Rituximab for the treatment of membranous nephropathy: a single-center experience.

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.
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Biocompatibility Parameters with Standard and Increased Dose of Citrate in Hemodialysis-A Randomized Trial.

BACKGROUND: The dose of citrate needed in regional citrate anticoagulation (RCA) to achieve optimal biocompatibility is unknown. We performed a randomized trial comparing two doses (ACTRN12613001340729). METHODS: In 30 patients a single hemodialysis with either standard (2.7 mmol/L) or increased dose of citrate (4 mmol/L) was performed. C5a-desArg, myeloperoxidase (MPO), thrombin-antithrombin complex (TAT), and platelet factor 4 (PF4) were measured and the inner surface of the dialyzer fibers was evaluated with scanning electron microscopy (SEM). RESULTS: A good separation of anticoagulation effect was achieved (post-filter ionized calcium 0.20 vs. 0.31 mmol/L, p < 0.05). There was no effect of citrate dose on any of the biocompatibility parameters; transient and parallel increase in PF4 after 30 min and parallel increase in TAT after 4 h were observed. There were no visually detected clotting problems within the circuit and no significant hypocalcemia in either group. SEM clotting score was excellent and comparable in both groups (p = 0.59). CONCLUSIONS: Given the excellent results in both groups, absence of between group differences and inability of the increased dose of citrate to completely blunt the small residual increase in PF4 and TAT, we conclude that the standard dose of citrate seems sufficient in RCA for chronic hemodialysis.

Calcium Mass Balance during Citrate Hemodialysis: A Randomized Controlled Trial Comparing Normal and Low Ionized Calcium Target Ranges.

BACKGROUND: Regional citrate anticoagulation (RCA) during hemodialysis interferes with calcium homeostasis. Optimal ionized calcium (iCa) target range during RCA and consequent calcium balance are unknown. METHODS: In a randomized controlled trial (ACTRN12613001029785) 30 chronic hemodialysis patients were assigned to normal (1.1-1.2 mmol/) or low (0.95-1.05 mmol/l) iCa target range during a single hemodialysis with RCA. The primary outcome was calcium mass balance during the procedure, using a partial spent dialysate collection method; magnesium mass balance was also measured. Intact parathormone (iPTH), total calcium (tCa) and magnesium were measured before and after procedures. RESULTS: Mean iCa during procedures was significantly different in the two groups (1.12±0.06 in normal and 1.06±0.07 mmol/l in low iCa group, p <0.001), resulting in different tCa (2.18±0.22 vs. 1.95±0.17, p = 0.003) after the procedure. Mean delivered calcium during the procedure was 58.3±4.8 mmol in the normal and 51.5±8.2 mmol in the low iCa group (p = 0.010), which resulted in a significantly higher mean positive calcium mass balance of 14.6±8.3 mmol (584±333 mg) per procedure in normal as compared to 7.2±8.5 mmol (290±341 mg) in low iCa group (p = 0.024). Linear mixed effects model showed a significant interaction effect of time and iCa target range group on iPTH, i.e. a significant increase in iPTH in the low as compared to normal iCa target group (p = 0.008). Magnesium mass balance was mildly negative and comparable in both groups. CONCLUSIONS: Low iCa target range resulted in a significantly less positive calcium mass balance, but in a significant increase in iPTH. To achieve a more neutral calcium balance, we recommend allowing a mild hypocalcemia during hemodialysis with RCA, especially when it is used for prolonged periods.