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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. .

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. .

Encapsulating peritoneal sclerosis (EPS) is a rare complication in patients on peritoneal dialysis (PD), the prevalence of which increases with the time spent on PD. Various causative factors have been proposed, but the pathogenesis still remains unclear. The aim of our retrospective study was to analyze the basic clinical characteristics and outcomes of five patients diagnosed with EPS out of 423 patients treated with PD between January 1983 and December 2003. One patient was admitted due to ultrafiltration failure of the peritoneal membrane, and four patients were admitted for acute peritonitis. All of our patients presented with clinical symptoms suggestive of obstructive ileus. We confirmed the diagnosis of EPS with a computer tomography scan, a diagnostic laparotomy or laparoscopy, and a biopsy of the parietal peritoneum. We treated all of our patients with catheter removal, transferal to hemodialysis, antibiotics, complete parenteral nutrition, methylprednisolone, and tamoxifen for 6 months. One patient was treated with surgical enterolysis and died of septic complications, another patient died of sudden cardiac death during treatment. Three patients were doing well for 4-7 months after the treatment was started. The incidence of EPS was 1.2% and the mortality rate was 40%. EPS is a rare complication in longstanding PD patients in our institution. Despite treatment with hemodialysis, complete parenteral nutrition, steroids, tamoxifen and surgical intervention, the mortality rate is high and comparable to other reports.

The aim of our retrospective study was to analyze the clinical course and outcome of patients with immunoglobulin A (IgA) nephropathy who presented with macroscopic hematuria and acute kidney injury (AKI). During the period from 1990 to 2005, seven out of 584 adult patients with IgA nephropathy (1.2%) fulfilled the criteria for macroscopic hematuria-induced AKI. There was an equal gender distribution among our patients, and a rather high average age at presentation (55.7 +/- 10.9 years). Four patients who were oliguric upon admission to hospital needed hemodialysis treatment. The average serum creatinine at the time of kidney biopsy was 429.8 +/- 377 micromol/L (median value 378). The percutaneous kidney needle biopsies showed focal proliferative crescentic glomerulonephritis of subclass III, according to the Haas scheme, associated with prominent red blood cell tubular casts and acute tubulointerstitial nephritis. Four patients with the most prominent crescents and tubulointerstitial involvement were treated with methylprednisolone. All patients, treated and untreated, recovered their kidney function (the serum creatinine at a median follow-up of 15 months was 111.7 +/- 38 micromol/L). In conclusion, AKI in IgA nephropathy accompanied by macroscopic hematuria appears to have been a reversible condition in our series of patients. Regarding pathogenesis, the kidney biopsy study points to the important role of glomerular bleeding with consequent, widespread obstructive red blood cell tubular casts accompanied by tubular injury and interstitial nephritis.

Background. This study was designed to compare the effects of a conventional lactate-based peritoneal dialysis (PD) solution (D) and a new biocompatible bicarbonate/lactate-based solution with a low concentration of glucose degradation products (P) on peritoneal ultrafiltration (UF) and other peritoneal membrane indices. Methods. Twenty-six stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the D solution and 3 months with the P solution in a randomized order. Daily, overnight and 4-h UF on PET were measured and other peritoneal membrane indices were also assessed using PET with 2.27% glucose solution. Results. Twenty-one patients successfully completed the study. The mean daily peritoneal UF with D was 1324 ± 602 ml and 881 ± 633 ml with P (P < 0.001) and this lower daily UF of 443 ml (95% CI 275-610 ml) with P was associated with a similarly lower daily total fluid removal of 394 ml (95% CI 210-577 ml), as urine volume did not differ between D and P. The decrement in UF with the P solution was reversible. There were no significant differences in other peritoneal membrane indices (D/P creatinine, D/D 0 glucose, 4-h UF at PET, weekly creatinine clearance, weekly urea Kt/V) or blood pressure and body weight between the solutions whereas calculated peritoneal fluid absorption rate was significantly higher with the P than with the D solution. Conclusion. This study shows that the daily UF with the P solution may be lower than with the D solution. The mechanism for this short-term and reversible effect that conceivably reflects differences in biocompatibility is not clear although our results implicate that the peritoneal fluid absorption rate may differ between the two solutions.

The presence of comorbidity is a risk factor for both poor nutrition and poor outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. In CAPD specifically, peritoneal glucose load is associated with a possible suppression of appetite, contributing to protein malnutrition. This study sought to explore the factors associated with malnutrition indices in stable peritoneal dialysis patients without significant comorbidity, and to assess the impact of peritoneal glucose absorption on nutrition parameters.This was a cross-sectional observational study.This study took place in the peritoneal dialysis department of a university hospital, and involved outpatients.There were 23 stable, comorbidity-free CAPD patients (9 women), aged 54 +/- 12 years, with a CAPD duration of 28 +/- 25 months (values are mean +/- SD unless otherwise noted).Nutritional status was evaluated by means of anthropometric and serum measurements. A peritoneal equilibration test was performed, and daily glucose absorption was measured. Lean body mass (LBM) was assessed through creatinine kinetics.A significant impact of CAPD duration was found. Patients in the upper quartile of CAPD duration had worse nutritional parameters compared with the rest of the group: their mid-upper-arm surface area and fat surface area were lower (65 +/- 9 cm(2) vs. 78 +/- 6.2 cm(2) and 16 +/- 5.3 cm(2) vs. 26 +/- 9.5 cm(2), respectively, P.05), their albumin concentration was lower (36 +/- 0.5 g/L vs. 42 +/- 4 g/L, P.05), and their cholesterol and triglycerides were lower (3.5 +/- 0.5 vs. 5.2 +/- 1 mmol/L and 1.3 +/- 0.6 vs. 2.3 +/- 1.1 mmol/L, respectively, P.05). No significant correlations between peritoneal glucose absorption and these indices were found.The duration of dialysis treatment, but not peritoneal glucose absorption, is a predictor of malnutrition in stable, comorbidity-free CAPD patients.

The clinical course of a young female patient with focal segmental glomerulosclerosis (FSGS) who failed to respond to any of the recommended therapeutic protocols will represent the background of a discussion of currently available alternative treatments for FSGS. Traditionally, FSGS has been believed to have a poor prognosis, with a low response rate to treatment and a progressive course terminating with end-stage renal disease (ESRD). Some 40% of patients respond to prolonged corticosteroid treatment. Steroid resistance in adults should perhaps be assumed only after failure to respond to a 6-month course of daily steroid therapy. Regarding recent recommendations, the use of cytotoxic therapy (cyclophosphamide, chlorambucil or azathioprine) may be considered as second-line therapy (evidence D). Treatment with cyclosporin A at doses of 4-6 mg/kg/day has been successful in reducing proteinuria. There is little information available on the effects of such treatment on the progression of FSGS. Even fewer data are available on the success rate of the use of tacrolimus in resistant forms of FSGS in adults. Mycophenolate mofetil has been used with impressive success in a few high-risk patients who failed on previous therapeutic regimens. There is preliminary evidence in an uncontrolled series of patients with resistant primary FSGS that the addition of plasmapheresis may provide effective long-term benefits in some patients. The accurate assessment of the role of plasmapheresis and possibly immunoadsorption in the management of patients with FSGS requires further evaluation. Non-immunosuppressive therapy (i.e. angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, lipid-lowering drugs, non-steroidal anti-inflammatory drugs) should be applied to almost all patients with primary FSGS.

Antineutrophil cytoplasmic antibodies (ANCA) and antibodies against glomerular basement membrane (anti-GBM) rarely coexist. Both antibodies may be associated with rapidly progressive glomerulonephritis and pulmonary hemorrhage. We describe the clinical, serological and histological features of our patients with dual antibodies. From 1977 to 2008, 48 patients with anti-GBM antibody-associated renal disease were observed. Eight out of the 30 tested patients (26.7%), all females, had positive myeloperoxidase (MPO)-ANCA coexistent with anti-GBM antibodies. The patients' mean age was 63.4 +/- 7.8 years. Five presented with pulmonary-renal syndrome, all but one were dialysis-dependent on admission. They had constitutional symptoms and different organ involvement. The kidney biopsies revealed intense linear staining for immunoglobulin G and C3 along the glomerular and distal tubular basement membrane associated with irregular diffuse or focal extracapillary crescentic glomerulonephritis with necrosis of varying extent. Lesions of varying ages were characteristically expressed. Seven patients were treated with methylprednisolone and plasma exchange, four with cyclophosphamide, and one with intravenous immunoglobulin. After 28-74 months, there were three dialysis-dependent survivors and one patient with stable chronic renal disease. Two clinical relapses with pulmonary involvement and MPO-ANCA positivity without anti-GBM antibodies occurred in two dialysis-dependent patients. In summary, screening for ANCA and anti-GBM antibodies should be undertaken in patients with clinical signs of systemic vasculitis. In dialysis-dependent patients, the goal of treatment is to limit the damage of other involved organs and not to preserve renal function. Careful follow-up is necessary due to the relapsing nature of the ANCA component of the disease.

To investigate the involvement of complement activation and apoptosis in the pathogenesis of membranous glomerulonephritis by determining the concentrations of apoptosis-associated 180 bp nucleosomes and complement activation products SC5b-9 and C3d/dg in the urine of patients with membranous glomerulonephritis.Morning urine was taken from 15 patients with immunohistologically established membranous glomerulonephritis. Apoptosis-associated 180 bp nucleosomes, complement activation products SC5b-9, C3d/dg, and immune complexes CIC-C3d, CIC-IgA, and CIC-IgG were detected in the urine samples by using antigen-specific enzyme-linked immunosorbent assay.Concentrations of measured parameters were expressed in units of standard deviation, ie, relatively to the average concentrations measured in healthy subjects. We found drastically increased concentrations of apoptosis-associated 180 bp nucleosomes (13.71+/-14.97; p=0.047), complement activation products SC5b-9 (197.07+/-134.88; p=0.003) and C3d/dg (38.70+/-43.35; p=0.048), and immune complexes CIC-C3d (11.01+/-13.39; p=0.74), CIC-IgA (7.93+/-4.38; p=0.001), and CIC-IgG (20.56+/-10.87; p=0.001) in the urine of patients with an active form of membranous glomerulonephritis. All studied molecules were absent, or present in very low concentrations, in healthy subjects and patients with membranous glomerulonephritis in remission. The mean differences between healthy controls and patients with the active disease were statistically significant in all parameters, except CIC-C3d.There is an association of complement activation and apoptosis with membranous glomerulonephritis. Correlation analysis suggests that the excretion of apoptosis-associated 180 bp nucleosomes, SC5b-9, C3d/dg, and immune complexes containing IgA and IgG in the urine of patients with active membranous glomerulonephritis does not depend solely on the passive transport together with other proteins, but is probably an independent active process.

Background. The purpose of the present study was to determine clinical prognostic factors on renal survival in 37 older patients with antineutrophil cytoplasmic autoantibody-associated pauci-immune necrotizing crescentic glomerulonephritis (ANCA-associated GN) who underwent renal biopsy at our Department between January 1996 and December 2000. Methods. The date of renal biopsy was used as the start date for entry into the study. Age, gender, 24 h proteinuria, serum creatinine level, blood pressure and ANCA were evaluated. The end-point for renal survival analysis was the start of chronic dialysis. Results. Twenty-six (70%) patients showed varying degrees of renal insufficiency, nine (24%) patients required dialysis, 13 (35%) were hypertensive (BP � 140/90 mmHg) and 33 (89%) had proteinuria. During follow-up (31.73±17.39 months), 16% of the patients (6/37) developed end-stage renal disease (ESRD). The actuarial renal survival rate for all patients was 92% at 1 year and 76% at 3 years, for Wegener’s granulomatosis 80% at 1 and 3 years, for microscopic polyangiitis 85% at 1 and 3 years, and for renal limited disease (GN) 75% at 1 and 37% at 3 years. Age (P ¼ 0.024), arterial hypertension (P ¼ 0.018), proteinuria (P ¼ 0.037) and serum creatinine � 400 mmol/l (P ¼ 0.047) were the most important risk factors for ESRD. Conclusion. The actuarial renal survival rate in elderly patients with ANCA-associated GN was 92% at 1 year and 76% at 3 years. Older age, arterial hypertension, proteinuria and serum creatinine � 400mmol/l related to ESRD.

The objective of the study was to evaluate and compare the safety and effectiveness of epoetin omega (produced in baby hamster kidney cells) and epoetin alfa (produced in Chinese hamster ovary cells) in sustaining the correction of anemia in maintenance hemodialysis patients. The study, a prospective and controlled crossover, was completed in 38 stable patients treated with both epoetins for 24 weeks. Group A (17 patients) started with epoetin omega, and Group B (21 patients) started with epoetin alfa. After 24 weeks, a 4 week crossover (wash out) was made: Group A was switched to epoetin alfa and group B to epoetin omega for the next test period of 24 weeks. Both epoetins were administered subcutaneously after each dialysis. Doses were adjusted with the aim of maintaining a target hemoglobin level between 10 and 12 g/dl (hematocrit 30% to 35%). The mean weekly dose of epoetin omega/kg body weight (BW) was 67 +/- 43 U. The mean weekly dose of epoetin alfa/kg BW was 86 +/- 53 U. The average of all mean values of hemoglobin (Hb) during treatment with epoetin omega was 11.4 +/- 0.7 g/dl (hematocrit 34 +/- 2%), and during treatment with epoetin alfa was 11.3 +/- 0.7 g/dl (hematocrit 33 +/- 2%) (not significant). Thromboses of vascular access occurred in 3 patients during an epoetin omega treatment and in 3 patients during epoetin alfa treatment. At the site of injection, only 1 patient described a mild pain when treated with epoetin omega and only 6 patients when treated with epoetin alfa. In conclusion, both epoetin omega and epoetin alfa were effective in correcting the anemia of all studied patients. However, lower doses of epoetin omega were needed to maintain the same target hemoglobin level. No serious side effects with either epoetin were noted. The authors believe that additional comparisons of different epoetin preparations should be performed and will provide better insight into their biological activity and clinical responsiveness.

The purpose of this study was to find out the influence of adsorption and desorption of plasma proteins on the sieving coefficient during membrane plasma exchange. Adsorption and desorption of plasma proteins on plasmafilter membrane was an important feature in the study. It was more intensive with proteins with higher molecular weight (for IgG, α-2 macroglobulin, and IgM) and was not important with albumin. Sieving coefficients for IgG, α-2 macroglobulin, and IgM were unexpectedly high, while that of albumin remained within normal limits.

ObjectivesThis study was designed to compare the local peritoneal and systemic inflammatory effects of a conventional lactate-based (Lac) peritoneal dialysis (PD) solution and a new biocompatible bicarbonate/lactate-based (Bic/ Lac) solution having low concentration of glucose degradation products.Methods26 stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the Lac solution and 3 months with the Bic/Lac solution in a randomized order. Flow cytometry was used to measure the expression of inflammatory molecules on peritoneal cells in overnight effluent collected at the end of each study period.Results21 patients successfully completed the study. Mean fluorescence intensity of human leukocyte antigen (HLA)-DR and CD14 expression by macrophages were not different between Lac and Bic/Lac. The peritoneal appearance rate of cancer antigen 125 (kU/minute) was 68 ± 37 with Lac and 133 ± 66 with Bic/Lac ( p < 0.001), and of interleukin (IL)-6 (ng/minute), 0.28 ± 0.2 with Lac and 0.18 ± 0.16 with Bic/Lac ( p = 0.014). HLA-DR macrophage expression and IL-6 peritoneal appearance rates did not correlate. Serum concentrations with Lac and Bic/Lac were, for IL-6, 3.49 ± 2.28 and 3.72 ± 2.46 ng/L ( p = 0.17), and for high-sensitivity C-reactive protein, 2.31 ± 2.98 and 2.71 ± 3.31 mg/L ( p = 0.32) respectively. The concentration of effluent macrophages (x106/L) with Lac was 1.6 ± 1.6 and with Bic/Lac 2.6 ± 3.3 ( p = 0.07).ConclusionsWe conclude that, although there was a significant reduction in peritoneal IL-6 in patients using Bic/ Lac solution, systemic levels of inflammatory markers did not differ between the two solutions and no changes were present in macrophage surface activation markers, suggesting perhaps a less important role of peritoneal macrophages in the intraperitoneal chronic inflammatory process. The number of effluent macrophages tended to be higher in patients using the Bic/Lac solution, possibly contributing to improved intraperitoneal defense.