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Transplant Outcomes in Patients with Idiopathic Membranous Nephropathy  [PDF]
Claire Kennedy,Carol Traynor,Patrick O'Kelly,Anthony Dorman,Peter J. Conlon
International Journal of Nephrology , 2013, DOI: 10.1155/2013/818537
Abstract: Background. The natural history of idiopathic membranous nephropathy and recurrent disease in transplants is variable. We performed a retrospective cohort study of renal transplant recipients with a primary diagnosis of idiopathic membranous nephropathy. We aimed to establish patterns of disease recurrence and to identify factors associated with disease recurrence. Methods. We accessed the Irish renal transplant database to identify patients with biopsy-proven idiopathic membranous nephropathy in receipt of a renal transplant between 1982 and 2010. A detailed medical chart review was performed in all cases, and a senior renal histopathologist reviewed all histology specimens. Results. The outcomes of 32 patients, in receipt of 36 grafts, are reported. There was a male preponderance ( ). Significant graft dysfunction, directly attributable to recurrent disease, was evident in 31% of cases at 10 years. There was no significant association between time on dialysis, HLA mismatch, occurrence of rejection, and the development of recurrent membranous disease. One patient was retransplanted twice; all three grafts were lost to aggressive recurrent membranous disease. Conclusions. It remains difficult to identify those that will develop recurrent membranous nephropathy. Almost one third of patients in this cohort developed clinically significant recurrent disease at 10 years. 1. Introduction Idiopathic membranous nephropathy is a relatively common cause of nephrotic syndrome in nondiabetic adults. In our centre, 28% of native renal biopsies performed in the setting of nephrotic syndrome yielded a diagnosis of idiopathic membranous nephropathy [1]. The disease occurs most frequently in Caucasian adult males. In females, the diagnosis is more unusual and should prompt consideration of membranous lupus nephritis. An autoimmune basis for idiopathic membranous nephropathy has been established with the recent identification of the M-type phospholipase receptor (PLA2R) as the major antigen [2]. Characteristic histological features include diffusely thickened glomerular basement membranes on light microscopy. Immunofluorescence reveals diffuse granular IgG and C3 deposition along the glomerular basement membranes. Discrete subepithelial deposits are visualised on electron microscopy [3]. Histological findings which favour idiopathic membranous nephropathy over secondary disease include IgG4-positive immune complexes and exclusively subepithelial deposits [4]. The natural history of idiopathic membranous nephropathy is variable. Spontaneous remission occurs in a
Outcomes of renal transplantation in patients with immunoglobulin A nephropathy in India  [cached]
Chacko B,George J,Neelakantan N,Korula A
Journal of Postgraduate Medicine , 2007,
Abstract: Background: There is a paucity of data on the course of renal transplant in patients with immunoglobulin A (IgA) nephropathy (IgAN) from India. While the natural history of IgAN in the Indian context is rapidly progressive, the post-transplant course remains speculative. Aim: To study the graft survival in renal transplant recipients whose native kidney disease was IgAN and the incidence and correlates of recurrent disease. Settings and Designs: Retrospective case control study from a Nephrology unit of a large tertiary care center. Materials and Methods: The outcomes of 56 transplant patients (58 grafts) with biopsy-proven IgAN and of 116 patients without IgAN or diabetic nephropathy, transplanted during the same period were analyzed. Correlates of biopsy-confirmed recurrent disease were determined. Statistical Analysis: Means were analyzed by Student′s t test and Mann-Whitney test; proportions were determined by Chi-square analysis and graft survival curves were generated using the Kaplan-Meier. Results: Five-year graft survival for IgA patients was not significantly different from that in the reference group (90% and 79%, P = 0.6). During a mean follow-up of 42 months (range, 1-144), 28 event graft biopsies were required in 20 grafts of IgAN. Histological recurrence was diagnosed in five of the 20 available biopsies (25%) after a mean duration of 28 months. Recurrence did not correlate with donor status, HLA B35 and A2, recipient age, gender or immunosuppression. Conclusions: Renal transplantation is an appropriate treatment modality for IgA nephropathy patients with end-stage renal disease in India, despite the potential for recurrent disease. The posttransplant course is an indolent one when compared to the malignant pretransplant phase.
Patterns of warfarin use and subsequent outcomes in atrial fibrillation in primary care practices  [cached]
Ewen E,Zhang Z,Simon TA,Kolm P
Vascular Health and Risk Management , 2012,
Abstract: Edward Ewen,1 Zugui Zhang,1 Teresa A Simon,2 Paul Kolm,1 Xianchen Liu,3,4 William S Weintraub11Christiana Care Health System, Newark, DE, USA; 2Bristol-Myers Squibb, Princeton, NJ, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Pfizer, Groton, CT, USABackground: Warfarin is recommended for stroke prevention in high-risk patients with atrial fibrillation. However, it is often underutilized and inadequately managed in actual clinical practice.Objectives: To examine the patterns of warfarin use and their relationship with stroke and bleeding in atrial fibrillation patients in community-based primary care practices.Design: Retrospective longitudinal cohort study.Participants: A total of 1141 atrial fibrillation patients were selected from 17 primary care practices with a shared electronic medical record and characterized by stroke risk, potential barriers to anticoagulation, and comorbid conditions.Main measures: Duration and number of warfarin exposures, interruptions in warfarin exposure > 45 days, stroke, and bleeding events.Results: Among 1141 patients with a mean age of 70 years (standard deviation 13.3) and mean follow-up of 3.4 years (standard deviation 3.0), 764 (67%) were treated with warfarin. Warfarin was discontinued within 1 year in 194 (25.4%), and 349 (45.7%) remained on warfarin at the end of follow-up. Interruptions in warfarin use were common, occurring in 32.6% (249 of 764) of patients. Those with two or more interruptions were younger and at lower baseline stroke risk when compared to those with no interruptions. There were 76 first strokes and 73 first-bleeding events in the follow-up period. When adjusted for baseline stroke risk, time to warfarin start, and total exposure time, two or more interruptions in warfarin use was associated with an increased risk of stroke (relative risk, 2.29; 95% confidence interval: 1.29–4.07). There was no significant association between warfarin interruptions and bleeding events.Conclusion: Warfarin was underutilized in a substantial portion of eligible atrial fibrillation patients in these community-based practices. In addition, prolonged interruptions in anticoagulation were common in this population, and multiple interruptions were associated with over twice the risk of stroke when compared to those treated continuously.Keywords: cardiovascular disease, primary care, quality assessment, outcomes
Estimated Glomerular Filtration Rate Decline Is a Better Risk Factor for Outcomes of Systemic Disease-Related Nephropathy than for Outcomes of Primary Renal Diseases  [PDF]
Shuo-Chun Weng, Der-Cherng Tarng, Chyong-Mei Chen, Chi-Hung Cheng, Ming-Ju Wu, Cheng-Hsu Chen, Tung-Min Yu, Kuo-Hsiung Shu, on behalf of the CKDBHPDH investigators
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092881
Abstract: Background Currently, the contribution of kidney function decline in renal and patient outcomes is unclear. There are few data on the associations of different etiologies of estimated glomerular filtration rate (eGFR) decline with outcomes in multidisciplinary care. The purpose of this investigation was to establish whether eGFR decline in patients with disease is an important risk factor for developing end-stage renal disease (ESRD) and death. Methods From December 1, 2001 to December 31, 2011, 5097 adults with chronic kidney disease (CKD) received biochemical tests, physical examinations, a pathological examination, and a comprehensive questionnaire. We used linear regression models and multivariate Cox proportional hazards model to examine the outcome of eGFR decline in renal diseases with different etiologies. Results Mean age was 68.1±16.1 (standard deviation, SD) years, and 63.3% patients were male. In the studied cohort, 58.2% of the patients had systemic disease-related nephropathy (SDRN), 29.4% had primary renal diseases (PRDs), and 12.4% had other etiologies. The eGFR decline in SDRN had a significant association with dialysis in the Cox proportional hazards model [crude hazard ratio (HR) = 1.07, 95% confidence interval (CI), 1.04 to 1.10; adjusted HR 1.05, 95% CI, 1.02 to 1.08]. Diabetic nephropathy (DN) had the most severe eGFR decline in CKD stages 3, 4, and 5, and all contributed to the initiation of dialysis and death regardless of whether DN with or without eGFR decline was considered to be the cause. Although hypertensive nephropathy (HN) was related to significant acceleration of eGFR decline, it did not lead to poor outcome. There were still discrepancies between eGFR decline and outcomes in PRDs, hypertensive nephropathy, and lupus nephritis. Conclusions eGFR decline and CKD staging provide an informative guide for physicians to make proper clinical judgments in the treatment of CKD, especially SDRN. Poor control of the underlying systemic disease will thus lead to more rapid progression of SDRN.
Autoantibodies against Phospholipase A2 Receptor in Korean Patients with Membranous Nephropathy  [PDF]
Yun Jung Oh, Seung Hee Yang, Dong Ki Kim, Shin-Wook Kang, Yon Su Kim
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062151
Abstract: The data were presented in abstract form at the 45th meeting of the American Society of Nephrology, October 30-November 04 2012, San Diego, CA, USA. Circulating autoantibodies against M-type phospholipase A2 receptor (PLA2R) are important pathogenic antibodies of idiopathic membranous nephropathy (MN) in adults. However, previous studies on the clinical impact of anti-PLA2R antibodies demonstrated several limitations, including insufficient numbers of study subjects and different time points and methods for anti-PLA2R antibody measurement. To verify the clinical significance of anti-PLA2R antibodies in Korean patients with MN, we measured autoantibodies in serum samples obtained at the time of biopsy from a total of 100 patients with idiopathic MN who had not yet received immunosuppressive treatment. We detected anti-PLA2R antibody in 69 patients, and we observed that autoantibody reactivity reflected the severity of disease activity. Proteinuria and hypoalbuminemia were more severe in patients with anti-PLA2R than in those without the autoantibodies (2.95 g/g vs. 6.85 g/g, P = 0.003; 3.1 g/dL vs. 2.5 g/dL, P = 0.004, respectively). Additionally, the clinical severities worsened proportionally as the levels of anti-PLA2R antibodies increased (P = 0.015 and P for trend <0.001 for proteinuria and hypoalbuminemia, respectively). However, neither the levels nor the presence or absence of anti-PLA2R antibody showed a significant correlation with clinical outcomes, such as remission rate and time to remission. In conclusion, we observed that anti-PLA2R antibodies are highly prevalent in Korean patients with idiopathic MN and that they reflect the clinical disease activity before the administration of immunosuppressive treatment. However, the levels of anti-PLA2R antibody at the time of kidney biopsy may not predict the clinical outcomes in current clinical practice.
Patterns of warfarin use and subsequent outcomes in atrial fibrillation in primary care practices
Ewen E, Zhang Z, Simon TA, Kolm P, Liu X, Weintraub WS
Vascular Health and Risk Management , 2012, DOI: http://dx.doi.org/10.2147/VHRM.S34280
Abstract: tterns of warfarin use and subsequent outcomes in atrial fibrillation in primary care practices Original Research (1114) Total Article Views Authors: Ewen E, Zhang Z, Simon TA, Kolm P, Liu X, Weintraub WS Published Date October 2012 Volume 2012:8 Pages 587 - 598 DOI: http://dx.doi.org/10.2147/VHRM.S34280 Received: 26 May 2012 Accepted: 15 June 2012 Published: 19 October 2012 Edward Ewen,1 Zugui Zhang,1 Teresa A Simon,2 Paul Kolm,1 Xianchen Liu,3,4 William S Weintraub1 1Christiana Care Health System, Newark, DE, USA; 2Bristol-Myers Squibb, Princeton, NJ, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Pfizer, Groton, CT, USA Background: Warfarin is recommended for stroke prevention in high-risk patients with atrial fibrillation. However, it is often underutilized and inadequately managed in actual clinical practice. Objectives: To examine the patterns of warfarin use and their relationship with stroke and bleeding in atrial fibrillation patients in community-based primary care practices. Design: Retrospective longitudinal cohort study. Participants: A total of 1141 atrial fibrillation patients were selected from 17 primary care practices with a shared electronic medical record and characterized by stroke risk, potential barriers to anticoagulation, and comorbid conditions. Main measures: Duration and number of warfarin exposures, interruptions in warfarin exposure > 45 days, stroke, and bleeding events. Results: Among 1141 patients with a mean age of 70 years (standard deviation 13.3) and mean follow-up of 3.4 years (standard deviation 3.0), 764 (67%) were treated with warfarin. Warfarin was discontinued within 1 year in 194 (25.4%), and 349 (45.7%) remained on warfarin at the end of follow-up. Interruptions in warfarin use were common, occurring in 32.6% (249 of 764) of patients. Those with two or more interruptions were younger and at lower baseline stroke risk when compared to those with no interruptions. There were 76 first strokes and 73 first-bleeding events in the follow-up period. When adjusted for baseline stroke risk, time to warfarin start, and total exposure time, two or more interruptions in warfarin use was associated with an increased risk of stroke (relative risk, 2.29; 95% confidence interval: 1.29–4.07). There was no significant association between warfarin interruptions and bleeding events. Conclusion: Warfarin was underutilized in a substantial portion of eligible atrial fibrillation patients in these community-based practices. In addition, prolonged interruptions in anticoagulation were common in this population, and multiple interruptions were associated with over twice the risk of stroke when compared to those treated continuously.
Angiotensin II antagonists: clinical experience in the treatment of hypertension, prevention of cardiovascular outcomes and renal protection in diabetic nephropathy and proteinuria
Ribeiro, Artur Beltrame;Gavras, Haralambos;
Arquivos Brasileiros de Endocrinologia & Metabologia , 2006, DOI: 10.1590/S0004-27302006000200019
Abstract: angiotensin ii antagonists (aiias) were introduced to treat hypertension about 10 years ago. during this period they were evaluated not only in terms of efficacy and safety but also in several large studies with clinical outcomes. they are efficacious in all clinical forms of hypertension and are effective also in all ethnic groups. cardiovascular and renal protection in proteinuric diabetic nephropathy beyond blood pressure reduction was proved in major clinical studies: losartan intervention for endpoint reduction in hypertension study (life), reduction of endpoint in non-insulin dependent diabetes mellitus with the aii antagonist losartan (renaal) and irbesartan type 2 diabetic nephropathy trial (idnt). their blood pressure independent protective effect is also mentioned by the blockade of at1 receptor. as a class aiis have a tolerability profile similar to placebo.
Survey of Slaughtered Pigs for Occurrence of Ochratoxin A and Porcine Nephropathy in Serbia  [PDF]
Dragan Mili?evi?,Verica Juri?,Sr?an Stefanovi?,Milijan Jovanovi?,Sa?a Jankovi?
International Journal of Molecular Sciences , 2008, DOI: 10.3390/ijms9112169
Abstract: Samples of blood, kidney and liver were randomly selected from slaughtered pigs (n=90) and analyzed for ochratoxin A by HPLC. In addition, in order to obtain information on the occurrence of nephropathy, histological examinations were carried out. Of the 90 liver samples, 26.6% contained OTA in the range of 0.22-14.5 ng/g. The incidence of OTA in serum and kidney were very similar (31%, 33.3%), with a maximum concentration of 220.8 ng/mL, and 52.5 ng/g, respectively. Histopathological examination of kidneys confirmed tubulopathies with edema and cell vacuolization. In addition, hemorrhages and necrosis of proximal kidney tubules’ cells were found.
Pregnancy Outcomes and Appropriate Timing of Pregnancy in 183 pregnancies in Korean Patients with SLE  [cached]
Hyun Sun Ko, Hyun Young Ahn, Dong Gyu Jang, Sae-Kyung Choi, Yong-Gyu Park, In Yang Park, Guisera Lee, Sung-Hwan Park, Jong Chul Shin
International Journal of Medical Sciences , 2011,
Abstract: This study was undertaken to investigate the pregnancy outcomes in patients with systemic lupus erythematosus (SLE) and the appropriate timing of pregnancy. We performed a retrospective evaluation of 183 pregnancies with SLE at Catholic University Medical Center during the 13-year period from 1998 to 2010. Pregnancy outcomes were compared according to SLE characteristics. The predictive value of the different cut-off points of the stable period before conception on adverse pregnancy outcomes was calculated by ROC (Receiver operating characteristics) curve analysis. In multivariate analysis, the presence of antiphospholipid antibodies (aPLs) increased the risk of pregnancy loss (p<0.0001) and premature birth (p=0.0040). Active disease at conception increased the risk of premature birth (p< 0.0001) and complications (IUGR, PIH, or both) (p= 0.0078). The other predictor of complications was found to be lupus flare (p=0.0252). At a cut-off level of stable period of 4 months before conception, sensitivity and specificity were 70.8% and 53.2%, 71.4% and 61.5%, and 63.6 % and 59.8 %, respectively on reducing pregnancy loss, premature birth, and complications. Pregnancies with aPLs, active disease at conception and SLE flares are at a higher risk of adverse outcomes. It is essential that disease activity remains stable at least 4 months before conception, for favorable pregnancy outcomes.
Prevalence and Outcomes of Frailty in Korean Elderly Population: Comparisons of a Multidimensional Frailty Index with Two Phenotype Models  [PDF]
Hee-Won Jung, Sun-Wook Kim, Soyeon Ahn, Jae-Young Lim, Ji-Won Han, Tae-Hui Kim, Ki-Woong Kim, Kwang-il Kim, Cheol-Ho Kim
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087958
Abstract: Background Frailty is related to adverse outcomes in the elderly. However, current status and clinical significance of frailty have not been evaluated for the Korean elderly population. We aimed to investigate the usefulness of established frailty criteria for community-dwelling Korean elderly. We also tried to develop and validate a new frailty index based on a multidimensional model. Methods We studied 693 participants of the Korean Longitudinal Study on Health and Aging (KLoSHA). We developed a new frailty index (KLoSHA Frailty Index, KFI) and compared predictability of it with the established frailty indexes from the Cardiovascular Health Study (CHS) and Study of Osteoporotic Fracture (SOF). Mortality, hospitalization, and functional decline were evaluated. Results The prevalence of frailty was 9.2% (SOF index), 13.2% (CHS index), and 15.6% (KFI). The criteria from CHS and KFI correlated with each other, but SOF did not correlate with KFI. During the follow-up period (5.6±0.9 years), 97 participants (14.0%) died. Frailty defined by KFI predicted mortality better than CHS index (c-index: 0.713 and 0.596, respectively; p<0.001, better for KFI). In contrast, frailty by SOF index was not related to mortality. The KFI showed better predictability for following functional decline than CHS index (area under the receiver-operating characteristic curve was 0.937 for KFI and 0.704 for CHS index, p = 0.001). However, the SOF index could not predict subsequent functional decline. Frailty by the KFI (OR = 2.13, 95% CI 1.04–4.35) and CHS index (OR = 2.24, 95% CI 1.05–4.76) were associated with hospitalization. In contrast, frailty by the SOF index was not correlated with hospitalization (OR = 1.43, 95% CI 0.68–3.01). Conclusion Prevalence of frailty was higher in Korea compared to previous studies in other countries. A novel frailty index (KFI), which includes domains of comprehensive geriatric assessment, is a valid criterion for the evaluation and prediction of frailty in the Korean elderly population.
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