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Collapsing glomerulopathy (CG) is a form of podocytopathy that is challenging to manage. CG can be idiopathic or associated with other conditions including autoimmune connective tissue diseases. In the setting of autoimmune connective tissue diseases, there are no current guidelines to guide therapy. Here we report a unique and challenging case of CG with mixed connective tissue disease (MCTD) that responded to steroids followed by mycophenolate. In PubMed, we identified three previously reported cases of CG with MCTD in addition to other forms of autoimmune diseases, including Sjogren syndrome, adult-onset still's disease, and vasculitis, etc. We are providing a literature review of collapsing glomerulopathy cases in the setting of autoimmune connective tissue diseases and with MCTD. CG in the setting of autoimmune connective tissue diseases is more common in females and black patients. Response to therapy was inconsistent. Many patients progressed to dialysis despite use of various treatment modalities.

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19) resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%) which associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19, demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney., Graphical abstract

Primary renal tubulointerstitial disease resulting from proximal tubule antigen-specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border. All but one of the patients also had segmental glomerular deposits on renal biopsy specimen. Patients with ABBA disease were elderly and presented with AKI and subnephrotic proteinuria. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that we identified as LDL receptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry. Immunostaining revealed that LRP2 specifically colocalized with IgG in the tubular immune deposits on the ABBA biopsy specimen but not the control specimen analyzed. Finally, ABBA serum samples but not control samples showed reactivity against recombinantly expressed N-terminal LRP2 fragments on Western blots and immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This case series details the clinicopathologic findings of patients with ABBA disease and shows that the antigenic target of these autoantibodies is LRP2. Future studies are needed to determine the disease prevalence, stimulus for ABBA, and optimal treatment.

Renal and urinary involvement has been reported to occur in 4% to 23% of inflammatory bowel disease (IBD) patients. Parenchymal renal disease is rare and most commonly affects glomerular and tubulointerstitial compartments. The most common findings on renal biopsy of IBD patients are IgA nephropathy and tubulointerstitial nephritis. Overall morbidity of IBD-related renal manifestations is significant, and there is often only a short window of injury reversibility. This, along with subtle clinical presentation, requires a high index of suspicion and routine monitoring of renal function. There are no established guidelines for the optimal screening and monitoring of renal function in IBD patients.

Introduction The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.

Background Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma and is often difficult to diagnose. Early-stage disease is particularly challenging and requires clinical and histopathologic correlation to make an accurate diagnosis. In order to facilitate the diagnosis of early MF, an algorithm has been proposed by the International Society for Cutaneous Lymphomas (ISCL) whereby clinical and histopathologic characteristics as well as immunohistochemistry and T-cell receptor gene rearrangement studies may be applied to suspected cases of MF. The diagnostic utility of this algorithm has not yet been validated. We sought to determine the validity of the proposed algorithm via an investigator-blinded, retrospective, case-control study. Methods A total of 34 cases were randomly selected from the database of a clinic for cutaneous T-cell lymphomas and included patients with MF and patients with clinicopathologic mimics. The proposed diagnostic algorithm was systematically applied to the entire cohort. Each case was assigned a composite score based on the parameters in the proposed algorithm. Results Among the 24 cases of MF, 21 cases achieved four or more points through application of the algorithm. Among the 10 cases of MF mimics, only four achieved four or more points. This difference was significant (Fisher's exact test, p = 0.009). The sensitivity of the 4-point threshold for a diagnosis of MF was 87.5% and the specificity was 60%. Conclusions The diagnostic algorithm proposed by the ISCL is a statistically valid method for defining cases of early MF and distinguishing these cases from other benign dermatoses. However, the clinical utility of the algorithm may be limited by its low specificity. Further refinement of the algorithm may improve its accuracy.

The effects of nephropathy risk variants in the apolipoprotein L1 gene (APOL1) on renal histopathology in African Americans with arterionephrosclerosis or putative 'hypertension-associated' nephropathy are unknown. APOL1 genotype-phenotype correlations were performed in a blinded manner from renal biopsies in 196 self-reported African Americans with arterionephrosclerosis on kidney biopsy at a large national nephropathology practice. Subjects had chronic kidney disease without nephrotic syndrome. A discovery analysis compared histopathologic changes in the glomerular and tubulointerstitial compartments in 58 subjects with 2 versus 56 subjects with 0 APOL1 risk variants. Validation was performed in biopsies from 82 additional subjects with 0, 1, and 2 risk variants. Two risk variant versus zero risk variant group genotype associations and subphenotypes were assessed by χ(2) analyses. ANOVA compared means of continuous variables. In discovery analyses, significantly less obsolescent glomerulosclerosis, more (solidified and disappearing) glomerulosclerosis, more thyroidization-type tubular atrophy, and more microcystic tubular dilatation were seen in patients with two versus zero APOL1 risk alleles. Greater degrees of arteriosclerosis were present in those with zero risk alleles. Segmental glomerulosclerosis did not differ significantly between groups. Presence of two of the following discriminatory histopathologic findings from discovery, that is

There have been recent reports and warnings of a thrombotic thrombocytopenic purpura-like illness associated with intravenous abuse of a prescription narcotic intended for oral use. Oral extended-release oxymorphone hydrochloride (Opana ER) is an opioid agonist that has undergone a tamper-resistant reformulation. However, instances of melting and dissolving tablets with subsequent injection continue to occur. We report 3 cases of hemolytic anemia and acute kidney injury associated with intravenous abuse of this reformulated drug. All 3 patients underwent native kidney biopsy that showed thrombotic microangiopathy characterized by severe arterial and arteriolar mucoid intimal edema with resultant glomerular and tubular ischemia. All 3 patients required hemodialysis and 2 also underwent therapeutic plasma exchange. Early follow-up suggests that kidney outcome is poor, with only partial recovery of function despite aggressive treatment. The specific component or components of this reformulated drug associated with endothelial injury is unknown. Most importantly, a high degree of clinical suspicion is needed when treating patients with a thrombotic thrombocytopenic purpura-like illness of unknown cause.

Kidney disease as a complication of inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), has been the subject of case reports. However, no cases series examining IBD and kidney disease has been published to date. This study aimed to evaluate a large series of kidney biopsy specimens from patients with IBD to better define the spectrum and relative frequencies of IBD-associated kidney pathology.A retrospective review of native kidney biopsy specimens obtained from March 2001 to June 2012 identified 83 patients with IBD. Standard processing of all biopsy specimens included light microscopy, immunofluorescence, and electron microscopy.There were 45 cases of CD and 38 cases of UC represented. The most common indication for kidney biopsy was acute or chronic kidney failure (63% [52 of 83]) and nephrotic-range proteinuria (16% [13 of 83]). IgA nephropathy was the most common diagnosis (24% [20 of 83]), followed by interstitial nephritis (19% [16 of 83]), arterionephrosclerosis (12% [10 of 83]), acute tubular injury (8% [7 of 83]), proliferative GN (7% [6 of 83]), and minimal-change disease (5% [4 of 83]). When compared, the frequency of IgA nephropathy in IBD was significantly higher than in all other native renal biopsy specimens from the same time period (24% [20 of 83] versus 8% [2734 of 33,630]; P0.001). Of the 16 cases of interstitial nephritis, 9 (56%) had current or recent past exposure to aminosalicylates, including all cases of granulomatous interstitial nephritis.IBD is associated with a spectrum of kidney diseases most commonly affecting the glomerular and tubulointerstitial compartments. IgA nephropathy is the most frequent kidney biopsy diagnosis in IBD and has a significantly higher diagnostic prevalence compared with all non-IBD kidney biopsy specimens. This may reflect a common pathogenic mechanism. Although many cases of tubulointerstitial nephritis are related to aminosalicylate exposure, the possibility of a direct relationship with IBD cannot be ruled out.

Objectives: To implement Lean principles to accommodate expanding volumes of gastrointestinal biopsies and to improve laboratory processes overall. Design: Our continuous improvement ( kaizen ) project analyzed the current state for gastrointestinal biopsy handling using value-stream mapping for specimens obtained at a 487-bed tertiary care pediatric hospital in Dallas, Texas. We identified non-value-added time within the workflow process, from receipt of the specimen in the histology laboratory to the delivery of slides and paperwork to the pathologist. To eliminate non-value-added steps, we implemented the changes depicted in a revised-state value-stream map. Results: Current-state value-stream mapping identified a total specimen processing time of 507 minutes, of which 358 minutes were non-value-added. This translated to a process cycle efficiency of 29%. Implementation of a revised-state value stream resulted in a total process time reduction to 238 minutes, of which 89 minutes were non-value-added, and an improved process cycle efficiency of 63%. Conclusions: Lean production principles of continuous improvement and waste elimination can be successfully implemented within the clinical laboratory. * GI : gastrointestinal SIPOC : suppliers, inputs, process, outputs and customers VA : value-added activities NVA : non-value-added activities PCE : process-cycle efficiency REQ : requisitions

Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma and is often difficult to diagnose. Early-stage disease is particularly challenging and requires clinical and histopathologic correlation to make an accurate diagnosis. In order to facilitate the diagnosis of early MF, an algorithm has been proposed by the International Society for Cutaneous Lymphomas (ISCL) whereby clinical and histopathologic characteristics as well as immunohistochemistry and T-cell receptor gene rearrangement studies may be applied to suspected cases of MF. The diagnostic utility of this algorithm has not yet been validated. We sought to determine the validity of the proposed algorithm via an investigator-blinded, retrospective, case-control study.A total of 34 cases were randomly selected from the database of a clinic for cutaneous T-cell lymphomas and included patients with MF and patients with clinicopathologic mimics. The proposed diagnostic algorithm was systematically applied to the entire cohort. Each case was assigned a composite score based on the parameters in the proposed algorithm.Among the 24 cases of MF, 21 cases achieved four or more points through application of the algorithm. Among the 10 cases of MF mimics, only four achieved four or more points. This difference was significant (Fisher's exact test, p = 0.009). The sensitivity of the 4-point threshold for a diagnosis of MF was 87.5% and the specificity was 60%.The diagnostic algorithm proposed by the ISCL is a statistically valid method for defining cases of early MF and distinguishing these cases from other benign dermatoses. However, the clinical utility of the algorithm may be limited by its low specificity. Further refinement of the algorithm may improve its accuracy.