Remission Of Nephrotic Syndrome Research Articles

Obinutuzumab versus rituximab for the treatment of refractory primary membranous nephropathy.

Rituximab has been shown effective in patients with primary membranous nephropathy refractory to glucocorticoids plus cyclophosphamide (GC+CTX) or calcineurin inhibitors (CNIs), but the response rates remain limited. Compared with rituximab, obinutuzumab is a humanized anti-CD20 monoclonal antibody with greater B-cell depletion capacity. This study was performed to investigate the effectiveness of obinutuzumab compared to rituximab in treating patients with refractory primary membranous nephropathy. A retrospective study was conducted at Huashan Hospital, Fudan University between January 1, 2015 and July 31, 2024, and included adult patients with primary membranous nephropathy who met the following criteria, 1) resistance to GC+CTX and/or calcineurin inhibitor (CNI) regimens, 2) dependence on CNIs, or 3) relapse within 1 year after CTX discontinuation. The patients subsequently received either obinutuzumab or rituximab. The primary endpoint was treatment response, which was defined as overall remission of nephrotic syndrome with no need for rescue therapy after obinutuzumab versus rituximab treatment. The secondary measures included immunological remission and safety profiles. Among the 51 participants, 20 received obinutuzumab and 31 received rituximab. The response rate was significantly greater in patients receiving obinutuzumab than in those receiving patients (90.0% vs. 38.7%, p<0.001) during a follow-up period of 24 (IQR, 10-34) months. Cox proportional hazards survival regression analysis also revealed the superior effectiveness of obinutuzumab (p<0.001). Immunological remission rates were higher in patients receiving obinutuzumab at both 3 months (75.0% vs. 20.0%, p<0.001) and 6 months (87.5% vs. 21.4%, p<0.001). The safety profiles of the two treatments were comparable. Among the 19 nonresponders treated with rituximab, 10 subsequently received obinutuzumab, and 8 achieved remission during a follow-up period of 20.0 (IQR, 18.5-22.3) months. This retrospective study suggests that obinutuzumab is an effective treatment option for patients with primary membranous nephropathy refractory to GC+CTX, CNI, and rituximab regimens.

Clinical relevance of proteinuria selectivity index and fractional excretion of sodium in patients with nephrotic syndrome

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09–0.19) for MCD, 0.33 (0.23–0.40) for FSGS, and 0.20 (0.14–0.30) for MN. FENa were 0.24 (0.09–0.68), 1.03 (0.50–2.14), and 0.78 (0.41–1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97–3.81] and HR 1.93 [95% CI 1.46–2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome.

Minimal change glomerular disease associated with solid neoplasms: a systematic review.

Paraneoplastic minimal change disease (MCD) has been associated with hematological malignancies, whereas solid malignancies are commonly associated with membranous glomerulonephritis. In this systematic review of the literature, we describe the clinical features, treatment and outcome of MCD associated with solid neoplasms. We performed a systematic review of the MEDLINE, COCHRANE, EMBASE and SCOPUS databases, including case reports of adult patients with biopsy-proven MCD and solid malignancy, without language or time restrictions. Sixty-seven papers were included, presenting 86 cases with a mean age of 57.8 ± 14.7years; 41.0% were women. Nephrotic syndrome was the initial presentation in 96.2% of patients; 67.2% had kidney function impairment, and 21.2% required kidney replacement therapy. The most frequent malignancies were malignant thymoma (34.9%), kidney (14.0%), lung (12.8%), and gastrointestinal tumors (12.8%). In 40.7% of cases, the neoplasm diagnosis preceded MCD by 33.8 ± 46.1months, while in 31.4%, it followed diagnosis ofMCD by 12.4 ± 22.6months. In 27.9%, the neoplasm and kidney disease were diagnosed simultaneously. Immunosuppressive therapy was started in 79.1% of cases and tumor-specific treatment in 83.7%. Remission of MCD was achieved in 80.2% of patients: 38.2% responded to immunosuppressive treatment alone and 29.6% to oncological treatment alone. The association between MCD and solid neoplasms is well-documented. Immunosuppressive therapy alone induced nephrotic syndrome remission in over one-third of cases; most others responded to tumor-specific treatment. Solid tumor screening should be considered in MCD independently of the steroid response, though more data on solid tumor-associated MCD prevalence are needed for a definitive statement. CRD42024521854.

A randomised, two-arm (1:1 ratio), double blind, placebo controlled phase III trial to assess the efficacy, safety, cost and cost-effectiveness of Rituximab in treating de novo or relapsing NS in patients with MCD/FSGS (TURING)

BackgroundMinimal Change Disease (MCD) and Focal Segmental Glomerulosclerosis (FSGS) are a spectrum of disease causing the nephrotic syndrome (NS), characterised by proteinuria with debilitating oedema, as well as a high risk of venous thromboembolic disease and infection. Untreated, 50–60% patients with FSGS progress to end stage kidney disease after 5 years. These diseases respond to immunosuppression with high dose glucocorticoids, but 75% will relapse as the glucocorticoids are withdrawn, leading to significant morbidity associated with prolonged use. In children, the B cell depleting monoclonal antibody rituximab reduces relapse risk, but this drug has not been tested in randomised controlled trial in adults.Methods130–150 adults with new or relapsing MCD/FSGS, from UK Renal Units, are being randomised to receive either rituximab (two 1 g infusions two weeks apart) or placebo. Partipicipants are recruited when they present with nephrosis, and all are treated with glucocorticoids as per KDIGO guidelines. Once in remission, prednisolone is withdrawn according to a pre-specified regimen. If in remission at 6 months, participants receive a further dose of trial drug. If they relapse, they are unblinded, and if they have received placebo, they are offered open label rituximab with protocolised prednisolone as in the main phase of the trial. The primary end point is time from remission to relapse. A number of secondary endpoints will be assessed including the effect of rituximab on: (1) NHS and societal resource use and hence cost: (2) safety: (3) other measures of efficacy, such as achievement of partial and complete remission of NS and the preservation of renal function: (4) health status of participant.Trial RegistrationTURING received ethical approval on 14 Jun 2019 - REC reference: 19/LO/0738. It is registered on EudraCT, with ID number: 2018-004611-50, with a start date of 2019-06-14.

#1795 Diverse histological findings of kidney injury in cancer patients on immunotherapy- impact on clinical management

Abstract Background and Aims Immune checkpoint inhibitors (CPIs) are becoming rapidly more used to treat various types of cancer. Acute interstitial nephritis (AIN) is considered the most common pattern of kidney injury in these patients, however other distinct histological lesions are increasingly reported. The aim of this study is to assess the histological findings and the value of kidney biopsy in the management of patients with CPI-associated nephrotoxicity. Method All records from patients treated with CPIs and kidney injury that underwent a kidney biopsy during the last 4 years were retrospectively assessed. Results We included 16 biopsied patients treated with CPIs and kidney injury, 8 males and 8 females. The mean age at the time of renal biopsy was 68 (± 8.2) years and the median follow up time was 11.5 (8-29) months. The most common primary malignancy was non-small cell lung cancer (n = 8), followed by melanoma (n = 3), endometrial cancer (n = 2), renal cell carcinoma (n = 1), breast cancer (n = 1) and hepatocellular carcinoma (n = 1). At the time of kidney biopsy eleven patients were treated with pembrolizumab, three patients with ipilimumab and nivolumab combination, one patient with ipilimumab and one patient with atezolizumab. Eleven patients were on immune-chemo combined therapy. Twelve patients presented with acute kidney injury (AKI), two with nephrotic syndrome, one with nephrotic range proteinuria and one with acute onset of hypertension and subnephrotic proteinuria [Urine Protein (UPr): 3 g/24 h]. The median time to developing kidney injury from CPI initiation was 9 (4.25-21.5) months. The prevalent histologic lesion was AIN (n = 5), followed by three cases of mixed AIN with acute tubular injury (ATI), and two cases of pure ATI. We recorded three cases of CPI-associated glomerulonephritis including membranous nephropathy (MN) with a lupus-like pattern on immunofluorescence, AA amyloidosis and Focal Segmental Glomerulosclerosis (FSGS) cellular variant. Two patients had diabetic nephropathy (DN) with ATI and one patient had thrombotic microangiopathy (TMA) with ATI. Immunotherapy was temporarily withheld in all patients at the time of kidney biopsy. After the establishment of the histological diagnosis: we continued treatment with corticosteroids in nine patients (five cases with AIN, one case with mixed AIN/ATI, one case with MN, one case with FSGS and one case with TMA/ATI). Withdrawal of corticosteroids was decided in five cases (two patients with diabetic nephropathy, two patients with mixed ATI/AIN and one with ATI). The patient with AA amyloidosis was treated with colchicine and cortisone with partial remission of nephrotic syndrome (UPr: 1.2 g/24 h). In one case with pure ATI, corticosteroids, and the concomitant chemotherapeutic agent (pemetrexed) were withdrawn with complete response of AKI. Partial remission of proteinuria occurred in the patient with FSGS (UPr: 1.3 g/24 h). At the end of follow up, kidney recovery occurred in all 12 patients with AKI (among them one patient who required renal replacement therapy at the time of biopsy). Rechallenge with a CPI was attempted in 8 patients. After rechallenging, one patient experienced relapse of nephrotic syndrome (MN) and immunotherapy was withdrawn. The other seven patients continued CPI treatment without recurrence of kidney injury. The overall patient survival was 62.5%. Conclusion AIN is only one of the possible causes of nephrotoxicity in patients receiving CPIs. Kidney biopsy establishes the accurate diagnosis of CPI-associated AKI. In selected cases it allows the continuation of immunotherapy and can prevent the unnecessary use of corticosteroids.

#1162 Paraneoplastic podocytopathy in patients with solid cancer: clinical characteristics and new insights into pathophysiological processes about 21 cases

Abstract Background and Aims Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) may occur in patients with solid cancer but this rare association has never been extensively investigated. Here, we report the first series of patients presenting this association, also named paraneoplastic podocytopathy with nephrotic syndrome (PPNS) . Previous study has demonstrated the specific induction in both podocytes and Reed-Sternberg cells of C-Maf Inducing Protein (CMIP) in patients with MCD and Hodgkin lymphoma. Here, we examined whether this molecular relationship was also relevant in patients developing PPNS in the setting of solid cancer. We have investigated the potential CMIP expression in kidney biopsies and in tumor tissues. Method We collected data from patients who presented with histologically proven cancer and concomitantly developed a nephrotic syndrome (± 3 months) related to MCD or FSGS Follow-up data were collected after 3, 6, 12 months and at last visit. We identified a control group of idiopathic nephrotic syndromes (INS) matched on sex, age and histological type, in order to compare the characteristics of these controls with patients with PPNS. Expression of CMIP was studied by immunohistochemistry and by immunofluorescence confocal microscopy on kidney biopsy and tumor samples. We used kidney biopsies from INS and tumors from patients without associated nephrotic syndrome as controls. Results Twenty-one PPNS patients and 21 controls with INS without cancer were identified. The median age of PPNS patients was higher (68 years) than usually observed in INS. Most of them (76%) had a MCD. A broad spectrum of cancers was found (bronchopulmonary, prostatic, colorectal…) . Baseline characteristics were similar between PPNS patients and INS controls, with a median urinary protein creatinine ratio of 865 and 900 mg/mmol, blood albumin t 15 and 15.3 g/L. Estimated glomerular filtration rate were 48 and 60 ml/min/1.73 m² respectively (no significant difference) . At presentation, PPNS patients were more likely to have hematuria (p = 0.031) , a lower median hemoglobin level than controls (p = 0.039) . Moreover, PPNS patients were less often treated with immunosuppressive drugs (p = 0.004) . After 12 months of follow-up, PPNS patients had a less favorable outcome than INS controls, with a mortality rate three times higher (30% vs 9.5%, p = 0.098) and a much lower rate of complete remission of nephrotic syndrome (25% vs 73.7%, p = 0.008, Table 1). CMIP labeling was performed on 13 tumor samples and 16 kidney biopsies in PPNS patients, and on 5 kidney biopsies with INS, and on 5 control tumor samples. Podocyte labeling of CMIP is observed on all but one kidney biopsy. CMIP labeling was positive on all case tumors, but only a scarce staining was detected in control patients with solid cancer without nephrotic syndrome (Fig. 1). In PPNS patients, confocal microscopy analysis on tumoral tissue showed high expression of CMIP in some epithelial cells and in immune infiltrating cells.. In addition, we found that CMIP was specifically express in CD4 T lymphocyte subset (Fig. 2), but not in CD20, FOXP3 or PD1 lymphocytes, defining a novel FOXP3−/PD1− CMIP high CD4+T lymphocyte subpopulation, within immune cell infiltrates. Conclusion We report the first series of patients with PPNS, who have a more severe renal and overall prognosis than controls. We show that patients with PPNS display higher induction of CMIP, both in the tumor and in podocytes. Strikingly, we identified within immune infiltrates a new subset of T-cell harboring a particular phenotype (CD4+, CMIPhigh, FOXP3−, PD1−) , which is not detected in patients with solid tumor without nephrotic syndrome and which could play a key role in the pathophysiology of PPNS.

#2691 Treatment naive membranous nephropathy patients treated with rituximab in COVID19 era

Abstract Background and Aims Standard of care of high-risk idiopathic membranous nephropathy patients is immunosuppressive treatment with cyclophosphamide and corticosteroids or rituximab. Our aim was to assess outcome and safety of rituximab therapy in COVID19 era in comparison to modified Ponticelli protocol. Method In this retrospective study all adult patients with biopsy proven membranous nephropathy treated with rituximab as a first line therapy from 2020 till 2022 were enrolled and compared with MN patients treated with modified Ponticelli protocol from 2013 till 2020. Renal outcome was defined as composite of partial and complete remission defined according KDIGO guidelines. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels. Results During the COVID 19 era, between 2020 and 2022, 8 MN patients were treated with rituximab as a first line therapy. One was lost from follow up and one had allergic infusion reaction and therefore was excluded from further analysis. Ten patients were treated with modified Ponticelli protocol. There was no difference in age (60 vs. 59 years; p = 0.669), gender (M 57.1 vs. 60%), BMI (26.3 vs. 29.1cm/kg; p = 0.906), systolic (140. vs. 150 mmHg; p = 0.161) or diastolic (90 vs. 91.5 mmHg; p = 0.230) blood pressure between rituximab and cyclophosphamide treated group. Also, there was no difference in proteinuria between rituximab and cyclophosphamide treated group (16.2 (5.7–31.3) vs. 8.7 (6.5–12.5) g/dU; p = 0.201) Patients treated with cyclophosphamide had lower eGFR compared with patients treated with rituximab (51 (34-79) vs. 93 (72-98) ml/min/1,73 m²; p = 0.005). At 6 months follow up only 2 (28.6%) in rituximab group and 6 (60%) in cyclophosphamide group achieved outcome defined as composite of complete and partial remission. At one year follow up, there was no difference in outcome between groups and all patients from rituximab group compared to 8 patients (88.9%) from cyclophosphamide group accomplished composite favorable renal outcome (p = 398). At the end of follow up, one year after cyclophosphamide therapy eGFR was better (57 (43-96) vs. 51 (34-79) ml/min/1,73 m²). Rituximab was safe in our cohort. Three (50%) of patients acquired SARS CoV2 infection and there was no adverse outcome regarding COVID 19 disease. Conclusion Cyclophosphamide is faster than rituximab in accomplishing remission of nephrotic syndrome and improves deteriorated kidney function. Nevertheless, at 1 year follow up rituximab efficiency is proven to be excellent. Cyclophosphamide should be reserved for MN patients with nephrotic syndrome with reduced glomerular filtration rate.

Implication of acute tubular injury in minimal change nephrotic syndrome.

While acute tubular injury (ATI) is known to occur in a significant number of minimal change disease (MCD) nephrotic syndrome cases with acute kidney injury (AKI), the clinical significance is not certain, and AKI may also occur without ATI. This study aimed to evaluate whether the severity of AKI defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria correlated with the presence or severity of ATI in a series of adult patients with MCD. We also looked at whether time to remission of nephrotic syndrome (NS) with treatment correlated with the presence of ATI in those with and without AKI. We excluded patients with secondary MCD. Of 61 patients, 20 had AKI (33%). ATI was significantly more likely to occur in those with AKI than in those without AKI (60 vs. 24%). Overall, the severity of AKI did not clearly correspond with the severity of ATI. Remission rates at 4 weeks were lowest (25%) in those with both AKI and ATI, while they were highest (100%) in those with neither AKI nor ATI. Patients with AKI but no ATI and those with no AKI but having ATI were intermediate in remission rates and similar to each other (60 and 62%, respectively). The time to remission in the group of those without AKI was significantly longer in those with ATI than in those without (p=0.0027), but the numerical difference in remission did not reach statistical significance in the smaller group of AKI patients. Patients with ATI were older and more often male than those without ATI. It appears that having ATI may predict a slower remission rate in MCD though the reason for this is unclear. The different demographics of those with ATI may also play a role.

A Case of Tiopronin-induced Membranous Nephropathy Presenting with IgG4-predominant Staining Pattern.

Tiopronin is a key drug used to treat cystinuria. A 41-year-old Japanese woman with cystinuria presented with eyelid edema and weight gain after the administration of tiopronin. Her serum albumin was 1.8 g/dL and her urinary protein level was 5.5 g/gCre. After cessation of tiopronin, she achieved remission of nephrotic syndrome (NS). Secondary NS due to tiopronin was evident based on the clinical course and laboratory values. A kidney biopsy showed membranous nephropathy (MN), and an immunofluorescence analysis revealed strong deposition of immunoglobulin G4 (IgG4). However, a previous case report of tiopronin-induced MN showed staining for IgG1 and IgG3. This case report suggests a novel etiology for tiopronin-induced MN.

Anti–Phospholipase A2 Receptor 1 and Anti–Cysteine Rich Antibodies, Domain Recognition and Rituximab Efficacy in Membranous Nephropathy: A Prospective Cohort Study

Rationale & ObjectiveProteinuria and anti-phospholipase A2 receptor 1 (anti-PLA2R1) antibody titers are associated with primary membranous nephropathy (MN) outcomes. We evaluated the association of antibodies against the cysteine-rich (CysR) and C-type lectin 1, 7, and 8 (CTLD1, CTLD7, and CTLD8) domains of PLA2R1 with MN outcomes. Study DesignProspective cohort study. Setting & ParticipantsOne-hundred-thirteen consecutive, consenting patients referred to the Nephology Unit of the Azienda-Socio-Sanitaria-Territoriale (ASST) Papa Giovanni XXIII (Bergamo, Italy) with PLA2R1-related, biopsy-proven MN whose persistent nephrotic syndrome (NS) was managed conservatively for >6 months and were monitored with serial evaluations of proteinuria, autoantibodies (by ELISA), and clinical outcomes. ExposureRituximab. OutcomesComplete (proteinuria <0.3 g/24h) or partial (proteinuria >0.3 g/24h and <3.0 g/24h with >50% reduction vs. basal) NS remission. Analytical ApproachUnivariable and multivariable Cox regression analyses. ResultsAll patients had anti-CysR antibodies; 62 (54.9%) were multi-domain recognizers. Anti-PLA2R1 and anti-CysR antibody titers were strongly correlated at baseline (p<0.001, r=0.934), 6 months (p<0.001, r=0.964), and 12 months (p<0.001, r=0.944). During a median (IQR) follow-up of 37.1 (20.3-56.9) months, 71 patients (62.8%) achieved either complete or partial remission of their NS. Lower baseline anti-PLA2R1 [HR (95% CI): 0.997 (0.996-0.999), p=0.002) and anti-CysR [HR (95% CI): 0.996 (0.993-0.998), p=0.001) titers were associated with a higher probability of remission, along with female sex, lower proteinuria, and lower serum creatinine levels (p<0.05 for all comparisons). Anti-CTLD antibodies were not associated with outcomes. At 6 and 12 months, compared to baseline, anti-PLA2R1 and anti-CysR antibody titers decreased more in patients progressing to partial or complete remission than in those without remission (p<0.05 for all comparisons). LimitationsObservational design. ConclusionsIn PLA2R1-related MN, anti-PLA2R1 and anti-CysR antibodies similarly predict rituximab efficacy, independent of PLA2R1 domain recognition. The choice between these tests should be dictated by feasibility and costs. Evaluating anti-CTLD antibodies appears unnecessary.

IgG4-Related Disease with IgG1-Dominant Membranous Nephropathy: A Rare Case Report

ABSTRACT Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder affecting various organs and tissues. Kidney involvement in IgG4-RD commonly manifests as IgG4-related tubulointerstitial nephritis or IgG4-related membranous nephropathy, with the latter occurring less frequently. The identification of the phospholipase A2 receptor (PLA2R) antigen has improved our understanding of primary membranous nephropathy. Here, we present the case of a 60-year-old Chinese man initially diagnosed with IgG4-related pancreatitis, who achieved clinical remission with glucocorticoid therapy followed by low-dose glucocorticoid maintenance therapy. Two years later, the patient developed nephrotic syndrome. A kidney biopsy revealed membranous nephropathy characterized by glomerular subepithelial deposition of IgG1 and positive PLA2R staining. Rituximab (RTX) treatment resulted in complete clinical remission of nephrotic syndrome, and no recurrence was observed during the 24-month follow-up period. IgG4-RD complicated by membranous nephropathy is a rare pathological feature characterized by glomerular subepithelial IgG1 deposition and positive PLA2R antigen staining. In the present case, RTX treatment was effective in achieving clinical remission. These findings contribute to the evolving understanding of the relationship between IgG4-RD and membranous nephropathy.

Ofatumumab in Rituximab-Resistant and Rituximab-Intolerant Patients With Primary Membranous Nephropathy: A Case Series

Rituximab is the first-choice therapy for patients with primary membranous nephropathy (MN) and nephrotic syndrome. However, approximately 30% of patients are treatment-resistant or become treatment-intolerant with hypersensitivity reactions upon repeated drug exposures. We aimed to assess whether ofatumumab, a fully human second-generation anti-CD20 antibody, could be a valuable alternative to rituximab in this population. Case series. 7 rituximab-intolerant and 10 rituximab-resistant patients with MN who consented to receive ofatumumab (50-300mg, single intravenous infusion) and were followed at the nephrology unit of Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII (Bergamo, Italy) between September 2015 and January2019. Over a median (IQR) follow-up of 5.0 (3.0-9.8) months, all 7 rituximab-intolerant and 3 of the 10 rituximab-resistant patients exhibited complete (proteinuria<0.3g/d) or partial (proteinuria<3.5g/d with≥50% reduction vs baseline) remission of nephrotic syndrome. Circulating B cells were similarly depleted in all patients by 1 week, and serum anti-phospholipase A2 receptor antibody concentrations decreased to<2.7 relative units/mL in 3 of 4 rituximab-intolerant and 4 of 8 rituximab-resistant patients with phospholipase A2 receptor-related disease. Ofatumumab significantly reduced 24-hour urinary protein and immunoglobulin G excretion and increased serum albumin and immunoglobulin G levels. These effects were greater in rituximab-intolerant than in rituximab-resistant patients. Measured glomerular filtration rate significantly increased by an average of 13.4% at 24 months compared with baseline (P=0.036) among all patients in the series. There were 14 nonserious infusion-related adverse events in 9 patients that recovered with temporary infusion interruption. Retrospective design, limited number of patients. Ofatumumab may represent an effective and safe treatment for rituximab-intolerant cases of MN. Larger prospective studies will be needed to validate these preliminary findings and explore the effectiveness of other second-generation anti-CD20 antibodies in this clinical setting. Primary membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome (NS) in adults. In this case series, we explored the efficacy of ofatumumab, a fully human second-generation anti-CD20 antibody, in 17 patients with MN and NS who were intolerant or unresponsive to rituximab. All 7 rituximab-intolerant patients exhibited complete or partial clinical remission, compared with only 3 of the 10 rituximab-resistant patients. Autoantibody levels decreased in all patients with phospholipase A2 receptor-related disease. Ofatumumab achieved a significant reduction in urinary protein and immunoglobulin G excretion while increasing serum albumin and immunoglobulin G levels. Ofatumumab may be a promising option for patients with MN who are rituximab-intolerant. Further investigations are warranted to validate these preliminary findings.

#5215 OFATUMUMAB AS A RESCUE THERAPY FOR PATIENTS WITH MEMBRANOUS NEPHROPATHY

Abstract Background and Aims Rituximab is the first-line treatment for patients with primary membranous nephropathy (MN) and nephrotic syndrome (NS) at high risk of progression to end-stage kidney disease. However, this drug is effective only in approximately two thirds of treated patients, and repeated rituximab infusions may be complicated by hypersensitivity reactions, which contraindicate retreatment. Ofatumumab, a fully human anti-CD20 antibody, could overcome these limitations. Method We retrospectively evaluated the response to a single 50–300 mg dose of intravenous ofatumumab in 17 MN patients referred to our institution who either experienced hypersensitivity reactions (rituximab-intolerant, n = 5) or failed to achieve NS remission after rituximab infusion (rituximab-resistant, n = 12). Results Over a median [IQR] follow-up of 5.0 [3.0-9.8] months, ten (58.8%) patients—five rituximab-resistant (41.7%) and all five rituximab-intolerant—achieved complete or partial NS remission, defined as proteinuria &amp;lt;0.3 g/day or proteinuria &amp;lt;3.5 g/day with ≥50% reduction from baseline, respectively. Ofatumumab infusion induced a progressive reduction in 24-hour urinary protein and IgG excretion, and a sharp increase in serum albumin and IgG levels. Peripheral B cells were depleted in all patients and started reconstituting by 3 months from baseline. Seven of the 12 subjects with PLA2R-related disease (i.e. with baseline anti-PLA2R antibody levels &amp;gt;2.7 RU/mL by ELISA) achieved antibody depletion during the follow-up (half of rituximab-resistant and all rituximab-intolerant). There were 14 non-serious infusion-related adverse events in nine patients, all of which completely resolved with temporary interruption of ofatumumab infusion. Conclusion Ofatumumab may be an effective and safe treatment option for all rituximab-intolerant and a substantial proportion of rituximab-resistant MN patients.

Duration of remission of steroid-dependent nephrotic syndrome after cyclosporin and mycophenolate sodium therapy in children with and without clinical manifestation of allergy

BACKGROUND. The problem of steroid-sensitive nephrotic syndrome is the developing of steroid dependency and toxicity.THE AIM: Evaluate duration of remission of steroid-dependent nephrotic syndrome (NS) after cyclosporine and mycophenolate sodium therapy in children with or without clinical manifestation of allergy.PATIENTS AND METHODS. Follow-up study with analysis of onset, clinical course and treatment includes 47 children ((31 boys (66 %) и 16 girls (34 %)) with steroid-dependent NS, 34 (72,3 %) had clinical manifestation of allergy, 13 (27,7 %) didn’t have clinical manifestation of allergy. The efficiency of therapy with cyclosporine in 16 patients and mycophenolate sodium in 27 patients with clinical manifestation of allergy is estimated in comparative study by analysis of 6, 12, 24 month remission rate after treatment. Median duration of remission of NS during 2 years after treatment is estimated. Out of 27 children 8 (29,6 %) had mycophenolate sodium treatment after cyclosporine and took part in both groups.RESULTS. Statistically significant differences in 6, 12, 24 month remission rates after cyclosporine and mycophenolate sodium treatment in children with clinical manifestation of allergy are established. Remission of NS during 6 months after mycophenolate sodium treatment was in 81,5 % (in 22 from 27 patients) unlike of that after cyclosporine – in 40 % (in 6 from 15 patients) in children with clinical manifestation of allergy (р&lt;0,05). Remission of NS during 12 months after mycophenolate sodium treatment was in 55,6 % (in 15 from 27 patients) unlike of that after cyclosporine – 13,3 % (in 2 from 15 patients) (р&lt;0,05) in children with clinical manifestation of allergy. Remission of NS during 24 months after mycophenolate sodium treatment was in 37 % (in 10 from 27 patients) unlike of that after cyclosporine – 6,7 % (in 1 from 15 patients) (р&lt;0,05) in children with clinical manifestation of allergy. Median duration of remission during 2 years after treatment with cyclosporine and mycophenolate sodium in children with clinical manifestation of allergy was 7,0 [2,0-11,0] and 17,0 [6,0-24,0] months, retrospectively, (р&lt;0,05).CONCLUSION. Remission of steroid-dependent NS during 6 months after therapy with mycophenolate sodium and cyclosporine in children was in 81,5 % and 40,0 % respectively, in children with clinical manifestation of allergy. Remission of steroid-dependent NS during 12 months after therapy with mycophenolate sodium and cyclosporine in children was in 55,6 % and 13,3 % respectively, in children with clinical manifestation of allergy. Remission of steroid-dependent NS during 24 months after therapy with mycophenolate sodium and cyclosporine in children was in 37 % and 6,7 % respectively, in children with clinical manifestation of allergy. Median duration of remission during 2 years after treatment with cyclosporine and mycophenolate sodium in children with clinical manifestation of allergy was 7,0 [2,0-11,0] and 17,0 [6,0-24,0] months, retrospectively. As the result of comparative study duration of remission of steroid-dependent NS in children with clinical manifestation of allergy was statistically significantly longer in children after therapy with mycophenolate sodium.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

A Case of Imatinib Induced Nephrotic Syndrome in a Child with Chronic Myeloid Leukaemia

Background:Tyrosin kinase inhibitors (TKI) are used as a targeted therapy for the treatment of chronic myeloid leukaemia and Philadelphia chromosome positive acute lymphoblastic leukaemia. Increasing use of TKI has been associated with hypertension, proteinuria and acute kidney injury. There are only afew reports of adults with TK -inhibitor associated nephrotic syndrome.But TK inhibitor associated Nephrotic syndrome is very rare in paediatric age group. Case:A -6- year old boy presented with fever, anaemia, splenomegaly, leucocytosis and finally diagnosed as accelerated phase of chronic myeloid leukaemia (CML) by bone marrow study.He achieved clinical and haematological remission with Imatinib. But developed generalized oedema and was found to have massive proteinuria and microscopic haematuria after three and half months. Renal biopsy revealed focal segmental glomerulosclerosis. Imatinib along with Prednisolone, 60 mg/m2/ day was added to treat nephrotic syndrome. Imatinib discontinued as the patient did not achieve complete remission. After one week of Imatinib withdrawal and five weeks of daily prednisolone the boy attained complete remission of nephrotic syndrome. Conclusion:Tyrosine Kinase inhibitors are important therapies in paediatric cancer and their use is expanding. Timely recognition of renal adverse effectsfor TK inhibitors can aid in the proper management of cancer patients. J Bangladesh Coll Phys Surg 2023; 41: 170-172

Urinary 8-oxoGuo as a potential novel evaluation index for patients with nephrotic syndrome

Urinary 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′- deoxyguanosine (8-oxodGuo) are considered biomarkers of oxidative stress, and patients with nephrotic syndrome have been reported to have increased oxidative stress levels. In this study, we aimed to assess the value of 8-oxoGuo and 8-oxodGuo as novel biomarkers to evaluate the severity of nephrotic syndrome. In total, 107 patients with nephrotic syndrome and 116 healthy controls were recruited for this study. The concentrations of urinary 8-oxoGuo and 8-oxodGuo were measured using isotope-labeled liquid chromatography with tandem mass spectrometry. Urinary creatinine was used to regulate 8-oxoGuo and 8-oxodGuo concentrations. Urinary 8-oxoGuo and 8-oxoGuo/Cr levels in patients with nephrotic syndrome were significantly higher than those in healthy control participants. 8-oxoGuo/Cr showed a positive correlation with the 24 h urinary total protein (UTP) and UTP levels and negative correlations with serum total protein and albumin levels. After treatment, urinary 8-oxoGuo and 8-oxoGuo/Cr levels were significantly lower in the group with a low 24 h-UTP value (<3.5 g/d) than in the high value group. 8-oxoGuo can be used as a feasible and reliable biomarker for the assessment of nephrotic syndrome. Highlights Urinary 8-oxoGuo level was significantly increased in patients with nephrotic syndrome. Urinary 8-oxoGuo level increased with an increase in plasma protein and a decrease in urine protein. Urinary 8-oxoGuo level decreased with nephrotic syndrome remission when urinary microalbumin showed no significant change. Urinary 8-oxoGuo level can be used as novel biomarkers of nephrotic syndrome.

Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

Traditional indigenous medicines are an etiologic consideration for NELL1-positive membranous nephropathy

P8.108: Therapeutic Plasma Exchange, Rituximab and Steroids in Pediatric Kidney Transplant Recipients With Early Recurrence of FSGS: A Single Large Pediatric Hospital Experience

Focal segmental glomerular sclerosis (FSGS) is the most common glomerular disease leading to end-stage renal disease (ESRD) in children. FSGS frequently recurs after kidney transplant and may cause graft failure. Therapeutic plasma exchange (TPE), rituximab and steroids have been used to treat post-transplant FSGS recurrence, but limited data is available to support their combined efficacy. We conducted a retrospective cohort study of all kidney transplant recipients at a single pediatric center between 2007 and 2018 to determine frequency of FSGS and early recurrence of nephrotic syndrome within 4 days of transplant. Primary outcome was graft survival and secondary outcome was remission of nephrotic syndrome. FSGS was the indication for renal transplant in 11% of cases(n=29). Of these, 24% of patients had early FSGS recurrence after transplant(n=7). Treatment was at the discretion of the treating physician, but generally included TPE, rituximab and steroids. Five responded; the other two returned to chronic dialysis. 22 patients without recurrence experienced 100% 1-year graft survival. For all FSGS recipients, including those with recurrence, 3-year graft survival was 94.4%. 5/7(71%) of recipients with recurrence achieved partial or full remission of nephrotic syndrome following treatment. This study, the largest to uniformly employ the combination of TPE, rituximab and high-dose steroids, supports the efficacy of this treatment for pediatric patients with FSGS recurrence.

Association between Toxoplasma gondii Infection and Nephrotic Syndrome Risk in Children: A Case-Control Study and Systematic Review.

Some evidence suggests toxoplasmosis as an etiology of nephrotic syndrome (NS) in children; however, no observational study evaluated this relationship. In a case-control study, we enrolled 35 children with NS and 37 healthy children. All participants were examined for anti-Toxoplasma immunoglobulin G and M (IgG and IgM) antibodies using enzyme-linked immunosorbent assay. We also systematically reviewed the literature to assess this relationship. Prevalence of anti-Toxoplasma IgG was 17.4% and 13.5% in cases and controls, respectively, indicating a non-significant association (adjusted odds ratio, 1.22, 95% confidence interval, 0.35-4.41). No subjects were seropositive for IgM. In a systematic review, we found that acute toxoplasmosis can induce NS in some children and anti-Toxoplasma treatment is effective in the remission of NS in these cases. In pediatrics with NS, acute toxoplasmosis should be considered as a neglected causative factor.