Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.

Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.

Hypoproteinemia as a prognostic risk factor for arteriovenous fistula failure.

INTRODUCTION: Any vascular access is of limited duration with many factors which influence survival in patients on chronic hemodialysis (HD). Hypoproteinemia as a marker of chronic illness is common among chronic HD patients. Our aim was to analyze the survival of the primary arteriovenous fistula (AVFs) and the risk factors which influence their patency and to test the hypothesis that patients with normal values of serum proteins have lower risk of AVF failure compared to patients with hypoproteinemia. METHODS: Seven hundred thirty-four consecutive patients were included who underwent creation of an AVF. The patients were prospectively followed-up for 2 years. Only patients with AVF function after a month from its creation were analyzed. The patients were divided into two subgroups, with normal and low serum protein levels (<65 g/L). FINDINGS: At follow-up 497 (67.7%) AVFs were still functional while 237 (32.3%) AVFs failed due to thrombosis or stenosis. Serum proteins and AVFs created on the forearm were positive predictors while diabetes was a negative predictor of longer AVF survival (P < 0.001; P = 0.003; P = 0.043). When comparing patients with normal and low serum protein levels (<65 g/L), mean survival time was significantly longer in patients with normal serum levels (P < 0.001). DISCUSSION: In this study, hypoproteinemia was an independent prognostic marker for AVF failure at 2 years. Hypoproteinemia, based on our results, is an independent, more sensitive and prognostic marker of possible vascular access failure than the presence of other common factors which influence shorter AVF survival.

Nutrition support can bring survival benefit to high nutrition risk gastric cancer patients who received chemotherapy.

PURPOSE: The aim of our study is firstly to evaluate the prevalence and prognostic value of nutrition risk in gastric cancer patients and secondly to explore whether the nutrition support can prolong the survival of advanced gastric cancer patients. METHODS: It contained two study periods. In the first period, we prospectively evaluated the nutritional risk of gastric adenocarcinoma patients from 2009 to 2011 using the method of European Nutritional Risk Screening (NRS) 2002. The Kaplan-Meier method and log-rank test were used to evaluate the prognostic value of high nutrition risk. The second period was between 2012 and 2013. We prospectively gave the nutrition support to stage IV gastric cancer patients whose NRS is ≥3. RESULTS: There were 830 patients in the first period, 50.7% patients with a NRS ≥ 3. Patients with NRS ≥ 3 presented a significantly higher percentage of stage IV diseases, elevated values of C-reactive protein, and hypoproteinemia. The median survival was significantly higher in NRS < 3 patients (31.9 vs. 25.7 months, P < 0.001). Multivariate analysis confirmed that NRS status was an independent prognostic factor. There were 347 patients in the second period. Young, male, and good response to chemotherapy were more likely to have the NRS shift to <3 after nutrition support. The median survival was 14.3 and 9.6 months for patients with and without NRS shift, respectively, P = 0.001. CONCLUSIONS: NRS ≥ 3 was an independent adverse prognostic factor in gastric cancer patients. For stage IV patients whose NRS ≥ 3, the nutrition support might be helpful to improve the prognosis.

A novel distal very long Roux-en Y gastric bypass (DVLRYGB) as a primary bariatric procedure--complication rates, weight loss, and nutritional/metabolic changes in the first 355 patients.

Proximal Roux-en Y gastric bypass (RYGB) representing the most frequently performed bariatric procedure yields a weight loss failure rate of around 20 %. In order to reduce failure rates, we established a novel distal RYGB variant characterized by a very long alimentary (Roux) limb and a short common channel. Up to 5 years, follow-up data (complication rates, weight loss, nutritional/metabolic changes) of the first 355 patients (mean ± SD preoperative age, 41.4 ± 10.8 years; BMI, 48.5 ± 11.5 kg/m(2)) who underwent the novel Distal Very Long Roux-en Y Gastric Bypass (DVLRYGB) were analysed. Overall follow-up rate was 98.9 %, mean follow-up time 1.6 ± 1.4 years. Limb lengths were as follows: common channel 76 ± 7 cm, biliopancreatic limb 79 ± 14 cm, and alimentary (Roux) limb 604 ± 99 cm. The operation was performed laparoscopically in 95.2 % of the cases. Thirty-day mortality was zero; major and minor complication rate was 4.5 % and 10.4 %, respectively. Average excess weight loss (EWL) was >74 % 3, 4, and 5 years after the operation and failure rate defined by an EWL < 50 % remained < 6 %. Annually blood measurements revealed a relatively low incidence rate of severe nutritional deficiencies, but mild anaemia and hypoproteinemia were frequently observed. Laparoscopic revision with a proximalization of the lower anastomosis was required in 4 (1.1 %) patients. Data indicate that our DVLRYGB leads to excellent weight loss results. Furthermore, within the setting of a structured multidisciplinary follow-up program, the incidence of severe malnutrition states was relatively low.

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.

Biochemical responses of juvenile and adult Japanese quails to cyanobacterial biomass.

OBJECTIVES: The aim of the present study was to evaluate differences between juvenile and adult Japanese quails in responses to the exposure to cyanobacterial biomass in the diet. DESIGN: The OECD 205 Guideline on Avian Dietary Toxicity Test (1984) was employed in the experiment. A total of 75 freshly hatched chicks and 30 adults were exposed to cyanobacterial biomass for 15 days and blood sampled daily and on days 5, 10 and 15, respectively. Japanese quail chicks and adults received the same daily dose of approximately 224.4 ng microcystins per gram of body weight. Biochemical responses were compared against controls. RESULTS: No Japanese quail chicks and adults died during the acute 15-day-cyanobacterial-biomass exposure. Biochemical responses to the biomass in diet were first observed from day 5 post exposure to cyanobacterial biomass both in chicks and adults and there were age-related differences in the parameters changed. The responses of adult birds included an increase in lactate dehydrogenase, a drop in glucose and the total antioxidant capacity as well as a 15 to 20 % inhibition of acetylcholinesterase activity. Japanese quail chicks exposed to cyanobacterial biomass for the first 15 days after hatching reacted by having hypoproteinaemia, increased concentrations of triglycerides, uric acid and the total antioxidant capacity and a drop in high-density lipoprotein cholesterol in the blood. CONCLUSIONS: Chicks were not found to be more susceptible to the effects of biomass exposure. It seems that, due to their physiological preparation for the oxidative stress associated with hatching, Japanese quail chicks were even better able to cope with the cyanobacterial-biomass-induced oxidative stress than adults.

Cosyntropin-stimulated salivary cortisol in hospitalized patients with hypoproteinemia.

Analysis of adrenocortical function in acutely ill, hospitalized patients can be challenging due to changes in plasma binding proteins. This study used dynamic testing of salivary cortisol levels to evaluate adrenal function in hospitalized patients with low/low-normal plasma protein concentration in whom adrenal insufficiency was suspected. Twenty-eight patients with low serum albumin and proteins hospitalized for acute illness were evaluated for decreased adrenocortical function because of clinical presentations suspicious for adrenal insufficiency. Baseline and post cosyntropin-stimulated levels of serum total and salivary cortisol levels were assessed. Data were gathered by a retrospective analysis of medical records. Eight patients had normal peak serum total and salivary cortisol responses, consistent with intact adrenocortical function. Five patients had abnormal peak serum total and salivary cortisol responses indicating decreased adrenocortical function. Fifteen patients had subnormal peak serum total cortisol, but normal peak salivary cortisol responses indicating normal adrenal function. Salivary cortisol testing can identify hospitalized patients with apparently intact adrenal function in whom low serum protein confounded interpretation of serum total cortisol measurements. Salivary cortisol is a clinically useful surrogate for serum free cortisol in dynamic testing of adrenocortical function.

Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta2-microglobulin gene.

Two siblings, products of a consanguineous marriage, were markedly deficient in both albumin and IgG because of rapid degradation of these proteins, suggesting a lack of the neonatal Fc receptor, FcRn. FcRn is a heterodimeric receptor composed of a nonclassical MHC class I alpha-chain and beta(2)-microglobulin (beta(2)m) that binds two ligands, IgG and albumin, and extends the catabolic half-lives of both. Eight relatives of the siblings were moderately IgG-deficient. From sera archived for 35 years, we sequenced the two siblings' genes for the heterodimeric FcRn. We found that, although the alpha-chain gene sequences of the siblings were normal, the beta(2)m genes contained a single nucleotide transversion that would mutate a conserved alanine to proline at the midpoint of the signal sequence. Concentrations of soluble beta(2)m and HLA in the siblings' sera were <1% of normal. Transfection assays of beta(2)m-deficient cultured cells with beta(2)m cDNA indicated that the mutant beta(2)m supported <20% of normal expression of beta(2)m, MHC class I, and FcRn proteins. We concluded that a beta(2)m gene mutation underlies the hypercatabolism and reduced serum levels of albumin and IgG in the two siblings with familial hypercatabolic hypoproteinemia. This experiment of nature affirms our hypothesis that FcRn binds IgG and albumin, salvages both from a degradative fate, and maintains their physiologic concentrations.

Time course analysis of serum and urinary proteins by SDS-PAGE in experimental nephrotic syndrome.

Serum and urinary proteins from rats with nephrotic syndrome (NS) induced by puromycin aminonucleoside (PAN) were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Analysis was made on days 2, 4, 6, 8, 10, 12, 16, 20, and 30 after PAN injection. Data were compared with control rats (C). Rats developed proteinuria on days 4-30 and hypoproteinemia on days 4-16. Total protein concentration in serum and urine was similar on day 6. SDS-PAGE revealed that urinary albumin augmented on days 4-30 and serum albumin decreased markedly on days 4-20. Albumin concentration in serum and urine was similar on days 4-16. In addition, the study examined serum changes of 7 other proteins (designed as A, B, C, D, E, F, and G) which appeared or increased in urine, and whose molecular weights were higher (A, B, and C) or lower (D, E, F, and G) than that of albumin. In serum, protein A remained unchanged; protein B and G increased; proteins C, D, E, and F decreased. The qualitative pattern of urinary proteins remained essentially unchanged on days 4-30. During the intense proteinuria, the serum concentrations of protein B and albumin were similar and the urine concentrations of proteins C and D became comparable to that found in serum. These 7 serum proteins did not show the same behavior although all of them were excreted in urine. These data indicate that in PAN-nephrotic rats: (a) urinary proteins can be of low and high molecular weight, (b) serum proteins can be regulated independently of their urinary excretion and molecular weight, (c) the urine concentration of total protein and some specific proteins can reach values similar to that found in serum during the intense hypoproteinemia, and (d) the qualitative pattern of urinary proteins was unrelated to the magnitude of proteinuria.

High-affinity interaction of long-chain fatty acids with serum albumin in nephrotic syndrome.

1. We have examined the effect of hypoalbuminaemia, a hallmark of nephrotic syndrome, on the albumin-fatty acid equilibrium in the plasma of 11 adult patients with nephrosis compared with 12 healthy subjects and six subjects with normoalbuminaemic hyperlipoproteinaemia. 2. We used a dialysis exchange rate method which allows the evaluation in relative terms of the binding affinity of albumin for plasma fatty acid and the fatty acid availability, tentatively equated with the unbound fatty acid fraction. 3. In nephrotic patients, an increase (P < 0.001) in albumin affinity for fatty acid was seen compared with healthy subjects, which was negatively correlated with albuminaemia (r = -0.69, P < 0.02). No change in fatty acid availability was seen for the group as a whole, but individual values showed a wide scatter, with the highest values in four patients with the highest fatty acid-albumin molar ratios. The increase in albumin affinity for fatty acid was specific to nephrotic syndrome since no such effect was seen in subjects with hyperlipoproteinaemia, who only showed a moderate increase (P < 0.01) in fatty acid availability. 4. The increased albumin affinity for fatty acid in nephrotic syndrome supports the hypothesis that an albumin component with lower affinity for fatty acid might filter out through the diseased glomerular membrane and leave the high-affinity albumin in plasma.

Increased lymphatic hyaluronan output and preserved hyaluronan content of the rat small intestine in prolonged hypoproteinaemia.

Nephrotic syndrome was induced in seven rats by daily aminonucleoside injections. Experiments were performed in anaesthesia 6 or 7 d later when protein loss in urine had reduced serum colloid osmotic pressure (COP) to 8.2 +/- 0.9 (SD) mmHg compared with 20.2 +/- 2.2 mmHg in controls (P < 0.01). Due to the decreased COP in the nephrotic rats, lymph flow in the main mesenteric lymphatic was 29.5 +/- 11.5 microliters min-1 compared with 4.2 +/- 2.2 microliters min-1 in the control rats (P < 0.01). The corresponding hyaluronan concentrations were 3.4 +/- 0.9 micrograms ml-1 and 12.0 +/- 3.5 micrograms ml-1, respectively (P < 0.01). Nevertheless lymphatic hyaluronan output was doubled in the nephrotic rats, but this did not affect the hyaluronan content of the small intestine of 192 +/- 58 micrograms g-1 dry wt compared with 215 +/- 69 micrograms g-1 in controls (P > 0.05). During a 20 min intravenous 0.9% saline infusion of 4 ml 100 g-1 rat, the hyaluronan concentration increased to 18.3 (6.0) micrograms ml-1 in mesenteric lymph in controls, whereas the concentration in lymph from the nephrotic rats remained unchanged. Lymphatic output increased, however, in this group as well due to the elevated flow. The amount of hyaluronan cleared daily by the main mesenteric lymphatic in awake rats corresponds to about half the tissue hyaluronan content in the drained area (østgaard & Reed 1993 b).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of post-operative hypalbuminaemia: a clinical study.

OBJECTIVE: Analysis of severity, causes and relevance of hypalbuminaemia developing after surgery. SUBJECTS: Patients undergoing elective aortic surgery (n = 11) or minor extra-abdominal surgery (n = 6). METHODS: Serum albumin concentration, blood loss, nitrogen balance and complications were determined until the fifth post-operative day. The contributions of haemodilution, albumin loss, albumin catabolism and redistribution were calculated using existing formula. The relation of hypalbuminaemia to the endocrine-metabolic response was determined. RESULTS: Significant hypalbuminaemia occurred after aortic surgery, in the absence of significant complications. No haemodilution occurred. Analysis indicated that 18% of hypalbuminaemia was caused by blood loss. Only 6% could be attributed to albumin catabolism, despite a significant correlation with the endocrine-metabolic response. Seventy-seven percent of hypalbuminaemia was attributed to albumin redistribution. No hypalbuminaemia occurred after minor surgery. CONCLUSION: Post-operative hypalbuminaemia is a normal finding early after aortic surgery. It is mainly caused by albumin redistribution, not by metabolic changes.

Glutamine and glutamate in ascitic fluid of dogs.

The amino acid pattern in the ascites of 79 dogs was examined. The concentration of glutamine in neoplastic ascites is significantly lower than in cardial effusions. In contrast, glutamate is significantly higher in neoplastic ascites than in cardial ascites. Using an arbitrary discrimination value of 0.28 for the glutamate/glutamine ratio, purulent or cardial ascites are easily differentiated, with a sensitivity of 100% and a specificity of 94%. The differentiation is very distinct, with no overlap between the group of patients with liver cirrhosis on the one hand and the groups of patients with purulent peritonitis, heart failure, or malignant ascites on the other hand. There was no diagnostically unsable correlation between the concentrations of the other 20 amino acids and the underlying causes of ascites formation.

Reduction in plasma protein does not affect body water content in fetal sheep.

We performed this study to determine if isolated hypoproteinemia and low colloid osmotic pressure cause formation of fetal edema. We successfully operated on six sets of twin fetal sheep at 114 d gestation to insert catheters into arteries and veins of both fetuses, allowing us to chronically perform partial exchange transfusions. One twin underwent protein reduction by repeated partial exchange transfusion over 3 d, and the other twin underwent simultaneous sham procedures. We removed an average of 18 g of protein, causing a 41% decrease in plasma protein concentration and a 44% decrease in colloid osmotic pressure. Vascular pressures, heart rate, hematocrit, plasma osmolarity, arterial pH, and arterial PO2 were not affected by protein reduction or by sham procedure, whereas PCO2 increased by a small amount in both groups. At autopsy, none of the fetuses in either group were edematous. Measurements of total body water by the wet to dry method, chloride space, and amniotic and allantoic fluid volumes were similar in both groups. We conclude that hypoproteinemia of a short duration does not affect the body water content of fetal sheep.

Influence of the plasma protein concentration on renal function.

1. The effect of the plasma protein concentration on renal function remains controversial. Most, but not all, experimental studies suggest that a reduced plasma protein concentration perfusing the kidney may reduce tubular sodium reabsorption. Hypoproteinaemic disease states are usually associated with sodium retention, which is not always volume-dependent. 2. We induced a 21% and 24% reduction in plasma total protein and plasma albumin, respectively, in unanaesthetized sheep by acute extracorporeal plasmapheresis. Arterial pressure did not change, and changes in circulatory volume were minimised by infusion of crystalloid to maintain pulmonary artery occlusion pressure, measured using a Swann-Ganz pulmonary artery catheter. 3. After plasmapheresis, there was no significant change in creatinine clearance, sodium excretion, plasma renin activity or urinary kallikrein excretion. 4. After plasmapheresis, there was no significant reduction in plasma osmolality, increase in urine osmolality and fall in free water clearance. 5. The results suggest that in the absence of detectable changes in circulating volume or arterial pressure, acute hypoproteinaemia is associated with significant changes in renal water handling, but has no direct effect on sodium excretion or on renal release of renin and kallikrein.

Pulmonary transvascular fluid filtration response to hypoproteinemia and Hespan infusion.

Management of major blood loss utilizing protein-free fluids for volume replacement frequently results in plasma protein depletion and plasma volume expansion. These factors can increase pulmonary transvascular fluid filtration which may lead to life-threatening pulmonary edema. We studied the combined effects of plasma protein depletion and plasma volume expansion on lung lymph flow (QL) in awake sheep prepared with chronic lung lymph fistulae. Animals were first chronically protein-depleted by batch plasmapheresis and then infused for 2 hr with either lactated Ringer's (Hypo/LR; n = 7) or 6% hydroxyethyl starch (Hespan) (Hypo/HES; n = 6). Control normoproteinemic animals (Norm/LR; n = 13) only received lactated Ringer's. Hypoproteinemia alone resulted in an average 2-fold increase in QL over normoproteinemic baseline levels (P less than or equal to 0.05). Infusion of LR into hypoproteinemic animals caused a 7.9-fold increase in QL (P less than or equal to 0.05). By comparison, HES infusion under similar hypoproteinemic conditions limited the increase in QL to 3.2-fold over baseline. We attributed this reduced rise in QL to Hespan's high oncotic pressure, which dramatically widened (by 4-5 mm Hg) the pulmonary-to-lymph oncotic pressure gradient. We did not observe this with LR infusion, or in previous studies employing intravenous infusion of plasma protein. Thus, the oncotic pressure of Hespan appears to significantly limit pulmonary fluid filtration during hypoproteinemia compared to LR. We do not believe that these effects are the results of any changes in microvascular porosity.

Intestinal absorption of peptide enteral formulas in hypoproteinemic (volume expanded) rats: a paired analysis.

Previous studies have confirmed the improved tolerance of a peptide enteral compared to standard enteral alimentation in hypoalbuminemic, critically ill patients. Animal studies, including hypoproteinemic, volume-expanded rats, demonstrated that the protein hydrolysate of a peptide enteral formula was responsible for the enhanced absorption. The purpose of this study was to determine whether the composition of small MW peptides (protein hydrolysate) in two commercially available peptide enteral formulas would affect the rate of intestinal absorption and albumin clearance in intact jejunal loops before and during hypoproteinemia induced by iv infusion of Tyrode's solution in Sprague-Dawley rats. Net transmucosal water movement was calculated using a volume recovery method; albumin clearance was calculated using iv radiolabeled albumin. We studied three groups of animals during luminal perfusion with either Tyrode's solution, diet A containing 21% peptides, or diet B containing 56% peptides. When compared to luminal perfusion with Tyrode's solution (control animals), both diets significantly enhanced net transmucosal water absorption before volume expansion (p less than .05). With the induction of hypoproteinemia, diet B continued to stimulate water absorption when compared to control animals (p less than .01). Luminal perfusion with diet A failed to attenuate net water secretion induced by hypoproteinemia. Capillary and mucosal albumin clearance was similar for all groups studied. These findings suggest the percentage of small MW peptides may affect the rate of intestinal absorption in patients with acute kwashiorkor-like hypoalbuminemia.

[A clinical study of amino acid metabolism in cancerous hypoproteinemia--the role of branched chain amino acids (BCAA) and appropriate compositions of BCAA in parenteral nutrition].

In order to determine the nutritional effects of BCAA compositions in the treatment of cancerous hypoproteinemia, the appropriate ratio of I-leu: Leu: Val and the proportion of BCAA to Total Amino Acids were investigated. As for results, indices such as the serum albumin, the RBP and N-balance quickly recovered to normal levels when the ratio of I-leu: Leu: Val was 1.0:1.8:1.0 and the proportion o BCAA to TAA was 31%. These composition thus may be suitable for the treatment of cancerous hypoproteinemia.

Plasma proteins in growing analbuminaemic rats fed on a diet of low-protein content.

1. Analbuminaemic and Sprague-Dawley (control) rats were fed on low- (60 g/kg) protein and control (200 g protein/kg) diets ad lib. from weaning. Males and females were studied separately. Body-weight and plasma protein concentrations were determined at 10 d intervals from 25 to 75 d of age. Electrophoresis of plasma proteins was performed in samples from day 75. Extracellular fluid volume was measured at 10 d intervals from day 45 onwards. Colloid osmotic pressure was measured in plasma and interstitial fluid (wick technique) at the start and end of the trial. 2. Body-weight increased much less on the low-protein diet than on the normal diet in both strains and sexes. The growth retardation was slightly more pronounced in the male analbuminaemic rats than in the male Sprague-Dawley controls. 3. Plasma protein concentration increased during normal growth in all groups, particularly in the female analbuminaemic rats. This increase was reduced by the 60 g protein/kg diet in all groups, with the exception of the male analbuminaemic rats. 4. Differences in plasma colloid osmotic pressure were similar to those seen in plasma protein concentration. Interstitial colloid osmotic pressure was higher in the control rats than in the analbuminaemic ones. The interstitial colloid osmotic pressure increased during growth in the control but not in the analbuminaemic rats. The difference in interstitial colloid osmotic pressure between the strains was maintained during low-protein intake, but at a lower level than during normal protein intake. 5. Subtracting interstitial from plasma colloid osmotic pressure, resulted in a rather similar transcapillary oncotic gradient in the various groups at 75 d, both on the control protein diet (11-14 mmHg), and on the low-protein diet (9-11 mmHg). 6. All protein fractions were reduced to a similar extent by the low-protein diet in the control rats, whereas in the analbuminaemic rats protein fractions produced in the liver were more severely depressed. 7. Extracellular fluid volume as a percentage of body-weight was similar in all groups, and decreased with increasing age. 8. In conclusion, the analbuminaemic rats were able to maintain the transcapillary oncotic gradient on both diets by reducing the interstitial colloid osmotic pressure. Oedema was not observed. 9. Despite the absence of albumin, the protein-malnourished analbuminaemic rat is no more susceptible to hypoproteinaemia and oedema than its normal counterpart.