100 ◽  
Author(s):  
F. Hawking ◽  
Tinousi Jennings ◽  
F. J. Louis ◽  
E. Tuira

ABSTRACT1. Investigations were made of the effect of various procedures in raising or lowering the microfilaria count of Pacific type Wuchereria bancrofti in the peripheral blood.2. Raising the body temperature in the early morning was followed by a moderate fall in the counts. Breathing increased oxygen, or reduced oxygen (hypoxia) or increased carbon dioxide, or the ingestion of sodium bicarbonate produced no consistent and significant changes in the count. Ingestion of glucose (in one volunteer) was followed by a small rise in the count. Muscular exercise was followed by a fall in the count, which is interpreted as probably being a response to a lower concentration of oxygen in the venous blood returning to the lung.3. It has not been possible to identify the physiological components of the circadian rhythm of the human body which entrain the cycle of these microfilariae. Attempts to obtain evidence incriminating the stimuli described above have been unsuccessful.


2012 ◽  
Vol 302 (11) ◽  
pp. R1235-R1249 ◽  
Author(s):  
Sara Stridh ◽  
Fredrik Palm ◽  
Peter Hansell

The glycosaminoglycan (GAG) hyaluronan (HA) is recognized as an important structural component of the extracellular matrix, but it also interacts with cells during embryonic development, wound healing, inflammation, and cancer; i.e., important features in normal and pathological conditions. The specific physicochemical properties of HA enable a unique hydration capacity, and in the last decade it was revealed that in the interstitium of the renal medulla, where the HA content is very high, it changes rapidly depending on the body hydration status while the HA content of the cortex remains unchanged at very low amounts. The kidney, which regulates fluid balance, uses HA dynamically for the regulation of whole body fluid homeostasis. Renomedullary HA elevation occurs in response to hydration and during dehydration the opposite occurs. The HA-induced alterations in the physicochemical characteristics of the interstitial space affects fluid flux; i.e., reabsorption. Antidiuretic hormone, nitric oxide, angiotensin II, and prostaglandins are classical hormones/compounds involved in renal fluid handling and are important regulators of HA turnover during variations in hydration status. One major producer of HA in the kidney is the renomedullary interstitial cell, which displays receptors and/or synthesis enzymes for the hormones mentioned above. During several kidney disease states, such as ischemia-reperfusion injury, tubulointerstitial inflammation, renal transplant rejection, diabetes, and kidney stone formation, HA is upregulated, which contributes to an abnormal phenotype. In these situations, cytokines and other growth factors are important stimulators. The immunosuppressant agent cyclosporine A is nephrotoxic and induces HA accumulation, which could be involved in graft rejection and edema formation. The use of hyaluronidase to reduce pathologically overexpressed levels of tissue HA is a potential therapeutic tool since diuretics are less efficient in removing water bound to HA in the interstitium. Although the majority of data describing the role of HA originate from animal and cell studies, the available data from humans demonstrate that an upregulation of HA also occurs in diabetic kidneys, in transplant-rejected kidneys, and during acute tubular necrosis. This review summarizes the current knowledge regarding interstitial HA in the role of regulating kidney function during normal and pathological conditions. It encompasses mechanistic insights into the background of the heterogeneous intrarenal distribution of HA; i.e., late nephrogenesis, its regulation during variations in hydration status, and its involvement during several pathological conditions. Changes in hyaluronan synthases, hyaluronidases, and binding receptor expression are discussed in parallel.


Physiology ◽  
2018 ◽  
Vol 33 (4) ◽  
pp. 269-280 ◽  
Author(s):  
Nathalie Vergnolle ◽  
Carla Cirillo

The intestinal epithelial barrier is the largest exchange surface between the body and the external environment. Its functions are regulated by luminal, and also internal, components including the enteric nervous system. This review summarizes current knowledge about the role of the digestive “neuronal-glial-epithelial unit” on epithelial barrier function.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Dimitrios Velissaris ◽  
Vasilios Karamouzos ◽  
Nikolaos Ktenopoulos ◽  
Charalampos Pierrakos ◽  
Menelaos Karanikolas

Introduction. Sepsis and its consequences such as metabolic acidosis are resulting in increased mortality. Although correction of metabolic acidosis with sodium bicarbonate seems a reasonable approach, there is ongoing debate regarding the role of bicarbonates as a therapeutic option.Methods. We conducted a PubMed literature search in order to identify published literature related to the effects of sodium bicarbonate treatment on metabolic acidosis due to sepsis. The search included all articles published in English in the last 35 years.Results. There is ongoing debate regarding the use of bicarbonates for the treatment of acidosis in sepsis, but there is a trend towards not using bicarbonate in sepsis patients with arterial blood gaspH>7.15.Conclusions. Routine use of bicarbonate for treatment of severe acidemia and lactic acidosis due to sepsis is subject of controversy, and current opinion does not favor routine use of bicarbonates. However, available evidence is inconclusive, and more studies are required to determine the potential benefit, if any, of bicarbonate therapy in the sepsis patient with acidosis.


2020 ◽  
Author(s):  
Haider Abdul-Lateef Mousa

Background: Earthig is a contact with earth by several means that could cause influx of electron into the body with subsequent anti-inflammatory effect, immunity enhancement, anticoagulation, rising blood oxygenation, and possible antipyretic effect. All these effects of earthing might have a substantial role in the management of patients with COVID-19 infection without deleterious side effects of ordinary medications.Objective: to investigate the role of earthing in treatment and prevention of COVID-19 infection.Design: Observational studySetting: University of Basrah, College of Medicine, Iraq.Patients: The study included 59 cases with COVID-19 infection.Interventions: All patients conducted earthing through direct contact with earth or connecting apparatus for about 15 min-3 hours/day.Measurements and Main Results: The diagnosis was confirmed by PCR test with or without chest CT-scan. There was spectacular response in a severely ill patient who was unable to speak due to dyspnea with blood oxygen level 38% on continuous oxygen supply. On the second day of three hours daily earthing, his oxygen level raised to 95% with oxygen supply and 77% without oxygen supply. After 1-3 days of earthing, most patients revealed improvement of the following symptoms: fever, dyspnea, cough, weakness, headache, chest pain, taste and smell sense loss, anorexia, and body pain. Six people were in contact with COVID-19 patients that had performed preventive earthing. They contracted mild or short-lived illness although their household were severely affected.Conclusions: The outcome of patients with COVID-19 who had performed regular and sufficient earthing showing significant curing or preventive effects that more studies on larger sample size are advocated.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hiroyuki Yamakawa ◽  
Tomoko S. Kato ◽  
Jaeduk Yoshimura Noh ◽  
Shinsuke Yuasa ◽  
Akio Kawamura ◽  
...  

Thyroid hormones (THs) are synthesized in the thyroid gland, and they circulate in the blood to regulate cells, tissues, and organs in the body. In particular, they exert several effects on the cardiovascular system. It is well known that THs raise the heart rate and cardiac contractility, improve the systolic and diastolic function of the heart, and decrease systemic vascular resistance. In the past 30 years, some researchers have studied the molecular pathways that mediate the role of TH in the cardiovascular system, to better understand its mechanisms of action. Two types of mechanisms, which are genomic and non-genomic pathways, underlie the effects of THs on cardiomyocytes. In this review, we summarize the current knowledge of the action of THs in the cardiac function, the clinical manifestation and parameters of their hemodynamics, and treatment principles for patients with hyperthyroid- or hypothyroid-associated heart disease. We also describe the cardiovascular drugs that induce thyroid dysfunction and explain the mechanism underlying the thyroid toxicity of amiodarone, which is considered the most effective antiarrhythmic agent. Finally, we discuss the recent reports on the involvement of thyroid hormones in the regulation of myocardial regeneration and metabolism in the adult heart.


2020 ◽  
Vol 21 (23) ◽  
pp. 9165
Author(s):  
Marina Chulkina ◽  
Ellen J. Beswick ◽  
Irina V. Pinchuk

The gastrointestinal (GI) mucosa is among the most complex systems in the body. It has a diverse commensal microbiome challenged continuously by food and microbial components while delivering essential nutrients and defending against pathogens. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut mucosal homeostasis. Recent lessons from cancer immunotherapy point out the critical role of the B7 negative co-stimulator PD-L1 in mucosal homeostasis. In this review, we summarize the current knowledge supporting the critical role of PD-L1 in gastrointestinal mucosal tolerance and how abnormalities in its expression and signaling contribute to gut inflammation and cancers. Abnormal expression of PD-L1 and/or the PD-1/PD-L1 signaling pathways have been observed in the pathology of the GI tract. We also discuss the current gap in our knowledge with regards to PD-L1 signaling in the GI tract under homeostasis and pathology. Finally, we summarize the current understanding of how this pathway is currently targeted to develop novel therapeutic approaches.


2021 ◽  
Vol 22 (15) ◽  
pp. 7775
Author(s):  
Ana Paredes ◽  
Rocio Santos-Clemente ◽  
Mercedes Ricote

The heart is the first organ to acquire its physiological function during development, enabling it to supply the organism with oxygen and nutrients. Given this early commitment, cardiomyocytes were traditionally considered transcriptionally stable cells fully committed to contractile function. However, growing evidence suggests that the maintenance of cardiac function in health and disease depends on transcriptional and epigenetic regulation. Several studies have revealed that the complex transcriptional alterations underlying cardiovascular disease (CVD) manifestations such as myocardial infarction and hypertrophy is mediated by cardiac retinoid X receptors (RXR) and their partners. RXRs are members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors and drive essential biological processes such as ion handling, mitochondrial biogenesis, and glucose and lipid metabolism. RXRs are thus attractive molecular targets for the development of effective pharmacological strategies for CVD treatment and prevention. In this review, we summarize current knowledge of RXR partnership biology in cardiac homeostasis and disease, providing an up-to-date view of the molecular mechanisms and cellular pathways that sustain cardiomyocyte physiology.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1286
Author(s):  
Andreea Kui ◽  
Smaranda Buduru ◽  
Anca Labunet ◽  
Silvia Balhuc ◽  
Marius Negucioiu

Background and aims. Vitamin D is synthesized in the skin with the aid of ultraviolet-B radiation, playing a variety of roles in the body. Temporomandibular disorders (TMDs) are a group of pathological conditions involving the temporomandibular joints as well as the masticatory muscles and othersurrounding tissues. In the present narrative review, we investigated the potential role of vitamin D in the etiology of temporomandibular disorders in order todetermine whether the current knowledge supports 25-hidroxyvitamin D (25-OHD) supplementation in temporomandibular disorders associated with insufficient or deficient levels of vitamin D. Methods. A literature research was performed in PubMed, Scopus, Science Direct, and Google Scholar databases, and a total of 10 articles were included for analysis. Results.Among the observational studies published to date, investigating the role for vitamin D in the etiology of TMDs, six of them suggest that there is a connection between the two aspects. In this context, patients suffering from TMD, with deficient levels of vitamin D (<30 ng/mL), are most likely to benefit from supplementation, whereas individuals with vitamin D level >50ng/mL probably have little benefit from supplementation.Conclusion.Vitamin D might be a safe, simple, and potentially beneficial way to prevent TMDs or to reduce pain; however, more randomized and placebo-controlled trials are required before any firm conclusions can be drawn.


2020 ◽  
Vol 17 (3) ◽  
pp. 330-335
Author(s):  
L. K. Moshetova ◽  
O. I. Abramova ◽  
K. I. Turkina ◽  
M. K. Nurbekov ◽  
O. P. Dmitrenko ◽  
...  

Visual impairment in elderly people is a serious problem that significantly affects the quality of life of millions people around the world. The magnitude of this problem is becoming increasingly apparent as the population ages and the number of older people increases. Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide and the main cause of vision loss in people over 60 years. It is expected that AMD will affect about 288 million people by 2040. AMD is a multifactorial disease with a progressive course. The arised dystrophic changes in the retina cannot be reversed by any of the known treatment methods. A lot of research and effort has already been invested in identifying various biomarkers for predicting the incidence rate, identifying people at risk, finding out the pathogenetic mechanisms of this disease, and finding effective methods of treatment and prevention.Aging is the basis of pathological changes that occur during AMD. Aging biomarkers are measurable vital signs that qualitatively and quantitatively change with the age of the body. DNA methylation is a molecular mechanism that is a potential biomarker of aging. Sirtuins indirectly participate in this process, regulating the activity of the DNMT1 enzyme. The article discusses current knowledge of the mechanisms underlying the action of sirtuins (Sirtuins / SIRT), with an emphasis on SIRT1. Analysis of the pathophysiological action of sirtuins can affect the prevention and treatment of pathological eye changes associated with AMD. The article provides literature sources containing the results of studies of the effect of SIRT1 as a marker of aging in body tissues. SIRT1 is an attractive candidate for developing therapeutic strategies preventing early eye aging, in particular, age-associated diseases such as AMD The impact on the genetic mechanisms of this disease is a promising direction in treatment.


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