Replacement of disposable by reusable care materiel is a mandatory question in sustainability management in nephrology. Recommandations have already been edited for individual protection in the operating room and the DGOS (Direction g & eacute;n & eacute;rale de l'offre de soins) will soon launch an experimentation in the reuse of some catheters and endoscopes. The literature is unanimous on the advantage, in the fields studied, of reuse over disposable material regarding green house gaz emissions. However, this advantage can be lost when considering water consumption that partly results from washing and sterilization activities. Our article aims to encourage nephrologists to start applying some measures in their clinical practice and be aware of the coming innovations.

Rationale & Objective: Atypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence fl uorescence 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 fi ed 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) mu mol/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.

IntroductionImmunoglobulin A nephropathy (IgAN) associated with cirrhosis is frequent but often overlooked because it is largely considered silent. Until now, little has been known about their presentation and outcomes.MethodsWe conducted a retrospective multicenter study on patients with kidney biopsy-proven cirrhosis-related IgAN (cirrhosis-IgAN), diagnosed between 2009 and 2022. We mixed them up with 83 primary IgAN (pIgAN) diagnosed during the same period, using a partitioning clustering approach, to determine common clinicopathological profiles.ResultsAll the 46 patients with cirrhosis-IgAN had an excessive alcoholic consumption. Clinical presentation was severe with acute kidney injury (AKI) in 79%; alternative causes of AKI was found in 62% of cases. Three clinicopathological clusters were identified as follows: the first one represented chronic involvement, the second one could be assimilated to mild disease, and the third one corresponded to a membranoproliferative glomerulonephritis (MPGN) pattern and was associated with heavy proteinuria and intrinsic AKI (without alternative causes). Whereas the first 2 clusters were equally distributed between pIgAN and cirrhosis-IgAN, the third was more frequent in patients with cirrhosis. The cumulative mortality rate in cirrhosis-IgAN was 26% and 46% at 1-year and 3-years, respectively. Steroid exposure and moderate or severe AKI were associated with higher mortality and steroid exposure was associated with the occurrence of severe infection.ConclusionOur results suggest that high AKI incidence is related to extrinsic causes in most cases but can also be driven by IgA-dominant MPGN in a subset of patients. Steroid use was associated with infectious disease and mortality. Further studies are needed to clarify the role of immunosuppressive treatment in cirrhosis-IgAN patients.

Intestinal microsporidiosis caused by Enterocytozoon bieneusi is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication. We aimed to describe therapeutic management of E. bieneusi infections in this context. We conducted a French nationwide observational retrospective study on reported cases of E. bieneusi infections in SOT recipients. We identified 154 cases: 64 (41.6%) were managed by simply modifying the immunosuppressive regimen, 54 (35.1%) were given fumagillin, and 36 (23.4%) were given nitazoxanide. Clinical remission rate ranged from 77.8% to 90.7% and was not significantly different between therapeutic strategies but tended to be lower with nitazoxanide. Stool negativization rate was highest with fumagillin (91.7%) and lowest with nitazoxanide (28.6%). Relapses occurred in 6.9% of cases and were more frequent with nitazoxanide (14.3%). This study shows that tapering immunosuppression can result in a satisfactory remission rate but is sometimes accompanied by relapses. Nitazoxanide had limited effectiveness, whereas fumagillin had good results that provide a solid rationale for bringing fumagillin back to market.Trial Registration NumberClinicalTrials.gov ID: NCT05417815.

Background IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. Methods We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR <= 30 ml/ min per 1.73 m(2) at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. Results We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m(2) in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR <= 30 ml/min per 1.73 m(2). Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level >= 5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. Conclusions IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (>= 5 g/L) had more severe kidney disease.

Background Cancer-associated thrombotic microangiopathy (TMA) is a rare disease, with a poor prognosis. The classical treatment is urgent chemotherapy. Few data are available on the efficacy of plasma exchange (PE) and eculizumab in these patients. Methods Cases of cancer-related TMA treated between January 2008 and December 2019 in 12 French treatment centres were retrospectively analysed, excluding cases associated with chemotherapy and stem cell transplantation. Patients were divided into four groups depending on the treatment received: none, PE therapy alone, chemotherapy, with or without PE therapy, or eculizumab, with or without chemotherapy and PE therapy. Results The data of 59 patients with cancer-associated TMA were analysed. Twenty of these cases were related to a cancer recurrence. The cancer was metastatic in 90% of cases (53/59). Bone marrow invasion was observed in 20/41 biopsies. Some laboratory results, including disseminated intravascular coagulation high ferritin and C-reactive protein, were suggestive of cancer. None of the 16 patients whose alternative complement pathway was assessed had abnormal levels of protein expression or activity. The median survival time was 27 days. Chemotherapy was significantly associated with improved survival, with a 30-day survival rate of 85% (17/20) among patients who received PE and chemotherapy, versus 20% (3/15) among patients who received PE alone. Patients treated with eculizumab in addition to chemotherapy and PE therapy did not have longer overall survival or higher haematological remission rates than those treated with chemotherapy and PE therapy alone. Renal remission rates were non-significantly higher, and times to remission non-significantly shorter, in the eculizumab group. Conclusions Nephrologists and oncologists should make themselves aware of cancer diagnoses in patients with TMA and bone marrow biopsies should be performed systematically in these cases. All 59 patients had poor survival outcomes, but patients treated with urgent initiation of chemotherapy survived significantly longer than those who were not.

Abstract Background and Aims Thrombotic microangiopathy (TMA) are a heterogeneous group of diseases characterized by mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. In patients with cancer, TMAs are frequently induced by antineoplastic drugs but may be related to the malignant disease itself. Small series have reported poor prognosis. Only chemotherapy succeeded in lengthening life expectancy, even if few reports have described efficacy of therapeutic plasma exchange (TPE) or Eculizumab. Complement regulation was not studied in these publications, as the pathophysiology was rarely explored. In this study, we investigated retrospectively 59 cases of cancer-associated TMAs, to describe characteristics at diagnosis and efficacy of treatment. Method We conducted a retrospective multicentric observational study including all patients with a diagnosis of cancer-associated TMA, hospitalized in nephrological intensive care units (members of the French Intensive Care Network), between 2008 and 2019. We excluded patients receiving chemotherapy known to cause TMAs. We analyzed clinical and biological characteristics at diagnosis. We reported complement analysis when available. We defined four distinct treatment groups: No treatment (N), Plasmapheresis (P), Chemotherapy with or without chemotherapy (C+P), Eculizumab with or without Chemotherapy or Plasmapheresis (E+C+P). Renal remission and global survival were compared according to treatment group. Results We included 59 patients admitted to intensive care units for cancer-associated TMA. Twenty patients had a past history of cancer. Fifty percent was female, and mean age was 62.8 years. The primary cancer was breast (23.7%), lung (18.6%), stomach (10.2%), and prostate (10.2%). Adenocarcinoma was the most frequent histologic subtype (47.5%). The cancer was metastatic in almost cases (89.8%). At presentation, TMA manifestations were pulmonary (57.6%), neurologic (49.2%), bone pain (30.5%), and disseminated intravascular coagulopathy (DIVC) (55.9%). Forty-one patients had a bone marrow aspiration and/or biopsy. Among them, medullar metastases were found in 20 patients (48.7%). We observed low C3 in 14.7% of cases suggesting an activation of the alternative pathway. No genetic analysis was performed. Only one patient had an undetectable ADAMTS13 <5% without inhibitory ADAMTS13 antibodies. Renal failure was seen in 28 patients whom 63.7% had severe grade 3 acute kidney injury. Renal biopsy was performed in 6 patients with severe arteriolar TMA lesions. Seventeen patients had no treatment (N), fifteen patients were treated with TPE (P), twenty patients received chemotherapy with TPE (C+P), and seven patients received Eculizumab with TPE (E). Hematological and renal remission was not significantly different between treatment groups (p=0.74 and p=0.10 respectively). Mortality was high, 52.5% at one month, 90% after one year of follow-up. The median duration of survival was 27 days [8.5;95.5] in patients who received treatment. Survival was improved in (C+P) and (E+C+P) groups, significantly (p<0.0001). Conclusion We report the largest series of cancer-associated TMAS since the advent of Eculizumab for the treatment of HUS. Typical presentation included old age, bone pain, dyspnea, and DIVC. These symptoms, when associated with TMA, should therefore suggest a diagnosis of cancer. Bone marrow aspiration or biopsy led to diagnosis of cancer in half of cases, and should be systematically performed to rapidly confirm diagnosis. The overall prognosis remained dramatically poor, with a mortality rate of 90% in the first year. Chemotherapy is probably the most efficient therapy to delay the death. C3 serum level was decreased in only 7 patients, suggesting that the pathophysiology of cancer-associated TMA is not linked to complement activation. As a result, neither TPE nor Eculizumab improved survival rate.

Microvascular injury, including thrombotic microangiopathy, has been widely reported as a hallmark pathologic feature of organ injury in the setting of coronavirus disease 2019 (COVID-19).1Ackermann M. Verleden S.E. Kuehnel M. et al.Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19.N Engl J Med. 2020; 383: 120-128Crossref PubMed Scopus (3871) Google Scholar Accumulating data suggest that complement activation is implicated in the pathogenesis of COVID-19, including endothelial cell damage.2Noris M. Benigni A. Remuzzi G. The case of complement activation in COVID-19 multiorgan impact.Kidney Int. 2020; 98: 314-322Abstract Full Text Full Text PDF PubMed Scopus (243) Google Scholar, 3Java A. Apicelli A.J. Liszewski M.K. et al.The complement system in COVID-19: friend and foe?.JCI Insight. 2020; 5e140711Crossref PubMed Scopus (254) Google Scholar, 4Shen B. Yi X. Sun Y. et al.Proteomic and metabolomic characterization of COVID-19 patient sera.Cell. 2020; 182: 59-72.e15Abstract Full Text Full Text PDF PubMed Scopus (962) Google Scholar, 5Peffault de Latour R. Bergeron A. Lengline E. et al.Complement C5 inhibition in patients with COVID-19 - a promising target?.Haematologica. 2020; 105: 2847-2850Crossref PubMed Scopus (59) Google Scholar Some of these features are characteristic of atypical hemolytic uremic syndrome (aHUS), a prototypic disease of complement-mediated endothelial cell injury. We report the first case of aHUS relapse triggered by COVID-19. The patient, a 28-year-old white woman, was diagnosed with aHUS at the age of 3. Genetic analysis revealed the presence of a heterozygous pathogenic variant (R59Stop) in the membrane cofactor protein–encoding gene. Subsequently, she presented 3 aHUS relapses at the age of 5, 20, and 27 years. The second relapse required dialysis before hematologic and renal remission was obtained following 4 plasma exchanges and treatment with eculizumab for 12 months. The third relapse, triggered by an extrauterine pregnancy, was treated with 3 months of eculizumab. Kidney biopsy performed at that time revealed moderate interstitial (20%) and glomerular (20%) fibrosis. The patient had chronic kidney disease stage 3B (glomerular filtration rate = 42 ml/min per 1.73 m2 estimated using the Modification of Diet in Renal Disease formula) and hypertension requiring a treatment combining a calcium channel blocker and an angiotensin-converting enzyme inhibitor. In September 2020, she presented with fever, dysphagia, and headache. Clinical examination showed moderate fever, an erythematous throat, infracentimetric cervical adenopathies, and hypertension (150/105 mm Hg). She had no lung involvement with a normal chest X-ray. Laboratory tests showed mechanical hemolytic anemia (hemoglobin = 8.4 g/dl, lactate dehydrogenase level at 1.5× the upper limit of normal, and undetectable haptoglobin), mild thrombocytopenia (platelet count = 106 G/l), acute kidney injury (serum creatinine = 2.6 mg/dl vs. 1.7 mg/dl at baseline), and significant proteinuria (protein-to-creatinine ratio of 0.21 g/mmol vs. 0.05 at baseline). aHUS relapse was diagnosed, and the patient was admitted to our nephrology department. In the context of the re-emergence of the SARS-CoV-2 pandemic in our region, COVID-19 was suspected and confirmed by a positive polymerase chain reaction test in a nasopharyngeal swab. Additional workup showed a decreased C3 serum level (0.65 g/L; normal range, 0.9–1.8) and a normal C4 level. Inflammatory markers were normal or moderately increased (C-reactive protein < 0.4 mg/dl [<10], ferritin = 392 μg/l [13–150], D-dimer = 512 ng/mL [<500], and interleukin-6 = 1.8 pg/mL [< 7]). Serum creatinine peaked at 2.9 mg/dl, and the platelet count decreased to 88 G/l. Treatment with the C5 blocker eculizumab was immediately restarted combined with penicillin prophylaxis and anticoagulation due to the increased risk of thrombosis in the setting of COVID-19.6Zhang L. Feng X. Zhang D. et al.Deep vein thrombosis in hospitalized patients with COVID-19 in Wuhan, China: prevalence, risk factors, and outcome.Circulation. 2020; 142: 114-128Crossref PubMed Scopus (332) Google Scholar Seven days after the start of eculizumab, the hematologic parameters (platelet count = 191 G/l) and renal function (serum creatinine = 2.2 mg/dl) improved, and the patient was discharged from the hospital. One month after diagnosis, the D-dimer level was normal (261 ng/ml), haptoglobin remained undetectable, and a mild decrease in the C3 plasma level persisted (0.65 g/l). Renal function improved, but serum creatinine (2.0 mg/dl) had not returned to baseline values. It is well established that aHUS relapse may be precipitated by infections, including viral pathogens such as influenza or H1N1 virus.7Allen U. Licht C. Pandemic H1N1 influenza A infection and (atypical) HUS--more than just another trigger?.Pediatr Nephrol. 2011; 26: 3-5Crossref PubMed Scopus (41) Google Scholar,8Fakhouri F. Fila M. Provôt F. et al.Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation.Clin J Am Soc Nephrol. 2017; 12: 50-59Crossref PubMed Scopus (142) Google Scholar This case is an illustration that COVID-19 is to be added to the list of the potential triggers of aHUS relapse. In this setting, the deleterious effect of the coronavirus 19 may arise from (i) a direct toxic effect on endothelial cells, as suggested by autopsies studies,1Ackermann M. Verleden S.E. Kuehnel M. et al.Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19.N Engl J Med. 2020; 383: 120-128Crossref PubMed Scopus (3871) Google Scholar and/or (ii) a complement activation with ultimately complement-mediated endothelial damage, most particularly in patients with a constitutional defect in complement regulation, as in the patient presented herein. Indeed, it has recently been shown that, in vitro, SARS-CoV-2 activates the complement alternative pathway via its spike surface protein.9Yu J. Yuan X. Chen H. et al.Direct activation of the alternative complement pathway by SARS-CoV-2 spike proteins is blocked by factor D inhibition.Blood. 2020; 136: 2080-2089Crossref PubMed Google Scholar Similarly, markers of complement activation, including soluble C5b-9, are increased in a significant proportion of COVID-19 patients and correlate to the severity and prognosis of the disease prognosis.4Shen B. Yi X. Sun Y. et al.Proteomic and metabolomic characterization of COVID-19 patient sera.Cell. 2020; 182: 59-72.e15Abstract Full Text Full Text PDF PubMed Scopus (962) Google Scholar,5Peffault de Latour R. Bergeron A. Lengline E. et al.Complement C5 inhibition in patients with COVID-19 - a promising target?.Haematologica. 2020; 105: 2847-2850Crossref PubMed Scopus (59) Google Scholar Furthermore, C3 deficiency protects against the development of SARS-CoV infection in mice.10Gralinski L.E. Sheahan T.P. Morrison T.E. et al.Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis.mBio. 2018; 9 (e01753-18)Crossref PubMed Scopus (520) Google Scholar Finally, complement activation may also contribute to the hypercoagulable state in COVID-19 patients.3Java A. Apicelli A.J. Liszewski M.K. et al.The complement system in COVID-19: friend and foe?.JCI Insight. 2020; 5e140711Crossref PubMed Scopus (254) Google Scholar Our patient had a clinically mild form of COVID-19 and no marked systemic inflammation. Nevertheless, virus-driven complement activation did occur and was most probably overamplified in the absence of a tight control of the complement alternative pathway, leading to the development of thrombotic microangiopathy. However, this is to date the only reported case of aHUS relapse triggered by COVID-19 despite the worldwide spread of COVID-19 epidemics. Nevertheless, our observation underlines the need for close monitoring of aHUS patients who discontinued eculizumab in the setting of COVID-19. It is also a further indication that complement blockade should not be discontinued in aHUS during infectious episodes, COVID-19 not being an exception. FF has received consultancy and/or speaker honoraria from Roche, Alexion, Apellis, Achillion, Novartis, and Alnylam. VF-B has received fees from Alexion Pharmaceuticals, Roche, Apellis, Novartis, and Baxter for invited lectures and/or board membership and is the recipient of a research grant from Alexion Pharmaceuticals and Apellis. All the other authors declared no competing interests. The case of complement activation in COVID-19 multiorgan impactKidney InternationalVol. 98Issue 2PreviewThe novel coronavirus disease COVID-19 originates in the lungs, but it may extend to other organs, causing, in severe cases, multiorgan damage, including cardiac injury and acute kidney injury. In severe cases, the presence of kidney injury is associated with increased risk of death, highlighting the relevance of this organ as a target of SARS-CoV-2 infection. COVID-19–associated tissue injury is not primarily mediated by viral infection, but rather is a result of the inflammatory host immune response, which drives hypercytokinemia and aggressive inflammation that affect lung parenchymal cells, diminishing oxygen uptake, but also endothelial cells, resulting in endotheliitis and thrombotic events and intravascular coagulation. Full-Text PDF

Mild eosinophilia is not uncommon in hemodialysis patients. It is historically related in most cases to allergic reactions to the extracorporeal circuit components and more rarely to various conditions ranging from infections to malignancies.1Hildebrand S. Corbett R. Duncan N. Ashby D. Increased prevalence of eosinophilia in a hemodialysis population: Longitudinal and case control studies.Hemodial Int. 2016; 20: 414-420Crossref PubMed Scopus (6) Google Scholar,2Gauckler P. Shin J.I. Mayer G. Kronbichler A. Eosinophilia and Kidney Disease: More than Just an Incidental Finding?.J Clin Med. 2018; 7Crossref PubMed Scopus (10) Google Scholar We report on six patients (Table 1) who developed an acute severe eosinophilia (median peak of eosinophil count, 8.6 ± 3.3 G/) that was induced by the insertion of tunneled central venous catheters. The link between eosinophilia and central venous catheters is substantiated by causality assessment,3Miremont-Salamé G. Théophile H. Haramburu F. et al.Causality assessment in pharmacovigilance: The French method and its successive updates.Therapie. 2016 Apr; 71: 179-186Crossref PubMed Scopus (166) Google Scholar based first on chronological criteria (Figure 1): while eosinophil blood count was normal for several years, it dramatically increased after the catheter insertion, persisted at high levels as long as the catheter was left in place and resolved shortly after catheter withdrawal. Besides, in patients 3 and 4, eosinophilia recurred after a further venous catheter insertion. Furthermore, comprehensive etiological work-up (parasites culture and serological tests, autoantibodies tests, bone marrow aspiration, tests for FIP1L1-PDGFRA and BCR-ABL rearrangements, thoraco-abdominal and pelvic CT-scan) for underlying malignancy, infection, allergy or autoimmune disease and assessment for medications and dialysis membrane replacement, failed to identify any alternative cause for eosinophilia (semiological criteria for causality).4Gotlib J. World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management.Am J Hematol. 2017; 92: 1243-1259Crossref PubMed Scopus (106) Google Scholar,S1Table 1Characteristics of six dialysis patients with tunneled catheter-related eosinophiliaPatientGender, Age (y)Type of venous catheter (brand)Time from catheter insertion to Eo (days)Eo peak (G/L) (time from catheter, days)Eo related manifestationsEo duration (months)Eo recovery time after catheter withdrawal (days)P1M, 48Tunneled jugular catheter (HEMOTECH®)90 (first available test after catheter)10 (183)Ulcerative colitisPulmonary nodules (Figure 2)1315P2M, 50Tunneled jugular catheter (HEMOTECH®)Intermittent use of fistula322 (first available test after catheter)4.8 (336)Urticarial rash12.50P3F, 57Tunneled jugular catheter (OPTIMED®)2771.9 (281)No0.5NATunneled jugular catheter (VYGON®)68 (first available test after catheter)1.8 (68)No630Tunneled jugular catheter (HEMOTECH®)185.2 (40)No115Tunneled jugular catheter (HEMOTECH®)218.5 (37)No1.5NAP4M, 57Tunneled jugular catheter (VYGON®)372 (112)No34Tunneled jugular catheter (VYGON®)3214.3 (37)Pruritus, sweats8.51P5F, 54Palindrome catheter (METRONIC®)936.1 (387)Pruritus, sweats and urticarial rash1421 (renal transplantation)P6M, 37Tunneled jugular catheter (HEMOTECH®)479.8 (1230)Pruritus, sweats and urticarial rash39NA (renal transplantation)Eo, eosinophilia; F, female; M, male; NA, not available; P, patient; y, year Open table in a new tab Eo, eosinophilia; F, female; M, male; NA, not available; P, patient; y, year The cases presented here are peculiar for the severity of eosinophilia. It was associated to rather mild symptoms in the majority of patients, mostly pruritus, sweating and urticarial rash during dialysis sessions. However, in one patient, eosinophilia was associated to the occurrence of pulmonary nodules, eosinophilic alveolitis and colitis (Figure 2). In this patient, as well as in two additional ones, eosinophilia work-up led to a significant delay in the access to renal transplantation, due to temporary contraindication. In two other patients, severe reactions with hypotension, dyspnea occurred repeatedly after start of dialysis session. To the best of our knowledge, this is the first description of severe eosinophilia induced by dialysis catheter. Nephrologists should be aware that indwelling venous catheter is a potential reversible cause of severe eosinophilia in hemodialysis patients whose mechanism remains to be understood. This will help avoiding useless etiological investigations and, more importantly, delays in the access to renal transplantation for these patients. Download .pdf (.1 MB) Help with pdf files Supplementary Reference

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is being more widely recognized but the precise epidemiology and outcome is lacking, particularly in Europe. We aimed to assess clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were retrospectively collected. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed correlation between histological presentation and outcome using the Chi square test (qualitative data) and Kruskal-Wallis test (quantitative data). Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Most of them had a Staphylococcus aureus infection (77.8%) and 44.4% were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine >4 mg/dL, and 16% had a hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis with tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression, found in 17.8% of the cases, was most frequently observed in biopsies with acute or subacute pattern and associated with a shorter delay between infection and renal biopsy compared to segmental and focal staining. After a median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphyloccus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Kidney transplant recipients have been supposed vulnerable to severe Covid-19 infection, due to their comorbidities and immunosuppressive therapies. Mild-term complications of Covid-19 are currently unknown, especially in this population. Herein, we report two cases of BKV replication after non-severe SARS-CoV-2 infection. The first case was a 59-year-old man, transplanted 3 months ago, with recent history of slight BKV viremia (3.3 log10 DNA copies/ml). Despite strong reduction of maintenance immunosuppression (interruption of mycophenolic acid and important decrease of calcineurin inhibitors), BKV replication largely increased after Covid-19 and viremia persisted at 4.5 log copy/ml few months later. The second case was a 53-year-old woman, transplanted 15 years ago. She had a recent history of BKV cystitis, which resolved with a decrease of MPA dosage. Few weeks after SARS-CoV-2 infection, she presented recurrence of lower urinary tract symptoms. Our reports highlight that SARS-CoV-2 infection, even without severity, could disrupt immune system and particularly lymphocytes, thus leading to viral replication. Monitoring of viral replications after Covid-19 in kidney transplant recipients could permit to confirm these preliminary observations.

Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007–2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Risk-to-benefit analysis of upper extremity allotransplantation (UEA) warrants a careful assessment of immunosuppression-related complications. This first systematic report of infectious complications after UEA aimed to compare incidence and pattern of infections to that observed after kidney transplantation (KT). We conducted a matched cohort study among UEA and KT recipients from the International Registry on Hand and Composite Tissue Transplantation and the French transplant database DIVAT. All UEA recipients between 1998 and 2016 were matched with KT recipients (1:5) regarding age, sex, cytomegalovirus (CMV) serostatus and induction treatment. Infections were analyzed at three posttransplant periods (early: 0-6 months, intermediate: 7-12 months, late: >12 months). Sixty-one UEA recipients and 305 KT recipients were included. Incidence of infection was higher after UEA than after KT during the early period (3.27 vs. 1.95 per 1000 transplant-days, P = 0.01), but not statistically different during the intermediate (0.61 vs. 0.45/1000, P = 0.5) nor the late period (0.15 vs. 0.21/1000, P = 0.11). The distribution of infectious syndromes was significantly different, with mucocutaneous infections predominating after UEA, urinary tract infections and pneumonia predominating after KT. Incidence of infection is high during the first 6 months after UEA. After 1 year, the burden of infections is low, with favorable patterns.

BACKGROUND:Informing kidney transplant recipients of their prognosis and disease progression is of primary importance in a patient-centred vision of care. By participating in decisions from the outset, transplant recipients may be more adherent to complex medical regimens due to their enhanced understanding.METHODS:We proposed to include repeated measurements of serum creatinine (SCr), in addition to baseline characteristics, in order to obtain dynamic predictions of the graft failure risk that could be updated continuously during patient follow-up. Adult recipients from the French Données Informatisées et VAlidées en Transplantation (DIVAT) cohort transplanted for the first or second time from a heart-beating or living donor and alive with a functioning graft at 1 year post-transplantation were included.RESULTS:The model was composed of six baseline parameters, in addition to the SCr evolution. We validated the dynamic predictions by evaluating both discrimination and calibration accuracy. The area under the receiver operating characteristic curve varied from 0.72 to 0.76 for prediction times at 1 and 6 years post-transplantation, respectively, while calibration plots showed correct accuracy. We also provided an online application tool (https://shiny.idbc.fr/DynPG).CONCLUSION:We have created a tool that, for the first time in kidney transplantation, predicts graft failure risk both at an individual patient level and dynamically. We believe that this tool would encourage willing patients into participative medicine.

Immune checkpoint inhibitors (CPIs) have opened a new era in the treatment of cancer, and their indications are increasing rapidly. To date, these CPIs include anti-CTLA4 (ipilimumab), anti-Programmed Death 1 (PD1) (nivolumab, pembrolizumab) and anti-Programmed Death-Ligand 1 (PD-L1) (atezolizumab, avelumab, durvalumab) antibodies (Abs). Solid organ transplant recipients have a higher risk of neoplastic complications because of immunosuppressive treatments and oncogenic viral infections [ [1] Engels E.A. Pfeiffer R.M. Fraumeni Jr., J.F. Kasiske B.L. Israni A.K. Sydner J.J. et al. Spectrum of cancer risk among US solid organ transplant recipients. J Am Med Assoc. 2011; 306: 1891-1901 Crossref PubMed Scopus (985) Google Scholar ]. Thus, cancer has now become the second cause of death among transplant patients [ [2] Buell J.F. Gross T.G. Woodle E.S. Malignancy after transplantation. Transplantation. 2005; 80: S254-S264 Crossref PubMed Scopus (477) Google Scholar ]. However, data are lacking regarding the use of CPI in these transplant patients because they were excluded from clinical trials because of the theoretical risk of organ rejection [ 3 Postow M.A. Chesney J. Pavlick A.C. Robert C. Grossman K. McDermott C. et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2010; 372: 2006-2017 Crossref Scopus (2098) Google Scholar , 4 Borghaei H. Paz-Ares L. Horn L. Spigel D.R. Steins M. Ready N.E. et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015; 373: 1627-1639 Crossref PubMed Scopus (6769) Google Scholar , 5 Ansell S.M. Lesokhin A.M. Borrello I. Halwani A. Scott E.C. Gutierrez M. et al. PD 1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015; 372: 311-319 Crossref PubMed Scopus (2635) Google Scholar ]. Only a few isolated cases of CPI use in transplant recipients have been reported in the literature so far (reviewed in [ [6] Kittai A.S. Oldham H. Cetnar J. Taylor M. Immune checkpoint Inhibitors in organ transplant patients. J Immunother. 2017; 40: 277-281 Crossref PubMed Scopus (94) Google Scholar ]). Therefore, although there is a clear medical need, the possibility of using these new therapies in transplant patients with cancer remains largely unknown. Here, we report a series of seven kidney allograft recipients treated with CPI for cancer.

Anti–programmed cell death 1 (PD-1) antibodies have demonstrated anticancer activities and survival benefit but, because of their mechanism of action, have been associated with autoimmune and alloimmune adverse events.1 We report the case of a kidney transplant patient who presented autoimmune hemolytic anemia (AIHA) and severe acute graft rejection after administration of nivolumab. A 73-year-old man received a diagnosis of a superficial spreading melanoma at a metastatic stage during 15 months posttransplant. Immunosuppression was reduced, and tacrolimus was switched to everolimus (2.5 mg/d). After 2 injections of 3 mg/kg of body weight of anti-PD-1 antibody at 30 days interval, he presented with acute renal failure 25 days after the last dose, with an enlarged kidney transplant and grade 2A acute cellular rejection on biopsy. No donor-specific antibodies were identified; the rejection was resistant to high doses of steroid, and the patient returned to dialysis. Simultaneously, he developed AIHA with a Coombs assay positive for complement and severe thrombocytopenia (nadir platelet count, 38 000 per mm3). There was no evidence of thrombotic microangiopathy, no platelet antibodies, and no local invasion on bone marrow histology. It resolved in 1 week, associated with use of high-dose steroids and cessation of nivolumab. The patient died from superficial spreading melanoma dissemination 3 months later. There have been 7 other reports of anti-PD-1 administration in kidney transplanted patients (6 nivolumab and 1 pembrolizumab). Among the total of 8 patients, 6 presented with acute cellular rejection (Banff grade 2A or 2B), including the 2 patients with areas of cortical necrosis. No patient had donor-specific antibodies, and the timing of rejection a few days or weeks after nivolumab suggest causality, especially in patients on stable immunosuppression for 10 years or more in whom reduction of immunosuppression would not be expected to result in immediate rejection. Mycophenolate had been stopped in all patients at the time of cancer diagnosis, and calcineurin inhibitors had been withdrawn, minimized, or switched to low-dose everolimus as in our patient. Two patients remained on full-dose immunosuppression and had no rejection. Tacrolimus was switched for full-dose everolimus in 1 patient, and the authors advocated for the maintenance of significant immunosuppression associated with the use of anti-PD-1 administration.2 Anti-PD-1 antibodies have also been associated with autoimmune manifestations with AIHA reported in 4 cases.3 It occurred after a mean of 4 cycles, was Coombs positive for immunoglobulin G and/or C3, and responded well to high dose of corticosteroids. Our case is the first description of AIHA in a transplant patient. The indication for anti-PD-1 therapy will likely increase in transplanted patients with cancer. The transplant community must therefore be aware of the risk of allograft rejection and transplant loss. Immunosuppression minimization, although it is the recommended approach to active neoplasia in a transplant recipient, must be reconsidered when the patient is treated with anti-PD-1 therapy.