Glomerular injury secondary to infection is a well-documented phenomenon. While the incidence of classic acute post-streptococcal glomerulonephritis (APIGN) has declined in developed countries over the past few decades, IgAdominant infection-associated glomerulonephritis (IgA PIGN) is emerging as a distinct renal pathology. Characterized by predominant deposition of IgA antibodies within the glomeruli following infection, IgA-dominant PIGN differs from classic PIGN, which typically involves IgG and C3 deposits. This condition is often associated with staphylococcal infections and carries a poor prognosis. It commonly affects older adults and presents with reduced glomerular filtration rate and heavy proteinuria. Due to its rarity and overlapping clinical features with other glomerular diseases, IgA PIGN can be challenging to diagnose, often progressing to end-stage renal disease (ESRD) in approximately 80 % of cases. Prompt diagnosis and management, often requiring renal biopsy, are crucial for improving outcomes. Here, we present a case of IgA-dominant postinfectious glomerulonephritis.

Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by the deposition of nonamyloid, typically Congo red-negative fibrils within the glomerular basement membrane and mesangium. Although the pathogenesis of FGN remains incompletely understood, several autoimmune conditions have been associated with its development, including systemic lupus erythematosus (SLE). The co-occurrence of SLE and FGN is rare, and the underlying pathophysiologic link, if any, remains poorly understood. We report 2 cases of biopsy-proven FGN with positive DnaJ homolog subfamily B member 9 (DNAJB9) immunostaining in patients with established SLE, one with concurrent membranous lupus nephritis (LN) and the other without LN. Both patients were treated with rituximab, achieving complete proteinuria remission with preserved kidney function in one case and improved creatinine levels in the other. Three cases of SLE-associated FGN with positive DNAJB9 staining have been previously reported. Two others have been described as such, but without documentation of relevant clinical details such as DNAJB9 status, making them unsuitable for the current discussion. Our cases add to the literature supporting a potential association between SLE and FGN and represent the first published evidence of the safety and efficacy of rituximab in this rare condition.

Fibrillary glomerulonephritis (FGN) is a rare kidney disease typically affecting individuals in middle age, frequently presenting with advanced renal failure, proteinuria, and hypertension. FGN can be associated with autoimmune diseases, hepatitis C infection, and malignancies. Its exact pathogenesis remains elusive, and the exact role of DnaJ homolog subfamily B member 9 is yet to be determined. On renal biopsy, FGN exhibits distinctive Congo-red-negative, nonbranching fibrils, approximately 20 nm in diameter. DnaJ homolog subfamily B member 9 immunohistochemical staining has become a gold standard for diagnosis. Atypical variants exist, including congophilic, monotypic, and crescentic FGN, highlighting the disease's heterogeneity. Treatment with immunosuppression, including rituximab, has shown variable success, with no standard therapy established. FGN often leads to end-stage kidney disease, with a median progression time of 2-4 years postdiagnosis. Kidney transplantation is a viable option for FGN-related end-stage kidney disease, but recurrence in transplanted kidneys is not rare.

Background: Membranous-like glomerulopathy with masked monoclonal IgG deposits (MGMID) is a newly recognized condition predominantly observed in young females, and its understanding in the pediatric population remains limited. Materials and methods: Four cases of MGMID are reported, including three pediatric patients. Results: All patients were female, with ages ranging from 12 to 26 years. None of the patients had malignancies. They presented with kidney dysfunction, proteinuria, or hematuria. Kidney biopsies of all cases exhibited a membranous pattern of injury with monoclonal IgG-kappa restriction, "unmasked" by pronase digestion. Pediatric cases were treated conservatively, while the adult case underwent immunosuppressive treatment. All patients had favorable outcomes, and none reached end stage kidney disease (ESKD). Conclusion: MGMID can affect both adult and pediatric patients. Further studies are needed to fully characterize its risk factors, optimal therapy, and outcomes.

We present 3 cases of biopsy-proven minimal change disease occurring in close temporal association with semaglutide (glucagon-like peptide 1 receptor agonists) exposure. The observed diffuse podocytopathy was associated with de novo formation of antinephrin antibodies in 2 of the 3 cases. All patients experienced complete remission shortly after discontinuing semaglutide and undergoing immunosuppressive therapy, which included either steroids or a combination of tacrolimus and rituximab. Although further research is needed to establish causality, this report highlights a new association of which prescribers need to be aware, particularly as the use of glucagon-like peptide 1 receptor agonists continues to expand.

Context. To determine the clinical-pathological features associated with cholesterol embolic renal disease, and review of literature. Design. This retrospective case series includes patients with cholesterol embolic renal disease (10 of 3087 kidney biopsies) who were diagnosed at Northwell Health, New York, between July 2017 and October 2022. Results. Cholesterol embolic renal disease is a rare disease with a prevalence of 0.32%. Four of 10 patients had intravascular interventional radiology procedures within 6 months prior to kidney biopsy. Four patients had remote interventional radiology history (6 months to 4 years). Seven patients presented with acute kidney injury; 3 patients underwent renal biopsy due to proteinuria. The average baseline creatinine was 2.0 ± 0.9 mg/dL; the creatinine at kidney biopsy and at follow-up was 4.3 ± 3.0 mg/dL and 2.8 ± 1.3 mg/dL, respectively. Eight patients had elevated serum eosinophil counts. Three patients died (mortality rate 30%) in an average follow-up of 4 months (range: 1-10 months). One patient progressed to end-stage kidney disease. The presence of cholesterol clefts is a hallmark of atherosclerotic emboli. Cholesterol clefts were present on the specimen for light microscopy (H&E and special stains) in 9 biopsies; 7 patients had cholesterol clefts in vascular lumens and/or walls. Cholesterol clefts were present on semi-thin sections for electron microscopy examination in 4 biopsies. One patient had cholesterol clefts present in semi-thin sections only. Conclusions. The clinical manifestation of cholesterol embolic renal disease in patients without recent intravascular interventional radiology history can be indolent but is associated with high mortality. Careful examination of all levels with light microscopy, including the perirenal tissue, and semi-thin sections can increase the detection rate of cholesterol embolic renal disease.

Journal of the American Society of Nephrology 34(11S):p 275-276, November 2023. | DOI: 10.1681/ASN.20233411S1275d

Atypical anti-glomerular basement membrane (anti-GBM) disease is characterized by linear immunoglobulin G (IgG) deposition along the GBM without circulating IgG anti-GBM antibodies. Compared to classic anti-GBM disease, atypical anti-GBM disease tends to be milder with a more indolent course in certain cases. Moreover, pathologic disease pattern is much more heterogenous in atypical anti-GBM disease than in the classic type, which is uniformly characterized by diffuse crescentic and necrotizing glomerulonephritis. Although there is no single well-established target antigen in atypical anti-GBM disease, the target antigen (within the GBM) and the autoantibody type are hypothesized to be different from the classic type. Some patients have the same antigen as the Goodpasture antigen that are detected only by a highly sensitive technique (biosensor analysis). Some cases of atypical anti-GBM disease have autoantibodies of a different subclass restriction like IgG4, or of monoclonal nature. Antibodies targeting antigen/epitope structure other than the Goodpasture antigen can be detected using modified assays in some cases. Patients with IgA- and IgM-mediated anti-GBM disease are known to have negative circulating antibodies because conventional assays do not detect these classes of antibodies. A significant proportion of cases with atypical anti-GBM disease do not have any identifiable antibodies despite extensive evaluation. Nevertheless, extensive evaluation of atypical autoantibodies using modified assays and sensitive techniques should be attempted, if feasible. This review summarizes the recent literature on atypical anti-GBM disease.

Context: African Americans (AA) may carry high risk Apolipoprotein L1 ( APOL1) genetic variants that predispose them to significantly higher incidence of chronic kidney disease (CKD) and renal cell carcinoma (RCC). Objective: To study the role of APOL1 risk alleles in patients of African descent with kidney neoplasms. Design: AA patients with nephrectomy procedure for kidney neoplasms were retrospectively studied for APOL1 genotype. Non-AA patients with kidney neoplasm served as control group. Results: Thirty-six AA patients with kidney neoplasms were included. Sixteen (44%) patients carried no APOL1 risk alleles; 13 (36%) patients carried one APOL1 risk allele and 7 (19%) patients carried two APOL1 risk alleles. Increased risk of end stage kidney disease (ESKD) was observed in patients with two APOL1 risk alleles (OR = 3.45). We also observed a higher papillary carcinoma (pRCC) percentage in patients with two risk alleles. Five (71.4%) of the seven patients with two risk-alleles had pRCC. In patients with zero or one APOL1 risk allele ( n = 29), 8 (28%) had pRCC. However, in AA patients with ESKD ( n = 6), only 2 (33%) had PRCC. Among the non-AA patients ( n = 319), 7 (2.2%) patients presented with ESKD, of which 2 (33%) had pRCC. Conclusions: We observed a cluster phenomenon in APOL1 high-risk genotype, ESKD, and kidney neoplasm. We observed significantly more frequent papillary RCC prevalence in AA patients with high-risk APOL1 genotype.

This review describes the clinical and pathological features of oxalate nephropathy (ON), defined as a syndrome of decreased renal function associated with deposition of calcium oxalate crystals in kidney tubules. We review the different causes of hyperoxaluria, including primary hyperoxaluria, enteric hyperoxaluria and ingestion-related hyperoxaluria. Recent case series of biopsy-proven ON are reviewed in detail, as well as the implications of these series. The possibility of antibiotic use predisposing to ON is discussed. Therapies for hyperoxaluria and ON are reviewed with an emphasis on newer treatments available and in development. Promising research avenues to explore in this area are discussed.

Introduction: The prevalence of chronic kidney disease (CKD) is high among kidney neoplasm patients because of the overlapping risk factors. Our purpose is to identify kidney cancer survivors with higher CKD risk. Methods: We studied a retrospective cohort of 361 kidney tumor patients with partial or radical nephrectomy. Linear mixed model was performed. Results: Of patients with follow-up >3 months, 84% were identified retrospectively to fulfill criteria for CKD diagnosis, although CKD was documented in only 15%. Urinalysis was performed in 205 (57%) patients at the time of nephrectomy. Multivariate analysis showed interstitial fibrosis and tubular atrophy (IFTA) >25% ( p = 0.005), severe arteriolar sclerosis ( p = 0.013), female gender ( p = 0.024), older age ( p = 0.012), BMI ⩾ 25 kg/m2 ( p < 0.001), documented CKD ( p < 0.001), baseline eGFR ⩽ 60 ml/min/1.73 m2 ( p < 0.001), and radical nephrectomy ( p < 0.001) were independent risk factors of lower eGFR at baseline and during follow-up. Average eGFR decreased within 3 months post nephrectomy. However, patients with different risk levels showed different eGFR time trend pattern at longer follow-ups. Multivariate analysis of time × risk factor interaction showed BMI, radical nephrectomy and baseline eGFR had time-dependent impact. BMI ⩾ 25 kg/m2 and radical nephrectomy were associated with steeper eGFR decrease slope. In baseline eGFR > 90 ml/min/1.73 m2 group, eGFR rebounded to pre-nephrectomy levels during extended follow-up. In partial nephrectomy patients with baseline eGFR ⩾ 90 ml/min/1.73 m2 ( n = 61), proteinuria ( p < 0.001) and BMI ( p < 0.001) were independent risk factors of decreased eGFR during follow up. Conclusions: As have been suggested by others and confirmed by our study, proteinuria and CKD are greatly under-recognized. Although self-evident as a minimum workup for nephrectomy patients to include SCr, eGFR, urinalysis, and proteinuria, the need for uniform applications of this practice should be reinforced. Non-neoplastic histology evaluation is valuable and should include an estimate of global sclerosis% (GS) and IFTA%. Patients with any proteinuria and/or eGFR ⩽ 60 at the time of nephrectomy or in follow-up with urologists, and/or >25% GS or IFTA, should be referred for early nephrology consultation.

Gastrointestinal neuroendocrine tumors, or GI-NETs are a highly diverse group of tumors derived from neuroendocrine cells of the GI tract. In GI-NET, a spectrum of histological and molecular parameters exists to predict prognosis and survival. Immunohistochemistry for Ki67, a nuclear antigen that is present in all but the G0 phase of the cell cycle with specificity for proliferating cells, can be used to determine a tumors proliferation index. With this in mind, grading of gastrointestinal neuroendocrine tumors is critical for prognosis and can impact clinical decision making. Recently, digital image analysis (DIA) has been shown in studies to be a superior and less time-consuming alternative to the manual scoring of Ki-67 in breast cancer, secondary to its theoretical diagnostic reproducibility. In DIA, the correct identification of tumor cells and non-tumor is paramount to avoid over or under calculation of biomarker expression. Additionally, DIA requires a pathologist to manually outline a tumor in large tissue areas of hematoxylin and eosin (H&E) sections, which is impractical. The findings in our study showed that ventana virtuoso software computer analyzed Ki-67 only correlated well with Neuroendocrine carcinomas while manual analysis of mitotic index and Ki67 were found to be gold standard. The performance of DIA in our study was plagued by software issues. In future, the advent of new digital imaging technologies such as virtual dual staining will hopefully improve diagnostic accuracy and reproducibility across different DIA platforms. Ultimately, determination of therapeutic strategies should be guided by an amalgamation of clinicopathologic characteristics not limited to mitotic index and Ki-67. As well, A visual check of the results should always be performed and correlated with other findings.

Recent studies have demonstrated that induction of a diverse repertoire of memory T cells ("immune education") affects responses to murine cecal ligation and puncture (CLP), the most widely - used animal model of sepsis. Among the documented effects of immune education on CLP are changes in T cell, macrophage and neutrophil activity, more pronounced organ dysfunction and reduced survival. Little is known, however, about the effects of CLP on B cell responses, and how these responses might be altered by immune education. Importantly, effective B cell responses are modulated by IL21 produced by CD4+/CXCR5+/PD1+ T follicular helper (Tfh) cells. We examined the B cell population in control and immune educated mice 24 h and 60 days after CLP. Education alone increased Tfh cells. Twenty-four hours after CLP, Tfh cells were depleted. However, this reduction was less pronounced in immune educated mice than in controls and the percentage of CD4 T cells expressing a Tfh phenotype increased in the animals. CLP did not alter splenic architecture and decreased numbers of follicular, marginal, and germinal center B cells. CLP induced changes were not, however, noted following CLP in immune educated mice. At 60 days post - CLP, numbers of follicular, germinal center and marginal zone B cells were increased; this increase was more pronounced in immune educated mice. Finally, while CLP reduced the induction of antigen specific B cells in controls, this response was maintained following CLP in immune educated mice. Our data suggest that preexisting Tfh assists in rescuing the B cell response to CLP.

Taylor, Matthew; Yang, Yihe; Reddy, Kalpana; Abraham, Mabel; Barnes, Betsy; Deutschman, Clifford Author Information

Aims: We aim to describe the clinical and histological findings in patients with the finding of any tubular oxalate deposits in kidney biopsy specimens. Background: The prevalence, manifestation, and outcome of secondary oxalate nephropathy have not been extensively studied. Materials and methods: In this retrospective cohort study, we analyzed the clinical and histological findings in all patients with the finding of any tubular oxalate deposits in kidney biopsy specimens between July 1, 2017, and December 31, 2018, at Northwell Health Pathology Department (Manhasset, NY, USA). Results: The prevalence of oxalate deposition on a kidney biopsy was 4.07% (25/615), and in 88% of cases was a major finding. Prior to biopsy, oxalate was anticipated in only 1 case. The etiology of oxalosis was clarified retrospectively in 14 cases, most commonly due to GI surgery (n = 10) and increased oxalate intake (n = 4). In 11 cases, etiology remained unknown, although at least 3 cases were exposed to antibiotics associated with secondary oxalosis. There was no significant clinical/pathological or survival difference between known vs. unknown cause groups. The overall 3-month renal survival rate was 76.0 +/- 8.5%. Multivariate Cox regression showed that creatinine at the time of biopsy (HR: 1.79, 95% CI: 0.71 - 4.51), background histological chronicity change (HR: 1.82, 95% CI: 0.70 - 4.72) and oxalate density (HR: 2.27, 95% CI: 0.49 - 10.55) are associated with end-stage kidney disease. Conclusion: Oxalate deposition is common but rarely anticipated biopsy finding. Nephrologists need to consider surgical history and other secondary causes of oxalosis as causes of acute kidney injury - and chronic kidney disease.

Mesenteric arteriovenous vasculopathy (MAVD/V) is an extremely rare and poorly understood disease and its incidence is probably underestimated. It is an uncommon, non-inflammatory and non-atherosclerotic form of mesenteric vascular injury, first reported in 2016, with characteristic histopathologic evidence of fibromuscular dysplasia-like vascular changes.