Regulation Of Acid-base Balance Research Articles

Role of Kir5.1 (Kcnj16) Channels in Regulating Renal Ammonia Metabolism during Metabolic Acidosis in Dahl Salt-Sensitive Rats

Maintaining acid-base homeostasis is critical for normal physiological function. The kidneys are essential for regulating acid-base homeostasis through maintaining systemic bicarbonate concentration. Chronic metabolic acidosis is an independent risk factor for chronic kidney diseases. Renal inwardly rectifying potassium channel Kir5.1 plays an essential role in maintaining resting membrane potential. Patients with loss-of-function mutations in KCNJ16 gene, which encodes Kir5.1, reveal tubulopathy with hypokalemia, salt wasting, and hearing loss. Importantly, these mutations also disrupt acid-base balance, particularly causing metabolic acidosis. This study aimed to use Dahl salt-sensitive rats with a knockout of the Kcnj16 gene (SSKcnj16-/-) to investigate how the deletion of Kir5.1 affects the regulation of acid-base balance in salt-sensitive hypertension. Results indicated that SSKcnj16-/- rats displayed metabolic acidosis under a normal salt (NS) diet. Further analysis using RNA-Sequncing and Western blotting showed unchanged expression of proteins responsible for ammonia metabolism in the kidney of SSKcnj16-/- rats despite observed acidosis. However, there was a significant increase in the expression of bicarbonate transporter NBCe1 while a significant decrease in pendrin. In conclusion, the current study demonstrated that the loss of Kir5.1 impairs the sensitivity of ammonia metabolism in the kidney in response to metabolic acidosis, which provides mechanistic insights into developing potential therapeutics for conditions involving hypokalemia and acid-base abnormalities.

Origins and molecular mechanisms underlying renal vascular development.

Kidneys play a crucial role in maintaining homeostasis within the body, and this function is intricately linked to the vascular structures within them. For vascular cells within the kidney to mature and perform their functions effectively, it is imperative that there is a meticulous and well-coordinated spatial alignment between the nephrons and the intricate network of blood vessels within the organ. This spatial arrangement ensures efficient filtration of blood and regulation of the electrolyte balance, blood pressure, and fluid levels. Additionally, the kidneys play a vital role in the regulation of acid-base balance and the production of hormones involved in erythropoiesis and blood pressure regulation. Thus, the close interaction between the vascular system and the kidney's structural organization is essential for maintaining overall physiological balance and health. This article focuses on the vascular development of the kidneys, summarizing the current understanding of the origin and formation of the renal vasculature, and the crucial molecules involved. By elucidating the cellular and molecular mechanisms governing renal vascular development, this article aims to promote advancements in renal regenerative medicine and provide potential avenues for therapeutic interventions to address kidney disease.

Regulation of renal acid-base balance by Epac isoforms in proximal tubule and collecting duct

Proper regulation of acid-base homeostasis has utmost significance for well-being and survival of the living organisms. Up to 50% of emergency room patients have notable disturbances in pH and associated morbific manifestations, which impedes effective treatment. Kidneys play a central role in regulation of acid-base balance by reabsorbing HCO3− via NHE-3 in the proximal tubule (PT) and secreting H+ via V-ATPase pump by the intercalated cells of collecting duct (CD). Exchange proteins directly activated by cAMP (Epac) are most prominently expressed in the proximal tubule and collecting ducts, the sites critical for acid-base transport in the renal tubule. However, the significance and physiological relevance of Epac isoforms (Epac1 and Epac2) for controlling HCO3− reabsorption and H+ secretion and by extension, the systemic pH regulation is not known. Here, we used transgenic mouse models lacking both or individual Epac1 and Epac2 isoforms to examine the systemic adaptation to acid-base insults and to inquire on the perturbed molecular signaling mechanisms and end-effectors in freshly isolated split-opened PTs and CDs using biochemical and fluorescent imaging tools. Deletion of Epac1&2 caused a dramatic decrease in NHE-3 protein levels in an additive manner. Moreover, we detected a marked redistribution of NHE-3 to the base of brush border in proximal tubule cells rendering its inactivation. Consistently, NHE-3 activity was more than 70% decreased upon Epac1&2 deletion, as was assessed by a rate of recovery after intracellular acidification in freshly isolated split-opened PTs. Furthermore, V-ATPase activity was similarly decreased in A-type of intercalated cells in freshly isolated CDs despite compensatory accumulation on the apical side, as monitored with confocal microscopy in cortical and medullary kidney sections of the knockout. In unstressed conditions, Epac1&2 deletion did not affect arterial pH and HCO3− levels, while urinary pH was significantly reduced. Dietary acid load (280 mM NH4Cl in drinking water for 3 days) unmasked severe hyperchloremic metabolic acidosis with pH 7.17±0.01 and HCO3− 14.5±0.6 mM and impaired urinary acidification. Deletion of Epac2 alone recapitulated the phenotype of double knockout, whereas Epac1−/− mice did not demonstrate notable deficiencies in response to dietary acid load. Overall, we concluded that Epac signaling plays a major role in urinary acidification with the dominant contribution of Epac2 isoform by regulating acid-base transport in both proximal tubule (via NHE-3) and the collecting duct (via V-ATPase). Epac1&2 and Epac2 deletion of impairs renal adaptation to the acid load resulting in severe metabolic acidosis. This research was supported by NIH-NIDDK DK117865, DK119170, AHA EIA35260097 (to O. Pochynyuk) and AHA-23POST1020372 (to K. Pyrshev). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Role of the Endocrine System in the Regulation of Acid-Base Balance by the Kidney and the Progression of Chronic Kidney Disease.

Systemic acid-base status is primarily determined by the interplay of net acid production (NEAP) arising from metabolism of ingested food stuffs, buffering of NEAP in tissues, generation of bicarbonate by the kidney, and capture of any bicarbonate filtered by the kidney. In chronic kidney disease (CKD), acid retention may occur when dietary acid production is not balanced by bicarbonate generation by the diseased kidney. Hormones including aldosterone, angiotensin II, endothelin, PTH, glucocorticoids, insulin, thyroid hormone, and growth hormone can affect acid-base balance in different ways. The levels of some hormones such as aldosterone, angiotensin II and endothelin are increased with acid accumulation and contribute to an adaptive increase in renal acid excretion and bicarbonate generation. However, the persistent elevated levels of these hormones can damage the kidney and accelerate progression of CKD. Measures to slow the progression of CKD have included administration of medications which inhibit the production or action of deleterious hormones. However, since metabolic acidosis accompanying CKD stimulates the secretion of several of these hormones, treatment of CKD should also include administration of base to correct the metabolic acidosis.

Does sodium bicarbonate based extra-cellular buffering support reduce high intensity exercise-induced fatigue and enhance short-term recovery assessed by selected blood biochemical indices?

Exercise-induced metabolic processes induce muscle acidification which contributes to a reduction in the ability to perform repeated efforts. Alkalizing agents such as sodium bicarbonate (NaHCO3) prevent large blood pH changes, however, there is no evidence on whether regulation of acid-base balance may also support whole body homeostasis monitored through heamatological and biochemical blood markers in a dose-dependent manner. Thirty Cross-Fit-trained participants were studied in a randomized, multi cross-over, placebo (PLA)-controlled double-blind manner in which they performed a control session (CTRL, without supplementation), three NaHCO3 visits (three different doses) and PLA (sodium chloride in an equimolar amount of sodium as NaHCO3). Each visit consisted of two 30-s Wingate tests separated by CrossFit-specific benchmarks (Wall Balls and Burpees - both performed for 3 min). Blood samples were collected at rest, immediately post-exercise and after 45 min recovery. Significant differences between visits appeared for blood pH, percentage of lymphocytes and granulocytes, red blood cells count and haemoglobin concentration at post-exercise and 45-min recovery, and for white blood cells count, percentage of monocytes, concentration of magnesium and creatinine at 45-min recovery. Most of the observed differences for heamatological and biochemical markers were significant compared to CTRL, but not different after PLA. NaHCO3 supplementation compared to PLA did not significantly affect exercise or recovery shifts in studied blood indicators. However, the changes in these markers after NaHCO3 and PLA in relation to CTRL indicate a possible role of sodium.

Regulation of Acid-Base Balance in Patients With Chronic Kidney Disease.

Normallly the kidneys handle the daily acid load arising from net endogenous acid production from the metabolism of ingested animal protein (acid) and vegetables (base). With chronic kidney disease, reduced acid excretion by the kidneys is primarily due to reduced ammonium excretion such that when acid excertion falls below acid porduction, acid accumulation occurs. With even mild reductions in glomerular filtration rate (60 to 90 ml/min), net acid excretion may fall below net acid production resulting in acid retention which may be initially sequestered in interstitial compartments in the kidneys, bones, and muscles resulting in no fall in measured systemic bicarbonate levels (eubicarbonatemic metabolic acidosis). With greater reductions in kidney function, the greater quantities of acid retained spillover systemically resulting in low pH (overt metabolic acidosis). The evaluation of acid-base balance in patients with CKD is complicated by the heterogeneity of clinical acid-base disorders and by the eubicarbonatemic nature of the early phase of acid retention. If supported by more extensive studies, blood gas analyses to confirm the acid-base disorder and newer ways for assessing the presence of acidosis such as urinary citrate measurements may become routine tools to evaluate and treat acid-base disorders in individuals with CKD.

FC 001ACIDOSIS AND ALKALI THERAPY ARE ASSOCIATED WITH TRANSCRIPTIONAL CHANGES AND ALTERED ABUNDANCE OF GENES INVOLVED IN CELL METABOLISM AND BICARBONATE TRANSPORT IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Metabolic acidosis is a common event in kidney transplant recipients and has been associated to a higher risk of graft loss and mortality. In patients with CKD and acidosis, alkali therapy ameliorating acidosis appears to protect kidney function. However, it is still poorly understood how acidosis causes the detrimental effects to kidney graft function and how alkali therapy would interact with these mechanisms. Here we aim to identify transcriptomic alterations in kidney transplant recipients without metabolic acidosis in comparison to patients with metabolic acidosis with and without alkali therapy. Moreover, we examined immunolocalization of key proteins involved in acid-base base regulation in biopsies from these patients. Method We obtained 22 biopsies of patients 4-6 years after kidney transplantation. Among these patients, nine were not acidotic (serum [HCO3-] ≥ 22 mM), nine had acidosis ([HCO3-] < 22 mM), and four had acidosis and received sodium bicarbonate (alkali therapy) fully correcting acidosis. Age, immunosuppressive drugs, time after transplantation, and eGFR were not statistically different between groups. RNA was extracted from biopsies and RNAseq was performed. Immunohistochemistry was performed for key proteins involved in the renal regulation of acid-base balance. Additionally, a control group of 6 non-transplanted healthy kidneys was included in the histology analysis. Results RNAseq analysis revealed 40 genes differentially expressed between acidosis and no acidosis groups. While most of the genes tended to be recovered by alkali therapy, only three fully recovered with bicarbonate supplementation (p-value < 0.05 and log2(fold change) above 0.5). These genes were KCNJ15 (Kir4.2), SHMT1, and ACADSB. Renal localization of the genes was determined using single-cell RNA sequencing data (Ransick et al., Developmental Cell, 2019, doi.org/10.1016/j.devcel.2019.10.005). Most of the genes were expressed in the proximal tubule and were organized in the model shown in Figure 1A. Several of these genes participate in cell metabolism, such as beta-oxidation, and iron, folate, and methionine metabolism. Moreover, the K+-channel Kir4.2 regulates the activity of the electrogenic sodium bicarbonate cotransporter 1 (NBCe1, SLC4A4) and ammoniagenesis in renal proximal tubules. Immunofluorescence analysis showed that NBCe1 expression in proximal tubules was strongly reduced in patients who developed acidosis and was partially recovered in patients who received alkali therapy (Figure 1B). In type B intercalated cells, a similar pattern was observed for Pendrin (SLC26A4). No alteration in the expression of GDH (GLUD1), AE1 (SLC4A1), AQP2, CA2, RhCG (SLC42A3), and B1 subunit of the H+ATPase (ATP6V1B1) was observed in kidneys of treated or untreated patients with acidosis. Conclusion Kidney transplant recipients suffering from metabolic acidosis show distinct expression pattern of genes involved in cell metabolism and acid-base transport.

Nutrition and Functions of Amino Acids in Fish.

Aquaculture is increasingly important for providing humans with high-quality animal protein to improve growth, development and health. Farm-raised fish and shellfish now exceed captured fisheries for foods. More than 70% of the production cost is dependent on the supply of compound feeds. A public debate or concern over aquaculture is its environmental sustainability as many fish species have high requirements for dietary protein and fishmeal. Protein or amino acids (AAs), which are the major component of tissue growth, are generally the most expensive nutrients in animal production and, therefore, are crucial for aquatic feed development. There is compelling evidence that an adequate supply of both traditionally classified nutritionally essential amino acids (EAAs) and non-essential amino acids (NEAAs) in diets improve thegrowth, development and production performance of aquatic animals (e.g., larval metamorphosis). The processes for the utilization of dietary AAs or protein utilization by animals include digestion, absorption and metabolism. The digestibility and bioavailability of AAs should be carefully evaluated because feed production processes and AA degradation in the gut affect the amounts of dietary AAs that enter the blood circulation. Absorbed AAs are utilized for the syntheses of protein, peptides, AAs, and other metabolites (including nucleotides); biological oxidation and ATP production; gluconeogenesis and lipogenesis; and the regulation of acid-base balance, anti-oxidative reactions, and immune responses. Fish producers usually focus on the content or digestibility of dietary crude protein without considering the supply of AAs in the diet. In experiments involving dietary supplementation with AAs, inappropriate AAs (e.g., glycine and glutamate) are often used as the isonitrogenous control. At present, limited knowledge is available about either the cell- and tissue-specific metabolism of AAs or the effects of feed processing methods on the digestion and utilization of AAs in different fish species. These issues should be addressed to develop environment-friendly aquafeeds and reduce feed costs to sustain the global aquaculture.

THE ROLE OF THE KIDNEYS IN THE REGULATION OF THE ACID – BASE BALANCE OF THE BLOOD IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

The aim: To study the regulation of acid-base balance and blood acid - renal excretory function in patients with COPD. Materials and methods: We examined 82 people, suggests that even during the most severe stages of COPD. Group 1 included 56 patients with COPD, group C. The average age was 60.54 + 2.04 years old, including 24 men and 32 women. The second group included 16 patients with COPD, group B, whose average age was 55.37 + 3.21 years old, including 7 men and 9 women. The third group included 10 healthy individuals, with an average age of 34.30 + 2.21 years, including 6 men and 4 women. Respiration function was evaluated on the basis of the forced expiratory curve recorded on a Spirolab II MIR S / N computer spirograph. The following indicators were evaluated: forced vital capacity (FVC), forced expiratory volume (FEV1) and FEV1 / FVC ratio. Results: For all patients with COPD there is a characteristic presence of acidosis (pH in patients with COPD group B - 7,34 ± 0,01, in patients with COPD group C - 7,31 ± 0,07). For patients with COPD group C there are pronounced respiratory disorders (pCO2 - 48,25 + 1,14 mm Hg, p02 - 28.07 +1.37 mm Hg). For patients with COPD group B characteristic metabolic disorders (BE--3,71 + 0,57), which increase as the disease progresses. For patients with COPD group C this figure is equal to 7.62 + 0.49. Thus, the analysis of indicators indicates the presence for all patients of mixed (respiratory and metabolic) acidosis, which increases as the chronic obstructive pulmonary disease progresses. Conclusions: There is activation of acid - renal excretory function and the inclusion of renal mechanisms in the regulation of acid-base balance.

The Effect of Long-Term Antihypertensive Therapy on the Change in Secretion and Calcium, Bicarbonate and Phosphate Ion Concentration in Non-Stimulated and Stimulated Saliva.

ObjectiveThe aim of this study was to evaluate the amount of saliva secreted and calcium, bicarbonate, and phosphate ion concentration in patients receiving antihypertensive for five years or over five years (patient group) and in healthy patients (control group).Material and methodsThe patient or experimental group included 31 subjects who were admitted to a cardiovascular clinic and had been receiving an antihypertensive drug therapy for more than five years. The control group included 31 healthy subjects. The measured amount of saliva was further used to determine the calcium, phosphate and bicarbonate ion concentration values. Calcium and phosphate ions were determined spectrophotometrically, while bicarbonate ions were determined by titration.ResultsA two-way-test (Student's test) was used to compare the values of variables. The amount of excreted saliva was statistically significantly lower in the patient group in non-stimulated (1.739 mL/5 min) and stimulated saliva (3.594 mL/5 min). Calcium ion concentration was statistically significantly lower in patient group in resting saliva (6.143 mg/dL). Bicarbonate and phosphate ion concentration in patient group was statistically significantly higher in non-stimulated (bicarbonate ion = 14.041 mmol/L, phosphate ion = 2.818 μmol/L) and stimulated saliva (bicarbonate ion = 10.872 mmol/L, phosphate ion = 1.454 μmol/L), respectively.ConclusionA reduced amount of saliva and calcium ion concentration indicates the possibility of a higher frequency of hard dental tissue demineralization process. On the contrary, the increase in the phosphate and bicarbonate ion concentration in the patient group affects the regulation of acid-base balance, thus having a preventive effect.

Global REACH 2018: renal oxygen delivery is maintained during early acclimatization to 4,330 m

Early acclimatization to high altitude is characterized by various respiratory, hematological, and cardiovascular adaptations that serve to restore oxygen delivery to tissue. However, less is understood about renal function and the role of renal oxygen delivery (RDO2) during high altitude acclimatization. We hypothesized that 1) RDO2 would be reduced after 12 h of high altitude exposure (high altitude day 1) but restored to sea level values after 1 wk (high altitude day 7) and 2) RDO2 would be associated with renal reactivity, an index of acid-base compensation at high altitude. Twenty-four healthy lowlander participants were tested at sea level (344 m, Kelowna, BC, Canada) and on day 1 and day 7 at high altitude (4,330 m, Cerro de Pasco, Peru). Cardiac output, renal blood flow, and arterial and venous blood sampling for renin-angiotensin-aldosterone system hormones and NH2-terminal pro-B-type natriuretic peptides were collected at each time point. Renal reactivity was calculated as follows: (Δarterial bicarbonate)/(Δarterial Pco2) between sea level and high altitude day 1 and sea level and high altitude day 7. The main findings were that 1) RDO2 was initially decreased at high altitude compared with sea level (ΔRDO2: -22 ± 17%, P < 0.001) but was restored to sea level values on high altitude day 7 (ΔRDO2: -6 ± 14%, P = 0.36). The observed improvements in RDO2 resulted from both changes in renal blood flow (Δ from high altitude day 1: +12 ± 11%, P = 0.008) and arterial oxygen content (Δ from high altitude day 1: +44.8 ± 17.7%, P = 0.006) and 2) renal reactivity was positively correlated with RDO2 on high altitude day 7 (r = 0.70, P < 0.001) but not high altitude day 1 (r = 0.26, P = 0.29). These findings characterize the temporal responses of renal function during early high altitude acclimatization and the influence of RDO2 in the regulation of acid-base balance.

Ruolo del citrato nel metabolismo osseo

Citrate is an organic compound involved in tricarboxylic acid cycle, regulation of acid-base balance, lipid metabolism and bone formation. The 90% of body citrate is deposited in bone tissue and is released with calcium ions during bone resorption; therefore, bone resorption contributes to maintain normal plasma levels of citrate together with kidney excretion. The parallel release of citrate and calcium from bones decreases the possibility of calcium-phosphate precipitation in soft tissues, as citrate can bind calcium ions in organic fluids. Citrate may also take part to the bone formation as it sustains the correct mineralization of bone organic matrix: its molecule binds calcium ions at the surface of hydroxyapatite nanocrystals and maintains the correct spatial disposition of nanocrystals, thus, stabilizing the structure of bone lamellae and sustaining biomechanical characteristics of bone tissue. Multiple studies observed that citrate administration significantly increased areal and volumetric bone mineral density at different locations of 1-2% per year and improved bone resorption markers as well. Therefore, it has been hypothesised a therapeutic role of citrate in osteoporosis; however, this role has to be better clarified to understand its real anti-fracture effect.

Amino Acid Metabolism in the Kidneys: Nutritional and Physiological Significance.

The kidneys are developed from the intermediate mesoderm of the embryo. They are important for osmoregulation, regulation of acid-base balance, reabsorption of nutrients, and excretion of metabolites. In fish, the kidneys also serve as a hematopoietic, lymphoid and endocrine organ for the generation of red blood cells, the development of lymphocytes, and the production of hormones (e.g., glucocorticoids, catecholamines, and thyroid hormones). In humans and all animals, kidneys play a vital role in the metabolism and reabsorption of amino acids (AAs) and glucose. Specifically, this organ contributes to glucose synthesis from AAs, lactate and pyruvate via the gluconeogenesis pathway; regulates acid-base balance via inter-organ metabolism of glutamine; and synthesizes arginine, tyrosine, and glycine, respectively, from citrulline, phenylalanine, and 4-hydroxyproline. In mammals and birds, kidneys participate in creatine synthesis. Renal dysfunction adversely alters the concentrations of AAs in blood, while promoting muscle protein breakdown, inflammation, mitochondrial abnormalities, defects in the immune response, and cardiovascular diseases. Moderation of dietary AA intake has a protective and therapeutic effect on chronic kidney disease. Understanding the functions and metabolism of AAs in kidneys is essential for maintaining whole-body homeostasis, improving health and well-being, and preventing or treating renalmetabolic diseases in humans and farm animals (including swine, poultry, ruminants, fish and shrimp).

Острое повреждение почек при пневмонии

Mutual complications of impaired lung and kidney function in severe pneumonia (SP) complicated by acute kidney damage (AKP) are considered. The lungs and kidneys perform some similar functions, such as detoxification and regulation of acid-base balance. Lung damage is complicated by dysfunction or impaired renal function, and vice versa, AKI depressively affects lung function. Initially, all organs and tissues, including the kidneys, suffer from hypoxemic respiratory failure. SP is characterized by increased production of inflammatory mediators, decay products of microorganisms and their toxins and ejection them into the bloodstream. Endothelial vascular insufficiency, disseminated microvascular thrombosis, central hemodynamic disorders develop, and as a result, multiple organ failure develops. With the development of AKI, the elimination of uremic toxins and water is disrupted, hyperhydration is formed with an increase in the volume of extravascular water in the lungs on the background of the already existing broken airborne barrier. Uremic toxins depressively affect the heart muscle on the background of an acute pulmonary heart. There is evidence of a negative effect of mechanical ventilation on kidney function, and, conversely, of an adverse effect of AKI on the need and duration of ventilation. The progression of TP and AKP disrupts the acid - base balance due to excess CO2, impaired H+ ion release, and impaired synthesis of HCO3. The pathophysiological mechanisms underlying these relationships are complex, and their effect on the course of the disease is significant.

Evidence that Rh proteins in the anal papillae of the freshwater mosquito Aedes aegypti are involved in the regulation of acid-base balance in elevated salt and ammonia environments.

Aedes aegypti commonly inhabit ammonia-rich sewage effluents in tropical regions of the world where the adults are responsible for the spread of disease. Studies have shown the importance of the anal papillae of A. aegypti in ion uptake and ammonia excretion. The anal papillae express ammonia transporters and Rhesus (Rh) proteins which are involved in ammonia excretion and studies have primarily focused on understanding these mechanisms in freshwater. In this study, effects of rearing larvae in salt (5 mmol l-1 NaCl) or ammonia (5 mmol l-1 NH4Cl) on physiological endpoints of ammonia and ion regulation were assessed. In anal papillae of NaCl-reared larvae, Rh protein expression increased, NHE3 transcript abundance decreased and NH4+ excretion increased, and this coincided with decreased hemolymph [NH4+] and pH. We propose that under these conditions, larvae excrete more NH4+ through Rh proteins as a means of eliminating acid from the hemolymph. In anal papillae of NH4Cl-reared larvae, expression of an apical ammonia transporter and the Rh proteins decreased, the activities of NKA and VA decreased and increased, respectively, and this coincided with hemolymph acidification. The results present evidence for a role of Rh proteins in acid-base balance in response to elevated levels of salt, whereby ammonia is excreted as an acid equivalent.

Regulation of Acid-Base Balance in Chronic Kidney Disease.

The kidneys play a major role in the regulation of acid-base balance by reabsorbing bicarbonate filtered by the glomeruli and excreting titratable acids and ammonia into the urine. In CKD, with declining kidney function, acid retention and metabolic acidosis occur, but the extent of acid retention depends not only on the degree of kidney impairment but also on the dietary acid load. Acid retention can occur even when the serum bicarbonate level is apparently normal. With reduced kidney function, acid transport processes in the surviving nephrons are augmented but as disease progresses ammonia excretion and, in some individuals, the ability to reabsorb bicarbonate falls, whereas titratable acid excretion is preserved until kidney function is severely impaired. Urinary ammonia levels are used to gauge the renal response to acid loads and are best assessed by direct measurement of urinary ammonia levels rather than by indirect assessments. In individuals with acidosis from CKD, an inappropriately low degree of ammonia excretion points to the pathogenic role of impaired urinary acid excretion. The presence of a normal bicarbonate level in CKD complicates the interpretation of the urinary ammonia excretion as such individuals could be in acid-base balance or could be retaining acid without manifesting a low bicarbonate level. At this time, the decision to give bicarbonate supplementation in CKD is reserved for those with a bicarbonate level of 22mEq/L, but because of potential harm of overtreatment, supplementation should be adjusted to maintain a bicarbonate level of <26mEq/L.

Metabolic Acidosis: Diagnostics and Treatment

Metabolic acidosis is the most common child acid-base balance disorder. This condition accompanies a variety of diseases, and the degree of its severity correlates with the patients’ survival: although not a separate disease in itself, metabolic acidosis, however, can worsen the disease course and even lead to death. The pathology causes are various (in connection with life-threatening changes in various organs and systems — lungs, heart and blood vessels, kidneys, and also due to a violation of lipid metabolism, in case of diabetes, poisoning, etc.), which determines the fact that a wide range of specialists are interested in the issue. Approaches to the diagnosis simplify the search for the etiology of metabolic acidosis. This study presents data on the physiological basis of acid-base balance regulation, and its etiology and pathophysiology; the principles of therapy are observed.

Time course of lead induced proteomic changes in gill of the Antarctic limpet Nacella Concinna (Gastropoda: Patellidae)

The effect of increasing levels of metals from anthropogenic sources on Antarctic invertebrates is poorly understood. Here we exposed limpets (Nacella concinna) to 0, 0.12 and 0.25μgL−1 lead for 12, 24, 48 and 168h. We subsequently quantified the changes in protein abundance from gill, using 2D gel electrophoresis and mass spectrometry. We identified several antioxidant proteins, including the metal binding Mn-superoxide dismutase and ferritin, increasing abundances early on. Chaperones involved in the redox-dependent maturation of proteins in the endoplasmic reticulum (ER) showed higher abundance with lead at 48h. Lead also increased the abundance of Zn-binding carbonic anhydrase at 12h, suggesting a challenge to acid-base balance. Metabolic proteins increased abundance at 168h, suggesting a greater ATP demand during prolonged exposure. Changes in abundance of the small G-protein cdc42, a signaling protein modifying cytoskeleton, increased early and subsequently reversed during prolonged exposure, possibly leading to the modification of thick filament structure and function. We hypothesize that the replacement of metals initially affected antioxidant proteins and increased the production of reactive oxygen species. This disrupted the redox-sensitive maturation of proteins in the ER and caused increased ATP demand later on, accompanied by changes in cytoskeleton. SignificanceProteomic analysis of gill tissue in Antarctic limpets exposed to different concentrations of lead (Pb) over a 168h time period showed that proteomic changes vary with time. These changes included an increase in the demand of scavenging reactive oxygen species, acid-base balance and a challenge to protein homeostasis in the endoplasmic reticulum early on and subsequently an increase in energy metabolism, cellular signaling, and cytoskeletal modifications. Based on this time course, we hypothesize that the main mode of action of lead is a replacement of metal-cofactors of key enzymes involved in the scavenging of reactive oxygen species and the regulation of acid-base balance.

Kidney-lung connections in acute and chronic diseases: current perspectives.

Lung and kidney functions are intimately related in both health and disease. The regulation of acid-base equilibrium, modification of partial pressure of carbon dioxide and bicarbonate concentration, and the control of blood pressure and fluid homeostasis all closely depend on renal and pulmonary activities. These interactions begin in fetal age and are often responsible for the genesis and progression of diseases. In gestational age, urine is a fundamental component of the amniotic fluid, acting on pulmonary maturation and growth. Moreover, in the first trimester of pregnancy, kidney is the main source of proline, contributing to collagen synthesis and lung parenchyma maturation. Pathologically speaking, the kidneys could become damaged by mediators of inflammation or immuno-mediated factors related to a primary lung pathology or, on the contrary, it could be the renal disease that determines a consecutive pulmonary damage. Furthermore, non immunological mechanisms are frequently involved in renal and pulmonary diseases, as observed in chronic pathologies such as sleep apnea syndrome, pulmonary hypertension, progressive renal disease and hemodialysis. Kidney damage has also been related to mechanical ventilation. The aim of this review is to describe pulmonary-renal interactions and their related pathologies, underscoring the need for a close collaboration between intensivists, pneumologists and nephrologists.

Formation renal function in children born prematurely

A premature baby needing resuscitation after birth, is exposed to damaging factors affecting the entire body, including the kidneys. Aim — analysis of current data on the issue of the formation of kidney function in children born prematurely. Materials and methods. The review publications domestic and foreign authors studied data from randomized clinical and epidemiological studies. Results and discussion. Events intensive care, which include mechanical ventilation, infusion therapy, parenteral nutrition, intravenous drugs, lead to an increased load on the immature kidney premature baby in the neonatal period. A special risk factor for preterm is still imperfect glomerular and tubular function, renal large capillary surface, high renal blood flow, inadequate regulation of acid-base balance and the ability to concentrate, are under the influence of external loads become insolvent. Under the influence of damaging factors on the kidney nephron deficit increases the risk of further decline in kidney function. It is assumed that no additional nephrons deficit is not negative factors leads to chronic diseases in the future. Conclusion. Analyzing conducted research on the formation of kidney function in children born prematurely, it can be assumed that children with a gestational age less than 32 weeks and weighing less than 1500 grams at birth, who are exposed to adverse environmental factors on the developing buds in the perinatal and neonatal periods. They are in the zone of risk of chronic disease of the kidneys in later life.