Dialysis-associated hyperglycemia: manifestations and treatment.

PURPOSE: Dialysis-associated hyperglycemia (DAH), is associated with a distinct fluid and electrolyte pathophysiology. The purpose of this report was to review the pathophysiology and provide treatment guidelines for DAH. METHODS: Review of published reports on DAH. Synthesis of guidelines based on these reports. RESULTS: The following fluid and solute abnormalities have been identified in DAH: (a) hypoglycemia: this is a frequent complication of insulin treatment and its prevention requires special attention. (b) Elevated serum tonicity. The degree of hypertonicity in DAH is lower than in similar levels of hyperglycemia in patients with preserved renal function. Typically, correction of hyperglycemia with insulin corrects the hypertonicity of DAH. (c) Extracellular volume abnormalities ranging from pulmonary edema associated with osmotic fluid shift from the intracellular into the extracellular compartment as a consequence of gain in extracellular solute (glucose) to hypovolemia from osmotic diuresis in patients with residual renal function or from fluid losses through extrarenal routes. Correction of DAH by insulin infusion reverses the osmotic fluid transfer between the intracellular and extracellular compartments and corrects the pulmonary edema, but can worsen the manifestations of hypovolemia, which require saline infusion. (d) A variety of acid-base disorders including ketoacidosis correctable with insulin infusion and no other interventions. (e) Hyperkalemia, which is frequent in DAH and is more severe when ketoacidosis is also present. Insulin infusion corrects the hyperkalemia. Extreme hyperkalemia at presentation or hypokalemia developing during insulin infusion require additional measures. CONCLUSIONS: In DAH, insulin infusion is the primary management strategy and corrects the fluid and electrolyte abnormalities. Patients treated for DAH should be monitored for the development of hypoglycemia or fluid and electrolyte abnormalities that may require additional treatments.

Symptomatic Hyperglycemia in a Patient with Dialysis Ascites.

An anuric woman with ascites rapidly developed extreme hyperglycemia and seizures after hemodialysis. During development of hyperglycemia, the decrease in serum sodium concentration (Δ[Na]) was nearly twice the value predicted by a formula accounting for the degree of hyperglycemia and the intracellular-to-extracellular volume ratio. The prediction assumed that ascitic fluid is part of the extracellular volume. Potential contributors to the development of seizures include the rapid development of severe hypertonicity, a remote history of seizure disorder and development of dialysis disequilibrium syndrome. Observations in peritoneal dialysis suggest that fluid with sodium concentration lower than in the ascitic fluid is transferred from the abdominal cavity into the blood during rapid development of hyperglycemia. In this case, Δ[Na], which determines the tonicity level expected after correction of hyperglycemia, resulted from exit of both intracellular and ascitic fluid into the extracellular compartment and, therefore, ascitic fluid functions as an extension of the intracellular fluid.

Principles of quantitative water and electrolyte replacement of losses from osmotic diuresis.

Osmotic diuresis results from urine loss of large amounts of solutes distributed either in total body water or in the extracellular compartment. Replacement solutions should reflect the volume and monovalent cation (sodium and potassium) content of the fluid lost. Whereas the volume of the solutions used to replace losses that occurred prior to the diagnosis of osmotic diuresis is guided by the clinical picture, the composition of these solutions is predicated on serum sodium concentration and urinary sodium and potassium concentrations at presentation. Water loss is relatively greater than the loss of sodium plus potassium leading to hypernatremia which is seen routinely when the solute responsible for osmotic diuresis (e.g., urea) is distributed in body water. Solutes distributed in the extracellular compartment (e.g., glucose or mannitol) cause, in addition to osmotic diuresis, fluid transfer from the intracellular into the extracellular compartment with concomitant dilution of serum sodium. Serum sodium concentration corrected to euglycemia should be substituted for actual serum sodium concentration when calculating the composition of the replacement solutions in hyperglycemic patients. While the patient is monitored during treatment, the calculation of the volume and composition of the replacement solutions for losses of water, sodium and potassium from ongoing osmotic diuresis should be based directly on measurements of urine volume and urine sodium and potassium concentrations and not by means of any predictive formulas. Monitoring of clinical status, serum sodium, potassium, glucose, other relevant laboratory values, urine volume, and urine sodium and potassium concentrations during treatment of severe osmotic diuresis is of critical importance.

Fluid balance concepts in medicine: Principles and practice.

The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.

The function of probiotics on the treatment of ventilator-associated pneumonia (VAP): facts and gaps.

Probiotics have been used for centuries in making fermented dairy products. The health benefits related to probiotics consumption are well recognized and they are generally regarded as safe (GRAS). Their therapeutic effects are due to the production of a variety of antimicrobial compounds, such as short-chain fatty acids, organic acids (such as lactic, acetic, formic, propionic and butyric acids), ethanol, hydrogen peroxide and bacteriocins. Ventilator-associated pneumonia (VAP) is a nosocomial infection associated with high mortality in intensive care units. VAP can result from endotracheal intubation and mechanical ventilation. These interventions increase the risk of infection as patients lose the natural barrier between the oropharynx and the trachea, which in turn facilitates the entry of pathogens through the aspiration of oropharyngeal secretions containing bacteria into the lung. In order to prevent this, probiotics have been used extensively against VAP. This review is an update containing information extracted from recent studies on the use of probiotics to treat VAP. In addition, probiotic safety, the therapeutic properties of probiotics, the probiotic strains used and the action of the probiotics mechanism are reviewed. Furthermore, the therapeutic effects of probiotic treatment procedures for VAP are compared to those of antibiotics. Finally, the influences of bacteriocin on the growth of human pathogens, and the side-effects and limitations of using probiotics for the treatment of VAP are addressed.

Reproducibility of serial creatinine excretion measurements in peritoneal dialysis.

AIM: To test whether muscle mass evaluated by creatinine excretion (EXCr) is maintained in patients with end-stage kidney disease (ESKD) treated by peritoneal dialysis (PD), we evaluated repeated measurements of EXCr in a PD population. METHODS: One hundred and sixty-six PD patients (94 male, 72 female) receiving the same PD dose for the duration of the study (up to approximately 2.5 years) had repeated determinations of total (in urine plus spent dialysate) 24-h EXCr (EXCr T) to assess the adequacy of PD by creatinine clearance. All 166 patients had two EXCr T determinations, 84 of the 166 patients had three EXCr T determinations and 44 of the 166 patients had four EXCr T measurements. EXCr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times. RESULTS: In patients who were studied twice, with the first and second EXCr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD, respectively, EXCr T did not differ between the first and second study. In patients studied three times and whose final assessment occurred 24.7 ± 16.3 mo after initiating PD, EXCr T did not differ between the first and second study, but was significantly lower in the third study compared to the first study. In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD, EXCr T did not differ between any of the studies. The average EXCr T value did not change significantly, with the exception of the third study in the patients studied thrice. However, repeated determinations of EXCr T in individuals showed substantial variability, with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more. CONCLUSION: The average value of EXCr T remains relatively constant for up to 2.5 years of follow-up in PD patients who adhere to the same PD schedule. However, repeated individual EXCr T values vary considerably in a large proportion of the patients. Further studies are needed to evaluate the clinical significance of varying EXCr T values and the stability of EXCr T beyond 2.5 years of PD follow-up.

Advanced wasting in peritoneal dialysis patients.

AIM: To identify patients with end-stage renal disease treated by peritoneal dialysis (PD) who had zero body fat (BF) as determined by analysis of body composition using anthropometric formulas estimating body water (V) and to compare nutritional parameters between these patients and PD patients whose BF was above zero. METHODS: Body weight (W) consists of fat-free mass (FFM) and BF. Anthropometric formulas for calculating V allow the calculation of FFM as V/0.73, where 0.73 is the water fraction of FFM at normal hydration. Wasting from loss of BF has adverse survival outcomes in PD. Advanced wasting was defined as zero BF when V/0.73 is equal to or exceeds W. This study, which analyzed 439 PD patients at their first clearance study, used the Watson formulas estimating V to identify patients with VWatson/0.73 ≥ W and compared their nutritional indices with those of PD patients with VWatson/0.73 < W. RESULTS: The study identified at the first clearance study two male patients with VWatson/0.73 ≥ W among 439 patients on PD. Compared to 260 other male patients on PD, the two subjects with advanced wasting had exceptionally low body mass index and serum albumin concentration. The first of the two subjects also had very low values for serum creatinine concentration and total (in urine and spent peritoneal dialysate) creatinine excretion rate while the second subject had an elevated serum creatinine concentration and high creatinine excretion rate due, most probably, to non-compliance with the PD prescription. CONCLUSION: Advanced wasting (zero BF) in PD patients, identified by the anthropometric formulas that estimate V, while rare, is associated with indices of poor somatic and visceral nutrition.

Renal systems biology of patients with systemic inflammatory response syndrome.

A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.

Indices of serum tonicity in clinical practice.

Although disturbances of serum tonicity (effective osmolality) may have dire consequences, only surrogate indices of tonicity are available in practice. This report identifies the appropriate index for expressing clinical states of dystonicity. Serum sodium concentration ([Na]S) and osmolality ([Osm]S) may be incongruent. When the tonicity state shown by [Osm]S is higher than [Na]S and the difference between the 2 indices is caused by an excess of solute that distributes in total body water, tonicity is described by [Na]S. When this difference results from a gain of solute with extracellular distribution like mannitol or a decrease in serum water content, causing a falsely low measurement of [Na]S, [Osm]S accurately reflects tonicity. Two indices of tonicity are applicable during hyperglycemia: the tonicity formula (2 ·[Na]S + [Glucose]S/18) and the corrected [Na]S ([Na]S corrected to a normal [Glucose]S using an empirically derived coefficient). Clinicians should understand the uses and limitations of the tonicity indices.

Nephropathy in dietary hyperoxaluria: A potentially preventable acute or chronic kidney disease.

Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis, but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma, profound tubular damage and interstitial inflammation and fibrosis. Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to end-stage renal disease (ESRD). This sequence of events, well recognized in the past in primary and enteric hyperoxalurias, has also been documented in a few cases of dietary hyperoxaluria. Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide, thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions. Studies addressing this question have the potential of improving population health and should be undertaken, alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate, and into the mechanisms of development of oxalate-induced renal parenchymal disease. Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.

Management of severe hyponatremia: infusion of hypertonic saline and desmopressin or infusion of vasopressin inhibitors?

Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. Inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution after saline infusion. In this setting, desmopressin infusion helps prevent overcorrection of the hyponatremia. Monitoring of the changes in serum sodium concentration as a guide to treatment changes is imperative regardless of the initial treatment of severe hyponatremia.

Quality properties, fatty acids, and biogenic amines profile of fresh tilapia stored in ice.

This work determines quality properties and fatty acids content of Nile tilapia (Oreochromis niloticus) stored in ice for 21 d. The quality properties consist of thiobarbituic acid (TBA), total volatile basic nitrogen (TVB-N), trimethylamine (TMA), and microbiological analysis (total viable count (TVC), total coliform, Salmonella and Staphylococcus aureus) and determination of biogenic amines content (histamine, cadaverine, putrescine, spermine, spermidine, 2-phenylethylamine, agmatine, tyramine, and ammonia). Moreover, the fat, moisture, and ash composition as well as fatty acids profile have also been analyzed. The TBA, TVB-N, and biogenic amines analysis showed rather low levels of spoilage even after 21 d of storage. The microbiological analysis, however, showed that tilapia was unsuitable for consumption after just 10 d. The fat, ash, moisture, and fatty acids profile analysis showed that tilapia is not a good source of n-3 fatty acids. The research indicated that the microbiological analysis was the best method to establish spoilage of tilapia stored in ice, of all analytical methods performed in this study.

The importance of community in academic health centers.

BACKGROUND: A strong sense of community in any organization, whether it is a small business or a large academic medical center, positively impacts on productivity, efficiency, and morale and makes for an enjoyable workplace. Striking a balance between institutional interests and those of the individual is an ongoing challenge that demands vigilance on the part of faculty and administrators. A faculty comprising self-absorbed individuals, no matter how accomplished they are, will eventually devolve into dysfunction. As the emphasis on extramural grants and clinical productivity has intensified in recent years, this balance has tilted in favor of individualism at the expense of student success and community spirit. SUMMARY: This article examines factors that tend to undermine community and human behaviors that can counter these negative forces. CONCLUSIONS: If the various stakeholders in the academic health center--deans, chairpersons, faculty, students and staff--all take stock of their responsibilities and commit themselves to restoring a healthier balance between self-interest and institutional missions, beneficial returns are likely in terms of higher quality education and clinical care, increased research productivity and a more vibrant and enjoyable workplace.

Docosahexaenoic acid in maternal and neonatal plasma phospholipids and milk lipids of Taiwanese women in Kinmen: fatty acid composition of maternal blood, neonatal blood and breast milk.

BACKGROUND: Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid (LCPUFA) that is critically important for the structure, development and function of the retina and central nervous system (CNS), ultimately contributing to improved cognition. It is known that the DHA content of breast milk is positively correlated with maternal DHA intake. Since there is a lack of information about the DHA status of pregnant and lactating women in rural Taiwan. The aims of the present study were to: 1) assess the DHA status of mothers and babies in urban setting, and 2) determine the content of DHA in the milk of nursing mothers. METHODS: All pregnant women who attended the Obstetrics and Gynecology Outpatient Clinic of Kinmen Hospital on Kinmen Island in Taiwan between May 1 and May 30, 2011 were invited by research nurses to enroll in the study. The maternal blood sample was obtained on the day of their delivery. Cord blood was collected by the obstetrician following delivery. Participants were asked to visit the doctor forty-two days after the delivery, at which time a nurse collected breast milk on the day mothers were visiting the doctor for post-natal well-baby check-up. RESULTS: The DHA percentages of maternal and neonatal plasma phospholipids were 5.16% and 6.36%, respectively, which are higher than values reported for most populations elsewhere in the world. The DHA percentage for the breast milk of Kinmen mothers was also high (0.98%) relation to international norms. The DHA proportions in maternal and neonatal plasma phospholipids were positively correlated (r = 0.46, p = 0.01). CONCLUSIONS: We show that the DHA status of mothers and newborns on Kinmen Island is satisfactory, thereby providing an evidence-based argument for promoting breastfeeding in Taiwan.

Fatty acid, amino acid, mineral and antioxidant contents of acha (Digitaria exilis) grown on the Jos Plateau, Nigeria.

Digitaria exilis (Kippist) Stapf (also known as acha, hungry rice) has been cultivated for millennia in the dry savannahs of West Africa, but much remains to be learned about its nutritional properties. Acha was collected in four villages in Northern Nigeria and analyzed for fatty acids, minerals, amino acids and antioxidant content. Fatty acids accounted for 1.91% of the dry weight, with 47.4% linoleic acid and 30.5% oleic acid. The content of the essential minerals, copper, magnesium, molybdenum, zinc and calcium averaged 4.88, 1060, 0.23, 23.0 and 172 µg/g, respectively. The protein content was 6.53% and the essential amino acid pattern, except for lysine, compared favorably to a World Health Organization (WHO) reference protein. The total polyphenolic content of methanolic extracts of acha matched that of common cereals (for example, maize, rice, wheat) and the extracts contained substantial amounts of free-radical scavenging substances. Thus, acha is a source of many nutrients critical to human health.

Comparison of diets of urban American Indian and non-Hispanic whites: populations with a disparity for biliary tract cancer rates.

AIM: The incidnece of biliary tract cancer (BTC) is many-fold higher for American Indians (AI) relative to non-Hispanic whites (NHW). Neither gallstones nor genetics can account for this difference. There is speculation that certain fatty acids in bile may play a role in preventing BTC. Since diet may influence composition of bile, we compared the dietary intakes of urban AI and NHW adult women in New Mexico. METHODS: Design, a cross- sectional study of the diets of lactating AI and NHW women was conducted. Setting, the University of New Mexico Hospital. Participants, healthy lactating women 18 to 39 years of age were recruited. Main outcome measures, a three-day diet record for each participant was analyzed. RESULTS: The AI women consumed less calcium (p = 0.04) and significantly less short and intermediate chain-length fatty acids (C4-C12), but nearly twice as much proinflammatory arachidonic acid as the NHWs (p < 0.01). The intake of dairy products by AI women was less than NHW women (p = 0.01) while the intake of processed meat products was higher (p < 0.01). CONCLUSION: Dietary factors may account for the difference in the risk of BTC between AI and NHW women.

Repeated intoxication presenting with azotemia, elevated serum osmolal gap, and metabolic acidosis with high anion gap: differential diagnosis, management, and prognosis.

A man with a history of alcoholism presented on two different occasions with mental changes, clinical signs of volume depletion, elevated serum osmolal gap, metabolic acidosis with high anion gap, metabolic alkalosis, hyponatremia, and azotemia after binge drinking of only ethanol. In both episodes, the serum contained ethanol, acetone, and 2-propanol (isopropanol), but no methanol or ethylene glycol. In the first episode, the rates of excretion of acetoacetate and 3-hydroxybutyrate in the urine were greatly increased. Volume repletion was the only treatment. In both episodes, azotemia and metabolic acidosis were rapidly reversed, while modest metabolic alkalosis was noted after treatment. The triad of azotemia, elevated osmolal gap, and high anion gap metabolic acidosis, which characterizes intoxication with methanol or ethylene glycol, can also develop in alcoholic ketoacidosis (AKA), an entity with substantially different management and outcome. Finding 2-propanol in the serum of patients with AKA indicates either concomitant 2-propanol ingestion or formation of 2-propanol from acetone.

Comparison of the fatty acid composition of the serum phospholipids of controls, prediabetics and adults with type 2 diabetes.

OBJECTIVE: Although abnormalities in the fatty acid composition of serum and red cell membrane phospholipids of patients with type 2 diabetes are well-documented, lacking are studies of this issue in prediabetic individuals. MATERIALS/METHODS: For this cross-sectional study, we recruited 180 subjects (30-80 years), 56 of whom were normal with regard to glucose control (HbA1c, <5.7%), 61 who had prediabetes (HbA1c, 5.7%-6.4%) and 59 who had type 2 diabetes (HbA1c, >6.5%). Serum phospholipids were isolated and analyzed for fatty acids. RESULTS: Most importantly, the fatty acid compositions of the controls and prediabetic subjects were not different for 19 fatty acids. However, the fatty acid profile of the phospholipids of the patients with diabetes differed from the other two groups; the 14 to 18-carbon saturated fatty acids were decreased by 12%-26% whereas the unsaturated fatty acids 16:1n-7, 18:1n-9, 18:2n-6, 20:3n-6 and 20:4n-6 were increased by 45%-64%. Of note, the docosahexaenoic acid (DHA) status of individuals in all three study groups was remarkably low compared with international values, as indicated by DHA proportions in the 1.62%-2.07% range, and there were no differences between groups. The mean melting point of the phospholipid fatty acids of the diabetic patients (32.2°C) was significantly lower (p < 0.001) than that of the prediabetic subjects (38.1°C) and the controls (39.9°C) which were not different from each other. CONCLUSION: These observations indicate that the fatty acid changes associated with type 2 diabetes follow the onset of the disease as opposed to being a causative factor of poor glucose control and insulin insensitivity.