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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 When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months.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.

In renal transplant patients with de novo donor-specific antibodies (dnDSA) we studied the value of microcirculation inflammation (MI; defined by the addition of glomerulitis (g) and peritubular capillaritis (ptc) scores) to assess long-term graft survival in a retrospective cohort study. Out of all transplant patients with standard immunological risk (n = 638), 79 (12.4%) developed dnDSA and 58/79 (73%) had an indication biopsy at or after dnDSA development. Based on the MI score on that indication biopsy patients were categorized, MI0 (n = 26), MI1 + 2 (n = 21) and MI ≥ 3 (n = 11). The MI groups did not differ significantly pretransplantation, whereas posttransplantation higher MI scores developed more anti-HLA class I + II DSA (p = 0.011), showed more TCMR (p < 0.001) and showed a trend to C4d-positive staining (p = 0.059). Four-year graft survival estimates from time of indication biopsy were MI0 96.1%, MI1 + 2 76.1% and MI ≥ 3 17.1%; resulting in a 24-fold increased risk of graft failure in the MI ≥ 3 compared to the MI0 group (p = 0.003; 95% CI [3.0-196.0]). When adjusted for C4d, MI ≥ 3 still had a 21-fold increased risk of graft failure (p = 0.005; 95% CI [2.5-180.0]), while C4d positivity on indication biopsy lost significance. In renal transplant patients with de novo DSA, microcirculation inflammation, defined by g + ptc, associates with graft survival., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: A change in the licensing arrangements for the use of erythropoietin alpha in haemodialysis patients has required a switch in the route of administration from subcutaneous (SC) to intravenous (IV). Previous work suggested that the IV route was less efficacious but studies since the enforced switch have not confirmed this., Methods: We studied haemoglobin levels and the mean weekly dose of erythropoietin alpha in 86 haemodialysis patients at monthly intervals over the 6 month period before and after a change in the route of administration of erythropoietin alpha from SC to IV. Changes in other parameters known to be associated with erythropoietin response were also monitored., Results: Mean haemoglobin level fell following the switch from 11.9 g/dl+/-1.4 at baseline to 11.3 g/dl+/-1.4 at 1 month (P = 0.001) and to a trough of 11.0 g/dl+/-1.3 at 2 months (P<0.001) before partial recovery to 11.4 g/dl+/-1.2 (P = 0.007) at 6 months. Mean weekly dose of erythropoietin after 2 months was significantly higher than baseline (8791 IU+/-5314 vs 8035 IU+/-4893). The dose continued to increase and by 6 months was 10605 IU (P<0.001), 32% higher than baseline. There was a small reduction in residual renal function, which was an independent predictor of change in dose requirement. There was a small increase in parathyroid hormone levels, but no change in serum ferritin, dosing frequency, total Kt/V, serum albumin, normalised protein catabolic rate, C-reactive protein, hospitalization rate and dialyser reuse rate., Conclusions: Switching from SC to IV erythropoietin alpha caused a significant fall in haemoglobin levels in the first 2 months. This was partially reversed by 6 months at the expense of a 32% dose increase in the dose of erythropoietin alpha by 6 months. The economic impact may be considerable.