R De Smet

Intradialytic Parenteral Nutrition in Malnourished Hemodialysis Patients: A Prospective Long-Term Study

BACKGROUNDnMalnutrition is a frequent problem of patients on intermittent hemodialysis and substantially contributes to their morbidity and mortality.nnnMETHODSnIn 26 hemodialysis patients who, despite dietary advice and oral nutritional supplements, still had malnutrition, the feasibility and effects of a specific intradialytic parenteral nutritional (IPN) regimen were evaluated during a 9-month study period. An IPN solution consisting of 250 mL glucose 50%, 250 mL lipids 20%, and 250 mL amino acids 7% was infused i.v. three times a week during the dialysis session. At the end of each dialysis session an additional volume of 250 mL amino acids was infused as a rinsing fluid. Insulin was administered i.v. before dialysis.nnnRESULTSnOf the 26 enrolled patients, 16 completed the study. The remaining 10 patients withdrew mainly because of muscle cramps and nausea during the initiation phase of the treatment, when sodium was not present in the IPN fluid but was supplemented intermittently. In the 16 treated patients, body weight, which had decreased in the pretreatment period from 58.2+/-1.3 kg (-6 months) to 54.8+/-10.1 kg at the start of the study, increased again up to 57.1+/-10.7 kg after 9 months IPN (p < .05). Serum transferrin and prealbumin rose from 1.7+/-0.4 to 2.0+/-0.4 g/L and from 0.23+/-0.05 to 0.27+/-0.10 g/L, respectively. Bone densitometry showed an increase of tissue mass, mostly related to a rise in fat tissue. Triceps skinfold (p < .05) and arm muscle compartment of the midarm (p = .07) increased as well. No such changes were observed in the patients who withdrew from treatment.nnnCONCLUSIONSnAn i.v. hyperalimentation regimen applied to malnourished hemodialysis patients results in a rise of body weight and in a limited, but significant, change of some parameters of nutritional status. The rise in body weight is at least in part attributable to an increase of body fat, without changes in plasma lipid levels.

Influence of uraemia and haemodialysis on host defence and infection

Dysfunction of the host defence is one of the major functional disturbances in end-stage renal disease (ESRD) with substantial clinical and socioeconomic implications. The resulting higher susceptibility to infection may lead to life-threatening complications such as sepsis, septic shock, and abcess formation. The immune system defends against infection via a cascade of finely tuned mechanisms, which include (1) the functional involvement of immunocompetent cells, (2) the release of humoral substances upgrading immunocompetence, and (3) the attraction of cells towards regions of infection. All these elements cooperate to achieve ingestion and destruction of infectious agents by phagocytic cells. The effect of uraemia (and its treatment by dialysis) on the immune system will be considered in depth, to formulate therapeutic approaches and preventive measures.

Advanced glycation end products: specific fluorescence changes of pentosidine-like compounds during short daily hemodialysis.

Background Advanced glycation end products (AGE) accumulate in uremia and represent an important etiopathogenetic cause of morbidity in dialyzed patients. Conventional hemodialysis treatment seems to be ineffective in lowering AGE levels. We wished to investigate whether daily hemodialysis (DHD), a treatment that seems to result in better clinical condition in end-stage renal disease patients, is effective in the reduction of these compounds. Methods We evaluated 10 non-diabetic patients on standard hemodialysis (SHD = 3 × 4h/week) for more than 6 months by a crossover study. These patients were assigned randomly to 6 months of DHD (6 × 2h/week) or 6 months of SHD. Then, they were switched to 6 months of the alternative treatment. At the end of these two periods, we studied pentosidine-like AGE compounds by measuring the total fluorescence at a wavelength characteristic for these substances: Ex: 335nm / Em:385nm; we also measured protein-linked pentosidine at the same time points. Finally, we determined the AGE-related total fluorescence in the deproteinized serum of 13 uremic patients on peritoneal dialysis (CAPD) and of 10 healthy controls. Results Pre-HD AGE-related total fluorescence obtained after 6 months of DHD was significantly lower than that obtained with standard HD (DHD = 201.3 ± 36.4 AU/ml vs. SHD = 267.5 ± 141.4 AU/ml, p=0.03). The extraction rate per minute of dialysis was slightly, but not significantly higher during DHD than SHD (0.29 ± 0.11% vs. 0.23 ± 0.04, p = 0.07). AGE-related total fluorescence pre-HD values in patients treated by SHD and DHD were about 20-fold higher than in control subjects. They did not differ from CAPD patients. The pre-dialysis level of protein-linked pentosidine was significantly lower in DHD than in SHD (DHD = 16.12 ± 4.71 pmol/mg protein, SHD = 22.64 ± 6.86 pmol/mg protein, p < 0.01). Conclusions DHD showed a reduction in AGE-related total fluorescence, although the mean value remained higher than in control subjects. DHD is also accompanied by a decrease in protein-linked pentosidine.

Effect of regional citrate anticoagulation on leukopenia, complement activation, and expression of leukocyte surface molecules during hemodialysis with unmodified cellulose membranes

Background: Dialysis with complement-activating membranes is associated with leukopenia, which is related to an increased expression of adhesion molecules on leukocytes. Citrate chelates calcium and has been claimed to attenuate leukopenia. Methods: In this study, the effects of citrate anticoagulation on leukocyte and granulocyte counts, complement activation, and the expression of CD11b, CD11c, and CD45 on the surface of granulocytes were evaluated during hemodialysis with unmodified cellulose membranes. Standard heparin was compared to citrate in three different schedules: citrate was infused to obtain a concentration of either 7 or 10 mmol/l blood. CaCl2 was administered into the dialyzer outlet at 8.25 mmol Ca2+/h (citrate 10 mmol/l) or at 11 mmol Ca2+/h (citrate 7 and 10 mmol/l) to restitute the calcium levels in the blood returning to the patient. Results: The use of citrate at a high concentration (10 mmol/l) was associated with a blunted upregulation of CD11b, both at the inlet and at the outlet bloodline; for CD11c a reduced upregulation was observed on granulocytes harvested from the inlet bloodline. No effects of citrate were observed on leukopenia, granulocytopenia, or complement activation. A positive correlation between the decrease in systemic ionized Ca2+ concentration and the increase in CD11b and CD11c expression was found. Conclusion: Citrate/CaCl2 administration affects leukocyte adhesion molecule expression in a dose-dependent way; however, no significant effect could be demonstrated on leukopenia and complement activation.

Screening of UV-absorbing solutes in uremic serum by reversed phase HPLC ― Change of blood levels in different therapies

In order to screen UV-absorbing solutes in large numbers of uremic serum samples, an automated liquid chromatographic method was developed. The method proved to be reliable and reproducible in more than 500 analyses. HPLC separation was performed using gradient elution on a 25-cm Ultrasphere Octyl reversed phase column, with 5 microns particles. Characteristic profiles for the uremic state were obtained in the analyses of serum samples of 43 uremic patients before and just after artificial kidney treatment; hemodialysis (n = 14), hemodiafiltration (n = 13) and hemofiltration (n = 16). In these profiles 20-40 peaks were resolved of which nine were quantitated by peak height relative to a standard. Of these solutes creatinine, uracil, uric acid, hypoxanthine, indoxylsulfate, tryptophan and hippuric acid were identified. The heterogeneity of the population of uremic patients, with respect to the UV-absorbing solutes, was estimated. Significant differences of solute blood level changes during hemodialysis, hemodiafiltration and hemofiltration, were observed.

The Uraemic Syndrome

The uraemic syndrome is characterized by a deterioration of biochemical and physiologic functions, in parallel with the progression of renal failure, and results in important but variable symptomatology. Although well known for more than 160 years (1), our knowledge about the responsible factors remains inconsistent and incomplete. The quest for ‘the’ uraemic toxin has been overemphasized, not taking into account the uraemic syndrome as the result of a cumulative retention of innumerable compounds. The extrapolation of in vitro data to the clinical situation has sometimes resulted in incorrect hypotheses, whereas trivial factors with a potential bias on the results have not been taken into account

Correlation of a Colorimetric and a HPLC Method for the Determination of Serum Hippuric Acid Concentrations in Uremia

Hippuric acid has been recognized as a potential marker of uremic toxicity in chronic renal failure. However, in most studies, serum hippuric acid concentrations have been determined by sophisticated methods, such as high-performance liquid chromatography. The present study was undertaken to evaluate whether the less complicated colorimetric determination method could replace such methods. Based on 21 different samples, the results obtained by both methods appeared to be correlated to each other in a highly significant way (total hippuric acid: r = 0.99, p less than 0.001; free hippuric acid; r = 1.00, p less than 0.001). Mean total and free hippuric acid concentrations and mean percent protein binding, obtained with both determination methods, were also identical. It is concluded that both the colorimetric method and high-performance liquid chromatography are equally reliable for the study of the concentration of hippuric acid in uremic serum and of its importance as a marker of the clinical and biochemical epiphenomena of uremic toxicity.

The low nanomolar levels of Ng-monomethylarginine in serum and urine of patients with chronic renal insufficiency are not significantly different from control levels

Summary.u2002There are no reliable mean values of NG-monomethylarginine (NMMA) in blood and urine of patients with renal insufficiency available in the literature. Therefore we investigate whether the NMMA levels are changed in blood and urinary excretion of nondialysed and dialysed patients with chronic renal insufficiency to evaluate whether NMMA may reach sufficiently increased concentrations in blood of the patients to exert toxic biological activity.In nondialysed as well as in dialysed patients we find no significant difference in serum concentration of NMMA between patients and controls. In nondialysed patients (all with a residual creatinine clearance lower than 15u2009ml/min), we find 94.5 ± 26.1u2009nM (mean ± SD) versus 94.6 ± 19.5u2009nM in controls. Similar levels are found in serum of haemodialysed patients (each with serum creatinine levels >700u2009μM): 83.0 ± 20.2u2009nM. The urinary excretion of NMMA in nondialysed patients is also not significantly different from the excretion of controls: 123 ± 110 in patients versus 157 ± 117u2009nmol/24u2009hrs in controls. Furthermore, the clearance of NMMA is much lower compared to the clearance of the dimethylarginine derivatives.Based on the literature, the low nanomolar levels of NMMA found in blood of patients with renal insufficiency do not support the statement that NMMA proper may act as a uremic toxin.

Analytical isotachophoresis of uremic blood samples.

Uremic blood samples were analyzed for ionogenic substances using analytical isotachophoresis. Multicomponent separations proved that the uremic state shows significant differences from the normal state, especially with regard to anionic low-molecular-weight substances. As a quantitative parameter the ratio of anionic higher-molecular-weight substances to anionic low-molecular-weight substances is proposed: the HL ratio. Separation patterns and HL ratios were studied during nine weeks for one patient on chronic hemodialysis. The patient showed a low HL ratio due to excess of low-molecular-weight substances. Separation patterns before and after hemodialysis showed clear differences and the HL ratio increased. The method of analysis is neither time- nor sample-consuming and sample preparation is not needed. Experimental procedures are easily standardized and results are reliable.

Constructing the topological solution of jigsaw puzzles

In this paper we present a novel approach to the jigsaw puzzle solving problem. The main components are a shape based local contour matching followed by a global solving procedure that constructs the topological solution of the jigsaw puzzle. The shape based local contour matching is discussed briefly, but the main focus of the paper is the construction of the topological solution. The solving procedure starts with the classification of the puzzle pieces. Next, the edge topology is constructed and finally the internal topology is constructed. We tested the developed algorithms on five different jigsaw puzzles. Ultimately, we were able to solve a jigsaw puzzle consisting of 300 puzzle pieces, the largest one solved automatically to date.