First case of subcutaneous cystic phaeohyphomycosis due to Phialophora chinensis in a kidney transplant recipient in Martinique.

We report a case of subcutaneous mycosis in the form of a subcutaneous cyst of the index finger, successfully treated by surgery and posaconazole in an 84-year-old female kidney transplant patient. Intra-operative mycological analysis enabled the diagnosis of Phialophora chinensis phaeohyphomycosis. Phialophora chinensis is an environmental mold recently described in human pathology in cases of chromoblastomycosis. This is the first case of subcutaneous phaeohyphomycosis due to Phialophora chinensis in an immunocompromised patient.

C5b-9 Glomerular Deposits Are Associated With Poor Renal Survival in Membranous Nephropathy.

Introduction: Membranous nephropathy (MN) is the first cause of nephrotic syndrome in patients without diabetes. Its prognosis is variable, and treatment remains controversial because of potential toxicity. Currently, there is no reliable prognostic marker common to all etiologies of MN and routinely available to predict the disease course and guide therapeutic management. Despite the major role of complement in the glomerular damage of MN, its prognostic impact has never been studied. We investigated the frequency and prognostic impact of glomerular deposition of C5b-9 in MN. Methods: We retrospectively selected adults diagnosed with MN (primary or secondary) at Montpellier University Hospital between December 2004 and December 2015. To be included, all patients were required to have complete medical data and a kidney tissue sample for further immunohistochemistry. We performed PLA2R1, C4d, and C5b-9 staining by immunohistochemistry. Results: Sixty-four adults were included: 45 with primary MN and 19 with secondary MN. C4d was positive in the glomeruli of 61 adults (95.3%). Twenty-nine adults (45.3%) had glomerular deposition of C5b-9. Patients with glomerular deposition of C5b-9 had more severe nephrotic syndrome on diagnosis and lower remission and renal survival rates than adults without. Conclusion: C5b-9 glomerular staining is a powerful and easily accessible tool for stratifying adults according to their renal prognosis. The efficacy of complement inhibitors should be tested in adults with glomerular deposition of C5b-9.

Good Long-Term Prognosis of Lupus Nephritis in the High-Income Afro-Caribbean Population of Martinique with Free Access to Healthcare.

Lupus nephritis (LN) has been described as having worse survival and renal outcomes in African-descent patients than Caucasians. We aimed to provide long-term population-based data in an Afro-descendant cohort of LN with high income and easy and free access to specialized healthcare. STUDY DESIGN: We performed a retrospective population-based analysis using data from 2002-2015 of 1140 renal biopsies at the University Hospital of Martinique (French West Indies). All systemic lupus erythematosus patients with a diagnosis of LN followed for at least 12 months in Martinique or who died during this period were included. RESULTS: A total of 89 patients were included, of whom 68 (76.4%) had proliferative (class III or IV), 17 (19.1%) had membranous (class V), and 4 (4.5%) had class I or II lupus nephritis according to the ISN/RPS classification. At a mean follow-up of 118.3 months, 51.7% of patients were still in remission. The rates of end-stage renal disease were 13.5%, 19.1%, and 21.3% at 10, 15, and 20 years of follow-up, respectively, and mortality rates were 4.5%, 5.6%, and 7.9% at 10, 15, and 20 years of follow-up, respectively. CONCLUSIONS: The good survival of our Afro-descendant LN patients, similar to that observed in Caucasians, shades the burden of ethnicity but rather emphasizes and reinforces the importance of optimizing all modifiable factors associated with poor outcome, especially socioeconomics.

Interest of a Kidney Biopsy to Rule out ANCA-Associated Renal Vasculitis in Glomerulonephritis Patients with a Positive ANCA.

Kidney biopsy is the gold standard for diagnosing glomerular kidney disease. Some authors debate the necessity of systematically performing kidney biopsies in ANCA-associated vasculitis (AAV) to confirm the diagnosis and assess the severity of renal damage. Nevertheless, kidney involvement is considered an organ-threatening disease requiring an aggressive immunosuppressive regimen. We present a series of 4 cases with a high clinical suspicion of ANCA-associated crescentic glomerulonephritis based on rising serum creatinine, presence of proteinuria and/or hematuria, and presence of ANCA with specificity against PR-3 or MPO. The main diagnosis, however, was arterionephrosclerosis without renal AAV. Certain comorbidities, such as diabetes and/or high blood pressure, can quickly mimic progressive glomerulonephritis. In addition, some patients with AAV do not have high creatinine, proteinuria, or hematuria levels. ANCA alone is not specific to AAV and has a poor positive predictive value. The main concern is to prevent the unnecessary, inappropriate complications of heavy immunosuppression, i.e., serious infections or risk of future malignancies. Kidney pathological confirmation is important in patients with no compatible extra-renal manifestations of AAV or any other possible renal diagnosis such as may be found in polyvascular disease or diabetic patients.

Specificity of severe AKI aetiology and care in the elderly. The IRACIBLE prospective cohort study.

INTRODUCTION: Acute Kidney Injury (AKI) is increasingly common in people over 65 years of age, but its causes and management are poorly described. The purpose of this study was to describe the causes, management and prognosis of patients over 65 hospitalised for severe acute kidney injury (AKI) in all departments of a tertiary centre. METHOD: The prospective IRACIBLE (IRA: AKI in French; CIBLE: target in French) cohort included 480 patients hospitalised at a university hospital over 18 months for severe AKI or subgroup of AKIN3 (Acute Kidney Injury Network classification) defined by an acute creatinine increase > 354 µmol/L or managed with acute renal replacement therapy (RRT). The history, aetiology of AKI, management, and prognosis were compared in three age groups: < 65, 65-75, and > 75 years. RESULTS: The study population included 480 subjects (73% men) with a median body mass index (BMI) of 26.6 kg/m2 [23.3, 30.9], 176 (37%) diabetic patients, 124 (26%) patients < 65 years, 150 (31%) 65-75 years and 206 (43%) > 75 years. Increasing age class was associated with more comorbidities, a significantly lower median estimated glomerular filtration rate (eGFR) 6 months before inclusion (82; 62; 46 ml/min/1.73 m2, p < 0.05) and aetiology of AKI, which was more often obstructive (12%; 15%; 23%, p = 0.03) or part of a cardio-renal syndrome (6%; 9%; /15%, p = 0.04). Older patients were less often managed in the intensive care unit  (54%; 47%; 24%, p < 0.0001), were less frequently treated by RRT (52%; 43%; 31%, p < 0.001) and received fewer invasive treatments  (6%; 9%; 22%, p < 0.0001). Older survivors returned home less often (80%; 73%; 62%, p = 0.05) in favour of transfers to rehabilitation services (10%; 13%; 22%) with higher mortality at 3 months (35%; 32%; 50%, p < 0.0001). CONCLUSION: Older patients hospitalised for severe AKI have a specific profile with more comorbidities, lower baseline renal function, an aetiology of AKI of mainly extra-parenchymal causes and a complex pathway of care with an overall poor prognosis.

Two cases of secondary AA amyloidosis involving the skin and chronic kidney infection with a nephrotic syndrome in a high-income country.

We present two French cases of amyloid-associated (AA) amyloidosis secondary to chronic infections. Patient 1, a 51-year-old heroin addict, was hospitalised for chest pain and anasarca. During hospitalisation, a nephrotic syndrome with an inflammatory condition was discovered along with a chronic skin ulcer on his arm. Salivary gland and kidney biopsies confirmed the diagnosis of AA amyloidosis. Renal function quickly declined and haemodialysis was initiated 6 months later. Patient 2, a 55-year-old woman, was hospitalised for obstructive pyelonephritis secondary to coraliform lithiasis. Renal insufficiency with an impure nephrotic syndrome was found. After nephrectomy due to chronic pyelonephritis and an atrophic cortex on the abdominal scan, the histology revealed AA amyloidosis. Despite treatment with ACE inhibitors and control of inflammation, the nephrotic syndrome persisted with rapid decline of the kidney function.

Humanized anti CD-20 as an alternative in chronic management of relapsing thrombotic thrombocytopenic microangiopathy resistant to rituximab due to anti chimeric antibody.

Acquired Immune thrombotic thrombocytopenic purpura (iTTP) is considered among clinical situations that needs not only urgent treatment in acute setting but also long term management to prevent relapses. Important progresses have been made in management of these patients that are definitely associated with reduced mortality and relapse rate. However, there are still noticeable percentage of patients that may relapse despite application of modern treatment strategies including preemptive rituximab infusions. Hereby, we share our experience concerning a frequently relapsing iTTP due to development of anti-rituximab antibody. In our case administration of obinutuzumab, a humanized type II anti CD-20 antibody was associated with complete peripheral blood B cell depletion and increasing plasma ADAMTS-13 activity.

Physiological role of plasma and its components and the clinical implications of different methods of apheresis: A narrative review.

Nowadays, therapeutic plasmapheresis (TP) is accepted as part of the treatment for specific groups of diseases. The availability of different methods, including double filtration and adsorption, increases selectivity for the removal of substances. However, the use of these techniques requires a thorough understanding of the characteristics and components of plasma. By considering pivotal papers from several databases, the aim of this narrative review is to describe the characteristics of plasma related to apheresis techniques. We have tried to cover the clinical implications including physiology, estimation of plasma volume, viscosity, and a description of its components including the size, volume of distribution, and half-lives of the different substances to be removed or maintained depending on the clinical situation and applied apheresis technique. Applying this knowledge will help us to choose the right method and dosage and improve the efficacy of the procedure by preventing or addressing any complications.

Primary antiphospholipid syndrome associated with anti-phospholipase A2 receptor antibody-positive membranous nephropathy.

BACKGROUND: The kidney is a major target in primary antiphospholipid syndrome. Several types of nephropathy have been reported, the most frequent being acute or chronic specific vascular nephropathies and membranous nephropathy. CASE PRESENTATION: A 59-year-old male presented in our unit with nephrotic syndrome. He had a history of primary antiphospholipid syndrome with lupus anticoagulant treated with vitamin K antagonist therapy. On admission, antiphospholipid (lupus anticoagulant) and anti-PLA2R antibodies were positive. Screening for secondary etiologies was negative. In the context of primary antiphospholipid syndrome treated with vitamin K antagonist therapy, we did not perform a biopsy and we treated the patient with angiotensin-converting-enzyme inhibitor. No remission was observed at 6 months with persistent anti-PLA2R antibodies while antiphospholipid antibody level became negative. Consequently, kidney biopsy was performed showing both membranous nephropathy with PLA2R in deposits on immunohistochemistry with IgG4 dominance and antiphospholipid syndrome chronic vascular nephropathy. Following that, treatment with rituximab was started with secondarily a decrease in serum PLA2R antibody levels and partial remission. CONCLUSION: We report the first association between primary antiphospholipid syndrome and membranous nephropathy with anti-PLA2R antibodies. Our observations could suggest a causal link between primary antiphospholipid syndrome and PLA2R-related membranous nephropathy. Consequently, it would be interesting to screen for anti-PLA2R antibodies for further cases of nephrotic syndrome in patients with primary antiphospholipid syndrome and to search antiphospholipid antibodies in all membranous nephropathies.

Pneumocystis jirovecii pneumonitis: cause of acute hypercalcaemia in chronic haemodialysis patient.

A 76-year-old renal transplant patient due to autosomal dominant polycystic kidney disease who resumed chronic haemodialysis was admitted to our hospital for confusion and lassitude. He was afebrile and physical examination revealed diffuse bilateral rales with decreased respiratory sounds in lower right lung. Laboratory data showed hypercalcaemia (total calcium 3.92 mmol/L (normal range 2.2-2.6 mmol/L), ionised calcium 1.87 mmol/L (1.15-1.35 mmol/L)), low intact parathyroid hormone (iPTH) 15 ng/L, (15-65 ng/L) and high 1,25(OH)2D3 128.9 pg/mL, (15.2-90.1 pg/mL). Chest CT-scan revealed bilateral apical lung lesions after 15 days of antibiotics. Bronchoalveolar sample was PCR positive for Pneumocystis jirovecii He was treated with an extra session of haemodialysis with 1.25 mmol/L dialysate calcium concentration, oral trimethoprim-sulfamethoxazole was started and oral corticosteroid dose increased to 1 mg/kg for 1 week. Hypercalcaemia decreased progressively after initiation of these treatments. We concluded a case of hypercalcaemia secondary to P. jirovecii infection.

Use of double filtration plasmapheresis for the treatment of acquired thrombocytopenic thrombotic purpura.

Double filtration plasmapheresis (DFPP) could be an alternative method to simple plasma exchange plasmapheresis in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP). In a retrospective single center case series, we studied clinical presentation, management care, and prognosis of aTTP patients from our academic center treated with DFPP and IV infusion of fresh frozen plasma (FFP) between 2009 and 2018. Nine patients were included for 11 episodes. Median age was 38 years old (IQR 26-53) with 78% women. Six episodes (55%) required admission to the ICU, four of which required mechanical ventilation. Median FFP volume transfused was 35.2 mL/kg/d of session. Response was complete for nine episodes (82%). Four patients presented an early relapse, two a late relapse. Four patients died: one had an active untreated HCV infection, and two were over 80-year-old polymorbid patients. DFPP seems to be an efficient method of therapeutic plasmapheresis in TTP when combined with FFP transfusion and immunosuppressive treatments.

Heterogeneity of Cause, Care, and Prognosis in Severe Acute Kidney Injury in Hospitalized Patients: A Prospective Observational Study.

BACKGROUND: KDIGO (Kidney Disease: Improving Global Outcomes) defines acute kidney injury (AKI) solely by serum creatinine (SCr) and urine output variation. Severe AKI is a syndrome covering various clinical situations. OBJECTIVE: To describe severe AKI heterogeneity by department of hospitalization. DESIGN: This is a prospective observational single-center study. SETTING: Adult patients hospitalized in a French tertiary hospital from August 2016 to December 2017. PATIENTS: All adults with severe AKI, defined by dialysis for AKI or an increase in SCr above 354 µmol/L. MEASUREMENTS: Patient characteristics, clinical and laboratory presentation, AKI cause, medical indication for renal replacement therapy (RRT), planned palliative care, and vital status 30 days after severe AKI. METHODS: A global description of patient characteristics, care, and prognosis and comparison by department of hospitalization: intensive care unit (ICU), nephrology, and others. RESULTS: The study included 480 patients (73% men, median age: 72 years, range: 64-83), with medical histories including cardiovascular disease, diabetes, cancer, and chronic kidney disease. Principal causes were sepsis (104; 22%), hypovolemia (98; 20%), obstructive AKI (84; 18%), acute tubular necrosis (ATN; 74; 15%), and cardiorenal syndrome (51; 11%). Severe AKI was diagnosed in the ICU for 188 (39%) patients, the nephrology department for 130 (27%), and in other wards for 162 (34%). Patient characteristics differed by department for age, comorbidity, cause, and RRT use and indications. Palliative care was planned for 72 (15%) patients, most frequently in other wards. LIMITATIONS: We studied a subgroup of stage 3 KDIGO AKI patients in a single center without cardiac surgery. CONCLUSION: Patients hospitalized for severe AKI have frequent and various comorbidities, different clinical presentations, care, hospitalization in various departments, and different prognosis. The heterogeneity of this severe AKI implies the need for personalized care, which requires prognostic tools that include information besides SCr and diuresis.

CONTEXTE: Le KDIGO définit l'insuffisance rénale aigüe (IRA) uniquement par une variation de la créatinine sérique (SCr) et de la diurèse. L'IRA grave est un syndrome couvrant diverses situations cliniques. OBJECTIF: Décrire l'hétérogénéité de l'IRA grave selon l'unité d'hospitalisation. TYPE D'ÉTUDE: Étude observationnelle prospective menée dans un seul centre. SUJETS: Des adultes hospitalisés entre août 2016 et décembre 2017 dans un centre de soins tertiaires en France. PARTICIPANTS: Tous les adultes atteints d'IRA grave, définie par un traitement de dialyse ou un taux de SCr au-delà de 354 µmol/l. MESURES: Les caractéristiques du patient, le tableau clinique et de laboratoire, l'étiologie de l'IRA, l'indication médicale pour une thérapie de remplacement rénal (TRR), le plan de soins palliatifs et le statut vital 30 jours après l'épisode d'IRA grave. MÉTHODOLOGIE: Une description globale des caractéristiques des patients, des soins et du pronostic, ainsi qu'une comparaison selon l'unité d'hospitalisation: unité de soins intensifs (USI), néphrologie et autres. RÉSULTATS: L'étude portait sur 480 patients (73 % d'hommes) âgés de 64 à 83 ans (âge médian: 72 ans) avec des antécédents incluant maladies cardiovasculaires, diabète, cancer ou insuffisance rénale chronique. Les principales causes de l'IRA grave étaient une septicémie (104, 22 %), une hypovolémie (98, 20 %), une IRA obstructive (84, 18 %), une nécrose tubulaire aigüe (74, 15 %) ou un syndrome cardio-rénal (51, 11 %). Le diagnostic avait été posé à l'USI pour 188 patients (39 %), en néphrologie pour 130 patients (27 %) et dans d'autres unités pour 162 patients (34 %). Les caractéristiques des patients différaient entre les unités de soins en ce qui concerne l'âge, les comorbidités, l'étiologie et les indications de TRR. Un plan de soins palliatifs existait pour 72 patients (15 %), le plus souvent dans les autres unités. LIMITES: Nous avons étudié un sous-groupe de patients atteints d'IRA de stade 3 (classification KDIGO) dans un seul centre sans chirurgie cardiaque. CONCLUSION: Les patients hospitalisés pour une IRA grave présentent des comorbidités, des tableaux cliniques, des soins et des pronostics variés et sont admis dans différentes unités d'hospitalisation. Cette hétérogénéité de l'IRA grave met en relief le besoin de soins personnalisés qui nécessitent des outils pronostics basés sur des informations autres que la SCr et la diurèse.

A catastrophic antiphospholipid syndrome complicated with heparin-induced thrombocytopaenia, successfully managed with double filtration plasmapheresis, steroids and a direct thrombin inhibitor.

A middle-aged woman with history of antiphospholipid syndrome, admitted to our hospital for lethargy and persistent chest pain, developed during hospitalisation intracerebral transverse sinus and sigmoid vein thromboses, retinal thromboses, acute renal failure and cardiac involvement associated with thrombocytopaenia. Diagnosis of catastrophic antiphospholipid syndrome was made and treated with IV steroids, heparin infusion and double filtration plasmapheresis (DFPP) without fresh frozen plasma. Heparin-induced thrombocytopaenia was second diagnosed because of persistent severe thrombocytopaenia after 2 weeks of treatment associated with positive conversion of antibodies against platelet factor 4, and a positive functional assay. The clinical course was complicated by cerebellar haematomas that appeared a few days after the last session of DFPP. Heparin-induced thrombocytopaenia was managed by administration of argatroban, a direct thrombin inhibitor with an increase in platelet count. Neurologically, the patient recovered completely and was discharged on vitamin K antagonist treatment and regular dialysis.