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Original article
Clinical characteristics of membranous nephropathy with spontaneous remission: An analysis of 24 patients
Características clínicas de la nefropatía membranosa con remisión espontánea: análisis de 24 pacientes
Xu Wanga,1, Jiao Zhanga,b,1, Gu-ming Zoua, Xu-min Zhenga, Jia-yi Lia, Hong-mei Gaoa, Shi-min Jianga, Wen-ge Lia,
Corresponding author
wenge_lee2002@126.com

Corresponding author.
a Department of Nephrology, China-Japan Friendship Hospital, Beijing 100029, China
b Beijing University of Chinese Medicine, Beijing 100029, China
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Typical renal histopathological of complement pathway activation in patients with PLA2R-associated MN&#46; Immunohistochemical staining for C1q&#44; factor B&#44; and mannose-binding lectin &#40;MBL&#41; in the glomeruli to detect the complement pathway in patients with PLA2R-associated MN&#46; &#40;a&#41; Immunohistochemical staining for C1q&#44; factor B&#44; and MBL in patients with spontaneous remission&#46; The expression of C1q was slightly positive in only one patient &#40;C1q&#44; arrowheads&#41;&#46; &#40;b&#41; Immunohistochemical staining for C1q&#44; factor B&#44; and MBL in patients with nephrotic syndrome &#40;arrow&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Primary membranous nephropathy &#40;pMN&#41; has become a major glomerular disease&#59; however&#44; approximately one-third of the affected patients achieve spontaneous remission &#40;SR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a> The possibility of complete spontaneous remission has been reported in a few previous related case reports or case series&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">2&#8211;17</span></a> Among them&#44; one large-scale case series reported 29 cases with only 9 months of follow-up after SR&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a> Therefore&#44; the prognosis of phospholipase A2 receptor &#40;PLA2R&#41;-associated membranous nephropathy &#40;MN&#41; with SR remains unclear&#46; To the best of our knowledge&#44; we have tried to confirm the SR of MN from the perspective of renal histopathology for the first time and analyzed the complement activation state during remission&#46; Further&#44; our study highly focused on the prognosis of MN with SR and included a large number of samples and a long duration of follow-up&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Membranous nephropathy is an autoimmune renal disease&#44; and PLA2R is the major autoantigen of pMN&#44; which can be detected in approximately 70&#37; of patients with pMN&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">18&#44;19</span></a> In this study&#44; we detected anti-PLA2R antibodies in sera and PLA2R antigens in renal biopsy tissues of patients with SR of PLA2R-associated MN&#46; In addition&#44; an increasing number of studies have shown that complement activation is closely related to MN pathogenesis&#46; In this study&#44; we examined the immunohistochemical expression of C1q &#40;to measure the classical pathway&#41;&#44; mannose-binding lectin &#40;MBL&#44; to measure the lectin pathway&#41;&#44; and factor B &#40;to measure the alternative pathway&#41; in glomerular areas&#44; and the status of complement activation in patients with SR of MN was compared with that in nephrotic syndrome &#40;NS&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0015" class="elsevierStylePara elsevierViewall">Patients diagnosed with MN after examining their renal biopsy at the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021 were recruited for this study&#46; We defined PLA2R-associated MN with SR as patients with a positive glomerular PLA2R antigen who achieved spontaneous remission at the time of biopsy without previous treatment with glucocorticoids or immunosuppressants&#46; The inclusion criteria were as follows&#58; &#40;1&#41; patient with a minimum of 10 glomeruli&#59; &#40;2&#41; patient above 30 years&#59; &#40;3&#41; patient with initial 24-h urinary total protein level<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;d and serum albumin level<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>g&#47;L&#59; &#40;4&#41; patient with negative serum anti-PLA2R antibody and positive glomerular PLA2R antigen&#59; and &#40;5&#41; patient with no history of treatment with glucocorticoids&#44; immunosuppressants&#44; rituximab&#44; and other biological agents&#46; The exclusion criteria include &#40;1&#41; patients with comorbidity of severe systemic diseases or life-threatening diseases&#44; &#40;2&#41; patients with incomplete clinical or pathological data&#44; and &#40;3&#41; patients with comorbid renal diseases&#46; All patients were followed for<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>6 months&#46; Follow-up started at the time of renal biopsy and ended at either one of the following &#40;whichever arrived first&#41;&#58; &#40;1&#41; March 2022 or &#40;2&#41; the date of relapse events&#46; This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Clinical Research Ethics Committee of the China-Japan Friendship Hospital &#40;2021-113-K71&#41;&#46; All patients provided written informed consent at the time of biopsy&#44; including consent to publish and report their data&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Clinical data collection</span><p id="par0020" class="elsevierStylePara elsevierViewall">Patients&#8217; baseline characteristics were collected at the time of renal biopsy&#44; including age&#44; sex&#44; albumin&#44; proteinuria&#44; urinary albumin-to-creatinine ratio &#40;ACR&#41;&#44; complement &#40;C3&#44; C4&#41;&#44; serum creatinine&#44; and estimated glomerular filtration rate &#40;eGFR&#41;&#46; All clinical and laboratory data were collected from the electronic medical records of our hospital&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Detection of serum anti-PLA2R antibody and glomerular PLA2R antigen</span><p id="par0025" class="elsevierStylePara elsevierViewall">&#40;a&#41; Serum anti-PLA2R antibodies were detected using antigen-specific enzyme-linked immunosorbent assay &#40;ELISA&#41; in all patients at the time of diagnosis&#46; A standard ELISA was performed according to the manufacturer&#39;s instructions &#40;Euroimmun&#41;&#44; and the cutoff value was set at 20<span class="elsevierStyleHsp" style=""></span>RU&#47;ml&#46; Patients&#8217; sera at presentation were stored at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C until use&#46; &#40;b&#41; Glomerular PLA2R antigens were detected by immunofluorescence using a rabbit polyclonal PLA2R antibody &#40;Abcam&#44; UK&#41; in renal tissue&#44; according to standard protocols&#46; The specimens were embedded in paraffin&#44; sectioned at 3<span class="elsevierStyleHsp" style=""></span>&#956;m&#44; dewaxed&#44; hydrated&#44; antigen retrieved&#44; and incubated overnight at 4<span class="elsevierStyleHsp" style=""></span>&#176;C with rabbit polyclonal antibodies &#40;diluted 1&#58;500&#41; against human PLA2R&#44; followed by FITC-conjugated antibodies &#40;diluted 1&#58;100&#41;&#46; The sections were observed using immunofluorescence microscopy&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Renal histology</span><p id="par0030" class="elsevierStylePara elsevierViewall">The biopsy specimens were divided into three portions&#44; processed&#44; and evaluated according to a previously standardized protocol&#46; Briefly&#44; one portion was fixed in buffered formalin&#44; processed into paraffin blocks&#44; and stained routinely for light microscopy&#46; The second portion was frozen for direct immunofluorescence studies to detect IgG&#44; IgA&#44; IgM&#44; C3&#44; C4&#44; C1q&#44; and fibrinogen levels&#46; The third portion was processed into resin blocks&#44; and its ultrathin slices were used for transmission electron microscopy&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Immunohistochemistry of complement component</span><p id="par0035" class="elsevierStylePara elsevierViewall">The complement component in renal tissue was detected by immunohistochemistry according to a previously described protocol&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> The following primary antibodies were incubated overnight at 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; including anti-C1q &#40;ab268120&#41; diluted 1&#58;400&#44; anti-mannose binding lectin &#40;MBL&#41; &#40;ab23457&#41; diluted 1&#58;25&#44; and anti-factor B &#40;ab192577&#41; diluted 1&#58;400 separately&#44; and were all from Abcam&#44; Cambridge&#44; United Kingdom&#46; Phosphate buffer was used as a blank control instead of the primary antibody&#46; The reactions were visualized by staining with horseradish peroxidase and diaminobenzidine &#40;DAB&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Systematic review of literature</span><p id="par0040" class="elsevierStylePara elsevierViewall">A literature search was performed on PubMed&#44; Embase&#44; Web of Science&#44; and Cochrane Library&#44; as well as on our center&#39;s database &#40;from the establishment of the database to March 2022&#41;&#46; The keywords used include &#8220;Glomerulonephritis&#44; Membranous&#8221; &#91;Mesh&#93;&#44; &#8220;Receptors&#44; Phospholipase A2&#8221; &#91;Mesh&#93; and &#8220;remission&#8221; &#91;Mesh&#93;&#46; The inclusion criteria were&#58; &#40;1&#41; prospective or retrospective cohort study&#44; and &#40;2&#41; studies analyzing patients with proven MN based on biopsy reports with positive serum anti-PLA2R antibody or glomerular PLA2R antigen and who achieved spontaneous remission without immunosuppressive therapy during follow-ups&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Data are presented as median and interquartile range &#40;IQR&#41; for data that were not normally distributed or mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; for normally distributed data for continuous variables&#46; Statistical analyses were performed using SPSS 18&#46;0&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">General data of the patients</span><p id="par0050" class="elsevierStylePara elsevierViewall">A total of 899 patients diagnosed with MN in the Renal Department of China-Japan Friendship Hospital between June 2015 and September 2021 were analyzed retrospectively&#46; Among them&#44; 24 patients with SR of PLA2R-associated MN were recruited for this study&#59; 11 were male&#44; and 13 were female&#44; with an average age of 49&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;5 years &#40;range&#44; 30&#8211;77 years&#41; at diagnosis&#46; The initial 24-hour urinary total protein and serum albumin levels were 0&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;14<span class="elsevierStyleHsp" style=""></span>g&#47;d and 37&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;4<span class="elsevierStyleHsp" style=""></span>g&#47;L&#44; respectively&#46; The initial serum creatinine &#40;Normal value&#58; 35&#8211;106<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#41; and eGFR values were 65&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;8<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L and 103&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;0<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; respectively&#46; Normal renal function&#44; defined as an eGFR<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>90<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; occurred in 22 cases &#40;91&#46;7&#37;&#41;&#44; and renal tubular injury was rare&#44; as only one patient had elevated urinary N-acetyl-beta-glucosaminidase &#40;NAG&#41; levels&#46; Anti-nuclear antibody &#40;ANA&#41; was negative in all patients&#44; and the baseline mean serum Complement C3 &#40;normal value&#58; 70&#8211;128<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; and Complement C4 &#40;normal value&#58; 16&#8211;47<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; were 96&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;4<span class="elsevierStyleHsp" style=""></span>mg&#47;dl and 20&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;0<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; respectively&#46; For anti-PLA2R antibody&#44; all patients were negative to ELISA&#44; with a cutoff value of &#60;20<span class="elsevierStyleHsp" style=""></span>RU&#47;ml&#46; The general patient data are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Histopathological characteristics</span><p id="par0055" class="elsevierStylePara elsevierViewall">Kidney biopsies were performed in all patients&#44; and MN was diagnosed in all specimens collected&#46; An average number of 29&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;2 &#40;range&#58; 11&#8211;84&#41; glomeruli were sampled for light microscopy per renal biopsy specimen&#46; Immunofluorescence staining of the renal histology revealed PLA2R-associated MN&#46; Light microscopy showed diffuse thickening of the basement membrane and subepithelial deposition of fuchsinophilic proteins in most specimens&#44; together with focal segmental spike formation&#46; IgG subclasses were identified&#44; and the positivity rates of IgG1 and IgG4 in immunofluorescence staining were 100&#46;0&#37; and 87&#46;5&#37;&#44; respectively&#46; As mentioned above&#44; immunohistochemical staining for C1q&#44; MBL&#44; and factor B in the glomeruli was performed to detect the complement pathway in patients with PLA2R-associated MN with SR &#40;shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Among these patients&#44; MBL and factor B expressions were negative in 23 patients&#44; while C1q expression was weakly positive in one patient&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Likewise&#44; we recruited 24 age-&#44; sex-&#44; and Scr-matched patients with MN who presented with nephrotic syndrome at the initial onset as the control group&#46; Glomerular C1q&#44; MBL&#44; and factor B expressions were significantly positive in most of these patients&#44; thus suggesting that more than one complement pathway is activated during the progression of nephrotic syndrome in patients with MN&#44; whereas it is rarely activated in patients with SR&#46; The classical complement pathway may also play a role in the early or remission state of MN&#59; however&#44; more patients need to be further studied&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Treatment and outcomes</span><p id="par0065" class="elsevierStylePara elsevierViewall">All patients with SR of pMN received optimal supportive care&#46; Antihypertensive drugs belonging to the renin&#8211;angiotensin&#8211;aldosterone system inhibitor &#40;RASi&#41; group were administered to reduce proteinuria and blood pressure &#40;BP&#41;&#46; The RASi includes angiotensin-converting enzyme inhibitors &#40;ACEIs&#41; and angiotensin receptor blockers &#40;ARBs&#41;&#44; and the targeted BP range is 110&#8211;130&#47;60&#8211;80<span class="elsevierStyleHsp" style=""></span>mmHg&#46; Among the patients&#44; four were treated with ACEIs and 15 with ARBs&#44; a combination of ACEI and ARB was administered to two patients&#44; and the rest were treated without RASi due to their low basal blood pressure and low urinary protein &#40;UTP<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;3<span class="elsevierStyleHsp" style=""></span>g&#47;d&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">At the end of the follow-up period of 33&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;1 months &#40;range&#58; 6&#8211;73 months&#41;&#44; 22&#47;24 &#40;91&#46;7&#37;&#41; patients maintained remission&#44; while relapse occurred in one case&#46; Patient No&#46; 16 experienced a repeated relapse caused by respiratory tract infection at 50 and 70 months&#44; and glucocorticoids and cyclosporine were successively used for the immunosuppressive therapy&#59; however&#44; this patient maintained nephrotic proteinuria and deteriorated renal function&#46; The remaining patient had renal function impairment without increased urinary protein levels at 42 months of follow-up due to acute coronary syndrome and coronary angiography&#46; Notably&#44; none of the patients underwent hemodialysis or died&#46; Details of the outcomes are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">Membranous nephropathy is an autoimmune renal disease and a common cause of primary nephrotic syndrome in adults&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> Patients with MN tend to get spontaneous remission&#46; Although the possibility of SR has been reported in previous studies on patients with PLA2R-associated MN&#44;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">2&#8211;17</span></a> only a few completed SR cases have been reported&#44; including 16 case reports or case series with a total of 97 cases &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Mahmud et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a> performed a multicenter survey and reported 29 patients with SR of PLA2R-associated MN&#44; with only 9 months of follow-up after remission&#46; Similarly&#44; Rodas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">8</span></a> conducted a prospective observational study on patients with PLA2R-associated MN for 99 months and reported six patients with SR&#46; Since the prognosis of PLA2R-associated MN with SR remains unclear&#44; we decided to carry out this study at our hospital&#46; To the best of our knowledge&#44; this study had a large sample size and a long follow-up period for PLA2R-associated MN with SR&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">PLA2R is the major autoantigen of pMN&#44; highly expressed in glomerular podocytes&#44; and its autoantibodies are mainly IgG4 subtypes&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">22&#44;23</span></a> Serum anti-PLA2R antibodies play an important role in the clinical prediction of pMN at diagnosis and have been correlated with the disease activity&#46; Previous studies have shown that the PLA2R IgG4 subclass could improve the sensitivity and specificity of MN diagnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">24</span></a> Serum PLA2Rab levels at baseline may also be used independently to predict the timing of clinical remission&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> The risk factors influencing the long-term prognosis of PLA2R-associated MN include male sex&#44; increased proteinuria during the course of the disease&#44; decreased eGFR at onset&#44; high serum PLA2Rab levels&#44; and C3 positive deposition in renal biopsy samples&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a> In patients with pMN&#44; IgG deposition in renal tissue may be accompanied by C1q deposition&#44; where IgG1 is mainly in the early stage&#44; IgG4 is mainly in the late stage&#44; and C1q is positively correlated with IgG1&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> Thus&#44; activation of the classical complement pathway plays a role in the early stage of the disease but is probably not a major player&#46; Other studies have also suggested that the MBL pathway of complement activation commonly affects the prognosis of pMN&#44; as patients with MBL deposition reach incomplete remission faster&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a> Therefore&#44; we examined the immunohistochemical expression of C1q &#40;to measure the classical pathway&#41;&#44; MBL &#40;to measure the lectin pathway&#41;&#44; and factor B &#40;to measure the alternative pathway&#41; in glomeruli in our study&#46; The expression of C1q was slightly positive in only one patient&#44; while the expression of MBL and factor B was significantly weaker in patients with nephrotic syndrome&#46; Previous studies have shown that affinity-purified IgG4 anti-PLA2R antibodies can bind to MBL and promote C4 deposition&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a> which we also confirmed in patients with nephrotic syndrome&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Numerous studies have shown the correlation between proteinuria and renal prognosis&#44; and proteinuria might be the strongest predictor of outcome in patients with MN&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> Moreover&#44; it has also been reported that nearly 80&#37; of patients with subnephrotic proteinuria could survive this renal condition for more than 10 years&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a> A literature survey showed that after 6 months of conservative treatment&#44; the proportion of SR &#40;including complete remission and partial remission&#41; in patients with proteinuria<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>g&#47;d and patients with proteinuria<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>8<span class="elsevierStyleHsp" style=""></span>g&#47;d was 45&#37; and 34&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">11&#44;32</span></a> Patients with pMN in a persistent remission state usually have promising long-term prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">33</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">All patients included in this study were assessed by clinical and laboratory criteria&#44; which conformed to a low risk of progressive loss of kidney function&#44; and received adequate supportive care to reduce proteinuria by RASi&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">34&#44;35</span></a> Most patients remain in remission for a long period and do not receive treatment with immunosuppressive agents&#44; including glucocorticoids&#46; The identification of patients with expected SR is significant for those with a low risk of progressive loss of kidney function&#44; and the recurrence of MN should not be underestimated&#46; A retrospective cohort study of 395 patients with MN showed that 42&#37; of patients with subnephrotic proteinuria developed nephrotic syndrome within 1 year of follow-up&#44; and 61&#37; of patients developed nephrotic syndrome at 4 years of follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a> The patients with SR of MN in our study with low initial proteinuria &#40;&#60;0&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;d&#41; had a low recurrence rate and slow progression of renal function loss&#46; During follow-up&#44; only one patient experienced renal function loss due to contrast medium&#44; and one patient experienced relapse due to respiratory tract infection&#46; Comprehensive prevention of infection may benefit patients with MN in remission&#46; We speculate that the initial urinary protein level of &#60;0&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;d in patients with SR of MN is of great significance for lower recurrence rates and long-term renal prognosis&#46; This study had several limitations&#44; which included its relatively small sample size&#44; single-center design&#44; and limited follow-up time&#46; Therefore&#44; a multicenter study with larger sample size and longer follow-up period should be carried out in the future&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusion</span><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study investigated the prognosis of patients with SR of PLA2R-associated MN&#46; We found that most patients with baseline urinary protein levels of &#60;0&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;d had a good prognosis and lower recurrence rate&#46; Also&#44; we found that respiratory tract infection was one of the causes of MN recurrence in patients with remission&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Take-home-message of complement</span><p id="par0100" class="elsevierStylePara elsevierViewall">Complement activation is involved in the development of MN&#46; In particular&#44; activation of the classical complement pathway in glomeruli might accelerate the disease progression&#59; however&#44; it is not significant in patients with SR&#46; Therefore&#44; proteinuria and the titers of PLA2R&#44; together with complement&#44; should be used to predict SR in patients with MN&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Authors&#8217; contributions</span><p id="par0105" class="elsevierStylePara elsevierViewall">X&#46;W&#46; and J&#46;Z&#46; contributed to the research idea&#44; literature search&#44; study design&#44; statistical analysis and article draft&#46; G&#46;M&#46;Z&#46; and S&#46;M&#46;J&#46; were responsible for revising the article&#46; X&#46;M&#46;Z&#46;&#44; J&#46;Y&#46;L&#46; and H&#46;M&#46;G&#46; contributed to the data collection and interpretation of the results&#46; W&#46;G&#46;L&#46; contributed important intellectual content during manuscript drafting or revision&#46; All authors helped revising the paper and read and approved the final version of the manuscript&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Consent for publication</span><p id="par0110" class="elsevierStylePara elsevierViewall">All patients provided written informed consent including consent to publish and report individual patient data&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Data availability statement</span><p id="par0115" class="elsevierStylePara elsevierViewall">The datasets used and&#47;or analyzed during the current study are available from the corresponding author on reasonable request&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Ethics approval and informed consent</span><p id="par0120" class="elsevierStylePara elsevierViewall">Study approval statement&#58; The research was in compliance with the Declaration of Helsinki&#46; The study has been approved by the clinical research ethics committee of the China-Japan Friendship Hospital&#46; However&#44; since it was a retrospective study and patient&#39;s identity was anonymous&#44; the study had been granted an exemption from requiring ethics approval document and inform consent to participate statement&#44; which got a record number as 2021-113-K71&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Funding sources</span><p id="par0125" class="elsevierStylePara elsevierViewall">Not applicable&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To investigate the prognosis of patients with spontaneous remission &#40;SR&#41; of phospholipase A2 receptor &#40;PLA2R&#41;-associated membranous nephropathy &#40;MN&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Patients diagnosed with MN were recruited after examining their renal biopsy in the Renal Department of China-Japan Friendship Hospital between January 2015 and September 2021&#46; Among them&#44; 24 patients with SR were included in this study and follow-up&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Twenty-four patients diagnosed with SR of PLA2R-associated MN were recruited&#59; 11 were male&#44; and 13 were female&#44; with a mean age of 49&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;5 years &#40;range&#44; 30&#8211;77 years&#41;&#46; The initial 24-hour urinary total protein and serum albumin levels were 0&#46;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;14<span class="elsevierStyleHsp" style=""></span>g&#47;d and 37&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;4<span class="elsevierStyleHsp" style=""></span>g&#47;L&#44; respectively&#44; and the initial serum creatinine was 65&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;8<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;L&#46; During the follow-up of 33&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;1 months &#40;range&#44; 6&#8211;73 months&#41;&#44; 22 &#40;91&#46;7&#37;&#41; patients maintained remission&#59; however&#44; one patient had impaired renal function due to acute coronary syndrome and coronary angiography findings&#44; and one patient experienced a repeated relapse caused by respiratory tract infection&#44; at 50 and 70 months&#46; A systematic review of the relevant literature was conducted&#44; and records of patients with SR of PLA2R-associated MN were retrieved from 16 case reports or case series with a total of 97 cases&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Most patients with SR of MN had a promising long-term prognosis&#44; with only a few cases of relapse&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Investigar el pron&#243;stico de los pacientes con remisi&#243;n espont&#225;nea en la nefropat&#237;a membranosa &#40;MN&#44; por sus siglas en ingl&#233;s&#41; asociada al receptor fosfolipasa A2 &#40;PLA2R&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Pacientes con MN diagnosticados por biopsia renal en el Departamento Renal del China-Japan Friendship Hospital entre enero de 2015 y septiembre de 2021&#46; Entre ellos&#44; 24 pacientes con remisi&#243;n espont&#225;nea fueron reclutados y seguidos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se reclutaron 24 pacientes con MN en remisi&#243;n espont&#225;nea asociada a PLA2R&#59; 11 varones y 13 mujeres&#44; con una edad media de 49&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;5 a&#241;os &#40;rango&#58; 30-77 a&#241;os&#41; en el momento del diagn&#243;stico&#46; La prote&#237;na total y la alb&#250;mina s&#233;rica en orina de 24<span class="elsevierStyleHsp" style=""></span>h iniciales fueron de 0&#44;29<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;14 y 37&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;4<span class="elsevierStyleHsp" style=""></span>g&#47;l&#44; respectivamente&#59; la creatinina s&#233;rica inicial fue de 65&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;8<span class="elsevierStyleHsp" style=""></span>&#956;mol&#47;l&#46; Durante el seguimiento de 33&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#44;1 &#40;rango&#58; 6-73&#41; meses&#44; 22 pacientes &#40;91&#44;7&#37;&#41; mantienen la remisi&#243;n&#46; Un paciente present&#243; insuficiencia renal por s&#237;ndrome coronario agudo y angiograf&#237;a coronaria&#46; Otro paciente tuvo una reca&#237;da causada por una infecci&#243;n del tracto respiratorio 2 veces&#44; a los 50 y 70 meses&#46; Se realiz&#243; una revisi&#243;n sistem&#225;tica de la literatura&#46; Los pacientes con MN asociada con PLA2R en remisi&#243;n espont&#225;nea se recuperaron en 16 informes o series de casos&#44; de 97 casos en total&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La mayor&#237;a de los pacientes con MN en remisi&#243;n espont&#225;nea tuvieron un pron&#243;stico prometedor a largo plazo&#44; mientras que solo unos pocos casos tuvieron reca&#237;da&#46;</p></span>"
        "secciones" => array:4 [
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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    "NotaPie" => array:1 [
      0 => array:3 [
        "etiqueta" => "1"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Contributed equally to this paper&#46;</p>"
        "identificador" => "fn0005"
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      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Typical renal histopathological of complement pathway activation in patients with PLA2R-associated MN&#46; Immunohistochemical staining for C1q&#44; factor B&#44; and mannose-binding lectin &#40;MBL&#41; in the glomeruli to detect the complement pathway in patients with PLA2R-associated MN&#46; &#40;a&#41; Immunohistochemical staining for C1q&#44; factor B&#44; and MBL in patients with spontaneous remission&#46; The expression of C1q was slightly positive in only one patient &#40;C1q&#44; arrowheads&#41;&#46; &#40;b&#41; Immunohistochemical staining for C1q&#44; factor B&#44; and MBL in patients with nephrotic syndrome &#40;arrow&#41;&#46;</p>"
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        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; UTP&#44; 24-h urinary total protein&#59; Alb&#44; albumin&#59; Scr&#44; serum creatinine&#59; eGFR&#44; estimated glomerular filtration rate&#46;</p>"
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                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3334745.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">General data of the patients with spontaneous remission in PLA2R associated membranous nephropathy &#40;sort by age&#41;&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
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          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; UTP&#44; 24-h urinary total protein&#59; Alb&#44; albumin&#59; Scr&#44; serum creatinine&#59; eGFR&#44; estimated glomerular filtration rate&#59;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t" scope="col">Patient no&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Follow-up &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Scr &#40;&#956;mol&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">eGFR &#40;ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcome&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">105&#46;53&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Relapse&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;46&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">40&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;36&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">77&#46;9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">102&#46;64&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">95&#46;21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Remission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Renal function deterioration&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t" scope="col">No&#46; of cases with SR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col">Follow-up &#40;months&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;Serum&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;Renal tissue&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Jurubi&#539;&#259;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Jatem-Escalante&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Guo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cheng&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nikolopoulou&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Yin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Partially positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rodas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mahmud&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dettmar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Seitz-Polski&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2018&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Jullien&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pourcine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hoxha&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Negative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kim&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Timmermans&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hoxha&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "imagenFichero" => array:1 [
                0 => "xTab3334744.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Reports in literatures of patients with spontaneous remission of PLA2R associated membranous nephropathy&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0180"
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                  "host" => array:1 [
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            1 => array:3 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Jurubi&#539;&#259;"
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            2 => array:3 [
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                            0 => "E&#46; Jatem-Escalante"
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                            2 => "E&#46; Gr&#224;cia-Lavedan"
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                            4 => "J&#46; Gonzalez"
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                  ]
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                    0 => array:2 [
                      "doi" => "10.1093/ckj/sfab116"
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                        0 => array:2 [
                          "etal" => false
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                            0 => "Y&#46; Guo"
                            1 => "N&#46; Guo"
                            2 => "J&#46; Wang"
                            3 => "R&#46; Wang"
                            4 => "L&#46; Tang"
                          ]
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                    0 => array:2 [
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                0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46;J&#46; Cheng"
                            1 => "X&#46;Y&#46; Cheng"
                            2 => "Y&#46;M&#46; Zhang"
                            3 => "F&#46; Wang"
                            4 => "X&#46; Wang"
                            5 => "L&#46;Q&#46; Meng"
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                    0 => array:2 [
                      "doi" => "10.1007/s40620-021-01182-z"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Nikolopoulou"
                            1 => "C&#46; Teixeira"
                            2 => "H&#46;T&#46; Cook"
                            3 => "C&#46; Roufosse"
                            4 => "T&#46;H&#46;D&#46; Cairns"
                            5 => "J&#46;B&#46; Levy"
                          ]
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                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1093/ckj/sfaa026"
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            6 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes of primary membranous nephropathy based on serum anti-phospholipase A2 receptor antibodies and glomerular phospholipase A2 receptor antigen status&#58; a retrospective cohort study"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Yin"
                            1 => "J&#46; Wang"
                            2 => "W&#46; Liang"
                            3 => "L&#46; Zhan"
                            4 => "Y&#46; Liu"
                            5 => "J&#46; Lin"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
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                      "doi" => "10.1080/0886022x.2020.1792315"
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            7 => array:3 [
              "identificador" => "bib0215"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;M&#46; Rodas"
                            1 => "A&#46; Matas-Garc&#237;a"
                            2 => "X&#46; Barros"
                            3 => "M&#46; Blasco"
                            4 => "O&#46; Vi&#241;as"
                            5 => "A&#46; Llobell"
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                    0 => array:2 [
                      "doi" => "10.1093/ckj/sfy005"
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                        "tituloSerie" => "Clin Kidney J"
                        "fecha" => "2019"
                        "volumen" => "12"
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                ]
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            8 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of phospholipase A2 receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Mahmud"
                            1 => "H&#46;O&#46; Pinnschmidt"
                            2 => "L&#46; Reinhard"
                            3 => "S&#46; Harendza"
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Original language: English
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