scholarly journals Substitution of Oral for Intravenous Cyclophosphamide in Membranous Nephropathy

Kidney360 ◽  
2020 ◽  
Vol 1 (9) ◽  
pp. 943-949
Author(s):  
Leonella Luzardo ◽  
Gabriela Ottati ◽  
Jimena Cabrera ◽  
Hernando Trujillo ◽  
Mariela Garau ◽  
...  
Keyword(s):  
Complete Remission ◽  
Membranous Nephropathy ◽  
Immunosuppressive Treatment ◽  
Clinical Relapse ◽  
Oral Cyclophosphamide ◽  
Intravenous Cyclophosphamide ◽  
Safe Alternative ◽  
Observational Cohort ◽  
Retrospective Observational Cohort Study

BackgroundOptimal immunosuppressive treatment for membranous nephropathy is still a matter of controversy. Current recommendations include oral cyclophosphamide combined with steroids (modified Ponticelli regimen) as first-line treatment in patients who are high risk. However, concerns about the cumulative toxicity of oral cyclophosphamide persist. In the last 30 years, a protocol based on low-dose intravenous cyclophosphamide plus steroids has been used to treat membranous nephropathy in Uruguay. We aimed to assess the efficacy of this regimen to induce clinical remission in patients with membranous nephropathy.MethodsIn this retrospective, observational cohort study, we analyzed the outcome of 55 patients with membranous nephropathy treated between 1990 and 2017 with a 6-month course of alternating steroids (months 1, 3, and 5) plus intravenous cyclophosphamide (single dose of 15 mg/kg on the first day of months 2, 4, and 6).ResultsAt 24 months, 39 (71%) patients achieved clinical response with complete remission observed in 23 patients (42%) and partial remission in 16 (29%). Median time to achieve partial and complete remission was 5.9 and 11.5 months, respectively. Absence of response was observed in 16 patients (29%), five of whom started chronic RRT after a median follow-up of 3.5 years. Clinical relapse occurred in nine of 33 (27%) patients at a median of 34 months after treatment discontinuation.ConclusionsReplacement of oral cyclophosphamide with a single intravenous pulse on months 2, 4, and 6 of the modified Ponticelli regimen can be an effective and safe alternative for treatment of membranous nephropathy.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/K360/2020_09_24_KID0002802020.mp3

scholarly journals Circulating anti-phospholipase A2 receptor antibodies as a diagnostic and prognostic marker in Greek patients with idiopathic membranous nephropathy – a retrospective cohort study

2019 ◽  
Vol 57 (2) ◽  
pp. 141-150
Author(s):  
Simella Provatopoulou ◽  
Dimitra Kalavrizioti ◽  
Maria Stangou ◽  
Maria-Nikoleta Kouri ◽  
Pantellitsa Kalliakmani ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Complete Remission ◽  
Phospholipase A2 ◽  
Disease Activity ◽  
Membranous Nephropathy ◽  
Clinical Status ◽  
Immunosuppressive Treatment ◽  
Idiopathic Membranous Nephropathy ◽  
Phospholipase A2 Receptor

Abstract Introduction. Circulating autoantibodies against phospholipase A2 receptor (anti-PLA2R) are recognized as key elements in the pathogenesis of idiopathic membranous nephropathy. In current clinical practice, they are increasingly gaining attention as novel tools for diagnosis and disease monitoring. We investigated the diagnostic and prognostic utility of anti-PLA2R antibody measurements in Greek patients with biopsy-proven membranous nephropathy. Methods. Anti-PLA2R levels were measured in serum samples from 33 patients at diagnosis using ELISA and were associated with treatment outcome. Moreover, serial anti-PLA2R measurements were performed in 15 patients under different clinical conditions and level alterations were correlated with disease activity. Results. Positive anti-PLA2R antibodies at diagnosis were found in 16 of 33 patients (48.5%). Anti-PLA2R levels were independently associated with the achievement of complete remission of nephrotic syndrome after immunosuppressive treatment compared to partial remission (p = 0.02, R2 = 0.265, 95%CI -0.019 to -0.0003). Higher detectable antibody levels at diagnosis were correlated with higher proteinuria levels (r = 0.813, p = 0.0001, 95%CI 0.532 to 0.933) and lower eGFR at the end of follow-up (r = -0.634, p = 0.0083, 95%CI -0.86 to -0.202). Serial antibody measurements during follow-up showed that anti-PLA2R titers were significantly reduced at the end of treatment after complete remission was achieved, remained low under sustained clinical remission, and increased during relapse. Conclusions. Our findings confirm the usefulness of anti-PLA2R measurements in the diagnosis of idiopathic membranous nephropathy. Low levels of anti-PLA2R antibodies at diagnosis are predictive of complete remission of nephrotic syndrome following immunosuppressive treatment. Serial anti-PLA2R measurements correlate well with clinical status throughout the follow-up period and could be used routinely for monitoring of disease activity and treatment planning.

P0417THE ABSENCE OF C3 DEPOSIT IN MEMBRANOUS NEPHROPATHY IS ASSOCIATED WITH SPONTANEOUS REMISSION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Cristina Rabasco ◽  
Ana Martínez ◽  
Rosa Ortega ◽  
Mario Espinosa
Keyword(s):  
Membranous Nephropathy ◽  
Interstitial Fibrosis ◽  
Immunosuppressive Treatment ◽  
Spontaneous Remission ◽  
Glomerular Sclerosis ◽  
Tubular Atrophy ◽  
Positive Group ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of biopsied nephrotic syndrome in adults. Recently, it has been reported that the pathogenesis of MN may be associated with an activation of the complement system. The pathway of activation is not clearly established. The intensity of C3 deposition could be a good marker of this activation in MN as has been shown in other diseases (IgA nephropathy, crescentic GN). The aim of this study is to evaluate clinical-pathological data in a cohort of patients with MN and the significance of glomerular C3 staining as a possible predictor of renal outcomes. Method We analysed patients with idiopathic MN biopsied in our department between January 2000 and December 2019, excluding those who had no material for IF (n = 115). The patients were divided into positive (87 cases) and negative (28 cases) based on glomerular C3 deposition. We assessed the clinical and histological characteristics and the percentage of spontaneous remission (SR) and end-stage renal disease (ESRD). Results A total of 115 patients with MN were followed with a median follow-up of 65 (25-161) months. We found no differences in baseline characteristics between both groups, with the exception that patients with C3 deposit had less albumin at the time of biopsy that negative patients [2.4 (2-2.9) vs 2.8 (2.3-3.1) g/dl, P=0.011)]. Patients with C3-negative had a higher percentage of SR than patients with C3-positive (75 vs 24%, P = 0.000) and less need for immunosuppressive treatment (18 vs 56%, P =0.001). At the most recent follow-up, C3-positive group had higher creatinine [1.42 (0.8-1.7) vs 0.97 (0.71-1) mg/dl, P=0.045] and proteinuria [1.64 (0.08-3.2) vs. 0.62 (0.05-0.79) g / 24h, P = 0.039]. Regarding histology, we found no differences in glomerular sclerosis, tubular atrophy and interstitial fibrosis. The renal survival analysis showed no statistically significant differences between both groups (P = 0.091). We analysed a subgroup of patients (n = 23) with antibodies against the phospholipase receptor on blood at the time of the biopsy (13/23 were positive). 84% of this positive group presented C3-positive in the renal biopsy vs 25% of the C3-negative group (P =0.008). Conclusion Patients without C3 staining show a higher rate of SR and less need for immunosuppressive treatment than patients with C3-positive. These results would support the theory that complement activation in this entity can play an important role. It is possible that these patients with negative C3 deposit represent a MN with evolution to SR and in these patients and that these patients do not need immunosuppressive treatment.

scholarly journals Anti-PLA2R Antibodies as a Prognostic Factor in PLA2R-Related Membranous Nephropathy

2015 ◽  
Vol 42 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Sjoerd A.M.E.G. Timmermans ◽  
Myrurgia A. Abdul Hamid ◽  
Jan Willem Cohen Tervaert ◽  
Jan G.M.C. Damoiseaux ◽  
Pieter van Paassen ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Immunosuppressive Agents ◽  
Immunosuppressive Treatment ◽  
Survival Rates ◽  
Spontaneous Remission ◽  
Correct Selection ◽  
Persistent Proteinuria ◽  
Phospholipase A2 Receptor ◽  
Elisa Testing

Background: The natural course of idiopathic membranous nephropathy (MN) varies, as it is known through favorable outcomes in most patients. However, one third of patients with idiopathic MN will slowly progress to end-stage renal disease (ESRD). To prevent disease progression, patients at high risk to develop ESRD are treated with immunosuppressive agents. Therefore, a correct selection of patients who need immunosuppressive treatment is important. Methods: Here, we evaluated the prognostic value of anti-phospholipase A2 receptor 1 antibody (anti-PLA2R) levels regarding clinical outcome in a well-defined cohort of 73 PLA2R-related MN patients with long-term follow-up. At baseline, patients were subdivided into patients with either low or high antibody levels based on ELISA testing. Results: Spontaneous remission rates were highest among patients with low anti-PLA2R levels (79%; hazard ratio 2.72 (95% CI 1.22-6.08), p = 0.02) after a median follow-up of 2.9 (95% CI 0.8-5.0, p < 0.001) years, whereas high anti-PLA2R levels were associated with persistent proteinuria (p = 0.04) and/or the need for immunosuppressive therapy (p < 0.001). Renal survival rates were 97% at 5 years, 93% at 10 years, and 89% at 15 years; however, this was not different between the anti-PLA2R groups. ESRD occurred significantly faster in patients with severe proteinuria as compared to patients with either mild (p = 0.02) or moderate proteinuria (p = 0.05). Conclusions: Low anti-PLA2R levels may predict spontaneous remissions in patients with PLA2R-related MN. Therefore, we suggest that quantification of anti-PLA2R is of value to monitor these patients.

scholarly journals Diabetes increases severe COVID-19 outcomes primarily in younger adults Age and diabetes in COVID-19 severity

2021 ◽  
Author(s):  
Marc Diedisheim ◽  
Etienne Dancoisne ◽  
Jean-François Gautier ◽  
Etienne Larger ◽  
Emmanuel Cosson ◽  
...  
Keyword(s):  
Risk Factor ◽  
Outcome Measure ◽  
Orotracheal Intubation ◽  
Composite Outcome ◽  
Younger Adults ◽  
Confounding Variables ◽  
Patients With Diabetes ◽  
Observational Cohort ◽  
Retrospective Observational Cohort Study

Abstract Context Diabetes is reported as a risk factor for severe COVID-19, but whether this risk is similar in all categories of age remains unclear. Objective To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. Design Setting and Participants We conducted a retrospective observational cohort study of 6,314 consecutive patients hospitalized for COVID-19 between February and June 30 2020, and follow-up recorded until 30 September 2020, in the Paris metropolitan area, France. Main Outcome Measure(s) The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. Results Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (HR 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those &lt;50 to 35% for those &gt;80 years but reached a plateau after 70 in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in &lt;50 and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, p&lt;0.001), but adjusted HR for diabetes was significant only in patients under 50 (HR 1.81 [1.14-2.87]). Conclusions Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.

FP2-4 Paediatric posterior fossa tumour resection rates in a small volume centre: the past decade’s experience

2019 ◽  
Vol 90 (3) ◽  
pp. e26.2-e26
Author(s):  
H Bhatt ◽  
MI Bhatti ◽  
C Patel ◽  
P Leach
Keyword(s):  
Posterior Fossa ◽  
Extent Of Resection ◽  
Primary Outcome Measure ◽  
Tumour Resection ◽  
Clinical Notes ◽  
Observational Cohort ◽  
Csf Diversion ◽  
Paediatric Brain Tumours ◽  
Retrospective Observational Cohort Study

ObjectivesResection rates for paediatric brain tumours correlate with outcome. At the 2018 BPNG meeting a commitment to prospectively collect resection data was made. Here we review our posterior fossa resection rates for the last decade.DesignRetrospective observational cohort study of paediatric posterior fossa astrocytomas, medulloblastomas and ependymomas from 2008–2018. Primary outcome measure was extent of resection on post-op MRI, with secondary outcomes including post-op complications and need for temporary/permanent CSF diversion.Subjects57 patients had 62 operations for: 26 astrocytomas, 28 medulloblastomas and 8 ependymomas. Ages ranged from 7 months-16 years, with a median of 9, 7 and 6 years, respectively, and an even male: female split. Follow-up ranged from 2 months to >10 years.MethodsPatients were identified from a prospectively collected paediatric neuro-oncology database, with clinical notes and peri-operative imaging used for analysis. Our results were compared to the published literature.ResultsComplete resection (CR) rates after 1 st surgery for patients with astrocytomas, medulloblastomas and ependymomas were 77%, 79% and 63%, respectively. 5/57 patients had a 2nd operation later, 3 of whom had primary CR followed by recurrence.ConclusionsOur resection rates, complications and need for CSF diversion are comparable to the literature. Factors enabling this in a low-volume centre may include a robust paediatric neuro-oncology framework, fellowship-trained subspecialty surgeons and joint operating.

Carcinosarcoma of the ovary treated over a 10-year period at the Christie Hospital

1994 ◽  
Vol 4 (3) ◽  
pp. 200-205 ◽  
Author(s):  
J. Prendiville ◽  
D. Murphy ◽  
J. Renninson ◽  
H. Buckley ◽  
D. Crowther
Keyword(s):  
Soft Tissue ◽  
Complete Remission ◽  
Soft Tissue Sarcoma ◽  
Ovarian Tumor ◽  
Chemotherapy Regimen ◽  
Epithelial Ovarian Carcinoma ◽  
Time Span ◽  
Intravenous Cyclophosphamide ◽  
Initial Surgery

Carcinosarcomas (previously termed malignant mixed Müllerian tumors) are highly malignant but rare tumors of the ovary. Most patients have been treated according to a wide variety of protocols for soft tissue sarcoma or for epithelial ovarian carcinoma and as a result the optimal treatment for this neoplasm is unknown. We describe here 20 patients with this ovarian tumor (15 with heterologous sarcomatous elements and five with homologous sarcomatous elements) referred to our institute. Five patients were treated with surgery alone, two patients with chemotherapy alone and 13 patients with a combination of surgery and chemotherapy. A variety of chemotherapeutic regimens were used reflecting the 10-year time span it took to accrue these patients. Forty-five per cent of all patients died within 1 year of initial surgery and there was a median survival of 14 months. Two patients achieved a complete remission following treatment with 10 cycles of intravenous cyclophosphamide and are still alive at 103 and 106 months follow-up. We suggest that a chemotherapy regimen combining cyclophosphamide and a platinum analog may be useful for the management of patients with carcinosarcoma of the ovary requiring further therapy following surgery.

scholarly journals Evaluation of Tacrolimus Combined With Corticosteroids vs Modified Ponticelli Regimen as Treatments for Refractory Primary Membranous Nephropathy

2018 ◽  
Vol 10 (12) ◽  
pp. 63
Author(s):  
Elkin Navarro-Quiroz ◽  
Gustavo Aroca-Martinez ◽  
Alex Domínguez-Vargas ◽  
María José Alonso-López ◽  
Rebeca Alvarado-Echeverría ◽  
...  
Keyword(s):  
Treatment Response ◽  
Membranous Nephropathy ◽  
Analytical Study ◽  
Oral Corticosteroid ◽  
Response Rate ◽  
Immunosuppressive Treatment ◽  
Complete Response ◽  
Treatment Groups ◽  
Syndromic Diagnosis

OBJECTIVE: To evaluate the immunosuppressive treatment response to modified Ponticelli regimen (MPR) and oral corticosteroid (OC) plus tacrolimus (TAC) in patients with primary membranous nephropathy (PMN). METHODS: Retrospective cohort analytical study. Adults patients (&gt;18 years old) with diagnosis of refractory PMN (&gt;50% increase in serum creatinine or a level &gt;1.5mg/dl or proteinuria refractory to 6 months of supportive treatment), proved by renal biopsy and immunofluorescence between 2008 and 2016 from the Nephropathy Registry of Colombia (NEFRORED&copy;) were included. Immunosuppressive treatment response was evaluated from baseline to 6 months after the start of therapy. RESULTS: 128 patients with PMN were included, of which 74 (57%) were female. The most frequent syndromic diagnosis was nephrotic syndrome 90 (70%), followed by asymptomatic urinary disorders 31 (25%). Chronic kidney disease manifested concomitantly in 7 (5%) patients. At the end of 6 months, 86 (67%) cases achieved some degree of remission: 23 (18%) complete response (CR) and 63 (49%) cases with partial response (PR), while 42 (33%) cases did not achieved remission. In the TAC+OC group, CR and PR were seen in 14 (20%) and 33 (47%) patients, respectively; and 9 (16%) and 30 (51%) patients in the MPR group, respectively. No statistically significant differences were found when comparing the immunosuppressive treatment response rate with both treatment groups (p &gt; 0.05). CONCLUSIONS: In the PMN, both immunosuppressive treatments (TAC+OC vs MPR) are comparable. We suggest a clinical follow-up of the anti-PLA2R/THSD7A titres at 6/12 months to be correlated with renal function in subsequent studies.

scholarly journals P522 Effectiveness of tofacitinib in a real-world Israeli cohort of patients with moderate-severe ulcerative colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S498-S499
Author(s):  
I Avni Biron ◽  
A Bar-Gil Shitrit ◽  
B Koslowsky ◽  
U Kopylov ◽  
A Levartovsky ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Real World ◽  
Disease Duration ◽  
Activity Index ◽  
Albumin Level ◽  
Severe Ulcerative Colitis ◽  
Mayo Score ◽  
Observational Cohort ◽  
Retrospective Observational Cohort Study

Abstract Background We sought to define the effectiveness of tofacitinib in a real-world (RW) cohort of patients with moderate to severe ulcerative colitis (UC). Methods This was a multi-center retrospective observational cohort study (2017–2020). Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3, and SCCAI ≤2 or a PMS ≤1, respectively. Results We included 73 patients (47% male; median age 26 years [IQR 19.5–39.5], disease duration 7 years [IQR 2.5–14.5], follow-up 7.1 months [IQR 3–12]), 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant steroids. Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months (IQR 3.4–16). Based on per-protocol analysis, after induction (week-8–16), 33.3% achieved response, 23.3% remission, and 19% corticosteroid free remission. At early maintenance (week 26), 50% achieved response, 26.8% remission, and 24.4% corticosteroid free remission. There were no differences between biologics-experienced and naïve patients. Seventeen patients (23.2%) had an AE: herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%. Remitters had higher albumin level compared with non-remitters (4.2±0.35 Vs. 3.8±0.35, P=0.023, respectively). Conclusion In this multicenter RW cohort of highly biologics - experienced patients with UC, those who continued tofacitinib throughout induction achieved 50% response and 27% remission. Tofacitinib was well-tolerated.

scholarly journals Sentinel Node Biopsy for Conjunctival Melanoma; Single Centre Experience and Review of Current Literature

2021 ◽  
Vol 28 ◽  
pp. 107327482110421
Author(s):  
Barbara Peric ◽  
Spela Leiler ◽  
Gregor Hawlina ◽  
Boris Jancar ◽  
Marko Snoj ◽  
...  
Keyword(s):  
Overall Survival ◽  
Single Centre ◽  
Node Biopsy ◽  
Single Centre Experience ◽  
Observational Cohort ◽  
The Mean ◽  
The Moment ◽  
Retrospective Observational Cohort Study

Purpose To evaluate the role of sentinel lymph node (SLN) biopsy in patients with conjuctival melanoma (CjM). Study design Retrospective observational cohort study and literature review. Subjects Slovenian patients with CjM are included in the study. Methods Prospectively collected data of CjM patients treated from June 2005 to December 2016 were retrospectively analyzed. Main outcome measures The numbers of SLN biopsy procedures, positive and false positive SLN, and local and regional relapses have been described together with overall survival. Results From June 2005 until December 2016, 24 patients with CjM were treated. The median follow-up time was 65.3 months. The mean Breslow thickness was 1.5 mm (sd = 1.8 mm), and ulceration was present in 29% of cases. Altogether, 14/24 (58%) SLN biopsy procedures were performed. SLN was positive in 2/14 (14%) cases. The estimated 5-year overall survival (OS) of the group was 72.5%, with a median survival of 151 months (95% CI 77–224). From January 2013 to January 2020, five (5/140, 3%) authors reported results comparable to our study. Conclusion Our results confirm that CjM is a rare disease with approximately 14% of positive SLN. At the moment, there are no firm conclusions regarding who would benefit most from SLN biopsy or whether or not CLND should be offered. Data from literature emphasize the need for consistent and uniform staging and future multicentric studies.

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