2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis.

OBJECTIVE: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN). METHODS: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. RESULTS: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. CONCLUSIONS: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.

Longitudinal evaluation of a weight reduction program for patients on peritoneal dialysis.

OBJECTIVES: Patients on peritoneal dialysis (PD) are exposed to glucose-based dialysate solutions with consequent risk of obesity and its attendant health problems. We wished to examine the role of changes in dialysis prescription, individualized dietaryinput, and exercise on body weight and composition. DESIGN: A 1 year, prospective interventional study integrating the care of the renal nurse, dietitian, and physiotherapist to support, educate, and encourage overweight patients on PD in a weight-reduction program. PATIENTS: Patients were considered for the study if they had been on PD for more than 3 months, had a body mass index (BMI) > 25, and were considered medically fit to undergo the planned exercise program. Recruitment was intentionally limited to a maximum of 12 patients to facilitate group interaction. Weight, BMI, and bioimpedance were measured every 3 months. RESULTS: 8 of 11 enrolled patients completed the study; 3 received transplants. There was a significant fall in median body weight at initiation, from 94.6 kg to 92.4 kg at 6 months and 89.5 kg at 12 months (p = 0.017). This equates to a reduction in BMI from 33.2 (range 26.6 - 38.4) kg/m2 at initiation to 32.1 (range 24.5 - 37.6) kg/m2 at 6 months and 32.1 (range 23.9 - 36.5) kg/m2 at 12 months. There were no significant changes in total body water, lean body mass, or percentage body fat during the study. CONCLUSION: 7 of 8 patients achieved significant weight loss during the study. The use of an informal group setting motivated patients to continue with exercise and sensible eating patterns. This study demonstrates that, with adequate support, PD patients can achieve and maintain weight loss.

A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.

Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8(+) T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8(+) T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity.

Managing peritoneal dialysis (PD)--factors that influence patients' modification of their recommended dialysis regimen. A European study of 376 patients.

OBJECTIVES: The purpose of the study was to assess the prevalence and extent of missed peritoneal dialysis (PD) exchanges and to identify possible predictors for regimen modification. DESIGN: The study was a cross sectional postal survey of PD patients. Patients were asked to complete a single questionnaire looking at factors that influenced their management of the prescribed regimen. PATIENTS: 551 patients were invited to participate in the study from 17 centres across three European countries; 10 centres from Belgium, 5 from Italy and 2 from the UK. Patients on continuous ambulatory peritoneal dialysis (CAPD), CAPD and Quantum, or automated peritoneal dialysis (APD) for more than three months and at least 18 years old were included in the study. 376 out of 551 questionnaires were completed; a response rate of 68%. RESULTS: 20% (n=67) of those who responded to the questionnaire admitted to modifying their treatment in the previous month. Those who were more likely to modify their treatment were younger, employed, had greater contact with the PD team, were on APD 10 hours or longer and were less satisfied with their APD treatment. CONCLUSION: Many of the patients self-reported modifying their dialysis regimen and possible predictors were highlighted from this study. By trying to identifying individual patients who do modify treatment healthcare professionals can target information that can support the patient in making safer treatment modification choices.