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2 doses&#41; and oral tacrolimus &#40;with control of serum level&#41;&#44; requiring rituximab bolus at the sixth month&#46; At the ninth month of evolution&#44; due to progressive deterioration of renal function and persistence of nephrotic syndrome&#44; we withdrew tacrolimus and initiated treatment with cyclophosphamide in monthly boluses &#40;6 boluses&#41;&#46; We continued treatment with semiannual rituximab until 18 months of treatment &#40;a total of 5 boluses&#41;&#44; with persistence of renal function deterioration &#40;urea 42<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; creatinine 1&#46;86<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; GFR 42<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&#44; nephrotic syndrome &#40;albumin 2&#46;0<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; total protein 3&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; urine protein&#47;creatinine 5660&#46;65<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#41; and anti-PLA2R positivity &#40;positive&#58; 109&#46;44 UR&#47;ml&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In February 2022&#44; we decided to treat the patient with obinutuzumab &#40;100<span class="elsevierStyleHsp" style=""></span>mg&#44; 900<span class="elsevierStyleHsp" style=""></span>mg on consecutive days&#44; and 1<span class="elsevierStyleHsp" style=""></span>g after 14 days&#41;&#44; and observed a partial response in the sixth month &#40;albumin 2&#46;8<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; total protein 4&#46;7<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; protein&#47;creatinine 2510&#46;46<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#44; urea 71<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; creatinine 1&#46;99<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; GFR 38<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&#44; that was confirmed at the ninth month &#40;albumin 3&#46;1<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; total proteins 5&#46;0<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#44; protein&#47;creatinine 1643&#46;19<span class="elsevierStyleHsp" style=""></span>mg&#47;g&#41;&#44; with improvement of renal function &#40;urea 46<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; creatinine 1&#46;59<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#44; GFR 50<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41; and negativity of PLA2R antibodies&#46; The patient had no infusion-related adverse effects or infectious complications after treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Rituximab is a chimeric anti-CD20 type 1 monoclonal antibody that upon binding to the CD20 receptor internalizes and degrades it&#44; resulting in reduced macrophage recruitment and phagocytosis&#44; with reduced B-cell elimination and increased antibody requirement&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Obinutuzumab is a humanized anti-CD20 type 2 monoclonal antibody with greater cytotoxicity than rituximab against B cells <span class="elsevierStyleItalic">in vitro</span>&#46; It binds to a CD20 epitope different from rituximab&#44; preventing internalization of the CD20&#47;antibody complex&#46; Due to a modification in its carbohydrate&#44; it has a higher affinity for the Fc&#947; RIIIa of B cells&#44; which translates into greater ability to recruit effector cells&#44; greater direct cytotoxicity&#44; with less reliance on complement-dependent cytotoxicity compared to rituximab&#46; In addition&#44; it induces direct lysosome-mediated cell death and less dependence on high levels of B-cell activating factor&#44; which contributes to greater depletion of memory B cells&#44; which are more resistant to the action of rituximab&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The clinical experience of obinutuzumab in membranous glomerulonephritis is limited to&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Three patients with anti-PLA2R-positive membranous glomerulonephritis treated with rituximab&#44; without clinical and immunological remission&#44; and in whom&#44; after treatment with obinutuzumab&#44; complete immunological remission was achieved in all three patients&#44; followed by improvement in proteinuria and normalization of serum albumin&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">A sample of 10 patients with rituximab-resistant membranous glomerulonephritis&#44; in whom&#44; after treatment with obinutuzumab&#44; complete remission was achieved in 40&#37; and partial remission in 50&#37;&#44; with immunological remission in all cases and response maintained at 24 months&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Two patients with anti-PLA2R-positive membranous glomerulonephritis resistant to prednisone&#44; cyclosporine&#44; cyclophosphamide and rituximab&#44; with immunological remission 12 months after treatment with obinutuzumab&#44; with normalization of serum albumin&#44; improvement of proteinuria and stable renal function&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">A patient with membranous glomerulonephritis secondary to IgG4-related disease&#44; with anaphylactic reaction to rituximab&#44; with complete remission and normalization of IgG4 levels after treatment with obinutuzumab&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></li></ul></p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion&#44; obinutuzumab is a therapeutic alternative in patients with membranous glomerulonephritis in whom immunologic and clinical remission is not achieved with rituximab and avoids the need for treatments with greater toxicity&#46; Currently there is a phase <span class="elsevierStyleSmallCaps">iii</span> clinical trial to evaluate the efficacy and safety of obinutuzumab compared to tacrolimus in patients with primary membranous glomerulonephritis &#40;ClinicalTrials&#46;gov Identifier&#58; <a href="ctgov:NCT04629248">NCT04629248</a>&#41;&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Consent to publication</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that the patient presented in this article has given consent to use his or her medical information for this publication&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">This research has not received specific support from public sector agencies&#44; commercial sector or non-profit entities&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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