Letters to the Editor
Single rituximab dose as treatment for membranoproliferative glomerulonephritis relapse after kidney transplant
Dosis única de rituximab como tratamiento de recidiva de glomerulonefritis membranoproliferativa en trasplante renal
Leonidas Cruzado Vega
, Alba Santos García
Corresponding author
Hospital General Universitario de Elche, Alicante, Spain
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"Hospital General Universitario de Elche, Alicante, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Dosis única de rituximab como tratamiento de recidiva de glomerulonefritis membranoproliferativa en trasplante renal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1786 "Ancho" => 2833 "Tamanyo" => 232536 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes over time in proteinuria and plasma albumin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The current classification of membranoproliferative glomerulonephritis (MPGN) is based on immunofluorescence findings, with aetiological and therapeutic implications.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Idiopathic MPGN is uncommon.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> Treatment recommendations are therefore based on case series and non-randomised clinical trials. Current therapy consists of corticosteroids and antiproliferative agents (mycophenolate, cyclophosphamide), monoclonal antibodies (rituximab, bortezomib) or plasmapheresis.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">3–5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Worse kidney graft survival and a higher risk of relapse in kidney transplantation have been demonstrated in patients with MPGN compared to other forms of glomerulonephritis.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We report the case of a 66-year-old man with a history of arterial hypertension and diabetes mellitus who, in 2012, developed kidney failure (creatinine 1.5<span class="elsevierStyleHsp" style=""></span>mg/dl, glomerular filtration rate [GFR] 50<span class="elsevierStyleHsp" style=""></span>ml/min) associated with nephrotic syndrome (proteinuria >15<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h, hypoalbuminaemia and dyslipidaemia), with microscopic haematuria, without casts. The initial workup included antineutrophil cytoplasmic antibodies (ANCAs), antinuclear antibodies (ANAs), rheumatoid factor, protein electrophoresis in serum and urine (negative, normal C3 and C4).</p><p id="par0025" class="elsevierStylePara elsevierViewall">The results of a kidney biopsy were consistent with type 1 MPGN. Immunofluorescence showed deposits of immunoglobulin G (IgG) (3+), C3 (3+) and immunoglobulin M (IgM) (+) in the mesangium and capillary walls. Neoplasms and infections were ruled out as causes of glomerular injury (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Treatment was started with angiotensin-converting enzyme (ACE) inhibitors plus mycophenolate and steroids, with no response after three months. Given the patient's progressive decline in kidney function, a decision was made to switch to oral cyclophosphamide plus steroids. This treatment was suspended after four months due to lack of response. In 2014, the patient started peritoneal dialysis.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In 2016, he received his first kidney graft from a cadaver donor, with five human leukocyte antigen (HLA) incompatibilities. Induction therapy was administered with thymoglobulin (6<span class="elsevierStyleHsp" style=""></span>mg/kg), mycophenolate, prednisone and tacrolimus. In the post-transplantation period, he showed slow recovery of kidney function with creatinine levels of up to 1<span class="elsevierStyleHsp" style=""></span>mg/dl (GFR<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>70<span class="elsevierStyleHsp" style=""></span>ml/min) and proteinuria levels around 1.5<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h, on treatment with ACE inhibitors. Three months after transplantation, he presented cytomegalovirus infection, which was treated with valganciclovir with a good response.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Six months after transplantation, the patient presented nephrotic syndrome of new onset, with proteinuria levels of 12 g/day and hypoalbuminaemia, with stable kidney function. An immunology workup and HLA antibodies were negative. The results of a kidney graft biopsy were consistent with immune complex-mediated diffuse endocapillary proliferative glomerulonephritis and C3 deposits. Immunofluorescence showed IgG (3+) and C3 (2+) with a diffuse subepithelial and mesangial granular pattern. The C4d antibody was negative.</p><p id="par0055" class="elsevierStylePara elsevierViewall">To treat MPGN recurrence, the patient's initial therapy included increasing mycophenolate to a dose of 2<span class="elsevierStyleHsp" style=""></span>g/day and increasing prednisone to a dose of 50<span class="elsevierStyleHsp" style=""></span>mg/day. He presented moderate cytomegalovirus viral load reactivation. Despite treatment, his nephrotic syndrome did not improve, reaching proteinuria levels as high as 17<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h and serum albumin concentration of 2<span class="elsevierStyleHsp" style=""></span>g/dl. Changes over time in proteinuria and plasma albumin following transplantation are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Given that the prior cycle of cyclophosphamide had no response, a decision was made to administer treatment with rituximab (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>). He received a dose of 1<span class="elsevierStyleHsp" style=""></span>g, with no complications. His CD19 lymphocyte levels, monitored every three months, were suppressed during the first year. After starting rituximab, the patient showed gradual resolution of proteinuria as of the first month, and after one year his nephrotic syndrome resolved. As of 2019, he has developed skin spinocellular and squamous cell carcinoma; consequently, he has been switched from mycophenolate to a mammalian target of rapamycin (m-TOR) inhibitor and his tacrolimus dose has been reduced, with no repercussions on his proteinuria. Two years after treatment with rituximab, his proteinuria has continued to drop (<1<span class="elsevierStyleHsp" style=""></span>g/day) and his kidney function is stable.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Post-transplant MPGN recurrence is very common; some series have reported rates as high as 50% in the first 24 months.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> At present, the optimum treatment for recurrence is not clear.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Rituximab (an anti-CD20 monoclonal antibody) has been used in case series, achieving complete or partial remission, although its dosing remains unclear.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Other authors have used bortezomib in cases of MPGN with kappa chain deposits, with no prior diagnosis of dysproteinaemia, with a good clinical response.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In our case, a single dose of 1<span class="elsevierStyleHsp" style=""></span>g was administered with regular monitoring of CD19 lymphocyte levels. As they remained reduced for up to approximately one year, no new doses were proposed. In conclusion, in our case, rituximab was effective in achieving remission of post-transplant recurrent MPGN. Complete response to treatment with rituximab is not immediate, with effects beyond one year following administration. Monitoring of CD19 lymphocyte levels may be useful to minimise the dose taken, and is particularly useful in transplant recipients given the cumulative immunosuppression load with the onset of undesirable effects, such as tumours and infections.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Cruzado Vega L, Santos García A., Dosis única de rituximab como tratamiento de recidiva de glomerulonefritis membranoproliferativa en trasplante renal. Nefrologia. 2021;41:601–603.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1786 "Ancho" => 2833 "Tamanyo" => 232536 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes over time in proteinuria and plasma albumin.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "C3 glomerulopathy: consensus report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.C. Pickering" 1 => "V.D. D́Agati" 2 => "C.M. Nester" 3 => "R.J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 16 | 12 | 28 |
| 2024 October | 60 | 35 | 95 |
| 2024 September | 83 | 33 | 116 |
| 2024 August | 72 | 62 | 134 |
| 2024 July | 86 | 38 | 124 |
| 2024 June | 65 | 51 | 116 |
| 2024 May | 68 | 33 | 101 |
| 2024 April | 74 | 44 | 118 |
| 2024 March | 54 | 30 | 84 |
| 2024 February | 49 | 35 | 84 |
| 2024 January | 47 | 26 | 73 |
| 2023 December | 36 | 40 | 76 |
| 2023 November | 69 | 41 | 110 |
| 2023 October | 60 | 35 | 95 |
| 2023 September | 70 | 60 | 130 |
| 2023 August | 78 | 37 | 115 |
| 2023 July | 76 | 35 | 111 |
| 2023 June | 55 | 25 | 80 |
| 2023 May | 90 | 41 | 131 |
| 2023 April | 74 | 24 | 98 |
| 2023 March | 74 | 28 | 102 |
| 2023 February | 60 | 24 | 84 |
| 2023 January | 54 | 40 | 94 |
| 2022 December | 86 | 44 | 130 |
| 2022 November | 81 | 54 | 135 |
| 2022 October | 88 | 70 | 158 |
| 2022 September | 81 | 48 | 129 |
| 2022 August | 69 | 45 | 114 |
| 2022 July | 70 | 49 | 119 |
| 2022 June | 51 | 38 | 89 |
| 2022 May | 64 | 28 | 92 |
| 2022 April | 70 | 34 | 104 |
| 2022 March | 68 | 52 | 120 |
| 2022 February | 57 | 46 | 103 |
| 2022 January | 106 | 93 | 199 |
| 2021 December | 93 | 54 | 147 |
| 2021 November | 15 | 12 | 27 |
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