Rescue with obinutuzumab and daratumumab as combined B cell/plasma cell targeting approach in severe posttransplant focal segmental glomerulosclerosis recurrence.

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation is associated with a high graft loss rate with standard treatments based on plasmapheresis with/without rituximab. We present 2 consecutive cases of nongenetic early severe recurrent FSGS refractory to rituximab and anti-interleukin 1 treatment and with a partial response to plasmapheresis. Case 1 was a 22-year-old man who was rescue-treated for recurrence 36 weeks after transplantation with obinutuzumab (1000 mg/1.

Absence of IL-6 Receptor Blockade Effect on the Outcomes of Transplant Glomerulopathy in the Absence of Anti-HLA Donor-specific Antibodies.

Background: Transplant glomerulopathy (TG) is the hallmark of chronic antibody-mediated rejection but often occurs without anti-HLA donor-specific antibodies (DSAs) in the assumption that other DSAs may be the effectors of the tissue injury. Recently, we reported a positive effect of interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ) in TG/DSA. In the present study, we investigate the effect of TCZ in a cohort of TG cases without detectable anti-HLA DSAs.

Kidney transplants from elderly donors: what we have learned 20 years after the Crystal City consensus criteria meeting.

Based on the current projection of the general population and the combined increase in end-stage kidney disease with age, the number of elderly donors and recipients is increasing, raising crucial questions about how to minimize the discard rate of organs from elderly donors and improve graft and patient outcomes. In 2002, extended criteria donors were the focus of a meeting in Crystal City (VA, USA), with a goal of maximizing the use of organs from deceased donors. Since then, extended criteria donors have progressively contributed to a large number of transplanted grafts worldwide, posing specific issues for allocation systems, recipient management, and therapeutic approaches.

Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

Background: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts.

Methods: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists.

The Matter of Kidney Biopsy in Monoclonal Gammopathy of Renal Significance: A Case Report of a New Pattern of Immunoglobulin-Storing Histiocytosis.

Monoclonal gammopathy of renal significance (MGRS) represents a group of disorders, characterized by paraproteinemia which causes renal damage. These disorders never meet the diagnostic criteria for multiple myeloma (MM) or lymphoproliferative disease. Crystal-storing histiocytosis is one of the rarest patterns of MGRS, characterized by an accumulation of light chains of crystals within histiocyte's cytoplasm, located in bone marrow or other extramedullary sites such as the kidney, cornea, or thyme.

Antiphospholipid Syndrome and Kidney Involvement.

Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the development of autoantibodies and the impairment of the coagulation system. Knowledge about this syndrome is increasing over time, but kidney involvement, especially APS nephropathy, still represents a challenge for physicians.

Summary: A "two hit" model has been hypothesized to explain APS pathophysiology, and the role played by some factors, such as the complement system, is becoming more and more clear.

The need for kidney biopsy in the management of side effects of target and immunotherapy.

Introduction: The introduction of innovative therapies, resulting from revisiting cancer as a disease of the immune system, has changed the scenario of complications. These new classes of drugs, such as targeted therapies and immune checkpoint inhibitors, assure substantial advantages in cancer therapy, despite some side effects affecting various organs, including the kidney. Histological evaluations of kidney disorders induced by targeted/immunotherapy are limited.

Focal segmental glomerular sclerosis can be effectively treated using an intensive B-cell depletion therapy.

Background: Focal segmental glomerular sclerosis (FSGS) is a histologic lesion rather than a specific disease entity and represents a cluster of different conditions affecting both children and adults that includes primary, secondary and genetically mediated forms. These forms can be distinguished by electron microscopy and genetic assessment and show different responsiveness to steroids and immunosuppressants. Despite some promising effects of rituximab in nephrotic syndrome in children, the results in adults with FSGS are disappointing.

Clinical-Pathological Characteristics of Renal Injuries Identify Different Clusters in Patients With Antiphospholipid Antibodies.

Introduction: Significant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS).

Methods: We applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months.

DNAJB9 Is a Reliable Immunohistochemical Marker of Fibrillary Glomerulonephritis: Evaluation of Diagnostic Efficacy in a Large Series of Kidney Biopsies.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by a challenging diagnostic workup requiring ultrastructural identification of 20 nm-thick randomly oriented fibrillar deposits. However, the recent introduction of DNAJB9 as a putative diagnostic marker of FGN could thoroughly improve this diagnostic scenario. This study aims to assess the DNAJB9 immunohistochemical expression in a large series of FGN cases and to eventually confirm its role as a diagnostic marker of FGN.

Recognizing the new disorder "idiopathic hypocryoglobulinaemia" in patients with previously unidentified clinical conditions.

A considerable number of patients with high clinical suspicion for cryoglobulinaemic vasculitis either show negative results for the detection of cryoglobulins or show only trace amounts which cannot be characterized for composition. We aimed at establishing whether the failure to detect or the detection of trace amounts of cryoglobulin with conventional methods either identifies a peculiar subset of low level cryoglobulinaemia (from now on hypocryoglobulinaemia) or represents a separate entity. Using a modified precipitation technique in hypo-ionic medium, we prospectively identified between 2008 and 2021 237 patients (median age 60.

Protective effect of the tunneling nanotube-TNFAIP2/M-sec system on podocyte autophagy in diabetic nephropathy.

Podocyte injury leading to albuminuria is a characteristic feature of diabetic nephropathy (DN). Hyperglycemia and advanced glycation end products (AGEs) are major determinants of DN. However, the underlying mechanisms of podocyte injury remain poorly understood.

Treating Patients With ANCA-Associated Vasculitis and Very Severe Renal Injury With an Intensified B Cell Depletion Therapy: Comparison With a Control Cohort Receiving a Conventional Therapy.

Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown to be an effective induction treatment for small-vessel vasculitides associated with antineutrophil cytoplasm antibodies (AAV) in both newly diagnosed and relapsing patients. However, the role of RTX in the management of the most severe cases of AAV remains to be fully elucidated. The aim of this study was to assess both safety and efficacy of an intensified B-cell depletion therapy (IBCDT) protocol, including RTX, cyclophosphamide (CYC), and methylprednisolone pulses without additional maintenance immunosuppressive therapy in a cohort of 15 AAV patients with the most severe features of AVV renal involvement (as <15 ml/min GFR and histological findings of paucimmune necrotizing glomerulonephritis with more than 50% crescents of non-sclerotic glomeruli at the renal biopsy).

Renal Involvement in Transthyretin Amyloidosis: The Double Presentation of Transthyretin Amyloidosis Deposition Disease.

Transthyretin (TTR) amyloidosis (ATTR) is either an inherited condition or a non hereditary disease due to misfolding of wild-type (WT) TTR. Amyloid deposits can be mainly detected in nerves in the inherited form and in myocardium in the acquired variant. Renal involvement has been described only in the Val30Met mutation of the familial form and is thought to be extremely rare in the WT TTR.

Spectrum of Kidney Injury Following COVID-19 Disease: Renal Biopsy Findings in a Single Italian Pathology Service.

The onset of coronavirus disease (COVID-19) as a pandemic infection, has led to increasing insights on its pathophysiology and clinical features being revealed, such as a noticeable kidney involvement. In this study, we describe the histopathological, immunofluorescence, and ultrastructural features of biopsy-proven kidney injury observed in a series of SARS-CoV-2 positive cases in our institution from April 2020 to November 2021. We retrieved and retrospectively reviewed nine cases (two pediatric and seven adults) that experienced nephrotic syndrome (six cases), acute kidney injury (two cases), and a clinically silent microhematuria and leukocyturia.

PGNMID and anti-CD38 monoclonal antibody: a therapeutic challenge.

Monoclonal gammopathy of renal significance (MGRS) designates disorders induced by a monoclonal protein secreted by plasma cells or B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form MGRS. Until now, no guidelines to decide the best therapeutic approach to manage PGNMID exist, and most patients progress to End Stage Renal Disease (ESRD) without therapy.