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Background: The kidney and cardiovascular system are closely related to each other during the modulation of the cardiovascular homeostasis. However, the search for new alternatives for the treatment and diagnosis of cardiovascular diseases does not take into account this relationship, so their evaluation results and the advantages offered by their global and integrative analysis are wasted. For example, a variety of receptors that are overexpressed in both pathologies is large enough to allow expansion in the search for new molecular targets and ligands. Nanotechnology offers pharmacological targeting strategies to kidney, heart, and blood vessels for overcoming one of the essential restrictions of traditional cardiovascular therapies the ones related to their unspecific pharmacodynamics distribution in these critical organs., Recent Findings: Drug or contrast agent nano-targeting for treatment or diagnosis of atherosclerosis, thrombosis, renal cancer or fibrosis, glomerulonephritis, among other renal, cardiac and blood vessels pathologies would allow an increase in their efficacy and a reduction of their side effects. Such effects are possible because, through pharmacological targeting, the drug is mainly found at the desired site. Review Purpose: In this mini-review, active, passive, and physical targeting strategies of several nanocarriers that have been assessed and proposed for the treatment and diagnosis of different cardiovascular diseases, are being addressed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Chronic kidney disease (CKD) is characterized by progressive loss of renal functions. At present, there are only limited therapeutic strategies to slow down the progress of CKD and there is an urgent need to develop new therapeutic strategies to treat CKD patients. Numerous research evidence supports the potential role of EGCG in the renal protection of CKD. However, the clinical use is still limited due to the poor oral bioavailability. The aim of this study was to develop pH-sensitive polymeric nanoparticles of EGCG to improve this deficiency., Materials and Methods: EGCG-loaded nanoparticles (EGCG NPs) were prepared by an improved emulsion evaporation method. The formulation prepared was in spherical with uniform sizes, high encapsulation efficiencies and drug loading. The therapeutic efficacy of EGCG NPs on chronic kidney disease was investigated on model of rat Nephrotic syndrome by measuring urinary protein excretion and kidney pathology score., Results: The mean particle size was found to be 91.3±0.8 nm and the encapsulation efficiency% and drug loading% of the formulation were 80.8%±1.6% and 6.3%±1.4%, respectively. The powder X-ray diffraction and differential scanning calorimetry of EGCG NPs showed that EGCG existed in amorphous form in NPs. The release of EGCG from NPs exhibited the lower burst release at pH 1.2 (<10%) and with the increase of pH value, the release of EGCG also gradually increased. During the observation period (24 hours), the total release amount was almost 68%. EGCG NPs could significantly modify the pharmacokinetic profile and increase the bioavailability of EGCG by more than 2.4-fold in comparison with the EGCG powder group. At the end of the fourth and sixth week, proteinuria excretion of nephrotic syndrome rats treated with EGCG NPs was significantly lower than those treated with EGCG powder, and kidney pathology scores in EGCG NPs treated rats were also significantly lower than EGCG powder treated rats., Conclusion: The results of pharmacodynamics showed that compared with EGCG powder treatment group, EGCG NPs treatment group had better efficacy and reduce kidney damage., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The first-line drug therapy for patients with nocturnal enuresis (NE) associated with nocturnal polyuria and normal bladder function is desmopressin (dDAVP)., Objective: To evaluate if increasing dose of oral desmopressin lyophilisate (MELT) can improve response rates to dDAVP and is useful in enuretic children., Materials and Methods: We enrolled a total of 260 children all diagnosed with NE. Enuretic children were treated with increasing MELT at a dose of 120, 180 and 240 mcg a day., Results: We included in our study a total of 237 children, 164 males (69.2%) and 73 females (30.8%) aged between 5 and 18 years (mean age 10.32 ± 2.52 years). Of the 237 patients enrolled in the study and treated with MELT 120 mcg, a full response was achieved in 135 (56.9%). A partial response was achieved in 21 (8.9%) patients, therefore the dose was increased up to 180 mcg, with further improving symptoms (14.3%) or full response (9.5%), and up to 240 mcg, without usefulness., Conclusions: MELT at the dose of 120 mcg resulted efficacy and safety; the increased dose up to 180 mcg resulted poorly efficacy; finally, the further increase up to 240 mcg did not improve the symptoms with the increased risk of side effects.

Importance: Acute kidney injury (AKI) occurs commonly in preterm neonates and is associated with increased morbidity and mortality., Objectives: To examine the association between caffeine citrate administration and AKI in preterm neonates in the first 7 days after birth and to test the hypothesis that caffeine administration would be associated with reduced incidence and severity of AKI., Design, Setting, and Participants: This study was a secondary analysis of the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, a retrospective observational cohort that enrolled neonates born from January 1 to March 31, 2014. The dates of analysis were October 2016 to December 2017. The setting was an international, multicenter cohort study of neonates admitted to 24 participating level III or IV neonatal intensive care units. Participants met the original inclusion and exclusion criteria of the AWAKEN study. Additional exclusion criteria for this study included participants greater than or equal to 33 weeks' gestation at birth, admission after age 7 days, use of theophylline in the neonatal intensive care unit, or lack of data to define AKI. There were 675 preterm neonates available for analysis., Exposure: Administration of caffeine in the first 7 days after birth., Main Outcomes and Measures: The primary outcome was the incidence of AKI (based on the modified neonatal Kidney Disease: Improving Global Outcomes [KDIGO] definition) in the first 7 days after birth. The hypothesis that caffeine administration would be associated with reduced AKI incidence was formulated before data analysis., Results: The study cohort (n = 675) was 55.4% (n = 374) male, with a mean (SD) gestational age of 28.9 (2.8) weeks and a mean (SD) birth weight of 1285 (477) g. Acute kidney injury occurred in 122 neonates (18.1%) in the first 7 days after birth. Acute kidney injury occurred less frequently among neonates who received caffeine than among those who did not (50 of 447 [11.2%] vs 72 of 228 [31.6%], P < .01). After multivariable adjustment, administration of caffeine remained associated with reduced odds of developing AKI (adjusted odds ratio, 0.20; 95% CI, 0.11-0.34), indicating that for every 4.3 neonates exposed to caffeine one case of AKI was prevented. Among neonates with early AKI, those receiving caffeine were less likely to develop stage 2 or 3 AKI (adjusted odds ratio, 0.20; 95% CI, 0.12-0.34)., Conclusions and Relevance: Caffeine administration in preterm neonates is associated with reduced incidence and severity of AKI. Further studies should focus on the timing and dosage of caffeine to optimize the prevention of AKI.

Chronic kidney disease (CKD) has emerged as a major cause of morbidity and mortality worldwide. Interstitial fibrosis, glomerulosclerosis and inflammation play the central role in the pathogenesis and progression of CKD to end stage renal disease (ESRD). Transforming growth factor-β1 (TGF-β1) is the central mediator of renal fibrosis and numerous studies have focused on inhibition of TGF-β1 and its downstream targets for treatment of kidney disease. However, blockade of TGF-β1 has not been effective in the treatment of CKD patients. This may be, in part due to anti-inflammatory effect of TGF-β1. The Smad signaling system plays a central role in regulation of TGF-β1 and TGF-β/Smad pathway plays a key role in progressive renal injury and inflammation. This review provides an overview of the role of TGF-β/Smad signaling pathway in the pathogenesis of renal fibrosis and inflammation and an effective target of anti-fibrotic therapies. Under pathological conditions, Smad2 and Smad3 expression are upregulated, while Smad7 is downregulated. In addition to TGF-β1, other pathogenic mediators such as angiotensin II and lipopolysaccharide activate Smad signaling through both TGF-β-dependent and independent pathways. Smads also interact with other pathways including nuclear factor kappa B (NF-κB) to regulate renal inflammation and fibrosis. In the context of renal fibrosis and inflammation, Smad3 exerts profibrotic effect, whereas Smad2 and Smad7 play renal protective roles. Smad4 performs its dual functions by transcriptionally promoting Smad3-dependent renal fibrosis but simultaneously suppressing NF-κB-mediated renal inflammation via Smad7-dependent mechanism. Furthermore, TGF-β1 induces Smad3 expression to regulate microRNAs and Smad ubiquitination regulatory factor (Smurf) to exert its pro-fibrotic effect. In conclusion, TGF-β/Smad signaling is an important pathway that mediates renal fibrosis and inflammation. Thus, an effective anti-fibrotic therapy via inhibition of Smad3 and upregulation of Smad7 signaling constitutes an attractive approach for treatment of CKD., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Mizoribine (MZR) is used kidney transplant and various kidney diseases. However, few studies reported the association between pharmacokinetics and pharmacodynamics. The Pharmacokinetics Study Group for Pediatric Kidney Disease (PSPKD) used population pharmacokinetics (PPK) analysis and Bayesian analysis to investigate the usefulness of MZR. In this study, the fact that almost all MZR are excreted unchanged in urine was used to calculate its bioavailability (F) and true distribution volume (V d ), and analyzed these correlation with age., Methods: Ishida et al. reported a PPK analysis by the PSPKD. In the present study, 71 samples extracted from their study population of 105 pediatric chronic kidney disease patients aged between 1 and 20 years were investigated. The bioavailability was calculated by measuring total excreted MZR in 24 h urine samples, and this was compared to the oral dosage. The apparent distribution volume (V d /F) obtained from Bayesian analysis was then used to calculate true distribution volume (V d ), and the correlation of each parameter with age was investigated., Results: The median dose of MZR per weight was 5.17 mg/kg/day. Median bioavailability was 32.02%. Median V d per weight was 0.46 L/kg. There was a significant, weakly positive correlation between bioavailability and age (p = 0.026). There was also a significant, weakly negative correlation between V d per weight and age (p = 0.003)., Conclusion: Bioavailability and V d per weight tended to decrease depending on age. The younger patient required larger dose required to obtain the maximum effect from MZR, and this is important for immunosuppressive therapy.

In this study, we aimed to systematically review available literature on the efficacy of eculizumab for the treatment of renal involvement in patients with systemic lupus erythematosus (SLE). We conducted a literature search developed a priori, to identify articles reporting clinical experience with the use of eculizumab in SLE patients, focusing on renal involvement. The search strategy was applied to Ovid MEDLINE, EMBASE, In-Process and Other Non-Indexed Citation, Cochrane Central Register of Controlled Trials and Scopus from 2006 to present. Abstracts from EULAR and ACR congresses were also screened. We included six publications describing the renal outcome in SLE patients receiving eculizumab. Five out of six cases described the occurrence of thrombotic microangiopathy (TMA) in renal biopsies of patients with known SLE; three cases with biopsy-proven lupus nephritis (LN) and two patients with SLE-related antiphospholipid syndrome without histologic evidence of LN. One study reported the outcome of a patient with severe refractory LN successfully treated with eculizumab. All patients, regardless of the presence of concomitant LN, presented with severe hypocomplementemia and renal function impairment. All patients showed a sustained improvement of renal function and normalization of complement parameters after treatment with eculizumab[median follow-up 9 months (1-17)]. Despite the limitations of the currently available evidence, existing data are promising and provide preliminary support for the use of eculizumab in selected cases of SLE with renal involvement, especially in the presence of TMA, or in patients with refractory LN.

Background: Erythropoiesis stimulating agents (ESAs) were proposed to enhance survival of renal tissues through direct effects via activation of EPO receptors on renal cells resulting in reduced cell apoptosis, or indirect effects via increased oxygen delivery due to increased numbers of Hb containing red blood cells. Thus through several mechanisms there may be benefit of ESA administration on kidney disease progression and kidney function in renal patients. However conflicting ESA reno-protection outcomes have been reported in both pre-clinical animal studies and human clinical trials. To better understand the potential beneficial effects of ESAs on renal-patients, meta-analyses of clinical trials is needed., Methods: Literature searches and manual searches of references lists from published studies were performed. Controlled trials that included ESA treatment on renal patients with relevant renal endpoints were selected., Results: Thirty two ESA controlled trials in 3 categories of intervention were identified. These included 7 trials with patients who had a high likelihood of AKI, 7 trials with kidney transplant patients and 18 anemia correction trials with chronic kidney disease (predialysis) patients. There was a trend toward improvement in renal outcomes in the ESA treated arm of AKI and transplant trials, but none reached statistical significance. In 12 of the anemia correction trials, meta-analyses showed no difference in renal outcomes with the anemia correction but both arms received some ESA treatment making it difficult to assess effects of ESA treatment alone. However, in 6 trials the low Hb arm received no ESAs and meta-analysis also showed no difference in renal outcomes, consistent with no benefit of ESA/ Hb increase., Conclusions: Most ESA trials were small with modest event rates. While trends tended to favor the ESA treatment arm, these meta-analyses showed no reduction of incidence of AKI, no reduction in DGF or improvement in 1-year graft survival after renal transplantation and no significant delay in progression of CKD. These results do not support significant clinical reno-protection by ESAs.

Background: Nephropathic cystinosis is a rare lysosomal storage disease which is characterized by the accumulation of free cystine in lysosomes and subsequent intracellular crystal formation of cystine throughout the body. If not treated with cysteamine, a cystine-depleting agent, end-stage renal disease will develop early, followed by multiple organ failure as the disease progresses. The established cysteamine formulation requires a strict dosing regimen at 6-h intervals. An extended release (ER) twice-daily formulation has recently been developed. The aim of our study was to evaluate the implementation and outcomes of this option in routine care., Methods: All pediatric cystinosis patients' records in Hannover Medical School were screened, and data on cysteamine therapy, tolerability, dosing, estimated glomerular filtration rates (eGFR), white blood cell cystine levels, and proton pump inhibitor (PPI) use were extracted for the period January 2014 to January 2016., Results: The median age of the 12 patients enrolled in the study was 12.5 (range 1-18) years. At the end of the study period ten of these patients received ER-cysteamine. There were no additional side effects. Halitosis/bad breath was often subjectively judged as improved or eliminated, and PPI use could be stopped in one of three patients. The main reasons for switching to the ER formulation were difficult night-time administration and uncontrolled disease. Mean eGFR values remained stable with a median of 67 ml/min/1.73 m 2 before and after the transition. White blood cell (WBC) cystine values remained low after the switch (1 nmol/mg protein before and after transition; p = 0.64)., Conclusions: In this single-center cohort, the switch from IR- to ER-cysteamine was safe and effective over the short term and provided advantages in terms of frequency of administration and less halitosis/bad breath. The long-term benefit of this option needs to be evaluated in future studies.

Background: Contrast-induced nephropathy (CIN) remains to be a potentially serious complication of radiographic procedures and is the third leading cause of the acute kidney injury (AKI) among hospitalized patients. This clinical trial was performed to assess the preventive effect of oral nicorandil on CIN in high-risk patients undergoing cardiac catheterization., Methods: In this prospective, randomized, controlled trial, 128 patients with at least two risk factors for CIN undergoing elective percutaneous coronary intervention (PCI) were randomly assigned to either the nicorandil group or the control group. Patients in the nicorandil group (n = 64) received 10 mg nicorandil, daily from 30 min before and up to 3 days after procedure and intravenous hydration for 2 h before and 6 h after the procedure, whereas patients in the control group (n = 64) just received intravenous hydration. Serum creatinine (SCr) was measured before contrast exposure and at 72 h. CIN was defined as an increase of 25% in SCr or > 0.5 mg/dL 72 h after contrast administration., Results: Contrast-induced nephropathy occurred in 14 out of 64 (21.9%) patients in the control group and in 3 out of 64 (4.7%) patients in the nicorandil group. There was a significant difference in the incidence of CIN between the two groups at 72 h after administering the radiocontrast agent (p = 0.008). Moreover, there were significant differences between the two groups in SCr and estimated glomerular filtration rate 72 h after radiocontrast administration (p < 0.05)., Conclusions: The findings revealed that oral nicorandil had substantial efficacy over hydration protocol for the development of CIN in high-risk patients undergoing cardiac catheterization.

Many geriatric patients with multimorbidities have an increased risk for impaired renal function due to age and often the presence of comorbidities, such as diabetes mellitus, hypertension and heart failure. This impairment in kidney function in turn necessitates adjustments in drug therapy. A successful strategy for treating these patients includes treatment of the underlying diseases, a comprehensive review of the indications, selection of appropriate pharmacotherapeutic alternatives and for some drugs dose adjustment to the renal function. To achieve therapeutic success many patient individual factors, such as potentially complex medication regimens, polypharmacy, cognitive function and functional disabilities need to be considered when prescribing medications. This article describes the problems associated with drug therapy that is not adjusted to renal function and provides guidelines for assessment of the benefits and risks in patients with kidney failure. The characteristic features of geriatric patients in particular are considered and discussed.

Objective: To investigate the clinical effect of double dose of valsartan combined with tacrolimus in the treatment of diabetic nephropathy (DN)., Patients and Methods: HA total of 86 cases diagnosed with DN were selected from October 2013 to October 2014 in Zaozhuang Municipal Hospital, China. The study was approved by our hospital Ethics Committee and written consent was obtained from patients and their family members. Patients were randomly divided into three groups according to the sequence of admission, group A (conventional dose of valsartan group, n = 28 cases), group B (double dose of valsartan group, n = 29 cases) and group C (double dose of valsartan combined with tacrolimus group, n = 29). Clinical effects were compared by analyzing the renal function tests after 8 weeks., Results: 24h urine protein, serum creatinine level of patients in group B and group C were significantly lower than that of group A. Those in group C was much lower. The glomerular filtration rates were significantly higher for group B and C than that of group A, and those in group C were much higher. The difference is statistically significant (p < 0.05). High-sensitivity C-reactive protein (hs CRP) and adiponectin levels of patients in group B and C of were significantly lower than that of group A and those in group C were much lower. The difference is statistically significant (p < 0.05). The high mobility group protein 1 (HMGB1) and renal tubular and interstitial damage index (TDI) of patients in B and C groups were significantly lower than those in the A group, and those in C group were significantly lower. The difference was statistically significant p < 0.05). The clinical effective rates of patients in group B and C were significantly higher than that in group A, and those of group C were much higher. The difference is statistically significant (p < 0.05). The recurrence rates of patients in group B and group C were significantly lower than those of group A and those in group C were much lower. The difference is statistically significant (p < 0.05). Patients in three groups showed no obvious drug complications., Conclusions: Double dose of valsartan combined with tacrolimus treatment of DN patients can improve clinical symptoms, reducing inflammation, inhibiting or even reversing the interstitial fibrosis, which will improve the curative effect and reduce the recurrence, as to provide a new theoretical basis for the clinical treatment of the disease.

Lycium barbarum, extensively utilized as a medicinal plant in China for years, exhibits antitumor, immunoregulative, hepatoprotective, and neuroprotective properties. The present study aims to investigate the hyperglycemic and antidiabetic nephritic effects of polysaccharide which is separated from Lycium barbarum (LBPS) in high-fat diet-streptozotocin- (STZ-) induced rat models. The reduced bodyweight and enhanced blood glucose concentration in serum were observed in diabetic rats, and they were significantly normalized to the healthy level by 100 mg/kg of metformin (Met) and LBPS at doses of 100, 250, and 500 mg/kg. LBPS inhibited albuminuria and blood urea nitrogen concentration and serum levels of inflammatory factors including IL-2, IL-6, TNF-α, IFN-α, MCP-1, and ICAM-1 compared with diabetic rats, and it indicates the protection on renal damage. Furthermore, the activities of SOD and GSH-Px in serum were enhanced strikingly by LBPS which suggests its antioxidation effects. LBPS, compared with nontreated diabetic rats, inhibited the expression of phosphor-nuclear factors kappa B (NF-κB) and inhibitor kappa B alpha in kidney tissues. Collectively, LBPS possesses antidiabetic and antinephritic effects related to NF-κB-mediated antioxidant and antiinflammatory activities.

Background: Chronic kidney disease (CKD) is an important risk factor for cardiac surgery. In the most recently reported NU-HIT trial for CKD with CKD patients underwent coronary artery bypass grafting (CABG) as subjects, carperitide was reported to be effective in terms of renal function. In the present study, a subanalysis was performed on patients registered in the NU-HIT trial for CKD from the standpoint of renin-angiotensin system, natriuresis and renal function., Methods: 303 patients with CKD who underwent isolated CABG were divided into a group that received carperitide infusion and another group without carperitide. The renin activity, angiotensin-II, aldosterone, urine-sodium, urine- creatinine, fractional sodium excretion, renal failure index, and BNP levels., Results: There were significant lower in hANP group than the placebo group, in angiotensin-II at one day postoperatively, and in aldosterone from 0 day to one month postoperatively. FENa was significantly lower in the hANP group at 3 day and one week postoperatively., Conclusions: In on pump isolated CABG patients with CKD, carperitide showed a potent natriuretic action and inhibited the renin-angiotensin system, suggesting that it prevented deterioration of postoperative renal function. Our findings raise new possibilities for the perioperative and postoperative management of patients undergoing surgery with cardiopulmonary bypass.

Objective: To describe a practical solution for addressing body weight when using the Cockcroft-Gault equation to determine drug dosing., Data Sources: A literature search was conducted using PubMed MEDLINE (1980-April 2013) using creatinine clearance, Cockcroft and Gault, Cockcroft-Gault, body weight, and obesity as search terms. Reference citations from publications reviewed were included., Study Selection and Data Extraction: All English-language articles identified by the search were reviewed. Studies comparing the accuracy and bias of the Cockcroft-Gault equation using a variety of body weight designations in adult populations were included in the analysis., Data Synthesis: Study results indicated that, for obese patients, ideal body weight (IBW) underestimates creatinine clearance (CrCl) and total body weight (TBW) overestimates CrCl. Some studies suggest that adjusted body weight with a factor of 0.4 is most accurate, while others suggest the use of lean body weight. These studies have failed to produce a definitive resolution to the controversy. Despite many well-designed studies, the Cockcroft-Gault body weight controversy remains unresolved and uncertainty continues to exist as to which form of weight should be used in the equation. A different perspective is warranted. Since renal dosing guidelines are generally based on ranges of CrCl, applying a CrCl range to describe a patient's renal function might be more practical than relying on a specific CrCl value. Ultimately, CrCl-based drug dosing involves the use of an imperfect mathematical approximation, which is then applied as precisely as possible to the benefit versus risk analysis for a specific patient., Conclusions: We propose the use of a CrCl range for drug dosing purposes, with the lower boundary defined by using IBW in the Cockcroft-Gault equation and the upper boundary by using TBW.

Aims: To explore the durability of efficacy and gender differences during chronic administration of desmopressin in nocturia., Methods: This pooled analysis of three short-term efficacy studies, with extensions, of desmopressin administered as orally disintegrating tablet (ODT) or solid tablet in nocturia treatment, comprised 351 patients completing 40-56 weeks' treatment. Efficacy endpoints of change in number of nocturnal voids and duration of initial undisturbed sleep period from baseline were analyzed to determine response durability and gender differences., Results: The mean decrease in number of nocturnal voids during short-term treatment was maintained and further reduced during the long term. At 52 weeks, the mean decrease in number of nocturnal voids from baseline reached 1.4-2.1 voids for desmopressin ODT 25-100 µg. Following 40-week tablet treatment, the decrease in number of nocturnal voids was 0.8-1.5 for desmopressin 100-400 µg. The mean decrease in nocturnal voids (25-50 µg ODT) was greater for females than males. For females, the improvement in initial period of undisturbed sleep was 2.5-3 hr for desmopressin ODT 25-100 µg, compared with 1.3-2.6 hr for males. No gender difference in efficacy was seen in the tablet studies., Conclusions: The decrease in nocturnal voids and improvement in sleep with short-term desmopressin treatment were maintained throughout long-term treatment. A durable gender difference in efficacy in favor of females was observed with desmopressin ODT 25 µg. Further, large-scale long-term trials are needed to confirm the durability of efficacy with gender-specific doses of desmopressin., (Copyright © 2012 Wiley Periodicals, Inc.)

The potential clinical value of developing a novel, nonviral, ultrasound-directed gene and drug delivery system is immense. Investigators soon will initiate clinical trials with the goal of treating a wide variety of maladies using noninvasive, ultrasound-based technology. The ongoing, scientific validation associated with promising preclinical success portents a novel range of therapeutics. The clinical utility and eventual clinical successes await vigorous testing. This review highlights the recent successes and challenges within the field of ultrasound-mediated drug delivery.

The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously investigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic and tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28+/-0.36 vs. 0.39+/-0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical significance (0.18+/-0.05 vs. 0.10+/-0.02, P=0.07). The left renal FE(Na) was significantly lower in Group-2 (29.9+/-6.4 vs. 49.7+/-7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI.

Chronic kidney disease (CKD) is often complicated with advanced heart failure because of not only renal congestion and decreased renal perfusion but also prolonged use of diuretics at higher doses, which sometimes results in hyponatremia. Preoperative CKD is known to be associated with poor prognosis after heart transplantation (HTx). We experienced a stage D heart failure patient with CKD and hyponatremia who was switched from trichlormethiazide to tolvaptan. His hyponatremia was normalized, and his renal function was improved after conversion to tolvaptan. In patients with stage D heart failure, it may be useful to administer tolvaptan with a concomitant reduction in the dose of diuretics in order to preserve renal function and avoid hyponatremia before HTx.

Hepatocyte growth factor (HGF) is under development for treatment of renal failure. This study was designed to clarify changes in HGF pharmacokinetics in renal failure and to establish a pharmacokinetic model applicable to single and repeated doses. The plasma concentration profile in mice with glycerol-induced acute renal failure was similar to that in normal mice, indicating a minimal contribution of kidney to systemic clearance of HGF. Nevertheless, accumulation of fluorescein-4-isocyanate-labeled HGF in renal tubules in both cases suggests the occurrence of efficient endocytosis of HGF in kidney. A pharmacokinetic model including plasma and liver compartments was constructed, incorporating both high- and low-affinity receptors for association and subsequent endocytosis of HGF because HGF is eliminated via specific receptor c-Met and heparin-like substance. The model well explained the plasma concentration profiles at all doses examined after bolus injection in animals and humans, and those during infusion in rodents. It includes externalization of receptors, which is negatively regulated by HGF, and can explain the gradual increase in trough concentration during repeated dosing in monkeys. Overall pharmacokinetic profiles of HGF are governed by at least two receptors and are well described by this pharmacokinetic model, which should assist in safe management of clinical trials., (Copyright © 2012 Wiley Periodicals, Inc.)

Herbal medicines are being used with greater frequency by practitioners of natural medicine in the United States. Many categories of herbs are used, primarily angiotensin antagonists, nonspecific nephroprotective, and immunomodulating/adaptogenic herbs. The most common herbs in each category are discussed both from a historical and scientific perspective. For the first time, a case series of the use of the proposed herbal angiotensin antagonist herb indigenous to the United States, Lespedeza capitata, is reported based on the author's clinical practice.

Aims: The most effective regimen for the prevention of contrast-induced nephropathy (CIN) remains uncertain. Our purpose was to compare two regimens of sodium bicarbonate with 24 h sodium chloride 0.9% infusion in the prevention of CIN., Methods and Results: We performed a prospective, randomized trial between March 2005 and December 2009, including 258 consecutive patients with renal insufficiency undergoing intravascular contrast procedures. Patients were randomized to receive intravenous volume supplementation with either (A) sodium chloride 0.9% 1 mL/kg/h for at least 12h prior and after the procedure or (B) sodium bicarbonate (166 mEq/L) 3 mL/kg for 1 h before and 1 mL/kg/h for 6 h after the procedure or (C) sodium bicarbonate (166 mEq/L) 3 mL/kg over 20 min before the procedure plus sodium bicarbonate orally (500 mg per 10 kg). The primary endpoint was the change in estimated glomerular filtration rate (eGFR) within 48 h after contrast. Secondary endpoints included the development of CIN. The maximum change in eGFR was significantly greater in Group B compared with Group A {mean difference -3.9 [95% confidence interval (CI), -6.8 to -1] mL/min/1.73 m2, P = 0.009} and similar between groups C and B [mean difference 1.3 (95% CI, -1.7-4.3) mL/min/1.73 m(2), P = 0.39]. The incidence of CIN was significantly lower in Group A (1%) vs. Group B (9%, P = 0.02) and similar between Groups B and C (10%, P = 0.9)., Conclusion: Volume supplementation with 24 h sodium chloride 0.9% is superior to sodium bicarbonate for the prevention of CIN. A short-term regimen with sodium bicarbonate is non-inferior to a 7 h regimen. ClinicalTrials.gov Identifier: NCT00130598.

Introduction: The aim of this study was to examine the effects of oral administration of omega-3 fatty acid on kidney functional disturbances, histological damages, and oxidative stress due to reperfusion injury., Materials and Methods: Male Sprague Dawley rats received a standard diet for 2 weeks. Through gavage, the rats in acute kidney failure and omega-3 groups received 4 mL normal saline or omega-3 fatty acid (0.4 g/kg) daily. After 2 weeks, the rats underwent surgery and renal ischemia on both sides. During the last 6 hours, the rats were transferred to the metabolic cage for urine sampling. At the end of the period, blood samples were obtained from the aorta and the kidneys were removed for hematoxylin-eosin staining, histological analysis, and oxidative stress measurement. The sham group also received normal saline, but the operation was done without renal ischemia, whereas the control group did not received any substances or operation., Results: The decrease in glomerular filtration rate induced by reperfusion was relatively improved by omega-3 administration, which resulted in the decrease in plasma urea and creatinine concentrations. In addition, the relative excretion of sodium and potassium, and urine flow rate decreased in the omega-3 group as compared with the acute kidney failure group. The degrees of histologic damages and oxidative stress that had increased following reperfusion injury were also significantly lowered by omega-3 administration., Conclusions: Preventive oral administration of omega-3 supplement may decrease histological damages, oxidative stress, and kidney dysfunction following reperfusion injury.

Background: Endotoxins can cause serious organ damage and death by triggering the secretion of pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-1beta in bacterial infections., Objectives: The goal of this study was to evaluate the effects of a high dose (3000 U/kg) of erythropoietin-beta (EPO) on inflammatory cytokine levels, renal function and histological changes during the early period of Lipopolysaccharide (LPS)-induced endotoxemia using a rat model., Material and Methods: Male Sprague Dawley (350-400 g) rats were randomized into 3 groups: Control group (n = 7); LPS group (received 20 mcg/kg LPS through intraperitoneal (i.p.) injection (n = 7); LPS+EPO group (received 3000 U/kg, ip 30 minutes before LPS administration (n = 7). Four hours after the administration of LPS, kidney tissue and serum samples were collected. Kidney function parameters, TNF-alpha, IL-6, IL-1beta, C reactive protein (CRP) and complete blood counts (CBC) were measured. The severity of renal tubular injury and caspase-9 immunoreactive cells was expressed as a percentage., Results: Serum levels of urea, creatinine, TNF-alpha, IL-6 and IL-1beta were significantly increased in the LPS group (p < 0.0001 - p = 0.04) and were lower in LPS+EPO group (p < 0.0001, p = 0.01, p = 0.02, p = 01 and p < 0.0001, respectively). Pretreatment with EPO significantly increased platelet counts (p = 0.00) and decreased white blood cell counts (p = 0.02). The renal tubular injury percentage was significantly higher in the LPS group than in the control and LPS+EPO groups (p = 0.002, p = 0.003, and p = 0.005, respectively) and caspase-9 expression was lower in the LPS+EPO and control groups than in the LPS group., Conclusions: EPO might have renoprotective effects against the inflammatory process and cell apoptosis during endotoxemia.

Objective: To explore the Kidney-tonifying and abortion preventing effect of Shou Tai Wan (STW) by different extration methods on the SD Rats' abortion model., Methods: Applied hydroxycarbamide and mifepristone (RU-486) to establish the abortion model of corpus luteum inhibition due to Kidney deficiency (disease-syndorme combination model) on SD, rats. Treated the model rats with STW formula. Observed the uterus condition and recorded the embryo number and the miscarriage rate of each rat. 4 kinds of extractions including water extract of STW (A liquid), alcohol extract of STW (B liquid), after the ethanol water extract residue of STW (C liquid) and B + C liquid. Visual observed the uterine lesions embryos and calculated obortion rate. Used chemluninescence methed to cheek the serum estradiol (E2) and progesterone (P) level. Used quantitative RT-PCR (qRT-PCR) to analyze the different of the PR mRNR between the model group and the treated group., Results: Compared with the model group, the abortion rate of B + C liquid was greatly deduced and the embryo number of B + C liquid group, the E2 and P levels were obviously increased in the treated groups., Conclusion: STW (B + C) has the best effect of tonifying the kidney and preventing abortion.

In Mexican traditional medicine the orchid Prosthechea michuacana is highly valued as a food and in the treatment of various human diseases, including drug-related renal disease. Methanol, hexane, and chloroform extracts of bulbs of P. michuacana were studied in the cisplatin-induced renal injury model in rats. Results showed that treatment with cisplatin induced significant elevations in concentrations of blood urea and serum creatinine and in lipid peroxidation. Treatments with methanolic extract (200, 400 and 500 mg/kg) increased levels of biochemical markers of renal injury like reduced glutathione, glutathione S-transferase, and superoxide dismutase and inhibited the increases in blood urea and serum creatinine concentrations and lipid peroxidation induced by cisplatin. Hexane and chloroform extracts did not show any effect. The results obtained in the present study indicate that this orchid can be a potential source of natural nephroprotective activity.

Background: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine-dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and renal oxygen extraction (RO2Ex) in post-cardiac surgery patients., Methods: Twelve patients were studied during sedation and mechanical ventilation after cardiac surgery. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h. At each infusion rate, systemic haemodynamics were evaluated by a pulmonary artery catheter, and RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of 51chromium-ethylenediaminetetraacetic acid, respectively. RVO2 and RO2Ex were calculated by arterial and renal vein blood samples., Results: The mean arterial pressure was not affected by vasopressin while cardiac output and heart rate decreased. RBF decreased and GFR, filtration fraction, sodium reabsorption, RVO2, RO2Ex and renal vascular resistance increased dose-dependently with vasopressin. Vasopressin exerted direct antidiuretic and antinatriuretic effects., Conclusions: Short-term infusion of low to moderate, non-hypertensive doses of vasopressin induced a post-glomerular renal vasoconstriction with a decrease in RBF and an increase in GFR in post-cardiac surgery patients. This was accompanied by an increase in RVO2, as a consequence of the increases in the filtered tubular load of sodium. Finally, vasopressin impaired the renal oxygen demand/supply relationship.

Objectives: The purpose of this study was to test the hypothesis that local renal delivery of B-type natriuretic peptide (BNP) will overcome renal resistance to BNP without systemic hypotension., Background: BNP has vasodilating, natriuretic, and renin-inhibiting properties. In overt heart failure (HF), there is development of renal resistance to BNP., Methods: We defined the cardiorenal and humoral effects of systemic (n = 6) or local renal (n = 7) administration of canine BNP (0.01 microg/kg/min) in 2 separate groups of dogs with pacing-induced subacute overt HF complicated by renal dysfunction. We used a commercially available small (3.1-F) bifurcated renal catheter (FlowMedica Inc., Fremont, California) for direct bilateral infusion of BNP into both renal arteries., Results: With systemic BNP at this clinically used dose (without the bolus), urine flow increased, but there was only a trend for an increase in urinary sodium excretion and glomerular filtration rate (GFR). In contrast, local renal delivery of BNP resulted in significant diuresis and natriuresis and an increase in GFR. These diuretic and natriuretic responses were greater with local renal BNP compared with systemic BNP, and were associated with increased delivery of BNP to the renal tubules as evident by a greater urinary BNP excretion resulting in a decrease in distal reabsorption of sodium. Importantly, local renal BNP did not result in a significant decrease in mean arterial pressure that was observed with systemic BNP., Conclusions: We conclude that local renal BNP delivery is a novel strategy that may overcome renal assistance to BNP in overt HF by increasing local delivery of BNP to the renal tubules.

Introduction: Electromotive drug-administration (EMDA) represents a minimal-invasive method of intravesical instillation of therapeutic agents. We examined the therapeutic effect of EMDA in patients suffering from therapy-resistant idiopathic detrusor overactivity (IDO) with respect to urodynamics, micturition charts and quality of life (Kings Health Questionnaire)., Methods: Patients suffering from urge syndrome with and without urge incontinence and non-responding to oral anticholinergic drugs underwent EMDA therapy (2000 mg lidocaine-HCl 4% (50 ml), 2 mg epinephrine [1:1000] (2 ml), 40 mg dexamethason-21-dihydrogen phosphat (10 ml) in a total volume of 100 ml). Over a 27 months period, 84 patients (median age 63.1 years; 72 female, 12 male) with urge syndrome and urodynamically-proven idiopathic detrusor overactivity (IDO) were treated with EMDA. Following urodynamic measurements, quality of life (QoL) was evaluated using Kings Health Questionnaire (KHQ) and a micturition chart over 48 h, EMDA was performed once in four weeks for a period of three months. Patients continued to document drinking and micturition data during this time. Before each EMDA session urodynamic examination and KHQ were repeated., Results: All treated patients suffered from urge syndrome (25.6% OAB wet, 20.0% OAB dry and 54.4% mixed urinary incontinence). Mean daytime frequency (DF) was 14.1 +/- 7.7 per day and nocturia (N) 5.1 +/- 5.1 per night before EMDA. After two EMDA sessions, daytime frequency (DF) decreased to 9.4 +/- 6.2 per day (P < 0.0001) and 2.5 +/- 2.4 per night (P = 0.035). The use of pads could be lowered from 4.5 +/- 4.1 per 24 h to 1.8 +/- 2.4 (P < 0.0074). The first desire to void volume (FDV) assessed by urodynamics started at 94.0 +/- 60.5 ml before treatment and changed to 142.2 +/- 79.6 ml (P = 0.0064) after two sessions. Strong desire to void volume (SDV) was noticed at 155.6 +/- 84.8 ml filling of the bladder; after two EMDA sessions at 199.5 +/- 97.3 ml (P = 0.001). Uninhibited detrusor contractions (UIC) were seen in all patients before treatment and were reduced to 46.4% after two EMDA sessions (P < 0.001). Maximal cystometric bladder capacity (MCBC) increased from 192.3 +/- 106.6 ml to 239.6 +/- 114.9 ml (P = 0.018). Patient-documented bladder capacity (BC) as micturition volume increased from 186.0 +/- 108.7 ml to 234.2 +/- 134.2 ml (P = 0.043). A reduction of impact of Quality of Life (QoL) was observed from 11.8 +/- 0.4 to 7.0 +/- 0.3 (P < 0.001) during treatment. A fraction of 53.6% (45/84) of all patients reported a completely withdrawal of symptoms and 28.6% (24/84) indicated a remarkable reduction. Only 10.7% (9/84) of patients did not continue therapy after two sessions., Conclusion: EMDA significantly improves urodynamic parameters, QoL and pad usages in patients with urge syndrome and therapy-resistant IDO. Therefore we offer EMDA therapy as an alternative treatment modality to the standard approaches.

Aim: This study was designed to evaluate the cost-effectiveness of AST-120, an oral adsorbent that attenuates the progression of chronic kidney disease., Methods: We developed a Markov model with six health states, including four levels of serum creatinine, haemodialysis and death, using data from a randomized clinical trial conducted in Japan. Direct costs relevant to chronic kidney disease were calculated from a Japanese reimbursement perspective. Projected quality-adjusted life years (QALY) and costs were compared between the AST-120 and placebo groups. The target population was nondiabetic patients with serum creatinine levels from 5.0 to 8.0 mg/dL (442-707 micromol/L) at baseline. Probabilistic sensitivity analysis was performed to evaluate the stability of the results., Results: At 3 years, mean total costs per patient were estimated at 6.67 million yen (US$56,982) in the AST-120 group and 9.38 million yen (US$80,196) in the placebo group. Mean total costs were 2.72 million yen (US$23,205) lower among patients receiving AST-120. QALY per patient were 0.295 (approximately 3.5 months) greater for patients receiving AST-120 than for those receiving placebo over 3 years. The finding that treatment with AST-120 dominated placebo (i.e. was less costly and resulted in more QALY) was upheld in sensitivity analyses., Conclusion: The use of AST-120 in patients with advanced chronic kidney disease may help to slow the rate of growth in expenditures for kidney disease.

Background: Laboratory research and previous retrospective study suggest that vitamin D and its analogues have profound effects on immune system function and glomerular mesangial cell proliferation. We conducted an open-label study to evaluate the antiproteinuric effect of calcitriol on proteinuria in patients with immunoglobulin A (IgA) nephropathy., Study Design: Open-label prospective uncontrolled trial., Setting & Participants: 10 patients (3 men) with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy in a tertiary referral center., Intervention: Calcitriol, 0.5 microg, twice weekly for 12 weeks., Outcome Measures: Changes in proteinuria, renal function, serum transforming growth factor beta (TGF-beta) and angiotensin II levels., Results: After calcitriol treatment, there was a significant overall decrease in proteinuria with time by using a general linear model with repeated measures (P = 0.03). There was a progressive decrease in urine protein-creatinine ratio from 1.98 +/- 0.74 to 1.48 +/- 0.81 g/g (P = 0.007) during the first 6 weeks that persisted throughout the study period. No significant change in blood pressure or renal function was noted. There was a simultaneous decrease in serum TGF-beta level, and percentage of decrease in serum TGF-beta level significantly correlated with percentage of change in proteinuria (Spearman r = 0.643; P = 0.02). Serum angiotensin II level did not change throughout the study. One patient experienced transient hypercalcemia that normalized after a dosage decrease. No other major adverse effect was reported., Limitations: This small study is uncontrolled and does not examine the long-term effect of calcitriol therapy., Conclusion: Twice-weekly oral calcitriol has a modest antiproteinuric effect in patients with IgA nephropathy and persistent proteinuria despite angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy. Additional studies are needed to confirm the renal protecting effect of calcitriol in patients with chronic proteinuric kidney diseases.

Five cases of central diabetes insipidus (CDI) in domestic shorthair cats are described. All cats were under 3 years of age at the onset of clinical signs, and outdoor or outdoor/indoor cats, in which a prior trauma was either present or possible. The history included polydipsia and polyuria, and physical examination abnormalities included urinary bladder distention and dehydration. All cats had hyposthenuria with a urine specific gravity between 1.003 and 1.006. The diagnosis was confirmed by an observed inability to concentrate urine during a water deprivation test or compatible serum osmolality, followed by an increase in urine concentration after desmopressin administration. All cats in this report were treated successfully with oral desmopressin. The dose (25-50 microg q8-12h) and the response to therapy were variable. Oral desmopressin administration may serve as an effective alternative route for cat owners who find the conjunctival or nasal application of the solution an inconvenient mode of therapy.

Activation of P2Y2 receptor (P2Y2-R) in inner medullary collecting duct (IMCD) of rat decreases AVP-induced water flow and releases PGE(2). We observed that dehydration of rats decreases the expression of P2Y2 receptor in inner medulla (IM) and P2Y2-R-mediated PGE(2) release by IMCD. Because circulating vasopressin (AVP) levels are increased in dehydrated condition, we examined whether chronic infusion of desmopressin (dDAVP) has a similar effect on the expression and activity of P2Y2-R. Groups of rats were infused with saline or dDAVP (5 or 20 ng/h sc, 5 or 6 days) via osmotic minipumps and euthanized. Urine volume, osmolality, and PGE(2) metabolite content were determined. AQP2- and P2Y2- and V2-R mRNA and/or protein in IM were quantified by real-time RT-PCR and immunoblotting, respectively. P2Y2-R-mediated PGE(2) release by freshly prepared IMCD was assayed using ATPgammaS as a ligand. Chronic dDAVP infusion resulted in low-output of concentrated urine and significantly increased the AQP2 protein abundance in IM. On the contrary, dDAVP infusion at 5 or 20 ng/h significantly decreased P2Y2-R protein abundance (approximately 40% of saline-treated group). In parallel, the relative expression of P2Y2-R vs. AQP2- or V2-R mRNA was significantly decreased. Furthermore, the P2Y2-R-mediated PGE(2) release by IMCD was significantly decreased in rats infused 20 ng/h but not 5 ng/h of dDAVP. Urinary PGE(2) metabolite excretion, however, did not change with dDAVP infusion. In conclusion, chronic dDAVP infusion decreases the expression and activity of P2Y2-R in IM. This may be due to a direct effect of dDAVP or dDAVP-induced increase in medullary tonicity.

Our experiences of managing nocturnal enuresis in Greek children at our Outpatient Clinics of Pediatric Urology are described. Between March 2001 and October 2003, 142 children with primary nocturnal enuresis (93 boys and 49 girls), aged 7-18 years old (mean: 9.0+/-0.5) were included in this prospective study. Initially, behavioral conditioning therapy, using a body-worn urinary alarm, was instructed in all cases. If no improvement was recorded, 40 microg of intranasal desmopressin was administered, initially for three months. If urodynamic studies demonstrated pure detrusor instability, anticholinergics (5 mg oxybutinine or 2 mg tolterodine) were given instead. Combination medication (desmopressin and anticholinergics) was administered for coexisting diurnal enuresis, which was present in 8 children. Among the 142 children the overall response rate was 51.41%. Successful response was recorded in 16 children practicing conditioning behavioral therapy, in 47 receiving desmopressin (with or without anticholinergics), and in 10 children receiving only anticholinergics. During the follow-up period (mean: 6.2 months), no serious side effect was recorded. The use of desmopressin, and anticholinergics in specific subgroups, was found to be effective and safe for the management of nocturnal enuresis in children.

Acute renal failure (ARF) is common in the critically ill and is associated with a high mortality rate. Its pathogenesis is not understood. Because animal models use ischemia to induce experimental ARF, there is the widespread belief that lack of blood flow is responsible for ARF. Low-dose dopamine (LDD) has been shown to increase renal blood flow in animal and in human volunteers. Thus, it has been administered to humans for almost 3 decades in the belief that it would lead to renal arterial vasodilation and increase renal blood flow (RBF). However, the etiology of ARF in critical illness is likely multifactorial, and the contribution of hypovolemia and reduced renal perfusion is unknown. Furthermore, interindividual variation in the pharmacokinetics of dopamine typically results in poor correlation between blood levels and administered dose, making accurate and reliable delivery of LDD difficult. Finally, dopamine is a proximal tubular diuretic that increases Na(+) delivery to tubular cells, thus increasing their oxygen demands. Accordingly, even if LDD were able to preferentially increase RBF, there is no guarantee that it would restore renal parenchymal oxygen homeostasis. More important, 2 meta-analyses and a large double-blind, prospective, multiple-center, randomized controlled trial have failed to demonstrate that dopamine protects the kidney in critically ill patients with ARF. Currently, there is insufficient evidence to support the use of renal-dose dopamine in the intensive care unit.

Objective: Nocturia is a common reason for interrupted sleep in post-stroke patients. These patients often have neurogenic bladder overactivity. However, little is known about the possible contribution of nocturnal polyuria in the patients., Methods: We measured the number of nocturia, the circadian plasma arginine vasopressin (AVP) level and urinary excretion in 4 patients with stroke., Results: All patients had nocturnal urinary frequency (three times in one and twice in 3). All patients were revealed to have nocturnal polyuria, and the ratio of nocturnal urinary output to 24 hour volume ranged from 36% to 63%. Measurement of daily plasma AVP variation showed that all patients lost normal nocturnal rise of the plasma AVP concentration. Two patients were successfully treated with 5 mug of intranasal desmopressin once a night, a potent analogue of AVP, without hypertension particularly in the night, signs of congestive cardiac failure or any electrolyte abnormality such as hyponatremia., Conclusion: Our post-stroke patients had nocturnal polyuria with abnormal circadian rhythm of plasma AVP secretion. Desmopressin reduced nocturnal waking in urination. It also ameliorated nocturnal dehydration that might trigger a stroke recurrence in the patients.

Objective: To investigate the pharmacokinetic profile of oral desmopressin in elderly patients with nocturia, and to analyse any possible correlation between the absorption and clinical effect., Patients and Methods: In all, 32 patients were screened to determine the baseline number of nocturnal voids and the nocturia index; of these, 24 fulfilled the inclusion criteria and were enrolled for a pharmacokinetic evaluation of oral desmopressin 400 microg. A double-blind, randomized, placebo-controlled, crossover-effect evaluation period was then used to test the association between the absorption of desmopressin and pharmacodynamic effect. Serial plasma samples were collected for 8 h for a pharmacokinetic analysis of desmopressin. The pharmacodynamics after an equivalent oral dose before bedtime were assessed by measuring changes in the number of nocturnal voids, time to first nocturnal void and nocturnal diuresis, from placebo to active treatment., Results: There was a linear relationship between plasma desmopressin at 2 h after dosing and the area under the plasma concentration curve from 0 to infinity (Pearson's rho 0.923, P < 0.001). Women had a significantly higher plasma desmopressin concentration than men (P = 0.0012) and more adverse events. There was no correlation between plasma desmopressin at 2 h after dosing and the within-patient response in any of the effect variables. Generally, the number of nocturnal voids and nocturnal diuresis were half that with placebo. The time to the first nocturnal void was almost doubled compared with placebo., Conclusions: There seems to be a relationship between gender, plasma level of desmopressin and the incidence of adverse events. Plasma desmopressin at 2 h after dosing cannot be used to predict the pharmacodynamic response, although desmopressin lowers the nocturnal diuresis and the number of nocturnal voids.

Purpose: Obesity is a common consequence in patients with tumors of the hypothalamic region and of related treatment in children. Much less information is available on adult patients and long-term survivors. The aims of this study were to estimate the prevalence of obesity in adult patients with acquired structural hypothalamic damage and to define the characteristics of patients at greatest risk of obesity., Methods: A retrospective study was conducted of 52 patients (25 women; median age at diagnosis, 44 years; range, 17 to 78 years) with tumors involving the hypothalamic region. These included 22 craniopharyngiomas, 24 pituitary adenomas, and six other hypothalamic tumors. Changes in body mass index were determined, magnetic resonance imaging scans were scored by a radiologist for tumor size and the extent of involvement of the hypothalamus, and current hormone replacement therapy was recorded, to identify possible features associated with new or worsened obesity (defined as a body mass index > or =30 kg/m(2) at the latest follow-up, which had increased by at least 2 kg/m(2) since diagnosis of the tumor)., Results: Serial body mass index data from diagnosis to the latest follow-up were available for 42 patients. After a median of 5 years (range, 1 to 19 years) of follow-up, most patients with hypothalamic damage were obese (52% [n = 22] vs. 24% [n = 10] at the time of diagnosis, P < 0.0001). In a multivariate model, use of desmopressin (odds ratio [OR] = 13; 95% confidence interval [CI]: 2.0 to 86; P = 0.007) and growth hormone replacement (OR = 7.6; 95% CI: 1.1 to 51; P = 0.04) were associated with new or worsened obesity during follow-up. No correlation was found between the initial size or location of the tumor and subsequent weight gain., Conclusion: Obesity is highly prevalent in adult survivors of hypothalamic tumors. Use of desmopressin and growth hormone therapy, but not size or location of the tumor, were associated with weight gain and obesity following diagnosis. These findings may be helpful in identifying patients at increased risk of obesity, to whom earlier intervention could be offered.

Patients with renal colic are usually treated in emergency care units or by their family doctors and require immediate diagnosis and treatment. The life-time risk is up to 10 %. The prevalence amounts to 4.7 % in Germany. In addition to confirming the diagnosis and inducing an adequate pain therapy it's very important for patients to be directed correctly and, above all, prevention is important, too. Without treatment the recurrence rate ranges between 50 and 100 %. Particularly, these principals should give useful advice, wherever patients are treated without urological department.

This study was designed to determine the effectiveness of desmopressin in the treatment of adolescent nocturnal enuresis and factors that may predict responsiveness. Eighteen adolescents (14 boys, 4 girls) with monosymptomatic nocturnal enuresis were treated with oral desmopressin for three months, starting with 0.2 mg at night and controlling the symptoms every two weeks. After this period, desmopressin was used every other day and the dose was reduced gradually. The treatment was completed at the end of six months. As factors that may predict response before treatment, a range of variables (family history of enuresis, educational levels of parents, number of children, first child in family, birth weight) and urine osmolality was evaluated. Disappearance of bedwetting by using desmopressin has been observed in adolescents who have a high urine osmolality. We did not observe any relapse during reducing desmopressin dose gradually, but on complete cessation of the treatment, relapses were seen. Six months after the end of the therapy, we could not find any patient who recovered completely. Desmopressin seems to be effective in the treatment of primary nocturnal enuresis while on therapy but during the long-term follow-up, all cases relapsed.

Major vascular surgery patients are at great risk of renal failure. Several pharmacological and non pharmacological strategies have been developed to prevent renal failure in those patients. Renal doses of dopamine were used, based on its beneficial effects on renal function, in animals and healthy individuals. However, major vascular surgery patients are often critically ill, with diverse pathophysiological conditions and they cannot be easily compared to healthy individuals. There are, nowadays, enough scientific evidence demonstrating that renal doses of dopamine do not play a significant protective role of renal function in these critically ill patients.

Objective: To evaluate the influence of renal impairment on the pharmacokinetics of desmopressin., Methods: Twenty-four subjects were enrolled in the study, 18 with varying degrees of renal impairment and six healthy volunteers. Each subject received a single intravenous dose of 2 microg desmopressin. Blood and urine samples were collected for 24 h and assayed for desmopressin by radioimmunoassay. Plasma concentrations and the amounts of desmopressin excreted in the urine were analysed simultaneously by use of mixed effects modelling., Results: Only mild adverse events were observed. Both the renal and the nonrenal clearance of desmopressin were found to vary with the creatinine clearance (CrCL). A decrease of 1.67% in the CrCL (corresponding to 1 ml min(-1) from 60 ml min(-1)) was found to cause a 1.74% decrease in the renal clearance and a 0.93% decrease in the nonrenal clearance. The fall in renal clearance caused the amount of desmopressin excreted in urine to decrease from 47% in healthy subjects to 21% in the patients with severe renal impairment. The mean systemic clearance of desmopressin was 10 litres h(-1) in healthy subjects and 2.9 litres h(-1) in patients with severe renal impairment (difference -7.5 litres h(-1), 95% CI [-11; -4.3] litres h(-1)). Correspondingly, the mean terminal half-life, was 3.7 h in healthy subjects and 10 h in patients with severe renal impairment (difference 6.7 h, 95% CI [4.0; 9.4] h)., Conclusion: Although desmopressin appears to be safe and well-tolerated by patients with impaired renal function, great caution should be exercised when titrating towards an efficient dosage regimen if patients with moderately or severely impaired renal function are to be treated with desmopressin at all., (Copyright 2004 Blackwell Publishing Ltd)

Objective: To investigate (1) the pharmacokinetic and pharmacodynamic profiles of desmopressin in men from an age group with a high incidence of nocturia; and (2) circadian variation in the pharmacokinetic parameters., Methods: The study had an open, randomised, four-way cross-over design. Desmopressin was administered orally (0.2 mg) and intravenously (2 microg), daytime and night-time, yielding four in-hospital sessions, separated by at least 2 days. Blood samples were taken before and at predetermined time points up to 12 h after dosing. Pharmacokinetic parameters were derived using a two-compartmental model except for AUC(0-->t), which was derived using non-compartmental analysis. Bioavailability was estimated using AUC(0-->t) for the oral and the intravenous periods. Urine, for measurements of volume and osmolality, was collected in predetermined intervals before and until 12 h after dosing., Results: Fifteen healthy men aged 55-70 years were included in the analysis. The concentration-time curve after 2 microg intravenous desmopressin was best described using a biexponential term. The mean (95% CI) AUC at night was 302 (272-335) pg x h/ml and in the day was 281 (253-312) pg x h/ml. No statistically significant differences were detected between night and day except for terminal half-life, which was 3.1 h at night and 2.8 h in the daytime (P=0.02). After oral desmopressin, concentrations above the limit of quantification (2.5 pg/ml) were only detected in 51% of the samples. Peak plasma concentration (Cmax) was 6.2 (5.1-7.5) pg/ml at night and 6.6 (5.5-7.9) pg/ml in the daytime. Median time to reach Cmax (tmax) was 1.5 (range 1.0-4.1) h at night and 1.5 (range 0.5-3.0) h in the day. The bioavailability was 0.08%. The pharmacodynamic effects of oral and intravenous desmopressin given in the daytime were similar during the first 6 h after dosing. The night-time dosing and daytime intravenous dose resulted in antidiuresis throughout the measuring period, while the effect of the daytime peroral dose receded after 6 h., Conclusion: The pharmacokinetic profile of desmopressin is biexponential. Terminal half-life was longer at night than in the daytime, but the difference is considered too small to be of clinical importance. The plasma levels given by the intravenous dose resulted in a duration of action of 12 h or more. Despite low bioavailability, the pharmacodynamic effects of oral desmopressin were similar in magnitude to those after intravenous dose at night and during the first 6 h after daytime administration.

Purpose: In a prospective study we evaluate the efficacy of intermittent desmopressin (DDAVP) every other day for patients with nocturnal enuresis relapse who need additional therapy., Materials and Methods: Between January 2000 and August 2001, 71 boys and 52 girls 6 to 22 years old (mean age 12.5) were treated with 0.2 mg DDAVP daily for monosymptomatic nocturnal enuresis. After an initial 2 weeks of dose titration the nonresponders were given 0.4 mg DDAVP daily. Those who did not respond to this dose were excluded from study. The remaining patients took desmopressin for 3 months. Patients with persistent enuresis after 3 months of treatment were given intermittent 0.2 or 0.4 mg DDAVP every other day. Followup was performed 6 weeks later., Results: Of 123 patients 92 completed the study. Mean followup after beginning intermittent DDAVP therapy was 9.2 months (range 6 to 18). Of the 92 patients 45 responded to the 0.2 mg daily dose (group 1) and continued treatment for at least 3 months, while the dose was titrated to 0.4 mg for the remaining 47 (group 2). There were 23 patients who did not respond to 0.4 mg DDAVP and they were excluded from the study. After cessation of the drug 21 group 1 patients (46.6%) and 13 group 2 patients (54%) still had enuresis, and they were placed on intermittent therapy. After 6 weeks 15 of these 34 patients had complete and 13 of the remaining 19 had partial response, while the 6 nonresponders continued on daily DDAVP. Overall the complete and partial response rate of intermittent treatment was 20 of 21 group 1 patients (95%) and 8 of 13 group 2 (61.5%)., Conclusions: For some enuretic patients with relapse after cessation of initial 3-month therapy, intermittent DDAVP may be an effective alternative long-term treatment.