Efficacy and safety of desmopressin in nocturia and nocturnal polyuria control of neurological patients: A systematic review and meta-analysis.

PURPOSE: Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases. METHODS: Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration). RESULTS: Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality. CONCLUSIONS: Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.

Management of Central Diabetes Insipidus in Disabled Children with Diluted Oral Desmopressin Lyophilisate Formulation Administered Through Nasogastric Tube: A Retrospective Case Series.

BACKGROUND: Experience with nasogastric administration of oral DDAVP [desamino-D-arginine-8-vasopressin] lyophilisate (ODL) for central diabetes insipidus (CDI) in disabled children with swallowing coordination difficulties is limited. OBJECTIVE: We aimed to assess the safety and efficacy of nasogastric use of ODL in disabled children with CDI. Time to serum sodium normalisation was compared with that of children with normal intellect and CDI treated with sublingual DDAVP. METHODS: Clinical, laboratory and neuroimaging characteristics were evaluated for 12 disabled children with CDI treated with ODL through nasogastric tube at Dr Behcet Uz Children's Hospital, Turkey, between 2012 and 2022. RESULTS: Six boys and six girls with a mean (±SD) age of 43 (± 40) months were evaluated. These children (mean [±SD] weight standard deviation score [SDS] - 1.2 ± 1.7; mean [±SD] height SDS - 1.3 ± 1.4) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatraemia (mean serum sodium 162 [±3.6] mEq/L). At diagnosis, mean serum and urine osmolality were 321 (± 14) mOsm/kg and 105 (± 7.8) mOsm/kg, respectively. Arginine vasopressin (AVP) levels were undetectable (< 0.5 pmol/L) at diagnosis in all patients. Nasogastric tube administration of DDAVP lyophilisate (120 µg/tablet) dissolved in water (10 mL) was commenced at a dose of 1-5 µg/kg/day in two divided doses together with controlled water intake to avoid hyponatraemia. The frequency and dose of DDAVP were titrated based on urine output and serum sodium concentration. Serum sodium declined at a rate of 0.11 ± 0.03 mEq/L/h and reached normal range in a mean duration of 174 ± 46.5 h. Serum sodium declined faster in children with normal intellect and CDI treated with sublingual DDAVP (1.28 ± 0.39 mEq/L/h; p = 0.0003). Three disabled children needed rehospitalisation because of hypernatraemia due to unintentional DDAVP omission by caregivers. No episode of hyponatraemia was observed. Weight gain and growth were normal during the median (± interquartile range) follow-up duration of 32 ± 67 months. CONCLUSIONS: Nasogastric administration of oral DDAVP lyophilised formulation was safe and effective in the treatment of CDI in disabled children in this small retrospective series.

Seizure from water intoxication following bowel preparation: a case report.

BACKGROUND: Bowel preparation prior to colonoscopic examination is generally considered a safe process. Hyponatremia is a complication that has been reported in literature during bowel preparation. Individuals who develop severe symptomatic hyponatremia are often older and have comorbidities such as hypothyroidism, chronic kidney disease, or adrenal insufficiency. However, other mechanisms and circumstances can also lead to this potentially fatal complication. CASE PRESENTATION: We present a unique case of a patient who developed seizure prior to colonoscopy due to acute hyponatremia without any well-known risk factors. With the subsequent diagnosis of water intoxication, the use of desmopressin was believed to have contributed to this serious complication. CONCLUSION: In addition to the use of certain well-documented medications and the presence of comorbidities that can lead to hyponatremia, clinicians should also be aware of the use of desmopressin as an important risk factor. Thorough history taking can guide individualized bowel preparation regimens to minimize the risk of undesired complications.

Desmopressin Acetate in Percutaneous Ultrasound-Guided Native Kidney Biopsy in Patients with Reduced Kidney Function: A Double-Blind Randomized Controlled Trial.

INTRODUCTION: Bleeding events are the most common complications after kidney biopsy. This study aims to evaluate the effect of desmopressin administration on bleeding complication, in native kidney biopsy candidates with reduced kidney function. METHODS: This double-blind randomized clinical trial enrolled 18 to 80 years old patients with 15 < eGFR < 90 mL/min/ 1.73m² from July 2017 to August 2020. Patients were randomly assigned to receive either 3 µg/kg of intranasal desmopressin acetate or 1 mL/kg of intranasal sodium chloride 0.65%, one hour before ultrasound-guided, percutaneous native kidney biopsy. The primary outcome was the post-biopsy bleeding complications, and secondary outcomes were the volume of perirenal hematoma, and changes of post-biopsy hemoglobin and hematocrit level, plasma sodium and blood pressure (Clinical Trial Registration ID: IRCT20090701002112N3). RESULTS: A total of 120 patients (58 men and 62 women), 60 patients in each group, were analyzed. The mean age and eGFR of the patients were 45.29 ± 15.95 years and 51.77 ± 18.02 ml/min/ 1.73m², respectively. Desmopressin administration significantly decreased post-biopsy perirenal hematoma compared to placebo (7/60 [11.6%]) vs. 33/60 [40%]; P < .05), and the hematoma volume was significantly smaller in the desmopressin group, in case of hematoma formation (2.31 ± 1.17 vs. 7.72 ± 5.45 mm³, P < .05). CONCLUSION: Desmopressin administration before kidney biopsy is a safe and effective strategy to prevent bleeding complications. Considering absolute risk reduction of about 28%, the number needed to treat is about 4 procedures. We recommend considering desmopressin administration before percutaneous native kidney biopsy.  DOI: 10.52547/ijkd.6966.

The efficacy and safety of desmopressin acetate applied for nocturia in benign prostatic hyperplasia patients: A systematic review and meta-analysis.

BACKGROUND: Desmopressin acetate was recommended for nocturia in benign prostatic hyperplasia (BPH) patients recently, but its effect and safety is still controversial. We aimed to establish a systematic review and meta-analysis to confirm its effect on symptom relief and adverse effects. METHODS: A systematic search was performed in PubMed, Cochrane Library, EMBASE, Medline, Web of Science and Science Direct databases from January 2000 to October 2021 for controlled trials of BPH patients comparing oral desmopressin with control groups. The mean difference (MD) and odds ratio (OR) were meta-analyzed. RESULTS: Four articles with 500 patients were included. Significantly greater benefit was detected for the desmopressin group in the improvement of nocturia (P = .004), international prostate symptom score - storage (IPSS-S) (P = .03), and quality of life (QoL) (P = .04) scores. Patients treated with desmopressin were at higher risk than the control group for short-term adverse events (P < .001), including nausea (4.71%, P = .04), headache (20%, P < .00001), dizziness (5.88%, P = .02) and hyponatremia (4.71%, P = .04), but the long-term incidence might decrease. CONCLUSION: Desmopressin acetate can reduce nocturia frequency and improve the IPSS-S and QoL score in BPH patients. Some adverse reactions of desmopressin, such as hyponatremia, headache, dizziness and nausea, may be mild and short-term. No significant difference of desmopressin was found in improving the overall IPSS score and maximum urine flow.

Platelet dysfunction in patients with traumatic intracranial hemorrhage: Do desmopressin and platelet therapy help or harm?

BACKGROUND: Pre-injury anti-platelet use has been associated with increased risk of progression of traumatic intracranial hemorrhage (TICH) and worse outcomes. VerifyNow® assays assess platelet inhibition due to aspirin/clopidogrel. This study assesses the outcomes of patients with TICH and platelet dysfunction treated with desmopressin and/or platelets. METHODS: We performed a retrospective chart review of patients with mild TICH at a level 1 trauma center 1/1/2013-6/1/2016. Patients with documented platelet dysfunction who received desmopressin and/or platelets were compared to those who were untreated. Primary outcomes were progression of TICH and neurologic outcomes at discharge. RESULTS: Of 565 patients with a mild TICH, 200 patients had evidence of platelet dysfunction (a positive VerifyNow® assay). Patients had similar baseline demographics, injury characteristics, and rate of TICH progression; but patients who received desmopressin and/or platelets had worse Glasgow Outcomes Score at discharge. CONCLUSION: Treatment of patients with mild TICH and platelet dysfunction with desmopressin and/or platelets did not affect TICH progression but correlated with worse neurologic status at discharge.

Safety of renal biopsy bleeding prophylaxis with desmopressin.

BACKGROUND: Percutaneous renal biopsy (PRB) is invasive, and bleeding-related complications are a concern. Desmopressin (DDAVP) is a selective type 2 vasopressin receptor-agonist also used for haemostasis. AIM: To evaluate the side effects of intravenous (IV) weight-adjusted desmopressin preceding PRB. METHODS: This was a retrospective study of renal biopsies performed by nephrologists from 2013 to 2017 in patients who received single-dose DDAVP pre-PRB. RESULTS: Of 482 PRBs, 65 (13.5%) received DDAVP (0.3 µg/kg); 55.4% of the PRBs were native kidneys. Desmopressin indications were altered platelet function analyser (PFA)-100 results (75.3% of the patients), urea >24.9 mmol/L (15.5%), antiplatelet drugs (6.1%) and thrombocytopaenia (3%). Of the 65 patients, 30.7% had minor asymptomatic complications, and 3 patients had major complications. Pre-PRB haemoglobin (Hb) <100 g/L was a risk factor for Hb decrease >10 g/L, and altered collagen-epinephrine (Col-Epi) time was a significant risk factor for overall complications. Mean sodium decrease was 0.6 ± 3 mmol/L. Hyponatraemia without neurological symptoms was diagnosed in two patients; no cardiovascular events occurred. CONCLUSION: Hyponatraemia after single-dose DDAVP is rare. A single IV dose of desmopressin adjusted to the patient's weight is safe as pre-PRB bleeding prophylaxis.

Urinary reabsorption in the rat kidney by anticholinergics.

Anticholinergics, therapeutic agents for overactive bladder, are clinically suggested to reduce urine output. We investigated whether this effect is due to bladder or kidney urine reabsorption. Various solutions were injected into the bladder of urethane-anesthetized SD rats. The absorption rate for 2 h was examined following the intravenous administration of the anticholinergics imidafenacin (IM), atropine (AT), and tolterodine (TO). The bilateral ureter was then canulated and saline was administered to obtain a diuretic state. Anticholinergics or 1-deamino-[8-D-arginine]-vasopressin (dDAVP) were intravenously administered. After the IM and dDAVP administrations, the rat kidneys were immunostained with AQP2 antibody, and intracellular cAMP was measured. The absorption rate was ~ 10% of the saline injected into the bladder and constant even when anticholinergics were administered. The renal urine among peaked 2 h after the saline administration. Each of the anticholinergics significantly suppressed the urine production in a dose-dependent manner, as did dDAVP. IM and dDAVP increased the intracellular cAMP levels and caused the AQP2 molecule to localize to the collecting duct cells' luminal side. The urinary reabsorption mechanism through the bladder epithelium was not activated by anticholinergic administration. Thus, anticholinergics suppress urine production via an increase in urine reabsorption in the kidneys' collecting duct cells via AQP2.

Desmopressin acetate to prevent bleeding in percutaneous kidney biopsy: a systematic review.

BACKGROUND: Kidney biopsy is the gold standard for diagnosing kidney disease but may result in bleeding, especially in uraemia. DDAVP (1-deamino-8-d-arginine vasopressin) may reduce uraemic bleeding but guidelines on its use are lacking. AIM: To evaluate whether DDAVP reduced bleeding complications after percutaneous kidney biopsies. METHODS: We searched CENTRAL, PubMed, Embase, LILACS, WHO Trials Registry and ClinicalTrials.gov until May 2019 for randomised controlled trials (RCT), quasi-RCT and prospective cohort studies that compared DDAVP with placebo or no intervention, prior to native or allograft kidney biopsy. The primary outcome was post-biopsy bleeding. Secondary outcome was adverse events related to DDAVP. RESULTS: Abstracts of 270 identified papers were examined and 24 selected for evaluation. Two studies, one RCT and one prospective cohort that collectively evaluated 738 native kidney biopsies, met the inclusion criteria. One enrolled individuals with serum creatinine ≤1.5 mg/dL (132 µmol/L) and/or estimated glomerular filtration rate ≥60 mL/min/1.73 m2 while the other evaluated biopsies with serum creatinine >150 µmol/L. DDAVP was administered as a single subcutaneous dose of 0.3 µg/kg in both studies. Data were not pooled for meta-analysis due to clinical heterogeneity. GRADE quality of evidence from these two studies was low for DDAVP preventing any bleeding complication after native kidney biopsy. Low quality evidence suggested that adverse effects were not increased in DDAVP therapy. No prospective studies evaluated DDAVP in transplant kidney biopsies. CONCLUSION: Currently available prospective data are insufficient to support the routine use of DDAVP prior to percutaneous kidney biopsies hence high quality trials are required.

Comorbidities, Age, and Polypharmacy Limit the Use by US Older Adults with Nocturia of the Only FDA-approved Drugs for the Symptom.

PURPOSE: The goal of this study was to determine if the US adult population with nocturia (waking from sleep at night to void) can easily take medications (desmopressin acetate) approved by the US Food and Drug Administration for nocturia. The study examined: (1) the prevalence of comorbid conditions, laboratory abnormalities, and concomitant medications that increase risk of desmopressin use; and (2) whether these factors are associated with age or nocturia frequency. METHODS: Using a cross-sectional analysis of four US National Health and Nutrition Examination Survey (NHANES) waves (2005-2012), a total of 4111 participants aged ≥50 years who reported ≥2 nightly episodes of nocturia were identified. The main outcome was frequency of contraindications and drug interactions as described in US Food and Drug Administration-approved prescribing information. These prescribing concerns were matched to examination findings, medical conditions, concomitant medications, and laboratory results of NHANES participants. The associations between prescribing concerns and nocturia severity and age groups were examined. FINDINGS: The mean participant age was 65.7 years (95% CI, 65.3-66.1), and 45.5% were male. Desmopressin prescribing concerns were present in 80.5% (95% CI, 78.0-82.9) of those ≥50 years of age with nocturia; 50.0% (95% CI, 47.0-53.0) had contraindications, and 41.6% (95% CI, 39.3-44.0) took a concomitant drug that could increase risk of low serum sodium. Desmopressin contraindications were higher with older age (P < 0.001) and present in 73.2% (95% CI, 69.3-77.1) of those ≥80 years of age. IMPLICATIONS: Using NHANES data, this study showed that older US adults with nocturia have a high prevalence of medical conditions, concomitant medications, and baseline laboratory abnormalities that likely increase the risk of potentially severe adverse side effects from desmopressin use. A medication designed and approved for a clinical symptom that is most common in older adults could not be taken by most of the older adults with the symptom.

Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial.

Purpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted.Clinical trial registration www.clinicaltrials.gov NCT01623206.

The Role of Desmopressin on Hematoma Expansion in Patients with Mild Traumatic Brain Injury Prescribed Pre-injury Antiplatelet Medications.

BACKGROUND/OBJECTIVE: Desmopressin (DDAVP) has been suggested for antiplatelet medication reversal in patients with traumatic brain injury (TBI) but there are limited data describing its effect on clinical outcomes. The purpose of this study was to evaluate the effect of DDAVP on hematoma expansion and thrombosis in patients with TBI who were prescribed pre-injury antiplatelet medications. METHODS: Consecutive adult patients who were admitted to our level I trauma center and prescribed pre-injury antiplatelet medications between July, 2012, and May, 2018, were retrospectively identified. Patients were excluded if their hospital length of stay was < 24 h, if DDAVP was administered by any route other than intravenous, if they received a DDAVP dose < 0.3 mcg/kg or there was no evidence of brain hemorrhage on computed tomography (CT) scan. Patients were stratified based on the use of DDAVP, and the incidence of hematoma expansion was compared between groups. Thrombotic events were reviewed as a secondary outcome. Multivariate analysis was utilized to control for confounding variables. RESULTS: Of 202 patients included in analysis, 158 (78%) received DDAVP. The mean age was 76 ± 12 years; the most common injury mechanism was falls (76%); 69% had acute subdural hematoma, and 49% had multi-compartmental hemorrhage. Initial Glasgow coma score was between 13 and 15 for 91% of patients. Aspirin was the most common antiplatelet regimen prescribed (N = 151, 75%), followed by dual antiplatelet regimens (N = 26, 13%) and adenosine diphosphate (ADP)-receptor inhibitors (N = 25, 12%). The incidence of hematoma expansion was 14% and 30% for patients who did and did not receive DDAVP, respectively (p = 0.015). After controlling for age, injury severity score, multi-compartmental hemorrhage, and receipt of pre-injury high-dose aspirin (> 81 mg), ADP-receptor inhibitors, oral anticoagulants, prothrombin complex concentrates or platelets in a multivariate analysis, the association between DDAVP and hematoma expansion remained significant (adjusted OR 0.259 [95% CI 0.103-0.646], p = 0.004). Thrombotic events were similar between the two groups (DDAVP, 2.5%, no DDAVP, 4.5%; p = 0.613). CONCLUSIONS: DDAVP was associated with a lower incidence of hematoma expansion in patients with mild TBI who were prescribed pre-injury antiplatelet medications. These results justify a randomized controlled trial to further evaluate the role of DDAVP for this indication.

Desmopressin and bleeding risk after percutaneous kidney biopsy.

BACKGROUND: Desmopressin is used to reduce bleeding after kidney biopsy but evidence supporting its use is weak, especially in patients with elevated creatinine. The present study was undertaken to evaluate efficacy of desmopressin in reducing bleeding after percutaneous kidney biopsy. METHODS: Retrospective cohort study. 269 of 322 patients undergoing percutaneous kidney biopsy between January 1, 2014 and January 31, 2018 were included. Patients had normal bleeding time, platelet count and coagulation profile. Primary outcome was defined as composite of hemoglobin drop ≥1 g/dL, hematoma on post biopsy ultrasound, gross hematuria, erythrocyte transfusion or angiography to stop bleeding. Association of desmopressin with outcomes was assessed using linear (for continuous variables) and logistic (for binary variables) regression models. Propensity score was used to minimize potential confounding. RESULTS: Desmopressin was administered to 100/269 (37.17%) patients. After propensity score adjustment patients who received desmopressin had increased odds of post biopsy bleeding [OR 3.88 (1.95-7.74), p < 0.001]. Creatinine at time of biopsy influenced bleeding risk; gender, emergent vs elective biopsy, obesity, AKI, diabetes, hypertension or bleeding time did not influence bleeding risk. Administration of desmopressin to patients with serum creatinine ≥1.8 mg/dL decreased bleeding risk [OR 2.11 (95% CI 0.87-5.11), p = 0.09] but increased bleeding risk when serum creatinine was < 1.8 mg/dL (OR 9.72 (95% CI 2.95-31.96), p < 0.001). CONCLUSION: Desmopressin should not be used routinely prior to percutaneous kidney biopsy in patients at low risk for bleeding but should be reserved for patients who are at high risk for bleeding.

Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects.

PURPOSE: Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. METHODS: Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 µg and 0.12 µg desmopressin subcutaneous (SC) bolus injection. RESULTS: AV002 intranasal administration produced a time-to-maximum concentration (Tmax) between 15 and 30 min and a maximum concentration (Cmax) <10 pg/mL. Cmax and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 µg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5-6 h. CONCLUSIONS: AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).

Desmopressin for the prevention of bleeding in percutaneous kidney biopsy: efficacy and hyponatremia.

BACKGROUND: Desmopressin is used to reduce bleeding complications for kidney biopsies with azotemia but little is known about desmopressin-induced hyponatremia in these individuals. We aimed to evaluate the impact of desmopressin prophylaxis on severe hyponatremia and bleeding after kidney biopsies in individuals with renal impairment. METHOD: This is a single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 150 µmol/L and had ultrasound-guided percutaneous native or transplant kidney biopsies between June 2011 and July 2015. Data were retrieved from electronic medical records. Primary outcomes were the use of desmopressin prophylaxis and severe hyponatremia (serum sodium ≤ 125 mmol/L) within 7 days post-biopsy. Secondary outcome was post-biopsy bleeding. RESULTS: 240 native kidney and 196 allograft biopsies were performed. Median age was 51 (IQR 42.3, 60) years and eGFR was 21.9 (12.9, 30.1) ml/min/1.73 m2. Although patients prescribed desmopressin prophylaxis (n = 226) had higher serum creatinine [279 (201, 392) vs. 187 (160, 241), p < 0.001], bleeding (15.0% vs. 13.3%, p = 0.60) was not significantly different with and without desmopressin. Severe hyponatremia occurred in 30 biopsies (6.9%) with nadir serum sodium level of 122 (119, 124) mmol/L at 3 (2, 5) days after biopsy, more frequently among those with desmopressin prophylaxis (10.7% vs. 3.0%, p = 0.002). Multi-variate analysis found that pre-biopsy serum sodium level [adjusted OR 0.80 (95% CI 0.72, 0.90), p < 0.001] and desmopressin prophylaxis [adjusted OR 4.02 (95% CI 1.58, 10.21), p = 0.003] were independently associated with severe hyponatremia after kidney biopsy. CONCLUSION: Pre-biopsy desmopressin was associated with severe hyponatremia in individuals with renal impairment; hence, susceptible patients given desmopressin should be closely monitored.

Enhanced Local Disorder in a Clinically Elusive von Willebrand Factor Provokes High-Affinity Platelet Clumping.

Mutation of the cysteines forming the disulfide loop of the platelet GPIbα adhesive A1 domain of von Willebrand factor (VWF) causes quantitative VWF deficiencies in the blood and von Willebrand disease. We report two cases of transient severe thrombocytopenia induced by DDAVP treatment. Cys1272Trp and Cys1458Tyr mutations identified by genetic sequencing implicate an abnormal gain-of-function phenotype, evidenced by thrombocytopenia, which quickly relapses back to normal platelet counts and deficient plasma VWF. Using surface plasmon resonance, analytical rheology, and hydrogen-deuterium exchange mass spectrometry (HXMS), we decipher mechanisms of A1-GPIbα-mediated platelet adhesion and resolve dynamic secondary structure elements that regulate the binding pathway. Constrained by the disulfide, conformational selection between weak and tight binding states of A1 takes precedence and drives normal platelet adhesion to VWF. Less restrained through mutation, loss of the disulfide preferentially diverts binding through an induced-fit disease pathway enabling high-affinity GPIbα binding and firm platelet adhesion to a partially disordered A1 domain. HXMS reveals a dynamic asymmetry of flexible and ordered regions common to both variants, indicating that the partially disordered A1 lacking the disulfide retains native-like structural dynamics. Both binding mechanisms share common structural and thermodynamic properties, but the enhanced local disorder in the disease state perpetuates high-affinity platelet agglutination, characteristic of type 2B VWD, upon DDAVP-stimulated secretion of VWF leading to transient thrombocytopenia and a subsequent deficiency of plasma VWF, characteristic of type 2A VWD.

Effect of Desmopressin on the Amount of Bleeding and Transfusion Requirements in Patients Undergoing Heart Transplant Surgery.

One of the most common risks after a heart transplant is bleeding. In this study, the effect of desmopressin administration on the amount of bleeding and transfusion requirements after heart transplant surgery was investigated. In a double-blind clinical trial, 48 patients who were candidates for heart transplant surgery were randomly assigned to two groups. In the intervention group, patients received desmopressin of 0.3 µg/kg, 30 min. before surgery. Patients in the control group received normal saline at the same amount and time. Homeostasis was evaluated using activated clotting time (ACT), PT, PTT and PLT before, 12 and 24 hr after surgery, and also, chest tube drainage, blood products transfusion requirements during the first day in both groups. No significant differences were found between the groups in terms of ACT, PT, PTT and PLT at all times. Transfusion of packed red blood cells and the mean drainages of chest tube during the first 24 hr after surgery were significantly lower in the desmopressin group compared to the saline group. Desmopressin may reduce post-operative bleeding in patients undergoing heart transplant surgery. Further studies are required to confirm the potential effect of desmopressin on establishing haemostasis after heart transplantation.

Combination treatment of nocturnal enuresis with desmopressin and indomethacin.

BACKGROUND: We investigated the effect of combining indomethacin and desmopressin in treating children with monosymptomatic nocturnal enuresis (MNE) and desmopressin-resistant nocturnal polyuria. METHODS: Twenty-three children with MNE, nocturnal polyuria, and partial or no response to desmopressin were recruited from incontinence clinics of our tertiary referral center. We used a randomized single-arm crossover placebo-controlled study design consisting of two 3-week treatment periods with a combination of desmopressin (0.4 mg) and indomethacin (50 mg) or desmopressin and placebo at bedtime. Home recordings at baseline and for the final 2 weeks of each treatment period were performed and included nocturnal urine output measurements. The number of dry nights achieved and reduction in the nocturnal urine output were the main effect parameters. Student's t test and Pearson's correlation coefficient were used for statistical analysis. RESULTS: The addition of indomethacin to desmopressin significantly reduced nocturnal urine output (from 324 ± 14 ml to 258 ± 13 ml, p < 0.001). This did not lead to more dry nights in all children, and we found no statistically significant reduction in enuresis frequency (from 68 % ± 0.1 to 56 % ± 0.1, p = 0.24). CONCLUSIONS: Addition of indomethacin to desmopressin can further reduce nocturnal urine output in children with MNE and desmopressin-resistant nocturnal polyuria. The combination treatment does not, however, improve outcome in terms of frequency of nights with enuresis. The dissociation of antidiuretic and antienuretic effect may reflect nocturnal bladder reservoir dysfunction in children who present with normal daytime bladder function.