5 results on '"Patel, Rajan K."'
Search Results
2. Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway.
- Author
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Stevens, Kathryn K., Denby, Laura, Patel, Rajan K., Mark, Patrick B., Kettlewell, Sarah, Smith, Godfrey L., Clancy, Marc J., Delles, Christian, and Jardine, Alan G.
- Subjects
PHYSIOLOGICAL effects of phosphates ,NITRIC oxide ,HYPERPHOSPHATEMIA ,CARDIOVASCULAR diseases ,KIDNEY diseases ,VASODILATION ,PHOSPHODIESTERASE-5 inhibitors ,DISEASE risk factors - Abstract
Background. Hyperphosphataemia is an independent risk factor for accelerated cardiovascular disease in chronic kidney disease (CKD), although the mechanism for this is poorly understood. We investigated the effects of sustained exposure to a high-phosphate environment on endothelial function in cellular and preclinical models, as well as in human subjects. Methods. Resistance vessels from rats and humans (6 CKD) were incubated in a normal (1.18 mM) or high (2.5 mM) phosphate concentration solution and cells were cultured in normal- (0.5 mM) or high-phosphate (3 mM) concentration media. A single-blind crossover study was performed in healthy volunteers, receiving phosphate supplements or a phosphate binder (lanthanum), and endothelial function measured was by flowmediated dilatation. Results. Endothelium-dependent vasodilatation was impaired when resistance vessels were exposed to high phosphate; this could be reversed in the presence of a phosphodiesterase-5- inhibitor. Vessels from patients with CKD relaxed normally when incubated in normal-phosphate conditions, suggesting that the detrimental effects of phosphate may be reversible. Exposure to high-phosphate disrupted the whole nitric oxide pathway with reduced nitric oxide and cyclic guanosine monophosphate production and total and phospho endothelial nitric oxide synthase expression. In humans, endothelial function was reduced by chronic phosphate loading independent of serum phosphate, but was associated with higher urinary phosphate excretion and serumfibroblast growth factor 23. Conclusions. These directly detrimental effects of phosphate, independent of other factors in the uraemic environment, may explain the increased cardiovascular risk associated with phosphate in CKD. [ABSTRACT FROM AUTHOR]
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- 2017
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- View/download PDF
3. Research cardiac magnetic resonance imaging in end stage renal disease - incidence, significance and implications of unexpected incidental findings.
- Author
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Rutherford, Elaine, Weir-McCall, Jonathan, Patel, Rajan, Houston, J., Roditi, Giles, Struthers, Allan, Jardine, Alan, Mark, Patrick, Weir-McCall, Jonathan R, Patel, Rajan K, Houston, J Graeme, Struthers, Allan D, Jardine, Alan G, and Mark, Patrick B
- Subjects
KIDNEY disease diagnosis ,MAGNETIC resonance imaging ,KIDNEY diseases ,LEFT ventricular hypertrophy ,CHRONIC kidney failure ,PATIENTS ,CHRONIC kidney failure complications ,HEART disease complications ,DIAGNOSIS ,HEART ,HEART diseases ,MYOCARDIUM ,DISEASE incidence ,DISEASE prevalence ,RETROSPECTIVE studies - Abstract
Objectives: Left ventricular mass (LVM) at cardiac magnetic resonance imaging (CMR) is a frequent end point in clinical trials in nephrology. Trial participants with end stage renal disease (ESRD) may have a greater frequency of incidental findings (IF). We retrospectively investigated prevalence of IF in previous research CMR and reviewed their subsequent impact on participants.Methods: Between 2002 and 2006, 161 ESRD patients underwent CMR in a transplant assessment study. Images were used to assess LV mass and function. In the current study a radiologist reviewed the scans for IF. Review of patient records determined the subsequent clinical significance of IF.Results: There were 150 IF in 95 study participants. Eighty-four (56 %) were new diagnoses. One hundred and two were non-cardiac. Fifteen were suspicious of malignancy. There was a clinically significant IF for 14.9 % of the participants. In six cases earlier identification of an IF may have improved quality of life or survival.Conclusions: Without radiology support clinically important IF may be missed on CMR. Patients undergoing CMR in trials should be counselled about the frequency and implications of IF. Patients with ESRD have a higher prevalence of IF than reported in other populations. Nephrology studies require mechanisms for radiologist reporting and strategies for dealing with IF.Key Points: • Incidental findings on research cardiac magnetic resonance imaging can have significant consequences. • We considered incidental findings in historical renal cardiac resonance imaging clinical trials. • Incidental findings are common and important in the chronic kidney disease population. • Without radiology support, clinically significant incidental findings may be missed on imaging. • Study protocols, approvals and consent processes should take account of possible findings. [ABSTRACT FROM AUTHOR]- Published
- 2017
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- View/download PDF
4. Urinary corticosteroid excretion predicts left ventricular mass and proteinuria in chronic kidney disease.
- Author
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McQUARRIE, Emily P., FREEL, E. Marie, MARK, Patrick B. MARK, FRASER, Robert, PATEL, Rajan K., DARGIE, Henry G., CONNELL, John M. C., and JARDINE, Alan G.
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KIDNEY diseases ,CORTICOSTEROIDS ,VENTRICULAR outflow obstruction ,PROTEINURIA ,MINERALOCORTICOID receptors ,CORTICOSTERONE - Abstract
Blockade of the MR (mineralocorticoid receptor) in CKD (chronic kidney disease) reduces LVMI [LV (left ventricular) mass index] and proteinuria. The MR can be activated by aldosterone, cortisol and DOC (deoxycorticosterone). The aim of the present study was to explore the influence of mineralocorticoids on LVMI and proteinuria in patients with CKD. A total of 70 patients with CKD and 30 patients with EH (essential hypertension) were recruited. Patients underwent clinical phenotyping; biochemical assessment and 24 h urinary collection for THAldo (tetrahydroaldosterone), THDOC (tetrahydrodeoxycorticosterone), cortisol metabolites (measured using GC-MS), and urinary electrolytes and protein [QP (proteinuira quantification)]. LVMI was measured using CMRI (cardiac magnetic resonance imaging). Factors that correlated significantly with LVMI and proteinuria were entered into linear regression models. In patients with CKD, significant predictors of LVMI were male gender, SBP (systolic blood pressure), QP, and THAldo and THDOC excretion. Significant independent predictors on multivariate analysis were THDOC excretion, SBP and male gender. In EH, no association was seen between THAldo or THDOC and LVMI; plasma aldosterone concentration was the only significant independent predictor. Significant univariate determinants of proteinuria in patients with CKD were THAldo, THDOC, USod (urinary sodium) and SBP. Only THAldo excretion and SBP were significant multivariate determinants. Using CMRI to determine LVMI we have demonstrated that THDOC is a novel independent predictor of LVMI in patients with CKD, differing from patients with EH. Twenty-four hour THAldo excretion is an independent determinant of proteinuria in patients with CKD. These findings emphasize the importance of MR activation in the pathogenesis of the adverse clinical phenotype in CKD. [ABSTRACT FROM AUTHOR]
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- 2012
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5. Altered relative concentrations of high-energy phosphates in patients with uraemic cardiomyopathy measured by magnetic resonance spectroscopy.
- Author
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Patel, Rajan K., Mark, Patrick B., Macnaught, Gillian, Stevens, Kathryn K., McQuarrie, Emily P., Steedman, Tracey, Gillis, Keith, Dargie, Henry J., and Jardine, Alan G.
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CARDIOMYOPATHIES , *NUCLEAR magnetic resonance spectroscopy , *PHOSPHATES , *PHOSPHOCREATINE , *ADENOSINE triphosphate , *KIDNEY diseases , *UREMIA - Abstract
Background. Premature sudden cardiovascular death is the commonest cause of death in end-stage renal disease (ESRD) patients and is associated with uraemic cardiomyopathy [left ventricular hypertrophy (LVH), systolic dysfunction (LVSD) or LV dilation]. High-energy phosphates (HEP), quantified using phosphorus-31 magnetic resonance spectroscopy, are reduced in patients with diabetes, heart failure and uraemia. Phosphocreatine:β adenosine triphosphate (PCr:ATP) ratio is an index of metabolic activity. We compared resting HEPs in ESRD patients and hypertensive patients (with and without LVH) who had normal renal function (LVH-only or normal myocardia). We also assessed associations of HEP levels with abnormalities of uraemic cardiomyopathy. Methods. Fifty-three ESRD and 30 hypertensive patients (18 with LVH, 12 with normal myocardia) underwent phosphorus magnetic resonance spectroscopy of their left ventricle. PCr:ATP ratios were calculated from 31P-MR spectra obtained from long-axis views of the left ventricle. Results. There were no significant differences in age, LV mass, chamber sizes and ejection fraction between patient groups. PCr:ATP was significantly lower in ESRD patients compared to hypertensive patients, irrespective of the presence or absence of LVH (P = 0.01). In the ESRD group, PCr:ATP was significantly lower in patients with LVSD (P = 0.05) and LV dilation (P = 0.01). LVH was not associated with significant difference in PCr:ATP. Conclusions. ESRD patients have lower HEP levels compared to hypertensive patients. Lower PCr:ATP ratio, indicating altered myocardial metabolic function in ESRD patients, is associated with features of uraemic cardiomyopathy. [ABSTRACT FROM PUBLISHER]
- Published
- 2012
- Full Text
- View/download PDF
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