The first autopsy case of Epstein-Barr virus-positive marginal zone lymphoma that deteriorated after COVID-19 vaccination.

This is the first autopsy case of Epstein-Barr virus-positive marginal zone lymphoma (EBV + MZL) with an other iatrogenic immunodeficiency-associated lymphoproliferative disorders (LPD) (methotrexate [MTX]-associated LPD) that deteriorated after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. This case had a unique immunophenotype. A 71-year-old female patient with rheumatoid arthritis receiving MTX presented with fatigue 1 week after the SARS-CoV-2 vaccination. She was hospitalized due to hepatorenal dysfunction and pancytopenia. Computed tomography revealed systemic lymphadenopathy. Her physical condition deteriorated, and the patient died. The autopsy revealed systemic lymphadenopathy comprising medium-sized atypical lymphocytes and scattered Hodgkin/Reed-Sternberg (H/RS)-like cells. An immunohistochemical examination showed that atypical lymphocytes were positive for CD79a and MUM-1 and some were positive for CD20 and IRTA-1. H/RS-like cells were immunoreactive for CD30 and CD15 and ringed by T cells. Both cell types were positive for EBV-encoded small RNA. The majority of H/RS-like cells were positive for CD20, whereas a small number of CD3-positive cells were admixed. We herein presented the first autopsy case of EBV + MZL that deteriorated after the SARS-CoV-2 vaccination.

Morphological and etiological analyses of C3 and non-C3 glomerulonephritis in primary membranoproliferative glomerulonephritis using periodic acid-methenamine silver stain electron microscopy: a retrospective multicentered study.

This study elucidated the etiology of C3 glomerulonephritis (C3GN) and non-C3GN with primary membranoproliferative glomerulonephritis (MPGN) using transmission electron microscopy (TEM) and periodic acid-methenamine silver stain (PAM-EM). Thirty-one primary MPGN cases were analyzed by TEM and PAM-EM to distinguish among MPGN I, MPGN II, MPGN III Burkholder subtype (MPGN IIIB), and Anders and Strife subtype (MPGN IIIA/S). Each case was also classified into C3GN or non-C3GN according to the standard C3GN definition using immunostaining. Four cases of MPGN II met C3 glomerulopathy; whereas, four cases of MPGN IIIB did not meet C3 glomerulopathy. Seven of 11 cases (64%) of MPGN I without GBM disruption and 7 of 12 cases (58%) of MPGN IIIA/S with GBM disruption met the non-C3GN criteria with significant immunoglobulins' deposition. Regardless of the C3GN or non-C3GN diagnosis, the deposits in primary MPGN I and MPGN IIIA/S exhibited ill-defined, amorphous, and foggy characteristics similar to those found in postinfectious GN but were different from immune complex (IC) deposits seen in MPGN IIIB. Not only C3GN but also non-C3GN was due to mechanisms other than IC deposition as found in postinfectious GN. Consequently, GBM disruption of MPGN IIIA/S was not due to IC deposition.

Early Enhancement with Contrast-Enhanced Ultrasonography Relates to the Number of Small-Diameter Neovessels in the Carotid Plaque.

BACKGROUND AND PURPOSE: Intraplaque neovessels (INVs) have been recognized as a major cause of intraplaque hemorrhage and subsequent vulnerability of the carotid plaque. However, the exact mechanisms by which INVs cause intraplaque hemorrhage remain unclear. Various sizes of INVs coexist in carotid plaques pathologically, and we hypothesized that the size of INVs would be associated with carotid plaque histology, particularly in terms of intraplaque hemorrhage. Detection method of INV is important when determining whether carotid plaques are vulnerable, and contrast-enhanced ultrasonography (CEUS) is one of the most useful methods to detect them. The purpose of this study was to examine the relationship between findings from CEUS and vascular pathology obtained by carotid endarterectomy (CEA). We focused on associations between small and large INVs evaluated by CEUS and histologically defined intraplaque hemorrhage. METHODS: Participants comprised 115 patients (mean age, 73.0 ± 7.2 years; 96 men) who underwent preoperative CEUS and underwent CEA. CEUS findings were evaluated as vascular grade at 0 min (Vas-G0) and 10 min (Vas-G10) after contrast injection. Plaques were histologically evaluated quantitatively for the total area of intraplaque hemorrhage, cholesterol, and calcification and the thinnest fibrous cap. Immunohistochemical studies were conducted using anti-CD-34 antibody as a marker for endothelial cells. INVs were divided into two groups depending on diameter: small INVs, <50 µm; and large INVs, ≥50 µm. The numbers of small and large blood vessels in the plaque were quantified histologically. Associations of small and large INVs with CEUS, plaque histology, and clinical findings were assessed by uni- and multivariable analyses. RESULTS: Multivariable analyses indicated that CEUS Vas-G0 was associated with the 4th quartile of the number of small INVs compared with other quartiles, and Vas-G10 was associated with the 4th quartile of the number of large INVs. Histologically, the presence and area of intraplaque hemorrhage were associated with the number of small INVs, while the increased number of large INVs was associated with infrequent plaque disruption and thicker fibrous cap. CONCLUSIONS: Our study showed that early phase enhancement in the CEUS can help identify plaque vulnerability by predicting a larger number of small INVs. This information can also help determine treatment strategies for carotid plaque.

Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study.

BACKGROUND: Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin (Hb) concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression. METHODS: Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at renal biopsy were identified: age 56 (45-63) years; 62.6% men; Hb 13.3 (12.0-14.5) g/dL; eGFR 76.2 (66.6-88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio 534 (100-1480) mg/g Crea. Serum Hb concentration was divided into quartiles: ≤12, 12.1-13.3, 13.4-14.5 and ≥14.6 g/dL. The association between serum Hb concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum Hb concentration to the known risk factors of DKD was assessed. RESULTS: Serum Hb levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ = -0.52; P < 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second and third quartile (the fourth quartile was reference) were 2.74 [95% confidence interval (CI) 1.26-5.97], 2.33 (95% CI 1.07-5.75) and 1.46 (95% CI 0.71-3.64), respectively. Addition of the serum Hb concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global Chi-statistics increased from 55.1 to 60.8; P < 0.001). CONCLUSIONS: Serum Hb concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease.

Clinicopathological discordance in biopsy-proven nephrosclerosis: a nationwide cross-sectional study of the Japan Renal Biopsy Registry (J-RBR).

BACKGROUND: Patients with nephrosclerosis display heterogenous clinical phenotypes, often leading to a clinical diagnosis discordant with pathological nephrosclerosis diagnosis. However, little is known about clinical factors associated with clinicopathological discordance of biopsy-proven nephrosclerosis. METHODS: In a cross-sectional study of 891 patients with biopsy-proven nephrosclerosis registered in the Japan Renal Biopsy Registry (J-RBR) between July 2007 and June 2016, we examined clinical characteristics associated with a pre-biopsy clinical diagnosis discordant with pathological nephrosclerosis diagnosis using multivariable logistic regression with adjustment for relevant clinical characteristics. RESULTS: Overall, the mean (SD) age was 58.6 (13.7) years; 67.6% of patients were male; and 63.2% were on antihypertensive drugs. The median estimated glomerular filtration rate (eGFR) was 43.8 mL/min/1.73 m2 and the median proteinuria was 0.5 g/day. Of the 891 patients, 497 (55.8%) had a clinical diagnosis discordant with pathological nephrosclerosis diagnosis, with chronic nephritic syndrome being the most common (> 75%) discordant clinical diagnosis. After multivariable adjustment, age (odds ratio 1.34, [95% confidence interval, 1.16-1.55], per 10 years increase), eGFR (1.10 [1.00-1.21], per 10 mL/min/1.73 m2 increase), and proteinuria (1.20 [1.03-2.16], per 1 g/day decrease) were found to be significantly associated with the clinicopathological discordance. CONCLUSIONS: Patients with older age, higher eGFR, and lower proteinuria had significantly higher likelihood of being clinically diagnosed with other glomerular disease in patients with biopsy-proven nephrosclerosis. Our findings highlight the heterogeneous clinical phenotypes of nephrosclerosis and suggest the need for continuous improvement of clinical diagnostic accuracy as well as for wider kidney biopsy indications for nephrosclerosis.

An autopsy case of aortic dissection due to giant cell arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis affecting mainly large and medium-sized arteries. GCA sometimes involves the aorta and its major branches and causes aortic dissection as a rare complication. We have experienced an autopsy case of aortic dissection due to GCA. The patient was an 87-year-old Japanese woman with Stanford type A aortic dissection who died 7 days after admission. Two years previously she had been diagnosed as having abdominal aortic aneurysm and undergone endovascular aneurysm repair (EVAR). Although she had no characteristic symptoms of GCA, autopsy revealed marked granulomatous inflammation in the dissected area and coronary arteries. Active arteritis was evident not only in the arteries of the upper extremity but also those in the lower extremity. Granulomatous inflammation was not evident in the aneurysm. The aortic dissection might have been an initial manifestation of GCA. We report the regions of GCA extension and its histology in detail.

Utility of Columbia classification in focal segmental glomerulosclerosis: renal prognosis and treatment response among the pathological variants.

BACKGROUND: The utility of the Columbia classification (Col-class) for focal segmental glomerulosclerosis (FSGS) has not yet been fully proven. METHODS: We extracted 201 FSGS patients from 10 nephrology centers in Japan and investigated the difference of a composite renal endpoint, defined as doubling of serum creatinine and/or development of end-stage renal disease, in pathological variants. Sensitivity analysis was used to prove the utility of the Col-class to predict renal outcomes. Additionally, the renal protective effects of steroids and/or immunosuppression (steroid/IS) were investigated in patients stratified according to the Col-class. RESULTS: The patients were classified into the following variants: not otherwise specified [NOS; n = 121 (60.1%)], perihilar [n = 31 (15.4%)], cellular [n = 19 (9.5%)], tip [n = 17 (8.5%)] and collapsing [n = 13 (6.5%)]. No tip variant patients reached the renal endpoint. The renal outcome in the collapsing variant was significantly poorer than that in the NOS [hazard ratio (HR) 3.71; P = 0.005]. In the sensitivity analysis, the area under the receiver operating characteristic curve for the renal endpoint was increased by adding Col-class to a model including common risk factors (P = 0.021). In a subgroup treated without steroid/IS, the outcome in the cellular variant was worse than that in the NOS (HR 5.10; P = 0.040) but the difference was not observed in the subgroup with steroid/IS (HR 0.54; P = 0.539). CONCLUSIONS: The Col-class is useful to predict renal prognosis in Japanese patients with FSGS. In addition to good prognosis in the tip variant and poor in the collapsing variant, good clinical course in the cellular variant treated with steroid/IS was suggested.

Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes.

Background: The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-term observations are limited. Methods: Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results: During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. Conclusions: This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients.

Nationwide multicenter kidney biopsy study of Japanese patients with hypertensive nephrosclerosis.

BACKGROUND: Nephrosclerosis is an increasingly reason for dialysis in Japan. However, kidney biopsy specimens for hypertensive nephrosclerosis are very limited; thus, the pathologic evaluation of hypertensive nephrosclerosis currently remains unclear. METHODS: Clinical and pathologic data of a total of 184 biopsy-confirmed hypertensive nephrosclerosis patients were collected from 13 centers throughout Japan. Seven pathological findings were assessed in this study. The outcomes of interest for this study were dialysis, composite kidney events, cardiovascular events, and all-cause mortality. RESULTS: The Green and Yellow (G&Y), Orange, and Red groups of the chronic kidney diseases (CKD) heat map contained 36, 57, and 91 cases, respectively. The mean observation period was 7.3 ± 5.2 (median, IQR; 6.1, 2.6-9.7) years. Global glomerulosclerosis (GScle), interstitial fibrosis and tubular atrophy (IFTA), arteriolar hyalinosis in Red exhibited higher scores than those in G&Y and Orange. The incidence rates of the composite kidney end points in 100 person-years for the G&Y, Orange, and Red groups were 1.42, 2.16, and 3.98, respectively. In the univariate Cox analysis for the composite kidney end points, GScle, IFTA and interstitial cell infiltration exhibited statistically significant high hazard ratios (1.18, 1.84, 1.69, respectively). However, after adjustment for clinical and medication data, the Red group in the CKD heat map category was risk factor for the composite kidney end points (HR 9.51). CONCLUSIONS: In summary, although pathologic findings had minor impacts on the prediction of composite outcomes in this study, the clinical stage of the CKD heat map is a good predictor of composite kidney events.

Clinicopathological analysis of biopsy-proven diabetic nephropathy based on the Japanese classification of diabetic nephropathy.

BACKGROUND: The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. METHODS: The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy. RESULTS: The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m2/year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. CONCLUSIONS: This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.

An autopsy case of non-traumatic fat embolism syndrome.

Fat embolism syndrome (FES) occurs after long bone fractures and the symptoms appear 24-72 h after the initial trauma. Fat emboli can affect both the pulmonary and systemic circulation. Apart from the most common type of FES that originates from bone fracture, non-traumatic FES has been also reported. We have experienced an autopsy case of non-traumatic FES. An 81-year-old man with hepatocellular carcinoma associated with alcoholic liver cirrhosis suddenly lost consciousness before transcatheter arterial chemoembolization treatment for his disease and died 5 h after the episode. At autopsy, numerous fat droplets were detected in the alveolar capillaries of the lung and glomerular capillaries of the kidney. Lipid analysis of lung autopsy specimens by thin-layer chromatography showed that the emboli were composed mainly of tristearin. Free fatty acids (FFA) has been considered to be the main component of fat emboli and can be a cause of acute respiratory distress syndrome (ARDS). However, in the present case, the lung specimen contained tristearin and ARDS did not occur. This is the first report of non-traumatic FES in which lipid analysis of human autopsy specimens has been conducted.

Age-Related Renal Microvascular Changes: Evaluation by Three-Dimensional Digital Imaging of the Human Renal Microcirculation Using Virtual Microscopy.

The renal microvasculature is targeted during aging, sometimes producing chronic kidney disease (CKD). Overdiagnosis of CKD in older persons is concerning. To prevent it, a new concept of "healthy aging" is arising from a healthy renal donor study. We investigated the renal microcirculatory changes of three older persons and compared them with that of one patient with nephrosclerosis using a three-dimensional (3D) reconstruction technique that we previously developed. This method uses a virtual slide system and paraffin-embedded serial sections of surgical material that was double-immunostained by anti-CD34 and anti-α smooth muscle actin (SMA) antibodies for detecting endothelial cells and medial smooth muscle cells, respectively. In all cases, the 3D images proved that arteriosclerotic changes in large proximal interlobular arteries did not directly induce distal arterial change or glomerulosclerosis. The nephrosclerotic patient showed severe hyalinosis with luminal narrowing of small arteries directly inducing glomerulosclerosis. We also visualized an atubular glomerulus and intraglomerular dilatation of an afferent arteriole during healthy aging on the 3D image and showed that microcirculatory changes were responsible for them. Thus, we successfully visualized healthy aged kidneys on 3D images and confirmed the underlying pathology. This method has the ability to investigate renal microcirculatory damage during healthy aging.

High-resolution three-dimensional digital imaging of the human renal microcirculation: An aid to evaluating microvascular alterations in chronic kidney disease in humans.

We have developed a new virtual microscopy method, with two- and three-dimensional (2D, 3D) synchronization, that enables visualization of the human renal microvasculature. The method was used to evaluate 120-150 serially cut sections of paraffin-embedded human renal tissue from nephrectomized samples. Virtual microscopy images of sections double-immunostained with antibodies against CD34 (an endothelium marker) and smooth muscle actin (an arterial media marker) and stained with periodic acid-Schiff were processed using digital imaging analysis software. Image registration was conducted to generate 3D displays with red-green-blue color segmentation. The reconstructed images of the microvasculature, including the interlobular arteries and the glomeruli, allowed visualization of 3D structures and direct glomerular connections. Synchronizing these 3D images with the corresponding 2D images revealed the relationships between arteriosclerotic lesions and downstream glomeruli. Thus, interlobular arteries with moderate intimal thickening and afferent arterioles with segmental hyalinosis/sclerosis, as seen on the 2D images, exhibited wall irregularities on the corresponding 3D images. However, these lesions were not directly influenced by lesions in downstream glomeruli, such as sclerotic lesions. Our virtual-slide method based on 2D and 3D image synchronization provides a comprehensive view of the renal microcirculation and therefore novel insights into the pathogenesis of vascular-associated renal diseases.

Improvement of Light Chain Proximal Tubulopathy without Crystals in IgGλ-type Monoclonal Gammopathy of Undetermined Significance Using Bortezomib and Dexamethasone.

A 70-year-old woman with acute kidney injury, a high serum Creatinine (Cr) level (3.91 mg/dL), and proteinuria (protein/Cr ratio 1.59 g/gCr) was admitted. Serum IgG λ-type and urinary λ-type M proteins were observed. A bone marrow examination indicated monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy showed distended proximal tubular cells, and immunofluorescence identified tissue positive for proximal tubular cell λ light chains. Electron microscopy identified fibril-like structures in the lysosomes. The patient was diagnosed with light chain proximal tubulopathy without crystals in IgG λ-type MGUS and treated with bortezomib and dexamethasone therapy, which improved her renal function.

Relationship between false lumen morphology and entry tear in acute type A aortic dissection.

OBJECTIVES: This study aimed to investigate the relationship between false lumen morphology and the size, aortic segment and position of the entry tear for acute type A aortic dissection. METHODS: The records of patients who underwent emergency operation for acute type A aortic dissection in our institution between April 2011 and May 2022 were examined. Data regarding size, location and position of the entry tear and preoperative computed tomography findings were reviewed. The relationship of these variables with false lumen morphology was examined and retrospectively compared according to tear size. RESULTS: Of 243 cases, characteristics of the entry tear, visualized during surgery, were confirmed in 134 cases (age = 70.9 ± 12.6 years, male = 45.5%). Tear sizes at different aortic segments were not significantly different (P = 0.376). Tears posterior to the lesser curvature were significantly smaller than those anterior to the greater curvature (P = 0.004). A thrombosed false lumen was associated with a significantly smaller tear size and position on the posterior to the lesser curvature side in aortic cross-section (all P < 0.001). Multivariate analysis showed that tear size, the presence of re-entry and tear position anterior to the greater curvature were independent predictors of a patent false lumen. CONCLUSIONS: In acute type A aortic dissection, larger tear size, the presence of re-entry and tear position anterior to the greater curvature are risk factors for a patent false lumen. Although the results of this study are valid only for patients in whom intimal tears were detected during aortic surgery, this trend may provide information for pathophysiology of the disease.

Is Podocytopathy Associated with Gross Hematuria after COVID-19 Vaccination in Patients with Immunoglobulin A Nephropathy?

We experienced three cases of a fever and subsequent severe, prolonged gross hematuria after COVID-19 vaccination. A kidney biopsy revealed immunoglobulin A (IgA) nephropathy, and electron microscopy showed two types of podocytopathy (podocyte damage): loss of foot processes from the glomerular basement membrane and foot process effacement. Mesangial interposition was also present in cases 1 and 3 but not in case 2. Podocytopathy is known to be a cause of proteinuria; however, the reactions to COVID-19 vaccination described here suggest that it may also be related to hematuria in IgA nephropathy.

Aberrant Notch1-dependent effects on glomerular parietal epithelial cells promotes collapsing focal segmental glomerulosclerosis with progressive podocyte loss.

Collapsing focal segmental glomerulosclerosis (cFSGS) is a progressive kidney disease characterized by glomerular collapse with epithelial hyperplasia. Here we used a transgenic mouse model of cFSGS with immunotoxin-induced podocyte-specific injury to determine the role for Notch signaling in its pathogenesis. The mice exhibited progressive loss of podocytes and severe proteinuria concomitant with histological features of cFSGS. Hyperplastic epithelium was negative for genetic podocyte tags, but positive for the parietal epithelial cell marker claudin-1, and expressed Notch1, Jagged1, and Hes1 mRNA and protein. Enhanced Notch mRNA expression induced by transforming growth factor-ß1 in cultured parietal epithelial cells was associated with mesenchymal markers (α-smooth muscle actin, vimentin, and Snail1). Notch inhibition in vitro suppressed these phenotypic transcripts and Notch-dependent cell migration. Moreover, Notch inhibition in vivo significantly decreased parietal epithelial cell lesions but worsened proteinuria and histopathology in our cFSGS model. Thus, aberrant Notch1-mediated parietal epithelial cell migration with phenotypic changes appears to underlie the pathogenesis of cFSGS. Parietal epithelial cell hyperplasia may also represent an adaptive response to compensate for a disrupted filtration barrier with progressive podocyte loss.

Primary membranoproliferative glomerulonephritis on the decline: decreased rate from the 1970s to the 2000s in Japan.

BACKGROUND: A prolonged change in the rate of primary membranoproliferative glomerulonephritis (MPGN) was identified using a Japanese database of renal biopsies. METHODS: We retrospectively investigated 6,369 renal biopsies that were performed between 1976 and 2009. Primary MPGN patients were selected, and the clinical and pathological findings were examined. We also statistically analyzed the changing rate of the onset of primary MPGN according to each decade. RESULTS: Seventy-nine cases with primary MPGN (1.2 % of total biopsies) were diagnosed. The age of the patients ranged from 6-79 years (average 34.6 years). There were 24 children and 55 adults, including 37 male and 42 female patients. Thirty-six cases of primary MPGN (45.6 %) showed nephrotic syndrome-8 childhood and 28 adult cases. In the pathological classification of 44 samples using electron microscopy, 29 cases were MPGN type I, 1 case was MPGN type II, and 14 cases were MPGN type III. The secular change of the rate of primary MPGN onset showed a statistically significant reduction from the 1970s to the 2000s. The rate of primary MPGN onset in the child population also significantly decreased, but not in the adult population. Among the clinical parameters, disease severity and prognosis remained unchanged. Regarding treatment in recent years, steroid pulse therapy became more available but the administration of warfarin and anti-platelet drugs significantly decreased. CONCLUSION: We concluded that the rate of total primary MPGN and that of pediatric patients with primary MPGN decreased.

[A case of incidentally diagnosed retroperitoneal lymphangioleiomyomatosis with no respiratory symptoms].

A 39-year-old woman presented with a large retroperitoneal tumor found incidentally in a routine examination. The 138×37×26 mm mass was located in the left paraaortic region. Blood tests and urinalyses including endocrinological examinations revealed no abnormalities. A chest computed tomography revealed multiple thin-walled pulmonary cysts, which is a characteristic of lymphangioleiomyomatosis (LAM). Because the findings strongly suggested that the retroperitoneal tumor was an extrapulmonary manifestion of LAM, we performed laparoscopic resection of the tumor for diagnosis and treatment. The pathological diagnosis was LAM. The tumor cells were immunohistochemically positive for α -smooth muscle actin and weakly positive for HMB45, which is consistent with LAM. The cells were also positive for estrogen receptor (ER) and progesterone receptor (PgR). LAM is a rare progressive disease that affects mainly the lung, and leads to chronic respiratory failure. Extrapulmonary LAM without respiratory symptoms, is extremely rare. In the past, the prognosis of LAM was poor, with a median survival of 8-10 years, but now 85% survive more than 10 years. In the present case, deterioration of pulmonary lesions was not observed during the 10 months follow-up. Because ERand PgRfindings were positive, we will consider hormonal therapy as a treatment option, when the pulmonary lesions progress in the present case.

Seasonal variations in renal biopsy numbers and primary glomerular disease features based on the Japan renal biopsy registry.

We analyzed the seasonal variations in the number of renal biopsies and clinical characteristics of primary glomerular disease in Japan using the Japan Renal Biopsy Registry (J-RBR). We retrospectively collected clinical and pathological data of patients with primary glomerular disease who were registered in the J-RBR between 2007 and 2018. Immunoglobulin A nephropathy (IgAN), minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN), and postinfectious acute glomerulonephritis (PIAGN) constituted the four major glomerular disorders included in this study (total, 13,989; IgAN, 9121; MCNS, 2298; MN, 2447; and PIAGN, 123). The number of patients with IgAN or MCNS was higher during summer. However, no overt seasonal variations were observed in patients with MN or PIAGN. Subgroup analyses suggested that in the patients with IgAN, more renal biopsies of severe cases were performed during winter, probably owing to age and blood pressure. Furthermore, more renal biopsies of severe cases were performed during spring and winter in patients with MCNS even after adjusting for the abovementioned host factors. This study suggests that seasonal factors influence the decision to perform renal biopsy as well as the pathogenesis of primary glomerular disease. Thus, our findings may provide important insights regarding the pathophysiology of primary glomerular disease.