Elena V. Zakharova

Lupus nephritis (LN) is one of the most common and clinically significant manifestations of systemic lupus erythematosus (SLE) and is associated with a high risk of disability. Delayed diagnosis of SLE in the Russian Federation and insufficient efficacy of standard treatment regimens necessitate the search for and implementation of new therapeutic approaches to improve patient outcomes. During the Expert Council meeting, current Russian and international clinical guidelines, data on the effectiveness of standard therapy, and the results of the international randomized phase III REGENCY clinical trial evaluating the efficacy and safety of obinutuzumab in patients with active LN were reviewed. The Expert Council resolution emphasizes that LN therapy requires a multidisciplinary approach. At the same time, the use of biologics, particularly obinutuzumab, opens new opportunities for achieving sustained remission, reducing glucocorticoid doses, and improving long-term prognosis in patients with highly active LN, including those with inadequate response to standard therapy.

Проект инициативных клинических рекомендаций по диагностике и лечению поражения почек при АНЦА-ассоциированных васкулитах

C3 glomerulopathy (С3G) is a group of ultra-rare diseases with the incidence about 13 cases per 1 million population per year. Major role in the C3G pathogenesis play disturbances of the complement activation, deposition and degradation, resulting in the glomerular deposition of C3, which, in turn, leads to glomerular damage and inflammation in the kidney tissue. C3G commonly associated with the progressive course, poor kidney outcomes and high rate of recurrence after kidney transplantation. Efficacy of the current conventional approaches to C3G treatment, including nephroprotective measures and glucocorticoids and mycophenolic acid analogues is insufficient; the usage of targeted anti-B-cell therapy with rituximab also did not provide sustainable effect. Unsatisfactory results of the current clinical practice and a rapid progress in the development of new targeted medications recently lead to the active investigation of a number of molecules, targeting several factors of the complement cascade, which may enrich therapeutic armamentarium for the treatment of C3G and other glomerular diseases, associated with the complement dysregulation. Several studies, aiming the evaluation of blockade of various complement system components – C5, C5a receptor, factor D, factor B, C3, and mannose-binding lectin-associated serine proteases type 1 and type 2 for С3G treatment are currently in progress. This review of literature presents available data from the current clinical trials and discusses new options of the targeted treatment of C3G.

Severe kidney injury in ANCA-associated vasculitis remains a major challenge for healthcare practitioners due to the difficulty in defining the term and the limitations in the evidence base associated with the exclusion of the most severely ill patients from majority of clinical trial protocols. The ACR/VF, EULAR, and KDIGO recommendations intended to answer the questions regarding the management of this patient’s population, but some recommendations on both initial and supportive therapy, provided be the expert panels, differ, which increase the number of treatment options, but also leads to the uncertainty of the expected effect of the treatment. Kidney biopsy plays an important role in identifying patients with a favorable and unfavorable kidney prognosis. Timely histological assessment is necessary not only to confirm the diagnosis, but also to decide whether to intensify therapy if active changes are detected, or, conversely, to discontinue immunosuppressive treatment and switch to renal replacement therapy if chromic changes dominate and the extrarenal manifestations are quiescent. Several scoring systems for assessing kidney damage and risks in the in ANCA-associated vasculitis were proposed during the last decade. Glucocorticoid’s dosing and the choice between cyclophosphamide and rituximab for the initial therapy remains controversial, and the most controversial issue to date remain the indications for the plasma exchange usage. New treatment options for ANCA-associated nephritis, such as the usage of complementblocking therapy are likely to improve the prognosis for the patients with severe renal damage, taking into account the maximum effect on renal function restoration in this particular category.

Проект клинических рекомендаций по диагностике и лечению волчаночного нефрита

Background: Acute kidney injury (AKI) is a common complication in patients with leukemia and lymphoma. In this single-center non-interventional retrospective study from 2010 to 2022, we aimed to evaluate causes, clinical features, and pathology finding in patients with Hodgkin lymphoma (HL), non-Hodgkin lymphoma/leukemia (NHL/CLL), or lymphoplasmacytic lymphoma (LPL) and AKI. Methods: We identified 101 patients with HL, NHL/CLL, and LPL. We analyzed AKI incidence and various clinical, laboratory, and pathology parameters and outcomes. Results: About 46.5% of patients with HL, NHL/CLL, and LPL presented with AKI. The incidence of AKI was the highest in the CLL setting (65.0%), it was lower and almost equal (48.0% and 47.0%) in NHL and HL, respectively, and the lowest (14.2%) in LPL. Study group comprised of 47 patients, M/F 31/16, median age was 64.0 [52.0; 71.0] years, and the patients with HL were significantly younger ( p = 0.022). The median disease duration prior to the AKI presentation was 14 [5; 44] months. Pre-renal AKI was diagnosed in 48.9% of cases: tumor lysis syndrome (TLS), specific lymphoid infiltration (LI), and post-renal AKI presented in 12.7% each. Kidney biopsy in 49% of patients revealed LI in 39.1% of cases. Focal segmental glomerulosclerosis presented in 21.7% of cases, proliferative glomerulonephritis with monoclonal immunoglobulin deposits in 13.0%, AA amyloidosis, IgA nephropathy, and AA amyloidosis in 8.6% each. AKI recovered in 63.8% of patients and 59.5% of patients were alive and dialysis-free at last evaluation: 100% with HL versus 58.3%, 46.1%, and 0% with NHL, LL, and LPL, respectively ( p = 0.025); and 8.5% remained alive on dialysis. About 25.5% of patients died after discontinuation or without need for dialysis; and 6.3% died on dialysis. Conclusion: AKI in patients with leukemia and lymphoma is heterogeneous and most commonly caused by volume depletion. AKI recovery, though not complete, occurred in 63.8% of cases with 68% survival.