Objectives To determine factors influencing survival and need for hospitalisation in patients needing dialysis, and to define the potential basis for rationing access to renal replacement therapy. Design Hospital based cohort study of all patients starting dialysis over a 4 year recruitment period (follow up 15-63 months). Groups were defined on the basis of age, comorbidity, functional status, and whether dialysis initiation was planned or unplanned. Setting Renal unit in a district general hospital, which acts as the main renal referral centre for four other such hospitals and serves a population of about 1.15 million people. Subjects 292 patients, mean age 61.3 years (18-92 years, SD 15.8), of whom 193 (66%) were male, and 59 (20%) were patients with diabetes. Dialysis initiation was planned in 163 (56%) patients and unplanned in 129 (44%). Main outcome measures Overall survival, 1 year survival, and hospitalisation rate. Results Factors affecting survival in the Cox's proportional hazard model were Karnofsky performance score at presentation (hazard ratio 0.979, 95% confidence interval 0.972 to 0.986), comorbidity severity score

BACKGROUND.: Donor-specific anti-HLA antibodies (DSA) are a major cause of alloimmune injury. Transplant recipients with negative complement-dependent cytotoxic crossmatch (CDC-XM) and donor cell-based flow cytometric crossmatch (flow-XM) but low level DSA (i.e., by Luminex) have worse outcomes compared with nonsensitized patients. The aim of this study was to establish whether complement-activating ability in this low-level DSA, present before transplantation, as determined by this technique is important in dictating pathogenicity. METHODS.: We retrospectively studied 52 patients with preformed DSA detected by single-antigen flow cytometric fluorescent beads (SAFBs). Patients were transplanted using a steroid-sparing regimen consisting of alemtuzumab induction, 1 week of corticosteroids and tacrolimus monotherapy.Fifteen (29%) of 52 patients experienced antibody-mediated rejection (AMR), whereas 37 (71%) patients did not. There were no demographic differences between patients with AMR and those without. Pretransplant sera were retested using a modified (SAFB) assay, which detects the presence of the complement fragment C4d as a result of DSA-induced complement activation. RESULTS.: C4d+DSA were detected in 10 (19%) of 52 patients. Biopsy-proven AMR occurred in 7 (70%) of the 10 patients with C4d+DSA and in 8 (19%) of 42 patients with C4d-DSA. AMR-free survival was worse in patients with C4d+DSA (P<0.001). CONCLUSIONS.: The ability of preformed, low-level, DSA to trigger C4d fixation in vitro in patients with negative conventional crossmatch tests is predictive for AMR. C4d SAFB is potentially a powerful tool for risk stratification prior to transplantation and may allow identification of unacceptable donor antigens, or patients who may require enhanced immunosuppression.

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.

This is the first study to demonstrate a cut off titer for entry in to the ABO incompatible program using the relationship between ABO titer and amount of TPE required to reach transplantation. We now tailor the antibody removal protocol prior to transplantation and have introduced a cut-off entry titer to the program (≤1:256), because of the unacceptable risk of exposing patients with higher titers to long-lasting immunosuppression and costly, prolonged, courses of TPE without the guarantee of successful transplantation. Patients whose ABO titer exceeds the cut-off are counselled and offered alternative routes to transplantation.