Regulation Of Extracellular Fluid Volume Research Articles

The Renin‐Angiotensin System after Pig Kidney Transplantation in Baboons

Resolution of many technical and immune‐related issues have allowed long‐term survival of baboons with life‐supporting pig kidney grafts. However, episodes of hypovolemia and hypotension during the post‐transplant period occur via an unexplained mechanism. It has been reported that pig renin has low reactivity on human angiotensinogen (AGT). Because the renin‐angiotensin system (RAS) is vitally important in the regulation of extracellular fluid volume and blood pressure, we evaluated the activity of the RAS in baboon’s post‐pig kidney xenotransplantation. Kidneys from genetically‐modified pigs were transplanted into 5 baboons (6 to 10 kg) that were immunosuppressed by blockade of the CD40/CD154 costimulation pathway, after excision of the native kidneys. Plasma renin, AGT (only baboon AGT could be measured), and angiotensin II levels were measured by ELISAs in (i) healthy genetically‐modified pigs (n=3), healthy non‐immunosuppressed baboons (n=6), and (iii) immunosuppressed baboons with pig kidney grafts. Samples were collected for up to 120 days post‐transplantation. Plasma renin levels were significantly greater in healthy pigs (586±139 (SE) pg/ml) than in intact baboons (430±28 pg/ml). The plasma renin levels in baboons with pig kidney grafts were similar to values in intact baboons (367±18 pg/ml), indicating the continuing production of renin by the pig kidney grafts in absence of baboon kidneys. Plasma AGT (which reflected only baboon AGT) levels were augmented in the transplanted baboons (21±0.8 µg/ml) compared to the pre‐transplant concentrations (9.9±0.8). Plasma angiotensin II levels were 16±1.3 pg/ml in intact baboons and trended lower from pre‐transplant levels in the transplanted baboons (10±1.6 pg/ml). Lower plasma angiotensin II concentrations in baboons with pig kidney grafts, even in the presence of increasing plasma AGT levels, may be a consequence of reduced, but not absent, reactivity of pig renin to cleave baboon AGT. The reduced angiotensin II levels in the transplanted baboons suggest an impaired ability to elicit a robust response to hypovolemic and hypotensive episodes.

Ceramide-1-Phosphate as a Potential Regulator of the Second Sodium Pump from Kidney Proximal Tubules by Triggering Distinct Protein Kinase Pathways in a Hierarchic Way.

Kidney proximal tubules are a key segment in the reabsorption of solutes and water from the glomerular ultrafiltrate, an essential process for maintaining homeostasis in body fluid compartments. The abundant content of Na+ in the extracellular fluid determines its importance in the regulation of extracellular fluid volume, which is particularly important for different physiological processes including blood pressure control. Basolateral membranes of proximal tubule cells have the classic Na+ + K+-ATPase and the ouabain-insensitive, K+-insensitive, and furosemide-sensitive Na+-ATPase, which participate in the active Na+ reabsorption. Here, we show that nanomolar concentrations of ceramide-1 phosphate (C1P), a bioactive sphingolipid derived in biological membranes from different metabolic pathways, promotes a strong inhibitory effect on the Na+-ATPase activity (C1P50 ≈ 10 nM), leading to a 72% inhibition of the second sodium pump in the basolateral membranes. Ceramide-1-phosphate directly modulates protein kinase A and protein kinase C, which are known to be involved in the modulation of ion transporters including the renal Na+-ATPase. Conversely, we did not observe any effect on the Na+ + K+-ATPase even at a broad C1P concentration range. The significant effect of ceramide-1-phosphate revealed a new potent physiological and pathophysiological modulator for the Na+-ATPase, participating in the regulatory network involving glycero- and sphingolipids present in the basolateral membranes of kidney tubule cells.

Renal Function Impairment and Associated Factors Among Adult HIV-Positive Patients Attending Antiretroviral Therapy Clinic in Mettu Karl Referral Hospital: Cross-Sectional Study.

BackgroundHuman immunodeficiency virus (HIV) affects every organ system in the body through impairment or by rendering the patient vulnerable to opportunistic infections. The kidney is the vital organ in the excretion of waste products and toxins (urea, creatinine and uric acid), and regulation of extracellular fluid volume, serum osmolality and electrolyte concentrations. The risk of kidney disease is greater in HIV-infected individuals than in the general population. This study aimed to assess the magnitude of renal function impairment and its associated factors among adult HIV-positive patients attending an ART clinic in Mettu Karl Referral Hospital, Mettu town, south-west Ethiopia.MethodsThe institution-based, cross-sectional quantitative study was conducted from March 8 to May 30, 2020. A total of 352 clients participated and a systematic sampling technique was used to allocate study participants. Data were entered into Epi data and exported to SPSS version 22 for analysis. Bivariate analysis was conducted to identify candidate variables for multivariate analysis at P <0.25. Multivariable logistic regression analysis was conducted to determine the predictors of renal function impairment with ART. P value < 0.05 was considered to indicate statistical significance.ResultsA total of 352 HIV-infected patients participated in this study with a response rate of 98.1%. Out of 352 HIV patients on ART, 73 (20.7%) were found to have renal function impairment. Cigarette smoking [AOR = 9.60, 95% CI: 4.73–19.48], diabetes mellitus [AOR = 6.16, 95% CI: 2.79–13.59], hypertension [AOR = 4.71, 95% CI: 1.98–11.17] and low CD4 count [AOR = 6.47, 95% CI: 3.31–12.64] were found to be independent predictors of renal function impairment among adult HIV positive patients.ConclusionThe prevalence of renal function impairment among HIV patients on ART is high. Hypertension, diabetes, cigarette smoking and low CD4 count were associated factors of renal function impairment. HIV patients on ART should be regularly screened for early diagnosis and management of renal function impairment.

Epithelial Sodium Channel and Salt-Sensitive Hypertension.

The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in sodium handling and excretion. ENaC (epithelial sodium channel) is one of the key transporters responsible for the reabsorption of sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in renal sodium reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.

Analyses of epithelial Na+ channel variants reveal that an extracellular β-ball domain critically regulates ENaC gating

Epithelial Na+ channel (ENaC)-mediated Na+ transport has a key role in the regulation of extracellular fluid volume, blood pressure, and extracellular [K+]. Among the thousands of human ENaC variants, only a few exist whose functional consequences have been experimentally tested. Here, we used the Xenopus oocyte expression system to investigate the functional roles of four nonsynonymous human ENaC variants located within the β7-strand and its adjacent loop of the α-subunit extracellular β-ball domain. αR350Wβγ and αG355Rβγ channels exhibited 2.5- and 1.8-fold greater amiloride-sensitive currents than WT αβγ human ENaCs, respectively, whereas αV351Aβγ channels conducted significantly less current than WT. Currents in αH354Rβγ-expressing oocytes were similar to those expressing WT. Surface expression levels of three mutants (αR350Wβγ, αV351Aβγ, and αG355Rβγ) were similar to that of WT. However, three mutant channels (αR350Wβγ, αH354Rβγ, and αG355Rβγ) exhibited a reduced Na+ self-inhibition response. Open probability of αR350Wβγ was significantly greater than that of WT. Moreover, other Arg-350 variants, including αR350G, αR350L, and αR350Q, also had significantly increased channel activity. A direct comparison of αR350W and two previously reported gain-of-function variants revealed that αR350W increases ENaC activity similarly to αW493R, but to a much greater degree than does αC479R. Our results indicate that αR350W along with αR350G, αR350L, and αR350Q, and αG355R are novel gain-of-function variants that function as gating modifiers. The location of these multiple functional variants suggests that the αENaC β-ball domain portion that interfaces with the palm domain of βENaC critically regulates ENaC gating.

Epithelial sodium channel (ENaC) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The epithelial sodium channels (ENaC) are located on the apical membrane of epithelial cells in the distal kidney tubules, lung, respiratory tract, male and female reproductive tracts, sweat and salivary glands, placenta, colon and some other organs [20, 11, 7]. In these epithelia, ENaC allows flow of Na+ ions from the extracellular fluid in the lumen into the epithelial cell. Na+ ions are then pumped out of the cytoplasm into the interstitial fluid by the Na+/K+ ATPase located on the basolateral membrane [39]. As Na+ is one of the major electrolytes in the extracellular fluid (ECF), osmolarity change initiated by the Na+ flow is accompanied by a flow of water accompanying Na+ ions [6]. Thus, ENaC has a central role in the regulation of ECF volume and blood pressure, especially via its function in the kidney [25, 30]. The expression of ENaC subunits, hence its activity, is regulated by the renin-angotensin-aldosterone system, and other factors that are involved in electrolyte homeostasis [30, 1, 29]. In the respiratory tract and female reproductive tract large segments of the tracts are covered by multi-ciliated cells. In these cells ENaC has been shown to be located along the entire length of the cilia [14]. Cilial location greatly increases ENaC density per cell surface and allows ENaC to serve as a sensitive regulator of osmolarity of the periciliary fluid throughout the whole depth of the fluid bathing the cilia [14]. In contrast to ENaC, CFTR that is defective in cystic fibrosis is not located on non-cilial cell-surface [14]. Thus, ENaC function is also essential for the clearance of respiratory airways, transport of germ cells, fertilization, implantation and cell migration [14, 33]. ENaC has been recently localized in the germinal epithelium of the testis, Sertoli cells, spermatozoa, along the epididymis ducts, and smooth muscle cells [35, 36]. Evidence has been provided that rare mutations in ENaC are associated with female infertility [5].

Hypothalamic Signaling in Body Fluid Homeostasis and Hypertension.

The central nervous system plays a pivotal role in the regulation of extracellular fluid volume and consequently arterial blood pressure. Key hypothalamic regions sense and integrate neurohumoral signals to subsequently alter intake (thirst and salt appetite) and output (renal excretion via neuroendocrine and autonomic function). Here, we review recent findings that provide new insight into such mechanisms that may represent new therapeutic targets. Implementation of cutting edge neuroscience approaches such as opto- and chemogenetics highlight pivotal roles of circumventricular organs to impact body fluid homeostasis. Key signaling mechanisms within these areas include the N-terminal variant of transient receptor potential vannilloid type-1, NaX, epithelial sodium channel, brain electroneutral transporters, and non-classical actions of vasopressin. Despite the identification of several new mechanisms, future studies need to better define the neurochemical phenotype and molecular profiles of neurons within circumventricular organs for future therapeutic potential.

Interplay between renal endothelin and purinergic signaling systems.

Alterations in extracellular fluid volume regulation and sodium balance may result in the development and maintenance of salt-dependent hypertension, a major risk factor for cardiovascular disease. Numerous pathways contribute to the regulation of sodium excretion and blood pressure, including endothelin and purinergic signaling. Increasing evidence suggests a link between purinergic receptor activation and endothelin production within the renal collecting duct as a means of promoting natriuresis. A better understanding of the relationship between these two systems, especially in regard to sodium homeostasis, will fill a significant knowledge gap and may provide novel antihypertensive treatment options. Therefore, this review focuses on the cross talk between endothelin and purinergic signaling as it relates to the renal regulation of sodium and blood pressure homeostasis.

Paracellular transport in the collecting duct.

The paracellular pathway through the tight junction provides an important route for chloride reabsorption in the collecting duct of the kidney. This review describes recent findings of how defects in paracellular chloride permeation pathway may cause kidney diseases and how such a pathway may be regulated to maintain normal chloride homeostasis. The tight junction in the collecting duct expresses two important claudin genes - claudin-4 and claudin-8. Transgenic knockout of either claudin gene causes hypotension, hypochloremia, and metabolic alkalosis in experimental animals. The claudin-4 mediated chloride permeability can be regulated by a protease endogenously expressed by the collecting duct cell - channel-activating protease 1. Channel-activating protease 1 regulates the intercellular interaction of claudin-4 and its membrane stability. Kelch-like 3, previously identified as a causal gene for Gordon's syndrome, also known as pseudohypoaldosteronism II, directly interacts with claudin-8 and regulates its ubiquitination and degradation. The dominant pseudohypoaldosteronism-II mutation (R528H) in Kelch-like 3 abolishes claudin-8 binding, ubiquitination, and degradation. The paracellular chloride permeation pathway in the kidney is an important but understudied area in nephrology. It plays vital roles in renal salt handling and regulation of extracellular fluid volume and blood pressure. Two claudin proteins, claudin-4 and claudin-8, contribute to the function of this paracellular pathway. Deletion of either claudin protein from the collecting duct causes renal chloride reabsorption defects and low blood pressure. Claudins can be regulated on posttranslational levels by several mechanisms involving protease and ubiquitin ligase. Deregulation of claudins may cause human hypertension as exemplified in the Gordon's syndrome.

A noninvasive method to study regulation of extracellular fluid volume in rats using nuclear magnetic resonance

Time-domain nuclear magnetic resonance (TD-NMR)-based measurement of body composition of rodents is an effective method to quickly and repeatedly measure proportions of fat, lean, and fluid without anesthesia. TD-NMR provides a measure of free water in a living animal, termed %fluid, and is a measure of unbound water in the vascular and extracellular spaces. We hypothesized that injecting a bolus of fluid into the peritoneal cavity would lead to an abrupt increase in %fluid and the rate of clearance monitored with TD-NMR would provide a noninvasive assessment of the free water homeostasis in an awake rat. Several strains of laboratory rats were injected intraperitoneally with 10 ml/kg isotonic or hypertonic saline and %fluid was monitored repeatedly with a Bruker "Minispec" TD-NMR body composition system. Following isotonic saline, %fluid increased immediately by 0.5% followed by a recovery over ∼6 h. Injecting hypertonic (3 times normal saline) resulted in a significantly greater rise in %fluid and longer recovery. Intraperitoneal and subcutaneous fluid injection led to similar rates of clearance. The Wistar-Kyoto rat strain displayed significantly slower recovery to fluid loads compared with Long-Evans and Sprague-Dawley strains. Rats exercised chronically showed significant increases in %fluid, but the rate of clearance of fluid was similar to that of sedentary animals. We conclude that this technique could be used to study vascular and extracellular volume homeostasis noninvasively in rats.

Endogenous Digitalis-Like Factors: An Overview of the History

The sodium pump is a ubiquitous cell surface enzyme, a Na, K ATPase, which maintains ion gradients between cells and the extracellular fluid (ECF). The extracellular domain of this enzyme contains a highly conserved binding site, a receptor for a plant derived family of compounds, the digitalis glycosides. These compounds inhibit the enzyme and are used in the treatment of congestive heart failure and certain cardiac arrhythmias. The highly conserved nature of this enzyme and its digitalis receptor led to early suggestions that endogenous regulators might exist. Recent examination of this hypothesis emerged from research in two separate areas: the regulation of ECF volume by a natriuretic hormone (NH), and the regulation of peripheral vascular resistance by a circulating inhibitor of vascular Na, K ATPase. These two areas merged with the hypothesis that NH and the vascular Na, K ATPase inhibitor were in fact the same entity, and that it played a causative role in the pathophysiology of certain types of hypertension. The possibility that multiple endogenous digitalis-like factors (EDLFs) exist emerged from efforts to characterize the circulating enzyme inhibitory activity. In this review, the development of this field from its beginnings is traced, the current status of the structure of EDLFs is briefly discussed, and areas for future development are suggested.

Na+ Inhibits the Epithelial Na+ Channel by Binding to a Site in an Extracellular Acidic Cleft

The epithelial Na(+) channel (ENaC) has a key role in the regulation of extracellular fluid volume and blood pressure. ENaC belongs to a family of ion channels that sense the external environment. These channels have large extracellular regions that are thought to interact with environmental cues, such as Na(+), Cl(-), protons, proteases, and shear stress, which modulate gating behavior. We sought to determine the molecular mechanism by which ENaC senses high external Na(+) concentrations, resulting in an inhibition of channel activity. Both our structural model of an ENaC α subunit and the resolved structure of an acid-sensing ion channel (ASIC1) have conserved acidic pockets in the periphery of the extracellular region of the channel. We hypothesized that these acidic pockets host inhibitory allosteric Na(+) binding sites. Through site-directed mutagenesis targeting the acidic pocket, we modified the inhibitory response to external Na(+). Mutations at selected sites altered the cation inhibitory preference to favor Li(+) or K(+) rather than Na(+). Channel activity was reduced in response to restraining movement within this region by cross-linking structures across the acidic pocket. Our results suggest that residues within the acidic pocket form an allosteric effector binding site for Na(+). Our study supports the hypothesis that an acidic cleft is a key ligand binding locus for ENaC and perhaps other members of the ENaC/degenerin family.

Renal P2 receptors and hypertension.

The regulation of extracellular fluid volume is a key component of blood pressure homeostasis. Long-term blood pressure is stabilized by the acute pressure natriuresis response by which changes in renal perfusion pressure evoke corresponding changes in renal sodium excretion. A wealth of experimental evidence suggests that a defect in the pressure natriuresis response contributes to the development and maintenance of hypertension. The mechanisms underlying the relationship between renal perfusion pressure and sodium excretion are incompletely understood. Increased blood flow through the vasa recta increases renal interstitial hydrostatic pressure, thereby reducing the driving force for transepithelial sodium reabsorption. Paracrine signalling also contributes to the overall natriuretic response by inhibiting tubular sodium reabsorption in several nephron segments. In this brief review, we discuss the role of purinergic signalling in the renal control of blood pressure. ATP is released from renal tubule and vascular cells in response to increased flow and can activate P2 receptor subtypes expressed in both epithelial and vascular endothelial/smooth muscle cells. In concert, these effects integrate the vascular and tubular responses to increased perfusion pressure and targeting P2 receptors, particularly P2X7, may prove beneficial for treatment of hypertension.

Acute kidney injury in neonatal age

Acute kidney injury (AKI) is a pathology characterized by a sudden decrease in kidney function that results in the accumulation of nitrogenous waste products and alteration of the regulation of extracellular fluid volume, electrolytes, and acid-base homeostasis. Previously known as acute renal failure (ARF), in the most recent classifications the term “failure” is used only in conditions requiring renal replacement therapy, peritoneal dialysis or hemodialysis. The diagnosis and therapy of AKI, especially in the neonatal period, still present great difficulties and are the subject of ongoing research in the attempt to improve the prognosis of a pathology still featuring high rates of morbidity and mortality. Proceedings of the International Course on Perinatal Pathology (part of the 10 th International Workshop on Neonatology · October 22 nd -25 th , 2014) · Cagliari (Italy) · October 25 th , 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

Pressure natriuresis and the renal control of arterial blood pressure.

The regulation of extracellular fluid volume by renal sodium excretion lies at the centre of blood pressure homeostasis. Renal perfusion pressure can directly regulate sodium reabsorption in the proximal tubule. This acute pressure natriuresis response is a uniquely powerful means of stabilizing long-term blood pressure around a set point. By logical extension, deviation from the set point can only be sustained if the pressure natriuresis mechanism is impaired, suggesting that hypertension is caused or sustained by a defect in the relationship between renal perfusion pressure and sodium excretion. Here we describe the role of pressure natriuresis in blood pressure control and outline the cascade of biophysical and paracrine events in the renal medulla that integrate the vascular and tubular response to altered perfusion pressure. Pressure natriuresis is impaired in hypertension and mechanistic insight into dysfunction comes from genetic analysis of blood pressure disorders. Transplantation studies in rats show that blood pressure is determined by the genotype of the kidney and Mendelian hypertension indicates that the distal nephron influences the overall natriuretic efficiency. These approaches and the outcomes of genome-wide-association studies broaden our view of blood pressure control, suggesting that renal sympathetic nerve activity and local inflammation can impair pressure natriuresis to cause hypertension. Understanding how these systems interact is necessary to tackle the global burden of hypertension.

Role of a PH Sensitive Site in Enac Na+ Self-Inhibition

The epithelial Na+ channel (ENaC) is key to the regulation of extracellular fluid volume and blood pressure through its action in the aldosterone-sensitive nephron. Inhibition of ENaC by extracellular Na+, referred to as Na+ self-inhibition, likely occurs through an allosteric mechanism of Na+ binding to low affinity sites in the large extracellular regions of ENaC subunits. The effector binding sites and transduction pathways remain unidentified. A recent comparative model of the ENaC α subunit revealed an acidic cleft, analogous to the acidic region observed in the resolved structure of acid sensing ion channel 1 (ASIC1). We hypothesized that this cleft and analogous clefts in the and subunits host Na+ effector sites. Mutations of acidic residues in the subunit acidic cleft led us to identify an aspartate on the loop connecting the central palm and β-ball domains that reaches towards the finger domain. We also identified nearby sites on the loop and other structures that affected Na+ self-inhibition. To determine whether these sites were involved in effector coordination, we measured the ability of mutants to change the effector specificity of Na+ self-inhibition, which is Na+ > Li+ >> K+ for wild type mouse ENaC. Mutation of the palm/-ball loop aspartate and several nearby sites weakened Na+ inhibition relative to Li+ and K+ inhibition. We hypothesized that protonating any carboxylate groups involved in Na+ coordination would weaken Na+ binding. Consistent with this, lowering the pH to 4.7 increased ENaC currents and reduced Na+ self-inhibition. Mutation of the palm/β-ball loop aspartate reversed pH activation of ENaC. Our results suggest that an aspartate in the acidic cleft of the subunit may coordinate Na+ for Na+ self-inhibition.

Neonatal Acute Kidney Injury

Acute kidney injury (AKI) is characterized by a sudden deterioration in kidney function that results in the accumulation of nitrogenous waste products (e.g., urea) and alters the regulation of extracellular fluid volume, electrolytes, and acid-base homeostasis. Although the criteria for neonatal acute kidney injury have varied, a frequently used definition is a serum creatinine level of more than 1.5 mg/dL.The causes of neonatal acute kidney injury are multiple and can be divided into prerenal, renal, and postrenal categories. Prerenal azotemia is the most common type of acute kidney injury in the neonate and may account for up to 85% of all cases. There are currently no specific medical therapies to treat AKI. The basic approach in management of AKI should be planned according to the underlying etiology. To maximize the chance for survival, the clinician must support the cardiorespiratory system, maintain maximal nutrition, balance homeostasis, and manage the consequences of AKI. The prognosis for neonates with acute kidney injury is variable, and largely related to the infant’s underlying medical condition, with mortality rates ranging from 14% to 73%. (JAREM 2013; 3: 53-9)

Intestinal Na+ Loss and Volume Depletion in JAK3-Deficient Mice

Background/Aims: The Janus kinase 3 JAK3 participates in the signaling of immune cells. Lack of JAK3 triggers inflammatory bowel disease, which in turn has been shown to affect intestinal activity of the epithelial Na⁺ channel ENaC and thus colonic sodium absorption. At least in theory, inflammatory bowel disease in JAK3-deficient mice could lead to intestinal salt loss compromizing extracellular volume maintenance and blood pressure regulation. The present study thus explored whether JAK3 deficiency impacts on colonic ENaC activity, fecal Na⁺ exretion, blood pressure and extracellular fluid volume regulation. Methods: Experiments were performed in gene-targeted mice lacking functional JAK3 (jak3^-/-) and in wild type mice (jak3^+/+). Colonic ENaC activity was estimated from amiloride-sensitive current in Ussing chamber experiments, fecal, serum and urinary Na⁺ concentration by flame photometry, blood pressure by the tail cuff method and serum aldosterone levels by immunoassay. Results: The amiloride (50 µM)-induced deflection of the transepithelial potential difference was significantly lower and fecal Na⁺ excretion significantly higher in jak3^-/- mice than in jak3^+/+ mice. Moreover, systolic arterial blood pressure was significantly lower and serum aldosterone concentration significantly higher in jak3^-/- mice than in jak3^+/+ mice. Both, absolute and fractional renal Na⁺ excretion were significantly lower in jak3^-/- mice than in jak3^+/+ mice. Conclusions: JAK3 deficiency leads to impairment of colonic ENaC activity with intestinal Na⁺ loss, decrease of blood pressure, increased aldosterone release and subsequent stimulation of renal tubular Na⁺ reabsorption.

The role of plasma N-terminal pro-B-type natriuretic peptide in predicting the severity of transient tachypnea of the newborn

Background/AimTransient tachypnea of the newborn (TTN) is a consequence of inadequate neonatal lung fluid clearance. Natriuretic peptides play an important role in the regulation of extracellular fluid volume. The aim of the study was to investigate the relation between plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and TTN, and to find out its role in predicting disease severity. MethodsA prospective controlled study involving 67 infants with TTN and 33 controls ≥34weeks gestational age was conducted. Study and control groups were compared for plasma NT-proBNP levels measured on the 6th, 24th, 72nd and 120th hours of life. Cardiac systolic functions were evaluated by echocardiography. ResultsNT-proBNP levels were significantly higher in neonates with TTN compared to controls at 6th, 24th, 72nd and 120th hours (p<0.001). NT-proBNP levels at 24th and 72nd hours were significantly higher in infants with prolonged tachypnea (p=0.007 and p=0.03) and in those who required respiratory support (p=0.006 and p<0.001). Tachypnea duration was correlated with NT-proBNP levels at 24h (r=0.41, p=0.001). At a cut-off value of 6575pg/ml, NT-proBNP had a sensitivity of 85% and specificity of 64% to predict mechanical ventilation requirement. Cardiac systolic functions were normal in all TTN patients. ConclusionPlasma NT-proBNP levels are increased in neonates with TTN. Measurement of plasma NT-proBNP can be useful for predicting infants who will have prolonged tachypnea and mechanical ventilation requirement.

Prognostic markers in patients with ascites and hepatorenal syndrome.

Cirrhosis is a progressive liver disorder characterized by a distorted liver architecture due to fibrosis which eventually leads to portal hypertension. It is a common cause of mortality accounting for over 26,000 deaths annually in the United States [1]. The natural course of patients with cirrhosis is frequently complicated by the accumulation of fluid in the peritoneal space in the form of ascites. This is caused by an abnormal regulation of extracellular fluid volume which leads to alterations in renal function with renal sodium retention, solute-free water retention, and renal vasoconstriction. These changes are responsible for fluid accumulation in the form of ascites, dilutional hyponatremia and hepatorenal syndrome (HRS) respectively. Ascites is the most common complication of cirrhosis and poses and increased risk for infections, renal failure and mortality. Patients with cirrhosis and ascites have a poor prognosis and it is estimated that nearly half of these individuals will die in approximately 5 years without liver transplantation. Hypervolemic hyponatremia and HRS occur later and confer an even a worse prognosis. This article reviews common prognostic markers and models in cirrhotic patients with ascites, hypervolemic hyponatremia and HRS.