Plasma Exchange in the Management of Catastrophic Antiphospholipid Syndrome

Objective. Report of a case of catastrophic antiphospholipid syndrome (CAPS) with multiple organ involvement leading to a life-threatening condition despite early combination corticosteroid and heparin therapy. Initiation of plasma exchange led to rapid improvement of the patient’s general condition. Design. Case report. Setting. University teaching hospital medical intensive care unit. Patient. Single case: 52-year-old man hospitalized for catastrophic antiphospholipid syndrome (CAPS) with cardiac, renal, and cutaneous involvement. Despite early methylprednisolone and heparin therapy, the patient’s condition progressively deteriorated, resulting in acute renal failure, right adrenal hemorrhage, and pulmonary involvement, leading to acute respiratory distress on day 6, requiring high-flow nasal cannula oxygen therapy with FiO2 of 1.0. Interventions. Plasma exchange was started on day 6. Endpoints and Main Results. A marked improvement of the patient’s general condition was observed after initiation of plasma exchange, with successful weaning of oxygen therapy and normalization of platelet count, troponin, and serum creatinine within four days. Conclusions. This case illustrates the efficacy of plasma exchange in CAPS and the difficulty for physicians to determine the optimal timing of plasma exchange

Prognostic Value of C4d Immunolabelling in Adult Patients With IgA Vasculitis

International audienceBackground and Objectives: Glomerular C4d deposits are associated the severity and outcomes of IgA nephropathy. Whether this holds true in immunoglobulin A vasculitis (IgAV) is not known. The main objective of the study was to analyze the prognostic value of glomerular C4d immunolabelling on kidney impairment in adults with IgAV. Design, Setting, Participants, Measurements: This retrospective cohort study included 120 adults with IgAV and a kidney biopsy performed between 1995 and 2018 in two French university hospital centers. All paraffin-embedded biopsies were reassessed according to Oxford classification. Immunofluorescence for C4d was performed in all cases. For analysis, patients were grouped according to positivity for C4d in the glomerular area. The main outcome was a composite endpoint of 50% increase in 24 h-proteinuria, or eGFR decrease by 50%, or kidney replacement therapy. Results: The median follow-up was 28.3 months. Twenty-three patients met the composite endpoint, 12 for kidney replacement therapy, 6 for an eGFR decrease >50% and 5 for a >50% increase in proteinuria. At time of biopsy, the median proteinuria was 1.9 g/24 h and the median eGFR 73.5 mL/min/1.73 m 2 . Among the 102 patients evaluable for C4d, 24 were positive on >30% glomeruli, mainly with a parieto-mesangial pattern. In this group, the initial proteinuria was more frequently nephrotic than in the C4d– group (60% vs. 33%, P = 0.039). Mesangial hypercellularity was more frequent in the C4d+ group (42% vs. 13%; P = 0.006) whereas macroscopic hematuria was more frequent in the C4d– group (18% vs. 0%; P = 0.03). After a median follow-up of 28 months, kidney survival did not differ according to C4d status. Conclusion: In a population of adult IgAV patients, glomerular positivity for C4d was associated with the severity of the kidney disease at presentation, but not with subsequent renal function deterioration

The Role of Gut-Derived, Protein-Bound Uremic Toxins in the Cardiovascular Complications of Acute Kidney Injury

Acute kidney injury (AKI) is a frequent disease encountered in the hospital, with a higher incidence in intensive care units. Despite progress in renal replacement therapy, AKI is still associated with early and late complications, especially cardiovascular events and mortality. The role of gut-derived protein-bound uremic toxins (PBUTs) in vascular and cardiac dysfunction has been extensively studied during chronic kidney disease (CKD), in particular, that of indoxyl sulfate (IS), para-cresyl sulfate (PCS), and indole-3-acetic acid (IAA), resulting in both experimental and clinical evidence. PBUTs, which accumulate when the excretory function of the kidneys is impaired, have a deleterious effect on and cause damage to cardiovascular tissues. However, the link between PBUTs and the cardiovascular complications of AKI and the pathophysiological mechanisms potentially involved are unclear. This review aims to summarize available data concerning the participation of PBUTs in the early and late cardiovascular complications of AKI

Risk Factors for Early Graft Failure and Death After Kidney Transplantation in Recipients Older Than 70 Years

Introduction: Although kidney transplantation carries a survival benefit compared with dialysis, mortality, especially the first year after transplantation, is high in recipients older than 70. The aim of this study was to evaluate early death and graft failure, and to determine the risk factors associated with these events in this specific population. Methods: All patients older than 70 years who received a kidney transplant between January 2000 and December 2014 in the North-West of France were included (n = 171). Baseline characteristics and outcomes after transplantation were studied. Kaplan-Meier analysis was performed to assess patient and graft survival, and Cox regression analysis to evaluate risk factors for graft failure and patient death. Results: The mean recipient age was 73.3 ± 2.5 years. Death-censored graft survival at 1, 3, and 5 years were 82.6%, 78.7%, and 75.4%, respectively. Patient survival at 1, 3, and 5 years was 90.1%, 82.5%, and 68.1%, respectively. One year after transplantation, 17 patients (9.9%) were dead, mainly from infectious (58.5%) or cardiovascular disease (29.4%). According to the Cox multivariate analysis, the independent risk factors for death or graft failure during the first year were arrhythmia (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.08–4.8), left-ventricular ejection fraction (LVEF) under 56% (OR 2.38; 95% CI 1.18–4.83), human leucocyte antigen (HLA) antibodies (OR 2.1; 95% CI 1.04–4.2), deceased donor from cardiovascular cause (OR 5.18; 95% CI 1.22–6.3), and acute rejection (OR 2.77; 95% CI 1.2–6.3). Conclusion: In kidney transplant recipients older than 70 years, cardiac evaluation and immunosuppression optimization seem to be crucial to improve short-term patient and graft survival. Keywords: cardiovascular disease, elderly, graft failure, infectious disease, kidney transplantation, patient deat

Thrombotic Microangiopathy Revealing Bone Metastases from an Ethmoid Sinus Carcinoma

Cancer-related thrombotic microangiopathy (TMA) is a rare entity whose clinical and biological characteristics have been described in various tumors. Here we describe the first case of cancer-related TMA revealing diffuse bone metastases from an ethmoid sinus carcinoma

Urinary TIMP2 and IGFBP7 Identifies High Risk Patients of Short-Term Progression from Mild and Moderate to Severe Acute Kidney Injury during Septic Shock: A Prospective Cohort Study

Background. To examine whether the new urinary biomarkers TIMP2 and IGFBP7 can predict progression within 24 hours and 72 hours from mild and moderate (KDIGO 1 or 2) to severe (KDIGO 3) AKI in patients with septic shock. Methods. A prospective, multicenter observational study performed in three French ICUs. The urinary biomarkers TIMP2∗IGFBP7 were analyzed at the early phase (2.0 (ng/ml)2/1,000 identified the population at high risk of KDIGO 3 H24 (relative risk 4.19 (1.7-10.4)) with a sensitivity of 76% (60-87) and a specificity of 81% (69-89). But the diagnostic performance at H72 of baseline TIMP2∗IGFBP7 was poor (AUC: 0.69 (0.59-0.77)). Conclusion. The urinary TIMP2∗IGFBP7 concentration and the urine output at the early phase of septic shock are independent factors to identify the population at high risk of progression from mild and moderate to severe AKI over the next 24 but not 72 hours. A TIMP2∗IGFBP7 concentration>2.0 (ng/ml)2/1,000 quadruples the risk of KDIGO 3 AKI within 24 hours. This trial is registered with (NCT03547414)

Difference in Profiles of the Gut-Derived Tryptophan Metabolite Indole Acetic Acid between Transplanted and Non-Transplanted Patients with Chronic Kidney Disease

International audienceBackground: Uremic toxins have emerged as potential mediators of morbidity and mortality in patients with chronic kidney disease (CKD). Indole-3-acetic acid (IAA, a tryptophan-derived uremic toxin) might be a useful biomarker in patients with CKD. The objectives of the present study were to (i) describe IAA concentrations in a cohort of non-transplanted patients with CKD and a cohort of transplanted patients with CKD, and (ii) investigate the possible relationship between IAA levels and adverse outcomes in the two cohorts. Methods: Levels of free and total IAA were assayed in the two prospective CKD cohorts (140 non-transplanted patients and 311 transplanted patients). Cox multivariate analyses were used to evaluate the association between IAA levels and outcomes (mortality, cardiovascular events, and graft loss). Results: In the non-transplanted CKD cohort, free and total IAA increased progressively with the CKD stage. In the transplanted CKD cohort, free and total IAA levels were elevated at the time of transplantation but had fallen substantially at one-month post-transplantation. Indole acetic acid concentrations were lower in transplanted patients than non-dialysis non-transplanted patients matched for estimated glomerular filtration rate (eGFR), age, and sex. After adjustment for multiple confounders, the free IAA level predicted overall mortality and cardiovascular events in the non-transplanted CKD cohort (hazard ratio [95% confidence interval]: 2.5 [1.2-5.1] and 2.5 [1.3-4.8], respectively). In the transplanted CKD cohort, however, no associations were found between free or total IAA on one hand, and mortality, CV event, or graft survival on the other. Conclusion: We demonstrated that levels of IAA increase with the CKD stage, and fall substantially, even normalizing, after kidney transplantation. Free IAA appears to be a valuable outcome-associated biomarker in non-transplanted patients, but-at least in our study setting-not in transplanted patients

The Effect of Sevelamer on Serum Levels of Gut-Derived Uremic Toxins: Results from In Vitro Experiments and A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

High serum levels of gut-derived uremic toxins, especially p-cresyl sulfate (pCS), indoxyl sulfate (IS) and indole acetic acid (IAA), have been linked to adverse outcomes in patients with chronic kidney disease (CKD). Sevelamer carbonate could represent an interesting option to limit the elevation of gut-derived uremic toxins. The aim of the present study was to evaluate the adsorptive effect of sevelamer carbonate on different gut-derived protein-bound uremic toxins or their precursors in vitro, and its impact on the serum levels of pCS, IS and IAA in patients with CKD stage 3b/4. For the in vitro experiments, IAA, p-cresol (precursor of pCS) and indole (precursor of IS), each at a final concentration of 1 or 10 µg/mL, were incubated in centrifugal 30 kDa filter devices with 3 or 15 mg/mL sevelamer carbonate in phosphate-buffered saline at a pH adjusted to 6 or 8. Then, samples were centrifuged and free uremic toxins in the filtrates were analyzed. As a control experiment, the adsorption of phosphate was also evaluated. Additionally, patients with stage 3b/4 CKD (defined as an eGFR between 15 and 45 mL/min per 1.73 m2) were included in a multicenter, double-blind, placebo-controlled, randomized clinical trial. The participants received either placebo or sevelamer carbonate (4.8 g) three times a day for 12 weeks. The concentrations of the toxins and their precursors were measured using a validated high-performance liquid chromatography method with a diode array detector. In vitro, regardless of the pH and concentration tested, sevelamer carbonate did not show adsorption of indole and p-cresol. Conversely, with 10 µg/mL IAA, use of a high concentration of sevelamer carbonate (15 mg/mL) resulted in a significant toxin adsorption both at pH 8 (mean reduction: 26.3 ± 3.4%) and pH 6 (mean reduction: 38.7 ± 1.7%). In patients with CKD stage 3b/4, a 12-week course of treatment with sevelamer carbonate was not associated with significant decreases in serum pCS, IS and IAA levels (median difference to baseline levels: −0.12, 0.26 and −0.06 µg/mL in the sevelamer group vs. 1.97, 0.38 and 0.05 µg/mL in the placebo group, respectively). Finally, in vitro, sevelamer carbonate was capable of chelating a gut-derived uremic toxin IAA but not p-cresol and indole, the precursors of pCS and IS in the gut. In a well-designed clinical study of patients with stage 3b/4 CKD, a 12-week course of treatment with sevelamer carbonate was not associated with significant changes in the serum concentrations of pCS, IS and IAA