deamino-arginine-vasopressin and Kidney-Failure--Chronic

Kidney transplantation is a major medical improvement for patients with end-stage renal disease, but organ shortage limits its widespread use. As a consequence, the proportion of grafts procured from extended criteria donors (ECD) has increased considerably, but this comes along with increased rates of delayed graft function (DGF) and a higher incidence of immune-mediated rejection that limits organ and patient survival. Furthermore, most grafts are derived from brain dead organ donors, but the unphysiological state of brain death is associated with significant metabolic, hemodynamic, and pro-inflammatory changes, which further compromise patient and graft survival. Thus, donor interventions to preserve graft quality are fundamental to improve long-term transplantation outcome, but interventions must not harm other potentially transplantable grafts. Several donor pretreatment strategies have provided encouraging results in animal models, but evidence from human studies is sparse, as most clinical evidence is derived from single-center or nonrandomized trials. Furthermore, ethical matters have to be considered especially concerning consent from donors, donor families, and transplant recipients to research in the field of donor treatment. This review provides an overview of clinically proven and promising preclinical strategies of donor treatment to optimize long-term results after kidney transplantation.

Topics: Acetylcysteine; Animals; Antioxidants; Brain Death; Deamino Arginine Vasopressin; Delayed Graft Function; Dopamine; Graft Survival; Humans; Immune System; Insulin; Kidney Failure, Chronic; Kidney Transplantation; Methylprednisolone; Organ Preservation; Randomized Controlled Trials as Topic; Recombinant Proteins; Resuscitation; Superoxide Dismutase; Thyroid Hormones; Tissue and Organ Procurement; Tissue Donors

Topics: Amino Acid Sequence; Aquaporin 2; Aquaporin 6; Aquaporins; Arginine Vasopressin; Deamino Arginine Vasopressin; Dehydration; Diabetes Insipidus, Nephrogenic; Drug Resistance; Female; Founder Effect; Genetic Carrier Screening; Genetic Heterogeneity; History, 17th Century; History, 18th Century; Humans; Incidence; Infant; Infant, Newborn; Intellectual Disability; Ion Channels; Ireland; Kidney Failure, Chronic; Male; Models, Biological; Models, Molecular; Molecular Sequence Data; Mutation; Nephrons; Nova Scotia; Prenatal Diagnosis; Prevalence; Protein Conformation; Receptors, Vasopressin; X Chromosome

Topics: Bleeding Time; Deamino Arginine Vasopressin; Hemostasis; Humans; Kidney Failure, Chronic; Platelet Aggregation; Thrombocytopenia; von Willebrand Factor

High-dose desmopressin shortens the bleeding time in uraemia. The aim of this study was to investigate the pharmacokinetics and the antidiuretic effect of desmopressin when given in a dose normally used for haemostasis to patients with reduced renal function. Ten patients with chronic renal failure of varying aetiology were enrolled in the study. The age was 58 (20-76) years (median and range), serum creatinine 447 (309-691) micromol/l and plasma clearance of iohexol 16 (8-19) ml/min./1.73 m2 body surface. After baseline measurements, desmopressin was infused at a dose of 0.3 microg/kg. The plasma concentration of desmopressin was followed for 26 hr during and after the infusion and the pharmacokinetic parameters were estimated by compartmental analysis. Urine volume and osmolality, as well as body weight, blood pressure, heart rate, haematocrit, serum osmolality, electrolytes and creatinine, were measured repeatedly during the day before and for two days after the infusion. The total clearance of desmopressin was 0.35 (0.21-0.47) ml/min./kg, the volume of distribution at steady state was 0.30 (0.17-0.38) l/kg and the terminal half-life 9.7 (8.4-16) hr. After administration of desmopressin, urine osmolality increased significantly, by approximately 10%, and this increase lasted for 48 hr. Concomitantly, there was a modest but significant decrease in haematocrit. Thus, the clearance of desmopressin was on average decreased to approximately one quarter, and the terminal half-life was prolonged 2-3 times in the patients as compared to previously published values for healthy adults. The single haemostatic dose of desmopressin given to patients with severe renal failure did not cause fluid overload or changes in serum electrolytes.

Topics: Adult; Aged; Blood Pressure; Creatinine; Deamino Arginine Vasopressin; Diuresis; Dose-Response Relationship, Drug; Female; Half-Life; Heart Rate; Hematocrit; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Osmolar Concentration; Renal Agents; Sodium; Time Factors

The effect of 1 deamino-8-D-arginine vasopressin (DDAVP) on blood platelet serotonin and some parameters of haemostasis was investigated. DDAVP was administered intravenously in a dose of 0.4 micrograms/kg BW to 16 uraemic patients maintained on chronic haemodialysis in a double-blind crossover study compared with placebo. The bleeding time was significantly shortened after DDAVP administration from 21.3 +/- 8 minutes to 11.5 +/- 6 minutes (p less than 0.001). VIII: Ag increased from 239.1 +/- 94% to 473 +/- 293% (p less than 0.01). Euglobulin lysis time was shortened from 238 +/- 101 to 148 +/- 84 minutes (p less than 0.005). The platelet serotonin level was significantly reduced from 532 +/- 141 to 366 +/- 88 ng/10(9) platelets (p less than 0.02). There were no changes in haematocrit, platelet count, VIII: C levels and blood serotonin concentrations after DDAVP administration. In placebo group there were no changes in all investigated parameters. Our data indicate that DDAVP shortens prolonged bleeding time in uraemic probably by means of the serotonergic mechanism. Further studies are needed to confirm this suggestion.

Topics: Adult; Aged; Bleeding Time; Blood Coagulation Tests; Blood Platelets; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemostasis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Uremia

Topics: Adolescent; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Delayed Graft Function; Female; Hemostatics; Humans; Kidney Failure, Chronic; Kidney Transplantation; Renal Dialysis; Time Factors; Treatment Outcome

The development of intradialytic hypotension during hemodialysis (HD) in which fluid removal is the primary goal, contributes to the excessive morbidity that is associated with the dialysis procedure.. In a double blinded clinical trial, we compared the possible effect of intranasal DDAVP with intranasal distilled water as a placebo in prevention of intradialytic hypotension (IDH) in patients with known symptomatic IDH. In the first month of the study, nasal spray of distill water were administrated 30 minutes before all HD session (Placebo Group, Group 1) and then after a 30-day washout period we were used intranasal DDAVP 30 minutes before HD session (Vasopressin Group, Group 2). Blood pressure was measured just before HD, two hours later and after termination of HD. A hypotensive episode was defined as a decline of systolic blood pressure of more than 10mm Hg.. In overall Seventeen patients (nine men, eight women; mean age, 47.5 years) with known symptomatic IDH were enrolled in the study. The kind of dialysis membranes, mean of blood flow rate, dialyzate flow rate and ultrafiltration rate were the same in both groups. Each group has 204 HD session (17 * 12). Hypotensive episode occurred 18 times (8.82%) in vasopressin group compared with 125 times (61.27%) in placebo group and there was a significant association between them (p=0.0001). In addition mean arterial blood pressure in vasopressin group was 80.77 and in placebo group was 73.92 and also there was a significant association (p=0.0001). The mean Kt/v in group 1 and 2 were 1.29 and 1.28 without any differences between them (p=0.896).. These results indicate that Compared with placebo, Vasopressin is significantly associated with a decreased incidence of intradialytic hypotension episodes during hemodialysis.

Topics: Administration, Intranasal; Adult; Aged; Cross-Sectional Studies; Deamino Arginine Vasopressin; Female; Humans; Hypotension; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Young Adult

Recombinant activated factor VII (rFVIIa) is approved for prevention and treatment of bleeding in hemophilia patients with inhibitors to FVIII (hemophilia A) or IX (hemophilia B), patients with congenital and acquired hemophilia and in patients with FVII deficiency or Glantzmann thrombasthenia (last indication is approved only in Europe). Off-labeled, the drug has been prescribed for prevention, or treatment of bleeding in severe hepatic disease, neonatal coagulopathies, high-risk surgical procedures, trauma, thrombocytopenia and platelet function disorders, as well as for urgent reversal of oral anticoagulation. Here we report a case of a 53-year-old female patient with delayed graft function after kidney transplantation, who had kidney biopsy complicated with prolonged bleeding. After unsuccessful treatment with desmopressin, the patient was treated with rFVIIa and the bleeding stopped immediately. Only few anecdotal reports of use of rFVIIa for treatment of bleeding in uremic patients have been published thus far. To our knowledge, this is the first case that describes use of rFVIIa for management of bleeding as a complication of renal biopsy in a uremic patient in the early kidney posttransplantation period.

Topics: Biopsy; Deamino Arginine Vasopressin; Drug Administration Schedule; Factor VIIa; Female; Hemorrhage; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Recombinant Proteins; Uremia

Suboptimal kidney development resulting from a genetic deficit in nephron number can have lifelong consequences that may lead to cardiorenal complications upon exposure to secondary insults in later life. To determine whether the inherited reduced renal reserve compromises the ability to handle osmotic stress in the adult animal, we challenged the heterozygous 3H1 Brachyrrhine (Br/+) mouse, which displays heritable renal hypoplasia associated with reduced embryonic six2 expression, to a solution of 2% NaCl for 5 days or to fluid restriction for 48 h. Blood chemistry, fluid intake, and physiological parameters, including renal measurements, were determined. Systemic hypertonicity by prolonged salt loading led to significant increases in plasma osmolality and plasma Na(+), along with polydipsia and polyuria, with a significant urine-concentrating defect that was resistant to DDAVP treatment in the adult Br/+ mouse compared with wild-type littermates. The Br/+ mouse also developed a significant increase in blood urea nitrogen at baseline that was further elevated when 2% NaCl was given. Fluid restriction for 48 h further enhanced plasma osmolality and plasma Na(+) responses, although the Br/+ mouse was evidently able to produce a small amount of concentrated urine at this time. Hypothalamic c-Fos expression was appropriately activated in the Br/+ mouse in response to both osmotic challenges, indicating an intact central neuroendocrine pathway that was not affected by the lack of congenital six2 expression. Collectively, our results demonstrate impaired osmoregulatory mechanisms consistent with chronic renal failure in the Br/+ mouse and indicate that six2 haploinsufficiency has a direct effect on postnatal fluid and electrolyte handling associated with fluid imbalance.

Topics: Analysis of Variance; Animals; Antidiuretic Agents; Blood Urea Nitrogen; Deamino Arginine Vasopressin; Drinking; Gene Expression Regulation, Developmental; Haploinsufficiency; Homeodomain Proteins; Hypothalamus; Kidney Concentrating Ability; Kidney Failure, Chronic; Mice; Mice, Mutant Strains; Nephrons; Organogenesis; Osmolar Concentration; Polyuria; Proto-Oncogene Proteins c-fos; Saline Solution, Hypertonic; Sodium; Sodium Chloride, Dietary; Transcription Factors; Water-Electrolyte Balance

Topics: Aged, 80 and over; Aspirin; Blood Gas Analysis; Combined Modality Therapy; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Hematoma; Hemorrhage; Hemorrhagic Disorders; Humans; Kidney Failure, Chronic; Male; Platelet Aggregation Inhibitors; Platelet Transfusion; Punctures; Radial Artery; Respiratory Insufficiency

Topics: Bleeding Time; Blood Coagulation; Blood Platelets; Deamino Arginine Vasopressin; Factor VIIa; Hemostasis; Humans; Kidney Failure, Chronic; Kidney Transplantation; Platelet Aggregation; Recombinant Proteins; Thrombin

Topics: Antidiuretic Agents; Deamino Arginine Vasopressin; Hemostatics; Humans; Kidney Failure, Chronic

Central diabetes insipidus is clinically masked in dialysis patients. We report a 12-year-old girl receiving a living-related donor graft for renal failure from Alport syndrome, in whom a craniopharyngioma had been resected 6 months before transplantation. Pretransplant evaluation had documented central hypothyroidism, growth hormone deficiency, and presumptive hypogonadotropic hypogonadism. The corticotropin-releasing factor test had been normal. Four hours after transplantation, urine output exceeded 1,000 ml/h without diuretic therapy. Serum sodium concentration was 155 mmol/l, serum osmolality 333 mmol/kg, and plasma antidiuretic hormone 4.9 ng/l, while urine osmolality was 233 mmol/kg. Desmopressin acetate was started by continuous intravenous infusion at 1 microgram/day. Serum electrolytes rapidly normalized, urine output stabilized at 2 l/day. The patient was discharged 4 weeks after transplantation with good allograft function, receiving intranasal desmopressin acetate 10 micrograms twice daily. Pre-existing central diabetes insipidus is unmasked after successful kidney transplantation, leading to rapid dehydration and hypernatremia, which can be prevented by prompt institution of desmopressin therapy.

Topics: Child; Craniopharyngioma; Deamino Arginine Vasopressin; Diabetes Insipidus, Neurogenic; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Magnetic Resonance Imaging; Pituitary Neoplasms; Renal Agents

Topics: Brain Ischemia; Cerebral Infarction; Deamino Arginine Vasopressin; Female; Humans; Infant; Intraoperative Complications; Kidney Failure, Chronic; Nephrectomy; Peritoneal Dialysis; Preoperative Care

Circulating plasma immunoreactive thrombomodulin (i-TM) reflects the injury of vascular endothelium, and desmopressin stimulates tissue plasminogen activator (tPA) release from endothelium. Therefore, in order to estimate the damage of vascular endothelium in patients on regular dialysis treatment (RDT), we studied 1) basal plasma levels of i-TM and 2) a capability to release tPA by desmopressin. The basal plasma i-TM levels of the patients (n = 23) were significantly higher than those of the normal controls (p < 0.001). The basal plasma tPA levels of the patients (n = 8) were significantly lower than those of the controls (p < 0.05). The maximum increments of tPA from the basal levels by desmopressin in the patients were significantly reduced compared to those of the controls (p < 0.001). There was a significant inverse correlation in those cases between the maximum increments of tPA and the basal plasma levels of i-TM (p < 0.05, r = -0.75). The results actually suggested that there is a vascular endothelial damage in patients on RDT.

Topics: Adult; Deamino Arginine Vasopressin; Endothelium, Vascular; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Thrombomodulin; Tissue Plasminogen Activator

Topics: Benzamidines; Blood Transfusion; Deamino Arginine Vasopressin; Gabexate; Guanidines; Hemorrhage; Heparin; Humans; Kidney Failure, Chronic; Molecular Weight; Protease Inhibitors; Renal Dialysis; Uremia

Topics: Benzamidines; Deamino Arginine Vasopressin; Estrogens; Factor VIII; Fibrinogen; Guanidines; Hemorrhagic Disorders; Heparin; Humans; Kidney Failure, Chronic; Renal Dialysis; Thrombocytopenia

The fibrinolytic activity (FA) evaluated according to the euglobulin clot lysis time was in haemodialyzed patients (3.0 +/- 0.2 arb. u.) lower than in patients with chronic renal failure treated by conservative methods (4.7 +/- 0.6, p less than 0.05) and than in healthy subjects (4.2 +/- 0.4, p less than 0.05). After stimulation by intravenous administration of 1-deamino-8-D-arginine vasopressin the FA in haemodialyzed patients rose to (4.5 +/- 1.6), less than in conservatively treated (14.1 +/- 2.1, p = 0.06) and than in healthy subjects (18.2 +/- 3.9, p less than 0.001). By using specific methods it was proved that the inadequate rise of FA in haemodialyzed patients after stimulation is conditioned by a defect of the release of the plasminogen tissue activator from the vascular wall. Contrary to healthy subjects (7.0 +/- 1.3 vs. 16.7 +/- 2.3 ng/ml, p less than 0.01) is plasma concentration in haemodialyzed subjects (5.3 +/- 0.5 vs. 7.9 +/- 0.8, NS) did not increase significantly. Repeated examinations of some of the haemodialyzed patients revealed that almost 20 months of regular haemodialysis do not lead to further changes of basal (2.9 +/- 0.3 vs. 2.8 +/- 0.2) nor stimulated (4.2 +/- 0.5 vs. 4.8 +/- 0.9) FA. Basal plasma concentrations of the von Willebrand factor were in the dialyzed patients (89.1 +/- 8.8%) higher than in healthy subjects (67.2 +/- 4.4, p less than 0.05). After stimulation the concentration of the von Willebrand factor increased significantly in healthy subjects (99.1 +/- 4.3, p less than 0.01), but not in dialyzed patients (82.9 +/- 3.1, NS), obviously due to the pathological reactivity of their vascular wall. The above findings may be associated with thromboses and atherosclerosis in patients on long-term dialysis.

Topics: Adult; Deamino Arginine Vasopressin; Female; Fibrinolysis; Hemostasis; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

Topics: Blood Component Transfusion; Blood Platelet Disorders; Deamino Arginine Vasopressin; Hematologic Diseases; Humans; Kidney Failure, Chronic; Platelet Adhesiveness; Platelet Aggregation

Hemostatic defects resulting in life-threatening hemorrhagic episodes are a common occurrence in the chronic renal failure patient. Hemorrhagic tendencies correlate best with laboratory tests of bleeding times. The identification of a specific hemostatic defect and its role in bleeding dyscrasias has yet to be elucidated. Our studies demonstrate that factor VIII coagulant activity and factor VIII related antigen (vWF:Ag) are normal or greatly elevated in uremic renal failure patients with greatly prolonged bleeding times. The multimeric state of the von Willebrand factor is also normal in these patients. The bleeding times were normalized in all 15 patients, 90 minutes post-infusion with desmopressin (DDAVP). No significant changes in factor VIII/vWF associated properties, blood cell counts, or coagulation factors were observed post-DDAVP treatment. However, a significant increase in platelet serotonin uptake (p less than .025) and ATP release (p less than .025) was detected after DDAVP treatment. These results indicate that DDAVP acts on the platelet membrane. This is further substantiated by the ability of DDAVP to block vasopressin-induced platelet aggregation in a dose- and time-dependent fashion. Perturbations in the movement and storage of serotonin and the release of adenosine 5'-triphosphate (ATP) in the platelets of uremic individuals are proposed to play a critical role in regulating bleeding times.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adult; Aged; Bleeding Time; Blood Platelets; Deamino Arginine Vasopressin; Female; Hemostasis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Serotonin

The effect of 1-deamino-8-D-arginine vasopressin (DDAVP) on protein C was investigated in 10 uremics and 10 normal subjects. The protein C antigen was higher in the uremic patients than in the normal subjects. DDAVP had no influence on the level of protein C antigen. However, functional protein C in uremics was lower than in normals even before administration of DDAVP. Furthermore, there was a decrease in functional protein C in the uremics after administration of DDAVP. Further studies are needed to clarify the low functional protein C in uremics both before and during administration of DDAVP.

Topics: Adult; Antigens; Bleeding Time; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Protein C; Time Factors; Uremia; von Willebrand Factor

Topics: Adult; Aged; Bleeding Time; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; von Willebrand Factor

Topics: Adult; Deamino Arginine Vasopressin; Female; Fibrinolysis; Humans; Kidney Failure, Chronic; Male; Renal Dialysis

Topics: Adult; Deamino Arginine Vasopressin; Female; Humans; Kidney Failure, Chronic; Renal Dialysis; Risk Factors; Thrombosis

The roles of hemodialysis and 1-deamino-8-D-arginine vasopressin (DDAVP) in the control of hemorrhage following oral surgery in a severely uremic patient are described.

Topics: Adult; Deamino Arginine Vasopressin; Dental Care for Disabled; Hemostasis, Surgical; Humans; Kidney Failure, Chronic; Male; Oral Hemorrhage; Renal Dialysis; Tooth Extraction; Uremia

Topics: Adult; Deamino Arginine Vasopressin; Female; Half-Life; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Renal Dialysis

Fibrinolytic factors were measured before and after DDAVP-infusion in 18 patients on chronic, regular haemodialysis, 11 of whom underwent bilateral nephrectomy, and in 7 patients in whom non-functioning kidneys were still present. Baseline fibrinolytic activity was normal or high in all but two cases. Before haemodialysis, the response to DDAVP-infusion was greatly reduced in the majority of patients as compared with healthy controls, irrespective of the baseline level. This was in accordance with mean t-PA-antigen levels which increased only slightly after DDAVP. When DDAVP was given after haemodialysis, previous non-responders showed a normal increase in fibrinolytic activity. The level of free t-PA-inhibitors was normal in most cases as were levels of alpha 2-antiplasmin and alpha 2-macroglobulin.

Topics: alpha-2-Antiplasmin; alpha-Macroglobulins; Antigens; Deamino Arginine Vasopressin; Factor VIII; Fibrinolysis; Humans; Kidney Failure, Chronic; Nephrectomy; Plasminogen Activators; Renal Dialysis; von Willebrand Factor

The treatment of the bleeding diathesis of renal failure remains unsatisfactory. 1-Deamino-8-D-arginine vasopressin (DDAVP) has recently been shown to shorten the prolonged bleeding time of renal failure and may as a result diminish the risk of clinical hemorrhage. We describe 2 cases where DDAVP was used successfully in the management of hemorrhage in the setting of renal insufficiency.

Topics: Acute Kidney Injury; Aged; Arginine Vasopressin; Bleeding Time; Deamino Arginine Vasopressin; Female; Hemorrhagic Disorders; Humans; Kidney Failure, Chronic; Male

The prolonged bleeding times of 12 patients with chronic renal failure were significantly shortened at 1 and 2 h after an infusion of 0.4 microgram/kg 1-deamino-8-D-arginine vasopressin (DDAVP). In 5 of these patients, the bleeding times 24 h after infusion had returned to approximate baseline values, suggesting that the effect of DDAVP is a temporary one. The levels of factor VIII coagulant activity, factor VIII related antigen activity, and factor VIII ristocetin cofactor activity were all normal or elevated prior to infusion, and a tendency to further elevation, although significant only for the factor VIII ristocetin cofactor activity, was observed after infusion of DDAVP. The latter observation suggests that the effect of DDAVP infusion on the bleeding time is unrelated to alteration of factor VIII activities.

Topics: Adult; Arginine Vasopressin; Bleeding Time; Deamino Arginine Vasopressin; Factor VIII; Hemorrhagic Disorders; Humans; Kidney Failure, Chronic; Middle Aged; Platelet Function Tests