Glomerulonephritis following COVID-19 infection or vaccination: a multicenter study in South Korea

Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. Methods: Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19–related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. Results: Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. Conclusion: This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19’s impact on GN.

Histologic evaluation of activity and chronicity of lupus nephritis and its clinical significance

The National Institutes of Health (NIH) lupus nephritis activity and chronicity indices, which comprise six activity scores and four chronicity scores, have a long development history. The 2018 revised International Society of Nephrology/Renal Pathology Society classification for lupus nephritis adopted the most recent NIH indices to replace subclasses A, C, and A/C. Although an evidence-based approach should further evaluate the clinical significance of the modified NIH indices, recent validation studies demonstrated that the modified chronicity indices have a strong correlation with kidney outcome of lupus nephritis.

Clinical analysis of factors affecting the failure of free flaps used in head and neck reconstruction

Background@#Free tissue transfer is the preferred method of reconstructing head and neck defects, with a success rate of approximately 95%. Although flap failure is uncommon, it has a major impact on patient morbidity and diminishes quality of life, making it is important to investigate the causes of flap failure. @*Methods@#This retrospective chart review analyzed patients who underwent free tissue transfer during head and neck reconstruction at a single institution between 2016 and 2021. @*Results@#During the study period, 58 patients underwent 60 free flap procedures. Revision surgery was needed in 14 patients. Subsequent free flap surgery was performed in one patient, and three free flaps (5%) could not be salvaged. Cardiovascular disease was significantly associated with flap failure, and venous congestion (thrombosis) was the most common reason for revision surgery. @*Conclusion@#Cardiovascular disease clearly emerged as a factor related to the failure of free flap surgery, and this issue warrants particular attention in patients for whom free tissue transfer is planned.

Reduction in proteinuria after immunosuppressive therapy and long-term kidney outcomes in patients with immunoglobulin A nephropathy

Background/Aims@#Despite controversy regarding the benefits of immunosuppressive therapy in immunoglobulin A nephropathy (IgAN), clinical outcomes may vary depending on the patient’s responsiveness to this therapy. This study evaluated long-term kidney outcomes according to the extent of proteinuria reduction after immunosuppression in IgAN patients. @*Methods@#Among 927 patients with biopsy-proven IgAN, 127 patients underwent immunosuppression. Time-averaged urine protein-creatinine ratio before and within 1 year after start of immunosuppression were calculated, and responsiveness to immunosuppression was assessed as the reduction of proteinuria between the two periods. Patients were classified into tertiles according to the extent of proteinuria reduction. We compared the slopes of estimated glomerular filtration rate (eGFR) decline using a linear mixed model, and estimated hazard ratios (HRs) for disease progression (defined as development of a ≥ 30% decline in eGFR or end-stage renal disease) using a Cox proportional hazard model. @*Results@#Median extent of proteinuria reduction was –2.1, –0.9, and –0.2 g/gCr in the first, second, and third tertiles, respectively. There were concomitant changes in the slopes of annual eGFR decline: –2.03, –2.44, and –4.62 mL/min/1.73 m2 among the first, second, and third tertiles, respectively. In multivariable Cox analysis, the HRs (95% confidence intervals) for disease progression were 0.30 (0.12 to 0.74) in the first tertile and 0.70 (0.34 to 1.45) in the second tertile compared with the thirdtertile. @*Conclusions@#This study showed that greater proteinuria reduction after immunosuppression was associated with a lower risk of disease progression in patients with IgAN, suggesting that responsiveness to immunosuppression may be an important determinant of kidney outcomes.

Reduction in proteinuria after immunosuppressive therapy and long-term kidney outcomes in patients with immunoglobulin A nephropathy

Background/Aims@#Despite controversy regarding the benefits of immunosuppressive therapy in immunoglobulin A nephropathy (IgAN), clinical outcomes may vary depending on the patient’s responsiveness to this therapy. This study evaluated long-term kidney outcomes according to the extent of proteinuria reduction after immunosuppression in IgAN patients. @*Methods@#Among 927 patients with biopsy-proven IgAN, 127 patients underwent immunosuppression. Time-averaged urine protein-creatinine ratio before and within 1 year after start of immunosuppression were calculated, and responsiveness to immunosuppression was assessed as the reduction of proteinuria between the two periods. Patients were classified into tertiles according to the extent of proteinuria reduction. We compared the slopes of estimated glomerular filtration rate (eGFR) decline using a linear mixed model, and estimated hazard ratios (HRs) for disease progression (defined as development of a ≥ 30% decline in eGFR or end-stage renal disease) using a Cox proportional hazard model. @*Results@#Median extent of proteinuria reduction was –2.1, –0.9, and –0.2 g/gCr in the first, second, and third tertiles, respectively. There were concomitant changes in the slopes of annual eGFR decline: –2.03, –2.44, and –4.62 mL/min/1.73 m2 among the first, second, and third tertiles, respectively. In multivariable Cox analysis, the HRs (95% confidence intervals) for disease progression were 0.30 (0.12 to 0.74) in the first tertile and 0.70 (0.34 to 1.45) in the second tertile compared with the thirdtertile. @*Conclusions@#This study showed that greater proteinuria reduction after immunosuppression was associated with a lower risk of disease progression in patients with IgAN, suggesting that responsiveness to immunosuppression may be an important determinant of kidney outcomes.

Expression of Phospholipase A2 Receptor in PediatricHepatitis B Virus-Related Membranous Nephropathy

Purpose@#Hepatitis B virus (HBV) infection is among etiologies of secondarymembranousnephropathy (MN) in pediatric patients. We evaluated expressionof phospholipase A2 receptor (PLA2R), a specific target antigen of primary MN, inpediatric HBV-related MN. @*Methods@#We retrospectively reviewed patients with biopsy-proven HBV-relatedMN from the renal biopsy registry and electronic medical records of SeveranceHospital, Seoul, Korea, from 1993 to 2004. Paraffin-embedded human kidneytissues were retrieved and immunohistochemically stained for PLA2R. @*Results@#Ten pediatric patients with 13 biopsied specimens were reviewed. Thepredominant pathological stage was stage II–III, and second was stage II. Theintensity of staining for IgG was greatest, with less intense staining for IgM, IgA,C3, C4, and C1q. All the patients had angiotensin-converting enzyme inhibitorcombined with glucocorticoid, and four patients converted to cyclosporine treatmentfrom glucocorticoid monotherapy. Urinalysis of all the patients normalizedafter variable period. PLA2R staining was demonstrated in the outer glomerulus in3 out of 13 biopsies, 2 of which were obtained from the same patient over a 5-yearinterval. @*Conclusions@#PLA2R was expressed in a small number of cases diagnosed aspediatricHBV-related MN, indicating that some HBV-related MN cases may beprimary MN concurrent with HBV infection.

Pathology of C3 Glomerulopathy

C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.

Ultrasound Feature-Based Diagnostic Model Focusing on the “Submarine Sign” for Epidermal Cysts among Superficial Soft Tissue Lesions

OBJECTIVE: To develop a diagnostic model for superficial soft tissue lesions to differentiate epidermal cyst (EC) from other lesions based on ultrasound (US) features. MATERIALS AND METHODS: This retrospective study included 205 patients who had undergone US examinations for superficial soft tissue lesions and subsequent surgical excision. The study population was divided into the derivation set (n = 112) and validation set (n = 93) according to the imaging date. The following US features were analyzed to determine those that could discriminate EC from other lesions: more-than-half-depth involvement of the dermal layer, “submarine sign” (focal projection of the hypoechoic portion to the epidermis), posterior acoustic enhancement, posterior wall enhancement, morphology, shape, echogenicity, vascularity, and perilesional fat change. Using multivariable logistic regression, a diagnostic model was constructed and visualized as a nomogram. The performance of the diagnostic model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curve and calibration plot in both the derivation and validation sets. RESULTS: More-than-half-depth involvement of the dermal layer (odds ratio [OR] = 3.35; p = 0.051), “submarine sign” (OR = 12.2; p < 0.001), and morphology (OR = 5.44; p = 0.002) were features that outweighed the others when diagnosing EC. The diagnostic model based on these features showed good discrimination ability in both the derivation set (AUC = 0.888, 95% confidence interval [95% CI] = 0.825–0.950) and validation set (AUC = 0.902, 95% CI = 0.832–0.972). CONCLUSION: More-than-half-depth of involvement of the dermal layer, “submarine sign,” and morphology are relatively better US features than the others for diagnosing EC.

Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma

BACKGROUND: Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. METHODS: Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. RESULTS: WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. CONCLUSIONS: The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.

Pathogenesis of minimal change nephrotic syndrome: an immunological concept / 소아과

Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children.

Pathogenesis of Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs) has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

Concomitant inhibition of renin angiotensin system and Toll-like receptor 2 attenuates renal injury in unilateral ureteral obstructed mice

BACKGROUND/AIMS: There has been controversy about the role of Toll-like receptor 2 (TLR2) in renal injury following ureteric obstruction. Although inhibition of the renin angiotensin system (RAS) reduces TLR2 expression in mice, the exact relationship between TLR2 and RAS is not known. The aim of this study was to determine whether the RAS modulates TLR2. METHODS: We used 8-week-old male wild type (WT) and TLR2-knockout (KO) mice on a C57Bl/6 background. Unilateral ureteral obstruction (UUO) was induced by complete ligation of the left ureter. Angiotensin (Ang) II (1,000 ng/kg/min) and the direct renin inhibitor aliskiren (25 mg/kg/day) were administrated to mice using an osmotic minipump. Molecular and histologic evaluations were performed. RESULTS: Ang II infusion increased mRNA expression of TLR2 in WT mouse kidneys (p < 0.05). The expression of renin mRNA in TLR2-KO UUO kidneys was significantly higher than that in WT UUO kidneys (p < 0.05). There were no differences in tissue injury score or mRNA expression of monocyte chemotactic protein 1 (MCP-1), osteopontin (OPN), or transforming growth factor beta (TGF-beta) between TLR2-KO UUO and WT UUO kidneys. However, aliskiren decreased the tissue injury score and mRNA expression of TLR2, MCP-1, OPN, and TGF-beta in WT UUO kidneys (p < 0.05). Aliskiren-treated TLR2-KO UUO kidneys showed less kidney injury than aliskiren-treated WT UUO kidneys. CONCLUSIONS: TLR2 deletion induced activation of the RAS in UUO kidneys. Moreover, inhibition of both RAS and TLR2 had an additive ameliorative effect on UUO injury of the kidney.

Overview of IgG4-Related Tubulointerstitial Nephritis and Its Mimickers

Tubulointerstitial nephritis (TIN) is the most common form of renal involvement in IgG4-related disease. It is characterized by a dominant infiltrate of IgG4-positive plasma cells in the interstitium and storiform fibrosis. Demonstration of IgG4-positive plasma cells is essential for diagnosis, but the number of IgG4-positive cells and the ratio of IgG4-positive/IgG-positive plasma cells may vary from case to case and depending on the methods of tissue sampling even in the same case. IgG4-positive plasma cells can be seen in TIN associated with systemic lupus erythematosus, Sjogren syndrome, or anti-neutrophil cytoplasmic antibody-associated vasculitis, which further add diagnostic confusion and difficulties. To have a more clear view of IgG4-TIN and to delineate differential points from other TIN with IgG4-positive plasma cell infiltrates, clinical and histological features of IgG4-TIN and its mimickers were reviewed. In the rear part, cases suggesting overlap of IgG4-TIN and its mimickers and glomerulonephritis associated with IgG4-TIN were briefly described.

Smoking-Related Renal Histologic Injury in IgA Nephropathy Patients

PURPOSE: Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function. RESULTS: Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years. CONCLUSION: In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.

Aberrant Blood Vessel Formation Connecting the Glomerular Capillary Tuft and the Interstitium Is a Characteristic Feature of Focal Segmental Glomerulosclerosis-like IgA Nephropathy

BACKGROUND: Segmental glomerulosclerosis without significant mesangial or endocapillary proliferation is rarely seen in IgA nephropathy (IgAN), which simulates idiopathic focal segmental glomerulosclerosis (FSGS). We recently recognized aberrant blood vessels running through the adhesion sites of sclerosed tufts and Bowman's capsule in IgAN cases with mild glomerular histologic change. METHODS: To characterize aberrant blood vessels in relation to segmental sclerosis, we retrospectively reviewed the clinical and histologic features of 51 cases of FSGS-like IgAN and compared them with 51 age and gender-matched idiopathic FSGS cases. RESULTS: In FSGS-like IgAN, aberrant blood vessel formation was observed in 15.7% of cases, 1.0% of the total glomeruli, and 7.3% of the segmentally sclerosed glomeruli, significantly more frequently than in the idiopathic FSGS cases (p = .009). Aberrant blood vessels occasionally accompanied mild cellular proliferation surrounding penetrating neovessels. Clinically, all FSGS-like IgAN cases had hematuria; however, nephrotic range proteinuria was significantly less frequent than idiopathic FSGS. CONCLUSIONS: Aberrant blood vessels in IgAN are related to glomerular capillary injury and may indicate abnormal repair processes in IgAN.

The Effect of Bortezomib on Antibody-Mediated Rejection after Kidney Transplantation

PURPOSE: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR. MATERIALS AND METHODS: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11. RESULTS: Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91+/-22.15 mL/min/1.73 m2) versus eGFR at time of AMR diagnosis (17.00+/-9.25 mL/min/1.73 m2; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function. CONCLUSION: Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.

The Effects of N-acetylcystein and Epigallocatechin-3-Gallate in Ischemia-Reperfusion Injury of Rat Lungs / 대한이식학회지

BACKGROUND: Ischemia-reperfusion injury (IRI) is a major cause of early graft dysfunction after lung transplantation. The aim of this study was to assess the effects of N-acetylcystein (NAC) and epigallocatechin-3-gallate (EGCG) on IRI of rat lungs. METHODS: Sprague-Dawley rats were divided into four groups. Sham group (n=6) did not receive IRI. Rats in the control group (n=6), NAC group (n=6), and EGCG group (n=6) were treated with an intraperitoneal injection of normal saline, NAC, and EGCG, respectively, prior to IRI. In the latter three groups, IRI was induced by clamping the left pulmonary artery, vein, and main stem bronchus for a period of 60 minutes. After ischemia, reperfusion and ventilation of the lung was allowed for a period of 180 minutes. The expression levels of inducible nitric oxide synthase (iNOS), hemeoxygenase-1 (HO-1), AMP-activated protein kinase-alpha (AMPK), and caveolin-1 in lung tissues were evaluated by Western blot. The pathological findings and the extent of pulmonary edema after IRI were compared among the groups. RESULTS: The expression levels of iNOS decreased in the Sham and EGCG groups. The expression level of HO-1 was significantly higher in the EGCG group (P=0.0001). Although the expression levels of AMPK and caveolin-1 showed no differences, the extent of phosphorylation of AMPK and caveolin-1 was higher in the EGCG and NAC groups, respectively. In hematoxylin-eosin staining, the lungs in the NAC and EGCG groups showed fewer alveolar injuries and less hemorrhagic congestion compared with the control group. CONCLUSIONS: NAC and EGCG enhanced the phosphorylation of caveolin-1 and AMPK, respectively, and attenuated lung injury induced by ischemia-reperfusion.

Usefulness of Nuclear Protein in Testis (NUT) Immunohistochemistry in the Cytodiagnosis of NUT Midline Carcinoma: A Brief Case Report

No abstract available.

The Limitations of Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology in the Diagnosis of Pancreatic Serous Cystadenoma: A Brief Case Report

No abstract available.

Sirolimus Conversion Efficacy for Graft Function Improvement and Histopathology in Renal Recipients with Mild to Moderate Renal Insufficiency

This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.