Kidney involvement in myelodysplastic syndromes.

Introduction: The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. Methods: We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9 g/g, and median serum creatinine was 3.2 mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. Conclusion: The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

Daratumumab treatment in six highly sensitised solid organ transplant recipients: A case series and literature review.

We report data on six kidney or heart recipients who were administered daratumumab to treat or prevent antibody-mediated rejection (ABMR). To date, data are scarce concerning the use of daratumumab in solid organ transplantation and most reports show a decrease in donor-specific antigen (DSA) levels and an improvement in ABMR using a multiple myeloma daratumumab administration scheme, that is, with sequential systematic administration. Here, we report on the efficacy of daratumumab 1/ in reducing the histological signs of ABMR, 2/ in reducing the ability of DSA to bind to donor cells in vitro through negativation of flow cytometry crossmatching, 3/ in preferentially being directed towards antibodies sharing epitopes, suggesting that daratumumab may specifically target activated plasma cells, 4/ and when administered as a single dose. This last point suggests, for the first time, that, as for rituximab in auto-immune diseases, the scheme for daratumumab administration could be different for targeting DSA-producing plasma cells than for tumour cells.

Carfilzomib-associated thrombotic microangiopathy: clinical features and outcomes.

BACKGROUND AND HYPOTHESIS: Carfilzomib, a new proteasome inhibitor indicated for patients with relapsed/refractory myeloma, has been associated with cases of thrombotic microangiopathy (CFZ-TMA). The role of variants in the complement alternative pathway and therapeutic potential of complement blockade with eculizumab remain to be determined. METHODS: We report 37 cases of CFZ-TMA recorded in the French reference center for TMA with their clinical characteristics, genetic analysis and outcome according to treatments. RESULTS: A trigger was identified in more than half of cases, including 8 influenza and 5 SARS-CoV-2 cases. All patients presented with acute kidney injury (AKI) (KDIGO stage 3 in 31 (84%) patients) while neurological (n=13, 36%) and cardiac damage (n=7, 19%) were less frequent. ADAMTS13 and complement activity were normal (n= 28 and 18 patients tested) and no pathogenic variant in the alternative complement pathway was found in 7 patients tested.TMA resolved in most (n=34, 94%) patients but 12 (44%) still displayed stage 3 AKI at discharge. Nineteen (51%) patients were treated with therapeutic plasma exchange, 14 (38%) patients received corticosteroids and 18 (50%) were treated with eculizumab. However none of these treatments demonstrated a significant impact on outcomes. CONCLUSION: This study is the largest case series of CFZ-TMA since its approval in 2012. Patients present with severe AKI and experience frequent sequelae. Complement variants and blockade therapy do not seem to play a role in the pathophysiology and prognosis of the disease.

Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Series From the French Nephropathology Group.

RATIONALE & OBJECTIVE: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence without a diffuse crescentic glomerulonephritis nor serum anti-GBM antibodies by conventional enzyme-linked immunosorbent assay (ELISA). We characterized a series of patients with atypical anti-GBM disease. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022. FINDINGS: Among 38 potential cases, 25 were included, of whom 14 (56%) were female and 23 (92%) had hematuria. The median serum creatinine at diagnosis was 150 (IQR, 102-203) µmol/L and median urine protein-creatinine ratio (UPCR) was 2.4 (IQR, 1.3-5.2) g/g. Nine patients (36%) had endocapillary proliferative glomerulonephritis (GN), 4 (16%) had mesangial proliferative GN, 4 (16%) had membranoproliferative GN, 2 (8%) had pure and focal crescentic GN, 1 (4%) had focal segmental glomerulosclerosis, and 5 had glomeruli that were unremarkable on histopathology. Nine patients (36%) had crescents, involving a median of 9% of glomeruli. Bright linear staining for IgG was seen in 22 cases (88%) and for IgA in 3 cases (12%). The 9 patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at 1 year was 83% and did not appear to be associated with the light chain restriction. LIMITATIONS: Retrospective case series with a limited number of biopsies including electron microscopy. CONCLUSIONS: Compared with typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with an endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have a slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes. PLAIN-LANGUAGE SUMMARY: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized histologically by bright linear immunoglobulin staining along the GBM without diffuse crescentic glomerulonephritis or circulating anti-GBM antibodies. We report a case series of 25 atypical cases of anti-GBM nephritis in collaboration with the French Nephropathology Group. Compared with typical anti-GBM disease, we observed a slower disease progression. Patients frequently presented with heavy proteinuria and commonly had evidence of endocapillary or mesangial proliferative glomerulonephritis. About half of the patients displayed a monotypic immune staining pattern; they tended to be older, with less proteinuria, and commonly without glomerular crescents in biopsy specimens. No concomitant circulating monoclonal gammopathy was detected. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes.

C3 Glomerulopathy With Concurrent Thrombotic Microangiopathy: Clinical and Immunological Features.

RATIONALE & OBJECTIVE: C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients with C3GN and concomitant TMA lesions on biopsy registered from 2009 to 2019 in the French National Registry of C3GN. FINDINGS: Among 278 registered patients with C3GN, 16 (6%) had biopsy-proven glomerular and/or vascular TMA lesions. Their median age at diagnosis was 39 years (range, 7-76), and 59% were female. Fourteen of the 16 patients (88%) had an estimated glomerular filtration rate of<30mL/min/1.73m2 and 3 of 16 (19%) required dialysis. Twelve of the 14 evaluated patients (86%) showed evidence of mechanical hemolysis. Fifty percent of the patients had low C3 levels. Six of the 14 evaluated patients had a rare variant in complement genes, and 4 of the 16 patients (25%) had monoclonal gammopathy. Among the 16 patients, 10 (63%) received eculizumab, 5 (31%) received immunosuppressive therapy, and 4 (25%) received clone-targeted chemotherapy. Median kidney survival was 49 months. LIMITATIONS: Small retrospective case series with a limited number of biopsies including electron microscopy. CONCLUSIONS: Concomitant C3GN and TMA is extremely rare and is associated with poor kidney outcomes. Genetic or acquired abnormalities of the alternative complement pathway are common as is the presence of monoclonal gammopathy, which may inform the selection of treatment approaches.

Evaluation of Rituximab for Induction and Maintenance Therapy in Patients 75 Years and Older With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Importance: Older patients are underrepresented in studies of rituximab for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Little is known about outcomes and adverse events associated with the use of rituximab therapy among patients 75 years and older with ANCA-associated vasculitis. Objective: To examine outcomes and adverse events associated with the use of rituximab therapy in patients 75 years and older with ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Design, Setting, and Participants: This multicenter cohort study involved 93 patients 75 years and older with ANCA-associated vasculitis from 36 university and nonuniversity hospitals in France. Data were obtained from the French Vasculitis Study Group database between January 1, 2000, and July 1, 2018, and a call for observation sent to French Vasculitis Study Group members on June 6, 2019. Data analysis was performed from November 15 to December 31, 2021. Inclusion criteria included a diagnosis of GPA or MPA according to European Medicines Agency classification criteria and receipt of treatment with rituximab after age 75 years. Patients were excluded if they were missing relevant clinical or biological data. Data on race and ethnicity were not reported because inclusion of this information was not authorized by the ethics committee. Exposure: At least 1 infusion of rituximab as induction or maintenance therapy. Main Outcomes and Measures: Occurrence of remission, relapse, drug discontinuation, death, and serious infections (including types of serious infections). Results: Of 238 patients screened, 93 were included (median [IQR] age, 79.4 [76.7-83.1] years; 51 women [54.8%]); 52 patients (55.9%) had a diagnosis of GPA, and 41 (44.1%) had a diagnosis of MPA. Thirty patients (32.3%) received rituximab as induction therapy in combination with high-dose glucocorticoid regimens, 27 (29.0%) received rituximab as maintenance therapy, and 36 (38.7%) received rituximab as both induction and maintenance therapy. The median (IQR) follow-up was 2.3 (1.1-4.0) years. Among 66 patients who received rituximab as induction therapy, 57 (86.4%) achieved remission, and 2 (3.0%) experienced relapses. The incidence of serious infection was significantly higher when rituximab was used as induction therapy vs maintenance therapy (46.6 [95% CI, 24.8-79.7] per 100 patient-years vs 8.4 [95% CI, 3.8-15.9] per 100 patient-years; P = .004). Most infections (12 of 22 [54.5%]) were gram-negative bacterial infections. The incidence of death was 19.7 (95% CI, 7.2-42.9) per 100 patient-years among those who received rituximab as induction therapy and 5.3 (95% CI, 1.9-11.6) per 100 patient-years among those who received rituximab as maintenance therapy. Conclusions and Relevance: In this cohort study, rituximab therapy was associated with achievement and maintenance of remission in most patients 75 years and older with ANCA-associated vasculitis. The incidence of serious infections and death was high when rituximab was used as induction therapy in combination with high-dose glucocorticoid regimens but not when rituximab was used as maintenance therapy. Efforts might focus on reducing serious infections during the first months of therapy.

Patients of 75 years and over with ANCA-associated vasculitis have a lower relapse risk than younger patients: A multicentre cohort study.

BACKGROUND: Little is known about antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in older patients. We aim to study relapse risk of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in patients diagnosed after 75 years and compare it with those of patients aged 65-75 years. METHODS: Data from AAV patients aged ≥65 years were extracted from the French Vasculitis Study Group (FVSG) database and from a call for observation to FVSG members. Cox and Fine-Gray models were used to assess relapse risk, taking death into account either as a censoring or a competing event, respectively. RESULTS: The analysis included 219 patients aged ≥75 years (median 79) and 80 patients aged 65-75 years (median 70), of those 155 had GPA (52%), 136 MPA (45%), with 95 (32%) anti-proteinase 3 positivity and 179 (61%) anti-myeloperoxidase. Patients aged ≥75 years had a lower relapse risk in multivariate analysis (cause-specific hazards ratio [CSHR] 0.54, 95% CI [0.33-0.89], p = 0.016, Cox model; subdistribution hazard ratio [SHR] 0.46, 95% CI [0.29-0.74], p = 0.001, Fine-Gray model) after taking into account vasculitis type. Patients aged ≥75 years had a lower probability of being treated for remission maintenance with a combination of glucocorticoids and immunosuppressants (vs. glucocorticoids alone, HR 0.28, 95% CI [0.11-0.68], p = 0.005) after adjusting to Five Factor Score, although relapse-free survival was significantly longer when receiving such combination (CSHR 0.40, 95% [CI 0.24-0.67], p < 0.001). CONCLUSIONS: AAV patients ≥75 years have a lower relapse risk than patients aged 65-75 years despite a lower probability of having received maintenance therapy with a combination of glucocorticoids and immunosuppressants, but they still benefit from such treatment regimen.

Vasculitis associated with myelodysplastic syndrome and chronic myelomonocytic leukemia: French multicenter case-control study.

INTRODUCTION: Our objective was to evaluate characteristics, treatment and outcome of vasculitis associated with myelodysplastic syndrome (MDS) and chronic myelomonicytic leukemia (CMML) PATIENTS AND METHODS: Retrospective descriptive analysis of MDS/CMML-related vasculitis and comparison with MDS/CMML patients without dysimmune features. RESULTS: Seventy patients with vasculitis and MDS/CMML were included, with median age of 71.5 [21-90] years and male/female ratio of 2.3. Vasculitis was diagnosed prior to MDS/CMML in 31 patients (44%), and after in 20 patients. In comparison with MDS/CMML without autoimmune/inflammatory features, vasculitis with MDS/MPN showed no difference in MDS/CMML subtypes distribution nor International Prognostic Scoring System and CMML-specific prognostic (IPSS/CPSS) scores. Vasculitis subtypes included Giant cell arteritis in 24 patients (34%), Behçet's-like syndrome in 11 patients (20%) and polyarteritis nodosa in 6 patients (9%). Glucocorticoids (GCs) were used as first-line therapy for MDS/CMML vasculitis in 64/70 patients (91%) and 41 (59%) received combined immunosuppressive therapies during the follow-up. After a median follow-up of 33.2 months [1-162], 31 patients (44%) achieved sustained remission. At least one relapse occurred in 43 patients (61%). Relapse rates were higher in patients treated with conventional Disease Modifying Anti-Rheumatic Drug (DMARDs) (odds ratio 4.86 [95% CI 1.38 - 17.10]), but did not differ for biologics (odds ratio 0.59 [95% CI 0.11-3.20]) and azacytidine (odds ratio 1.44 [95% CI 0.21-9.76]) than under glucocorticoids. Overall survival in MDS/CMML vasculitis was not significantly different from MDS/CMML patients without autoimmune/inflammatory features (p = 0.5), but acute leukemia progression rates were decreased (log rank <0.05). CONCLUSION: This study shows no correlation of vasculitis diagnoses with subtypes and severity of MDS/CMML, and no significant impact of vasculitis on overall survival. Whereas conventional DMARDs seem to be less effective, biologics or azacytidine therapy could be considered for even low-risk MDS/CMML vasculitis.

Extracorporeal photopheresis for the treatment of graft rejection in 33 adult kidney transplant recipients.

Background - Extracorporeal photopheresis (ECP) has shown encouraging results in the prevention of allograft rejection in heart transplantation. However, the role of ECP in kidney transplant (KT) rejection needs to be determined. Methods - This multicentre retrospective study included 33 KT recipients who were treated with ECP for allograft rejection (23 acute antibody-mediated rejections (AMRs), 2 chronic AMRs and 8 acute cellular rejections (ACRs)). The ECP indications were KT rejection in patients who were resistant to standard therapies (n = 18) or in patients for whom standard therapies were contraindicated because of concomitant infections or cancers (n = 15). Results - At 12 months (M12) post-ECP, 11 patients (33%) had a stabilization of kidney function with a graft survival rate of 61%. The Banff AMR score (g + ptc + v) was a risk factor for graft loss at M12 (HR 1.44 [1.01-2.05], p < 0.05). The factorial mixed data analysis identified 2 clusters. Patients with a functional graft at M12 tended to have cellular and/or chronic rejections. Patients with graft loss at M12 tended to have acute rejections and/or AMR; higher serum creatinine levels; DSA levels and histologic scores of AMR; and a longer delay between the rejection and ECP start than those of patients with functional grafts. Conclusions - ECP may be helpful to control ACR or moderate AMR in KT recipients presenting concomitant opportunistic infections or malignancies when it is initiated early.

Predicting the Impact of Diffuse Alveolar Damage through Open Lung Biopsy in Acute Respiratory Distress Syndrome-The PREDATOR Study.

The aim of this retrospective and international study is to identify those clinical variables associated with diffuse alveolar damage (DAD), and to explore the impact of DAD on hospital mortality risk. Inclusion criteria were: adult patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy (OLB) during their intensive care unit (ICU) management. The main end-points were: DAD and hospital mortality. In the training (n = 193) and validation cohorts (n = 65), the respiratory rate (odd ratio (OR) 0.956; confidence interval (CI) 95% 0.918; 0.995) and coronary ischemia (OR 5.974; CI95% 1.668; 21.399) on the day of ARDS had an average area under the receiver operating characteristic curve (AUROC) of 0.660 (CI95% 0.585; 0.736) and 0.562 (0.417; 0.706), respectively. PEEP (OR 1.131; CI95% 1.051; 1.218) and coronary ischemia (OR 6.820; CI95% 1.856; 25.061) on the day of OLB had an average AUROC of 0.696 (CI95% 0.621; 0.769) and 0.534 (CI95% 0.391; 0.678), respectively, to predict DAD. DAD (OR 2.296; CI95% 1.228; 4.294), diabetes mellitus requiring insulin (OR 0.081; CI95% 0.009; 0.710) and the respiratory rate (OR 1.045; CI95% 1.001; 1.091) on the day of ARDS had an average AUROC of 0.659 (CI95% 0.583; 0.737) and 0.513 (CI95% 0.361; 0.664) to predict hospital mortality and DAD (OR 2.081; CI95% 1.053; 4.114), diabetes mellitus requiring insulin (OR 0.093; CI95% 0.009; 0.956), PaCO2 (OR 1.051; CI95% 1.019; 1.084), and platelets count (OR 0.999; CI95% 0.999; 0.999) the day of OLB had an average AUROC of 0.778 (CI95% 0.710; 0.843) and 0.634 (CI95%0.481; 0.787) to predict hospital mortalty in the training and validation cohorts, respectively. In conclusion, DAD could not to be predicted clinically and was significantly associated with hospital mortality.

Muscle wasting in patients with end-stage renal disease or early-stage lung cancer: common mechanisms at work.

BACKGROUND: Loss of muscle mass worsens many diseases such as cancer and renal failure, contributes to the frailty syndrome, and is associated with an increased risk of death. Studies conducted on animal models have revealed the preponderant role of muscle proteolysis and in particular the activation of the ubiquitin proteasome system (UPS). Studies conducted in humans remain scarce, especially within renal deficiency. Whether a shared atrophying programme exists independently of the nature of the disease remains to be established. The aim of this work was to identify common modifications at the transcriptomic level or the proteomic level in atrophying skeletal muscles from cancer and renal failure patients. METHODS: Muscle biopsies were performed during scheduled interventions in early-stage (no treatment and no detectable muscle loss) lung cancer (LC), chronic haemodialysis (HD), or healthy (CT) patients (n = 7 per group; 86% male; 69.6 ± 11.4, 67.9 ± 8.6, and 70.2 ± 7.9 years P > 0.9 for the CT, LC, and HD groups, respectively). Gene expression of members of the UPS, autophagy, and apoptotic systems was measured by quantitative real-time PCR. A global analysis of the soluble muscle proteome was conducted by shotgun proteomics for investigating the processes altered. RESULTS: We found an increased expression of several UPS and autophagy-related enzymes in both LC and HD patients. The E3 ligases MuRF1 (+56 to 78%, P < 0.01), MAFbx (+68 to 84%, P = 0.02), Hdm2 (+37 to 59%, P = 0.02), and MUSA1/Fbxo30 (+47 to 106%, P = 0.01) and the autophagy-related genes CTPL (+33 to 47%, P = 0.03) and SQSTM1 (+47 to 137%, P < 0.01) were overexpressed. Mass spectrometry identified >1700 proteins, and principal component analysis revealed three differential proteomes that matched to the three groups of patients. Orthogonal partial least square discriminant analysis created a model, which distinguished the muscles of diseased patients (LC or HD) from those of CT subjects. Proteins that most contributed to the model were selected. Functional analysis revealed up to 238 proteins belonging to nine metabolic processes (inflammatory response, proteolysis, cytoskeleton organization, glucose metabolism, muscle contraction, oxidant detoxification, energy metabolism, fatty acid metabolism, and extracellular matrix) involved in and/or altered by the atrophying programme in both LC and HD patients. This was confirmed by a co-expression network analysis. CONCLUSIONS: We were able to identify highly similar modifications of several metabolic pathways in patients exhibiting diseases with different aetiologies (early-stage LC vs. long-term renal failure). This strongly suggests that a common atrophying programme exists independently of the disease in human.

Ischemia reperfusion injury in kidney transplantation: A case report.

RATIONALE: Kidney transplantation is considered the best treatment for patients with end stage renal disease. Ischemia- reperfusion injury (IRI) is an evitable event after deceased donor transplantation and influences short term and long term graft outcome. Few data on IRI's histology in the setting of kidney transplantation are available in the literature despite its frequency and its severity. PATIENT CONCERNS: A 64-year-old patient was admitted for his 1st kidney transplantation. There were no pre-existing immunization. The surgery proceeded without complications; with cold ischemia estimated at 37 h 50 min and warm ischemia at 44 min. The immunosuppression protocol was as follows: induction by thymoglobulins, mycophelonate mofetil, corticosteroids. Few hours after transplantation, the patient remained anuric and the biological assessment highlighted in addition to renal failure, hyperlactatemia at 5 mmol/L and a high increase in lactate deshydrogenase (LDH) at 5239 U/L. An abdominopelvic angio-scanner was performed urgently to eliminate the hypothesis of thrombosis of the artery or vein of the graft. A kidney biopsy was performed the day after the transplant and revealed massive lesions of acute tubular necrosis including apoptosis, autophagy-associated cell death, and necrosis. Microvascular dysfunction with increased vascular permeability and endothelial cell inflammation were also present. Activation of coagulation is represented by thrombi in the lumens of the glomerular capillaries. DIAGNOSIS: The diagnosis was ischemia reperfusion injury responsible for delayed graft function (DGF). INTERVENTIONS: Immunosuppressive regimen was delayed use of calcineurin inhibitors, mycophenolate mofetil, and corticosteroids. OUTCOMES: At 1 year post transplant, the patient has a renal autonomy with a graft function stable and physiological proteinuria. LESSONS: The main clinical consequences of IRI in kidney transplant are DGF, acute and chronic graft rejection, and chronic graft dysfunction. Reducing IRI is one of the most relevant challenge in kidney transplantation.

Histologically proven acute tubular necrosis in a series of 27 ICU patients.

PURPOSE: Since renal biopsy is rarely performed for identifying acute tubular necrosis in ICU patients, there is little information on the real histopathological abnormalities observed in such situations. MATERIALS AND METHODS: The clinical data of 27 patients with a confirmed diagnostic of acute tubular necrosis issued from two recent series gathering 125 patients who had renal biopsy during their ICU stay were reviewed. They were divided into sepsis (n = 14) and non-sepsis (n = 13) groups. Histopathologic lesions were reanalyzed and semi-quantitatively graded by a pathologist without knowledge of clinical characteristics of the patients. RESULTS: SAPS2 and SOFA scores were identical in the two groups. Half of the patients had neither sepsis nor shock. The histopathological score was higher in the septic than in the non-septic group: 9 [IC; 9-11] vs 7 [IC 5.25-8.75]; p = 0.01. There was no striking histopathological difference between septic and non-septic patients. However, the cytotoxic edema score was higher (3 [1; 3] vs 1 [0; 1]; p = 0.006), and interstitial infiltration with polymorphonuclears was more frequent (p = 0.02) in septic than in non-septic patients. CONCLUSIONS: Septic and non-septic ICU patients with ATN had similar histopathologic features but lesions were more severe than in septic than in non-septic patients.

Diagnostic yield and therapeutic impact of open lung biopsy in the critically ill patient.

BACKGROUND: Open lung biopsy (OLB) is a rare procedure in intensive care units (ICUs) for therapeutic management of acute respiratory failure (ARF). The purpose of this study was to analyze the diagnostic yield, therapeutic contribution and complications of OLB in ICU patients with ARF of unclear etiology, including acute respiratory distress syndrome (ARDS) and ARDS mimics. METHODS: Retrospective study conducted in a 10-bed ICU over a 13-year period. Patients undergoing OLB for ARF with undiagnosed infiltrates on CT scan were included. ARDS was defined according to Berlin criteria, and ARDS mimics as a condition looking like ARDS except for the presence of a known cause. OLB was contributive when the OLB findings yielded a specific diagnosis resulting in a change in the patients' treatment or management. RESULTS: Forty six patients were included (sex ratio = 2.5, median and [interquartile range] age = 69 [59-77] years, and admission SAPS II = 42 [33-50]. ARF corresponded to ARDS in 22 patients and to ARDS mimics in 16. OLB yielded 61 diagnoses in 45 patients including diffuse alveolar damage (N = 21), lung fibrosis (N = 18), and organizing pneumonia (N = 11). OLB was contributive in 37 patients (80%), including 13/16 ARDS mimickers. The main contributions of OLB were the introduction or maintenance of steroids (N = 32) and discontinuation of antibiotics (N = 9). In 4 patients OLB resulted directly in the decision to forgo life-sustaining treatment. OLB complications occurred in 16 patients (35%), in one case associated with fatal outcome. CONCLUSION: OLB can play a useful role in the management of ICU patients with ARF of undetermined origin, including ARDS mimickers. Further studies should be done to identify the groups of ICU patients likely to benefit from the procedure with minimum risk.

Membranous Nephropathy and Intrarenal Extramedullary Hematopoiesis in a Patient With Myelofibrosis.

Kidney disease in the setting of a hematologic malignancy is common, with the frequency and type of kidney disease varying depending on the specific malignancy. Various glomerular diseases and tumor infiltration of the kidneys have been reported in patients with lymphoproliferative disorders. Descriptions of kidney involvement in myeloproliferative disorders have been much rarer. We report a case of membranous nephropathy accompanied by kidney injury in a patient with primary myelofibrosis with additional features considered related to the patient's myeloproliferative disorder. A 63-year-old patient with primary myelofibrosis underwent kidney biopsy to investigate nephrotic-range proteinuria and reduced kidney function. Histologic analysis revealed mesangial sclerosis and hypercellularity, changes indicative of membranous nephropathy, and infiltration of hematopoietic cells into the renal interstitium, peritubular capillaries, and perirenal tissue consistent with extramedullary hematopoiesis. He was treated with renin-angiotensin blockade and a Janus kinase inhibitor, resulting in improvement in kidney function and proteinuria.

Immunotactoid glomerulopathy leading to the discovery of POEMS syndrome
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Monoclonal gammopathy of renal significance (MGRS) can manifest in many different ways depending on the nature of the immunoglobulin and its physicochemical properties. MGRS can lead to the discovery of a hematological malignancy. We report the case of a 32-year-old female patient who underwent renal biopsy on account of an impure nephrotic syndrome associated with immunoglobulin (Ig)G κ monoclonal gammopathy. Histological analysis revealed membranoproliferative glomerulonephritis with IgG, IgM, κ, λ, and C3 deposits. Due to an unfavorable progression, a second renal biopsy was performed. Electron microscopy analysis revealed an immunotactoid glomerulopathy. At the same time, a POEMS syndrome diagnosis (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin abnormalities) was confirmed in light of the following: 1) IgG κ monoclonal gammopathy, 2) axonal neuropathy, 3) osteosclerosis, 4) melanoderma, 5) hepatosplenomegaly and adenopathies, 6) Castleman disease, and 7) edema. Our observation is the first case of immunotactoid glomerulopathy leading to the discovery of a POEMS syndrome. Renal involvement in POEMS syndrome typically exhibits a thrombotic microangiopathy-like membranoproliferative glomerulonephritis appearance associated with endothelial lesions stigmata. However, monoclonal immunoglobulin deposition disorder should be considered in the event of an atypical case. In this indication, electron microscopy is the examination of choice for assessing immunoglobulin deposition nephropathy.
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Bile Cast Nephropathy Caused by Obstructive Cholestasis.

Acute kidney injury (AKI) is a major complication in patients with liver disease. Although hepatorenal syndrome is frequently involved, bile cast nephropathy, characterized by tubular bile cast formation, has been scarcely described in the setting of severe liver failure. Few renal histology studies are available in these patients. We describe a case of bile cast nephropathy in a patient with obstructive cholestasis caused by stones in the common bile duct. The kidney biopsy confirmed this diagnosis, with several green casts in tubular lumens, tubular injury, and bilirubin composition of the tubular casts with Hall stain. The patient had no confounding cause of kidney failure, and complete kidney recovery followed removal of the bile duct obstruction. This case shows that severe cholestasis is sufficient to cause AKI, and that AKI can be reversible after treatment of the biliary obstruction.

Antineutrophilic cytoplasmic antibody-associated vasculitis and malignant hemopathies, a retrospective study of 16 cases.

OBJECTIVES: ANCA-associated vasculitis are severe autoimmune pathologies that are characterized by inflammation and necrosis of the small vessels. The physiopathological mechanisms are complex and have yet to be totally elucidated. Several environmental factors have been described as being associated: medications, infectious agents… and rarely, neoplasms. METHODS: We performed a retrospective multicenter study over a period of 12 years with a view to describing the association of ANCA-associated vasculitis and malignant hemopathies, excluding hemopathies secondary to vasculitis treatment. RESULTS: Sixteen patients with ANCA-associated vasculitis with an hemopathy were identified. The gender ratio was 7 and the mean age was 65 years. The frequency of this association is estimated at 1%. The ANCA-associated vasculitis were micropolyangiitis (n=7), followed by granulomatous polyangiitis (n=4), vasculitis limited to the kidney (n=3), and eosinophilic granulomatous polyangiitis (n=2). The associated malignant hemopathies were mainly non-Hodgkin's lymphoma in seven cases and myelodysplasia in five cases. The other hemopathies were: Hodgkin's disease, hypereosinophilic syndrome, and Waldenström's macroglobulinemia. Hemopathy treatment was associated with vasculitis treatment in seven cases. CONCLUSION: The association of ANCA-associated vasculitis and malignant hemopathy is rare but must nevertheless be recognized because: (i) the clinical signs of both pathologies are not specific, (ii) the survival scores that are used for ANCA-associated vasculitis do not appear to be applicable, (iii) both pathologies must be taken into account in order to implement an effective therapeutic strategy that limits the inherent risks.