Evidence that renal arginine transport is impaired in spontaneously hypertensive rats

Low renal nitric oxide (NO) bioavailability contributes to the development and maintenance of chronic hypertension. We investigated whether impaired L-arginine transport contributes to low renal NO bioavailability in hypertension. Responses of renal medullary perfusion and NO concentration to renal arterial infusions of the L-arginine transport inhibitor L-lysine (10 μmol·kg⁻¹·min⁻¹; 30 min) and subsequent superimposition of L-arginine (100 μmol·kg⁻¹·min⁻¹; 30 min), the NO synthase inhibitor N^G-nitro-L-arginine (2.4 mg/kg; iv bolus), and the NO donor sodium nitroprusside (0.24 μg·kg⁻¹·min⁻¹) were examined in Sprague-Dawley rats (SD) and spontaneously hypertensive rats (SHR). Renal medullary perfusion and NO concentration were measured by laser-Doppler flowmetry and polarographically, respectively, 5.5 mm below the kidney surface. Renal medullary NO concentration was less in SHR (53 ± 3 nM) compared with SD rats (108 ± 12 nM; P = 0.004). L-Lysine tended to reduce medullary perfusion (−15 ± 7%; P = 0.07) and reduced medullary NO concentration (−9 ± 3%; P = 0.03) while subsequent superimposition of L-arginine reversed these effects of L-lysine in SD rats. In SHR, L-lysine and subsequent superimposition of L-arginine did not significantly alter medullary perfusion or NO concentration. Collectively, these data suggest that renal L-arginine transport is impaired in SHR. Renal L-[³H]arginine transport was less in SHR compared with SD rats (P = 0.01). Accordingly, we conclude that impaired arginine transport contributes to low renal NO bioavailability observed in the SHR kidney.

Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet

Hypertension and elevated sympathetic drive result from consumption of a high-calorie diet and deposition of abdominal fat, but the etiology and temporal characteristics are unknown. Rabbits instrumented for telemetric recording of arterial pressure and renal sympathetic nerve activity (RSNA) were fed a high-fat diet for 3 weeks then control diet for 1 week or control diet for 4 weeks. Baroreflexes and responses to air-jet stress and hypoxia were determined weekly. After 1 week of high-fat diet, caloric intake increased by 62%, accompanied by elevated body weight, blood glucose, plasma insulin, and leptin (8%, 14%, 134%, and 252%, respectively). Mean arterial pressure, heart rate, and RSNA also increased after 1 week (6%, 11%, and 57%, respectively). Whereas mean arterial pressure and body weight continued to rise over 3 weeks of high-fat diet, heart rate and RSNA did not change further. The RSNA baroreflex was attenuated from the first week of the diet. Excitatory responses to air-jet stress diminished over 3 weeks of high-fat diet, but responses to hypoxia were invariant. Resumption of a normal diet returned glucose, insulin, leptin, and heart rate to control levels, but body weight, mean arterial pressure, and RSNA remained elevated. In conclusion, elevated sympathetic drive and impaired baroreflex function, which occur within 1 week of consumption of a high-fat, high-calorie diet, appear integral to the rapid development of obesity-related hypertension. Increased plasma leptin and insulin may contribute to the initiation of hypertension but are not required for maintenance of mean arterial pressure, which likely lies in alterations in the response of neurons in the hypothalamus.

Reduced preprandial dipping accounts for rapid elevation of blood pressure and renal sympathetic nerve activity in rabbits fed a high-fat diet

Consumption of a high-fat diet (HFD) by rabbits results in increased blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) within 1 wk. Here, we determined how early this activation occurred and whether it was related to changes in cardiovascular and neural 24-h rhythms. Rabbits were meal-fed a HFD for 3 wks, then a normal-fat diet (NFD) for 1 wk. BP, HR, and RSNA were measured daily in the home cage via implanted telemeters. Baseline BP, HR, and RSNA over 24 h were 71 ± 1 mm Hg, 205 ± 4 beats/min and 7 ± 1 normalized units (nu). The 24-h pattern was entrained to the feeding cycle and values increased from preprandial minimum to postprandial maximum by 4 ± 1 mm Hg, 51 ± 6 beats/min, and 1.6 ± .6 nu each day. Feeding of a HFD markedly diminished the preprandial dip after 2 d (79–125% of control; p < 0.05) and this reduction lasted for 3 wks of HFD. Twenty-four-hour BP, HR, and RSNA concurrently increased by 2%, 18%, and 22%, respectively. Loss of preprandial dipping accounted for all of the BP increase and 50% of the RSNA increase over 3 wks and the 24-h rhythm became entrained to the light-dark cycle. Resumption of a NFD did not alter the BP preprandial dip. Thus, elevated BP induced by a HFD and mediated by increased sympathetic nerve activity results from a reduction in preprandial dipping, from the first day. Increased calories, glucose, insulin, and leptin may account for early changes, whereas long-term loss of dipping may be related to increased sensitivity of sympathetic pathways.

Improving renal patient care without compromising safety: interactive simulated e-learning

The nephrology educators network [NEN] recognised in 2007 that inequities existed in the access and delivery of evidence based renal education programs particularly to nurses in regional and remote areas. To address this, a web-based approach to learning, through the development of peer reviewed, interactive nephrology e-learning programs was adopted. These programs aligned with the tenets of e-learning instructional design and afforded more effective and consistent clinical support and induction for nurses in the renal specialty. The e-learning programs promote a standardised evidence-based approach to nephrology education and were developed by content experts from across Australia and New Zealand. The design methodology avoided the duplication of resources while also encouraging knowledge transfer between participating health organisations.

This paper will discuss the development and successful implementation of these e-learning programs across renal healthcare units in Australasia. Implemented packages include: Introduction to Buttonhole Cannulation – featuring an interactive ultrasound and cannulation application; Introduction to Haemodialysis; Introduction to Peritoneal Dialysis [PD], featuring simulated PD machines, allowing for the teaching of troubleshooting without compromising patient safety. E-learning programs are further supported through interactive case scenarios that present unfolding real world simulations and enable learners to meet different patients and manage their care while learning about key messages relating to renal health. Modules currently in development include; Acute Kidney Injury; Fluid Assessment, Water Quality and Vascular Access. The implementation of these programs assist the facilitation of positive change in teaching and learning practices in nephrology nursing aimed at improving patient outcomes.

The development of a medication calculation competency and quality use of renal medicine e-learning program.

Medication calculation and administration are commonly performed nursing tasks. A consequence of this frequency is thepotential for a higher incidence of medication-related errors. One strategy to assess proficiency in medication calculation is an annual medication calculation competency quiz. Traditionally, these quizzes are done in paper form at an institutional level and require educators or managers to administer and mark the quiz manually by hand. This paper discusses the rationale, challenges and peer-review process associated with the development of an e-learning programme designed to assess proficiency in medication calculation and the quality use of renal medicines.

Renal access coordinators' impact on hemodialysis patient outcomes and associated service delivery: a systematic review

Background
Renal access coordinators contribute specifically to dialysis access care for people with chronic and end stage renal disease. Since the introduction of renal access coordinators into Australia in the early 2000s, there have been anecdotal examples of associated improvements in patient outcomes and service delivery; however scant published quantitative evidence exists. Thus, the impact of the implementation of renal access coordinators has not undergone a rigorous review to date.

Objective
The objective of this systematic review was to critically appraise and synthesize the best available evidence related to the impact of renal access coordinators on dialysis patient outcomes and associated service delivery.

INCLUSION CRITERIA

Types of participants
This review considered studies that included renal access coordinators (noting variations of the titles) and adult hemodialysis patients (aged 18 years and over).

Types of intervention(s)
This review considered studies that evaluated the effectiveness of the renal access coordinator. This role typically consists of clinical and administration duties such as providing pre dialysis access coordination, access surveillance patient education and nurse education.

Types of studies
The types of studies considered within this review included experimental and epidemiological study designs. Thus randomized controlled trials (RCT), non-randomized controlled trials, and quasi-experimental, before and after studies, prospective and retrospective cohort studies were considered as were case control studies, analytical cross sectional studies and descriptive cross sectional studies.

Types of outcomes
Patient outcomes considered included: days to first vascular access complication (such as stenosis or thrombosis) and/or primary intervention (such as angioplasty or surgical intervention); percentage of central line insertions (negative); rate of arteriovenous fistula (AVF)/arteriovenous graft (AVG)/central venous catheter (CVC) at start of dialysis (incidence); prevalent rate of AVF/AVG/CVC; time to occlusion of AVF and time from referral to surgery. Service outcomes included: knowledge/up skilling of renal nurses; cannulation skills, ultrasound skills, knowledge of anatomy and physiology and other access related knowledge.

Search strategy
The search strategy aimed to locate published and unpublished studies, utilizing a three-step searching approach. Studies published in English from 1990 to October 2013 were considered for inclusion in this review.

Methodological quality
The studies were assessed by two independent reviewers using the appropriate standardized critical appraisal instruments from the Joanna Briggs Institute.

Data collection
Data were extracted from papers included in the review using the standardised data extraction tool from the Joanna Briggs Institute, namely JBI Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI).

Data synthesis
This review aimed to conduct meta-analyses of the findings: however, because of the limitations of the data found, this was not possible and so the findings are presented in a narrative format.

Results
Five studies were identified for inclusion in the review. No RCTs were found, therefore four of the five studies were pre-post intervention cohort studies and one was a prospective quality assurance report. Data were heterogeneous and thus did not allow for meta-analysis. All studies included multidisciplinary teams with variable emphasis on the renal access coordinator role. The pre post intervention cohort studies measured incident and/or prevalent AVF, AVG and CVC rates in the hemodialysis population and the quality assurance report measured the difference in patency rates between AVF and AVG. All discussed the role of central coordination as a contributor to the success of vascular access care.

Conclusions
This review found insufficient data to make firm conclusions about the impact that renal access coordinators have on patient outcomes. The results of this review suggest an association between renal access coordinators and improved patient outcomes. These improved patient outcomes were apparent in an increase in incident and prevalent AVFs, and a decrease in the incidence and prevalence of CVCs. Both associations are correlated with a reduction in infection rates, length of hospital stay and healthcare costs.

Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits

The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (P<0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher (P<0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin (r=0.87; P<0.01). Intracerebroventricular leptin administration (5 to 100 μg) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: −54%, paraventricular: −69%, and dorsomedial hypothalamus: −65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked “selective leptin resistance” in these animals.

Altered responsiveness of the kidney to activation of the renal nerves in fat-fed rabbits

We tested whether mild adiposity alters responsiveness of the kidney to activation of the renal sympathetic nerves. After rabbits were fed a high-fat or control diet for 9 wk, responses to reflex activation of renal sympathetic nerve activity (RSNA) with hypoxia and electrical stimulation of the renal nerves (RNS) were examined under pentobarbital anesthesia. Fat pad mass and body weight were, respectively, 74% and 6% greater in fat-fed rabbits than controls. RNS produced frequency-dependent reductions in renal blood flow, cortical and medullary perfusion, glomerular filtration rate, urine flow, and sodium excretion and increased renal plasma renin activity (PRA) overflow. Responses of sodium excretion and medullary perfusion were significantly enhanced by fat feeding. For example, 1 Hz RNS reduced sodium excretion by 79 ± 4% in fat-fed rabbits and 46 ± 13% in controls. RNS (2 Hz) reduced medullary perfusion by 38 ± 11% in fat-fed rabbits and 9 ± 4% in controls. Hypoxia doubled RSNA, increased renal PRA overflow and medullary perfusion, and reduced urine flow and sodium excretion, without significantly altering mean arterial pressure (MAP) or cortical perfusion. These effects were indistinguishable in fat-fed and control rabbits. Neither MAP nor PRA were significantly greater in conscious fat-fed than control rabbits. These observations suggest that mild excess adiposity can augment the antinatriuretic response to renal nerve activation by RNS, possibly through altered neural control of medullary perfusion. Thus, sodium retention in obesity might be driven not only by increased RSNA, but also by increased responsiveness of the kidney to RSNA.

Do renal access coordinators make a difference? What is the evidence?

Background
Since the introduction of the renal access coordinator (RAC) role into Australia there have been only anecdotal examples of associated improvements in patient outcome and service delivery and scant published quantitative extant evidence exists.

Aim
To review the literature related to the impact of RACs on dialysis patient outcomes and associated service delivery, gauge the level of evidence available and identify gaps in the literature.

Method
A three stage Joanna Briggs Institute (JBI) systematic review process was used to collect and synthesise data. The review considered studies that explored and measured the RAC role in the adult haemodialysis context. All quantitative study designs were considered. Due to lack of homogeneity a narrative synthesis was undertaken.

Results
Five studies met the inclusion criteria for the review. All studies included multidisciplinary teams with variable emphasis on the RAC role. Four pre post intervention cohort studies measured incident and/or prevalent AVF, AVG and CVC rates in the haemodialysis population and the quality assurance report measured differences in patency rates between AVF and AVG and associated hospital length of stay. All discussed the role of central coordination as a contributor to the success of vascular access care.

Conclusion
The available reports do suggest an association between RACs and improved patient outcomes. These improved patient outcomes were apparent in an increase in incident and prevalent AVFs, and a decrease in the incidence and prevalence of CVCs. Both associations are correlated with a reduction in infection rates, length of hospital stay and healthcare costs
 

Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice

Recent evidence obtained from a rodent model of birth asphyxia shows that supplementation of the maternal diet with creatine during pregnancy protects the neonate from multi-organ damage. However, the effect of increasing creatine intake on creatine homeostasis and biosynthesis in females, particularly during pregnancy, is unknown. This study assessed the impact of creatine supplementation on creatine homeostasis, body composition, capacity for de novo creatine synthesis and renal excretory function in non-pregnant and pregnant spiny mice. Mid-gestation pregnant and virgin spiny mice were fed normal chow or chow supplemented with 5 % w/w creatine for 18 days. Weight gain, urinary creatine and electrolyte excretion were assessed during supplementation. At post mortem, body composition was assessed by Dual-energy X-ray absorptiometry, or tissues were collected to assess creatine content and mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) and the creatine transporter (CrT1). Protein expression of AGAT and GAMT was also assessed by Western blot. Key findings of this study include no changes in body weight or composition with creatine supplementation; increased urinary creatine excretion in supplemented spiny mice, with increased sodium (P < 0.001) and chloride (P < 0.05) excretion in pregnant dams after 3 days of supplementation; lowered renal AGAT mRNA (P < 0.001) and protein (P < 0.001) expressions, and lowered CrT1 mRNA expression in the kidney (P < 0.01) and brain (P < 0.001). Creatine supplementation had minimal impact on creatine homeostasis in either non-pregnant or pregnant spiny mice. Increasing maternal dietary creatine consumption could be a useful treatment for birth asphyxia.