Autosomal-dominant tubulointerstitial kidney disease with a novel UMOD mutation, overlapping with Sjogren's syndrome: a case report.

Autosomal-dominant tubulointerstitial kidney disease caused by UMOD (encoding uromodulin) mutation (ADTKD-UMOD) is a rare hereditary disease. A strong family history of hyperuricemia or gout and inherited kidney disease raises the suspicion of ADTKD-UMOD. Genetic testing can confirm the diagnosis without a kidney biopsy. However, when complicated by other diseases that can cause tubulointerstitial disease, renal biopsy is indispensable for the diagnosis and decisions on treatment strategy. We report the case of a 44-year-old woman referred for evaluation of kidney dysfunction. She had an attack of gout 1 month before referral and a family history of hyperuricemia. She was diagnosed with primary Sjogren's syndrome through an immune workup and ophthalmological examination. However, a kidney biopsy revealed histological features suggesting ADTKD rather than gouty kidney or tubulointerstitial nephritis associated with Sjogren's syndrome, and immunostaining revealed a characteristic staining pattern with UMOD. Comprehensive genetic testing of 93 genes responsible for polycystic kidney disease revealed a novel heterozygous missense variant (c.649 T > A:p. Cys217Ser) in UMOD, and the patient was diagnosed with ADTKD-UMOD. In this case, kidney biopsy contributed to the correct diagnosis of tubulointerstitial kidney disease. This case emphasizes the importance of suspecting ADTKD-UMOD based on family history and careful evaluation of kidney biopsy findings.

Cerebrovascular Disease Detected on Preprocedural Computed Tomography in Patients With Severe Aortic Stenosis Undergoing Aortic Valve Replacement.

BACKGROUND: There is a scarcity of data on the prevalence and clinical impact of cerebrovascular disease detected on preprocedural computed tomography (CT) before aortic valve replacement (AVR) in patients with severe aortic stenosis. METHODS AND RESULTS: Among patients with severe aortic stenosis undergoing AVR, the authors compared clinical outcomes between patients with and without cerebrovascular disease detected on preprocedural CT, which was defined as chronic brain infarction or hemorrhage. The primary outcome measure in this study was a composite of all-cause death or stroke. Among 567 study patients, 200 patients (35.3%) had cerebrovascular disease on preprocedural CT. Among 200 patients with cerebrovascular disease on preprocedural CT, only 28.5% of patients had a clinical history of symptomatic stroke. The cumulative 3-year incidence of death or stroke was higher in patients with cerebrovascular disease on preprocedural CT than in those without cerebrovascular disease on preprocedural CT (40.7% versus 24.1%, log-rank P<0.001). After adjusting for confounders, the higher risk of patients with cerebrovascular disease on preprocedural CT relative to those without remained significant for death or stroke (hazard ratio [HR], 1.42 [95% CI, 1.02-1.98]; P=0.04). Among 200 patients with cerebrovascular disease on preprocedural CT, patients with prior symptomatic stroke compared with those without were not associated with higher adjusted risk for death or stroke (HR, 1.18 [95% CI, 0.72-1.94]; P=0.52). CONCLUSIONS: Among patients with severe aortic stenosis undergoing AVR, a substantial proportion had cerebrovascular disease on preprocedural CT, with a clinical history of symptomatic stroke in one-fourth of patients. Regardless of history of symptomatic stroke, patients with cerebrovascular disease on preprocedural CT had worse clinical outcomes compared with those without cerebrovascular disease on preprocedural CT.

A Man with Primary Hyperchylomicronemia with Triglyceride Levels Exceeding 11,000 mg/dL was Well Controlled by Pemafibrate Combined with Dietary Therapy: A Case Report.

A 50-year-old man with a triglyceride (TG) level of 11,397 mg/dL was admitted to our hospital. He consumed a high-fat and high-carbohydrate diet as well as more than 100 g of alcohol per day. He had type 2 diabetes and obesity and had previously suffered from severe acute pancreatitis twice. A genetic analysis revealed compound heterozygous mutations in APOA5 (c.56C>G and c.553G>T). In addition to low-fat meals and alcohol cessation, administration of pemafibrate lowered his triglyceride levels to <150 mg/dL.

Foreign Body Granuloma After Embolization of Internal Iliac Artery Aneurysm Using N-Butyl-2-Cyanoacrylate: A Case Report.

Foreign body granulomas following endovascular treatment are rare complications and are mostly reported in the brain or cutaneous vascular tissues. To the best of our knowledge, no study to date has reported on foreign body granulomas in the abdomen after injection of N-butyl-2-cyanoacrylate (NBCA)-lipiodol mixture into the abdominal arteries. This study reports a case of foreign body granuloma that appeared 12 months after the embolization of a right internal iliac artery aneurysm using an NBCA-lipiodol mixture, which posed challenges in differentiation from malignant tumors. We present a 77-year-old man who underwent embolization of a right internal iliac artery aneurysm and open surgical repair of an abdominal aortic aneurysm. A contrast-enhanced CT performed 12 months postoperatively revealed a right-sided retroperitoneal mass surrounding the iliopsoas muscle. The mass contained multiple, small, hyperdense areas, suggesting the migration of the NBCA-lipiodol mixture casts from the embolized right internal iliac artery aneurysm. The differential diagnosis included foreign body granuloma, lymphoma, and sarcoma. A biopsy of the lesion revealed a granuloma with various stages of inflammation, no hemosiderin deposition, multinucleated giant cells, and foam cells containing fat, and was diagnosed with a foreign body granuloma. Special staining for microorganisms revealed no findings suggestive of infection. Because the patient was asymptomatic, no treatment was administered. Contrast-enhanced CT at 24 months postoperatively showed shrinkage of the mass, with no change in size noted at 48 months postoperatively. This report highlights a foreign body granuloma that mimicked malignant tumors. Extravascular migration of the NBCA-lipiodol mixture casts likely contributed to granuloma formation. Radiologists should consider foreign body granulomas after embolization using NBCA into the abdominal arteries.

Acute kidney tubular injury after ingestion of red yeast rice supplement.

A 47-year-old woman developed severe kidney dysfunction after taking a lipid-lowering supplement, Red Yeast Rice Cholestehelp, for approximately 7 months. The patient developed sudden nausea and had an elevated serum creatinine level of 4.26 mg/dL. A kidney biopsy showed findings consistent with acute tubular necrosis. Kidney dysfunction improved with discontinuation of supplementation, and corticosteroid therapy. Similar kidney involvement has been reported, raising concerns regarding supplements in Japan. An investigation of the nephrotoxic ingredients in the same product batches is currently underway. This report underscores the need for public awareness and warnings of health risk concerns associated with unregulated supplements.

Fractional excretion of total protein predicts renal prognosis in Japanese patients with primary membranous nephropathy.

Background: Primary membranous nephropathy (pMN) is one of the most common types of glomerulonephritis, with a third of patients progressing to renal insufficiency. Various prognostic factors have been reported, of which urinary protein and renal function are the most critical parameters. Fractional excretion of total protein (FETP) indicates protein leakage that accounts for creatinine kinetics and serum protein levels. In this study, we investigated the association between FETP and renal prognosis in pMN. Methods: We retrospectively identified 150 patients with pMN. FETP was calculated as follows: (serum creatinine × urine protein)/(serum protein × urine creatinine) %. We divided the patients into three groups according to FETP values and compared the clinicopathological findings. The primary outcome was an estimated glomerular filtration rate (eGFR) decrease of ≥30% from the baseline level. Results: FETP was associated with urinary protein and renal function, Ehrenreich and Churg stage, and global glomerulosclerosis. The primary outcome was observed in 38 patients (25.3%), and the frequency of the primary outcome was higher in the high FETP group (P = .001). FETP is higher than protein-creatinine ratio (PCR) in the area under the curve. In the multivariate analysis adjusted for age, eGFR, PCR and treatment, FETP was significantly associated with primary outcome (adjusted hazard ratio, 8.19; P = .019). Conclusions: FETP is a valuable indicator that can reflect the pathophysiology and is more useful than PCR as a predictor of renal prognosis in patients with Japanese pMN.

Association of variabilities in body mass index and waist circumference with newly achieved remission of metabolic dysfunction-associated fatty liver disease.

AIMS: Although body weight reduction is recommended to ameliorate nonalcoholic fatty liver disease, the effects of body mass index (BMI) and waist circumference (WC) variability on newly achieved remission of metabolic dysfunction-associated fatty liver disease (MAFLD) remain unclear. We aimed to investigate the longitudinal association between BMI and WC variabilities and newly achieved MAFLD remission in both sexes. METHODS: Among 26,952 patients, 1823 with MAFLD diagnosed by ultrasonography and with >2 health checkups over >2 years from April 2014 to March 2021 were included in this observational cohort study. A generalized estimation equation model analyzed the association between BMI and WC and newly achieved MAFLD remission according to repeated measures at baseline and the most recent stage. RESULTS: Rates of MAFLD remission in male and female patients were 7.4 % and 6.0 %, respectively. Regarding decreased BMI variability, newly achieved MAFLD remission prevalence among the subgroups differed significantly between sexes (p < 0.001). In male patients, a decrease in BMI variability of ≥1.5 kg/m2 and WC variability of ≥4.2 cm had adjusted odds ratios (ORs) of 5.215 and 2.820, respectively, for newly achieved MAFLD remission. Among female patients, regular exercise and breakfast consumption were accelerating factors for newly achieved MAFLD remission. Non-invasive liver fibrosis scores significantly differed between MAFLD and newly achieved MAFLD remission, including in the subgroups (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: Reducing BMI and WC variabilities in male patients and improving lifestyle habits in female patients may accelerate MAFLD remission.

Accelerated involution of germinal center in palatine tonsils in IgA nephropathy.

BACKGROUND: Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN. METHODS: The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated. RESULTS: In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis. CONCLUSIONS: The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.

Histological Correlation between Tonsillar and Glomerular Lesions in Patients with IgA Nephropathy Justifying Tonsillectomy: A Retrospective Cohort Study.

Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying mechanisms supporting tonsillectomy remain unclear. This study assessed palatine tonsils from 77 patients with IgAN, including 14 and 63 who received SPT before and after tonsillectomy, respectively. Tonsils from 21 patients with chronic tonsillitis were analyzed as controls. Specific tonsillar lesions were confirmed in patients with IgAN, correlating with active or chronic renal glomerular lesions and SPT. T-nodule and involution of lymphoepithelial symbiosis scores in tonsils correlated with the incidence of active crescents and segmental sclerosis in the glomeruli, respectively. The study revealed an essential role of the tonsil-glomerular axis in early active and late chronic phases. Moreover, the SPT-preceding group demonstrated no changes in the T-nodule score, which correlated with active crescent formation, but exhibited a considerable shrinkage of lymphatic follicles that produced aberrant IgA1. The study underscores the involvement of innate and cellular immunity in IgAN and advocates for tonsillectomy as a necessary treatment alongside SPT for IgAN, based on a stepwise process.

A 20-year follow-up study of identical twin sisters with immunoglobulin A nephropathy.

Immunoglobulin A nephropathy (IgAN) is characterized by diverse clinicopathological phenotypes. Herein we present a follow-up study of previously reported identical twin sisters with IgAN. The older sister exhibited more severe kidney histopathology and proteinuria and a lower birthweight than did her younger sister, and only the older sister experienced two childbirths. These raised concerns regarding her kidney outcomes. However, with timely multidisciplinary treatments, the older sister's kidney function remained preserved after 20 years of IgAN history. Our findings indicate the significant contribution of environmental/epigenetic factors to IgAN progression and the need for tailored medical care corresponding to life events.

Japanese Planocerid Flatworms: Difference in Composition of Tetrodotoxin and Its Analogs and the Effects of Ingestion by Toxin-Bearing Fishes in the Ryukyu Islands, Japan.

Tetrodotoxin (TTX), known as pufferfish toxin, is a potent neurotoxin blocking sodium channels in muscle and nerve tissues. TTX has been detected in various taxa other than pufferfish, including marine polyclad flatworms, suggesting that pufferfish toxin accumulates in fish bodies via food webs. The composition of TTX and its analogs in the flatworm Planocera multitentaculata was identical to those in wild grass puffer Takifugu alboplumbeus. Previously, Planocera sp. from Okinawa Island, Japan, were reported to possess high level of TTX, but no information was available on TTX analogs in this species. Here we identified TTX and analogs in the planocerid flatworm using high-resolution liquid chromatography-mass spectrometry, and compared the composition of TTX and analogs with those of another toxic and non-toxic planocerid species. We show that the composition of TTX and several analogs, such as 5,6,11-trideoxyTTX, dideoxyTTXs, deoxyTTXs, and 11-norTTX-6(S)-ol, of Planocera sp. was identical to those of toxic species, but not to its non-toxic counterpart. The difference in the toxin composition was reflected in the phylogenetic relationship based on the mitochondrial genome sequence. A toxification experiment using predatory fish and egg plates of P. multitentaculata demonstrated that the composition of TTX and analogs in wild T. alboplumbeus juveniles was reproduced in artificially toxified pufferfish. Additionally, feeding on the flatworm egg plates enhanced the signal intensities of all TTX compounds in Chelonodon patoca and that of deoxyTTXs in Yongeichthys criniger.

Transarterial Embolization of Renal Arteriovenous Malformations: Treatment Outcomes According to Angiographic Classification.

PURPOSE: To assess the different adjunctive catheter techniques required to achieve complete occlusion of renal arteriovenous malformations (rAVMs) of different angioarchitectural types. MATERIALS AND METHODS: Overall, data on 18 patients with rAVM (Type 1, n = 7; Type 2, n = 2; Type 3, n = 9; mean age, 53.8 years) who underwent 25 procedures between 2011 and 2022 were reviewed. The clinical presentations, endovascular techniques, arteriovenous malformation (AVM) occlusion rate, adverse events (including the incidence of renal infarction), and clinical symptoms and outcomes (including recurrence/increase of AVM) were analyzed according to the Cho-Do angioarchitectural classification. Posttreatment renal infarction was classified as no infarction, small infarction (<12.5%), medium infarction (12.5%-25%), and large infarction (>25%) using contrast-enhanced computed tomography or magnetic resonance imaging. RESULTS: Hematuria and heart failure were presenting symptoms in 10 and 2 patients, respectively. The embolic materials used were as follows: Type 1 rAVM, coils alone or with n-butyl-2-cyanoacrylate (nBCA); Type 2 rAVM, nBCA alone or with coils; and Type 3 rAVMs, nBCA alone. Fourteen patients underwent adjunctive catheter techniques, including flow control with a balloon catheter and multiple microcatheter placement, alone or in combination. Immediate postprocedural angiography revealed complete occlusion in 15 patients (83%) and marked regression of rAVM in 3 (17%). Small asymptomatic renal infarctions were observed in 6 patients with Type 3 rAVMs without any decrease in renal function. No major adverse events were observed. All symptomatic patients experienced symptom resolution. Recurrence/increase of rAVM was not observed during the mean 32-month follow-up period (range, 2-120 months). CONCLUSIONS: Transarterial embolization using adjunctive catheter techniques according to angioarchitectural types can be an effective treatment for rAVMs.

Association of metabolic dysfunction-associated steatotic liver disease with erosive esophagitis development: a longitudinal observational study.

BACKGROUND AND AIM: Although erosive esophagitis (EE) is associated with fatty liver and metabolic dysregulation, the association between EE and metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Thus, this study aimed to investigate the longitudinal association between MASLD and EE. METHODS: We included 1578 patients without EE at baseline who underwent more than two health checkups over 2 years. Generalized estimation equations were used to analyze associations between MASLD and EE according to repeated measures at baseline and most recent stages. RESULTS: EE development rates in men and women were 14.5% and 7.2%, respectively. After adjusting for lifestyle habits, the odds ratios of MASLD for EE development in men and women were 1.907 (95% confidence interval [CI]: 1.289-2.832, P < 0.005) and 1.483 (95% CI: 0.783-2.811, P = 0.227), respectively. In the subgroup analysis, after adjusting for lifestyle habits, among men and women aged ≥50 years with more than three MASLD components, the odds ratios for EE development were 2.408 (95% CI: 1.505-3.855, P < 0.001) and 2.148 (95% CI: 1.093-4.221, P < 0.05), respectively. After adjusting for various factors, the significant risk factors for EE development were different between men and women. CONCLUSION: The influence of MASLD and other factors on EE development differed by sex and age. Particularly, patients aged ≥50 years with MASLD and with an increased number of MASLD components should be considered at increased risk for EE.

Active flare of IgA nephropathy during long-term therapy with anti-tumor necrosis factor-α antibody drugs for Crohn's disease: three case reports and literature review.

In recent years, increasing numbers of reports have described new onset or active disease flare of IgA nephropathy (IgAN) during administration of TNF-α inhibitor (TNFi) therapy for chronic inflammatory diseases. Crohn's disease (CD) is the most common indication for TNFi therapy in this clinical setting, but the underlying etiology of IgAN in such patients remains unclear. We report our experience with three patients who developed acute worsening of preexisting urinalysis abnormalities and kidney dysfunction approximately 2 to 6 years after TNFi administration for CD. Kidney biopsies at the time of kidney disease flare revealed IgAN in two patients and IgAN complicated by acute tubulointerstitial nephritis in one patient. The CD and IgAN in all three patients were successfully managed with additional corticosteroid therapy and tonsillectomy without discontinuing TNFi therapy. The clinical course of our patients and similar patients described in the literature suggests that TNFi therapy for CD is associated with a relatively high risk for new onset or disease flare of IgAN. This report discusses the possible involvement of Th1/Th2 imbalance on the immunological background of CD or IgAN.

Neural epidermal growth factor-like 1 protein (NELL1)-associated membranous nephropathy with heterogeneous underlying diseases: a case report.

Neural epidermal growth factor-like 1 protein (NELL1) is a target antigen of membranous nephropathy (MN). NELL1-associated MN (NELL1-MN) was originally described as a primary form but has subsequently been associated with other diseases, including malignancies, pre-exposure to certain drugs, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and rheumatoid arthritis (RA). We present a case of a 78-year-old woman with long-standing RA who developed persistent proteinuria and was diagnosed with MN. Evaluation of the underlying cause revealed chronic active HCV infection and past HBV infection. The underlying cause was less likely to be drug-related; however, there was no evidence of malignancy. The patient was diagnosed with HCV-associated MN. At 4 years after the diagnosis of MN, the patient died of breast cancer with multiple metastases. Subsequent immunohistological analysis revealed that she had NELL1-MN, and her breast cancer tissue stained positive for NELL1. Our case illustrates the difficulty in establishing the underlying cause of NELL1-MN, even after diagnosis. However, the incidence of malignancies, particularly breast and prostate cancers, is higher in NELL1-MN than in MN with other target antigens. Therefore, malignancies are considered a priority for investigation because of their frequency and prognosis among patients with NELL1-MN.

Early Recurrence of Immunoglobulin A Nephropathy after Kidney Transplantation in a Patient with Down Syndrome.

A 39-year-old male kidney transplant recipient with Down syndrome (DS) was admitted to our hospital for biopsy. He had proteinuria at age 9, was diagnosed with immunoglobulin A nephropathy (IgAN) at age 22, had a tonsillectomy at age 35, and underwent ABO-compatible kidney transplantation (from his mother) at age 36. His serum creatinine was stable at 2.21 mg/dL 3 months after the kidney transplant, and his urine protein was 0.11 g/day. A protocol biopsy was performed 7 months after the kidney transplant, and there was suspicion of early recurrence of IgAN. One year after the transplant, urine erythrocytes were elevated and proteinuria was 0.41 g/day; at 3 years and 5 months after the kidney transplant, hematuria was evident along with proteinuria (0.74 g/day). Therefore, an episode biopsy was performed. A total of 23 glomeruli were obtained, four of which exhibited global sclerosis; three others showed intra- and extracapillary proliferative glomerulonephritis compatible with IgAN recurrence. Here, we report a rare case of early recurrence of IgAN with disease progression despite tonsillectomy in a patient with DS.