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Revised Date: 22 May 2017. Accepted Date: 25 May 2017. Please cite this .... the admission to renal replacement therapy (dialysis or transplant); deaths were.
Accepted Manuscript Lupus Nephritis in Males: Clinical Features, Course and Prognostic Factors for End Stage Renal Disease A. Urrestarazú, G. Otatti, R. Silvariño, M. Garau, Coitiño R, A. Alvarez, E. Gonzalez, L. Gadola, M. Praga, O. Noboa PII:

S2468-0249(17)30129-8

DOI:

10.1016/j.ekir.2017.05.011

Reference:

EKIR 165

To appear in:

Kidney International Reports

Received Date: 4 December 2016 Revised Date:

22 May 2017

Accepted Date: 25 May 2017

Please cite this article as: Urrestarazú A, Otatti G, Silvariño R, Garau M, R C, Alvarez A, Gonzalez E, Gadola L, Praga M, Noboa O, Lupus Nephritis in Males: Clinical Features, Course and Prognostic Factors for End Stage Renal Disease, Kidney International Reports (2017), doi: 10.1016/ j.ekir.2017.05.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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LUPUS NEPHRITIS IN MALES: Clinical Features, Course and Prognostic Factors for End Stage Renal Disease

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Brief title: Lupus Nephritis in Males A Urrestarazú 1, G Otatti1, R Silvariño 1, M Garau 1, Coitiño R1,4, A Alvarez 3, E Gonzalez 2, L Gadola 1, M Praga2, O Noboa1.

Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, Universidad de la

República, Montevideo, Uruguay.

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Servicio de Nefrología, Hospital 12 de Octubre,

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Madrid, Spain.3 Casa de Galicia, Nefrología, Montevideo, Uruguay.

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ISN Fellow

Hospital 12 de Octubre, Madrid , Spain

Oscar Noboa

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Correspondence

Nephrology Center of the Hospital de Clínicas Avenida Italia s/n CP11600

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Montevideo, Uruguay

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[email protected]

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ABSTRACT

Introduction: Given their rarity in males, systemic lupus erythematous (SLE) and lupus

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nephritis (LN) are poorly known in men. Objective: To analyse the clinical presentation and course of histology-proven SLE and LN in males, and to determine the risk factors for progression to end-stage renal disease (ESRD). Material and methods: Fifty

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patients taken from two historical cohorts from Spain (Hospital 12 de Octubre) and Uruguay were retrospectively analysed and compared with a female cohort adequately

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selected. Results: The median age at RB was 27 years (8-79). The main presentation form was nephrotic syndrome (NS), 26/50 patients (52%), and class IV LN 34/50 (68%). After treatment, 21 patients (45.6%) achieved complete renal remission. During follow-up, 12 patients required renal replacement therapy (RRT) and 3 patients died due

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to infectious causes. Patients that required RRT were compared with those that did not require it, several parameters showed significant differences (p 60 ml/min/1.73 m2 measured by CKD EPI.



The Nephrotic Syndrome (NS) was defined by the presence of oedemas, proteinuria ≥ 3.5g/24hrs, and serum albumin levels < 3.5g/dl.

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Rapidly progressive kidney failure (RPKF) was cataloged as a renal failure with a drop of over 50% of the eGFR from baseline levels in less than 3 months, together with active sediment, micro-haematuria and proteinuria.



Complete remission (CR) was defined as the drop of serum creatinine values to

proteinuria to less than 0.5g/24hrs14. 

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baseline values (or eGFR > 60ml/min.), associated with a reduction of

Partial remission (PR) was defined as the stabilization of serum creatinine levels

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(± 25%), together with a drop of at least 50% in the baseline levels of

responders (NRs)14. 

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proteinuria. The patients not included in these classes are tagged as non

Initiation of RRT was defined as the need for chronic dialysis or renal transplant.

Involvement of any extra renal organs, including joints, skin, mucosa, and

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cardiovascular, pleuropulmonary or neurological impairment, should meet the criteria

RESULTS

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Population

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suggested by the ACR12.

The records of 50 patients were analyzed; 49/50 were white of European descent, and one was of African descent. Twenty-five males came from the registries of the Hospital 12 de Octubre (Madrid), and the remaining 25 cases came from the Uruguayan Program for the Prevention of Glomerular Disease; all of them have been diagnosed with SLE and RPB-confirmed LN. The mean age at the time of RPB was 27 years (8-79). There were 4 cases diagnosed at an age between 0 and 14 years, 24 cases between 15 and 29

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ACCEPTED MANUSCRIPT years, 18 between 30 and 44, and there were 4 cases recorded in subjects over 45 years of age.

Presentation at the time of biopsy

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Tables 1 and 2 show the clinical presentation at the time of the renal biopsy, as well as the extra-renal involvement.

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Renal involvement was observed concomitantly with the onset of SLE in 29/50 patients (58%).

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The most frequent clinical form of presentation was NS: 26/50 (52%), followed by RPKF with 19/50 (38%) and 5 patients presented with Asymptomatic Urinary Abnormalities (AUA).

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Histology

The most common histological finding was type IV LN: 34/50 (68%), followed by type

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V LN with 9 (18%), type III LN with 5 cases (10%) and finally 2 cases of type II LN.

During follow-up, 10 new biopsies were performed in 8 patients, leading to 8 re-

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classifications of the dominant injury pattern. The changes observed went from initial type II to type IV in one case, from III to IV in two patients, from IV to III in two other cases, and to V in another, and from V to III and IV, respectively. Worsening of the histological pathology was shown in 5 cases.

Management and Course

All patients received corticosteroids as initial therapy. Cyclophosphamide (CPH) was associated in 39 patients (84.7%), 33 of which were administered as intravenous boluses 8

ACCEPTED MANUSCRIPT and 6 per os. Azathioprine was used in 10 and Mycophenolate Mofetil (MMF) in 3 patients. Twenty-three patients received Azathioprine and 6 received MMF as maintenance therapy.

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The cohort had a median follow-up of 54 months (2-360). At the end of follow-up, 31 patients were in follow up, 12 (26%) had initiated RRT (one in the early kidney transplant modality), 8/12 after the year 2000, and 4 patients were lost to follow-up. The

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three deaths recorded were all due to infections; respiratory in 2 cases (severe pneumonia, respiratory sepsis), and finally one with invasive mycosis.

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Complete Remission (CR) was achieved in 21 patients, 18 had a partial remission (PR), and 7 had no remission (NR) (Figure 2).

Therapy-related complications were found in 15 patients. Of these 15 patients, 12 had

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received cyclophosphamide. There were patients with more than one complication. Infectious complications were the most common (8/15), with a predominance of respiratory infections. Haemorrhagic complications were observed in 7 patients: (5

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gastrointestinal bleedings, 1 complication of renal biopsy and one (1) haematoma of the abdominal wall in a case of severe thrombocytopenia). Three of the seven patients with

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haemorrhagic complications also had an associated Antiphospholipid Syndrome (APLS) and were on anti-coagulation therapy. There were three reports of steroidassociated psychosis and one patient had an aseptic necrosis of the femur.

Risk factors for initiating RRT

The median renal survival was 229 months (2-360). Five-year renal survival was close to 78% and over 70% at 10 years. (Figure 1).

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ACCEPTED MANUSCRIPT The remission of the lupus nephritis had an impact on renal survival. Significant differences were found between the renal survival of the CR group, the PR group (p=0.005), and the Non Remission (NR) group (p