The association between renal medullary and cortical fibrosis, stiffness, and concentrating capacity: an observational, single-center cross-sectional study.

BACKGROUND: Fibrosis is a common final pathway leading to end-stage renal failure. As the renal medulla and cortex contain different nephron segments, we analyzed the factors associated with the progression of renal medullary and cortical fibrosis. METHODS: A total of 120 patients who underwent renal biopsy at Kawashima Hospital between May 2019 and October 2022 were enrolled in this retrospective study. Renal medullary and cortical fibrosis and stiffness were evaluated using Masson's trichrome staining and shear wave elastography, respectively. Maximum urine osmolality in the Fishberg concentration test was also examined. RESULTS: Medullary fibrosis was positively correlated with cortical fibrosis (p < 0.0001) and log-converted urinary ß2-microglobulin (MG) (log urinary ß2-MG) (p = 0.022) and negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.0002). Cortical fibrosis also correlated with log urinary ß2-MG, eGFR, and maximum urine osmolality. Multivariate analysis revealed that cortical fibrosis levels (odds ratio [OR]: 1.063) and medullary stiffness (OR: 1.089) were significantly associated with medullar fibrosis (≧45%). The severe fibrosis group with both medullary fibrosis (≧45%) and cortical fibrosis (≧25%) had lower eGFR and maximum urine osmolality values and higher urinary ß2-MG levels than the other groups. CONCLUSIONS: Patients with disorders involving both renal medullary and cortical fibrosis had decreased maximum urine osmolality but had no abnormalities in the urinary concentrating capacities with either condition. Renal medullary and cortical fibrosis were positively correlated with urinary ß2-MG, but not with urinary N-acetyl-beta-D-glucosaminidase.

A case of destination therapy for post-fulminant myocarditis with myelodysplastic syndrome.

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome.

Clinical Efficacy and Safety of Low-Dose Pemafibrate in Patients With Severe Renal Impairment: A Retrospective Study.

BACKGROUND: The management of hypertriglyceridemia in patients with chronic kidney disease (CKD) is important. Pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator with less toxic effects on liver and kidney function than those of other fibrates, has recently been approved for the treatment of patients with an estimated glomerular filtration rate (eGFR) lower than 30 mL/min/1.73 m2. However, the efficacy and safety of pemafibrate in patients with severe renal impairment have not yet been established. METHODS: This single-center, retrospective observational study included 12 outpatients with CKD and hypertriglyceridemia, who were newly started on low-dose pemafibrate (0.1 mg/day) treatment between December 2021 and May 2023 and whose eGFRs were less than 30 mL/min/1.73 m2 at baseline. Blood samples were collected before and at 12 weeks after pemafibrate treatment. RESULTS: After 12 weeks of treatment, the serum triglyceride level was significantly decreased, whereas the high-density lipoprotein cholesterol level was significantly increased. The serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and uric acid levels were also significantly decreased, without worsening of the eGFR and serum creatinine levels. In the subgroup analysis, there were no significant differences in the changes in clinical parameters regardless of statin use and CKD stage at baseline. CONCLUSIONS: Low-dose pemafibrate administration in patients with severe renal impairment resulted in significant improvements in triglyceride, high-density lipoprotein cholesterol, and serum uric acid levels, and liver function, without adverse events.

Impact of Albumin Leakage on the Mortality of Patients Receiving Hemodialysis or Online Hemodiafiltration.

Background: Online hemodiafiltration (OHDF) has a lower mortality rate than hemodialysis (HD). We aimed to investigate the impact of the albumin leakage on the mortality of patients receiving HD or OHDF. Methods: In this single-center study, consecutive patients receiving renal replacement therapy between January and April 2018 were retrospectively registered. Using (1:1) propensity score matching, 3-year all-cause mortality was compared between patients receiving HD and OHDF, and the impact of albumin leakage on the mortality rate in both groups was investigated. Results: Of the 460 patients, 137 patients receiving HD were matched with an equal number of patients receiving OHDF. OHDF was associated with higher albumin leakage (p < 0.001) and a lower mortality than HD (log-rank test, p < 0.001). Albumin leakage was associated with mortality in patients receiving HD (per 1 g increase, hazard ratio (HR): 0.495, 95% confidence interval (CI): 0.275-0.888) and patients receiving OHDF (per 1 g increase, HR: 0.734, 95% CI: 0.588-0.915). Patients receiving HD, with the highest albumin leakage tertile (>3 g), had a similar mortality rate to patients receiving OHDF, with similar albumin leakage. Conclusions: The negative relationship between albumin leakage and mortality suggests the benefit of removing middle- to -large-molecular-weight substances to improve survival.

Successful management of HeartMate 3 in a patient with arrhythmogenic right ventricular cardiomyopathy.

The management of right heart failure during durable left ventricular assist device (LVAD) support remains an unsolved issue so far. We had a 44-year-old male patient who was diagnosed with arrhythmogenic right ventricular cardiomyopathy and received HeartMate 3 LVAD (Abbott, USA) implantation as a bridge-to-transplant indication. The pump speed was adjusted as low as 4500 rpm to avoid the left ventricular narrowing and interventricular septal leftward shift. Riociguat was administered to decrease the afterload of the right ventricle and increase the preload of the left ventricle, in addition to the combination of neurohormonal blockers. Frequent low-flow alarm events eventually disappeared after amlodipine administration, and he was successfully returned to work. We here present a unique management in a patient with right heart failure due to arrhythmogenic right ventricular cardiomyopathy during HeartMate 3 LVAD support.

Low-density Lipoprotein Receptor Activities, Lipids, Apolipoprotein, and Clinical Course of Patients with Steroid-resistant Nephrotic Syndrome Treated with Low-density Lipoprotein Apheresis: A Case Series.

We herein report three cases of steroid-resistant nephrotic syndrome successfully treated with low-density lipoprotein apheresis (LDL-A). All patients were treated with a combination of steroids, cyclosporine, and LDL-A. In all cases, the serum concentrations of LDL, total and high-density lipoprotein cholesterol, and triglycerides were significantly lowered following LDL-A administration. Furthermore, the estimated LDL receptor activity increased, while both serum LDL and total cholesterol levels decreased, suggesting that LDL-A increases LDL receptor activity by driving changes in serum cholesterol concentration. This case series suggests that LDL-A increases LDL receptor activity, which may improve the intracellular uptake of cyclosporine.

Effects of switching from agalsidase-α to agalsidase-ß on biomarkers, renal and cardiac parameters, and disease severity in fabry disease forming neutralizing antidrug antibodies: a case report.

Fabry disease is an X-linked hereditary disorder caused by deficient α-galactosidase A (GLA) activity. Patients with Fabry disease are often treated with enzyme replacement therapy (ERT). However, ERT often induces the formation of neutralizing antidrug antibodies (ADAs), which may impair the therapeutic efficacy. Here, we report the case of a 32-year-old man with Fabry disease and resultant neutralizing ADAs who was treated by switching from agalsidase-α to agalsidase-ß. We monitored biomarkers, such as plasma globotriaosylsphingosine (lyso-Gb3), urinary globotriaosylceramide (Gb3), urinary mulberry bodies, renal and cardiac parameters, and disease severity during the treatment period. Although plasma lyso-Gb3 and urinary Gb3 levels quickly decreased within two months after the initiation of ERT with agalsidase-α, they gradually increased thereafter. The urinary mulberry bodies continued to appear. Both the ADA titer and serum mediated GLA inhibition rates started to increase after two months. Moreover, 3.5 years after ERT, the vacuolated podocyte area in the renal biopsy decreased slightly from 23.1 to 18.9%. However, plasma lyso-Gb3 levels increased, and urinary Gb3, mulberry body levels, and ADA titers remained high. Therefore, we switched to agalsidase-ß which reduced, but did not normalize, plasma lyso-Gb3 levels and stabilized renal and cardiac parameters. Disease severity was attenuated. However, urinary Gb3 and mulberry body levels did not decrease noticeably in the presence of high ADA titers. The kidneys take up a small amount of the administered recombinant enzyme, and the clearance of Gb3 that has accumulated in the kidney may be limited despite the switching from agalsidase-α to agalsidase-ß.

[Thoracic Endovascular Aortic Repair for Mycotic Thoracic Aortic Aneurysm After BCG Intravesical Therapy].

Bacille Calmette-Guérin( BCG) intravesical therapy is an effective and safe treatment for bladder cancer; however, mycotic aneurysms have been reported as a rare complication. Case 1:A 64-year-old man with a history of BCG intravesical therapy underwent emergent thoracic endovascular aortic repair (TEVAR) for a ruptured thoracic aortic aneurysm (TAA). He was diagnosed with BCG infection by hemosputum specimen culture five months later;then, antituberculous therapy was initiated. However, his follow-up computed tomography scan revealed stent-graft infection and new aneurysm formation. Therefore, we performed a repeated TEVAR with abdominal 4-vessel debranching. There was no recurrence of infection for six years while continuing postoperative antituberculous therapy. Case 2:A 72-year-old man who had undergone BCG intravesical therapy underwent TEVAR for a rapidly enlarging mycotic TAA. He received anti-tuberculous therapy for one year with no recurrent infection for one year. TEVAR may be an effective alternative to the open surgical procedure;however, multidisciplinary treatment including anti-tuberculous therapy and careful long-term follow up are required.

Reducing the Sodium Intake of Patients With Chronic Kidney Disease Through Education and Estimating Salt Excretion: A Propensity Score Matching Analysis.

BACKGROUND: Japanese people traditionally consume high quantities of salt. This study aimed to investigate the effects of educating patients with chronic kidney disease (CKD) on simple methods for reducing their daily dietary salt intake. METHODS: This single-center, retrospective observational study included 115 outpatients with CKD at Kawashima Hospital (Tokushima, Japan). One physician routinely recommended that patients should reduce their salt intake and provided tips for salt restriction. The physician estimated the patients' daily salt intake using spot urine samples at each medical examination (education group; n = 61). The other physicians' outpatients only received dietary guidance on recommended salt intake (control group; n = 54). The estimated 24-hour urinary sodium excretion (24hUNaV) and 24-hour potassium excretion (24hUKV) were calculated using Tanaka's equation. RESULTS: Estimated 24hUNaV was positively correlated with body mass index (BMI), estimated 24hUKV, and urinary Na/K ratio. The patients in the education group were younger and had a lower BMI, higher estimated glomerular filtration rate, and lower systolic blood pressure (SBP). Using 38 pairs of patients obtained by propensity score matching with these variables, estimated 24hUNaV, estimated 24hUKV, and diastolic blood pressure (DBP) after one year were significantly reduced in the education group. CONCLUSION: A simple salt reduction education may reduce salt intake in outpatients with CKD.

Safety and Clinical Results of Continuous Low-Dose Aspirin in Microendoscopic Laminectomy.

Introduction: It remains controversial whether it is better to continue oral low-dose aspirin (LDA) during the perioperative period in spinal surgery. This study aims to evaluate the safety of continued LDA administration in the perioperative periods of microendoscopic laminectomy (MEL) by assessing perioperative complications and clinical outcomes. Methods: We ultimately included 88 patients (35 males, 53 females) who underwent one level of MEL for lumbar spinal canal stenosis from April 2016 to March 2022. Patients who did not undergo anticoagulation therapy were classified into Group A (65 patients), those who stopped anticoagulation therapy at the perioperative periods were classified into Group B (9 patients), and those who continued oral administration of LDA throughout the perioperative periods were classified into Group C (14 patients). Surgery time, intraoperative estimate blood loss (EBL), differences between hemoglobin (Hb) and platelet (Plt) before and after surgery, perioperative complications, and cross-sectional area of hematoma and dural sac on MRI taken within 1 week and at 6 months or more after surgery were assessed between three groups. The EuroQol-5 dimensions (EQ-5D), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were also evaluated as the clinical outcomes. Results: There was no statistically significant difference between the three groups in operation time, intraoperative EBL, differences between Hb and Plt before and after surgery, and cross-sectional area of hematoma and dural sac on MRI. A case of hematoma removal was confirmed in Group A. There was also no statistically significant difference between the three groups in EQ-5D, ODI, and each domain of JOABPEQ. Conclusions: The continuation of LDA throughout the perioperative periods did not affect perioperative complications and clinical outcomes of one-level MEL. In MEL, it might be possible to continue oral administration of LDA throughout the perioperative periods.

X-linked Alport Syndrome with Type IV Collagen α5 Chain Staining Revealing Normal Expression in the Glomerular Basement Membrane and Negative on Bowman's Capsule and Distal Tubular Basement Membrane: A Case Report.

X-linked Alport syndrome is a hereditary progressive renal disease resulting from the disruption of collagen α3α4α5 (IV) heterotrimerization caused by pathogenic variants in the COL4A5 gene. This study aimed to report a male case of X-linked Alport syndrome with a mild phenotype accompanied by an atypical expression pattern of type IV collagen α5 [α5 (IV)] chain in glomerulus. A 38-year-old male presented with proteinuria (2.3 g/day) and hematuria. He has been detected urinary protein and occult blood since childhood. A renal biopsy was performed at the age of 29 years; however, a diagnosis of Alport syndrome was not considered. A renal biopsy 9 years later revealed diffuse thinning and lamellation of the glomerular basement membrane. Α staining for α5 (IV) revealed a normal expression pattern in the glomerular basement membrane and a complete negative expression in Bowman's capsule and distal tubular basement membrane. Using next-generation sequencing, we detected a COL4A5 missense variant within exon 35 (NM_000495.5: c.3088G>A, p. G1030S). The possibility of X-linked Alport syndrome should be considered when negative expression of α5 (IV) staining on Bowman's capsule was observed.

Adrenal Insufficiency Associated With Empty Sella Syndrome and Steroid Malabsorption Complicated With Septic Shock Due to Post-transplant Pyelonephritis: A Case Report.

Renal transplant recipients are immunocompromised and predisposed to develop hyponatremia because they are exposed to immunological, infectious, pharmacological, and oncologic disorders. A 61-year-old female renal transplant recipient was admitted with diarrhea, anorexia, and headache for about a week during the tapering of oral methylprednisolone for chronic renal allograft rejection. She also presented hyponatremia and was suspected to have secondary adrenal insufficiency based on a low plasma cortisol level of 1.9 µg/dL and a low adrenocorticotropic hormone level of 2.6 pg/mL. Brain magnetic resonance imaging to assess the hypothalamic-pituitary-adrenal axis revealed an empty sella. She also developed septic shock and disseminated intravascular coagulation due to post-transplant pyelonephritis. She had reduced urine output and underwent hemodialysis. Both plasma cortisol and adrenocorticotropic hormone levels were relatively low (5.2 µg/dL and 13.5 pg/mL, respectively), which also suggested adrenal insufficiency. She was treated with hormone replacement therapy and antibiotics, successfully recovered from septic shock, and was withdrawn from dialysis. In empty sella syndrome, the somatotropic and gonadotropic axis are the most affected, followed by the thyrotropic and corticotropic axis. She did not present these abnormalities, which may suggest that empty sella syndrome is a separate pathology, and the axis suppression had occurred due to long-term steroid treatment. Diarrhea due to cytomegalovirus colitis might have induced steroid malabsorption and manifested adrenal insufficiency. Secondary adrenal insufficiency should be investigated as a cause of hyponatremia. It should always be borne in mind that diarrhea during oral steroid treatment may cause adrenal insufficiency associated with steroid malabsorption.

Association between intraoperative pulmonary artery pressure and cardiovascular complications after off-pump coronary artery bypass surgery: a single-center observational study.

BACKGROUND: The impact of intraoperative pulmonary hemodynamics on prognosis after off-pump coronary artery bypass (OPCAB) surgery remains unknown. In this study, we examined the association between intraoperative vital signs and the development of major adverse cardiovascular events (MACE) during hospitalization or within 30 days postoperatively. METHODS: This retrospective study analyzed data from a university hospital. The study cohort comprised consecutive patients who underwent isolated OPCAB surgery between November 2013 and July 2021. We calculated the mean and coefficient of variation of vital signs obtained from the intra-arterial catheter, pulmonary artery catheter, and pulse oximeter. The optimal cut-off was defined as the receiver operating characteristic curve (ROC) with the largest Youden index (Youden index = sensitivity + specificity - 1). Multivariate logistic regression analysis ROC curves were used to adjust all baseline characteristics that yielded P values of < 0.05. RESULTS: In total, 508 patients who underwent OPCAB surgery were analyzed. The mean patient age was 70.0 ± 9.7 years, and 399 (79%) were male. There were no patients with confirmed or suspected preoperative pulmonary hypertension. Postoperative MACE occurred in 32 patients (heart failure in 16, ischemic stroke in 16). The mean pulmonary artery pressure (PAP) was significantly higher in patients with than without MACE (19.3 ± 3.0 vs. 16.7 ± 3.4 mmHg, respectively; absolute difference, 2.6 mmHg; 95% confidence interval, 1.5 to 3.8). The area under the ROC curve of PAP for the prediction of MACE was 0.726 (95% confidence interval, 0.645 to 0.808). The optimal mean PAP cut-off was 18.8 mmHg, with a specificity of 75.8% and sensitivity of 62.5% for predicting MACE. After multivariate adjustments, high PAP remained an independent risk factor for MACE. CONCLUSIONS: Our findings provide the first evidence that intraoperative borderline pulmonary hypertension may affect the prognosis of patients undergoing OPCAB surgery. Future large-scale prospective studies are needed to verify the present findings.

Successful treatment of nephrotic syndrome due to pregnancy-related crescentic IgA nephropathy: a case report.

BACKGROUND: Crescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy. CASE PRESENTATION: A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia. CONCLUSION: Although the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.

Usefulness of the femoral vein as a graft for portal vein/superior mesenteric vein reconstruction during pancreatectomy.

Shibuya and colleagues describe their innovative technique using the femoral vein as a graft for portal vein/superior mesenteric vein reconstruction during pancreatectomy. The femoral vein has an appropriate diameter and is particularly useful when long resection of the superior mesenteric vein is required in surgery for locally advanced pancreatic ductal adenocarcinoma.

Intraoperative Heparin Resistance after Administration of Andexanet Alfa to Manage an Internal Iliac Artery Aneurysm Rupture: A Case Report.

Antithrombotic agents are increasingly prescribed to older adults; however, they are associated with bleeding-related complications. We describe a case of intraoperative heparin resistance after administration of andexanet alfa (AA). An 81-year-old man was diagnosed with a ruptured internal iliac artery aneurysm. The patient required emergency endovascular aneurysm repair and was treated with AA because he was receiving apixaban. Despite high-dose intraoperative heparin administration, his activated coagulation time was not prolonged. Our findings suggest that AA should be administered with caution in patients experiencing potentially fatal bleeding (requiring surgical intervention) who are also receiving direct oral anticoagulants.

Mitral valve plasty in a patient with multiple cerebral cavernous malformations: A case report.

Cerebral cavernous malformations (CCMs) are blood vessel malformations, often untreated if asymptomatic. However, upon cardiac surgery with cardiopulmonary bypass, cerebral edema/hemorrhage may occur. We successful performed mitral valve plasty for a case of severe mitral regurgitation with multiple CCMs. Preoperative head magnetic resonance imaging and strict perioperative management are important.

A Rescue Use of ECPELLA for Sepsis-Induced Cardiogenic Shock Followed by Mitral Valve Replacement.

The use of veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with sepsis-induced cardiogenic shock has been reported, but the clinical implication of the Impella percutaneous axial-flow left ventricular assist device for such patients remains unknown. We had a 37-year-old man with septic shock and severely reduced cardiac function. Veno-arterial ECMO and concomitant Impella CP support ameliorated his end-organ dysfunction and achieved cardiac recovery, whereas severe mitral valve regurgitation due to chordal rupture developed later. Mitral valve replacement concomitant with ECMO removal as well as an Impella upgrade successfully treated the patient. ECMO and Impella support might be an effective therapeutic strategy for the bridge to recovery in patients with sepsis-induced cardiogenic shock; however, paying attention to mitral chordal rupture is highly encouraged.

A case of chronic myocarditis remitted by immunosuppressive and central extracorporeal membrane oxygenation therapy.

The concept and therapeutic strategy for chronic lymphocytic myocarditis remain unestablished. We had a 57-year-old man with advanced biventricular (predominantly right ventricular) failure due to chronic lymphocytic myocarditis. He received central extracorporeal membrane oxygenation therapy that was explanted on day 129 following the aggressive steroid pulse and plasma exchange therapy. Infiltration of inflammatory cells persisted even after the device removal, which required long-term oral steroid administration after the index discharge on day 200. High-sensitivity cardiac troponin T level was normalized and inflammatory cell infiltration was remitted following post-discharge 4-month 10 mg/day prednisolone therapy. Aggressive immunosuppressive therapy under mechanical circulatory support might be a promising strategy for those with chronic lymphocytic myocarditis. .

Takayasu Arteritis Complicated by Ischemic Colitis: A Case Report.

Takayasu arteritis is an inflammatory disease of the aorta and its major branches, which results in stenosis and aneurysm formation. Lesions of the abdominal aorta and renal arteries are common. Nevertheless, lesions of the celiac and superior mesenteric arteries are less common. Since the inferior mesenteric artery is usually preserved and functions as a collateral pathway, developing intestinal ischemia is very rare in patients with Takayasu arteritis. In this study, we report the case of a patient with Takayasu arteritis complicated by ischemic colitis. The patient was treated with surgical repair, which resolved the patient's symptoms.