Your article #3579 from the Clinical Journal of the American Society of Nephrology is available fordownload. _______________________ The Clinical Journal of the American Society of Nephrology is published by The American Society ofNephrology. Dear Author: Congratulations on having your manuscript "Recurrence of Secondary Glomerular Disease after RenalTransplantation: An In-Depth Review" accepted for publication in the Clinical Journal of the AmericanSociety of Nephrology! Your proof is available for review at:http://rapidproof.cadmus.com/RapidProof/retrieval/index.jspLogin: your e-mail addressPassword: 88JQxEn9mSLF Adobe Acrobat® Reader software is needed to read the PDF file of your article. The free software can bedownloaded at:http://www.adobe.com/products/acrobat/readstep.html. The PDF file includes: 1) a publication fee and reprint order form, 2) a proofreading marks guide, and 3) theproofs of your manuscript. Please view or print the PDF file, read the page proofs carefully and:- return the publication fee and reprint order form with payment directly to the address specified on the orderform;- mark changes or corrections in the margins of the page proofs or directly on the PDF using the guidelinesprovided;- answer all queries (AQ:A, AQ:B, AQ:C, etc.) on the last page of the proof;- proofread all contributing author names, tables, and equations carefully;- check that Greek characters have been translated properly;- check figure numbering, positioning, cropping, and quality of the image against your original figures; and- note concerns about figure quality (if any) in the margin of the relevant page. The final printed version of the figures will be of better quality than the proof. The PDF proof does notshow a true rendering of color figures. Modifications to the figures are not allowed unless requested by theeditorial office or when the quality of the image at the proof stage seems insufficient. Iris proofs of colorfigures are available for review upon request. WITHIN 24 HOURS, please return the following to my attention either by fax, email, or expediated mail atthe address below and INCLUDE YOUR ARTICLE NO. (3579) WITH ALL CORRESPONDENCE:1. the page proofs with corrections; and2. electronic files of figures needing correction. Proofs are a work in progress, property of ASN, and not meant for distribution to those outside of theeditorial process. ASN retains the copyright at all times. An author must not forward the proof or publishedPDF of his/her manuscript. The author may instruct those who request digital copies of his/her manuscript,to obtain access to the PDF via http://www.asn-online.org/publications/. Within 12 months of publication,publications are accessible only to ASN members and paid subscribers, and accessible via pay-per-view.Twelve months after publication, the publications are openly accessible. Sincerely,

Clinical Journal of the American Society of NephrologyCopy of e-mail Notification cjn3579

Jessica HeiseJournal Production ManagerCadmus Communications, a Cenveo companyPublisher Services Group8621 Robert Fulton Dr., Suite 100Columbia, MD 21046Tel: (410) 694-4176Fax: (410) 684-2792E-mail: Jessica.Heise@cenveo.comwww.cenveo.com

Instructions for Authors

T he Clinical Journal of the American Society of Nephrology(CJASN) is a monthly publication of the American Soci-ety of Nephrology (ASN). It was first published in 2006.

Scope of PublicationCJASN publishes original manuscripts that present high-qual-

ity clinical research that is relevant to the broad area of clinicalnephrology, hypertension, organ transplantation, and criticalcare. Accepted articles will be judged by peer review to berelevant to the clinical care of patients. Topic areas includestudies of clinical outcomes, natural history of renal diseases,chronic kidney disease, dialysis, hypertension, metabolism/physiology, cardiovascular disease in the context of renal dys-function, diagnostic/therapeutic interventions in renal disease,pharmacokinetics, and critical care medicine. CJASN’s contentalso includes solicited review articles, special features, and ed-ucational materials focused on the clinical aspects of nephrol-ogy.

CJASN considers the following categories of manuscripts:

Original Articles

• Word limit: 3000• Abstract word limit: 250• Reference limit: 50• Figure limit: 4• Table limit: 4

Supplemental material that is of interest to the readership, suchas additional figures or tables, is welcome and will be postedonline. If you submit supplemental files that may only be postedonline, then upload one PDF file that contains all of the supple-mental information.

Editorials. Editorials are invited by the editors. Word limit is1500, and no abstract is required.

Mini-Reviews. Mini-reviews are invited by the editors.Word limit is 2000, and reference limit is 50. These will be sentout for peer review.

In-Depth Reviews. In-depth reviews are invited by the ed-itors. Word limit is 3000, and reference limit is 100. These will besent out for peer review.

Expedited Reports. Authors who believe that their findingsare of unusual interest or importance to nephrology are invitedto submit a more succinct report to be considered for acceleratedreview and publication in the category Expedited Reports. Thegoal of Expedited Reports is the rapid publication of new find-ings that are of unique importance in clinical research or thatlead to a new direction in research.

Word limit is 2000, abstract word limit is 150, figure limit is 3,and reference limit is 50. Materials and Methods should becondensed to the essentials required for review, and the Resultsand Discussion sections may be combined. Manuscripts shouldotherwise meet the criteria listed for submission to CJASN.Letters of submission must contain a succinct description of whythe paper should be considered for publication as an ExpeditedReport.

Manuscripts submitted as an Expedited Reports will be peer-reviewed through the usual process and considered for publi-cation only if they are acceptable with no or very minor revi-sions, thereby removing the usual time required for revisions.

They will be published in the next available issue after accep-tance. Manuscripts that are not selected for publication as Ex-pedited Reports may be expanded and submitted as regularoriginal articles.

Submissions that do not meet these guidelines will be re-turned without further review.

Cover Image. The editors welcome the submission of high-resolution cover photographs. These pictures must be saved asTIFF files using CMYK rather than RGB color. The resolutionspecification for TIFF files should be 1200 dpi for monochromefigures that are black and white and 600 dpi for CMYK colorphotographs; all submissions should be accompanied by a brieflegend. To submit your image, go to www.cjasn.org, click on“Submit Manuscripts Online,” and select manuscript type “Un-solicited Feature.”

Manuscript SubmissionCJASN requires manuscripts to be submitted online through

Manuscript Central at http://mc.manuscriptcentral.com/cjasn,or from www.cjasn.org, click on “Online Submission.” An ac-count is required for the submission process; authors should usetheir existing account or create a new account by following theinstructions at http://mc.manuscriptcentral.com/cjasn.

Manuscript Central SupportIf at any time during the online submission process you have

a question or need help, click on “Get Help Now” in the upperright corner of each page.

Manuscript PreparationManuscripts must be typed in English and double-spaced

with line numbers and page numbers. The title page shouldinclude the manuscript title; all authors’ full names (first name,middle initial, last name); highest academic degrees and affili-ations; the name, address, telephone and fax numbers, ande-mail address of the corresponding author; a running title; andkey words. It should also include the word count for the abstractand the word count for the text, excluding references, figures,and tables.

Abstract

• The use of abbreviations is discouraged. Any abbreviations usedmust be defined in the abstract.

• The abstract should be less than 250 words. It should consist offour paragraphs labeled as follows:

• Background and objectives• Design, setting, participants, and measurements• Results• Conclusions

Text

• Double-spaced• Abstract (structured, less than 250 words)• Introduction• Materials and Methods• Results• Discussion

Copyright © 2011 by the American Society of Nephrology

• Acknowledgments (include funding information)• References (50 or fewer for original articles)• Tables (all cited) with appropriate descriptive titles• Figures and legends (all cited)

Presentation of Results. Follow these guidelines for thepresentation of data within the text, tables, and figures:

• For parameter estimates (e.g., relative risks, hazard ratios, �values), use 95% confidence intervals whenever possiblerather than P values.

• Do not use “NS” for P values; provide the actual P values.• P values should have only two significant decimal places;

however, lower values (e.g., 0.002) are acceptable. Valuessmaller than 0.001 should be listed as �0.001.

Figures. The fee for publishing color figures is $600.00 perprinted journal page. Authors must pay the cost of color pages.(Figures submitted in color will be published in color.) Figuresmust be cited in the text, in numerical order, using Arabicnumerals.

If your manuscript is accepted, the Editorial Office will re-quire you to upload your figures as high-resolution EPS or TIFFfiles. These will also need to pass Rapid Inspector, an artworkreview program designed to check figures for compliance withthe printer’s requirements (http://rapidinspector.cadmus.com/asn). If a figure does not meet the requirements, RapidInspector will indicate that the graphic has failed, give a briefsummary of the problem, and suggest methods to correct theproblem. Therefore, we recommend that graphics be pre-pared using a program that can save files in a format that canultimately be saved and submitted as EPS or TIFF. Graphicsshould be saved in CMYK (cyan, magenta, yellow, black)rather than RGB (red, green, blue). The resolution specifica-tion for TIFF and EPS files is 1200 dpi for monochrome (i.e.,figures that are black and white only) and line shots; 300 dpifor gray/CMYK or color photographs; and 600 dpi for com-binations, such as photographs labeled with letters or othermarkings.

Graphic Preparation Guidelines

• Figures that are similar in appearance should be created to look“uniform” (e.g., in bar graphs, the bars should be the same widthfor all figures).

• One-column figures: Create with a width of 2.5 to 3.5 inches.• Two-column figures: Create with a width between 5 and 7

inches.• The type within the figure should be set in 6-point type, using

fonts of Times New Roman, Helvetica, or Arial.• Figure labels should be set 10-point Helvetica, bold caps, upper

left corner.• Supply the source file whenever possible.• When providing a multipart figure, space between parts should

be 0.2 inches.• When submitting line shots, submit as vector .eps figures when-

ever possible.

References. Limit references to 50 per original article. List allauthors for each article cited. Journal names should be abbrevi-ated according to the BIOSIS list of serials.

Journal articles, books, and abstracts:

1. Holden RM, Harman GJ, Wang M, Holland D, Day AJ:Major bleeding in hemodialysis patients. Clin J Am SocNephrol 3: 105–110, 2008

PoliciesEmbargo Policy. All information regarding the content and

publication date of accepted manuscripts is strictly confidential.Information contained in or about accepted articles may notappear in print, on radio or television, or in electronic form or bereleased by the news media until after 5 p.m. ET on the day thearticle appears in the Publish-before-Print page on the CJASNweb site (CJASN ePress) or on the day the published version ofCJASN is mailed, whichever comes first. This policy is not meantto inhibit the presentation of the work to or its discussion amongother researchers. For information about publication dates forspecific articles, contact Bob Henkel at 202-557-8360 or e-mailbhenkel@asn-online.org.

Access. ASN recognizes and strongly supports the efforts ofsponsoring agencies and institutions to increase access to theresearch that they fund. On behalf of its authors, CJASN submitsall original research articles directly to PubMed Central, wherethey will be freely available within 12 months of publication. Inaddition, in response to the requirement of some funding agen-cies for the research that they fund to be freely available imme-diately upon publication and their willingness to cover the costsassociated with doing so, CJASN offers the Author Choice pro-gram (see below), whereby, for an additional fee, articles aremade freely available immediately upon publication. In addi-tion, authors are encouraged to archive their version of themanuscript in their institution’s repositories (as well as on theirpersonal web sites). Authors should cite the publication refer-ence and doi number on any deposited version and provide alink from it to the published article on the CJASN web site.CJASN articles are also freely available to researchers in devel-oping countries through the Health InterNetwork Access toResearch Initiative (HINARI).

Transfer of Copyright. ASN requires authors of submittedpapers to assign to ASN copyright of their published contribu-tions. CJASN’s author copyright license form (http://mc.manu-scriptcentral.com/cjasn) provides details of the policy. Aftersubmission of an article, each author will receive an e-mail witha link to a copyright form. Each author must sign and date theform and submit electronically. This is done through Manu-script Central and will guarantee that each author understandsand consents to our publication policy.

Duplicate Submission/Redundant Publication. All manu-scripts submitted to CJASN must include in the cover letter astatement indicating that neither the manuscript nor any signif-icant part of it is under consideration for publication elsewhereor has appeared elsewhere in a manner that could be construedas a previous or duplicate publication of the same or verysimilar work. Abstracts for scientific meetings are not consid-ered previous publication but should be cited in the Acknowl-edgments section. Should there be doubt concerning such pre-vious publications, all related manuscripts submitted forpublication at other journals should be included with the sub-mitted paper.

Authors and Contributors. With regard to authorship credit,ASN journals have adopted the criteria recommended by the In-ternational Committee of Medical Journal Editors (ICMJE) in thecurrent update of the Uniform Requirements for Manuscripts Sub-mitted to Biomedical Journals: “Authorship credit should be based

Clinical Journal of the American Society of Nephrology

on 1) substantial contributions to conception and design, or acqui-sition of data, or analysis and interpretation of data; 2) drafting thearticle or revising it critically for important intellectual content; and3) final approval of the version to be published. Authors shouldmeet conditions 1, 2, and 3.” Note the full text of the UniformRequirements for Manuscripts Submitted to Biomedical Journals(www.icmje.org/). In addition, with regard to contributors, ASNjournals have adopted the following statement of editorial policyfrom the Information for Authors (www.annals.org/shared/au-thor_info.shtml) of the Annals of Internal Medicine: “Medical writ-ers and industry employees can be legitimate contributors, andtheir roles, affiliations, and potential conflicts of interest should bedescribed when submitting manuscripts. These writers should re-ceive acknowledgment on the byline or in the Acknowledgmentssection in accord[ance] with the degree to which they contributedto the work reported in the manuscript. The Editors considerfailure to acknowledge these contributors ghostwriting, and ghost-writing is unacceptable.”

Declaration of Helsinki. For all clinical experimentation de-scribed in the manuscript, CJASN requires that authors state inthe Methods section their adherence to the Declaration of Hel-sinki. A statement that informed consent was obtained mustalso appear in the manuscript. Also specify the name of theinstitutional review board or equivalent that approved thestudy. For the full text of the Declaration of Helsinki, seewww.wma.net/en/30publications/10policies/b3/index.html.

Animal Experimentation. For all animal experimentation de-scribed in the manuscript, CJASN requires that authors state inthe Methods section their adherence to the NIH Guide for theCare and Use of Laboratory Animals or the equivalent. For thefull text of the NIH guidelines, see http://grants.nih.gov/olaw/references/phsol.htm.

Statement of Financial Support. CJASN requires authors todivulge any relationships with pharmaceutical firms or otherentities (e.g., employment contracts, consultancy, advisoryboards, speaker bureaus, membership of Board of Directors,stock ownership) that could be perceived to represent a financialconflict of interest by completing the CJASN author disclosureform or to declare that no financial conflict of interest exists.Financial conflict of interest statements will be published at theend of the text of the article.

Permission to Reprint Letters. Letters granting permission toreprint must be included from the publisher and author of allpreviously printed or adapted material. They should be up-loaded during the submission process as supplemental files.

Requirement for Registration of Clinical Trials. As a condi-tion of consideration for publication, CJASN requires registra-tion in a public trials registry. Trials must register at or beforethe onset of patient enrollment. This policy applies to any clin-ical trial starting enrollment after January 1, 2006. For trials thatbegan enrollment before this date, CJASN requires registrationby April 1, 2006, before considering the trial for publication. Wedefine a clinical trial as any research project that prospectivelyassigns human subjects to intervention or comparison groups tostudy the cause-and-effect relationship between a medical inter-vention and a health outcome. Studies designed for other pur-poses, such as to study pharmacokinetics or major toxicity (e.g.,phase 1 trials) are exempt. We do not advocate one particularregistry, but registration must be with a registry that meets thefollowing minimum criteria: Accessible to the public at nocharge, searchable by standard electronic (Internet-based) meth-ods, open to all prospective registrants free of charge or at

minimal cost, validation of registered information, and identifi-cation of trials with a unique number. An acceptable registryalso includes information on the investigator(s), the researchquestion or hypothesis, methodology, intervention and compar-isons, eligibility criteria, primary and secondary outcomes mea-sured, date of registration, anticipated or actual start date, an-ticipated or actual date of last follow-up, target number ofsubjects, status (anticipated, ongoing, or closed), and fundingsource(s). The registration number and the date of registrationshould be provided on the title page.

Registries that currently meet these criteria include the fol-lowing:

• The registry sponsored by the US National Library of Medi-cine (www.clinicaltrials.gov)

• The International Standard Randomized Controlled Trial Num-ber registry (www.controlled-trials.com)

• The Cochrane Renal Group registry (www.cochrane-renal.org)• The National (UK) Research Register (www.update-software-

.com)• European Clinical Trials Database (http://eudract.emea.eu.int/)

ASN Policy on Scientific Misconduct. ASN journals upholdthe highest standards of peer review and academic publishing.The work of authors and reviewers contributes to our commonaim of understanding the latest advances in basic, clinical, andtranslational research. In very rare instances, editors receivenotification or allegations of misconduct related to studies sub-mitted to ASN journals, and our process for responding to suchnotification is detailed next.

Concerns raised before publication:If a reviewer or a concerned co-author raises a question about

a manuscript that is undergoing peer review and the Editor-in-Chief agrees, then we will notify the author(s) and request aresponse to the reviewer’s concerns. (Such concerns include butare not limited to questions regarding plagiarism, duplicatepublication, access to data, and integrity of data or undeclaredconflicts of interest.) In most instances, these concerns are read-ily addressed and resolved and involve honest errors or differ-ences in interpretation rather than any intent to deceive.

If the authors do not respond satisfactorily (or at all) to theconcerns raised or if the Editor-in-Chief is presented with evi-dence that indicates serious concerns regarding the conduct ofthe study, then the Editor-in-Chief will notify the Chair of theCommunications Committee and will determine a course ofaction, in part determined by applicable laws, which may in-clude any or all of the following:

a. rejecting the manuscriptb. prohibiting future submissions from the authors of the man-

uscript for a specified period of timec. obtaining an advisory opinion from the Committee on Pub-

lication Ethics (COPE)d. reporting their concerns to the authors’ institutionse. reporting their concerns to the funding agencyf. reporting their concerns to the Office of Research Integrity or

other authorized investigative agency

If the matter has been deemed serious enough to warrant theattention of the Publications Committee, then the Communica-tions Chair will keep the ASN President informed of all devel-opments.

Concerns raised after electronic and/or print publication:If questions are raised by a reader regarding a published

Instructions to Authors

study and the Editor-in-Chief agrees, then the journal will notifythe author(s) and request a response to the stated concerns.(Such concerns include but are not limited to questions regard-ing plagiarism, duplicate publication, access to data, and integ-rity of data or undeclared conflicts of interest.) In most in-stances, these concerns are readily resolved and involve honesterrors or differences in interpretation rather than any intent todeceive.

If the authors do not respond satisfactorily (or at all) to theconcerns raised or if the editors are presented with evidencethat indicates serious concerns regarding the conduct of thestudy, then the Editor-in-Chief will notify the Chair of theCommunications Committee and determine a course of ac-tion, in part determined by applicable laws, which may in-clude any or all of the following:

a. reporting their concerns to the authors’ institutionsb. prohibiting future submissions from the authors of the man-

uscript for a specified period of timec. obtaining an advisory opinion from the Committee on Pub-

lication Ethics (COPE)d. reporting their concerns to the funding agencye. reporting their concerns to the Office of Research Integrity or

other authorized investigative agencyf. publishing a statement of concern in the journalg. issuing a retractionh. notifying any other publication involved (in the case of du-

plicate publication or plagiarism)

If the matter has been deemed serious enough to warrant theattention of the Communication Committee, then the Publica-tions Chair will keep the ASN President informed of all devel-opments.

Review ProcessIt is the policy of CJASN to expedite manuscript review.

Manuscripts that are judged by the Editor-in-Chief and DeputyEditor to fall below the top 50% of manuscripts submitted toCJASN or that fail to satisfy technical requirements may bepromptly returned to the authors without further review. Arti-cles in the top 50% will be sent for review. All manuscripts willbe reviewed by at least two reviewers in addition to the Asso-ciate Editor. On the basis of the reviewers’ comments and rec-ommendations, a decision will be made to allow the authors torevise and resubmit (either as a major or minor revision) or toreject and not consider further. Revised manuscripts should beresubmitted within 90 days. Most revised manuscripts will besent out for review again. On the basis of the responsiveness ofthe authors and the reviewers’ comments, a decision will bemade to accept, request additional revisions, or reject. Note thatnot all manuscripts that are revised and resubmitted will beaccepted.

Submitting a Revised ManuscriptIf you received a decision letter on your submission that

indicated that CJASN would reconsider your manuscript if re-visions are made, then you can create a revision by clicking onyour Corresponding Author Center, then clicking on Manu-scripts with Decisions. You will then click on Create a Revisionon the specific manuscript. You may then follow the prompts tocontinue submission of the revised version.

Accepted ManuscriptsAfter a manuscript has been accepted for publication, the au-

thors will need to upload a final set of files as a revised manuscript.The text and tables will need to be submitted as a Word Document(one file) and the figures as either TIFF or EPS files. Use RapidInspector at http://rapidinspector.cadmus.com/asn. This pre-flight program will check graphics for compliance and printerrequirements. If your graphic fails, then Rapid Inspector will sug-gest methods to correct the problem. Manuscripts submitted toCJASN with failed graphics will be charged a $25.00 failed figurefee and returned to the author for correction.

Material submitted for online publication only should be up-loaded in one PDF file as a supplemental file.

On behalf of its authors, CJASN submits all original researcharticles directly to PubMed Central, where they will be freelyavailable within 12 months of publication.

Author ChoiceAuthors may choose to have the digital posting of his/her man-

uscript freely accessible as soon as the issue is posted onlinethrough a program called, “Author Choice”. The “Author Choice”flat fee to make an author’s manuscript openly accessible when theissue is posted online is $3,000, which must be prepaid before themanuscript can be made accessible. Authors will have the oppor-tunity to make this choice when page proofs and invoice arereceived.

ProofsManuscripts will be copyedited, and electronic proofs will be

made available for author approval. Authors will be notified bye-mail when their proofs are ready. Download, print, read,correct, and return the proofs within 48 hours. Be sure that all ofthe editor’s or printer’s queries are answered. Only minor cor-rections are permitted.

Publication Fees• Page charges: Authors will be charged $70.00 per manuscript

page.• Color charges: Authors will be charged $600.00 per color page.

(Figures submitted in color will be published in color.)• Failed figure charges: Authors will be charged $25.00 per failed

figure.

Invited reviews and editorials are exempt from these charges.

ReprintsAuthors of articles published in CJASN will receive reprint

order forms with the page proofs. Alternatively, reprints may beordered via Cadmus Professional Communications. ContactMenna Burgess, Reprint Account Manager, at burgessm@cadmus.com or 410-943-3147.

Pricing includes the purchase of reprints by the author(s) forpersonal use only. Nonauthors can purchase reprints via Sheri-dan Content Services. Contact Hope Robinson at 800-635-7181,ext. 8065, or hrobinson@tsp.sheridan.com.

Contact InformationBonnie O’Brien, Managing Editor3324 W. University Avenue, PMB #269Gainesville, FL 32607Phone: 352-35-1100Fax: 352-335-8100E-mail: bonnie@acceleration.net

Clinical Journal of the American Society of Nephrology

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Recurrence of Secondary Glomerular Disease afterRenal Transplantation: An In-Depth ReviewClaudio Ponticelli,* Gabriella Moroni,† and Richard Glassock‡

SummaryThe risk of a posttransplant recurrence of secondary glomerulonephritis (GN) is quite variable. Histologic re-currence is frequent in lupus nephritis, but the lesions are rarely severe and usually do not impair the long-term graft outcome. Patients with Henoch-Schonlein nephritis have graft survival similar to that of other re-nal diseases, although recurrent Henoch-Schonlein nephritis with extensive crescents has a poor prognosis.Amyloid light-chain amyloidosis recurs frequently in renal allografts but it rarely causes graft failure. Amy-loidosis secondary to chronic inflammation may also recur, but this is extremely rare in patients with Beh-cet’s disease or in those with familial Mediterranean fever, when the latter are treated with colchicine. Dou-ble organ transplantation (liver/kidney; heart/kidney), chemotherapy, and autologous stem celltransplantation may be considered in particular cases of amyloidosis, such as hereditary amyloidosis or multi-ple myeloma. There is little experience with renal transplantation in light-chain deposition disease, fibrillary/immunotactoid GN, or mixed cryoglobulinemic nephritis but successful cases have been reported. Diabeticnephropathy often recurs but usually only after many years. Recurrence in patients with small vessel vasculi-tis is unpredictable but can cause graft failure. However, in spite of recurrence, patient and graft survivalrates are similar in patients with small vessel vasculitis compared with those with other renal diseases. Manysecondary forms of GN no longer represent a potential contraindication to renal transplantation. The mainissues in transplantation of patients with secondary GN are the infectious, cardiovascular, or hepatic compli-cations associated with the original disease or its treatment.

Clin J Am Soc Nephrol 6: ●●●–●●●, 2011. doi: 10.2215/CJN.09381010

IntroductionThe possibility of recurrence in a renal transplant ofthe original disease that lead to end-stage renal dis-ease has been known for almost 50 years (1). We haverecently reviewed the topic of recurrence of primaryglomerular disease in renal grafts (2) and here we willreview the topic of recurrence of secondary glomerularand vascular diseases, including lupus nephritis, He-noch-Schonlein nephritis, amyloidosis, light-chaindeposition disease, fibrillary/immunotactoid glo-merulonephritis cryoglobulinemic nephritis, dia-betic nephropathy, and small vessel vasculitis. Em-phasis will be placed on recent developments.

Lupus NephritisThe reported risk of recurrence of lupus nephritis

(LN) after renal transplantation has been quite vari-able. Some investigators found that the recurrencerate was quite low, �5% (3–9), whereas others re-ported that about 10% of patients with LN experi-enced recurrence (10–13). An additional group of in-vestigators pointed out that the risk of recurrence waseven higher, when diligently searched for, rangingbetween 30 and 54% (14–16). A number of reasonsmay account for these discrepancies: (1) The indica-tion for renal allograft biopsy varies among transplantunits; (2) some studies reported the results seen insingle centers whereas others collected data through

national or multinational registries; (3) the follow-upwas short in many studies—an important point be-cause recurrences may occur more than a decade aftertransplantation (11,17); (4) the risk of recurrence mayvary in different ancestral groups (10,18); (5) a diag-nosis of recurrence of LN requires a graft biopsyexamined by light microscopy, immunofluorescence,and electron microscopy, which were not always rou-tinely performed (19).

Clinically, recurrence of GN in the renal allograftmay be heralded by mild proteinuria and microscopichematuria, and is seldom accompanied by arthralgiasor cutaneous rash. The histologic lesions of recurrentLN are usually mild, mostly consisting of mesangiallesions or atypical pauci-immune proliferative GN inthose studies which adopted a policy of elective sur-veillance biopsy (14–16,19). However, patients of dif-fuse proliferative nephritis have been reported whenthe decision to undertake a renal biopsy was made onclinical grounds (6,10).

The effect of recurrent LN on graft survival is usu-ally of minor significance. In a retrospective analysis(6) only 4 out of 97 patients with LN lost their graftbecause of recurrence. In a multicenter French studyof 60 transplants in patients with LN, no graft was lostbecause of recurrence (7). A review of the UnitedNetwork for Organ Sharing (UNOS) data reportedthat graft failure in patients with recurrent LN was

*Division ofNephrology, ScientificInstitute Humanitas,Rozzano, Milano, Italy;†Division ofNephrology andDialysis, IRCCSFondazione OspedaleMaggiore, Mangiagalli,Regina Elena, Milano,Italy; and ‡Departmentof Medicine, DavidGeffen School ofMedicine at UCLA, LosAngeles, California

Correspondence: Dr.Richard J. Glassock, 8Bethany, Laguna Niguel,CA 92677. E-mail:glassock@cox.net

www.cjasn.org Vol 6 May, 2011 Copyright © 2011 by the American Society of Nephrology 1

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attributable to recurrence in only 7% of patients, rejectionbeing the main cause of graft failure (11). Single-centerstudies also pointed out that the main causes of graftfailure in transplant patients with LN was either rejection(4,13,20,21) or chronic allograft nephropathy (16), ratherthan recurrence of LN.

Factors that tend to be associated with recurrent LN areblack non-Hispanic ancestry, female gender, and youngage (10,11). Patients with antiphospholipid (aPL) autoan-tibodies (13) and those receiving the kidney from livingdonors (16) also have a higher risk of recurrence.

Some studies reported a higher risk of graft failure in LN(4,6,10), whereas others reported patient and graft survivalin LN patients comparable to those seen in other renaldiseases (22–25). The studies that compared the results ofrenal transplantation in LN patients with those of well-matched controls usually reported that patient and graftsurvival were similar in the two groups even in the long-term (3,6,7,12,13,21). Also, morbidity after transplantationwas similar in patients with LN and in well-matched con-trols, with the exception of thrombotic events that weremore frequent in LN (26). Several retrospective analyses ofUNOS and United States Renal Data System (USRDS) re-ported no difference in patient and graft survival ratesbetween adults with LN and other transplant recipients ofliving or deceased donor kidneys, after adjusting for con-founding factors (10,11,27,28). Also a retrospective analysisof the North American Pediatric Renal Transplant Coop-erative Study (NAPRTCS) database found that the resultsof renal transplantation in young patients with LN werecomparable to those seen in an age-, ancestry-, and gender-matched control group, in spite of an unexplained increasein recurrent rejections in the living donor LN patients (22).

The clinical condition of the patient at transplantationcan markedly influence the outcome. In patients who havereceived vigorous immunosuppression or long-term glu-cocorticoid therapy for their disease before transplantation,it may be advisable to postpone transplantation for severalmonths after initiating dialysis to minimize the possiblecontribution of prior therapy on the risk of infectious,cardiovascular, and other complications after transplanta-tion (29). An issue also manifests itself when the aPLsyndrome is present. This can be associated with vascularthrombosis and early graft failure (30,31). Anticoagulationwith heparin can reduce the risk of vascular thrombosis(32). However, not all patients respond and bleeding com-plications remain a serious side effect of anticoagulationtherapy (31).

The basic posttransplant immunosuppression for LNpatients does not differ from that normally used in man-agement. In patients with LN recurrence, an intensificationof immunosuppression should be reserved for the excep-tional cases showing a severe (life threatening) lupusflare-up because of the potential risks of serious or lethalinfection.

In summary, LN may recur after renal transplantationbut in most patients recurrence neither causes severe his-tologic lesions nor has a relevant clinical effect on thelong-term outcome (29). The results of renal transplanta-tion are at least as good in LN patients as in patients withother renal diseases. Pretransplantation screening for aPL

antibodies in renal transplant candidates with LN is rec-ommended as it may indicate which patients will benefitfrom anticoagulant therapy (30).

Henoch-Schonlein NephritisA review of the literature reported that histologic recur-

rence of IgA mesangial deposits occurred in 52 out of 67(78%) renal allografts in patients with Henoch-Schonleinnephritis (HSN), whereas a clinical recurrence occurred inonly 15 out of 67 (22%) patients at 5 years posttransplan-tation (33). However, after longer follow-up clinical recur-rence may be evident in 29 to 42% of patients (34,35), morefrequently in children (36). Henoch-Schonlein nephritis pa-tients with circulating IgA-ANCA (ANCA, antineutrophilcytoplasm antibody) are particularly prone to recurrenceafter transplantation (37). Hematuria, sometimes macro-scopic, moderate proteinuria, and hypertension are com-mon in patients with clinical evidence of recurrence. His-tologically, focal and segmental necrotizing GN withmesangial IgA deposits is observed.

Recurrence of HSN can lead to graft failure in about 10%of patients, the prognosis being more guarded in adultsthan in children (33). In a European survey, graft survivalin patients with HSN recurrence was 57% at 2 years (38).Alternatively, in a small single-center study (39), the 5-yeargraft survival was 78%. In another small study, out of eightadults with recurrent HSN one patient died and four re-started dialysis in mean after 55 months after renal trans-plant (35). Therefore, recurrent HSN should not be re-garded as a benign condition.

Recurrence is more frequent and severe in patients whohad a rapidly progressive course and necrotizing/crescen-tic GN in the native kidneys (35,39). Living related donortransplantation also shows a trend of higher recurrencecompared with those receiving unrelated grafts. However,the graft survival rate in related-donor recipients was notless than that found in unrelated-donor recipients (34).

A comparison of the graft outcome of kidney recipientswith HSN with age-, sex-, and donor source-matched con-trols revealed an actuarial 15-year patient survival of 80%in 17 HSN patients and 82% in 34 controls. The death-censored graft survival was 64% in both of the two groups.The risks of rejection, chronic graft dysfunction, arterialhypertension, and infection were also similar in the twogroups (35). In addition, in another study, 20 patients withHSN were compared with 40 patients with IgA nephrop-athy and 40 patients with other renal diseases. The 10-yeargraft survival was 88% in HSN, similar to that seen in theother two groups. Recurrence of HSN occurred in 29% ofpatients (34).

Patients with recurrent HSN and extensive crescents inthe transplant biopsy have a decidedly poor prognosis.Methyl prednisolone pulses (MPP), antiplatelet agents, orcytotoxic drugs have been used without any notable ben-efits (33–35). In a single patient proteinuria resolved andrenal biopsy demonstrated marked reduction in mesangialIgA deposition after 4 cycles of plasmapheresis (40).

In summary, HSN recurs more frequently in childrenbut the outcome after recurrence is more severe in adultsand in patients with extensive crescentic GN. In spite ofrecurrence, the cumulative long-term graft survival in pa-

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tients with HSN is similar to that seen in patients withother renal diseases.

AmyloidosisPrevious studies have shown that amyloid light-chain

(AL) amyloidosis and hereditary amyloidosis regularly re-cur after kidney transplantation, but only a few have beenreported in the literature (41–43). However, a successfulrenal transplant without recurrence of amyloidosis after 9years was described in a patient with familial apolipopro-tein II amyloidosis (44) and a recent series of 22 renaltransplant recipients with AL amyloidosis reported that norenal graft failed because of recurrent amyloidosis after amean follow-up of 48 months. The patient survival was95% at 1 year and 67% at 5 years (45).

The risk of recurrence for secondary AA amyloidosisdepends on the type and the activity of original disease. Upto 26% of patients with amyloidosis secondary to chronicinflammation (such as rheumatoid arthritis) may develop arenal recurrence (46) whereas no case of recurrent renalamyloidosis has yet been reported in patients with amy-loidosis secondary to Behcet’s disease (47–49). Amyloido-sis may also recur after transplantation in patients withfamilial Mediterranean fever, but the early administrationof colchicine, 1 to 2 mg/d indefinitely, can prevent thedeposition of amyloid in the transplanted kidney (50).

Recurrence of renal amyloidosis is often associated withvarious degrees of proteinuria. When present, nephroticproteinuria heralds the relentless progression to graft fail-ure. The graft survival in patients with amyloidosis hasimproved with time and with better immunosuppression.In a series of 105 renal transplants in 96 patients withamyloidosis (primary amyloidosis in 5 patients and sec-ondary amyloidosis in the other 91 patients), graft survivalwas comparable to that seen in transplant patients withdiabetes (51). The Collaborative Transplant Study (CTS)reported that the patient and renal graft survival at 5 yearswere inferior in patients with secondary amyloidosis thanin patients with GN or polycystic kidney disease, but ad-equate enough to justify kidney transplantation (52). Twomain issues with renal transplantation in amyloidosis arelife-threatening infections and cardiovascular complica-tions (53,54), particularly when cardiac involvement ispresent.

In summary, patients with renal amyloidosis withoutother organ involvement (especially cardiac) may undergokidney transplantation. However, in view of the increasedrisk of postoperative complications, a preoperative cardio-vascular evaluation is mandatory even in asymptomaticpatients. Specific treatment should be considered for par-ticular forms of amyloidosis, that is, chemotherapy andautologous stem cell transplantation followed by kidneytransplantation in progressive primary AL amyloidosis(55), a dual liver and kidney transplantation in hereditaryamyloidosis and multivisceral involvement (42,43,56), adual heart and kidney transplantation in severe and irre-versible cardiac and renal involvement (57). Patients withfamilial Mediterranean fever should be treated regularlywith colchicine (58,59).

Light-Chain Deposition DiseasePatients with light-chain deposition disease (LCDD)

have a very high risk of recurrence of the monoclonal � or� chain deposition in the graft (60–67). Recurrence ofLCDD developed in 5 out of 7 renal transplant patientsafter a mean period of 33 months (64).

The prognosis is poor in patients with recurrence ofLCDD. Four of the 5 patients with recurrence quoted abovedied and the fifth patient entered dialysis (64). Of the othertwo patients one died from multiple myeloma and anotherwas still alive with graft functioning 13 years posttrans-plantation. However, a review of the ERA/EDTA registryreported that the mean survival in 35 transplanted patientswith LCDD was 9.6 years (65).

In spite of a high risk of recurrence and death, renaltransplantation may be offered to patients with LCDD whorespond satisfactorily to chemotherapy, as demonstratedby serial serum-free light-chain assays. Preliminary resultshave shown the possibility of preventing an early recur-rence of LCDD with the proteasome inhibitor bortezomib(66) or with rituximab (67). The best current therapeuticapproach is chemotherapy and autologous stem cell trans-plantation followed by kidney transplantation in case ofgood hematologic response (68). We suggest that renaltransplantation should not be performed until after thelight-chain production has been curtailed with appropriatechemotherapy and documented with serum-free light-chain assays repeated every 3 months until transplanta-tion.

Fibrillary/Immunotactoid GlomerulonephritisThe high risk of early graft failure due to recurrent

fibrillary/immunotactoid glomerulonephritis (F/ITGN)(69,70) was considered as a contraindication to renal trans-plant in the past. However, Samaniego et al. (71) reported14 cases of F/ITGN in which, in spite of histologic recur-rence in 6 cases, the allografts functioned in four patientsfor 4, 5, 11, and 13 years whereas a fifth patient died withstable graft function 7 years posttransplantation. Rosen-stock et al. (72) reported two other cases of renal transplantin patients with FGN. One patient had normal serum cre-atinine, no proteinuria, and no signs of recurrence 8 yearsposttransplantation. The other patient died from colon can-cer 4 years after transplantation with a stable serum creat-inine of 2.2 mg/dl. In a third series, five patients withF/ITGN were followed in mean for 52 months posttrans-plantation (73). Only one patient lost the graft (because ofthrombo-embolism). Thus, in spite of an increased risk ofrecurrence, renal transplantation may be considered as aviable option for patients with F/ITGN.

Mixed Cryoglobulinemic NephritisUp to 40% of patients, particularly those who are HCV-

positive, may develop mixed IgG/IgM cryoglobulinemiaand eventually a membranous or a membranoproliferativeGN after renal transplantation (74). However, only 13 pa-tients with mixed cryoglobulinemic nephritis (MCN) whosubmitted to renal transplantation have been reported inthe literature (75–80). In all patients cryoglobulinemia wasdetected after transplantation and 7 (54%) showed a recur-rence of MCN, characterized by proteinuria and hematu-

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ria. Histology usually showed a membranoproliferative-type GN with extensive monocyte and polymorphonuclearleukocyte accumulation in capillary loops and small cellu-lar crescents. Immunofluorescence showed C3, IgG, andIgM deposition in a mesangial and capillary wall pattern inall cases.

It is unclear whether the recurrence of MCN will inter-fere with the long-term survival of the transplanted kid-ney; as in reported cases graft failure was usually causedby rejection whereas some patients showed good graftfunction for 4 to 10 years in spite of histologic recurrence(78,80). Rituximab has proven to be an effective treatmentfor de novo MCN in transplant patients (81) but in sometransplant patients rituximab may cause life-threateninginfections (82).

Because chronic hepatitis (with cirrhosis), cardiovasculardisease, and infection are the main causes of death inpatients with MCN (83,84), we recommend that the clinicalcondition of the potential recipient should be carefullyevaluated before a patient can be considered a suitablecandidate for renal transplantation.

Diabetic NephropathyIt is difficult to estimate the actual rate of recurrence of

diabetic nephropathy (DN) in renal allografts becauseabout 20% of transplant patients may develop de novo onsetof diabetes posttransplantation (PTDM), which can alsoeventually lead to de novo DN (85). Recurrence of DNaccounted for only 1.8% of graft losses in one of the largestseries of renal transplants in diabetic recipients (86). Thislow risk may depend on the short duration of follow-upbecause the mean interval between the onset of insulin-dependent diabetes and the development of overt ne-phropathy in renal transplant recipients requires severalyears (87). A more recent series demonstrated a histologicrecurrence in almost 40% of diabetic patients in a mean of6.7 years after transplantation (88). Cases of recurrent DNhave also been reported in patients with type 1 diabeteswho were receiving a simultaneous pancreas and kidneytransplantation (89). Vendrame et al. (90) demonstratedthat recurrence of diabetes was associated with autoanti-bodies and reappearence of CD4 T cells capable of medi-ating � cell destruction. Microalbuminuria heralds thepresence of DN, whereas overt proteinuria and nephroticsyndrome develop later, preceding the onset of progres-sive renal failure. In transplanted patients with DM whodevelop overt proteinuria and renal insufficiency, the typ-ical nodular intercapillary glomerulosclerosis (Kimmel-stiel-Wilson lesion) is infrequent, whereas vascularchanges are prominent (87). The progression of histologic,diabetes-related lesions in the transplanted kidney is slow,but more rapid than in the original disease, perhaps be-cause of the lower nephron mass, the use of nephrotoxiccalcineurin inhibitors, and glucocorticoid therapy, and thefrequency of concomitant hypertension. Thus, recurrentDN has little effect on graft function in the short term butcan eventually contribute to graft loss in the long term.

A number of single-center series reported that, withmodern immunosuppression, the patient and renal graftsurvival were similar in patients who had diabetes (type1or 2) to those who did not have diabetes, at least up to 2 to

5 years (91–93). A major problem for patients with diabetesremains—the high incidence of coronary artery diseaseand peripheral vascular events that can impair the survivaland quality of life.

Present day, DN is not considered a contraindication torenal transplantation. However, measures are recom-mended to prevent the development of DN and otherdiabetes-related complications, including strict glycemiccontrol (94), early use of ACE inhibitors and/or angioten-sin receptor antagonists (95,96), a preemptive kidney trans-plantation in patients with type 2 diabetes (97), and adouble pancreas and kidney transplantation in selectedpatients with type 1 diabetes (98).

Small Vessel VasculitisThe risk of small vessel vasculitis (SVV) recurrence on

renal graft is approximately 6% (99–110). The number ofrelapses of SVV per patients per year varied in three dif-ferent studies, being respectively 0.02 (107), 0.076 (108),and 0.10 patients per year (101). Recurrence may developwithin a few weeks after renal transplantation or manyyears later, with an average time from transplantation torecurrence of 31 months (105). Around 60% of recurrencesinvolved the graft alone or in association with other or-gans, whereas the other 40% were primarily extrarenal(104,105). Microscopic hematuria and proteinuria are theheralding signs for renal recurrences of SVV. These aregenerally associated with or followed by the deteriorationof graft function. The histologic picture is characterized byfocal or diffuse pauci-immune extracapillary necrotizingglomerulonephritis.

The ANCA pattern or titers at time of transplantation,the duration of the original disease, the duration of dialy-sis, treatment with cyclosporine, and the source of donorsdo not influence the risk of recurrence (105,107–109), norare clinical parameters very useful in predicting the risk ofrecurrence of SVV (108,109). No differences in the rate ofrecurrence after transplantation was observed betweenWegener granulomatosis, microscopic polyarteritis, or re-nal limited vasculitis (105,108–110).

An Australian registry reported a graft loss of only 7.7%at 10 years caused by recurrence of SVV in transplantpatients (111). By reviewing the data of single centers, wefound that 7 of 323 (2%) SVV transplant patients lost theirgraft because of recurrence, but the risk of graft loss was35% for patients who had clinical recurrence of SVV(14,100–110).

Patient and graft survival are quite similar in SVV and inthe general transplant population. The UNOS registry re-ported a 3-year graft survival rate of 78% for deceaseddonor transplants, and 84% for living donor transplants in114 recipients with Wegener granulomatosis (112). TheERA-EDTA registry reported a 70% graft survival at 3years in 115 patients with SVV (38). In an abstract, the CTS(113) reported a 10-year patient survival of 80% and a graftsurvival of 65% for renal transplant recipients with We-gener granulomatosis. Relapses of SVV seldom occur afterrenal transplantation (101,102,109,110), perhaps because ofconcomitant immunosuppression.

The optimal timing for renal transplant in patients withSVV remains an unresolved question. Because clinical re-

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mission of SVV for �1 year is associated with a highmortality rate (103,110), SVV candidates for renal trans-plantation should be in stable clinical remission at the timeof transplantation. Prolonged immunosuppression mayalso expose patients to the risk of life-threatening infec-tions after transplantation (114); thus, we believe thattransplantation should be delayed for several months afterstarting dialysis in patients who have received a prolongedor intense period of immunosuppression for treatment oftheir underlying disease (108).

Despite the unpredictable potential for recurrence, trans-plantation is an acceptable option for patients with SVV.Persistent positivity of ANCA tests should not precludetransplantation (100,110). A careful monitoring of the uri-nary sediment during the first few years after transplanta-tion may help in making a prompt diagnosis and treatmentof a recurrence or relapse of SVV. Treatment of relapses ismainly based on MPP, cyclophosphamide, and plas-mapheresis or possibly rituximab (14,108,115).

Summary and ConclusionsGlomerulonephritis (GN) secondary to systemic diseases

may recur after transplantation, although the risk of recur-rence and its effect on short- and long-term graft outcomedepend on the type of the original disease as well as on thetimeliness of diagnosis and treatment. In spite of the risk ofrecurrence, the long-term patient and graft survival ratesin transplanted patients with LN, HSN, or SVV are similarto those reported patients with other kidney diseases un-dergoing renal transplantation. A recurrence of AA amy-loidosis may be prevented by a careful management of theunderlying disease. New management protocols or com-bined organ transplants are now available for treating therecurrence of AL amyloidosis. Diabetic nephropathy doesnot represent a contraindication to renal transplantation;the main risks for diabetic transplant recipients rests oncardiovascular disease not on recurrence of DN. Sporadic,successful cases of renal transplantation have been re-ported in diseases such as LCDD, IT/FGN, and MCN thatwere considered until recently as a contraindication tokidney transplantation. Much work is still needed to fur-ther improve the long-term results of renal transplantationin patients with secondary GN, but today most patientswith secondary GN can be considered suitable candidatesfor a renal transplant, if there are no contraindicationsdictated by extrarenal complications.

DisclosuresNone.

References1. Glassock RJ, Feldman D, Reynolds ES, Dammin GJ, Merrill

JP: Human renal isografts: A clinical and pathologic analysis.Medicine (Baltimore) 47: 411–454, 1968

2. Ponticelli C, Glassock RJ: Post-transplant recurrence of pri-mary glomerulonephritis: An in-depth review. Clin J Am SocNephrol 5: 2363–2372, 2010

3. Bumgardner GL, Mauer SM, Payne W, Dunn DL, SutherlandDE, Fryd DS, Ascher NL, Simmons RL, Najarian JS: Single-center 1–15 year results of renal transplantation in patientswith systemic lupus erythematosus. Transplantation 46: 703–709, 1988

4. Lochhead KM, Pirsch JD, D’Alessandro AM, Knechtle SJ, Ka-

layoglu M, Sollinger HW, Belzer FO: Risk factors for renalallograft loss in patients with systemic lupus erythematosus.Kidney Int 49: 512–517, 1996

5. Mojcik CF, Klippel JH: End-stage renal disease and systemiclupus erythematosus. Am J Med 101: 100–107, 1996

6. Stone JH: End-stage renal disease in lupus: Disease activity,dialysis, and the outcome of transplantation. Lupus 7: 654–659, 1998

7. Grimbert P, Frappier J, Bedrossian J, Legendre C, Antoine C,Hiesse C, Bitker MO, Sraer JD, Lang P: Long-term outcome ofkidney transplantation in patients with systemic lupus ery-thematosus: A multicenter study. Groupe Cooperatif deTransplantation d’Ile de France. Transplantation 66: 1000–1003, 1998

8. Ghafari A, Etemadi J, Ardalan MR: Renal transplantation inpatients with lupus nephritis: A single-center experience.Transplant Proc 40: 143–144, 2008

9. Dong G, Panaro F, Bogetti D, Sammartino C, Rondelli D,Sankary H, Testa G, Benedetti E: Standard chronic immuno-suppression after kidney transplantation for systemic lupuserythematosus eliminates recurrence of disease. Clin Trans-plant 19: 56–60, 2005

10. Burgos PI, Perkins EL, Pons-Estel GJ Kendrick SA, Liu JM,Kendrick WT, Cook WJ, Julian BA, Alarcon GS, Kew CE 2nd:Risk factors and impact of recurrent lupus nephritis in pa-tients with systemic lupus erythematosus undergoing renaltransplantation: Data from a single US institution. ArthritisRheum 60: 2757–2766, 2009

11. Contreras G, Mattiazzi A, Guerra G, Ortega LM, Tozman EC,Li H, Tamariz L, Carvalho C, Kupin W, Ladino M, LeClercqB, Jaraba I, Carvalho D, Carles E, Roth D: Recurrence of lu-pus nephritis after kidney transplantation. J Am Soc Nephrol21: 1200–1207, 2010

12. Azevedo LS, Romao JE, Malheiros D, Saldanha LB, Ianhez LE,Sabbaga E: Renal transplantation in systemic lupus erythema-tosus. A case control study of 45 patients. Nephrol DialTransplant 13: 2894–2898, 1998

13. Moroni G, Tantardini F, Galleli B Quaglini S, Banfi G, Poli F,Montagnino G, Meroni P, Messa P, Ponticelli C: The long-term prognosis of renal transplantation in patients with lupusnephritis. Am J Kidney Dis 45: 903–911, 2005

14. Nyberg G, Akensson P, Norden G, Wieslander J: Systemicvasculitis in a kidney transplant population. Transplantation63: 1273–1277, 1997

15. Goral S, Ynares C, Shappell SB, Snyder S, Feurer ID, Kazan-cioglu R, Fogo AB, Helderman JH: Recurrent lupus nephritisin renal transplant recipients revisited: It is not rare. Trans-plantation 75: 651–656, 2003

16. Norby GE, Strøm EH, Midtvedt K, Hartmann A, Gilboe IM,Leivestad T, Stenstrøm J, Holdaas H. Recurrent lupus nephri-tis after kidney transplantation: A surveillance biopsy study.Ann Rheum Dis 69: 1484–1487, 2010

17. Ahuja TS, Boughton J, Weiss V, Memon A, Remmers A Jr.,Rajaraman S: Late recurrence of lupus nephritis in a renaltransplant recipient: Response to mycophenolate mofetil.Am J Med Sci 322: 166–169, 2001

18. Yu TM, Chen YH, Lan JL, Cheng CH, Chen CH, Wu MJ, ShuKH: Renal outcome and evolution of disease activity in Chi-nese lupus patients after renal transplantation. Lupus 17:687–694, 2008

19. Weng F, Goral S: Recurrence of lupus nephritis after renaltransplantation: If we look for it, will we find it? Nat ClinPract Nephrol 1: 62–63, 2005

20. Meehan SM, Chang A, Khurana A, Baliga R, Kadambi PV,Javaid B: Pauci-immune and immune glomerular lesions inkidney transplants for systemic lupus erythematosus. ClinJ Am Soc Nephrol 3: 1469–1478, 2008

21. Deegens JK, Artz MA, Hoijtsma AJ, Wetzels JF: Outcome ofrenal transplantation in patients with systemic lupus erythem-atosus. Transplant Int 16: 411–418, 2003

22. Bartosh SM, Fine RN, Sullivan EK: Outcome after transplanta-tion of young patients with systemic lupus erythematosus: Areport of the North America pediatric renal transplant cooper-ative group. Transplantation 72: 973–978, 2001

23. Haubitz M, Kliem V, Koch KM, Nashan B, Schlitt HJ, Pichl-

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mayr R, Brunkhorst R: Renal transplantation for patients withautoimmune disease: Single-center experience with 42 pa-tients. Transplantation 15: 1251–1257, 1997

24. Alarcon-Segovia D: Kidney transplantation is a safe therapeu-tic tool in systemic lupus erythematosus. Clin Exp Rheumatol18: 185–186, 2000

25. Nossent HC, Swaak TJG, Berden JHM: Systemic lupus ery-thematosus after renal transplantation: Patient and graft sur-vival and disease activity. Ann Intern Med 114: 183–188,1991

26. Moroni G, Ventura D, Riva P, Panzeri P, Quaglini S, Banfi G,Simonini P, Bader R, Meroni PL, Ponticelli C: Antiphospho-lipid antibodies are associated with an increate risk forchronic renal insufficiency in patients with lupus nephritis.Am J Kidney Dis 43: 28–36, 2004

27. Ward MM: Outcomes of renal transplantation among patientswith end-stage renal disease caused by lupus nephritis. Kid-ney Int 57: 2136–2143, 2000

28. Bunnapradist S, Chung P, Peng A, Hong A, Chung P, Lee B,Fukami S, Takemoto SK, Singh AK: Outcomes of renal trans-plantation for recipients with lupus nephritis: Analysis of theOrgan Procurement and Transplantation Network database.Transplantation 82: 612–618, 2006

29. Ponticelli C, Moroni G: Renal transplantation in lupus ne-phritis. Lupus 14: 95–98, 2005

30. Wagenknecht DR, Fastenau DR, Torry RJ, Becker DG, LeForWM, Carter CB, Haag BW, McIntyre JA: Risk of early renalallograft failure is increased for patients with antiphospho-lipid antibodies. Transpl Int 13 [Suppl 1]: S78–S81, 2000

31. Vaidya S, Gugliuzza K, Daller JA: Efficacy of anticoagulationtherapy in end-stage renal disease patients with antiphospho-lipid antibody syndrome. Transplantation 77: 1046–1049,2004

32. McIntyre JA, Wagenknecht DR: Antiphospholipid antibodiesand renal transplantation: A risk assessment. Lupus 12: 555–559, 2003

33. Meulders Q, Pirson Y, Cosyns JP, Squifflet JP, van Yperselede Strihou C: Course of Henoch–Schonlein nephritis afterrenal transplantation. Transplantation 58: 1172–1186, 1994

34. Han SS, Sun HK, Lee JP, Ha JW, Kim SJ, Kim YS: Outcome ofrenal allograft in patients with Henoch-Schonlein nephritis:single-center experience and systematic review. Transplanta-tion 89: 721–726, 2010

35. Moroni G, Gallelli B, Diana A, Carminati A, Banfi G, Poli F,Montagnino G, Tarantino A, Messa P: Renal transplantationin adults with Henoch-Schonlein purpura: Long-term out-come. Nephrol Dial Transplant 23: 3010–3016, 2008

36. Hasegawa A, Kawamura T, Ito H, Hasegawa O, Ogawa O,Honda M, Ohara T, Hajikano H: Fate of renal grafts with re-current Henoch-Schonlein purpura nephritis in children.Transplant Proc 21: 2130–2133, 1989

37. Martin SJ, Audrain MA, Baranger T, Moreau A, Dantal J,Testa A, Esnault VL. Recurrence of immunoglobulin A ne-phropathy with immunoglobulin A antineutrophil cytoplas-mic antibodies following renal transplantation. Am J KidneyDis 29: 125–131, 1997

38. Briggs JD, Jones E: Renal transplantation for uncommon dis-eases. Nephrol Dial Transplant 14: 570–575, 1999

39. Soler MJ, Mir M, Rodriguez E, Orfila A, Munne A, VazquezS, Lloveras J, Puig JM: Recurrence of IgA nephropathy andHenoch-Schoenlein purpura after kidney transplantation: Riskfactors and graft survival. Transplant Proc 37: 3705–3709,2005

40. Lee J, Clayton F, Shihab F, Goldfarb-Rumyantzev A: Success-ful treatment of recurrent Henoch-Schonlein purpura in a re-nal allograft with plasmapheresis. Am J Transplant 8: 228–231, 2008

41. Chen DJ, Jiang H, Yang H, He Q, Wang HP, Chen JH: Un-usual cause of proteinuria and re-renal failure after kidneytransplantation: De novo localized AL amyloidosis in renalallograft. Int Urol Nephrol 42: 507–511, 2010

42. Mousson C, Heyd B, Justrabo E, Rebibou JM, Tanter Y,Miguet JP, Rifle G. Successful hepatorenal transplantation inhereditary amyloidosis caused by a frame-shift mutation in

fibrinogen A alpha-chain gene. Am J Transplant 6: 632–635,2006

43. Gillmore JD, Booth DR, Rela M, Heaton ND, Rahman V,Stangou AJ, Pepys MB, Hawkins PN: Curative hepatorenaltransplantation in systemic amyloidosis caused by theGlu526Val fibrinogen alpha-chain variant in an English fam-ily. QJM 93: 269–275, 2000

44. Magy N, Liepnieks JJ, Yazaki M, Kluve-Beckerman B, BensonMD: Renal transplantation for apolipoprotein AII amyloidosis.Amyloid 10: 224–228, 2003

45. Sattianayagam PT, Gibbs SDJ, Pinney JH, Wechalekar AD,Lachmann HJ, Whelan CJ, Gilbertson JA, Hawkins PN, Gill-more JD: Solid organ transplantation in AL amyloidosis. Am JTransplant 10: 2124–2131, 2010

46. Harrison KL, Alpers CE, Davis CL: De novo amyloidosis in arenal allograft: A case report and review of the literature.Am J Kidney Dis 22: 468–476, 1993

47. Akpolat T, Diri B, Oguz Y, Dilek M, Odabas AR, Ozen S:Behcet’s disease and renal failure. Nephrol Dial Transplant18: 888–889, 2003

48. Moises J, Torregrosa JV, Ybarra J, Oppenheimer F: Renaltransplantation in a C-ANCA(�) patient with Behcet diseaseand rapidly progressive glomerulonephritis. Clin Nephrol 61:357–359, 2004

49. Lai KN, Lai AS, Yap DY, Ng MM: Recurrent oral ulcers anddiarrhea in a renal transplant patient. Behcet’s disease (asso-ciated with IgA nephropathy) and acute tacrolimus nephro-toxicity. Kidney Int 76: 1211–1212, 2009

50. Sever MS, Turkmen A, Sahin S, Yildiz A, Ecder T, KayacanMS, Nane I, Aydin AE, Eldegez U: Renal transplantation inamyloidosis secondary to familial Mediterranean fever. Trans-plant Proc 33: 3392–3393, 2001

51. Isoniemi H, Kyllonen L, Ahonen J, Hockerstedt K, Salmela K,Pasternack A: Improved outcome of transplantation in amy-loidosis. Transpl Int 7 [Suppl 1]: S298–S300, 1994

52. Heering P, Hetzel R, Grabensee B, Opelz G: Renal transplan-tation in secondary systemic amyloidosis. Clin Transplant 12:159–164, 1998

53. Turkmen A, Yildiz A, Erkoc R, Ecder T, Gorcin B, Turk S, Ay-din AE, Eldegez U, Ark E, Sever MS: Transplantation in renalamyloidosis. Clin Transplant 12: 375–378, 1998

54. Haq A, Hussain S, Meskat B, Mohan P, Conlon P, HickeyDP: Complications of renal transplantation in patients withamyloidosis. Transplant Proc 39: 120–124, 2007

55. Merlini G, Remuzzi G: Autologous stem cell and kidneytransplantation for primary amyloidosis associated with ESRD:Which should come first? Am J Transplant 5: 1585–1586,2005

56. Gillmore JD, Stangou AJ, Lachmann HJ, Goodman HJ,Wechalekar AD, Acheson J, Tennent GA, Bybee A, Gilbert-son J, Rowczenio D, O’Grady J, Heaton ND, Pepys MB,Hawkins PN: Organ transplantation in hereditary apolipopro-tein AI amyloidosis. Am J Transplant 6: 2342–2347, 2006

57. Audard V, Matignon M, Weiss L, Remy P, Pardon A, HaiounC, Belhadj K, Salomon L, Hillon ML, Sahali D, Vermes E,Lang P, Grimbert P: Successful long-term outcome of the firstcombined heart and kidney transplant in a patient with sys-temic Al amyloidosis. Am J Transplant 9: 236–240, 2009

58. Celik A, Saglam F, Dolek D, Sifil A, Soylu A, Cavdar C, Tem-izkan A, Bora S, Gulay H, Camsari T: Outcome of kidneytransplantation for renal amyloidosis: A single-center experi-ence. Transplant Proc 38: 435–439, 2006

59. Ozdemir BH, Ozdemir FN, Sezer S, Sar A, Haberal M: Doescolchicine have an antifibrotic effect on development of in-terstitial fibrosis in renal allografts of recipients with familialmediterranean fever? Transplant Proc 38: 473–476, 2006

60. Short AK, O’Donoghue DJ, Riad HN, Short CD, Roberts IS:Recurrence of light chain nephropathy in a renal allograft. Acase report and review of the literature. Am J Nephrol 21:237–241, 2001

61. Alchi B, Nishi S, Iguchi S, Shimotori M, Sakatsume M, UenoM, Narita I, Saito K, Takahashi K, Gejyo F: Recurrent lightand heavy chain deposition disease after renal transplanta-tion. Nephrol Dial Transplant 20: 1487–1491, 2005

62. Tanenbaum ND, Howell DN, Middleton JP, Spurney RF:

6 Clinical Journal of the American Society of Nephrology

tapraid4/cjn-cjasn/cjn-cjasn/cjn00511/cjn35791z xppws S�1 3/12/11 8:20 Art: 09381010 Input-jmk

Lambda light chain deposition disease in a renal allograft.Transplant Proc 37: 4289–4292, 2005

63. Larsen T, Hammer A, Jørgensen KA: Recurrence of light-chain deposition disease after renal transplantation. ScandJ Urol Nephrol 42: 187–188, 2008

64. Larsen T, Hammer A, Jørgensen KA, Wilson K, Kanakiriya S,Fervenza FC: Long-term outcome of renal transplantation inlight-chain deposition disease. Am J Kidney Dis 43: 147–153,2004

65. Tsakiris DJ, Stel VS, Finne P, Fraser E, Heaf J, de Meester J,Schmaldienst S, Dekker F, Verrina E, Jager KJ. Incidence andoutcome of patients starting renal replacement therapy forend-stage renal disease due to multiple myeloma or light-chain deposit disease: An ERA-EDTA Registry study. NephrolDial Transplant 25: 1200–1206, 2010

66. Kaposztas Z, Kahan BD, Katz SM, Van Buren CT, Cherem L:Bortezomib successfully reverses early recurrence of light-chain deposition disease in a renal allograft: A case report.Transplant Proc 41: 4407–4410, 2009

67. Kuypers DR, Lerut E, Claes K, Evenepoel P, VanrenterghemY: Recurrence of light chain deposit disease after renal allo-graft transplantation: Potential role of rituximab? Transpl Int20: 381–385, 2007

68. Lorenz EC, Gertz MA, Fervenza FC, Dispenzieri A, Lacy MQ,Hayman SR, Gastineau DA, Leung N. Long-term outcome ofautologous stem cell transplantation in light chain depositiondisease. Nephrol Dial Transplant 23: 2052–2057, 2008

69. Calls Ginesta J, Torras A, Ricart MJ, Ramirez J, Campo E,Darnell A, Andreu J, Revert L: Fibrillary glomerulonephritisand pulmonary hemorrhage in a patient with renal transplan-tation. Clin Nephrol 43: 180–183, 1995

70. Palanichamy V, Saffarian N, Jones B, Nakhleh RE, Oh HK,Provenzano R, Tayeb JS. Fibrillary glomerulonephritis in arenal allograft. Am J Kidney Dis 32: E4, 1998

71. Samaniego M, Nadasdy GM, Laszik Z, Nadasdy T: Outcomeof renal transplantation in fibrillary glomerulonephritis. ClinNephrol 55: 159–166, 2001

72. Rosenstock JL, Markowitz GS, Valeri AM, Sacchi G, AppelGB, D’Agati VD: Fibrillary and immunotactoid glomerulone-phritis: Distinct entities with different clinical and pathologicfeatures. Kidney Int 63: 1450–1461, 2003

73. Czarnecki PG, Lager DJ, Leung N, Dispenzieri A, Cosio FG,Fervenza FC: Long-term outcome of kidney transplantation inpatients with fibrillary glomerulonephritis or monoclonalgammopathy with fibrillary deposits. Kidney Int 75: 420–427, 2009

74. Faguer S, Kamar N, Boulestin A, Esposito L, Durand D,Blancher A, Rostaing L: Prevalence of cryoglobulinemia andautoimmunity markers in renal-transplant patients. ClinNephrol 69: 239–243, 2008

75. McIntosh RM, Griswold WR, Chernack WB, Williams G,Strauss J, Kaufman DB, Koss MN, McIntosh JR, Cohen R,Weil R 3rd: Cryoglobulins. III. Further studies on the nature,incidence, clinical, diagnostic, prognostic, and immuno-pathologic significance of cryoproteins in renal disease. QJ Med 44: 285–307, 1975

76. Andrejak M, Bariety J, Bedrossian J, Callard P, Druet P,Duboust A, Idatte JM, Kuhn J: Cryoglobulinaemia in renaltransplant recipients. Transplantation 26: 446–447, 1978

77. Hiesse C, Bastuji-Garin S, Santelli G, Moulin B, CantarovichM, Lantz O, Charpentier B, Fries D: Recurrent essentialmixed cryoglobulinemia in renal allografts. Report of twocases and review of the literature. Am J Nephrol 9: 150–154,1989

78. Tarantino A, Moroni G, Banfi G, Manzoni C, Segagni S, Pon-ticelli C: Renal replacement therapy in cryoglobulinemic ne-phritis. Nephrol Dial Transplant 9: 1426–1430, 1994

79. Brunkhorst R, Kliem V, Koch KM: Recurrence of mem-branoproliferative glomerulonephritis after renal transplanta-tion in a patient with chronic hepatitis C. Nephron 72: 465–467, 1996

80. Takeda A, Ootsuka Y, Suzuki T, Yamauchi Y, Tsujita M,Kawaguchi T, Horike K, Oikawa T, Goto N, Nagasaka T,Watarai Y, Uchida K, Morozumi K: A case report of recur-rence of mixed cryoglobulinemic glomerulonephritis in a re-

nal transplant recipient. Clin Transplant 24 [Suppl 22]: 44–47, 2010

81. Basse G, Ribes D, Kamar N, Mehrenberger M, Sallusto F, Es-posito L, Guitard J, Lavayssiere L, Oksman F, Durand D, Ros-taing L: Rituximab therapy for mixed cryoglobulinemia inseven renal transplant patients. Transplant Proc 38: 2308–2310, 2006

82. Basse G, Ribes D, Kamar N, Esposito L, Rostaing L: Life-threatening infections following rituximab therapy in renaltransplant patients with mixed cryoglobulinemia. Clin Neph-rol 66: 395–396, 2006

83. Tarantino A, Campise M, Banfi G, Confalonieri R, Bucci A,Montoli A, Colasanti G, Damilano I, D’Amico G, Minetti L,Ponticelli C: Long-term predictors of serviva in essential cryo-globulinemic glomerulonephritis. Kidney Int 47: 618–623,1995

84. Della Rossa A, Tavoni A, D’Ascanio A, Catarsi E, Marchi F,Bencivelli W, Salvadori S, Migliorini P, Bombardieri S: Mor-tality rate and outcome factors in mixed cryoglobulinaemia:The impact of hepatitis C virus. Scand J Rheumatol 39: 167–170, 2010

85. Burroughs TE, Swindle J, Takemoto S, Lentine KL, MachnickiG, Irish WD, Brennan DC, Schnitzler MA: Diabetic compli-cations associated with new-onset diabetes mellitus in renaltransplant recipients. Transplantation 83: 1027–1034, 2007

86. Basadonna G, Matas AJ, Najarian JS. Transplantation in dia-betic patients: The University of Minnesota experience. Kid-ney Int 42: S193–S198, 1992

87. Hariharan S, Smith RD, Viero R, First MR: Diabetic nephrop-athy after renal transplantation. Transplantation 62: 632–635,1996

88. Ishida-Oku M, Iwase M, Sugitani A, Masutani K, Kitada H,Tanaka M, Iida M. A case of recurrent type 1 diabetes melli-tus with insulitis of transplanted pancreas in simultaneouspancreas-kidney transplantation from cardiac death donor.Diabetologia 53: 341–345, 2010

89. Bhalla V, Nast CC, Stollenwerk N Tran S, Barba L, Kamil ES,Danovitch G, Adler SG: Recurrent and de novo diabetic ne-phropathy in renal allografts. Transplantation 75: 66–71,2003

90. Vendrame F, Pileggi A, Laughlin E, Allende G, Martin-PagolaA, Molano RD, Diamantopoulos S, Standifer N, Geubtner K,Falk BA, Ichii H, Takahashi H, Snowhite I, Chen Z, MendezA, Chen L, Sageshima J, Ruiz P, Ciancio G, Ricordi C,Reijonen H, Nepom GT, Burke GW 3rd, Pugliese A: Recur-rence of type 1 diabetes after simultaneous pancreas-kidneytransplantation, despite immunosuppression, is associatedwith autoantibodies and pathogenic autoreactive CD4T-cells. Diabetes 59: 947–957, 2010

91. Shaffer D, Simpson MA, Madras PN, Sahyoun AI, ConwayPA, Davis CP, Monaco AP. Kidney transplantation in diabeticpatients using cyclosporine. Five-year follow-up. Arch Surg130: 283–287, 1995

92. Boucek P, Saudek F, Pokorna E, Vitko S, Adamec M, Kozn-arova R, Lanska V: Kidney transplantation in type 2 diabeticpatients: A comparison with matched non-diabetic subjects.Nephrol Dial Transplant 17: 1678–1683, 2002

93. Rømming Sørensen V, Schwartz Sørensen S, Feldt-RasmussenB: Long-term graft and patient survival following renal trans-plantation in diabetic patients. Scand J Urol Nephrol 40:247–251, 2006

94. Schiel R, Heinrich S, Steiner T, Ott U, Stein G: Long-termprognosis of patients after kidney transplantation: A compari-son of those with or without diabetes mellitus. Nephrol DialTransplant 20: 611–617, 2005

95. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, MitchWE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahin-far S; RENAAL Study Investigators: Effects of losartan on renaland cardiovascular outcomes in patients with type 2 diabetesand nephropathy. N Engl J Med 345: 861–869, 2001

96. Jacobsen P, Andersen S, Jensen BR, Parving HH. Additiveeffect of ACE inhibition and angiotensin II receptor blockadein type I diabetic patients with diabetic nephropathy. J AmSoc Nephrol 14: 992–999, 2003

97. Luan FL, Samaniego M: Transplantation in diabetic kidney

Clin J Am Soc Nephrol 6: ●●●–●●●, May, 2011 Recurrence of Secondary Glomerular Disease, Ponticelli et al. 7

tapraid4/cjn-cjasn/cjn-cjasn/cjn00511/cjn35791z xppws S�1 3/12/11 8:20 Art: 09381010 Input-jmk

failure patients: modalities, outcomes, and clinical manage-ment. Semin Dial 23: 198–205, 2010

98. Becker BN, Rush SH, Dykstra DM, Becker YT, Port FK: Pre-emptive transplantation for patients with diabetes-related kid-ney disease. Arch Intern Med 166: 44–48, 2006

99. La Rocca E, Fiorina P, di Carlo V, Astorri E, Rossetti C, Lucig-nani G, Fazio F, Giudici D, Cristallo M, Bianchi G, Pozza G,Secchi A: Cardiovascular outcomes after kidney-pancreas andkidney-alone transplantation. Kidney Int 60: 1964–1971,2001

100. Kuross S, Davin T, Kjellstrand CM: Wegener’s granulomatosiswith severe renal failure: clinical course and results of dialy-sis and transplantation. Clin Nephrol 16: 172–180, 1981

101. Schmitt WH, Haubitz M, Mistry N, Brunkhorst R, Erbsloh-Moller B, Gross WL. Renal transplantation in Wegener’sgranulomatosis. Lancet 342: 860, 1993

102. Rostaing L, Modesto A, Oksman F, Cisterne JM, Leao G, Du-rand D: Outcome of patients with antineutrophil cytoplasmicautoantibody-associated vasculitis following ceased kidneytransplantation. Am J Kidney Dis 29: 96–102, 1997

103. Wrenger E, Pirsch JD, Cangro CB, D’Alessandro AM,Knechtle SJ, Kalayoglu M, Sollinger HW: Single-center expe-rience with renal transplantation in patients with Wegener’sgranulomatosis. Transpl Int 10: 152–156, 1997

104. Allen A, Pusey C, Gaskin G: Outcome of renal replacementtherapy in antineutrophil cytoplasmic antibody-associatedsystemic vasculitis. J Am Soc Nephrol 9: 1258–1266, 1998

105. Nachman PH, Segelmark M, Westman K, Hogan SL, SatterlyKK, Jennette JC, Falck R: Recurrent ANCA-associated smallvessel vasculitis after transplantation: A pooled analysis. Kid-ney Int 56: 1544–1550, 1999

106. Deegens JK, Artz MA, Hoitsma AJ, Wetzels JF: Outcome ofrenal transplantation in patients with pauci-immune smallvessel vasculitis or anti-GBM disease. Clin Nephrol 59: 1–9,2003

107. Elmedhem A, Adu D, Savage CO: Relapse rate and outcome

of ANCA-associated small vessel vasculitis after transplanta-tion. Nephrol Dial Transplant 18: 1001–1004, 2003

108. Moroni G, Torri A, Gallelli B, Quaglini S, Pozzi C, Banfi G,Poli F, Montagnino G, Ponticelli C, Messa P: The long-termprognosis of renal transplant in patients with systemic vascu-litis. Am J Transplant 7: 2133–2139, 2007

109. Gera M, Griffin MD, Specks U, Leung N, Stegal MD, Fer-venza FC: Recurrence of ANCA-associated vasculitis follow-ing renal transplantation in the modern era of immunosup-pression. Kidney Int 71: 1296–1301, 2007

110. Little MA, Hassan B, Jacques S, Game D, Salisbury E, Court-ney AE, Brown C, Salama AD, Harper L: Renal transplanta-tion in systemic vasculitis: When is it safe? Nephrol DialTransplant 24: 3219–3225, 2009

111. Briganti EM, Russ GR, McNeil JJ, Atkins RC, Chadban SJ: Riskof renal allograft loss from recurrent glomerulonephritis.N Engl J Med 347: 103–109, 2002

112. Cecka JM, Terasaki PI. The UNOS Scientific Renal TransplantRegistry. In: Clinical transplants, edited by Cecka JM, Tera-saki PI, Los Angeles, UCLA Tissue Typing Laboratory, 1995,pp 1–18

113. Schimtt WH, Opelz G, Ven Der Woude FJ: Renal transplan-tation is safe and successful in Wegener granulomatosis: Datafrom the Collaborative Transplant Study (abstract): J Am SocNephrol 13: 564A–565A, 2002

114. Van der Woude FJ. Kidney transplantation and ANCA associ-ated vasculitis. Cleve Clin J Med 69 [Suppl 2]: S143–S145,2002

115. Lobbedez T, Comoz F, Renaudineau E, Pujo M, RyckelynckJP, Hurault de Ligny B: Recurrence of ANCA positive glomer-ulonephritis immediately after renal transplantation. Am JKidney Dis 42: E2–E6, 2003

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JOBNAME: AUTHOR QUERIES PAGE: 1 SESS: 1 OUTPUT: Sat Mar 12 08:21:04 2011/tapraid4/cjn-cjasn/cjn-cjasn/cjn00511/cjn35791z

1—Your abbreviation “AL” was used only once and thus has been deleted. Is “amyloid lightchain” the correct expanded form of “AL”?

2—At the end of the sentence that ends as “. . . multiple myeloma”, you originally had “and” after“multiple myeloma”. It appeared as such: “. . . multiple myeloma and.” Is there a term orphrase that is missing here?

3—Your abbreviations “FMF”, “DN”, and “LCDD” were used only once and thus have beendeleted.

4—Per journal style, most nonstandard abbreviations must be used at least 3 times in the abstractto be retained; “HSN” and “SVV” were used only two times and have thus been deleted andwritten out.

5—References 14 and 103 were duplicate references; thus, reference 103 was deleted and referencesrenumbered. References 22 and 29 were duplicate references; thus, reference 29 was deletedand references renumbered. References 39 and 114 were duplicate references; thus, reference114 was deleted and references renumbered.

6—Reference 98 was originally combined with the previous reference. Per journal style, these tworeferences were split into two separate references and all the subsequent references wererenumbered. Please verify that all references in the reference list and those cited in the text arecorrect.

7—Please provide the corresponding author’s phone number and fax number.

AUTHOR QUERIES

AUTHOR PLEASE ANSWER ALL QUERIES 1