chondroitin-sulfates and Kidney-Failure--Chronic

The present review illustrates the state of the art of regenerative medicine (RM) as applied to surgical diseases and demonstrates that this field has the potential to address some of the unmet needs in surgery. RM is a multidisciplinary field whose purpose is to regenerate in vivo or ex vivo human cells, tissues, or organs to restore or establish normal function through exploitation of the potential to regenerate, which is intrinsic to human cells, tissues, and organs. RM uses cells and/or specially designed biomaterials to reach its goals and RM-based therapies are already in use in several clinical trials in most fields of surgery. The main challenges for investigators are threefold: Creation of an appropriate microenvironment ex vivo that is able to sustain cell physiology and function in order to generate the desired cells or body parts; identification and appropriate manipulation of cells that have the potential to generate parenchymal, stromal and vascular components on demand, both in vivo and ex vivo; and production of smart materials that are able to drive cell fate.

Topics: Animals; Biocompatible Materials; Blood Vessel Prosthesis; Cell Transplantation; Chondroitin Sulfates; Collagen; Dermatologic Surgical Procedures; Gastrointestinal Tract; General Surgery; Heart Failure; Humans; Kidney Failure, Chronic; Larynx; Liver Transplantation; Regenerative Medicine; Respiratory Tract Diseases; Skin, Artificial; Tissue Scaffolds; Wound Healing; Wounds and Injuries

Low molecular weight heparins (LMWHs) and danaparoid are an alternative to unfractionated heparin (UH) for anticoagulation during hemodialysis. Few data are available concerning their duration of action and whether drug accumulation occurs with continued use. We performed a prospective randomized study of the pharmacokinetics of dalteparin and enoxaparin plus danaparoid in 21 hemodialysis patients.. Patients were randomly assigned to administration of enoxaparin, 40 mg; dalteparin, 2,500 U; or danaparoid, 34 U/kg, for 4 weeks. Antifactor Xa levels were measured at the end of weeks 1 and 4 immediately before the injection and at prescribed intervals up to 48 hours postinjection.. No bleeding or thrombotic episodes occurred during the study. Mean antifactor Xa activities 4 hours postinjection were 0.2 +/- 0.035 (SEM), 0.38 +/- 0.028, and 0.54 +/- 0.051 U/mL week 1 and 0.26 +/- 0.038, 0.40 +/- 0.055, and 0.64 +/- 0.050 U/mL week 4 for dalteparin, enoxaparin, and danaparoid, respectively. Both weeks 1 and 4, antifactor Xa activity 3 hours postdose was significantly greater for danaparoid sodium compared with enoxaparin and dalteparin. There were no significant differences between antifactor Xa activity week 4 versus week 1 for enoxaparin and dalteparin; however, danaparoid sodium levels during dialysis were significantly greater after 4 weeks of treatment (P = 0.0328, 1 hour; P = 0.003, 2 hours; P = 0.0128, 3 and 4 hours).. Dalteparin and enoxaparin provide adequate anticoagulation for hemodialysis using single bolus injections at relatively low doses. Danaparoid sodium at the current recommended dosage resulted in greater anticoagulation than enoxaparin or dalteparin and may have an

Topics: Anticoagulants; Chondroitin Sulfates; Dalteparin; Dermatan Sulfate; Enoxaparin; Factor Xa Inhibitors; Female; Heparinoids; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Prospective Studies; Renal Dialysis

A low molecular weight heparinoid (Org 10172) was compared with unfractionated heparin in 36 patients on chronic hemodialysis in an open randomized cross-over study with three anti-coagulant treatment regimens for a single hemodialysis session. The anti-coagulant regimens were: a) standard heparin (3250-4750 I.U. heparin at start of hemodialysis followed by continuous infusion of 2000-2700 I.U. per hour); b) Org 10172 administered as a single intravenous bolus of 2400 anti-Xa units at start of dialysis; c) Org 10172 administered as a single bolus of 3200 anti-Xa units at start of dialysis. Plasma anti-Xa activity during hemodialysis was highest in regimen; d) and significantly lower when heparin was used. Mean beta-thromboglobulin concentrations changed to the same extent in the three groups. Plasma platelet factor 4 concentrations were higher after the use of heparin. The extracorporeal circuit was maintained patent in all groups; the volume of blood retained in the dialyzers did not differ markedly. Org 10172 proved safe and its anticoagulant effect was sufficient at the dose levels studied.

Topics: Anticoagulants; Bleeding Time; Blood Cell Count; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparin; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Partial Thromboplastin Time; Renal Dialysis

A new low molecular weight heparinoid, Org 10172 was compared to heparin in a randomized single blind cross-over study in 55 patients with end-stage renal failure undergoing chronic intermittent haemodialysis. The heparinoid administered as a single pre-dialysis i.v. injection of 34.4 anti-Xa units/kg body weight was compared to standard heparin (loading dose 2,500 IU + continuous infusion of 1,800 IU/hr). Mean anti-Xa plasma levels reached were 0.55 and 0.94 anti-Xa units/ml midway dialysis respectively. All 110 dialysis procedures were successfully performed without clotting or bleeding complications. Analysis of the number of clotted hollow-fibres within the dialysers showed a slight statistically calculated advantage in favour of heparin. Clinically no difference was detected. In conclusion, the heparinoid seems to be a good alternative means of anticoagulation in haemodialysis. As it is administered as a single i.v. predialysis injection it will simplify the dialysis procedure.

Topics: Adult; Aged; Antibodies; Chondroitin Sulfates; Dermatan Sulfate; Factor X; Factor Xa; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Middle Aged; Molecular Weight; Renal Dialysis; Time Factors

A constant finding in beta (2)-microglobulin (beta 2m) amyloidosis is an increase in tissue heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) at sites of amyloid deposits. However, the binding characteristics of PGs with beta 2m have not been elucidated yet.. Using affinity retardation chromatography, beta 2m- and glycosaminoglycan (GAG)-anchored columns, an affinity between beta 2m and GAGs was analyzed. Five peptides which spanned the entire beta 2m amino acid sequence were prepared, and an affinity between these peptides and heparin (HP) was examined. Furthermore, the specific binding of biotinylated beta 2m peptide for AA amyloid deposits via GAGs was examined on tissue sections.. Using beta 2m-anchored column, HP showed the smallest dissociation constant (K(d)), i.e. the strongest affinity, among the GAGs examined. At 0.4 M NaCl, the K(d)s of beta 2m relative to BSA-anchored columns for HP, HS, CS-A, CS-B, and CS-C were 94, 620, 130, 660 and 190 microM, respectively. Using GAG-anchored columns, at 0.15 M NaCl, pH 7.4, beta 2m also showed an affinity for HP, with the K(d) relative to a reference column being 370 microM. Under the latter conditions, no beta 2m affinity for CSA was demonstrated. Among the five peptides, peptide-1, which is composed of residues 1-24, showed the highest affinity for HP, the K(d) being 190 microM. Peptides analogous to peptide-1, in which each basic amino acid was individually replaced by alanine, showed a remarkable decrease in affinity for HP. The specific binding of biotinylated beta 2m peptide for AA amyloid deposits via HS and CS was confirmed in situ by pretreatment with heparitinase and chondroitinase ABC.. The present data indicate that HP/HS is effective in the binding of the beta 2m monomer, and the anatomic localization of beta 2m amyloid precursor protein.

Topics: Amino Acid Sequence; Amyloidosis; beta 2-Microglobulin; Chondroitin Sulfates; Chromatography, Affinity; Heparitin Sulfate; Humans; Kidney; Kidney Failure, Chronic; Molecular Sequence Data; Peptide Fragments; Protein Binding; Renal Dialysis

We report two pediatric patients with end-stage renal failure who developed heparin-induced thrombocytopenia type II (HIT II) on hemodialysis (HD). Both developed acute respiratory distress and chest pain within 30 min of initiating the 5th HD session. The platelets dropped during HD from 168 to 38x10(9)/l and from 248 to 109x10(9)/l, respectively. Marked clots were observed in the dialyzers. Substitution of heparin with the low molecular weight heparin dalteparin had no effect. Switching from anticoagulation to the heparinoid danaparoid resulted in immediate disappearance of all adverse effects, and further long-term HD was uneventful. HIT II was diagnosed clinically; heparin-induced platelet activation test (HIPA) and serum IgG, IgA, and IgM to heparin-platelet factor 4 complexes (HPF4) were both negative. We conclude that HIT II may occur in children on HD. HIT II is essentially a clinical diagnosis, as HIPA and antibodies to HPF4 are not always positive. Once HIT II is suspected, heparin (and low-molecular-weight heparins) should be stopped immediately. Long-term anticoagulation with danaparoid is a valuable option for patients on HD.

Topics: Adolescent; Anticoagulants; Child; Chondroitin Sulfates; Dalteparin; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Platelet Count; Renal Dialysis; Thrombocytopenia

Topics: Anticoagulants; Body Weight; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Drug Monitoring; Heparin; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Renal Dialysis; Thrombocytopenia

Danaparoid sodium is an antithrombin composed of 3 glycosaminoglycans: heparan sulfate, dermatan sulfate and chondroitin sulfate. Similar to heparin, danaparoid operates by activating antithrombin 3, but does not contain heparin or heparin fragments, and is therefore antigenically distinct. Danaparoid has been advocated as a safe and effective anticoagulant for heparin-associated thrombocytopenia. However, there is little experience in its use as a substitute for heparin in hemodialysis. We report 2 men, aged 82 and 73 years, respectively, who developed thrombocytopenia while undergoing hemodialysis with heparin, and who subsequently underwent successful dialysis with danaparoid. There was a rise in platelet levels in both while receiving danaparoid, and dialysis was completed without hemorrhagic or thrombotic complications. Danaparoid is a safe and effective substitute for heparin, and may be used as an anticoagulant in hemodialysis.

Topics: Aged; Aged, 80 and over; Antithrombin III; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Nephrotic Syndrome; Platelet Aggregation; Renal Dialysis; Thrombocytopenia

A 52-year-old man had been in terminal renal failure for 6 years. On haemodialysis under heparin without complications, acral skin necroses occurred. Even with low-molecular heparin anticoagulation further lesions developed. Within 12 weeks of haemodialysis being performed without heparin the necroses healed, but they recurred when heparin was again added for dialysis. On admission the patient was in poor general condition, with a weight of 55 kg (height 175 cm). LABORATORY INVESTIGATIONS: The heparin-induced platelet aggregation (HIPA) test was positive in the absence of thrombocytopenia. Na-heparin reacted positively in three out of four tests, but Danaparoid did not react.. The skin necroses once again healed after the heparinoid Danaparoid, which had not reacted in the HIPA test, had been substituted for heparin.. This case illustrates that skin necroses, thrombocytopenia and thromboembolism can be independent signs of immunologically induced platelet aggregation.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Foot Dermatoses; Heparin; Heparinoids; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Necrosis; Platelet Aggregation; Renal Dialysis; Skin; Skin Diseases

This study describes experiments that compare the proteoglycans (PGs) extracted from the dialysate from patients receiving continuous peritoneal ambulatory dialysis (CAPD) with those secreted by metabolically labeled human peritoneal mesothelial cells in vitro. The PGs isolated from both sources were predominantly small chondroitin sulfate/dermatan sulfate PGs. Western blot of the core proteins obtained after chondroitin ABC lyase treatment with specific antibodies identified decorin and biglycan. With [35S]sulfate and [35S]methionine as labeling precursors it was shown that dermatan sulfate rather than chondroitin sulfate were the major glycosaminoglycan chains and that decorin was the predominant species. These data provide the first evidence that human peritoneal mesothelial cells may be the principal source of PGs in the peritoneum. Given the proposed functions of decorin and biglycan, the results suggest that these PGs may be involved in the control of transforming growth factor-beta activity and collagen fibril formation in the peritoneum.

Topics: Ascitic Fluid; Biglycan; Chondroitin Sulfates; Decorin; Dermatan Sulfate; Epithelium; Extracellular Matrix Proteins; Humans; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Proteoglycans

Topics: Aged; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Molecular Weight; Renal Dialysis; Thrombocytopenia

The heparinoid of natural origin Org 10172 has anti-factor Xa activity but minimal anti-thrombin activity, and little effect upon broad spectrum assays such as the KCCT in vitro. Its anticoagulant effects have been compared to those of commercial heparin in 7 patients undergoing haemodialysis for chronic renal failure. Commercial heparin was administered in a dose (5,000 iu bolus + 1,500 iu/hour continuous iv infusion) previously shown to inhibit fibrin formation during haemodialysis. This produced mean anti-factor Xa levels in plasma between 0.7-1.0 iu/ml and largely suppressed fibrin formation for 5 h dialysis measured as mean FPA levels in plasma. Administration of Org 10172 as a bolus of 1,350 anti-factor Xa u or 2,000-2,400 anti-factor Xa u produced plasma anti-factor Xa levels of less than 0.5 u/ml and allowed fibrin clot and FPA generation during dialysis. Org 10172 administered as a bolus dose of 4,000-4,800 anti-factor Xa u produced mean anti-factor Xa levels of greater than 0.5 u/ml, allowed dialysis of 6 patients for 5 h and appreciably suppressed FPA generation during dialysis, with little effect on the KCCT. It is concluded that the anti-factor Xa activity of Org 10172 may reflect its ability to inhibit fibrin during dialysis and that single bolus injection of Org 10172 may be a useful alternative method of achieving anticoagulation.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Evaluation Studies as Topic; Factor X; Factor Xa; Fibrinopeptide A; Glycosaminoglycans; Heparin; Heparitin Sulfate; Humans; Injections, Intravenous; Kidney Failure, Chronic; Male; Platelet Aggregation; Renal Dialysis

Org 10172, a new, natural heparinoid, was used as the sole anticoagulant in twelve patients with acute or acute-on-chronic renal failure, who underwent haemodialysis 55 times. All patients had either intercurrent bleeding or a high risk of severe haemorrhagic complications if given standard heparin therapy. After a single loading dose of 300-600 mg of Org 10172, plasma anti-Xa levels in the range 0.42 - 0.93 U/ml were achieved. All haemodialysis runs were completed without adverse side-effects. There were no haemorrhagic complications and deposition of 125I-fibrinogen on the renal dialysis membrane was successfully inhibited in the 4 patients in whom this was studied. Org 10172 seems to prevent thrombosis during renal haemodialysis. It may have a lower risk/benefit ratio than other anticoagulants, such as heparin, in patients at high risk of haemorrhagic complications undergoing haemodialysis.

Topics: Acute Kidney Injury; Adult; Aged; Blood Platelet Disorders; Chondroitin Sulfates; Dermatan Sulfate; Drug Evaluation; Female; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk