Clinical Nephrology
Rituximab for the treatment of membranous nephropathy: a single-center experience
Andreja Aleš Rigler, Alexander Jerman, Aleša Orsag, Nika Kojc, Damjan Kovač, Andrej Škoberne, Špela Borštnar, Željka Večerić Haler, Nuša Avguštin, Radoslav Kveder, Dušan Ferluga, Alenka Vizjak, and Jelka Lindič
Volume 88 (2017) p. 27 - 31
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S27-S31)
Rituximab for the treatment of membranous nephropathy: a single-center experience
Andreja Aleš Rigler1, Alexander Jerman1, Aleša Orsag1, Nika Kojc2, Damjan Kovač1, Andrej Škoberne1, Špela Borštnar1, Željka Večerić Haler1, Nuša Avguštin1, Radoslav Kveder1, Dušan Ferluga2, Alenka Vizjak2, and Jelka Lindič1
1Department of Nephrology, University Medical Center Ljubljana, and
2Institute of Pathology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
Background: Treatment of idiopathic membranous nephropathy with rituximab was introduced more than a decade ago following experimental data that suggested involvement of B-cell-mediated reactions in its pathogenesis. It was a logical step towards a more selective therapy with less severe side effects as compared to the recommended first-line immunosuppressive therapy with corticosteroids and different immunosuppressant drugs. Methods: We retrospectively analyzed the anonymous data of patients who were treated with rituximab for idiopathic membranous nephropathy at our institution from January 2006 to July 2016. Daily proteinuria and serum creatinine were analyzed 3, 6, 9, and 12 months after rituximab application. The patients were divided into 4 groups according to proteinuria. We separately analyzed remission rates in the whole group and in groups with different quantity of daily proteinuria. Other history data and laboratory parameters were also compared within different groups of patients. Results: The study involved 29 rituximab treatments in 26 patients: 7 (26.9%) female and 19 (73.1%) male patients. In 16 out of 29 treatment cases (55.1%), patients had been previously treated with cyclophosphamide and steroids, or cyclosporine with low dose of steroids, or both. In 72.4% of patients, antiphospholipase A2 receptor antibodies were present. In 2 cases of treatment (6.9%), patients received rituximab 375 mg/m2 of body surface area in 3 and 4 weekly doses, respectively. In all other cases, repeated rituximab applications were given as needed according to the levels of circulating CD-20 B-cells. The total remission rate in our cohort of patients was 37.9% (11 out of 29 cases). The average serum creatinine in the group of patients who achieved remission was significantly lower than in the group without remission (86.5 vs. 155.5 µmol/L, p = 0.003). There was no difference in the duration of the disease prior to treatment with rituximab between the groups (53.6 and 56.4 months, respectively). The remission rate was highest in the group with daily proteinuria less than 4 g per day (83.3%). There were no remissions in the group of patients with daily proteinuria more than 12 g per day. Conclusion: The remission rate after rituximab treatment in our cohort of patients with idiopathic membranous nephropathy was lower than in other studies. The reason for this is possibly the application of a single dose of rituximab in the majority of patients, which might have been insufficient in patients with higher proteinuria.
Correspondence to:
Andreja Aleš Rigler, MD, PhD
Department of Nephrology
University Medical Center Ljubljana
Zaloška 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Kidney Transplantation
Treatment of antibody-mediated rejection of kidney grafts with bortezomib and/or rituximab compared to standard regimen: experience of Slovene National Center
Teja Oblak, Jelka Lindič, Jakob Gubenšek, Radoslav Kveder, Andreja Aleš Rigler, Andrej Škoberne, Željka Večerić Haler, Špela Borštnar, Nuša Avguštin, Rafael Ponikvar, Gregor Mlinšek, Dušan Ferluga, Nika Kojc, Uroš Godnov, and Damjan Kovač
Volume 88 (2017) p. 91 - 96
Abstract
Clinical Nephrology, Vol. 88 – Suppl. 1/2017 (S91-S96)
Treatment of antibody-mediated rejection of kidney grafts with bortezomib and/or rituximab compared to standard regimen: experience of Slovene National Center
Teja Oblak1, Jelka Lindič1, Jakob Gubenšek1#2, Radoslav Kveder1, Andreja Aleš Rigler1, Andrej Škoberne1, Željka Večerić Haler1, Špela Borštnar1, Nuša Avguštin1, Rafael Ponikvar1#2, Gregor Mlinšek1, Dušan Ferluga2#3, Nika Kojc2#3, Uroš Godnov4, and Damjan Kovač1
1Department of Nephrology, University Medical Center Ljubljana, 2Faculty of Medicine, 3Insititute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, and 4Faculty of Management, University of Primorska, Koper, Slovenia
Background: The aim of our study was to determine outcomes of standard treatment of antibody-mediated rejection (ABMR) of kidney grafts as compared to the addition of bortezomib or rituximab. Methods: The cohort of this retrospective study included patients treated for ABMR of kidney grafts at our national center in the period of 2005 – 2017, divided into two groups: standard (ST) group treated standardly with plasmapheresis or immunoadsorption, intravenous immunoglobulins, and corticosteroids, and BR group treated with the addition of bortezomib and/or rituximab. Patient and graft survival at 2 years was analyzed by Kaplan-Meier method, and predictors of graft survival were analyzed by Cox regression. Results: There were 78 patients with ABMR (48 in the ST group, 30 in the BR group), 41 (53%) were men, mean age 49.5 ± 13.8 years. In ST and BR, respectively, mean serum creatinine was 267 ± 164 and 208 ± 112 µmol/L (p = 0.088), donor-specific antibodies (DSA) were positive in 75% and 97% (p = 0.022), and ABMR was acute in 50% and 33% (p = 0.149). Patient survival at 2 years was 89% in the ST and 100% in the BR group (p = 0.125). Cumulative proportion of kidney graft survival at 1 and 2 years was 67% and 53% in the ST group and 73% and 48% in the BR group, respectively, (p = 0.641). Chronic ABMR (HR 5.22, p = 0.004) was significant, while dialysis dependency at biopsy (HR 3.28, p = 0.072), serum creatinine at kidney biopsy (HR 1.003, p = 0.082), and presence of DQ-DSA (HR 3.37, p = 0.062) were borderline significant predictors of worse graft outcome. Infections were relatively common in both groups, with a trend towards more rehospitalizations due to infections in the first 6 months after treatment in the BR group (p = 0.066). In 5 patients (17%), treatment with bortezomib was discontinued prematurely due to cytopenia. Conclusions: Bortezomib or rituximab, added to standard treatment, did not significantly improve kidney graft survival and was also not associated with significant side effects, except cytopenia in some cases. Treatment of acute ABMR resulted in better graft survival than chronic ABMR.
Correspondence to:
Assoc. Prof. Damjan, Kovač, MD, PhD
Department of Nephrology
University Medica Centre Ljubljana
Zaloška cesta 7, 1525 Ljubljana, Slovenia
Email: [email protected]
Complement activation and cryoglobulinemia are common in monoclonal gammopathy of renal significance: Data from a case series
Andrej Škoberne, Matevž Škerget, Nika Kojc, Maja Frelih, Andreja Aleš Rigler, Željka Večerić Haler, Špela Borštnar, Nuša Avguštin Rotar, Damjan Kovač, Jelka Lindič, and Samo Zver
Volume 96 (2021) p. 16 - 23
Abstract
Clinical Nephrology, Vol. 96 – Suppl. 1/2021 (S16-S23)
Complement activation and cryoglobulinemia are common in monoclonal gammopathy of renal significance: Data from a case series
Andrej Škoberne1,3, Matevž Škerget2,3, Nika Kojc4, Maja Frelih4, Andreja Aleš Rigler1,3, Željka Večerić Haler1,3, Špela Borštnar1,3, Nuša Avguštin Rotar1,3, Damjan Kovač1,3, Jelka Lindič1,3, and Samo Zver2,3
1Department of Nephrology, 2Department of Hematology, University Medical Center Ljubljana, 3Faculty of Medicine, and 4Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Introduction: Monoclonal gammopathy of renal significance (MGRS) denotes kidney diseases caused by monoclonal immunoglobulins in patients who do not have an overt hematological malignancy. Treatment is primarily directed against the underlying clone. Complement activation and cryoglobulinemia are known factors that can contribute to tissue damage, however, the full extent of their involvement is not clear. Materials and methods: This was a retrospective study including all patients with MGRS referred for consultation to our hospital over a 3-year period. Results: We identified 17 patients, of which 12 had proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Treatment with anti-clonal or immunosuppressive therapy was successful in 60% of patients with PGNMID, and treatment success was more common in patients with λ chain (100%) compared to κ chain deposits (20%). Serum markers of complement involvement were identified in 41% of all patients (88% of tested samples), most commonly high serum C5b-9 values or anti-factor H autoantibodies (both 24%). Patients with complement involvement did not respond well to treatment, which was unsuccessful in all treated patients with anti-factor H autoantibodies and 75% of patients with high serum C5b-9 values. Cryoglobulinemia was identified in 29% of all patients (71% tested samples) and was monoclonal in 40% of positive cases and mixed in 60%. None of the patients with cryoglobulinemia had organized deposits, however, there was a trend toward more common intramembranous deposits. In patients with monoclonal cryoglobulinemia both anti-clonal and immunosuppressive treatment were unsuccessful. All patients with mixed cryoglobulinemia were treated successfully with immunosuppressive therapy. Conclusion: Treatment of patients with PGNMID was successful in most cases. Complement involvement as well as monoclonal and mixed cryoglobulinemia were relatively common in our cohort, with the first two generally associated with unsuccessful treatment and the latter with successful treatment.Correspondence to:
Andrej Škoberne, MD, PhD, Department of Nephrology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia
Email: [email protected]
Histomorphological and clinical characteristics of patients with thin glomerular basement membrane nephropathy
Aleksandra Pečovnik, Željka Večerić Haler, Karmen Wechtersbach, Jerica Pleško, Maja Frelih, Jelka Lindič, and Nika Kojc
Volume 96 (2021) p. 24 - 30
Abstract
Clinical Nephrology, Vol. 96 – Suppl. 1/2021 (S24-S30)
Histomorphological and clinical characteristics of patients with thin glomerular basement membrane nephropathy
Aleksandra Pečovnik1, Željka Večerić Haler2,3, Karmen Wechtersbach4, Jerica Pleško4, Maja Frelih4, Jelka Lindič2,3, and Nika Kojc4
1Department of Pathology and Cytology, General Hospital Celje, Celje, 2Clinical Department of Nephrology, University Clinical Center Ljubljana, 3Faculty of Medicine, and 4Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
Background: Thin basement membrane nephropathy (TBMN) is a disorder characterized by ultrastructural abnormalities of the glomerular basement membrane (GBM), representing a spectrum of genetic and clinical phenotypes ranging from benign hematuria to proteinuria and chronic kidney disease. Recent studies have shown that a significant percentage of patients who initially present with hematuria later develop proteinuria and worsening renal function. Materials and methods: We retrospectively analyzed records of patients diagnosed with TBMN, including their clinical, laboratory, and histological features, in Slovenia from 2015 to 2020. Results: TBMN was the main diagnosis at kidney biopsy in 34 (65%) of 52 included patients, while in 18 patients (35%) TBMN was diagnosed in addition to other renal diseases. In the isolated TBMN group, 29 of 34 patients had glomerulosclerosis (global, global and segmental, segmental only) accompanied by interstitial fibrosis/tubular atrophy of varying degrees. 13 patients with isolated TBMN had signs of advanced chronic kidney disease at the time of diagnosis, with estimated glomerular filtration rate < 60 mL/min/1.73m2. 29 patients had proteinuria, which exceeded 3 g/day in 4 patients. TBMN represents a proportion of patients with focal segmental glomerulosclerosis (FSGS) that have often been classified in the past as etiologically indeterminate FSGS. Conclusion: Ultrastructural examination showing diffuse thinning of the GBM is crucial for the TBMN diagnosis. TBMN was the main diagnosis of kidney biopsy in 2/3 of our patients, while it was accompanied by other renal diseases in 1/3. Up to 1/3 of patients with isolated TBMN had evidence of advanced chronic kidney disease at the time of diagnosis.Correspondence to:
Nika Kojc, MD, PhD, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia
Email: [email protected]
