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1.
A swan song for Kt/Vurea.
Vanholder, R, Van Biesen, W, Lameire, N
Seminars in dialysis. 2019;(5):424-437
Abstract
Dialyzer clearance of urea multiplied by dialysis time and normalized for urea distribution volume (Kt/Vurea or simply Kt/V) has been used as an index of dialysis adequacy since more than 30 years. This article reviews the flaws of Kt/V, starting with a lack of proof of concept in three randomized controlled hard outcome trials (RCTs), and continuing with a long list of conditions where the concept of Kt/V was shown to be flawed. This information leaves little room for any conclusion other than that Kt/V, as an indicator of dialysis adequacy, is obsolete. The dialysis patient might benefit more if, instead, the nephrology community concentrates in the future on pursuing the optimal dialysis dose that conforms with adequate quality of life and on factors that are likely to affect outcomes more than Kt/V. These include residual renal function, volume status, dialysis length, ultrafiltration rate, the number of intra-dialytic hypotensive episodes, interdialytic blood pressure, serum potassium and phosphate, serum albumin, and C reactive protein.
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2.
Non-invasive diagnostic tests for Helicobacter pylori infection.
Best, LM, Takwoingi, Y, Siddique, S, Selladurai, A, Gandhi, A, Low, B, Yaghoobi, M, Gurusamy, KS
The Cochrane database of systematic reviews. 2018;(3):CD012080
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Abstract
BACKGROUND Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. OBJECTIVES To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. SEARCH METHODS We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. SELECTION CRITERIA We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as 13C or 14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. DATA COLLECTION AND ANALYSIS Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. MAIN RESULTS We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. AUTHORS' CONCLUSIONS In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.
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3.
Quantification of NGAL in Urine of Endurance Cycling Athletes.
Machado, JCQ, Volpe, CMO, Vasconcellos, LS, Nogueira-Machado, JA
Journal of physical activity & health. 2018;(9):679-682
Abstract
BACKGROUND Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released during early phases of a postischemic kidney in response to kidney injury, inflammation, and oxidative stress. It can be detected in urine after 2 hours of an ischemic event. The aim was to measure and to correlate the level of urine NGAL (uNGAL) with urea, creatinine, and glomerular filtration rate (GFR) of endurance cycling athletes (n = 19) and physically active individuals (control, n = 17). METHODS Quantification of urea and creatinine were performed by dry chemical method, and GFR was calculated using the modification of diet in renal disease formula, according to Brazilian Society of Nephrology. uNGAL analyses were performed by enzyme linked immunoabsorbent assay. Analyses were performed 48 hours after exercises. RESULTS uNGAL (in ng/mL) levels, expressed as median, minimum, and maximum, in cyclist group, 387.7 (109.7-1691.0), was significantly higher than that observed in control (physically active) group, 141.5 (4.8-657.0), (P < .05). No significant correlations were observed between uNGAL and creatinine, urea, or GFR (P > .05). CONCLUSIONS Results have pointed to increased uNGAL levels in endurance cycling athletes. Increase of uNGAL in absence of clinical signs or alterations in creatinine, urea, or GFR might suggest that there is metabolic adaptation to endurance exercise, or possibly predisposition to acute kidney injury over time.
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Glucagon revisited: Coordinated actions on the liver and kidney.
Bankir, L, Bouby, N, Speth, RC, Velho, G, Crambert, G
Diabetes research and clinical practice. 2018;:119-129
Abstract
Glucagon secretion is stimulated by a low plasma glucose concentration. By activating glycogenolysis and gluconeogenesis in the liver, glucagon contributes to maintain a normal glycemia. Glucagon secretion is also stimulated by the intake of proteins, and glucagon contributes to amino acid metabolism and nitrogen excretion. Amino acids are used for gluconeogenesis and ureagenesis, two metabolic pathways that are closely associated. Intriguingly, cyclic AMP, the second messenger of glucagon action in the liver, is released into the bloodstream becoming an extracellular messenger. These effects depend not only on glucagon itself but on the actual glucagon/insulin ratio because insulin counteracts glucagon action on the liver. This review revisits the role of glucagon in nitrogen metabolism and in disposal of nitrogen wastes. This role involves coordinated actions of glucagon on the liver and kidney. Glucagon influences the transport of fluid and solutes in the distal tubule and collecting duct, and extracellular cAMP influences proximal tubule reabsorption. These combined effects increase the fractional excretion of urea, sodium, potassium and phosphates. Moreover, the simultaneous actions of glucagon and extracellular cAMP are responsible, at least in part, for the protein-induced rise in glomerular filtration rate that contributes to a more efficient excretion of protein-derived end products.
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5.
Expression of an Acid Urease with Urethanase Activity in E. coli and Analysis of Urease Gene.
Liu, X, Zhang, Q, Zhou, N, Tian, Y
Molecular biotechnology. 2017;(2-3):84-97
Abstract
Urea in alcoholic beverage is a precursor of ethyl carbamate (EC), which is carcinogenic. Enzymatic elimination of urea has attracted much research interest. Acid urease with good tolerance toward ethanol and acid is ideal enzyme for such applications. In the present work, the structural genes of urease from Providencia rettgeri JN-B815, ureABC were efficiently expressed in E. coli BL21(DE3) in an active form (apourease) exhibiting both urease and urethanase (hydrolyze EC) activities. The specific activities of the purified apourease were comparatively low, which were 2.1 U/mg for urease and 0.6 U/mg for urethanase, respectively. However, apourease exhibited good resistance toward ethanol and acidic conditions. The relative activities of urease and urethanase remained over 80% in the buffers within pH 4-7. And the recoveries of both urease and urethanase activities were more than 50% in 5-25% ethanol solution. Apourease was utilized to eliminate urea in wine, and the residual urea in model wine was less than 50% after treatment with apourease for 30 h. Then 3D structure of UreC was predicted, and it was docked with urea and EC, respectively. The docking result revealed that three hydrogen bonds were formed between urea and amino acid residues in the active site of urease, whereas only one hydrogen bond can be formed between EC and the active center. Moreover, EC exhibited greater steric hindrance than urea when combined with the active site. Due to the low specific activities of apourease, both structural genes and accessory genes of urease were co-expressed in E. coli BL21(DE3). The holoenzyme was expressed as inclusion body. After renaturation and purification, the specific activities of urease and urethanase reached 10.7 and 3.8 U/mg, which were 5.62-fold and 6.33-fold of those of apourease, respectively. Therefore, accessory subunits of urease play an important role in enhancing urease and urethanase activities.
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6.
Molecular and physiological interactions of urea and nitrate uptake in plants.
Pinton, R, Tomasi, N, Zanin, L
Plant signaling & behavior. 2016;(1):e1076603
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Abstract
While nitrate acquisition has been extensively studied, less information is available on transport systems of urea. Furthermore, the reciprocal influence of the two sources has not been clarified, so far. In this review, we will discuss recent developments on plant response to urea and nitrate nutrition. Experimental evidence suggests that, when urea and nitrate are available in the external solution, the induction of the uptake systems of each nitrogen (N) source is limited, while plant growth and N utilization is promoted. This physiological behavior might reflect cooperation among acquisition processes, where the activation of different N assimilatory pathways (cytosolic and plastidic pathways), allow a better control on the nutrient uptake. Based on physiological and molecular evidence, plants might increase (N) metabolism promoting a more efficient assimilation of taken-up nitrogen. The beneficial effect of urea and nitrate nutrition might contribute to develop new agronomical approaches to increase the (N) use efficiency in crops.
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Kt/V (and especially its modifications) remains a useful measure of hemodialysis dose.
Daugirdas, JT
Kidney international. 2015;(3):466-73
Abstract
Removal of small molecular weight solutes shows a strong relationship to hemodialysis outcomes. In contrast, survival with high-flux dialysis or hemodiafiltration is only slightly better than with low-flux hemodialysis. Despite laboratory evidence regarding toxicity of protein-bound uremic solutes, few data exist showing that increased removal of this class of molecules impacts outcomes. In the FHN trials, there was no effect of frequent dialysis, including frequent and long dialysis, on nutrition or control of anemia, outcomes expected to be sensitive to uremic toxin removal; the main benefit appeared to be better volume control. Scaling of hemodialysis dose to total body water may not be optimal. Kt/V scaling to body surface area and use of a continuous measure such as standard Kt/V reduces the likelihood of underdialysis of small patients, including children, and women. Minimum hemodialysis time may best be considered in respect to ultrafiltration rate, and a maximum target ultrafiltration rate unscaled to body size may be optimal. Intensive, extended dialysis may cause adverse effects to residual kidney function, and more information needs to be collected to better understand how urine volume modifies dose requirements, and how to maximize the chances of preserving residual kidney function.
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8.
Once upon a time in dialysis: the last days of Kt/V?
Vanholder, R, Glorieux, G, Eloot, S
Kidney international. 2015;(3):460-5
Abstract
After its proposal as a marker of dialysis adequacy in the eighties of last century, Kt/V(urea) helped to improve dialysis efficiency and to standardize the procedure. However, the concept was developed when dialysis was almost uniformly short and was applied thrice weekly with small pore cellulosic dialyzers. Since then dialysis evolved in the direction of many strategic alternatives, such as extended or daily dialysis, large pore high-flux dialysis, and convective strategies. Although still a useful baseline marker, Kt/V(urea) no longer properly covers up for most of these modifications so that urea kinetics are hardly if at all representative for those of other solutes with a deleterious effect on morbidity and mortality of uremic patients. This is corroborated in several clinical studies showing a dissociation between removal of urea and that of other uremic toxins. In addition, randomized controlled trials showed no benefit of increasing Kt/V(urea). Finally, this parameter also hardly is evocative for metabolic or intestinal generation of toxins, for their removal by residual renal function and for the complex interaction of dialysis length with removal pattern and patient outcomes. We conclude that apart from being a baseline parameter of dialysis adequacy, Kt/V(urea) insufficiently represents all novel strategic changes of modern dialysis. Kt/V(urea) is too simple a concept for the complexities of uremia and of today's dialysis.
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Review on materials & methods to produce controlled release coated urea fertilizer.
Azeem, B, KuShaari, K, Man, ZB, Basit, A, Thanh, TH
Journal of controlled release : official journal of the Controlled Release Society. 2014;:11-21
Abstract
With the exponential growth of the global population, the agricultural sector is bound to use ever larger quantities of fertilizers to augment the food supply, which consequently increases food production costs. Urea, when applied to crops is vulnerable to losses from volatilization and leaching. Current methods also reduce nitrogen use efficiency (NUE) by plants which limits crop yields and, moreover, contributes towards environmental pollution in terms of hazardous gaseous emissions and water eutrophication. An approach that offsets this pollution while also enhancing NUE is the use of controlled release urea (CRU) for which several methods and materials have been reported. The physical intromission of urea granules in an appropriate coating material is one such technique that produces controlled release coated urea (CRCU). The development of CRCU is a green technology that not only reduces nitrogen loss caused by volatilization and leaching, but also alters the kinetics of nitrogen release, which, in turn, provides nutrients to plants at a pace that is more compatible with their metabolic needs. This review covers the research quantum regarding the physical coating of original urea granules. Special emphasis is placed on the latest coating methods as well as release experiments and mechanisms with an integrated critical analyses followed by suggestions for future research.
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10.
Hyponatremia: an update on current pharmacotherapy.
Shchekochikhin, D, Tkachenko, O, Schrier, RW
Expert opinion on pharmacotherapy. 2013;(6):747-55
Abstract
INTRODUCTION Hyponatremia is the most common electrolyte disorder in clinical practice, and it is associated with adverse outcomes. Severe hyponatremia can result in cerebral edema and hypoxia. Moreover, even mild hyponatremia can lead to gait instability and cognitive dysfunction, especially in the elderly. The main cause of hyponatremia is nonosmotic secretion of arginine vasopressin with resultant electrolyte-free water retention. Thus, the available management for chronic hyponatremia must increase solute-free water excretion, such as occurs with blocking vasopressin receptors with selective V2 antagonists. AREAS COVERED Several recent trials have assessed the efficacy and safety of hyponatremia treatment using vasopressin receptor antagonists (vaptans). These trials documented the efficacy of vaptans to reverse hyponatremia. Moreover, treatment of hypervolemic hyponatremia, such as in heart failure or liver cirrhosis, with vasopressin receptor antagonist results in increased solute-free excretion without activation of the neurohumoral systems. The current review covers results on management of hyponatremia with different vasopressin receptor antagonists. EXPERT OPINION Approaches, such as vasopressin receptor antagonists or urea, have been shown to reverse moderate hyponatremia. However, these agents have not been used to treat severe hyponatremia in clinical trials. Future studies in severe hyponatremic states are required to assess the impact of vaptans on clinically significant end points, such as morbidity and mortality.