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IgG4-related disease (IgG4-RD) is still an underestimated disorder which affects multiple organs, and its recognition as a distinct clinical disease has been only proved in the recent decades. The renal involvement has been documented in approximately 15% of patients with IgG4-RD, and the typical manifestation is a tubulo-interstitial nephritis. The main histological findings in IgG4-RD are typically a dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis, and frequently elevated IgG4 serum levels. Herein we report our atypical and peculiar clinical presentation of an IgG4-related nephropathy (IgG4-RN) and the remarkable response to rituximab (RTX) treatment at the renal imaging with computerized tomography assessment. The current nephrological evidences support the renal function recovery after steroids or steroids plus RTX therapy, even if the renal imaging data are not always shown. In a complex and enigmatic clinical scenario such as the IgG4-RN, both the renal biopsy and the renal imaging before and after the immunosuppressive therapy become mandatory tools to thoroughly define the diagnosis, the management and the response to the immunological therapy.

Background/aims: First-line immunosuppression with the B-cell depleting antibody rituximab reduced proteinuria and induced remission of the disease in patients with nephrotic syndrome (NS) secondary to idiopathic membranous nephropathy (IMN). Here we evaluated whether rituximab is equally effective in patients who failed to respond to previous immunosuppressive treatment., Methods: This academic, matched-cohort study, compared 2-year outcomes of 11 consecutive IMN patients who received second-line rituximab therapy for NS persisting or relapsing after previous treatment with steroids alone or combined with alkylating agents, cyclosporine, or immunoglobulin G, with those of 11 age- (± 5 years), gender- and proteinuria- (± 1 g/24h) matched reference patients given first-line rituximab therapy., Results: Patients' and reference patients' baseline characteristics were similar. Compared to baseline, 24-hour proteinuria similarly declined at 1 and 2 years post-rituximab (by 50.5 ± 25.1% and 60.9 ± 17.4% in patients and by 52.7 ± 31.5% and 69.4 ± 40.4% in reference patients, respectively; p < 0.01 for all comparisons vs. baseline). 8 patients and 7 reference patients achieved full (3 vs. 2) or partial (5 per cohort) proteinuria remission. Hypoalbuminemia and hyperlipidemia normalized in both groups. Self-limited infusion-related reactions occurred in 1 subject per cohort., Conclusion: Rituximab reduced proteinuria in IMN patients with no or only transient response to unselective immunosuppression as effectively and safely as in patients without previous immunosuppression., (Copyright © 2011 S. Karger AG, Basel.)

Objectives: Daily nocturnal hemodialysis (NHD) has been proposed as a valuable strategy to improve outcomes for patients on conventional hemodialysis (CHD), but it is burdened by high costs and logistic issues. Thrice NHD might represent a more affordable approach to improve hemodialysis patient outcome., Methods: Here we retrospectively analyzed the data on blood pressure, body weight, and hematochemical parameters in a cohort of 7 patients (mean age 50.4-/+11.0 years, duration of CHD 14.3-/+11.5 years) who registered in the NHD program at the dialysis unit of Ospedali Riuniti, Bergamo, Italy. Data for the 2 first years of NHD were compared with those of the last year on CHD., Results: At 2 years after start of NHD, we found a significant decrease in systolic (149.4-/+16.6 vs. 128.4+/-26.0 mm Hg, p<0.001) and diastolic (87.7-/+11.1 vs. 79.6-/+16.7 mm Hg, p<0.05) blood pressure, along with a significant reduction in the use of per-patient antihypertensive agents (1.17-/+1.19 vs. 0.47-/+0.89, p<0.05 and an increase in dry body weight (61.4-/+21.8 vs. 67.1-/+16.4 kg, p<0.001). Moreover, patients had a significant reduction in phosphate levels (6.2-/+2.4 vs. 5.4-/+3.0 mg/dL, p<0.01). The procedure was safe and well tolerated and did not require extra cost for ad hoc facilities., Conclusion: NHD is an effective approach to optimize chronic dialysis therapy.

Background and Objectives: In idiopathic membranous nephropathy (IMN), CD(20) B-cell depletion by rituximab may induce nephrotic syndrome (NS) remission. Whether this is associated with kidney function restoration and regression of the glomerular pathology was evaluated., Design, Setting, Participants, & Measurements: Treatment-induced morphofunctional changes were evaluated in 7 IMN patients consenting to repeat functional and morphologic evaluations after stable disease remission achieved by four weekly rituximab (375 mg/m(2)) infusions., Results: Over a median of 21 mo from rituximab administration, NS remission was associated with 8.5-fold increase versus baseline in sodium fractional clearance from 1.56 to 13.25, decrease in renal plasma flow from 440.8 to 276.6 ml/min per 1.73 m(2), stable glomerular filtration rate, and increased renal vascular resistances. Changes in sodium fractional clearance and hemoglobin concentration were positively correlated (r = 0.82). Biopsy reevaluations showed complete or partial reabsorption of subepithelial deposits. Median (interquartile range) IgG4 staining score decreased from 3 (3-3) to 1 (0-2), whereas total numbers of slit diaphragms (0.27; range, 0.19 to 0.30 versus 0.86; range, 0.53 to 1.16 slits/mum glomerular basement membrane) and percentages of those with electron-dense diaphragm (55.2; range, 42.0 to 62.0 versus 78.5; range, 73.0 to 82.7 of all slits) significantly increased in parallel with amelioration of glomerular ultrastructural changes. Changes in slit frequency and albumin fractional clearance were negatively correlated (r = -0.79)., Conclusions: In human IMN, treatment-induced NS remission is associated with restoration of sodium homeostasis and kidney hemodynamics, and regression of the glomerular changes underlying proteinuria. These effects are likely to translate into long-term renoprotection.

After the negative results of the HEMO study there is renewed interest in alternative, more ''physiological'' dialysis schemes, such as short daily or nocturnal dialysis. Considerable experience has been acquired with short daily hemodialysis, especially in Italy and the Netherlands. Nocturnal daily hemodialysis is mostly performed in Canada, the USA and Australia. Long hemodialysis three times a week is used in Tassin, France. Many observational studies and the prospective controlled London Study have suggested improvements in many intermediate patient outcomes such as dialysis-related symptoms, blood pressure and volume control, phosphate control (only for nocturnal daily dialysis), nutritional status, and quality of life. These studies are, however, too small and underpowered to evince differences in the primary outcomes, mortality and morbidity. An International Registry of Daily Dialysis has been created to obtain further information, and the US National Institutes of Health have sponsored two large-scale trials to compare short and nocturnal daily dialysis with conventional schemes. Organizational problems, higher costs especially initially, and the unavailability of simpler dialysis machines are the main factors that hamper the widespread use of these new schemes. Long nocturnal hemodialysis either in hospital or at home, three times a week or every other night, appears overall the best arrangement and the most attractive solution at present. It provides significant advantages with a minimal increase in cost. It would be interesting if the Italian National Health Service would prioritize funding for these promising schemes of hemodialysis.

Background and Objectives: Rituximab, given in four weekly doses, is a promising treatment for idiopathic membranous nephropathy and other immune-mediated diseases and lymphoproliferative disorders. This multidose regimen, however, may cause hypersensitivity reactions and is extremely expensive. This study was aimed at evaluating whether titrating rituximab to circulating CD20 B cells may improve safety and limit costs of treatment., Design, Setting, Participants, & Measurements: In a matched-cohort, single-center, controlled study, the outcome of 12 new incident patients who had idiopathic membranous nephropathy and nephrotic syndrome and received a B cell-driven treatment was compared with that of 24 historical reference patients who were given the standard protocol of four weekly doses of 375 mg/m2., Results: Only one patient needed a second dose to achieve full CD20 cell depletion. At 1 yr, time course of the components of nephrotic syndrome and the proportion of patients who achieved disease remission (25%) was identical in both groups. Persistent CD20 cell depletion was achieved in all patients. Costs for rituximab treatment and hospitalizations totalled 3770.90 euros ($4902.20) and 13,977.60 euros ($18,170.80) with the B cell-driven and the four-dose protocol, respectively. One patient on standard protocol had a severe adverse reaction at second rituximab dose. Thus, B cell titrated as effectively as standard rituximab treatment achieves B cell depletion and idiopathic membranous nephropathy remission but is fourfold less expensive, allowing for more than 10,000 euros, approximately $13,000 in savings per patient., Conclusions: Avoiding unnecessary reexposure to rituximab is extremely cost-saving and may limit the production of antichimeric antibodies that may increase the risk for adverse reactions and prevent re-treatment of disease recurrences.