Lionaki S.,Laiko Hospital |
Lionaki S.,Kidney Center |
Derebail V.K.,Kidney Center |
Hogan S.L.,Kidney Center |
And 11 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2012
Background and objectives The aims of this study were to determine the frequency of venous thromboembolicevents in a large cohort of patients with idiopathic membranous nephropathy and to identify predisposing risk factors.Design, setting, participants, & measurements We studied patients with biopsy-proven membranous nephropathy from the Glomerular Disease Collaborative Network (n=412) and the Toronto Glomerulonephritis Registry (n=486) inception cohorts. The cohorts were pooled after establishing similar baseline characteristics (total n=898). Clinically apparent and radiologically confirmed venous thromboembolic events were identified. Potential risk factors were evaluated using multivariable logistic regression models.Results Sixty-five (7.2%) subjects had at least one venous thromboembolic event, and this rate did not differ significantly between registries. Most venous thromboembolic events occurred within 2 years of first clinical assessment (median time to VTE = 3.8 months). After adjusting for age, sex, proteinuria, and immunosuppressive therapy, hypoalbuminemia at diagnosis was the only independent predictor of a venous thromboembolic event. Each 1.0 g/dl reduction in serum albumin was associated with a 2.13-fold increased risk of VTE. An albumin level,2.8 g/dl was the threshold below which risk for a venous thromboembolic event was greatest.Conclusions We conclude that clinically apparent venous thromboembolic events occur in about 7% of patients with membranous nephropathy. Hypoalbuminemia, particularly,2.8 g/dl, is the most significant independent predictor of venous thrombotic risk. © 2012 by the American Society of Nephrology.
Kawanishi K.,Kidney Center |
Nitta K.,Kidney Center |
Yamato M.,Tokyo Women's Medical University |
Okano T.,Tokyo Women's Medical University
Therapeutic Apheresis and Dialysis | Year: 2015
Mesothelial cells are an integral part of the peritoneum and play an important role in maintaining its structural and functional properties. In recent years a number of studies on mesothelial cells have been performed to evaluate the localization, secretional properties and the ability of regeneration and transdifferentiation of these cells. They are also involved in the repair of the peritoneum damage following surgery or peritonitis. Mesothelial cells produce several cytokines, growth factors and extracellular matrix components, possessing anti-inflammatory and immunomodulatory properties. Based on previous research, cell sheet engineering has made it possible to transplant cells that retain the cells' function, and stacking different cells in layers has also become possible. Arranging blood vessels between the cell layers is a problem when stacking cells in layers. Whether adequate blood flow can be obtained for the cell layers to survive long-term is the difference between success and failure. Mesothelial cell transplantation for peritoneal regeneration needs to be performed under conditions in which the surface area of the visceral peritoneum is large and the mesothelial cell damage area is small. In this article we explain cell sheet engineering as one of the technologies for transplanting cells with a variety of intercellular adhesion and cell membrane molecules maintained intact, and its application to peritoneal regeneration. © 2014 International Society for Apheresis.
Nitta K.,Kidney Center |
Ogawa T.,Tokyo Women's Medical University
Contributions to Nephrology | Year: 2015
Vascular calcification is very common in patients with end-stage renal disease (ESRD) and has been found to be associated with mineral and bone disorders. There are two types of vascular calcification: intimal and medial calcification. The transformation of vascular smooth muscle cells into osteoblast-like cells seems to be a key element in the pathogenesis of medial calcification in the presence of calcium and phosphate deposition. Vascular calcification causes increased arterial stiffness by medial calcification, which leads to left ventricular hypertrophy and decreased coronary artery perfusion and causes myocardial ischemia by intimal calcification. Thus, vascular calcification is thought to be associated with increased cardiovascular morbidity and mortality. Although current treatment strategies focus on correcting abnormal calcium, phosphate, parathyroid hormone, or vitamin D levels in ESRD patients, a better understanding of the mechanisms of vascular calcification may lead to the development of new therapeutic strategies that are capable of reducing vascular calcification and improving the cardiovascular outcome of ESRD patients. This review summarizes the pathophysiology, diagnostic procedure and therapeutic implication of vascular calcification in ESRD patients. © 2015 S. Karger AG, Basel.
Stanton M.L.,University of Florida |
Joy M.S.,Kidney Center |
Frye R.F.,University of Florida
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2010
A rapid method to determine fexofenadine concentrations in human plasma using protein precipitation in 96-well plates and liquid chromatography-tandem mass spectrometry was validated. Plasma proteins were precipitated with acetonitrile containing the internal standard fexofenadine-d6, mixed briefly, and then filtered into a collection plate. The resulting filtrate was diluted and injected onto a Phenomenex Gemini C18 (50 mm × 2.0 mm, 5 μm) analytical column. The mobile phase consisted of 0.1% formic acid, 5 mM ammonium acetate in deionized water and methanol (35:65, v/v). The flow rate was 0.2 ml/min and the total run time was 2 min. Detection of the analytes was achieved using positive ion electrospray ionization and high resolution multiple reaction monitoring mode (H-SRM). The linear standard curve ranged from 1 to 500 ng/ml and the precision and accuracy (intra- and inter-run) were within 4.3% and 8.0%, respectively. The method has been applied successfully to determine fexofenadine concentrations in human plasma samples obtained from subjects administered a single oral dose of fexofenadine. The method is rapid, sensitive, selective and directly applicable to human pharmacokinetic studies involving fexofenadine. © 2009 Elsevier B.V. All rights reserved.
Geetha D.,Johns Hopkins University |
Eirin A.,Rochester College |
True K.,Kidney Center |
Valentina Irazabal M.,Rochester College |
And 4 more authors.
Transplantation | Year: 2011
Background. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of rapidly progressive glomerulonephritis resulting in end-stage renal disease (ESRD). The optimal timing of kidney transplantation (KTX) for ESRD as a result of AAV and the risk of AAV relapse after KTX are not well defined. We report our experience with AAV patients who underwent KTX at our institutions between 1996 and 2010. Median follow-up was 64 months. Methods. Retrospective multicenter cohort study. Results. Eighty-five patients (45 men/40 women; mean age 49 years) received a KTX for ESRD secondary to microscopic polyangiitis (n=43) or Wegener's granulomatosis (n=42). Twenty-four patients underwent preemptive KTX and 69 received a living-donor KTX. All patients were in remission at the time of KTX. Fifty-eight patients received induction therapy. In 64 patients, maintenance immunosuppression was with prednisone, mycophenolate mofetil, and tacrolimus. At the time of KTX, 29 patients were ANCA-positive. The vasculitis relapse rate was 0.02 per patient-years and was not influenced by disease category, ANCA subtype, or remission duration before KTX. There were 23 rejection episodes in 13 patients with seven graft losses. Median serum creatinine at 1 year was 1.3 mg/dL in 75 patients with more than 1 year follow-up and 1.4 mg/dL at last follow-up. The graft and patient survival rates were 100% at 1 year, 97.9% and 93.4% at 5 years, and 79.0% and 67.4% at 10 years, respectively. CONCLUSIONS.: KTX is a safe and an effective option for treating ESRD secondary to AAV. Relapses are rare with current immunosuppression. Copyright © 2011 by Lippincott Williams & Wilkins.
Babayev R.,Columbia University |
Whaley-Connell A.,University of Missouri |
Kshirsagar A.,Kidney Center |
Klemmer P.,Kidney Center |
And 5 more authors.
American Journal of Kidney Diseases | Year: 2013
Background: A recent cross-sectional analysis of Kidney Early Evaluation Program (KEEP) participants suggested that obesity is a heterogeneous disease state in African Americans and whites with chronic kidney disease (CKD). Study Design: In longitudinal analyses spanning 8 years of follow-up, we examined whether race and body mass index (BMI) influence end-stage renal disease (ESRD) and mortality rates in participants with CKD stages 3-4. Setting & Participants: KEEP participants were included in this analysis if they met the following criteria: (1) estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m2, (2) white or African American race, and (3) no previous dialysis or transplantation. Outcomes & Measurements: Survival analyses were performed for the outcomes of ESRD, death, and combined outcome of ESRD or death. Results: Of 14,631 participants with CKD stages 3-4, 28% were African American and 72% were white. African American participants had higher rates of obesity and hypertension, with a higher baseline mean eGFR, higher prevalence of albuminuria, and greater degree of anemia compared with whites. In multivariable models, African American race increased the risk of ESRD (HR, 1.66; 95% CI, 1.26-2.07), but not death (HR, 0.89; 95% CI, 0.76-1.03). In these models, male sex, hypertension, diabetes, lower baseline eGFR, and albuminuria were predictive of higher rates of ESRD; age, male sex, diabetes, lower baseline eGFR, and albuminuria were predictive of overall mortality. There was no significant interaction between race and BMI in the adjusted model for outcomes of ESRD (P = 0.7) or death (P = 0.3). Limitations: Baseline values used in the analysis are from a cross-sectional data set. Dyslipidemia and secondary hyperparathyroidism were not accounted for in the analysis. Conclusions: African American race was associated with a higher incidence of ESRD, but not mortality. Although obesity may be a heterogeneous disease state in African Americans and whites with CKD, there does not appear to be a significant interaction between race and BMI in progression to ESRD or death. © 2013 National Kidney Foundation, Inc.
Ciavatta D.,Kidney Center |
Falk R.J.,Kidney Center |
Falk R.J.,University of North Carolina at Chapel Hill
Clinical and Experimental Immunology | Year: 2011
Although studies on the immunopathogenesis of anti-neutrophil cytoplasm antibody (ANCA) vasculitis have been directed at understanding the autoantibody, there is growing evidence that points to the importance of ANCA autoantigen genes and their regulation. Transcriptional analysis indicates that ANCA autoantigen genes are active in mature neutrophils of ANCA vasculitis patients compared to healthy controls. The unusual transcriptional state of neutrophils from ANCA vasculitis patients appears to be a consequence of failed or disrupted epigenetic silencing. Defective epigenetic silencing could have global effects, by altering the transcriptional and phenotypic state of neutrophils, or local effects by permitting transcription of autoantigen genes from both strands resulting in anti-sense transcripts. Although the role of anti-sense transcripts is currently unknown, there are two intriguing possibilities. Anti-sense transcripts could function (as described for other genes) in transcriptional silencing of autoantigen genes, which takes place in normal neutrophil progenitors. In the setting of failed epigenetic silencing, the fate of anti-sense transcripts may be pathological and serve as a template for production of complementary autoantigens. The observation that ANCA vasculitis patients have anti-sense transcripts and antibodies to complementary proteins is consistent with a role of anti-sense transcripts in complementary protein production. A better understanding of epigenetic silencing and complementary proteins in ANCA vasculitis may unlock the underlying pathology of this condition. © 2011 The Authors; Clinical and Experimental Immunology © 2011 British Society for Immunology.
Jennette C.E.,Kidney Center
Rural and remote health | Year: 2010
INTRODUCTION: Chronic kidney disease (CKD) and its progression to end-stage kidney disease (ESKD), requiring lifelong dialysis or kidney transplant, has become a public health epidemic and a financial burden on healthcare systems. The lack of available and appropriately targeted kidney disease education may account for the low awareness of kidney disease, especially among high risk populations. This low awareness can lead to late detection of CKD and an increased likelihood of progression to ESKD. This study utilized focus groups to assess community perceptions of kidney disease, barriers to health care, and educational interventions. METHODS: Seventeen focus groups were conducted with 201 participants in 5 rural North Carolina counties to assess perceptions of kidney disease, barriers to health care and strategies for raising awareness. Qualitative data analysis was performed based on a grounded theory approach. RESULTS: Of the 201 participants, 74% were African-American, 96% knew someone with diabetes or hypertension, and 76% of groups contained at least one participant with a family member or friend diagnosed with ESKD. Participants were aware that kidneys acted as filters and mechanisms to cleanse the blood, and stated that alcohol, soda, obesity, diet, and urination problems were risk factors for developing CKD. Participants consistently mentioned that symptoms and risk factors for CKD were key pieces of knowledge. Affordability of health services, medicine, and insurance was seen as the biggest barrier to health care in the communities studied; knowing how to better communicate with physicians was also important. Television and word-of-mouth were mentioned most often as the best tools for outreach and education. Wal-Mart (a chain of large, discount department and grocery stores) and community churches were most commonly mentioned as potential places for screenings. CONCLUSION: Results indicate that there is some basic community knowledge about kidney disease but the risk of developing kidney disease is often directly attributed to lifestyle behaviors rather than diabetes, hypertension, or cardiovascular disease. Future educational interventions need to be focused on the risk factors for kidney disease, and must address financial and geographic barriers to health care and poor communication between consumers and healthcare professionals.
Stern A.B.,Kidney Center |
Klemmer P.J.,Kidney Center
Hemodialysis International | Year: 2011
In the hemodialysis patient population, a surgically created arteriovenous fistula is the preferred vascular access option. Development of high-output heart failure may be an underappreciated complication in patients who have undergone this procedure. When a large proportion of arterial blood is shunted from the left-sided circulation to the right-sided circulation via the fistula, the increase in preload can lead to increased cardiac output. Over time, the demands of an increased workload may lead to cardiac hypertrophy and eventual heart failure. Patients may present with the usual signs of high-output heart failure including tachycardia, elevated pulse pressure, hyperkinetic precordium, and jugular venous distension. Typically, the AV fistula is quite large and is likely located in the upper arm, more proximal to the heart. Routine access flow monitoring should demonstrate blood flows (Qa) >2000ML/min. Echocardiogram may reveal either a low or high left ventricular ejection fraction, and right-heart catheterization demonstrates an elevated cardiac output with a low to normal systemic vascular resistance. When addressing the problem of high-output heart failure, the nephrologist is faced with the dilemma of preventing progression of heart failure at the expense of loss of vascular access. Nevertheless, treatment should be directed at correcting the underlying problem by surgical banding or ligation of the fistula. © 2011 The Authors. Hemodialysis International © 2011 International Society for Hemodialysis.
Laurin L.-P.,Kidney Center |
Nachman P.H.,Kidney Center |
Desai P.C.,Ohio State University |
Ataga K.I.,University of North Carolina at Chapel Hill |
Derebail V.K.,Kidney Center
Nephrology Dialysis Transplantation | Year: 2014
Background. Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients. Methods. We performed a cross-sectional study of 149 adult patients followed between 2000 and 2011 in a comprehensive sickle cell clinic. All patients were assessed for albuminuria either by direct measurement or by urinary chemical strip (dipstick) testing. Urinary albumin-to-creatinine ratios (UACRs) were available for 112 patients. Hydroxyurea exposure was defined as ≥3 months of therapy before the assessment of albuminuria. Albuminuria was defined as either UACR ≥30 mg/g or ≥1+ proteinuria on two separate dipsticks. We constructed a multivariate logistic regression model to assess the association between hydroxyurea and albuminuria. Results. The prevalence of albuminuria was lower among patients on hydroxyurea (34.7 versus 55.4%; P = 0.01) as was median albumin excretion (17.9 versus 40.5 mg/g; P = 0.04). In multivariate analysis, hydroxyurea was associated with a lower likelihood of albuminuria (odds ratio 0.28, 95% CI: 0.11-0.75, P = 0.01), adjusting for age, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, tricuspid regurgitant jet velocity, hypertension and acute chest syndrome. Conclusions. In our population of sickle cell patients, those using hydroxyurea were less than one-third as likely to exhibit albuminuria. Hydroxyurea use may prevent development of overt nephropathy or the progression of sickle cell disease nephropathy to end-stage renal disease, and its use for this indication merits further investigation. © 2013 The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.