Daratumumab, an anti-CD38 monoclonal antibody targeting plasma cells, has emerged as a potential therapy for recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation; however, data on subcutaneous administration and its use in de novo disease are limited. We report 3 kidney transplant recipients with recurrent (n = 1) and de novo (n = 2) FSGS who were plasma exchange-dependent and/or rituximab-resistant and treated with subcutaneous daratumumab. All patients achieved remission, with sustained reductions in albuminuria and stable graft function at follow-up. Treatment was well tolerated, with no injection-related reactions; 1 patient developed transient neutropenia and oral ulcers. Subcutaneous daratumumab may represent a feasible and effective option for recurrent and de novo FSGS after kidney transplantation, including refractory cases, in conjunction with anti-CD20 therapy. Prospective studies are needed to define its role as monotherapy and the durability of response.

Relapsing polychondritis (RP) is a rare autoimmune disorder with minimal reported renal involvement. We describe the first case of tip lesion variant of focal segmental glomerulosclerosis (FSGS) in a 60-year-old male with familial RP. The patient initially presented with nephrotic syndrome concomitant with RP, which was diagnosed 17 years ago; renal biopsy revealed minimal change disease at that time. Over the subsequent 17 years, he experienced four RP flares without nephrotic syndrome recurrence until his recent presentation with severe nephrotic syndrome. Repeated renal biopsy confirmed tip lesion variant of FSGS, demonstrating excellent response to corticosteroid therapy with prednisolone 1 mg/kg/day; proteinuria declined from 7g/24h to 0.98g/24h and serum albumin increased from 0.9g/dL to 2.2g/dL within three months. This case underscores the importance of considering FSGS in RP-associated nephrotic syndrome and suggests potential shared immune/genetic mechanisms. To our knowledge, this represents both the first report of tip lesion FSGS in RP and the first documented familial RP case with FSGS development.

Thrombotic microangiopathies (TMAs) that occur during pregnancy or the postpartum period-including preeclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), thrombotic thrombocytopenic purpura (TTP), and atypical hemolytic uremic syndrome (aHUS)-present a diagnostic challenge due to their overlapping clinical features. We report a case of a 21-year-old primigravida of African origin who developed the HELLP syndrome followed by postpartum aHUS. The clinical course was marked by thrombocytopenia, hemolytic anemia, acute kidney injury, and massive proteinuria. Kidney biopsy revealed TMA with collapsing focal segmental glomerulosclerosis (FSGS), suggesting concomitant podocyte injury. Genetic analysis identified a novel heterozygous deletion in CFHR5, resulting in a shorter-than-normal FHR5 protein, as revealed by Western blot, consistent with the predicted product of the deleted gene. Functional assays using endothelial cells demonstrated abnormal C5b-9 formation, indicating complement dysregulation. The patient achieved clinical recovery with mild residual proteinuria after plasma infusion and supportive therapy. This case highlights a potential pathogenic role of aberrant FHR5 proteins in postpartum aHUS and suggests a link between complement-mediated endothelial dysfunction and podocyte injury in TMA with collapsing FSGS. Complement genetic and functional testing should be considered in postpartum TMA, even in absence of overt complement consumption, to guide diagnosis, prognosis, and treatment.

We report the case of a patient with a severe neuro-renal syndrome characterized by acute-onset autoimmune nodopathy and nephrotic syndrome with acute kidney injury. The presence of IgG3 antibodies anti-pan-neurofascin (Nfasc155/186) confirmed the autoimmune nature of this pathology and justified treatment with plasma exchange, corticosteroids, tacrolimus, and subsequently rituximab. Kidney biopsy revealed focal segmental glomerulosclerosis lesions. This therapeutic approach led to complete remission of the clinical presentation. APOL1 genotyping revealed G1/G1 alleles. One year after discontinuation of maintenance therapy with corticosteroids and tacrolimus, the patient experienced a relapse of the neuro-renal syndrome. This relapse was concomitant with the reappearance of anti-pan-neurofascin antibodies, which were undetectable during the first remission. Resumption of plasma exchange therapy guided by decreasing antibody titers along with corticosteroids and tacrolimus enabled neurologic remission, although chronic kidney disease persisted. Maintenance therapy with rituximab was initiated to prevent further relapses. This first reported case of late recurrence of anti-pan-neurofascin-associated neuro-renal syndrome highlights the importance of comprehensive immunologic and genetic evaluation, close immunomonitoring, and targeted immunotherapies, including plasma exchange and long-term rituximab maintenance.

Kidney retransplantation-the reuse of a previously transplanted allograft-is rare, though limited reports suggest clinical feasibility and an underrecognized opportunity within the existing donor pool. We present a novel case involving a living individual donating a previously transplanted deceased-donor kidney after early graft failure from recurrent focal segmental glomerulosclerosis (FSGS). Five days later, that kidney was transplanted into a second recipient, where it has continued to function for over eight years. This case also exposes structural barriers that limit broader adoption. The current system lacks standardized mechanisms to identify appropriate allografts for regifting. Even when identified, accurate characterization requires attributing the graft to the original donor's profile rather than the interim recipient's, while also accounting for cumulative calcineurin inhibitor exposure and the interim recipient's clinical course. Most consequentially, the interim donor in this case report met criteria for neither living nor deceased donation, leaving him unclassifiable under either existing donor framework. These findings underscore gaps in donor classification, data capture and organ allocation that constrain wider implementation of allograft reuse. Addressing these gaps represents a unique opportunity to expand the donor pool without requiring a single additional donor.

Primary adult glomerular diseases (GDs), including immunoglobulin A nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis, are important causes of chronic kidney disease and may progress to kidney failure. Nonimmunosuppressive foundation drug therapy for primary adult GD focuses on renin-angiotensin-aldosterone system inhibition to reduce proteinuria, alleviate hypertension, and reduce the risk of kidney disease progression. Additional agents with a distinct mechanism of action may be added or substituted in patients with a high progression risk or who are intolerant to renin-angiotensin-aldosterone system inhibitors. This review highlights the role of lifestyle optimization as well as summarizing the currently nonimmunosuppressive pharmacologic treatment options, for the management of primary adult GDs. We also provide an overview of the key pathophysiologic processes contributing to disease progression. Given the safety concerns associated with immunosuppressive therapies, we discuss the future role of newer nonimmunosuppressive agents including finerenone (a nonsteroidal mineralocorticoid receptor antagonist), sparsentan (a dual endothelin-angiotensin II receptor antagonist), atrasentan (an endothelin receptor antagonist), and iptacopan (complement inhibitor), which are currently Food and Drug Administration approved or are under investigation in clinical trials for primary GDs. These and other agents may expand the currently limited treatment landscape for patients with primary adult GD. Plain-Language Summary Each kidney contains about 1 million tiny functional units called nephrons, and each nephron has a filter called a glomerulus. The glomeruli filter waste products and remove excess fluids from the blood, which exit the body through urine. When the glomeruli are damaged, there is loss of protein through the urine. This can result in a condition called glomerular disease (GD). Treatments for GD include eating a diet that is low in sodium, potassium, and protein because eating these in excess can make GD worse. People with GD may also be advised to exercise, stop smoking, and aim for an ideal target weight. Drug medicines are also an important part of treatment for GD. A type of drug called a renin-angiotensin-aldosterone system (RAAS) inhibitor helps to reduce the amount of damage to the glomeruli and also helps to reduce blood pressure in people who also have high blood pressure (called hypertension). If a person is taking a RAAS inhibitor drug (or an appropriate alternative) but their GD does not improve, then they are at a high risk of kidney disease progression. In this scenario, the person will be offered an additional drug (to take alongside their RAAS inhibitor drug) or an alternative drug that targets their GD in a different way. Some of these work by inhibiting parts of the immune system (called immunosuppressive drugs), whereas others do not do this (called nonimmunosuppressive drugs). Our review focuses on nonimmunosuppressive drugs for GD. We consider nonimmunosuppressive drugs already available for treating GD, ones that have only recently been made available, and drugs that are being tested in large clinical trials involving people with GD.

Living-donor kidney transplantation (KT) offers the best outcomes for patients with kidney failure (KF). However, recurrence of primary kidney disease in the allograft remains a major concern and represents 1 of the leading causes of graft loss, significantly influencing donor and recipient selection. The recurrence risk varies substantially among kidney diseases and must be carefully assessed during pretransplant evaluation. For diseases associated with low-to-intermediate recurrence risk, such as lupus nephritis, antineutrophil cytoplasmic antibodies-associated vasculitis, or IgA nephropathy, living-donor KT is generally safe, although appropriate counseling remains essential. In contrast, diseases such as membranous nephropathy (MN), primary focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), primary hyperoxaluria (PH), and amyloid light-chain (AL) amyloidosis are associated with higher recurrence rates and often require complex, individualized assessment. Recent advances have significantly transformed this field. Biomarkers such as anti-phospholipase A2 receptor (anti-PLA2R) antibodies in MN and antinephrin antibodies in FSGS enable refined risk stratification and tailored pre- and post-transplant strategies. Complement gene analysis and targeted therapies, including eculizumab, have markedly improved outcomes in aHUS, whereas novel complement inhibitors show promise for recurrent C3G. RNA interference therapy has expanded kidney-alone transplantation options in PH, and modern hematologic therapies have improved post-transplant prognosis in AL amyloidosis. These developments are reshaping the decision-making landscape for living-donor KT in diseases with a high risk of recurrence, highlighting the need for multidisciplinary evaluation, individualized strategies, and transparent donor-recipient communication to optimize transplant outcomes.

Artificial intelligence now plays a central role in computational pathology, enabling large-scale analysis of whole slide images for segmentation, classification, and quantitative feature extraction. Despite these advances, the development of robust and generalizable models remains constrained by the limited availability of high-quality, expertly annotated datasets. This limitation is particularly acute in renal pathology, where ground-truth generation is challenged by labor-intensive workflows, limited subspecialty expertise, inter-observer variability, heterogeneous imaging protocols, and restricted data accessibility. To address these challenges, we present Fusion Annotator, a cloud-first, pathologist-centered digital annotation platform designed to accelerate and standardize expert-driven dataset creation through consensus-oriented workflows. Unlike conventional desktop-based annotation tools that require local installation and hinder collaborative scalability, Fusion Annotator operates entirely within a web browser, enabling secure multi-institutional access, real-time updates, and centralized data management. The platform integrates with the Computational Renal Pathology Suite, leveraging open-source machine learning models to pre-identify regions of interest and functional tissue units, thereby reducing manual annotation burden. Fusion Annotator supports customizable descriptor schemas tailored to specific disease cohorts and study objectives, enabling structured and flexible annotation protocols. Additional features include reference image guidance to support annotator training, multi-expert annotation to facilitate consensus building, and iterative refinement informed by continuous feedback from practicing renal pathologists. The platform is currently being used to generate expert-annotated datasets for focal segmental glomerulosclerosis, diabetic nephropathy, and renal transplant cohorts. Fusion Annotator provides an extensible pathway for producing high-quality renal pathology datasets to support scalable AI development in computational pathology.

Disseminated adenovirus infection is a rare but often fatal complication of hematopoietic stem cell transplantation (HSCT), particularly uncommon in the autologous setting. We report the case of a 59-year-old man with stage IVB diffuse large B-cell lymphoma who underwent autologous HSCT after multiple lines of therapy. Following conditioning regimen, he developed persistent fever, mucositis, dysuria, and gross hematuria, with imaging showing bilateral pyelonephritis, ureteritis, and cystitis. Despite broad-spectrum antibiotics, symptoms persisted. Quantitative PCR revealed rapidly rising adenovirus viremia (> 1,000,000 copies/mL), and renal biopsy demonstrated viral cytopathic changes on light microscopy together with focal segmental glomerulosclerosis (FSGS). The patient progressed to fulminant oliguric renal failure and died before dialysis could be initiated. This case highlights a rare presentation of adenovirus infection with renal involvement consistent with adenovirus-associated nephropathy and concurrent FSGS after autologous HSCT, highlighting the potential convergence of viral, neoplastic, and transplant-related mechanisms in catastrophic renal injury.