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      A Systematic Review of Prophylactic Anticoagulation in Nephrotic Syndrome

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          Abstract

          Introduction

          Nephrotic syndrome is associated with an increased risk of venous and arterial thromboembolism, which can be as high as 40% depending on the severity and underlying cause of nephrotic syndrome. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend prophylactic anticoagulation only in idiopathic membranous nephropathy but acknowledge that existing data are limited and of low quality. There is a need for better identification of vulnerable patients in order to balance the risks of anticoagulation.

          Methods

          We undertook a systematic search of the topic in MEDLINE, EMBASE and COCHRANE databases, for relevant articles between 1990 and 2019.

          Results

          A total of 2381 articles were screened, with 51 full-text articles reviewed. In all, 28 articles were included in the final review.

          Conclusion

          We discuss the key questions of whom to anticoagulate, when to anticoagulate, and how to prophylactically anticoagulate adults with nephrotic syndrome. Using available evidence, we expand upon current KDIGO guidelines and construct a clinical algorithm to aid decision making for prophylactic anticoagulation in nephrotic syndrome.

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          Adult minimal-change disease: clinical characteristics, treatment, and outcomes.

          Jennifer Crew, J Busch, B T Stokes … (2007)
          Minimal-change disease (MCD) counts for 10 to 15% of cases of primary nephrotic syndrome in adults. Few series have examined this disease in adults. A retrospective review was performed of 95 adults who had MCD and were seen at a single referral center. Examined were presenting features, response to daily versus alternate-day steroids, response to second-line agents, relapse patterns, complications of the disease and therapy, presence of acute renal failure (ARF), and outcome data. Sixty-five patients received daily and 23 received alternate-day steroids initially. There were no differences in remissions, time to remission, relapse rate, or time to relapse between daily- and alternate-day-treated patients. More than one quarter of patients were steroid resistant. At least one relapse occurred in 73% of patients; 28% were frequently relapsing. A significant proportion of frequently relapsing patients became steroid dependent. Second-line agents were used for steroid dependence, steroid resistance, or frequent relapses. No single agent proved superior. There were more remissions with second-line agents in steroid-dependent patients compared with steroid-resistant patients, and remissions were more likely to be complete in steroid-dependent patients. ARF occurred in 24 patients; they tended to be older and hypertensive with lower serum albumin and more proteinuria than those without ARF. At follow up, patients with an episode of ARF had higher serum creatinine than those without ARF. Four patients progressed to ESRD. These patients were less likely to have responded to steroids and more likely to have FSGS on repeat renal biopsy. In this referral MCD population, response to daily and alternate-day steroids is similar. Second-line agents give greater response in patients who are steroid dependent. ARF occurs in a significant number of adult MCD patients and may leave residual renal dysfunction. Few patients progress to ESRD.
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            Epidemiology and pathophysiology of nephrotic syndrome-associated thromboembolic disease.

            William E. Smoyer, Bryce Kerlin, Rose Ayoob (2012)
            After infections, thromboembolism is considered by many experts to be the most significant life-threatening complication of nephrotic syndrome. The purpose of this review is to summarize the epidemiology, clinical and molecular pathophysiology, and management of this complication. Children (2.8%) are less likely than adults (26.7%) with nephrotic syndrome to develop thromboembolism. However, infants and children aged >12 years are at much greater risk. Membranous histologic changes increase thromboembolic risk at all ages; in particular, adults with membranous nephropathy have the highest reported risk (37.0%) and children with membranous histology have a rate (25%) that approaches the overall adult rate. There are striking, but variable, pathologic alterations of molecular hemostasis associated with nephrotic syndrome. No clear molecular therapeutic targets have been identified, but most studies show that the major pathologic changes involve antithrombin, fibrinogen, and factors V and VIII. There is inadequate evidence to support routine prophylactic therapy. Therapy includes anticoagulation in all cases, with thrombolysis reserved for those with the most severe thromboembolic disease. Future hemostatic research in nephrotic syndrome should focus on identifying cohorts at highest risk for thrombosis through the use of clinical markers and biomarkers as well as searching for molecular targets to correct the prothrombotic pathophysiology of this disease.
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              High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study.

              Edith ten Broeke, Carlo P J M Brouwer, B. Mahmoodi … (2008)
              No data are available on the absolute risk of either venous thromboembolism (VTE) or arterial thromboembolism (ATE) in patients with nephrotic syndrome. Reported risks are based on multiple case reports and small studies with mostly short-term follow-up. We assessed the absolute risk of VTE and ATE in a large, single-center, retrospective cohort study and attempted to identify predictive factors in these patients. A total of 298 consecutive patients with nephrotic syndrome (59% men; mean age, 42+/-18 years) were enrolled. Mean follow-up was 10+/-9 years. Nephrotic syndrome was defined by proteinuria > or =3.5 g/d, and patients were classified according to underlying histological lesions accounting for nephrotic syndrome. Objectively verified symptomatic thromboembolic events were the primary study outcome. Annual incidences of VTE and ATE were 1.02% (95% confidence interval, 0.68 to 1.46) and 1.48% (95% confidence interval, 1.07 to 1.99), respectively. Over the first 6 months of follow-up, these rates were 9.85% and 5.52%, respectively. Proteinuria and serum albumin levels tended to be related to VTE; however, only the predictive value of the ratio of proteinuria to serum albumin was significant (hazard ratio, 5.6; 95% confidence interval, 1.2 to 26.2; P=0.03). In contrast, neither the degree of proteinuria nor serum albumin levels were related to ATE. Sex, age, hypertension, diabetes, smoking, prior ATE, and estimated glomerular filtration rate predicted ATE (P< or =0.02). This study verifies high absolute risks of symptomatic VTE and ATE that were remarkably elevated within the first 6 months. Whereas the ratio of proteinuria to serum albumin predicted VTE, estimated glomerular filtration rate and multiple classic risk factors for atherosclerosis were predictors of ATE.
              Article 0 comments Cited 94 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Bobby Chacko
                Journal
                Journal ID (nlm-ta): Kidney Int Rep
                Journal ID (iso-abbrev): Kidney Int Rep
                Title: Kidney International Reports
                Publisher: Elsevier
                ISSN (Electronic): 2468-0249
                Publication date PMC-release: 12 December 2019
                Publication date Collection: April 2020
                Publication date (Electronic): 12 December 2019
                Volume: 5
                Issue: 4
                Pages: 435-447
                Affiliations
                [1 ]Nephrology and Transplantation Unit, John Hunter Hospital, Newcastle, New South Wales, Australia
                [2 ]School of Medicine and Public Health, University of Newcastle, New South Wales, Australia
                Author notes
                [∗ ] Correspondence: Bobby Chacko, Nephrology and Transplantation Unit, John Hunter Hospital, Newcastle, New South Wales 2310, Australia; or School of Medicine and Public Health, University of Newcastle, New South Wales 2310, Australia. Bobby.Chacko@ 123456health.nsw.gov.au
                Article
                Publisher ID: S2468-0249(19)31570-0
                DOI: 10.1016/j.ekir.2019.12.001
                PMC ID: 7136344
                PubMed ID: 32274450
                SO-VID: 46bfc222-6ebe-46cc-ad2f-f4a97eebb636
                Copyright © © 2019 International Society of Nephrology. Published by Elsevier Inc.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 17 October 2019
                Date revision received : 27 November 2019
                Date accepted : 2 December 2019
                Categories
                Subject: Clinical Research

                Keywords: anticoagulation,arterial thromboembolism,nephrotic syndrome,prophylaxis,venous thromboembolism
                Data availability:
                Keywords: anticoagulation, arterial thromboembolism, nephrotic syndrome, prophylaxis, venous thromboembolism

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