The role played by angiotensin (1-7) in the regulation of renal haemodynamics and excretory function in anesthetized rats

Initial studies have demonstrated that intra- renal infusion of Ang (1-7) caused a diuresis and natriuresis that was proportional to the degree of activation of the Renin Angiotensin Aldosterone System (RAAS). This raised the question as why the magnitude of this diuresis and natriuresis was compromised in rats receiving a high sodium diet (suppressed RAAS) and enhanced in low sodium fed rats (activated RAAS)? Could the answer lie with changes in intra-renal AT1 or Mas receptor expression? Interestingly, the observed Ang (1-7) induced increases in sodium and water excretion in rats receiving either a low or normal sodium diet were and blocked in the presence of the AT 1 receptor antagonist (Losartan) in the presence of the, 'Mas' receptor antagonist (A-779). These data suggest that both AT1 and 'Mas' receptors need to be functional in order to fully mediate the renal responses to intra-renal Ang (1-7) infusion. Importantly, further experimentation also revealed that there is a proportional relationship between AT 1 receptor expression in the rat renal cortex and the magnitude of the excretory actions of intra renal Ang (1-7) infusion, which is only partially dependent on the level of 'Mas' receptor expression. These observations suggest that although Ang (1-7) induced increases in sodium and water excretion are mediated by the Mas receptor, the magnitude of these excretory responses appear to be dependent upon the level of AT 1 receptor expression and more specifically Ang II/ AT 1 receptor signalling. Thus in rats receiving a low sodium diet, Ang (1-7) acts via the Mas receptor to inhibit Ang II/ AT 1 receptor signalling. In rats receiving a high sodium diet the down regulated AT 1 receptor expression implies a reduction in Ang II/ AT 1 receptor signalling which renders the counter-regulatory effects of intra-renal Ang (1-7) infusion redundant.

Evolution of immunoglobulin and mannose binding protein levels after renal transplantation: association with infectious complications.

Hypogammaglobulinemia (hypo-Ig) and low mannose binding protein (MBP) levels might be involved in the infectious risk in renal transplantation. In 152 kidney transplant recipients treated with calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF), during the first year, we prospectively recorded the incidence of hypogammaglobulinemia, and low MBP levels. Their influence on infectious complications was evaluated in 92 patients at 3 and 12 months (T3 and T12). The proportion of deficiency increased significantly: hypo-IgG: 6% (T0), 45% (T3), and 30% (T12) (P < 0.001); hypo-MBP: 5%, 11%, and 12% (P = 0.035). Hypo-IgG at T3 was not associated with an increased incidence of first-year infections. A significantly higher proportion of patients with combined hypogammaglobulinemia [IgG+ (IgA and/or IgM)] at T3 and with isolated hypo-IgG at T0 developed infections until T3 compared with patients free of these deficits (P < 0.05). Low MBP levels at T3 were associated with more sepsis and viral infections. Hypogammaglobulinemia is frequent during the first year after renal transplantation in patients treated with a CNI and MMF. Hypo-IgG at T0 and combined Igs deficts at T3 were associated with more infections. MBP deficiency might emerge as an important determinant of the post-transplant infectious risk.

Large decrease of anti-tetanus anatoxin and anti-pneumococcal antibodies at one year after renal transplantation

info:eu-repo/semantics/published

Large decrease of anti-tetanus anatoxin and anti-pneumococcal antibodies at one year after renal transplantation.

Aims: In kidney transplant recipients (KTR), antibody (Ab) synthesis is hampered by AZA and CsA. We here report in a prospective cohort study, the effects of mycophenolate mofetil (MMF) associated to a calcineurin inhibitor on plasma levels of anti-tetanus anatoxin Ab (TAnAb) and anti-pneumococcal Ab (PnPsAb). Methods: Serum titers of the TAnAb and the PnPsAb against serotypes 14, 19F and 23F were measured in 94 KTR on Day 0 (T0) and 1 year (T12) after renal transplantation and in 49 healthy controls. Results: 1) At T0, TAnAb were detected in only 71% of patients vs. 98% of controls (p < 0.0001) and the titers were significantly lower in KTR (1.46 UI/ml vs. 2.74 in controls, p = 0.01); they further decreased between T0 and T12 (1.46 UI/ml to 0.31, p < 0.0001). The calculated half-life (t1/2) of TAnAb was 7.7 months, as compared to more than 10 years in a normal population. 2) In KTR, PnPsAb titers decreased significantly between T0 and T12 (p < 0.005); the t1/2 of the different PnPsAb ranged from 9.2 to 11.9 months. Conclusions: In KTR treated by MMF and CNI, the TAnAbs and PnPsAbs titers decrease significantly and profoundly during the first year. Immunization pre-transplantation should be encouraged to maintain adequate post-transplant Abs levels.

Glutamine supplementation and renal health

Gemstone Team Juiced

Development of a decision aid to inform patients' and families' renal replacement therapy selection decisions.

BACKGROUND: Few educational resources have been developed to inform patients' renal replacement therapy (RRT) selection decisions. Patients progressing toward end stage renal disease (ESRD) must decide among multiple treatment options with varying characteristics. Complex information about treatments must be adequately conveyed to patients with different educational backgrounds and informational needs. Decisions about treatment options also require family input, as families often participate in patients' treatment and support patients' decisions. We describe the development, design, and preliminary evaluation of an informational, evidence-based, and patient-and family-centered decision aid for patients with ESRD and varying levels of health literacy, health numeracy, and cognitive function. METHODS: We designed a decision aid comprising a complementary video and informational handbook. We based our development process on data previously obtained from qualitative focus groups and systematic literature reviews. We simultaneously developed the video and handbook in "stages." For the video, stages included (1) directed interviews with culturally appropriate patients and families and preliminary script development, (2) video production, and (3) screening the video with patients and their families. For the handbook, stages comprised (1) preliminary content design, (2) a mixed-methods pilot study among diverse patients to assess comprehension of handbook material, and (3) screening the handbook with patients and their families. RESULTS: The video and handbook both addressed potential benefits and trade-offs of treatment selections. The 50-minute video consisted of demographically diverse patients and their families describing their positive and negative experiences with selecting a treatment option. The video also incorporated health professionals' testimonials regarding various considerations that might influence patients' and families' treatment selections. The handbook was comprised of written words, pictures of patients and health care providers, and diagrams describing the findings and quality of scientific studies comparing treatments. The handbook text was written at a 4th to 6th grade reading level. Pilot study results demonstrated that a majority of patients could understand information presented in the handbook. Patient and families screening the nearly completed video and handbook reviewed the materials favorably. CONCLUSIONS: This rigorously designed decision aid may help patients and families make informed decisions about their treatment options for RRT that are well aligned with their values.

Selecting renal replacement therapies: what do African American and non-African American patients and their families think others should know? A mixed methods study.

BACKGROUND: Little is known regarding the types of information African American and non-African American patients with chronic kidney disease (CKD) and their families need to inform renal replacement therapy (RRT) decisions. METHODS: In 20 structured group interviews, we elicited views of African American and non-African American patients with CKD and their families about factors that should be addressed in educational materials informing patients' RRT selection decisions. We asked participants to select factors from a list and obtained their open-ended feedback. RESULTS: Ten groups of patients (5 African American, 5 non-African American; total 68 individuals) and ten groups of family members (5 African American, 5 non-African American; total 62 individuals) participated. Patients and families had a range (none to extensive) of experiences with various RRTs. Patients identified morbidity or mortality, autonomy, treatment delivery, and symptoms as important factors to address. Family members identified similar factors but also cited the effects of RRT decisions on patients' psychological well-being and finances. Views of African American and non-African American participants were largely similar. CONCLUSIONS: Educational resources addressing the influence of RRT selection on patients' morbidity and mortality, autonomy, treatment delivery, and symptoms could help patients and their families select RRT options closely aligned with their values. Including information about the influence of RRT selection on patients' personal relationships and finances could enhance resources' cultural relevance for African Americans.

Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study.

BACKGROUND: Evidence is lacking to inform providers' and patients' decisions about many common treatment strategies for patients with end stage renal disease (ESRD). METHODS/DESIGN: The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003-2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006-2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. DISCUSSION: The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD community will enhance studies' impact on clinical care and patients' outcomes.

Magnetic Resonance Imaging Biomarkers of Renal Structure and Function

The kidney's major role in filtration depends on its high blood flow, concentrating mechanisms, and biochemical activation. The kidney's greatest strengths also lead to vulnerability for drug-induced nephrotoxicity and other renal injuries. The current standard to diagnose renal injuries is with a percutaneous renal biopsy, which can be biased and insufficient. In one particular case, biopsy of a kidney with renal cell carcinoma can actually initiate metastasis. Tools that are sensitive and specific to detect renal disease early are essential, especially noninvasive diagnostic imaging. While other imaging modalities (ultrasound and x-ray/CT) have their unique advantages and disadvantages, MRI has superb soft tissue contrast without ionizing radiation. More importantly, there is a richness of contrast mechanisms in MRI that has yet to be explored and applied to study renal disease.

The focus of this work is to advance preclinical imaging tools to study the structure and function of the renal system. Studies were conducted in normal and disease models to understand general renal physiology as well as pathophysiology. This dissertation is separated into two parts--the first is the identification of renal architecture with ex vivo MRI; the second is the characterization of renal dynamics and function with in vivo MRI. High resolution ex vivo imaging provided several opportunities including: 1) identification of fine renal structures, 2) implementation of different contrast mechanisms with several pulse sequences and reconstruction methods, 3) development of image-processing tools to extract regions and structures, and 4) understanding of the nephron structures that create MR contrast and that are important for renal physiology. The ex vivo studies allowed for understanding and translation to in vivo studies. While the structure of this dissertation is organized by individual projects, the goal is singular: to develop magnetic resonance imaging biomarkers for renal system.

The work presented here includes three ex vivo studies and two in vivo studies:

1) Magnetic resonance histology of age-related nephropathy in sprague dawley.

2) Quantitative susceptibility mapping of kidney inflammation and fibrosis in type 1 angiotensin receptor-deficient mice.

3) Susceptibility tensor imaging of the kidney and its microstructural underpinnings.

4) 4D MRI of renal function in the developing mouse.

5) 4D MRI of polycystic kidneys in rapamycin treated Glis3-deficient mice.

Specialist and primary care physicians' views on barriers to adequate preparation of patients for renal replacement therapy: a qualitative study.

BACKGROUND: Early preparation for renal replacement therapy (RRT) is recommended for patients with advanced chronic kidney disease (CKD), yet many patients initiate RRT urgently and/or are inadequately prepared. METHODS: We conducted audio-recorded, qualitative, directed telephone interviews of nephrology health care providers (n = 10, nephrologists, physician assistants, and nurses) and primary care physicians (PCPs, n = 4) to identify modifiable challenges to optimal RRT preparation to inform future interventions. We recruited providers from public safety-net hospital-based and community-based nephrology and primary care practices. We asked providers open-ended questions to assess their perceived challenges and their views on the role of PCPs and nephrologist-PCP collaboration in patients' RRT preparation. Two independent and trained abstractors coded transcribed audio-recorded interviews and identified major themes. RESULTS: Nephrology providers identified several factors contributing to patients' suboptimal RRT preparation, including health system resources (e.g., limited time for preparation, referral process delays, and poorly integrated nephrology and primary care), provider skills (e.g., their difficulty explaining CKD to patients), and patient attitudes and cultural differences (e.g., their poor understanding and acceptance of their CKD and its treatment options, their low perceived urgency for RRT preparation; their negative perceptions about RRT, lack of trust, or language differences). PCPs desired more involvement in preparation to ensure RRT transitions could be as "smooth as possible", including providing patients with emotional support, helping patients weigh RRT options, and affirming nephrologist recommendations. Both nephrology providers and PCPs desired improved collaboration, including better information exchange and delineation of roles during the RRT preparation process. CONCLUSIONS: Nephrology and primary care providers identified health system resources, provider skills, and patient attitudes and cultural differences as challenges to patients' optimal RRT preparation. Interventions to improve these factors may improve patients' preparation and initiation of optimal RRTs.

Apparent treatment-resistant hypertension and chronic kidney disease: another cardiovascular-renal syndrome?

To identify patients at increased risk of cardiovascular (CV) outcomes, apparent treatment-resistant hypertension (aTRH) is defined as having a blood pressure above goal despite the use of 3 or more antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. Recent epidemiologic studies in selected populations estimated the prevalence of aTRH as 10% to 15% among patients with hypertension and that aTRH is associated with elevated risk of CV and renal outcomes. Additionally, aTRH and CKD are associated. Although the pathogenesis of aTRH is multifactorial, the kidney is believed to play a significant role. Increased volume expansion, aldosterone concentration, mineralocorticoid receptor activity, arterial stiffness, and sympathetic nervous system activity are central to the pathogenesis of aTRH and are targets of therapies. Although diuretics form the basis of therapy in aTRH, pathophysiologic and clinical data suggest an important role for aldosterone antagonism. Interventional techniques, such as renal denervation and carotid baroreceptor activation, modulate the sympathetic nervous system and are currently in phase III trials for the treatment of aTRH. These technologies are as yet unproven and have not been investigated in relationship to CV outcomes or in patients with CKD.

Late referral for assessment of renal failure

It has been recommended that adult patients with a serum creatinine above 150 µmol/l should be referred to a nephrologist for specialist assessment. This study ascertained all patients in Northern Ireland with creatinine above this concentration in 2001 (n?=?19 286 ) to see if this triggered referral within the subsequent year. After exclusion of those who were already known to a nephrologist and those who had acute renal failure, it was found that younger patients and diabetic patients were more likely to be referred. There was no difference in referral rates between male and female patients. However, only 6.5% of all non-diabetic subjects and 19% of diabetic patients were referred within 12 months after a first increased serum creatinine test.