Calcium phosphate deposition, tertiary hyperparathyroidism, and the long-term effect on kidney allografts.

Background: Tertiary hyperparathyroidism adversely affects kidney allografts, with calcium phosphate deposition hypothesized to be an underlying cause. We analyzed allograft biopsies to investigate risk factors for calcium phosphate deposition and understand its impact on allograft function.

Methods: We reviewed patients who underwent kidney transplantation from 2017 to 2019.

Donor-derived posttransplant lymphoproliferative disease detection by donor-derived cell-free DNA.

Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of organ transplantation, commonly diagnosed after patients present with nonspecific constitutional symptoms and/or transplant organ dysfunction. In this article, we report a case of a kidney transplant recipient who was found to have highly elevated circulating donor-derived cell-free DNA (dd-cfDNA) levels on routine serum surveillance for allograft rejection, initially without organ dysfunction or evidence of allograft rejection on biopsy. Later, for cause imaging revealed retroperitoneal lymphadenopathy and an allograft hilar mass, which was biopsied to show PTLD/diffuse large B cell lymphoma.

Characteristics and Outcomes of NELL1 Membranous Nephropathy in Lipoic Acid Users and Nonusers.

Introduction: Neural epidermal growth factor like 1 membranous nephropathy (NELL1 MN) is associated with various secondary etiologies. However, previous studies on the frequency of these associations and their impact on outcomes are limited. We report a large multiinstitutional series of patients with NELL1 MN with a focus on secondary associations, pathology findings, and their impact on outcome.

Parental recovered acute kidney injury causes prenatal renal dysfunction and fetal growth restriction with sexually dimorphic implications for adult offspring.

Acute kidney injury (AKI) is rapidly increasing in global incidence and a healthcare burden. Prior maternal AKI diagnosis correlates with later pregnancy complications. As pregnancy influences developmental programming, we hypothesized that recovered parental AKI results in poor pregnancy outcomes, impaired fetal growth, and adult offspring disease.

NELL1 membranous nephropathy: clinical associations provide mechanistic clues.

Neural epidermal growth factor-like 1 (NELL1) membranous nephropathy (MN) is notable for its segmental deposit distribution, IgG1 dominant deposits, and comparatively high rate of spontaneous remission. It has been associated with a variety of exposures and secondary conditions, specifically use of thiol-containing medications - including lipoic acid, bucillamine, and tiopronin - as well as traditional indigenous medications (TIM) particularly those with high mercury content, and non-steroid anti-inflammatory drugs (NSAIDs). Malignancies, graft host disease (GVHD), infection, and autoimmune conditions have also been associated with NELL1 MN.

Diagnostic Challenges and Emerging Pathogeneses of Selected Glomerulopathies.

Recent progress in glomerular immune complex and complement-mediated diseases have refined diagnostic categories and informed mechanistic understanding of disease development in pediatric patients. Herein, we discuss selected advances in 3 categories. First, membranous nephropathy antigens are increasingly utilized to characterize disease in pediatric patients and include phospholipase A2 receptor (PLA2R), Semaphorin 3B (Sema3B), neural epidermal growth factor-like 1 (NELL1), and protocadherin FAT1, as well as the lupus membranous-associated antigens exostosin 1/2 (EXT1/2), neural cell adhesion molecule 1 (NCAM1), and transforming growth factor beta receptor 3 (TGFBR3).

Clinicopathologic Features of Antibrush Border Antibody Disease.

Introduction: Antibrush border antibody disease (ABBA) is an autoimmune tubulointerstitial kidney disease that primarily affects older individuals and results in progressive kidney failure. It is rare with only 20 reported cases. Here, we describe a case series to further define the clinicopathologic spectrum and natural history, and to inform management.

AA amyloidosis With Ig-Dominant Staining and Diagnostically Unusual Features.

Introduction: Although serum amyloid A (AA) amyloid may occasionally show nonspecific staining by immunofluorescence (IF), the correct diagnosis can usually be determined by integrating pathologic features and clinical scenario, and using AA amyloid immunohistochemistry (IHC) and/or mass spectrometry. A recent mass spectrometry-based study described false-positive Ig IF staining in a subset of AA amyloid cases.

Methods: We sought to delineate clinicopathologic features of AA amyloid with Ig-dominant staining by using a retrospective review.

Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations.

Introduction: Cure Glomerulonephropathy (CureGN) is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy. We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility, and correlation with clinical parameters at biopsy.

Methods: Definitions were established for glomerular, tubular, interstitial, and vascular lesions evaluated semiquantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence.

Legal Performance-enhancing Drugs Alter Course and Treatment of Rhabdomyolysis-induced Acute Kidney Injury.

Introduction: Rhabdomyolysis-induced acute kidney injury (RIAKI) can interrupt physical training and increase mortality in injured warfighters. The legal performance-enhancing drugs caffeine and ibuprofen, which can cause renal injury, are widely used by service members. Whether caffeine or ibuprofen affects RIAKI is unknown.

ANCA-associated kidney disease preceded by orbital pseudotumor.

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are distinct immune disorders with overlapping clinical and laboratory features. While ANCA positivity excludes IgG4-RD in the 2019 ACR/EULAR classification, this criterion is not uniformly applied, and AAV can form inflammatory masses in various organs and show increase in IgG4 + plasma cells, similar to IgG4-RD.

Case Diagnosis/treatment: A 5-year-old female with history of orbital mass diagnosed as IgG4-RD presents with acute kidney injury.

Sustained Response to Eculizumab in a Patient With COVID-19-Associated Acute Thrombotic Microangiopathy of the Allograft Kidney: A Case Report.

Acute thrombotic microangiopathy (TMA) developing in association with SARS-CoV-2 infection is a rare but recognized phenomenon in native kidneys. In the allograft kidney, a diagnosis of TMA has a broad etiologic differential, including antibody-mediated rejection and recurrent and de novo causes of TMA that affect the native kidney. Prior case reports have described plasma exchange or eculizumab use in patients with COVID-19-associated TMA.

Targeted Transcriptional Analysis of IgA Vasculitis, IgA Nephropathy, and IgA-Dominant Infection-Related Glomerulonephritis Reveals Both Distinct and Overlapping Immune Signatures.

Key Points: Skin IL-9, calprotectin, and KIR gene expression may be predictive of subsequent kidney involvement in patients with IgAV. Histologically similar patients with IgAN, IgAV, and IgA-IRGN can be distinguished by their immune transcriptomes. Kidney biopsies from patients with IgA-IRGN are enriched for transcripts involved in granulocyte chemotaxis.

The role of HLA antigens in recurrent primary focal segmental glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS), typically characterized by diffuse podocyte foot process effacement and nephrotic syndrome (diffuse podocytopathy), is generally attributed to a circulating permeability factor. Primary FSGS can recur after transplantation where it manifests as diffuse foot process effacement in the early stages, with subsequent evolution of segmental sclerotic lesions. Previous published literature has been limited by the lack of stringent selection criteria to define primary FSGS.

Fibrillary Glomerulonephritis, DNAJB9, and the Unfolded Protein Response.

Background: Fibrillary glomerulonephritis (FGN) is found in approximately 1% of native kidney biopsies and was traditionally defined by glomerular deposition of fibrils larger than amyloid (12-24 nm diameter) composed of polyclonal IgG. Recent identification of DNAJB9 as a sensitive and specific marker of FGN has revolutionized FGN diagnosis and opened new avenues to studying FGN pathogenesis. In this review, we synthesize recent literature to provide an updated appraisal of the clinical and pathologic features of FGN, discuss diagnostic challenges and pitfalls, and propose molecular models of disease in light of DNAJB9.

NELL1-Positive HIV-Associated Lupus-Like Membranous Nephropathy with Spontaneous Remission.

Introduction: Kidney biopsy findings in patients with human immunodeficiency virus (HIV) are diverse, and optimal therapy for the various immune complex diseases in the setting of HIV is unknown.

Case Presentation: A man with well-controlled HIV developed nephrotic range proteinuria, and kidney biopsy revealed lupus-like glomerulonephritis with a predominantly membranous pattern of injury. He opted for conservative therapy and experienced spontaneous and sustained remission.

The pathologic spectrum of adenovirus nephritis in the kidney allograft.

Adenovirus nephritis (ADVN) is a rare and understudied complication of kidney transplantation. Unlike BK virus nephropathy (BKVN), our knowledge of clinicopathologic manifestations of ADVN remains rudimentary and essentially limited to case reports. To expand on this, we retrospectively studied 11 kidney transplant recipients with ADVN and compared their allograft biopsies to 33 kidney transplant recipients with BKVN using conventional microscopy and the 770 gene Nanostring Banff Human Organ Transplant Profiling Panel.

Increased Rates of Supplement-Associated Oxalate Nephropathy During COVID-19 Pandemic.

Introduction: Causes of secondary oxalate nephropathy include enteric dysfunction and excessive intake of oxalate or oxalate precursors. During the COVID-19 pandemic, there has been a dramatic rise in sales of supplements and vitamin C, during which time we observed an apparent increase in the proportion of ingestion-associated oxalate nephropathy.

Methods: We retrospectively reviewed secondary oxalate nephropathy and compared pre-pandemic (2018-2019) and pandemic (2020-early 2022) time periods.

The characteristics of seronegative and seropositive non-hepatitis-associated cryoglobulinemic glomerulonephritis.

The clinicopathologic characteristics and long-term outcome of non-hepatitis-associated cryoglobulinemic glomerulonephritis (CryoGN) are not well-defined and cases with undetectable serum cryoglobulin (seronegative CryoGN) have not been investigated. To resolve this, we retrospectively identified 81 patients with biopsy-proven non-hepatitis CryoGN, including 22 with seronegative CryoGN. The median age was 61 years and 76% presented with nephritic syndrome.

A Diverse Spectrum of Immune Complex- and Complement-Mediated Kidney Diseases Is Associated With Mantle Cell Lymphoma.

Introduction: There are limited reports on kidney biopsy findings in patients with mantle cell lymphoma (MCL).

Methods: We initiated a multi-institutional, retrospective review of kidney biopsy findings in patients with active and treated MCL.

Results: A total of 30 patients with MCL and kidney biopsies were identified, with a median age of 67 (range 48-87) years, 73% of whom were men.

Pathology findings in pediatric patients with COVID-19 and kidney dysfunction.

Background: Acute kidney injury (AKI) is seen in one-fifth of pediatric patients with COVID-19 requiring hospital admission, and is associated with increased morbidity, mortality, and residual kidney impairment. The majority of kidney pathology data in patients with COVID-19 is derived from adult case series and there is an overall lack of histologic data for most pediatric patients with COVID-19.

Methods: We assembled a multi-institutional cohort of five unvaccinated pediatric patients with COVID-19 and associated kidney dysfunction with available histology.

One Hundred Years of the Pathology Medical Student Fellowship.

Context.—: The Pathology Medical Student Fellowship (PSF) is a unique, year-long immersive educational experience. Review of institutional archives describes a medical student "Fellowship in Pathology" founded in 1919.