Objectives Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). All current treatment regimens include oral steroids, which are associated with severe adverse events and long-term damage. We have piloted a steroid-avoiding protocol (rituxilup) for the treatment of biopsy-proven active International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or class V LN. Methods We report the findings from the first 50 consecutive patients, treated with 2 doses of rituximab (1 g) and methyl prednisolone (500 mg) on days 1 and 15, and maintenance treatment of mycophenolate mofetil. Patients on maintenance steroids or with lifethreatening SLE or requiring dialysis were excluded. Renal remission was defined as serum creatinine no greater than 15% above baseline; complete biochemical remission (CR) was defined as urine protein : creatinine ratio (PCR)<50 mg/mmol or partial remission (PR) if PCR>50 mg/mmol but non-nephrotic and >50% reduction. Results A total of 45 (90%) patients achieved CR or PR by a median time of 37 weeks (range 4-200). Overall, 72% (n=36) achieved CR (median time 36 weeks (11-58)) and a further 18% (n=9) achieved persistent PR (median time 32 weeks (19-58)). By 52 weeks, CR and PR had been achieved in 52% (n=26) and 34% (n=17) respectively. In all, 12 relapses occurred in 11 patients, at a median time of 65.1 weeks (20-112) from remission. A total of 6/50 patients had systemic flares. Of the 45 responders, only 2 required >2 weeks of oral steroids. Adverse events were infrequent; 18% were admitted, 10% for an infective episode. Conclusions The rituxilup cohort demonstrates that oral steroids can be safely avoided in the treatment of LN. If findings are confirmed, it could mark a step change in the approach to the treatment of LN.

Background and objectives Venous thromboembolism (VTE) occurs in 7%-40% of nephrotic patients. The risk of VTE depends on the severity and underlying cause of nephrotic syndrome. This study investigated the use of low-dose prophylactic anticoagulation to prevent VTE in patients with nephrotic syndrome caused by primary glomerulonephritis.Design, setting, participants, & measurements Since 2006, all patients presenting with nephrotic syndrome to Imperial College Kidney and Transplant Centre have been considered for treatment with a novel anticoagulation prophylaxis regimen. All cases of nephrotic syndrome secondary to primary membranous nephropathy, minimal-change disease, and FSGS over a 5-year period were retrospectively reviewed. Patients with serum albumin,2.0 g/dl received prophylactic-dose low-molecular-weight heparin or low-dose warfarin; patients with albumin levels of 2.0-3.0 g/dl received aspirin, 75 mg once daily. All thrombotic events and bleeding complications were recorded.Results A total of 143 patients received the prophylactic anticoagulation regimen. Median follow-up was 154 weeks (range, 30-298 weeks). The cohort had features associated with a high risk of developing VTE; 40% of the cohort had an underlying diagnosis of membranous nephropathy, and the initial median serum albumin was 1.5 g/dl (range, 0.5-2.9 g/dl). No VTE occurred in patients established on prophylaxis for at least 1 week. VTE was diagnosed in 2 of 143 patients (1.39%) within the first week after presentation and starting prophylaxis. In both cases, it is unclear whether the thrombus had developed before or after the start of prophylaxis. One of 143 (0.69%) patients receiving prophylaxis was admitted urgently with gastrointestinal hemorrhage. Two of 143 patients (1.40%) had elective blood transfusions and procedures to manage occult gastrointestinal bleeding. No other bleeding events occurred in patients receiving prophylaxis.Conclusions This regimen of prophylactic antiplatelet or anticoagulant therapy appears effective in preventing VTE in nephrotic syndrome, with relatively few hemorrhagic complications.

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Background and objectives: Minimal change disease is an important cause of nephrotic syndrome in adults. Corticosteroids are first-line therapy for minimal change disease but a prolonged course of treatment is often required, and relapse rates are high. Patients with minimal change disease are therefore often exposed to high cumulative corticosteroid doses and are at risk of associated adverse effects. This study investigated whether tacrolimus monotherapy without corticosteroids would be effective for the treatment of de novo minimal change disease. Design, setting, participants and measurements: This was a multicenter prospective, open-label, randomized controlled trial involving 6 nephrology units across the UK. Adult patients with first presentation of minimal change disease and nephrotic syndrome were randomized to treatment with either oral tacrolimus at 0.05mg/kg twice daily, or prednisolone at 1mg/kg daily up to 60mg daily. The primary outcome was complete remission of nephrotic syndrome after 8 weeks of therapy. Secondary outcomes included remission of nephrotic syndrome at 16 and 26 weeks, rates of relapse of nephrotic syndrome and changes from baseline renal function. Results: There were no significant differences between the tacrolimus and prednisolone treated cohorts in the proportion of patients in complete remission at 8 weeks, 21 of 25 (84%) for prednisolone and 17 of 25 (68%) for tacrolimus (p=0.32, differences in remission rates were 16% (95% CI-10.5% to 40.1%)), at 16 weeks, 23 of 25 (92%) for prednisolone and 19 of 25 (76%) for tacrolimus (p=0.25, difference in remission rates 16% (95% CI-7.9% to 38.0%)), or at 26 weeks, 23 of 25 (92%) for prednisolone and 22 of 25 (88%) for tacrolimus (p=0.99, difference in remission rates 4% (95% CI-17.4% to 25.4%)). There was no significant difference in relapse rates (17 of 23 (74%) for prednisolone and 16 of 22 (73%) for tacrolimus) for patients in each group who achieved complete remission (p=0.99), or in the time from complete remission to relapse. Conclusion: Tacrolimus monotherapy can be effective alternative treatment for patients wishing to avoid steroid therapy for minimal change disease.

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Background Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate. Methods Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy ( n = 20) or TAC combined with MMF ( n = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function. Results 16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group ( p = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group ( p = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group ( p = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment. Conclusions Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN. Trial registration This trial is registered with EudraCTN2008–001009-41 . Trial registration date 2008-10-08.

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