Nephrogenic diabetes insipidus induced by ureter obstruction due to benign prostatic hyperplasia: A case report.

INTRODUCTION: Diabetes insipidus can be a common cause of polyuria and hydronephrosis in the kidneys. However, there is few reported case of urinary obstruction induced nephrogenic diabetes insipidus. PATIENT CONCERNS: A 60-year-old Chinese man came to our hospital with the complaints of polydipsia and polyuria for 1 month. His examination showed chronic kidney disease stage III with eGFR of 48.274 ml/min, and the plasma osmolality was 338.00 mOsm/(kg·H2O) with a urinary osmolality of 163.00 mOsm/(kg·H2O). Moreover, imagological examination of the urinary system showed benign prostatic hyperplasia and hydronephrosis. DIAGNOSIS: He was considered with benign prostatic hyperplasia induced ureter hydronephrosis and nephrogenic diabetes insipidus. INTERVENTIONS: He got the transurethral resection of the prostate to alleviate urinary retention. OUTCOMES: After that, the urine output gradually decreased, and the administered hydrochlorothiazide was stopped due to the improved renal function. CONCLUSION: Our study presents a case of nephrogenic diabetes insipidus caused by urinary obstruction. Differential diagnoses for diabetes insipidus as well as the relationship between nephrogenic diabetes insipidus and urinary obstruction are also considered in this study.

Synthesis of bio-mediated silver nanoparticles from Silybum marianum and their biological and clinical activities.

The purpose of current study was green synthesis of silver nanoparticles (AgNPs) from seeds and wild Silybum plants in comparison with their respective extracts followed by characterization and biological potency. The biologically synthesized AgNPs were subjected to characterization using techniques like XRD, FTIR, TEM, HPLC and SPE. Highly crystalline and stable NPs were obtained using Silybum wild plant (NP1) and seeds (NP3) with size range between 18.12 and 13.20 nm respectively. The synthesized NPs and their respective extracts revealed a vast range of biological applications showing antibacterial, antioxidant, anti-inflammatory, cytotoxic and anti-aging potencies. The highest antioxidant activity (478.23 ± 1.9 µM, 176.91 ± 1.3 µM, 83.5 ± 1.6% µgAAE/mg, 156.32 ± 0.6 µgAAE/mg) for ABTS, FRAP, FRSA, TRP respectively was shown by seed extract (NP4) followed by highest value of (117.35 ± 0.9 µgAAE/mg) for TAC by wild extract (NP2). The highest antifungal activity (13 mm ± 0.76) against Candida albicans was shown by NP3 while antibacterial activity of (6 mm against Klebsiella pneumonia) was shown by NP3 and NP4. The highest anti-inflammatory activity (38.56 ± 1.29 against COX1) was shown by NP2. Similarly, the high value of (48.89 ± 1.34 against Pentosidine-Like AGEs) was shown by NP4. Also, the high anti-diabetic activity (38.74 ± 1.09 against α-amylase) was shown by NP4. The extracts and the synthesized NPs have shown activity against hepato-cellular carcinoma (HepG2) human cells. The HPLC analysis revealed that the highest value of silymarin component (silybin B 2289 mg/g DW) was found for NP4. Silydianin is responsible for capping. Among the green synthesized AgNPs and the extracts used, the effect of NP4 was most promising for further use.

Diuretic and Antidiuretic Activities of Ethanol Extract and Fractions of Lagopsis supina in Normal Rats.

Lagopsis supina is a well-known traditional Chinese medicine and used as an agent for diuresis in China for centuries. This is the first time to evaluate the diuretic activity of the ethanol extract of L. supina (LS) and its four fractions (LSA, LSB, LSC, and LSD) in normal rats. After the administration of LS-H, LS-M, LSB-H, and LSC-L, the urine output of the rats was significantly increased, while the urine excretion was significantly reduced after treatment with LSB-L. The urine Na+ excretion was remarkably increased with LS-H, LS-M, LSA-H, LSA-L, LSB-H, LSC-L, and LSD-L, and the urine K+ excretion was significantly increased after administration of LS-H and LSB-H. Moreover, the urine Na+ and K+ excretion was significantly reduced after treatment with LSC-H and LSD-H. However, the urine pH values and urine and serum Na+-K+-ATPase levels did not show remarkable change after administration of LS or its four fractions in comparison with the control group. On the contrary, LS and its four fractions can suppress the renin-angiotensin-aldosterone system (RAAS), including ADH arrest by LSB-H, LSB-L, LSC-L, LSD-L, and LSD-H and ALD arrest by LSD-L, as well as promote ANP release by LS-M, LSB-H, LSC-H, and LSD-H, while furosemide can suppress only arrest of ADH within 24 h compared with the control group. In addition, LS and its four fractions did not change the urine and serum TNF-α and IL-6 levels in normal rats within 24 h. This study will provide a quantitative basis for explaining the natural medicinal use of LS as a diuretic agent for edema and promoting the diuretic process.

Anti-Diabetic Effects of Gynura Bicolor Aqueous Extract in Mice.

The effects of Gynura bicolor aqueous extract (GAE) upon glycemic control, coagulation disorder, lipid accumulation, and glycative, oxidative, and inflammatory stresses in diabetic mice were investigated. Mice were treated with streptozotocin to induce type 1 diabetes. Diabetic mice were divided into four groups, consumed GAE at 0%, 0.25%, 0.5%, or 1%. Normal group consumed standard mouse basal diet. After 8-week treatments, mice were sacrificed after overnight fasting. Results showed that GAE supplement at 0.5% and 1% decreased plasma glucose level and increased plasma insulin level. Diabetes lowered plasma level of protein C and anti-thrombin III; and raised plasminogen activator inhibitor-1 activity and fibrinogen level in plasma. GAE supplement at 0.5% and 1% reversed these alterations. Histological data, assayed by Oil Red O stain, indicated that GAE supplement decreased lipid accumulation in liver. GAE supplement at 0.5% and 1% reduced aldose reductase activity in heart and kidney; and lowered the levels of carboxymethyllysine and pentosidine in plasma and two organs. Diabetes decreased glutathione content, and increased reactive oxygen species, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α production in heart and kidney. GAE supplement at three test doses reversed these changes. Diabetes upregulated the mRNA expression of p38 and nuclear factor kappa (NF-κ)B in heart and kidney. GAE supplement suppressed the mRNA expression of both p38 and NF-κB. These novel findings suggest that Gynura bicolor is a potent functional food for diabetic prevention or alleviation.

Robust hybrid enzyme nanoreactor mediated plasmonic sensing strategy for ultrasensitive screening of anti-diabetic drug.

Enzyme inhibition based drug screening strategy has been widely employed for new drug discovery. But this strategy faces some challenges in practical application especially for the trace active compound screening from natural products such as the stability of enzyme and the sensitivity of screening approach. Inspired by the above, we for the first time demonstrate the self-assembly of α-glucosidase (GAA) and glucose oxidase (GOx) into one multi-enzymes-inorganic nanoreactor with hierarchical structure (flower shape). The hybrid enzyme nanoreactor enjoys the merits including the character of assembly line, the enhanced enzymatic activity and robust stability. The flower shape of enzyme nanoreactor possessed a bigger specific surface area, facilitating the trace GAA inhibitor detection. Based on the above, we proposed an enzyme nanoreactor mediated plasmonic sensing strategy for anti-diabetic drug screening. First, maltose was chosen as the substrate for GAA and the generated glucose were immediately utilized by GOx to generate H2O2, and finally, H2O2 etched the Ag nanoprism to round nanodiscs, resulting in the blue shift of surface plasmon resonance (SPR) absorption band. With the aid of hybrid enzyme nanoreactor guided SPR, the ultrasensitive screening of GAA inhibitor (i.e. anti-diabetic drug) can be realized with the detection limit of 5nM for acarbose. The proposed approach was successfully utilized for GAA inhibitor screening from natural products. We anticipate that the proposed sensing method may provide new insights and inspirations in the enzyme inhibition based drug discovery and clinical diagnosis.

Role of caftaric acid in lead-associated nephrotoxicity in rats via antidiuretic, antioxidant and anti-apoptotic activities.

Background Lead is a toxic metal that is widely distributed in the environment where caftaric acid (CA) is the ester form of caffeic acid where CA is the major dietary polyphenol present in various foods and beverages. The aim of this study was to evaluate the effect of CA in lead acetate (LA)-associated nephrotoxicity through antidiuretic, antioxidant and anti-apoptotic activities. Methods Forty-eight male albino rats divided into six equal groups; group 1 control injected intraperitoneally (ip) with saline (1 mL/kg of bw) over two weeks period, group 2 injected ip with CA (80 mg/kg of bw) over two weeks period, groups 3, 4, 5 and 6 injected ip with 100 µmol/kg of bw LA over two weeks period where groups 4, 5 & 6 co-injected ip with 1-deamino-8-D-arginine vasopressin (dDAVP) drug (1 mg/kg of bw), CA (40 mg/kg of bw), and CA (80 mg/kg of bw), respectively. Results The results obtained revealed that LA induced a significant decrease in kidney weight and serum sodium, potassium and chloride, but caused a significant increase in urinary volume, urinary excretion of sodium, potassium and chloride, serum urea, creatinine and uric acid. The LA also caused a significant decrease in kidney superoxide dismutase, glutathione peroxidase and induced a significant decrease in glutathione level while caused an increase in lipid peroxidation level. In addition, LA caused a decrease in p53 expression while induced an increase in bcl-2 expression in the kidney tissues. Co-injection of CA to LA-treated group restored all the above parameters to approach the normal values. The results supported with histopathological examinations. Conclusions In conclusion, the effect of CA on LA-related nephrotoxicity was occurred through antidiuretic, antioxidant, anti-apoptotic activities where the effect of CA was dose dependent.

Effect of traditional Chinese and Western medicine on nocturnal enuresis in children and indicators of treatment success: Randomized controlled trial.

BACKGROUND: Nocturnal enuresis (NE) is a common pediatric developmental disorder. Desmopressin is frequently used for NE and is an evidence-based therapy. Suoquan capsule is a Chinese medicine commonly used for treating NE in children but is poorly understood by most scholars. METHODS: A total of 369 children with NE were randomized to receive either suoquan, desmopressin plus suoquan, desmopressin, or behavioral intervention for 2 months, and the response rates evaluated. Subsequently, the viable demographic factors that could lead to success were investigated on logistic regression analysis. Moreover, after 3 months of follow up, the relapse rate was investigated. RESULTS: The complete response (CR) rate in the desmopressin plus suoquan group (37.5%) was higher than that in the behavioral intervention group (6.3%, P < 0.007). The desmopressin group had a lower CR rate (22.5%) and a higher non-response rate (25.0%) than the desmopressin plus suoquan group (non-response rate, 21.9%; P > 0.007). The relapse rate in the desmopressin group was significantly higher than that in the desmopressin plus suoquan group (72.2% vs. 30.6%, P < 0.007). On Multivariate analysis, treatment group, NE frequency, and age were independent predictors of CR at 2 months (P < 0.05). CONCLUSIONS: Combined traditional Chinese and Western treatment in children with NE is effective and has a low relapse rate. NE frequency, treatment method, and age are important predictive factors for CR after treatment.

Primary and Secondary Enuresis: Pathophysiology, Diagnosis, and Treatment.

CONTEXT: Enuresis is a common and possibly underestimated condition. While 5-10% of school-aged children suffer from the condition, a lack of background knowledge may impede timely child-adapted and successful therapy. OBJECTIVE: To provide a comprehensive overview of the pathophysiology, diagnosis, and treatment of enuresis. EVIDENCE ACQUISITION: Guideline and position papers from the European Society of Pediatric Urology, the European Association of Urology, and the International Children's Continence Society were acquired. PubMed was searched for literature on enuresis, and all papers published in the last 5 yr were considered. The most relevant information from the papers with the highest level of evidence was extracted and incorporated into the review. EVIDENCE SYNTHESIS: An altered antidiuretic hormone profile, arousal failure, and delayed bladder maturation are the main pathophysiological factors in primary enuresis. Coexisting constipation, obstructive airway disease, attention deficit hyperactivity disorder, obesity, and genetic preconditions influence its prevalence. Diagnosis relies on history-taking and simple noninvasive examinations to differentiate monosymptomatic enuresis and patients with daytime symptoms. It is essential to exclude daytime voiding symptoms, overactive bladder, dysfunctional voiding, and urinary tract infections. Further imaging is indicated in complex cases with a suspicion of underlying congenital malformations or systemic or endocrine diseases and in children refractory to initial therapy. In secondary enuresis, psychological causes should also be taken into consideration. While desmopressin melt tablets and alarm systems constitute the mainstays of treatment in monosymptomatic enuresis, anticholinergics and urotherapy play an additional role in nonmonosymptomatic enuresis. For therapy-refractory cases, after a thorough re-investigation to identify any missed comorbidities and anatomical or functional causes of enuresis, combination therapy and stationary urotherapy might be promising options. CONCLUSIONS: While enuresis seems to be an often underestimated condition in terms of the suffering that children and their families, there are efficacious therapy options once a correct and full diagnosis is made. PATIENT SUMMARY: This article reviews primary and secondary nocturnal enuresis, which is the medical term for the condition whereby children wet their beds regularly after their first birthday. We describe the background of enuresis,including its complex underlying mechanisms, as well as diagnosis and treatment in the light of current scientific publications. We conclude that while enuresis seems to be an often underestimated condition in terms of the suffering that children and their families may undergo, there are efficacious therapy options once a correct and full diagnosis is made.

[Trends in antidiabetic treatment prescribed for patients with type 2 diabetes in Hungary between 2001 and 2014 - results from the database analysis of the National Health Insurance Fund]. / A 2-es típusú diabetes antihyperglykaemiás kezelésének alakulása Magyarországon 2001­2014 között ­ az Országos Egészségbiztosítási Pénztár adatbázis-elemzésének eredményei.

In the last couple of years, significant developments in antidiabetic treatment have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the changes in prescribing patterns of glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to 33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in 2014 with a number of registered patients of 727,000. Sulfonylurea-monotherapy decreased from 64% to 35% while metformin-monotherapy increased from 19% to 42% in this period. The most frequently used drug at first treatment initiation was metformin (66%) and sulfonylurea (16%) as monotherapy in 2014. DPP4-inhibitors were newly administered in 20,362 cases while GLP1-mimetics were newly used by 4,996 patients in 2014. Five years later after initiating sulfonylurea therapy between 2010 and 2014, metformin was more frequently used as second drug (39%) than sulfonylurea in patients with previous metformin treatment (22.9%). The prescribing patterns of glucose-lowering drugs have changed over time in accordance with new guidelines. Further changes in prescribing habits can be expected in the near future. Orv Hetil. 2017; 158(20): 770-778.

Reset Osmostat: The Result of Chronic Desmopressin Abuse?

A reset osmostat as a cause of hyponatremia can be found in a variety of clinical settings, including pulmonary and neurologic diseases, as well as in physiologic circumstances such as pregnancy. This teaching case describes a 72-year-old white man with a long-standing history of self-medicating with desmopressin acetate (DDAVP) who presented with profound hyponatremia. On discontinuation of DDAVP treatment, he was found to have a reset osmostat. The mild hyponatremia persisted on follow-up. We theorize that the reset osmostat may have developed secondary to long-standing DDAVP use.

DIURETIC AND ANTI-DIURETIC BIOACTIVITY DIFFERENCES OF THE SEED AND SHELL EXTRACTS OF ALPINIA OXYPHYLLA FRUIT.

BACKGROUND: Alpinia oxyphylla fruit (AOF, Yizhi in Chinese) is a well-known traditional Chinese medicine as an anti-diuretic agent and composed of two parts i.e. seed and shell. These two parts have different components, but the bioactivity differences of the two parts are not clear. This study aims to evaluate the different anti-diuretic effects of the seed and shell of AOF. MATERIALS AND METHODS: The potential bioactive components were analyzed by UPLC-Q-TOF-MS. The diuretic and anti-diuretic activity was determined with saline-loads rats. RESULTS: The results showed that the 200 mg/kg and 400mg/kg of SREAO displayed a short-time anti-diuretic activity 1h after administration and then a significant diuretic activity was being observed at 5-6 h in 400mg/kg group of SREAO. And the 400mg/kg doses of SREAO also showed a remarkable increase for electrolyte excretion of K+. Three sesquiterpene compounds, namely oxyphyllol A (1), oxyphyllol B (2), and nootkatone (3) were identified from the active SREAO fraction by UHPLC-ESI-Q-TOF/MS. CONCLUSION: The seed part of Alpinia oxyphylla possessed pronounced diuretic and anti-diuretic effect. The sesquiterpene components are the major constituents and possibly contributed the diuretic and anti-diuretic activity.

The confounding effect of the development of idiopathic orthostatic edema and thyrotoxcosis on weight fluctuation related to effects on free water clearance in a woman with long-standing surgically induced panhypopituitarism and diabetes insipidus.

PURPOSE: To evaluate the effect of idiopathic orthostatic edema and the effect of thyrotoxicosis on weight fluctuation and fluid retention in the presence of surgically induced panhypopituitarism and diabetes insipidus controlled with hormone replacement. MATERIALS AND METHODS: Dextroamphetamine sulfate was used for weight gain when no other etiologic factor was found. Methimazole was used when weight loss occurred when serum T4 and free T4 indicated thyrotoxicosis. RESULTS: Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. CONCLUSIONS: Hypopituitarism and diabetes insipidus controlled with hormone replacement do not protect against fluid retention from idiopathic edema.

Comparative resuscitation measures for the treatment of desipramine overdose.

A toxic dose of desipramine (tricyclic antidepressant) causes cardiac arrhythmias and ultimately asystole. Resuscitation is difficult and almost always unsuccessful. Anecdotal evidence suggests that an infusion of lipid emulsion may be an effective treatment. The purpose of this study was to determine the optimal combination of lipid rescue and traditional Advanced Cardiac Life Support therapy for the treatment of desipramine overdose. We use a prospective, experimental, between subjects design with a swine model investigating the effectiveness of the drugs and drug combinations administered with cardiopulmonary resuscitation. Subjects were randomly assigned to 1 of 8 cardiopulmonary resuscitation/drug combination interventions, and the results from each group were compared using an analysis of variance and post hoc Tukey where appropriate. The groups that received vasopressin were more likely to survive than those that did not receive vasopressin, and the groups that received lipid emulsion were more likely to survive than those that did not receive lipid emulsion. Vasopressin alone was shown to be the most effective treatment in the management of desipramine overdose. The results of this study may warrant changes in treatment protocols for desipramine overdose.

Diuretic and anti-diuretic activities of fractions of Alismatis rhizoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in China and Japan. In this paper, we report the diuretic activities of the petroleum ether fraction, the ethyl acetate fraction, the n-buthanol fraction, and the remaining fraction, of the ethanol extract of Alismatis rhizoma (AR). MATERIALS AND METHODS: The single dose of the petroleum ether fraction, the ethyl acetate fraction, the n-buthanol fraction, and the remaining fraction, of the ethanol extract of AR were orally administered to rats. Urinary excretion rate, pH and electrolyte excretion were measured in the urine of saline-loaded rats. RESULTS: In this study, the 100 and 400mg/kg doses of the ethyl acetate fraction and the 12.5, 25 and 50mg/kg doses of the n-butanol fraction all produced an increase in urine volume excretion, and all produced a remarkable increase in urine electrolyte excretion. Although the 800mg/kg doses of the ethyl acetate fraction, the 75 and 100mg/kg doses of the n-butanol fraction and the 12.5, 25 and 50mg/kg doses of the remaining fraction significantly decreased the urine output in 6h, the urine Na(+) and Cl(-) excretion were markedly decreased with the n-butanol fraction (75 and 100mg/kg doses) and the remaining fraction (12.5, 25 and 50mg/kg doses) while the ethyl acetate fraction at 800mg/kg doses had slight effect on urine electrolyte excretion. The petroleum ether fraction did not show remarkable diuretic activity in comparison with control group. CONCLUSIONS: Our present study determined that the ethyl acetate fraction and the n-butanol fraction present notable diuretic effects, and we found a dual effect on renal function showed by AR, including promoting diuretic activity and inhibiting diuretic activity. The components with strong polarities in AR may have anti-diuretic activities, which might be an effect of promoting the sodium-chloride co-transporter in the distal tubule.

Combined laser acupuncture and desmopressin for treating resistant cases of monosymptomatic nocturnal enuresis: a randomized comparative study.

OBJECTIVE: Monosymptomatic nocturnal enuresis (MNE) is a common sociomedical problem affecting children that may persist until adulthood despite various lines of therapy. The aim of this study was to assess the efficacy of combined laser acupuncture and desmopressin in managing patients with resistant MNE, compared with their efficacy when used as monotherapy. MATERIAL AND METHODS: The study included 186 patients with a mean age of 15.7 years (range 10-21 years) presenting with persistent MNE. All patients were evaluated clinically and investigated with urine analysis, plain X-ray of the urinary tract and abdominal ultrasonography. They were randomized into three equal groups based on the line of management: group A, managed with laser acupuncture alone; group B, managed with desmopressin alone; and group C, managed with a combination of laser acupuncture and desmopressin, with a treatment course of 3 months and follow-up period of 6 months to record the efficacy of therapy, side-effects and bladder capacity. RESULTS: A statistically significant higher cure rate was reported in group C patients, being reported in 33, 35 and 46 patients in groups A, B and C, respectively. Improvement was reported in 18, 17 and 13 cases in groups A, B and C, respectively, but the difference was not statistically significant. Bladder capacity significantly increased only in patients receiving acupuncture (groups A and C). CONCLUSION: Combined laser acupuncture and desmopressin is a promising and valid option to manage resistant cases of MNE.

Diuretic and anti-diuretic activities of the ethanol and aqueous extracts of Alismatis rhizoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Alismatis rhizoma or Alisma orientale (Zexie in Chinese), the dried rhizome of Alisma orientale Juzepzuk (Alismataceae), is a well-known traditional Chinese medicine and is used as an agent for diuresis and for excreting dampness in Asia and Europe. In this paper, we report the diuretic activities of the ethanol extract (EE) and the aqueous extract (AE) of A. rhizoma (AR). MATERIALS AND METHODS: The EE and AE were orally administered to rats. The urinary excretion rate and pH, and electrolyte excretion were measured in the urine of saline-loaded rats. RESULTS: The results showed that EE could increase the urine output at 2.5, 5 and 10mg/kg doses but decrease the urine output at 20, 40 and 80mg/kg doses compared with the control group. The 5 and 10mg/kg doses of EE increased the urine electrolyte excretion, but the effects on Na(+)/K(+) values were too weak to reach statistical significance. The Na(+) excretion and Cl(-) excretion were markedly decreased with the 20, 40 and 80mg/kg doses of EE, but the effect on K(+) excretion was notably slight. All of the tested doses of AE produced an increase in urinary excretion, but the increase did not reach statistical significance. CONCLUSIONS: This study identified that EE but not AE presents a notable diuretic effect, and EE had diuretic and anti-diuretic effects, which appears to be related to the sodium-chloride co-transporter in the renal distal convoluting tubule. This study demonstrated for the first time that the EE of AR has a dual effect on renal function, including promotion of diuretic activity at lower doses and inhibiting diuretic activity at higher doses, and the AR dose should be given more attention in clinical applications. This study will play a critical and guiding role in the dosing of AR as a diuretic drug in clinical applications.

Outcome of a standardized approach to childhood urinary symptoms-long-term follow-up of 720 patients.

AIMS: To investigate the relevance of enuresis subtyping for selection of treatment modality and for long-term outcome in a large consecutive patient cohort. MATERIALS AND METHODS: We included all patients referred for urinary incontinence during a 5-year period but excluding recurrent urinary tract infections (UTI). Type and severity of incontinence, prior history, results of examinations performed, number of visits, and effect of all treatments provided, were included in a clinical database. RESULTS: Seven hundred twenty children aged 4-16 years (mean 8.5 ± 2.2 years, 239 girls) were included in the analysis (42% with monosymptomatic (MNE), 55% with non-MNE, and 3% with isolated daytime incontinence). Initial evaluation revealed only few underlying causes (one neurological and eight anatomical). Investigations showed significant differences between MNE and non-MNE patients as both maximal voided volume and nocturnal urine volume was lower in non-MNE patients (P < 0.001). Follow-up for average 1,587 days (3.4 years) was performed in 660 (92%) patients. A higher number of visits and a longer treatment period were needed for non-MNE patients (on average 4.7 ± 2.8 visits) than MNE patients (3.1 ± 1.6 visits, P < 0.001). The most common treatment regimen that resulted in dryness in both MNE (40%) and non-MNE (36%) was the alarm system. Interestingly, of the 539 patients who initially were referred due to desmopressin resistance 177 (33%) of these were dry on desmopressin monotherapy. CONCLUSIONS: The study indicated that MNE and non-MNE are two distinct disease entities with different optimal treatments and showed that the latter patients are more difficult and time-consuming to manage.

Quantitative apical membrane proteomics reveals vasopressin-induced actin dynamics in collecting duct cells.

In kidney collecting duct cells, filamentous actin (F-actin) depolymerization is a critical step in vasopressin-induced trafficking of aquaporin-2 to the apical plasma membrane. However, the molecular components of this response are largely unknown. Using stable isotope-based quantitative protein mass spectrometry and surface biotinylation, we identified 100 proteins that showed significant abundance changes in the apical plasma membrane of mouse cortical collecting duct cells in response to vasopressin. Fourteen of these proteins are involved in actin cytoskeleton regulation, including actin itself, 10 actin-associated proteins, and 3 regulatory proteins. Identified were two integral membrane proteins (Clmn, Nckap1) and one actin-binding protein (Mpp5) that link F-actin to the plasma membrane, five F-actin end-binding proteins (Arpc2, Arpc4, Gsn, Scin, and Capzb) involved in F-actin reorganization, and two actin adaptor proteins (Dbn1, Lasp1) that regulate actin cytoskeleton organization. There were also protease (Capn1), protein kinase (Cdc42bpb), and Rho guanine nucleotide exchange factor 2 (Arhgef2) that mediate signal-induced F-actin changes. Based on these findings, we devised a live-cell imaging method to observe vasopressin-induced F-actin dynamics in polarized mouse cortical collecting duct cells. In response to vasopressin, F-actin gradually disappeared near the center of the apical plasma membrane while consolidating laterally near the tight junction. This F-actin peripheralization was blocked by calcium ion chelation. Vasopressin-induced apical aquaporin-2 trafficking and forskolin-induced water permeability increase were blocked by F-actin disruption. In conclusion, we identified a vasopressin-regulated actin network potentially responsible for vasopressin-induced apical F-actin dynamics that could explain regulation of apical aquaporin-2 trafficking and water permeability increase.