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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

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      A Prospective Observational Survey on the Long-Term Effect of LDL Apheresis on Drug-Resistant Nephrotic Syndrome

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          Abstract

          Background/Aims: LDL apheresis (LDL-A) is used for drug-resistant nephrotic syndrome (NS) as an alternative therapy to induce remission by improvement of hyperlipidemia. Several clinical studies have suggested the efficacy of LDL-A for refractory NS, but the level of evidence remains insufficient. A multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was conducted to evaluate its clinical efficacy with high-level evidence. Methods: Patients with NS who showed resistance to primary medication for at least 4 weeks were prospectively recruited to the study and treated with LDL-A. The long-term outcome was evaluated based on the rate of remission of NS 2 years after treatment. Factors affecting the outcome were also examined. Results: A total of 58 refractory NS patients from 40 facilities were recruited and enrolled as subjects of the POLARIS study. Of the 44 subjects followed for 2 years, 21 (47.7%) showed remission of NS based on a urinary protein (UP) level <1.0 g/day. The UP level immediately after LDL-A and the rates of improvement of UP, serum albumin, serum creatinine, eGFR, and total and LDL cholesterol after the treatment session significantly affected the outcome. Conclusions: Almost half of the cases of drug-resistant NS showed remission 2 years after LDL-A. Improvement of nephrotic parameters at termination of the LDL-A treatment was a predictor of a favorable outcome.

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          Lipid nephrotoxicity in chronic progressive glomerular and tubulo-interstitial disease.

          Thomas Moorhead, Z Varghese, Wafaa El-Sadr … (1982)
          It is hypothesised that chronic progressive kidney disease may be mediated by abnormalities of lipid metabolism. A series of self-perpetuating secondary events follows an initial glomerular injury. Increased glomerular basement membrane permeability leads to loss of lipoprotein lipase activators, resulting in hyperlipidaemia. Circulating low-density lipoprotein binds with glycosaminoglycans in the glomerular basement membrane and increases its permeability. Filtered lipoprotein accumulates in mesangial cells and stimulates them to proliferate and produce excess basement membrane material. The proximal tubular cells metabolise some of the filtered lipoprotein and the remainder are altered on passage down the nephron. Luminal apoprotein precipitates, initiating or aggravating tubulo-interstitial disease, if the intraluminal pH is close to the isoelectric point of the apoprotein. The hypothesis offers new approaches to the study of chronic progressive kidney disease by proposing a major pathogenetic role for lipid abnormalities.
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            Prognostic factors in mesangial IgA glomerulonephritis: an extensive study with univariate and multivariate analyses.

            E Alamartine, J C Sabatier, C Guérin … (1991)
            To clarify the risk factors for chronic renal failure in idiopathic IgA glomerulonephritis (IgA-GN), we performed a dual study on 282 patients using both standard univariate statistical methods and the multivariate regression model of Cox. During a follow-up ranging from 1 to 36 years, with a mean of 8 years, 18% of the patients (50/282) had gone into chronic renal failure (CRF), with 18 of them in end-stage renal disease (ESRD) (6%). The univariate comparison of patients with CRF versus patients without CRF showed multiple risk factors: mainly arterial hypertension, an amount of proteinuria, nephrotic syndrome, a high level of serum IgA, presence of HLA-B35 antigen, and the intensity of most pathological lesions on light microscopy. The actuarial survival rate for a normal renal function (serum creatinine less than 135 mumol/L [1.5 mg/dL]) was 84% at 10 years and 64% at 20 years. The multivariate study allowed the isolation of only four risk factors with a significant effect on survival rate. These were the amount of proteinuria, the global optical score on first renal biopsy, the presence of an initial hypertension, and the presence of the HLA-B35 antigen. From these results, the probability of renal survival for individual patients may be calculated and a high-risk subgroup defined. Our data confirm the greater usefulness of multivariate over univariate statistical analyses in finding risk factors for CRF in IgA-GN.
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              Factors predicting progression of IgA nephropathies.

              Rosanna Coppo, Giuseppe D’Amico (2015)
              The difficulties in defining the natural history of primary IgA nephropathy (IgAN) depend upon the pre-selection of patients for renal biopsy, a true individual variability - ranging from asymptomatic to rapidly progressive forms - as well as the use of different classifications of the renal lesions and statistical analyses sometimes carrying incorrect modalities. Long-term natural history studies have demonstrated that the rate of progression has an extremely wide range, from 5 to 25% after 10 years and 25-50% at 20 years, and complete remission is reported as well in 5 to 30% of cases. A geographic variability has been confirmed in a tri-continental study, explainable only partly by the earlier referral. Among the factors predicting progression, the more frequent in cohorts showing worse actuarial survival at 10 years are those associated with the advanced phases of renal damage, as increased creatinine level, arterial hypertension and nephrotic range proteinuria. A multivariate statistical approach showed the relevance of proteinuria during follow-up (percent duration of massive proteinuria or proteinuria at 1 year) more than proteinuria at the onset. Mean blood pressure value (MAP) and proteinuria during follow-up were independent predictors of end-stage CKD. Note the predictive value of severe microscopic hematuria in several studies. As far as histological features are concerned, strong independent predictors of progression at Cox multivariate analysis are the severity of glomerular sclerosis and interstitial fibrosis. The presence of crescents was a risk factor in almost all studies at univariate analysis, but did not maintain a significant predictor value at multivariate analysis. Conversely the association between crescents and tuft adhesions, possibly resulting from previous segmental necrosis, was found to be a significant risk factor. The extent of mesangial proliferation and parietal expansion of deposits was not significantly associated to unfavourable prognosis at multivariate analysis. The analysis of risk factors for progression of IgAN related to Henoch-Schoenlein purpura (HSP) failed to demonstrate any prognostic value for the presence and severity of extra-renal signs of vasculitis or presence of triggering factors. At multivariate Cox analysis, age and mean proteinuria during follow-up were powerful independent prognostic predictors. Proteinuria at baseline was not significantly related to renal progression, nor were hypertension or impaired renal function at onset. It is of interest that data at onset and at renal biopsy (renal function impairment, hypertension, nephrotic-range proteinuira) were not significantly related with renal detrimental progression. Neither had prognostic value the finding of crescents involving up to 75% of glomeruli.
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                Author and article information

                Journal
                Journal ID (publisher-id): NNE
                Journal ID (pmc): NNE
                Journal ID (doi): 10.1159/issn.1664-5529
                Title: Nephron Extra
                Publisher: S. Karger AG
                ISSN (Electronic): 1664-5529
                Publication date Subscription-year: 2015
                Publication date Collection: May – August 2015
                Publication date (Electronic): 29 August 2015
                Volume: 5
                Issue: 2
                Pages: 58-66
                Affiliations
                aDivision of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Institute, bDepartment of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, and cDepartment of Pediatrics, Kinki University School of Medicine, Osaka, dRyoshukai Takaishi Fujii Hospital, Takaishi, eDepartment of Diabetes, Metabolism and Endocrinology, and fDivision of Nephrology, Department of Medicine, Showa University School of Medicine, gDepartment of Pediatric Nephrology, Tokyo Women's Medical University, hDepartment of Internal Medicine, Teikyo University School of Medicine, iDepartment of Nephrology, Nippon Medical School, and jSiratori Clinic, Tokyo, kDepartment of Nephrology and Hypertension, Internal Medicine, St. Marianna University School of Medicine, Kawasaki, lDepartment of Nephrology, Hypertension, Diabetology, Endocrinology and Metabolism, Fukushima Medical University School of Medicine, Fukushima, mDivision of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, nDepartment of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, oDepartment of Laboratory Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, pDepartment of Nephrology, Fujita Health University School of Medicine, Toyoake, qDivision of Nephrology and Rheumatology, Department of Internal Medicine, and rGeneral Medical Research Center, Faculty of Medicine, Fukuoka University, Fukuoka, sDivision of Nephrology, Kanayama Clinic, and tDepartment of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, uKodama Hospital, Wakayama, vHiroshima Kidney Organization, Hiroshima, and wNakayamadera Imai Clinic, Takarazuka, Japan
                Author notes
                *Dr. Eri Muso, Division of Nephrology and Dialysis, Kitano Hospital, Tazuke Kofukai Medical Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480 (Japan), E-Mail muso@kitano-hp.or.jp
                Article
                Publisher ID: 437338 Pmcid ID: PMC4592509 Other ID: Nephron Extra 2015;5:58-66
                DOI: 10.1159/000437338
                PMC ID: PMC4592509
                PubMed ID: 26557843
                SO-VID: 442d0a66-41a4-452f-87f1-d4baa8d0317d
                Copyright © © 2015 The Author(s) Published by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 2, Tables: 4, References: 33, Pages: 9
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Urinary protein,Nephrotic syndrome,POLARIS study,Prospective study,LDL apheresis,Drug-resistant nephrotic syndrome,Long-term outcome
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Urinary protein, Nephrotic syndrome, POLARIS study, Prospective study, LDL apheresis, Drug-resistant nephrotic syndrome, Long-term outcome

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