7 results on '"Patel, Rajan K."'
Search Results
2. Left ventricular dysfunction with preserved ejection fraction: the most common left ventricular disorder in chronic kidney disease patients.
- Author
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Mark, Patrick B, Mangion, Kenneth, Rankin, Alastair J, Rutherford, Elaine, Lang, Ninian N, Petrie, Mark C, Stoumpos, Sokratis, and Patel, Rajan K
- Subjects
HEART failure ,LEFT ventricular dysfunction ,CHRONIC kidney failure ,DISEASE risk factors ,CHRONICALLY ill ,LEFT ventricular hypertrophy - Abstract
Chronic kidney disease (CKD) is a risk factor for premature cardiovascular disease. As kidney function declines, the presence of left ventricular abnormalities increases such that by the time kidney replacement therapy is required with dialysis or kidney transplantation, more than two-thirds of patients have left ventricular hypertrophy. Historically, much research in nephrology has focussed on the structural and functional aspects of cardiac disease in CKD, particularly using echocardiography to describe these abnormalities. There is a need to translate knowledge around these imaging findings to clinical outcomes such as unplanned hospital admission with heart failure and premature cardiovascular death. Left ventricular hypertrophy and cardiac fibrosis, which are common in CKD, predispose to the clinical syndrome of heart failure with preserved left ventricular ejection fraction (HFpEF). There is a bidirectional relationship between CKD and HFpEF, whereby CKD is a risk factor for HFpEF and CKD impacts outcomes for patients with HFpEF. There have been major improvements in outcomes for patients with heart failure and reduced left ventricular ejection fraction as a result of several large randomized controlled trials. Finding therapy for HFpEF has been more elusive, although recent data suggest that sodium-glucose cotransporter 2 inhibition offers a novel evidence-based class of therapy that improves outcomes in HFpEF. These observations have emerged as this class of drugs has also become the standard of care for many patients with proteinuric CKD, suggesting that there is now hope for addressing the combination of HFpEF and CKD in parallel. In this review we summarize the epidemiology, pathophysiology, diagnostic strategies and treatment of HFpEF with a focus on patients with CKD. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
3. Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway
- Author
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Stevens, Kathryn, Denby, Laura, Patel, Rajan K., Mark, Patrick B., Kettlewell, Sarah, Smith, Godfrey L., Clancy, Marc J., Delles, Christian, and Jardine, Alan G.
- Subjects
cardiovascular risk ,Male ,Nitric Oxide Synthase Type III ,Nitric Oxide ,Rats, Inbred WKY ,Phosphates ,endothelial function ,Risk Factors ,Animals ,Humans ,Single-Blind Method ,Renal Insufficiency, Chronic ,Cyclic GMP ,Cells, Cultured ,phosphate ,Cross-Over Studies ,Endothelial Cells ,Original Articles ,Rats ,Fibroblast Growth Factors ,Hyperphosphatemia ,Vasodilation ,Fibroblast Growth Factor-23 ,Basic Research ,Cardiovascular Diseases ,Endothelium, Vascular ,chronic kidney disease ,Signal Transduction - 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 (± 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 flow-mediated 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 serum fibroblast 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.
- Published
- 2016
4. Ascorbic acid lowers central blood pressure and asymmetric dimethylarginine in chronic kidney disease.
- Author
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Gillis, Keith, Stevens, Kathryn K, Bell, Elizabeth, Patel, Rajan K, Jardine, Alan G, Morris, Scott T W, Schneider, Markus P, Delles, Christian, and Mark, Patrick B
- Abstract
Background Premature cardiovascular disease in patients with chronic kidney disease (CKD) is not explained by traditional risk factors and oxidative stress may contribute via endothelial and vascular dysfunction. We investigated the effect of ascorbic acid on oxidative stress and vascular function in CKD patients compared with controls with hypertension (HTN). Methods A crossover study of intravenous saline and ascorbic acid was conducted. Biomarkers of oxidative stress were measured, while pulse wave analysis and brachial flow - mediated dilatation were performed to assess large artery and endothelial function. Results Twenty HTN and 30 CKD patients Stages 3–5 were recruited. Serum ascorbic acid was significantly lower in patients with CKD. In both groups, ascorbic acid significantly increased total antioxidant potential and superoxide. Asymmetric dimethylarginine (ADMA) was reduced significantly by ascorbic acid in the CKD group and on multivariate regression analysis, age and the presence of CKD were predictors of ADMA response to ascorbic acid. Although no effect on FMD was observed, central blood pressure and augmentation index were reduced significantly in both groups. Conclusions Ascorbic acid has pro- and antioxidant effects, reducing central blood pressure and augmentation index in HTN and CKD. Ascorbic acid reduces serum ADMA in CKD, which may have longer-term benefits. [ABSTRACT FROM AUTHOR]
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- 2018
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- View/download PDF
5. 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]
- Published
- 2017
- Full Text
- View/download PDF
6. Serum phosphate and social deprivation independently predict all-cause mortality in chronic kidney disease.
- Author
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Solbu, Marit D., Thomson, Peter C., Macpherson, Sarah, Findlay, Mark D., Stevens, Kathryn K., Patel, Rajan K., Padmanabhan, Sandosh, Jardine, Alan G., and Mark, Patrick B.
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SOCIAL isolation ,CHRONIC kidney failure ,LONGITUDINAL method ,PHOSPHATES ,RESEARCH evaluation ,RISK assessment ,SURVIVAL analysis (Biometry) ,COMORBIDITY ,DISEASE incidence ,HYPERPHOSPHATEMIA ,PSYCHOLOGY ,DIAGNOSIS - Abstract
Background: Hyperphosphataemia is linked to cardiovascular disease and mortality in chronic kidney disease (CKD). Outcome in CKD is also affected by socioeconomic status. The objective of this study was to assess the associations between serum phosphate, multiple deprivation and outcome in CKD patients.Methods: All adult patients currently not on renal replacement therapy (RRT), with first time attendance to the renal outpatient clinics in the Glasgow area between July 2010 and June 2014, were included in this prospective study. Area socioeconomic status was assessed as quintiles of the Scottish Index of Multiple Deprivation (SIMD). Outcomes were all-cause and cardiovascular mortality and commencement of RRT.Results: The cohort included 2950 patients with a median (interquartile range) age 67.6 (53.6-76.9) years. Median (interquartile range) eGFR was 38.1 (26.3-63.5) ml/min/1.73 m(2), mean (± standard deviation) phosphate was 1.13 (± 0.24) mmol/L and 31.6 % belonged to the most deprived quintile (SIMD quintile I). During follow-up 375 patients died and 98 commenced RRT. Phosphate ≥ 1.50 mmol/L was associated with all-cause (hazard ratio (HR) 2.51; 95 % confidence interval (CI) 1.63-3.89) and cardiovascular (HR 5.05; 95 % CI 1.90-13.46) mortality when compared to phosphate 0.90-1.09 mmol/L in multivariable analyses. SIMD quintile I was independently associated with all-cause mortality. Phosphate did not weaken the association between deprivation index and mortality, and there was no interaction between phosphate and SIMD quintiles. Neither phosphate nor SIMD predicted commencement of RRT.Conclusions: Multiple deprivation and serum phosphate were strong, independent predictors of all-cause mortality in CKD and showed no interaction. Phosphate also predicted cardiovascular mortality. The results suggest that phosphate lowering should be pursued regardless of socioeconomic status. [ABSTRACT FROM AUTHOR]- Published
- 2015
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7. A descriptive analysis of non-human leukocyte antigens present in renal transplant donor-recipient pairs.
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Sisk, Louis J., Patel, Rajan K., and Stevens, Kathryn K.
- Subjects
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CHRONIC kidney failure , *KIDNEY transplantation , *ANTIGENS , *PROTEIN microarrays , *KIDNEY failure - Abstract
End stage renal disease (ESRD) is the irreversible deterioration of renal function requiring renal replacement therapy by dialysis or transplant. Human leucocyte antigens (HLA) have been well examined however research still is required into the non-HLA antibodies. Antibody mediated rejection (AMR) can be seen in the absence of HLA antibodies on biopsies of patients who have received identical transplants; anti-endothelial cell antibodies may explain this. Investigation into endothelial cell antigens on donor and recipient endothelium may elucidate and stratify the degree of risk of any given transplant and may guide towards the best matched donor. Protein array analysis was carried out on 8 patient pairs using nitro-cellulose membranes and biotinylated detection antibodies. The fluorescence emitted was captured by X-Ray film and results were recorded with ImageJ software. A fold increase of more than 2 was considered to be positive. 11 proteins identified had a fold increase of increase ≥2 and were present in ≥2 patient pairs which may point to potential clinical utility. Nectin2/CD112 may be measured in order analyse graft survival time in transplant recipients. Prognosticating renal failure has clinical importance and potential markers that have been identified to aid which include MEPE, CRELD2, and TIMP-4. Novel pharmacological therapies for specific biomarkers identified in this study include JAM-A, E -Selectin, CD147, Galectin-3, JAM-C, PAR-1, and TNFR2. Protein analysis showed differences in expression of antigens between patients with and without Chronic Kidney Disease (CKD). This information could be used at the matching stage of renal transplantation and also in the treatment of rejection episodes. The results highlight biomarkers that potentially prognosticate and pharmacological therapies that may ameliorate kidney disease and rejection in ESRD and transplant recipients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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