Extracellular Vesicle Transplantation Is Beneficial for Acute Kidney Injury.

Under vasculogenic conditioning, certain pro-inflammatory subsets within peripheral blood mononuclear cells (PBMCs) undergo phenotypic transformation into pro-regenerative types, such as vasculogenic endothelial progenitor cells, M2 macrophages, and regulatory T cells. These transformed cells are collectively termed regeneration-associated cells (RACs). In this study, we aimed to investigate the therapeutic efficacy of RAC-derived extracellular vesicles (RACev) compared with a vehicle-treated group in the context of renal ischemia-reperfusion injury (R-IRI). Human PBMCs were cultured with defined growth factor cocktails for seven days to harvest RACs. EV quantity and size were characterized by nanoparticle tracking analysis. Notably, the systemic injection of RACev significantly decreased serum creatinine and blood urine nitrogen at day three compared to the control group. Histologically, the treatment group showed less fibrosis in the cortex and medullary areas (p < 0.04 and p < 0.01) compared to the control group. The CD31 staining confirmed enhanced capillary densities in the treatment group compared to the control group (p < 0.003). These beneficial effects were accompanied by angiogenesis, anti-fibrosis, anti-inflammation, and anti-apoptosis RACev miR delivery to ischemic injury to control inflammatory, endothelial mesenchymal transition, and hypoxia pathways. In vivo bioluminescence analysis demonstrated a preferential accumulation of RACev in the IR-injured kidney. The systemic transplantation of RACev beneficially restored kidney function by protecting from tissue fibrosis and through anti-inflammation, angiogenesis, and anti-apoptosis miR delivery to the ischemic tissue.

Hepatic arterial infusion of autologous CD34+ cells for hepatitis C virus-related decompensated cirrhosis: A multicenter, open-label, exploratory randomized controlled trial.

Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G-CSF)-mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

Dialysis-related Amyloidosis Presenting as a Fever of Unknown Origin: Symptoms and Management.

A 74-year-old woman with a 34-year history of hemodialysis presented with an intermittent fever, which later coincided with recurrent bilateral shoulder and hip joint pain. Imaging studies suggested amyloid arthropathy, which was histologically confirmed by a synovial biopsy. Increasing ß2-microglobulin clearance during dialysis alone attenuated the intermittent fever and joint pain, but the symptoms did not disappear until the administration of prednisolone 10 mg/day. Reported cases of dialysis-related amyloidosis with a fever imply that changing to blood purification methods with high ß2-microglobulin clearance is crucial for controlling the condition long-term, whereas concurrent use of anti-inflammatory agents promptly alleviates the symptoms.

Impact of Contrast-Induced Nephropathy on Long-Term Renal Function after Coronary Angiography and Contrast-Enhanced Computed Tomography.

Background: It remains unclear whether contrast-induced nephropathy (CIN) has a prognostic impact on subsequent renal dysfunction and whether deteriorating renal function is a risk factor for CIN. This study aimed to evaluate the occurrence of CIN in patients with pre-existing renal dysfunction and investigate the long-term effects of worsening renal function after coronary angiography or contrast-enhanced computed tomography (CT). The prognostic factors of worsening renal dysfunction were also analyzed. Methods: This was a prospective cohort study of patients at risk for CIN, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 on coronary angiography or eGFR <45 mL/min/1.73 m2 on contrast-enhanced CT. Serum creatinine levels and the 2-year prognosis were evaluated. CIN was defined as an increase in serum creatinine level by more than 0.5 mg/dL or a 25% increase from the previous value within 72 hours after contrast administration. The primary endpoint was the proportion of patients who had serum Cr doubling or induction of dialysis within 2 years according to CIN occurrence. Results: Of the 410 patients, 19 patients developed CIN (8/142 patients on coronary angiography and 11/268 patients on contrast-enhanced CT), and 38 patients had worsened renal function (21/142 patients on coronary angiography and 17/268 patients on contrast-enhanced CT). CIN was not associated with worsening renal function at 2 years. Analysis by renal function at the time of coronary angiography or contrast-enhanced CT (i.e., eGFR ≥30 ml/min/1.73 m2 and eGFR ≤1.73 m2) found no between-group difference in the occurrence of CIN. Conclusions: CIN is not a prognostic risk factor for the long-term of chronic kidney disease after coronary angiography or contrast-enhanced CT. Pre-existing renal dysfunction is also not a risk factor for CIN, even if the eGFR is <30 ml/min/1.73 m2.

Acquired aplastic anemia complicated with anti-glomerular basement membrane disease successfully treated with immunosuppressive therapy: a case report.

BACKGROUND: Aplastic anemia (AA) is a rare but fatal disorder characterized by pancytopenia due to bone marrow hypoplasia. Anti-glomerular basement membrane disease (anti-GBM disease) is an immune complex small-vessel vasculitis that presents as rapidly progressive glomerulonephritis and/or pulmonary hemorrhage. Although both involve autoreactive T cells that are partially triggered by human leukocyte antigen (HLA)-DR15, there have been no reports of their co-existence and the treatment strategy is not well understood. CASE PRESENTATION: A 67-year-old woman presented with fever, malaise, and acute kidney injury with proteinuria and hematuria requiring hemodialysis. She was diagnosed with anti-GBM antibody disease based on high serum anti-GBM antibody titer and crescentic glomerulonephritis on a renal biopsy. Pulse administration of methylprednisolone (MP), oral prednisolone (PSL), and plasmapheresis were performed. Only 2 weeks after the diagnosis of anti-GBM disease, the patient developed pancytopenia requiring frequent blood transfusions. The blood cell count did not recover even 1 month after discontinuing the drugs that could cause pancytopenia. Bone marrow examination showed hypocellularity without abnormal infiltrates or fibrosis, which led to the diagnosis of severe acquired AA. Further HLA phenotyping revealed that she had HLA-DR15. Increased dose of PSL with the secondary MP pulse and the addition of cyclosporine improved pancytopenia. Although she remained dialysis-dependent, anti-GBM disease and pancytopenia did not recur for more than 2 years. CONCLUSIONS: We report the first case of acquired AA complicated with anti-GBM disease in an elderly woman with HLA-DR15, which was successfully treated with immunosuppressive therapy (IST). This report is valuable not only because it shows they may co-occur, but also because it provides a therapeutic option for this complex condition. It was also suggested that pancytopenia in patients with anti-GBM disease recalls serious hematologic diseases including AA that require immediate treatment based on bone marrow examination.

Recurrent hemorrhagic shock from hemorrhagic cystitis due to neurogenic bladder.

INTRODUCTION: Hemorrhagic cystitis is characterized by gross hematuria, with hemorrhagic shock a rare complication. However, to our knowledge, its exact frequency has not been reported. CASE PRESENTATION: We report a case of an 86-year-old woman who showed repeated hemorrhagic cystitis with massive bleeding and hemorrhagic shock. The hemorrhagic cystitis was supposedly caused by the administration of aspirin and a neurogenic bladder. A urethral catheter was indwelled and hemorrhagic cystitis subsequently ceased. CONCLUSION: A review of patients with hemorrhagic cystitis at our hospital showed that only 3.3% experienced hemorrhagic shock. This case was even rarer because the patient experienced recurrent hemorrhagic shocks. A neurogenic bladder, which reduces the bladder's ability to function as a uroepithelial barrier against recurrent bacterial infections, caused the condition in this case. This report highlights how hemorrhagic cystitis can sometimes cause hemorrhagic shock.

Acute kidney injury successfully treated with autologous granulocyte colony-stimulating factor-mobilized peripheral blood CD34-positive cell transplantation: A first-in-human report.

A 36-year-old man with severe acute kidney injury (AKI) was admitted to Shonan Kamakura General Hospital in Japan. He was diagnosed with refractory hypertension based on a severely elevated blood pressure of 224/116 mmHg and retinal, cardiac, and brain damage revealed by electrocardiogram, fundoscopy, and magnetic resonance imaging, respectively. Although hemodialysis was withdrawn following strict blood pressure control by an angiotensin receptor blocker, severe kidney insufficiency persisted. Therefore, we performed an autologous granulocyte colony-stimulating factor-mobilized peripheral blood CD34-positive cell transplantation. Collected CD34-positive cells were directly infused to both renal arteries. The patient's general condition was unremarkable after intervention, and the serum creatinine level gradually improved to 2.96 mg/dL 23 weeks after cell therapy. Although transient fever and thrombocytosis were observed after intervention, no major adverse events were observed. This patient is the first case in a phase I/II clinical trial of autologous granulocyte colony-stimulating factor-mobilized peripheral blood CD34-positive cell transplantation for severe AKI with a CD34-positive cell dose-escalating protocol (trial number jRCTb030190231).

Renal hemosiderosis presenting with acute kidney Injury and macroscopic hematuria in Immunoglobulin A nephropathy: a case report.

BACKGROUND: Macroscopic hematuria-associated acute kidney injury (AKI) is a well-known complication of immunoglobulin A (IgA) nephropathy. In such cases, intratubular obstruction by red blood cell (RBC) casts and acute tubular necrosis are mainly observed pathologically. Herein, we report the case of a patient with IgA nephropathy presenting with AKI following an episode of macrohematuria. The patient presented with severe renal tubular hemosiderosis and acute tubular necrosis and without any obvious obstructive RBC casts. CASE PRESENTATION: A 68-year-old woman, who was diagnosed with IgA nephropathy on renal biopsy 6 years ago, was admitted to our hospital after an episode of macroscopic glomerular hematuria and AKI following upper respiratory tract infection. Renal biopsy showed mesangial proliferation of the glomeruli, including crescent formation in 17 % of the glomeruli, and acute tubular necrosis without obvious hemorrhage or obstructive RBC casts. The application of Perls' Prussian blue stain showed hemosiderin deposition in the renal proximal tubular cells. Immunofluorescence showed granular mesangial deposits of IgA and C3. Based on these findings, she was diagnosed with acute tubular necrosis with a concurrent IgA nephropathy flare-up. Moreover, direct tubular injury by heme and iron was considered to be the cause of AKI. She was treated with intravenous pulse methylprednisolone followed by oral prednisolone. Thereafter, the gross hematuria gradually faded, and her serum creatinine levels decreased. CONCLUSIONS: IgA nephropathy presenting with acute kidney injury accompanied by macrohematuria may cause renal hemosiderosis and acute tubular necrosis without obstructive RBC casts. Hemosiderosis may be a useful indicator for determining the pathophysiology of macroscopic hematuria-associated AKI. However, renal hemosiderosis may remain undiagnosed. Thus, Perls' Prussian blue iron staining should be more widely used in patients presenting with hematuria.

De novo ulcerative colitis after kidney transplantation treated with infliximab.

Diarrhea is a common complication in kidney transplant recipients. Common causes of diarrhea include infection, side effect from medication, rejection, and malignancy. A less common but important cause of diarrhea is de novo inflammatory bowel disease (IBD). This is unexpected, as these patients are already immunosuppressed. Herein, we present the case of a 45-year-old man with end-stage kidney disease because of focal segmental glomerulosclerosis who underwent preemptive kidney transplantation, with his mother as donor. His immunosuppressive regimen included methylprednisolone, mycophenolate mofetil, and tacrolimus. He had no episodes of graft dysfunction, rejection, or infectious events. Two and a half years post-transplantation, he developed bloody diarrhea. After excluding infections, colonoscopy was performed and revealed edematous mucosa and erythema with pigmentation, which are typical findings in ulcerative colitis. Despite therapy with 5-aminosalicylate and granulocyte monocyte apheresis, he presented with massive bloody diarrhea. We initiated infliximab, an anti-tumor necrosis factor-α (TNF-α) agent. He responded very well and achieved remission within 6 months after initiation of infliximab, while administration of the other immunosuppressants was maintained. His course was uneventful and no complications developed. Management of immunosuppressants for de novo IBD after organ transplantation is complicated, because treatment of IBD, graft function protection, and prevention of infection must be considered. Therefore, cooperation between transplantation physicians and gastroenterologists is essential during therapy.

Peritoneal dialysis-related peritonitis complicated with nonocclusive mesenteric ischemia.

Peritoneal dialysis (PD)-related peritonitis is a common complication of PD. Nonocclusive mesenteric ischemia (NOMI) is a rare complication of PD-related peritonitis, has a high mortality rate, and therefore should be detected early once it occurs. We describe a case of a 70-year-old woman on PD presented with moderate abdominal pain and low blood pressure, which contributed to the early diagnosis of PD-related peritonitis complicated with NOMI. Increased white cell count of 7150/µL (neutrophil, 84%) in dialysate effluent was diagnostic of PD-related peritonitis, which was later found to be caused by Pseudomonas putida. Computed tomography with contrast performed after administering crystalloids revealed hepatic portal venous gas, pneumatosis intestinalis in the ascending colon, and normal enhancement of the bowel wall and mesenteric arteries, which suggested a reperfusion of the previously ischemic ascending colon. Colonoscopy on hospital day seventeen revealed mucosal hemorrhage and ulcers in the entire right colon and the terminal ileum while the remaining colon was normal. These findings are compatible with the consequence of NOMI. Increased peak systolic velocity of the superior mesenteric artery (SMA) implied its stenosis. Past studies show that ischemia of the colon in patients with chronic kidney disease commonly occurs in the right colon. Arteriosclerosis of the SMA due to the long history of chronic kidney disease and diabetes might have caused its vulnerability to low blood pressure. Abdominal complications including NOMI should be screened for when a patient presents with low blood pressure and strong abdominal pain. This is the first case report that shows colonoscopy images of the colonic ulcers post-NOMI and PD-related peritonitis.

Angiectasia of the parietal pleura in a hemodialysis patient with central venous stenosis and bloody pleural effusion: a case report.

Pleural effusion in hospitalized patients with long-term hemodialysis (HD) has been frequently reported. The most common causes of unilateral pleural effusions include hypervolemia, parapneumonic, uremic effusion, and malignancy. In contrast, central venous stenosis (CVS) has rarely been shown to result in pleural effusion. CVS is often diagnosed by percutaneous angiography, yet there are no reports of cases where percutaneous angiography missed CVS and instead intrathoracic endoscopy was performed. Herein, we report a case of CVS with angiectasia of the parietal pleura detected on intrathoracic endoscopy. A 62-year-old man with HD presented with massive unilateral pleural effusion. Although the cause of pleural effusion was suspected to be CVS, percutaneous angiography did not show apparent stenosis, and as a result, other potential causes of bloody effusion were investigated. The intrapleural cavity was assessed using intrathoracic endoscopy, which revealed angiectasia and no malignancy. As these findings might be suggestive of congestive and dilated vessels with venous stenosis or occlusion, 3D-computed tomography (CT) scans were performed instead of percutaneous angiography to determine whether a stenosis or occlusion was present. Brachiocephalic vein stenosis was found near the aortic arch. CVS was treated through ligation of the arteriovenous fistula (AVF), resulting in a dramatic decrease in the left pleural effusion. This case would suggest that CVS should be suspected when angiectasia of the parietal pleura is observed in HD patients. In addition, the benefit of utilizing 3D-CT should be considered when HD patients present with a unilateral hemothorax on the same side as that of the AVF, particularly when on the left side.

Efficacy of repeat-dose rituximab maintenance therapy for minimal change disease in adults.

BACKGROUND: Rituximab (RTX) has been reported to effectively treat minimal change disease (MCD) in adults. However, the efficacy of RTX as maintenance therapy, especially in older patients, remains unclear. This study aimed to evaluate the efficacy of repeat-dose RTX maintenance therapy regardless of age. METHODS: We retrospectively reviewed the clinical courses of 13 biopsy-proven adult MCD patients receiving RTX and evaluated the relapse rate, concomitant steroid and immunosuppressant use, relationship between B-cell depletion time and relapse, and adverse events. RESULTS: Mean patient age at start of RTX therapy was 51.5 ± 20.1 years. Each RTX induction consisted of a single 375 mg/m2 dose. One patient received two RTX doses with a 1-year interval. The remaining 12 patients received RTX at 6-month intervals up to four times after RTX introduction. The median observation period was 28 (16-60) months after RTX induction, median relapse frequency was significantly decreased from 0.83 (0.18-1.92) to 0 (0-0.71) times/year (P < 0.001), and median prednisolone dose was reduced from 25 (5-40) mg to 2.5 (0-10) mg (P < 0.001). CD19-positive B cells remained depleted during RTX administration in 6-month intervals. No serious adverse events were observed after RTX administration. CONCLUSIONS: Repeat-dose RTX as maintenance therapy efficiently prevented recurrence and was well tolerated in adult MCD patients including older. This regimen has the potential to maintain prolonged remission. Future studies in larger cohorts are needed to identify the optimal dose and frequency and evaluate the long-term effectiveness and safety of this regimen.

The Clinical Course of Acute Kidney Disease after Cardiac Surgery: A Retrospective Observational Study.

Acute kidney disease (AKD), or renal dysfunction persisting >7 days after an initiating event of acute kidney injury, is a rising concern. This study aimed to elucidate the clinical course of AKD after cardiac surgery with data on post-cardiac surgery patients admitted to intensive care units (ICU) at 18 Japanese hospitals during 2012-2014. Using multivariable logistic models, we evaluated the association of AKD with 90-day mortality and the 50% eGFR decline during 2-year follow-up compared to eGFR at 90 days. AKD was defined as an elevation in serum creatinine to at least 1.5-fold from baseline in >7 days after ICU admission. Of the 3,605 eligible patients undergoing cardiac surgery, 403 patients (11.2%) had AKD. Multivariable analysis revealed that the adjusted odds ratio (OR) of AKD for 90-day mortality was 63.0 (95% confidence interval [CI], 27.9-180.6). In addition, the adjusted OR of AKD for 50% eGFR decline was 3.56 (95% CI, 2.24-5.57) among hospital survivors. In conclusion, AKD after cardiac surgery was associated with higher 90-day mortality and renal function decline after hospital discharge.

Association of pre-operative chronic kidney disease and acute kidney injury with in-hospital outcomes of emergency colorectal surgery: a cohort study.

BACKGROUND: Pre-operative kidney function is known to be associated with surgical outcomes. However, in emergency surgery, the pre-operative kidney function may reflect chronic kidney disease (CKD) or acute kidney injury (AKI). We examined the association of pre-operative CKD and/or AKI with in-hospital outcomes of emergency colorectal surgery. METHODS: We conducted a retrospective cohort study including adult patients undergoing emergency colorectal surgery in 38 Japanese hospitals between 2010 and 2017. We classified patients into five groups according to the pre-operative status of CKD (defined as baseline estimated glomerular filtration rate < 60 mL/min/1.73 m2 or recorded diagnosis of CKD), AKI (defined as admission serum creatinine value/baseline serum creatinine value ≥ 1.5), and end-stage renal disease (ESRD): (i) CKD(-)AKI(-), (ii) CKD(-)AKI(+), (iii) CKD(+)AKI(-), (iv) CKD(+)AKI(+), and (v) ESRD groups. The primary outcome was in-hospital mortality, while secondary outcomes included use of vasoactive drugs, mechanical ventilation, blood transfusion, post-operative renal replacement therapy, and length of hospital stay. We compared these outcomes among the five groups, followed by a multivariable logistic regression analysis for in-hospital mortality. RESULTS: We identified 3002 patients with emergency colorectal surgery (mean age 70.3 ± 15.4 years, male 54.5%). The in-hospital mortality was 8.6% (169/1963), 23.8% (129/541), 15.3% (52/340), 28.8% (17/59), and 32.3% (32/99) for CKD(-)AKI(-), CKD(-)AKI(+), CKD(+)AKI(-), CKD(+)AKI(+), and ESRD, respectively. Other outcomes such as blood transfusion and post-operative renal replacement therapy showed similar trends. Compared to the CKD(-)AKI(-) group, the adjusted odds ratio (95% confidence interval) for in-hospital mortality was 2.54 (1.90-3.40), 1.29 (0.90-1.85), 2.86 (1.54-5.32), and 2.76 (1.55-4.93) for CKD(-)AKI(+), CKD(+)AKI(-), CKD(+)AKI(+), and ESRD groups, respectively. Stratified by baseline eGFR (> 90, 60-89, 30-59, and < 30 mL/min/1.73 m2) and AKI status, the crude in-hospital mortality and adjusted odds ratio increased in patients with baseline eGFR < 30 mL/min/1.73 m2 among patients without AKI, while these were constantly high regardless of baseline eGFR among patients with AKI. Additional analysis restricting to 2162 patients receiving the surgery on the day of hospital admission showed similar results. CONCLUSIONS: The differentiation of pre-operative CKD and AKI, especially the identification of AKI, is useful for risk stratification in patients undergoing emergency colorectal surgery.

Intradialytic hypotension is an important risk factor for critical limb ischemia in patients on hemodialysis.

BACKGROUND: Critical limb ischemia (CLI) and intradialytic hypotension (IDH) are common complications in patients on hemodialysis (HD). However, limited data are available on whether IDH is related to CLI in these patients. The aim of this retrospective study was to evaluate whether IDH is a risk factor for CLI in HD patients. METHODS: We examined the frequency of IDH in 147 patients who received HD between January 1 and June 30, 2012. Blood pressure was measured during HD every 30 min and IDH was defined as a ≥ 20 mmHg fall in systolic blood pressure compared to 30 min before and a nadir intradialytic systolic blood pressure < 90 mmHg. The primary study outcome was newly developed CLI requiring revascularization treatment or CLI-related death. We assessed the association of IDH with outcome using a multivariable subdistribution hazard model with adjustment for male, age, smoking and history of cardiovascular disease. RESULTS: The median follow-up period was 24.5 months. Fifty patients (34%) had episodes of IDH in the study entry period. During follow-up, 14 patients received endovascular treatment and CLI-related death occurred in 1 patient. Factors associated with incident CLI in univariate analysis were age, smoking, diabetes mellitus, peripheral arterial disease, history of cardiovascular disease, and IDH. IDH was significantly associated with the outcome with the subdistribution hazard ratio of 3.13 [95% confidence interval, 1.05-9.37]. CONCLUSIONS: IDH was an independent risk factor for incident CLI in patients on HD.

Intravascular large B-cell lymphoma involving large blood vessels, three autopsy cases.

Although intravascular large B-cell lymphoma (IVLBCL) is an extranodal lymphoma characterized by the selective growth of lymphoma cells within the lumina of small vessels, we here report three autopsy cases of IVLBCL characterized by the proliferation within large blood vessels. These three cases were diagnosed as IVLBCL of the bone marrow or skin biopsy. Two cases died suddenly before treatment, whereas the other died during treatment. Autopsies showed a large embolus of dense lymphoma cells extending from the truncus pulmonalis to the pulmonary arteries in Case 1, emboli of lymphoma cells in the aorta and carotis in Case 2, and a mass of lymphoma cells blocking the lumen of the aortic arch in Case 3. This is the first report of IVLBCL involving large blood vessels, and it is essential to note that this type of IVLBCL might cause sudden death because of tumor emboli within large blood vessels.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Intravascular lymphoma forming massive aortic tumors complicated with sarcoidosis and focal segmental glomerulosclerosis: a case report and literature review.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma characterized by proliferation of B cells within small vessels. Herein, we report a case of a 77-year-old man who presented with IVLBCL and massive tumor formation on the aortic wall who was previously diagnosed with sarcoidosis and focal segmental glomerulosclerosis (FSGS). To our knowledge, this is the first reported case of an IVLBCL with aortic tumor formation. CASE PRESENTATION: A 77-year-old ambulatory man with sarcoidosis and FSGS had neurological symptoms for nine months. The patient presented to the emergency department with sudden left leg pain, and was diagnosed with acute femoral artery occlusion. Emergency thrombectomy was performed subsequently. Pathological evaluation of the thrombi revealed that its surface was filled with large atypical B cells. Bone marrow biopsy showed infiltration of large atypical B cells within the small vessels. IVLBCL was suspected and further examination was planned, but the patient died due to sudden respiratory and cardiac arrest on hospital day twelve. Autopsy revealed intravascular tumors adherent to the aortic arch, left ventricle, and the abdominal aorta. All enlarged lymph nodes and the ventricular septum of the heart showed hyalinized lesions with granular formation consistent with sarcoidosis. The patient was diagnosed with IVLBCL with aortic tumor formation complicated with sarcoidosis and FSGS. CONCLUSIONS: IVLBCL may present with tumor formation on the aortic wall. Although the cause of its affinity to the aortic wall is yet unknown, autopsy findings imply that arteriosclerosis may have contributed to the tumor formation. The literature suggests that T-cell abnormalities could possibly be the common etiology of intravascular lymphoma, sarcoidosis, and FSGS.