Peritoneal Protein Loss, Leakage or Clearance In Peritoneal Dialysis, Where Do We Stand?

Peritoneal protein loss (PPL) through peritoneal effluent has been a well-recognized detrimental result of peritoneal dialysis (PD) treatment since its inception. Investigation has focused mainly on PPL quantitative and qualitative determinations and evaluation of its prognostic value.A comprehensive review of the pathophysiology of PPL (3-pore model revisited), methods of quantification, dialysate protein composition, and impact on clinical outcomes is presented herein. The author summarizes a brief analysis of associated cardiovascular disease and nutritional consequences, exploring the controversial cause-effect on mortality and technique failure.Therapeutic modalities aiming to reduce PPL (angiotensin-converting enzyme inhibitors [ACEI]s and vitamin D therapies) were explored, although it is unclear whether PPL represents a valid therapeutic target or, on the other hand, is solely a manifestation of endothelial dysfunction.

Primary Intestinal Lymphangiectasia Manifested as Unusual Edemas and Effusions: A Case Report.

Primary intestinal lymphangiectasia (PIL) is a rare disorder of unknown etiology characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via the affected lymphatic vessels causing hypoproteinemia and lymphopenia. The main symptom is variable degrees of pitting edemas of bilateral lower limbs. But edemas of any other parts of body, and mild serous effusions may also occur sometimes. PIL occurs in conjunction with a right hemifacial edema, a right upper limb lymphedema, asymmetric bilateral calves edemas, and a unilateral massive pleural effusion seems never to be reported before. In addition, increased enteric protein loss that may cause severe hypoproteinemia usually get overlooked, and the lymphatic system disorders always put the diagnoses in a dilemma.We described a case of a 17-year-old Chinese girl with a history of gradually progressive swellings of right-sided face, right upper limb, and bilateral calves since 3 to 4 months of age. A right-sided massive pleural effusion, a moderate pericardial effusion, and a mild ascites have been proved unchanged by a series of computerized tomography (CT) scans since 5 years ago. The diagnosis of PIL was finally confirmed by severe hypoproteinemia, endoscopic changes, and histology of jejunum biopsy. Further lymphoscintigraphy and lymphangiography also identified lymph leakage in her bowel and several abnormal lymphatic vessels. A high-protein, low-fat diet supplemented with medium-chain triglycerides (MCT) showed some benefit.This case suggested that PIL was a rare but important etiology of hypoproteinemia, effusions, and edemas. PIL, effusions, and lymphedema can be the features of multisegmental generalized lymphatic dysplasia. In addition, both lymphoscintigraphy and intranodal lymphangiography could be considered when lymphatic system disorders are suspected.

[Pathogenetic grounds of trophological impact of chronic pancreatitis complex therapy].

In chronic pancreatitis patients was found persistent state of oxidative stress on the level of malonic aldehyde, which ran against the lowered levels of antioxidant enzymatic and non-enzymatic composition, and it has been found in the state of hypoproteinemia proteinogram indices (P < 0.05). The use of complex treatment of patients with chronic pancreatitis multivitamin-aminoacid drug Moriamin forte contributes to a significant regression effects oxidative stress and reduces the effects of hypoproteinemia (P < 0.05).

Maternal prolactin inhibition during lactation affects physical performance evaluated by acute exhaustive swimming exercise in adult rat offspring.

Maternal prolactin inhibition at the end of lactation programs for metabolic syndrome and hypothyroidism in adult offspring, which could negatively affect exercise performance. We evaluated the effects of maternal hypoprolactinemia in late lactation on physical performance in adult progeny. Lactating Wistar rats were treated with bromocriptine (BRO, 1 mg per day) or saline on days 19, 20, and 21 of lactation and offspring were followed until 180 days old. Physical performance was recorded in untrained rats at 90 and 180 days by an acute exhaustive swimming test (exercise group-Ex). At day 90, BRO offspring showed higher visceral fat mass, higher plasma thiobarbituric acid reactive substances, lower total antioxidant capacity, higher liver glycogen, lower glycemia, and normal insulinemia. Although thyroid hormones (TH) levels were unchanged, mitochondrial glycerol phosphate dehydrogenase (mGPD) activity was lower in muscle and in brown adipose tissue (BAT). At this age, BRO-Ex offspring showed higher exercise capacity, lower blood lactate, higher serum T3, and higher muscle and BAT mGPD activities. At day 180, BRO offspring showed central obesity, hypothyroidism, insulin resistance, and lower EDL (extensor digitorum longus) muscle glycogen with unaltered plasma oxidative stress markers. This group showed no alteration of exercise capacity or blood lactate. After exercise, EDL and liver glycogen were lower, while T3 levels, BAT and muscle mGPD activities were normalized. Liver glycogen seem to be related with higher exercise capacity in younger BRO offspring, while the loss of this temporary advantage maybe related to the hypothyroidism and insulin resistance developed with age.

Hypoproteinemia does not alter plasma volume expansion in response to a 0.9% saline bolus in awake sheep.

OBJECTIVE: To test the hypothesis that hypoproteinemia reduces plasma volume expansion produced by a bolus of crystalloid solution given to awake sheep. DESIGN: Prospective and observational. SETTING: Laboratory. SUBJECTS: Five female merino sheep (n = 5) weighing 37 ± 3 kg were anesthetized. INTERVENTIONS: Each animal was subjected to a 5-day test period: day 1: 50 mL/min 0.9% saline infusion over 20 mins. Days 2-4: daily plasmapheresis and replacement of the shed plasma with 6 L of 0.9% saline were performed in increments. MEASUREMENTS AND MAIN RESULTS: Fractional plasma volume expansion after rapid infusion of saline on days 1 and 5 was calculated from changes in hemoglobin concentration. There was a significant reduction in total plasma protein concentration after plasmapheresis (p < .05). Colloid osmotic pressures were also significantly lowered (p < .05). A crystalloid infusion of 0.9% saline did not alter any of these values compared with baseline. The hemodynamic measurements did not show significant differences between the experiments. The plasma volume expansion reached approximately 20% at the end of infusion and stayed at 10-15% during the experiments. No difference was found in plasma volume expansion produced by a bolus of 50 mL/min of 0.9% in the hypoproteinemic state when compared with the euproteinemic state (p = .61). No difference in cumulative urinary output was found between the two states. CONCLUSIONS: In contrast to our hypothesis, severe acute hypoproteinemia does not reduce plasma volume expansion in response to 50 mL/min 0.9% saline infusion in nonspleenectomized sheep when compared with the resultant plasma volume expansion after a 50 mL/min of 0.9% infusion in the euproteinemic state.

Understanding and managing fluid balance in patients with acute lung injury.

PURPOSE OF REVIEW: Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) affect hundreds of thousands of people each year worldwide, resulting in a significant healthcare burden. Over the past four decades, much has been discovered regarding the pathophysiology of lung injury, yet little progress has been made in advancing effective treatment strategies. In this article, we discuss the current knowledge as to fluid balance in the pathophysiology of ALI/ARDS and the recent innovations that have been described related to manipulations of hydrostatic or oncotic pressure in this condition. RECENT FINDINGS: Hypoproteinemia is a clear marker for ALI/ARDS and may play a pathophysiologic role given its independent prognostic value. Fluid balance and oncotic pressure alterations induced by diuretic and colloid therapy improve respiratory physiology and likely alter net flux of fluid across the injured capillary-alveolar membrane. Chest radiographs serve as a useful adjunctive tool in monitoring longitudinal fluid balance manipulations in ALI/ARDS. SUMMARY: Manipulation of Starling forces in established ALI/ARDS produces significant physiologic benefit and may influence outcome. Future research should focus on determining a mortality benefit with this readily available intervention.

Pressure sores and blood and serum dysmetabolism in spinal cord injury patients.

STUDY DESIGN: Spinal cord injury (SCI) patients with pressure sores were studied before and after surgical intervention for ulcer healing and compared with matched SCI patients without sores and with patients with pressure sores and other diseases. OBJECTIVE: To analyse the relationship between pressure sores and anaemia and serum protein alteration in SCI patients. To study the pathogenesis of these alterations and suggest appropriate therapy. SETTING: Spinal cord unit in Rome, Italy. SUBJECTS: A total of 13 SCI patients with pressure sores, 13 comparable patients without pressure sores and four patients with other diseases and pressure sores. MAIN MEASURES: Haematochemical parameters. RESULTS: Patients with pressure sore showed significant decreased red cells, decreased haemoglobin and haematocrit, increased white cells and ferritin and decreased transferrin and transferrin saturation; total hypoproteinemia and hypoalbuminemia with increased Alfa-1 and gamma globulins increased erythrocyte sedimentation rate and C-reactive protein were also present. The alterations returned to normal after surgical intervention for pressure sore healing. CONCLUSIONS: Patients with pressure sores suffer from anaemia and serum protein alteration that fells within the range of metabolic alteration of chronic disorders and neoplastic diseases. The alterations depend on a decreased utilisation of iron stores in the reticuloendothelial system and on inhibition of the hepatic synthesis of albumin. With regard to treatment, iron treatment should be avoided because of the risk of haemochromatosis.

Utilization of knockout mice to examine the potential role of gastric histamine H2-receptors in Menetrier's disease.

Menetrier's disease is characterized by giant gastric folds with foveolar hyperplasia and cystic dilatation, hypoproteinemia, and enhanced mucus secretion. The etiology remains unresolved and an effective treatment has yet to be established. Here we show that histamine H(2)-receptor deficient mice developed gastric pathophysiological changes resembling Menetrier's disease for up to 17 months of observation. Mutant mice were found to have an increased stomach weight, enlarged gastric folds with cystic dilatation, hypergastrinemia, hypoalbuminemia, increased mucus secretion and overexpression of mucosal transforming growth factor (TGF) alpha. Both a cholecystokinin (CCK)(2)-receptor antagonist and an epidermal growth factor (EGF)-receptor tyrosine kinase inhibitor significantly reduced the increase in stomach weight. It appears that lack or downregulation of histamine H(2)-receptors might be involved in the pathogenesis of Menetrier's disease.

[Albumin--biological functions and clinical significance]. / Albumina--funkcje biologiczne i znaczenie kliniczne.

Albumin is a simple protein present both in animal and plant physiological fluids and tissues. It plays many important roles including maintenance of appropriate osmotic pressure, binding and transport of various substances like hormones, drugs etc. in blood, and neutralisation of free radicals. Both acute and chronic disorders lead to hypoalbuminemia, oedema and many other disturbances. Albumin preparations obtained by separation of human plasma are used clinically for more than 50 years to reverse hypoalbuminemia and to allow for reversal of abnormalities in substance transport. These problems are discussed through out this paper.

Effect of hydroxyethyl starch infusion on colloid oncotic pressure in hypoproteinemic horses.

OBJECTIVE: To determine the effect of hydroxyethyl starch (HES) on colloid oncotic pressure (pi) during fluid resuscitation of hypoproteinemic horses and to evaluate the clinical usefulness of direct and indirect methods for determination of pi before and after infusion of a synthetic colloid. DESIGN: Prospective clinical study. ANIMALS: 11 hypoproteinemic horses. PROCEDURE: Horses received IV infusions of 8 to 10 ml of a 6% solution of HES/kg (3.6 to 4.5 ml/lb) of body weight during fluid resuscitation. Blood samples were obtained for determination of plasma measured colloid oncotic pressure (pi meas) and plasma total protein and albumin (A) concentrations. Plasma globulin concentration (G) was calculated as the difference between plasma total protein and albumin concentrations. Calculated values for colloid oncotic pressure (piA + G) were determined by use of a predictive nomogram previously developed for horses. RESULTS: There was no significant difference between the means of pi meas and piA + G at the beginning of HES infusion. After HES infusion, the mean of pi meas was increased significantly from baseline for 6 hours. Mean plasma total protein and albumin concentrations and piA + G were decreased significantly from baseline for 24 hours. Differences between mean pi meas and piA + G after HES infusion were significant for 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: There was good agreement between plasma pi meas and piA + G in blood samples obtained from hypoproteinemic horses immediately before infusion of HES. Use of a predictive nomogram did not, however, account for the oncotic effect of HES. Results of comparison of pi meas to piA + G after HES infusion suggest that a significant oncotic effect was maintained for 24 hours in the study horses.

Hypoproteinemia predicts acute respiratory distress syndrome development, weight gain, and death in patients with sepsis. Ibuprofen in Sepsis Study Group.

OBJECTIVE: Starling's equation indicates that reduced oncotic pressure gradients will favor edema formation, and the current consensus definition of acute respiratory distress syndrome (ARDS) excludes only the hydrostatic pressure contribution. We hypothesized that low serum total protein levels might correlate with the likelihood of ARDS in at-risk patients because serum total protein is the chief determinant of oncotic pressure in humans. DESIGN: Regression analysis to compare outcomes in patients with low serum total protein levels with outcomes in patients with normal serum total protein levels with respect to weight change, development of ARDS, and mortality. SETTING: Intensive care units (ICUs) of seven clinical centers in North America. PATIENTS: A total of 455 ICU patients who met consensus criteria for severe sepsis (178 of whom developed ARDS) from a recently completed prospective clinical trial. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We found that 92% of the patients developing ARDS had low or borderline serum total protein levels (<6 g/dL). Logistic and multiple regression analyses confirmed that of 18 clinical variables, initial serum total protein level and protein change over time were the most statistically significant predictors of weight gain, prolonged mechanical ventilation, ARDS development, and mortality in the study population. This correlation remained significant after adjustment for the other major predictors of outcome present at baseline (ie, Acute Physiology and Chronic Health Evaluation II score). CONCLUSIONS: Hypoproteinemia is significantly correlated with fluid retention and weight gain, development of ARDS and poor respiratory outcome, and mortality in patients with sepsis. Prospective, randomized trials of serum protein manipulation are needed to establish whether there is a cause-effect relationship to this association.

Enfermedad de ménétrier: presentación de un caso infantil con diez años de seguimiento y degeneración maligna / Gastric adenocarcinoma in a patient with ménétrier disease after ten years of follow-up

Introducción. La enfermedad de Ménétrier ocurre con menor frecuencia en los niños que en los adultos. En los niños se reconoce como una enfermedad benigna, autolimitada, de buen pronóstico; en adultos por el contrario, puede malignizarse y degenerar en linfoma gástrico o adenocarcinoma. Se caracteriza por hipertrofia de los pliegues gástricos, hipoproteinemia con hipoalbuminemia e hipersecreción gástrica, con hipoclorhidria o aclorhidria. Caso clínico. Se presenta el caso de una niña con enfermedad de Ménétrier diagnosticada a los 12 años de edad con evolución atípica y seguimiento durante 10 años. Se describen los hallazgos clínicos, bioquímicos, endoscópicos e histológicos durante su evolución, así como tratamientos recibidos y su respuesta. Se describe la evolución atípica, degeneración maligna de la enfermedad. Se hace una revisión de la literatura en cuanto a las causas de la enfermedad, su fisiopatología, evolución natural y las posibilidades terapéuticas existentes. Conclusión. En este caso se demuestra la degeneración maligna de la enfermedad de Ménétier, con evolución a adenocarcinoma gástrico intramucoso, después de diez años de evolución, en una niña de doce años de edad, este tipo de evolución se ha descrito solamente en adultos.

Body growth of children with steroid-resistant nephrotic syndrome.

Whilst it is assumed that body growth is retarded in children with steroid-resistant nephrotic syndrome (NS), the degree of growth failure and the pathomechanisms involved are poorly understood. We collected serial growth data in 45 children (24 males) with steroid-resistant NS usually from onset to end-stage renal disease (ESRD) during childhood (n=10) or until final height was attained (n=27). Mean follow-up time was 9 (2-19) years. Mean initial standardized height was -0.3+/-1.2 standard deviation scores (SDS). Mean final height was +0.4 SDS in males and -1.0 SDS in females (sex difference not significant). In 16 patients with serum creatinine levels consistently <1.2 mg/dl, mean final height SDS was 0.3 SDS higher than that obtained within 6 months of onset. In contrast, 9 children who entered ESRD lost an average of 1.3 SDS from the initial record to ESRD (P=0.017). In prepubertal patients without renal insufficiency, mean height SDS decreased during corticosteroid treatment by 0.3 SDS, followed by a partial catch-up after discontinuation of treatment; the change from initial to final height SDS was inversely correlated with the total prednisone dose given (r=-0.50, P=0.03). In 16 prepubertal children with serial height and serum protein measurements who were off steroids and maintained normal creatinine levels, mean individual albumin concentrations correlated with the change in height SDS per year (r=0.65, P=0.0006) and in boys with final height (r=0.73, P=0.03). In conclusion, growth in steroid-resistant NS depends on the preservation of renal function, the cumulative dose of steroids applied, and the severity of hypoproteinemia.

Hypoproteinemia, strong-ion difference, and acid-base status in critically ill patients.

The present study was a prospective, nonrandomized, observational examination of the relationship among hypoproteinemia and electrolyte and acid-base status in a critical care population of patients. A total of 219 arterial blood samples reviewed from 91 patients was analyzed for arterial blood gas, electrolytes, lactate, and total protein. Plasma strong-ion difference ([SID]) was calculated from [Na+] + [K+] - [Cl-] - [La-]. Total protein concentration was used to derive the total concentration of weak acid ([A]tot). [A]tot encompassed a range of 18.7 to 9.0 meq/l, whereas [SID] varied from 48.1 to 26.6 meq/l and was directly correlated with [A]tot. The decline in [SID] was primarily attributable to an increase in [Cl-]. A direct correlation was also noted between PCO2 and [SID], but not between PCO2 and [A]tot. The decrease in [SID] and PCO2 was such that neither [H+] nor [HCO-3] changed significantly with [A]tot.

Effects of hypoproteinemia-induced myocardial edema on left ventricular function.

In previous studies, we observed left ventricular (LV) systolic and diastolic dysfunction in association with interstitial myocardial edema (IME) induced by either coronary venous hypertension (CVH) or lymphatic obstruction. In the present study, we examined the effects of myocardial edema induced by acute hypoproteinemia (HP) on LV systolic and diastolic function. We also combined the methods of HP and CVH (HP-CVH) to determine their combined effects on LV function and myocardial water content (MWC). We used a cell-saving device to lower plasma protein concentration in HP and HP-CVH groups. CVH was induced by inflating the balloon in the coronary sinus. Six control dogs were treated to sham HP. Conductance and micromanometer catheters were used to assess LV function. Contractility, as measured by preload recruitable stroke work, did not change in control or HP groups but declined significantly (14.5%) in the HP-CVH group. The time constant of isovolumic LV pressure decline (tau) increased significantly from baseline by 3 h in the HP (24.8%) and HP-CVH (27.1%) groups. The end-diastolic pressure-volume relationship (stiffness) also increased significantly from baseline by 3 h in the HP (78.6%) and HP-CVH (42.6%) groups. Total plasma protein concentration decreased from 5.2 +/- 0.2 g/dl at baseline to 2.5 +/- 0.0 g/dl by 3 h in the HP and HP-CVH groups. MWC of the HP (79.8 +/- 0.25%) and HP-CVH groups (79.8 +/- 0.2%) were significantly greater than that of the control group (77.8 +/- 0.3%) but not different from one another. In conclusion, hypoproteinemia-induced myocardial edema was associated with diastolic LV dysfunction but not systolic dysfunction. The edema caused by hypoproteinemia was more than twice that produced by our previous models, yet it was not associated with systolic dysfunction. CVH had a negative inotropic effect and no significant influence on MWC. IME may not have the inverse causal relationship with LV contractility that has been previously postulated but appears to have a direct causal association with diastolic stiffness as has been previously demonstrated.

Spontaneous remission of hypertrophic lymphocytic gastritis associated with hypoproteinemia.

A 54-year-old woman came to our office because of pretibial edema. She had no gastrointestinal symptoms. Laboratory tests revealed severe hypoproteinemia. Upper gastrointestinal endoscopy demonstrated enlarged gastric folds and multiple aphthoid nodules on the body and the fornix of the stomach. The biopsy specimen revealed a large number of CD8 positive intraepithelial T-lymphocytes infiltrating the gastric mucosa. Both serum total protein and the gastric lesions improved eight months after her first visit without any therapy for peptic ulcer or eradication of Helicobacter pylori. The data suggest that spontaneous remission may occur in lymphocytic gastritis without any gastrointestinal symptoms.

Intestinal lymphangiectasia: value of Tc-99m dextran lymphoscintigraphy.

Intestinal lymphangiectasia is a common cause of protein-losing enteropathy characterized by diarrhea, generalized edema, enteric protein loss, hypoproteinemia, and lymphopenia. Diagnosis is based on demonstration of enteric protein loss and characteristic small bowel mucosal histology. Various imaging modalities including barium studies, computed tomography, and lymphangiography have had limited clinical use. The authors report a case of intestinal lymphangiectasia in which Tc-99m dextran lymphoscintigraphy played a significant role in the patient management.