Fluindione is well known to induce acute drug-induced interstitial nephritis (IN). Most cases occurred soon after the onset of treatment. We report a unique case of severe subacute fluindione-induced ...IN diagnosed 2 years after the treatment was begun. Renal function dramatically improved after fluindione withdrawal and steroid therapy.
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well ...as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well ...as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.
Abstract Background and Aims Membranous nephropathy (MN) is a rare, but severe autoimmune disease affecting kidney glomeruli. Clinical evolution is variable, ranging from spontaneous remission to ...persistent nephrotic syndrome and kidney failure. The major autoantigen in MN is PLA2R1 protein associated with 50-70% of all cases. Patients may present antibodies against a single immunodominant CysR domain or may develop additional antibodies against CTLD1 and/or CTLD7 and/or CTLD8 domains of PLA2R1 defining a cascade immunization or epitope spreading. The mechanism of epitope spreading has been described in a variety of contexts: it can reinforce immune response to eliminate a pathogen, but can also be associated with the aggravation of autoantibody-mediated autoimmune pathologies. The value of this marker in the management of MN patients remains debated. Our initial study (confirmed on an independent cohort) has shown that the single domain recognition (non-spreader patients) is associated with a higher chance of spontaneous remission (45% vs 0.05% in GEMRITUX cohort) and a better response to treatment (100% of remission regardless of the dose of rituximab used). The patients with multi domain recognition (spreader patients) of CTLD1 and/or CTLD7 domains, on the other hand, have poor prognosis and are less likely to achieve remission requiring high doses of rituximab. Based on these studies we have proposed a personalized treatment protocol with either low or high dose Rituximab based on patients’ PLA2R1 epitope spreading status. The aim of this study was to evaluate the efficacy of this personalized treatment in comparison to the established GEMRITUX protocol. Method A multicenter, randomized, controlled, prospective clinical trial was conducted in 12 French hospitals. Sixty-four consecutive patients with PLA2R1-related MN were randomly assigned to either the control group following the GEMRITUX protocol (symptomatic treatment for 6 months, two 375 mg/m2 rituximab infusions at month-6 in case of persistent nephrotic syndrome (NS)) or the personalized treatment (PMMN) group (patients with no epitope spreading at month-0 were treated as per GEMRITUX protocol, while patients with epitope spreading at month-0 or month-6 with persistent NS were treated immediately with two 1 g rituximab infusions). The primary study outcome was the rate of clinical remission at month-12. The secondary outcomes were complete and partial remission, immunological remission, proteinuria, albuminuria, serum creatinine, and PLA2R1 antibody titer. Results From 64 patients included, three were excluded from final analyses due to loss to follow-up. There was no difference in age, gender, albumin, UPCR, anti-PLA2R1 titer and the rate of PLA2R1 epitope spreading at baseline between the two groups. At M12, 34% of patients from the GEMRITUX group and 69% of patients from PMMN group achieved partial clinical remission (P = .0105) defined as UPCR < 3.5 g/g with a decrease greater than 50% from baseline; improvement or normalization of serum albumin; and increase of serum creatinine lower than 20%. While there was no difference in remission rate between the GEMRITUX group and PMMN group for patients with single domain recognition (38% vs 50%, respectively, P = .7107), multi-domain recognizers (spreaders) were more likely to achieve remission with personalized protocol (36% vs. 87%, P = .0078). The rate of complete clinical remission between the two experimental groups, defined as UPCR <0.3 g/g and normal albumin, was close to statistical significance (0% vs 16%, P = .0538). Conclusion Personalized treatment protocol based on the stratification of patients with PLA2R1-related MN according to their epitope spreading status, is superior to the standard GEMRITUX protocol in achieving partial clinical remission at 12 months. Patients with multiple domain recognition should be treated immediately with high doses of rituximab to increase their chances of remission.
Background
Few studies have focused on risk stratification for premature death after transplantation. However, stratification of individual risk is an essential step in personalized care.
Material ...and methods
We have developed a risk score of early post‐transplant death (ORLY score) in a prospective multicentre cohort including 942 patients and validated our model in a retrospective independent replication cohort including 874 patients.
Results
60 patients (6.4%) from the prospective cohort died during the first three‐year post‐transplant. Age, male gender, diabetes, dialysis duration and chronic respiratory failure were associated with early post‐transplant death. The multivariable model exhibited good discrimination ability (C‐index = 0.78, 95%CI 0.75‐0.81). ORLY score highly predicted early death after transplantation (1.34; 95%CI, 1.22 to 1.48 for each increase of 1 point in score; P < .001). The predictive value of the score in the validation cohort was close to that observed in the experimental cohort (1.41; 95%CI, 1.27 to 1.56 for each increase of 1 point in score; P < .001). Merging the two cohorts, four categories of risk could be individualized: low, 0‐5 (n = 522, mean risk, 1%); intermediate, 6‐7 (n = 739, mean risk 4.7%); moderate, 8‐10 (n = 429, mean risk 10%); and high risk 11‐15 (n = 132, mean risk 19%).
Conclusions
The ORLY score discriminates patients with high risk of early death.
•Only one quarter of kidney transplant recipients have strong humoral responses after three doses of mRNA anti-SARS-CoV-2 vaccine.•Anti-SARS-CoV-2 levels decreased by 50% each 3 months.•Passive ...immunization is safe and efficient and should be considered in patients with no or low response to vaccine.•Low-responders are at risk of severe COVID-19 infection.
ABSTRACT
Background
Interstitial inflammation and peritubular capillaritis are observed in many diseases on native and transplant kidney biopsies. A precise and automated evaluation of these ...histological criteria could help stratify patients’ kidney prognoses and facilitate therapeutic management.
Methods
We used a convolutional neural network to evaluate those criteria on kidney biopsies. A total of 423 kidney samples from various diseases were included; 83 kidney samples were used for the neural network training, 106 for comparing manual annotations on limited areas to automated predictions, and 234 to compare automated and visual gradings.
Results
The precision, recall and F-score for leukocyte detection were, respectively, 81%, 71% and 76%. Regarding peritubular capillaries detection the precision, recall and F-score were, respectively, 82%, 83% and 82%. There was a strong correlation between the predicted and observed grading of total inflammation, as for the grading of capillaritis (r = 0.89 and r = 0.82, respectively, all P < .0001). The areas under the receiver operating characteristics curves for the prediction of pathologists’ Banff total inflammation (ti) and peritubular capillaritis (ptc) scores were respectively all above 0.94 and 0.86. The kappa coefficients between the visual and the neural networks' scores were respectively 0.74, 0.78 and 0.68 for ti ≥1, ti ≥2 and ti ≥3, and 0.62, 0.64 and 0.79 for ptc ≥1, ptc ≥2 and ptc ≥3. In a subgroup of patients with immunoglobulin A nephropathy, the inflammation severity was highly correlated to kidney function at biopsy on univariate and multivariate analyses.
Conclusion
We developed a tool using deep learning that scores the total inflammation and capillaritis, demonstrating the potential of artificial intelligence in kidney pathology.
Graphical Abstract
Graphical Abstract
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.
Case series.
Patients with C3GN and concomitant TMA lesions on biopsy registered from 2009 to 2019 in the French National Registry of C3GN.
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.
Small retrospective case series with a limited number of biopsies including electron microscopy.
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.
Kidney transplant recipients (KTRs) have an increased risk of cardiovascular (CV) events (CVEs) compared with the general population. The impact of insulin resistance on CV risk after transplantation ...is not well defined.
We tested whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, may predict posttransplant CVEs in a cohort of 715 consecutive KTRs all included 1 year after transplant.
Follow-up was 9.1 ± 4.6 years. Mean TyG at inclusion was 4.75 ± 0.29 (median, 4.73 4.14–5.84). In multiple regression analysis, having a TyG above the median value was associated with higher body mass index (BMI), low high-density lipoprotein (HDL) cholesterol level, and greater urinary protein excretion. A total of 127 CVEs (17.7%) occurred during the study period. In univariate analysis, TyG was strongly associated with CVE occurrence (hazard ratio HR 2.06, 95% CI 1.42–3.50, for each increase of 0.1 in TyG, P < 0.001). The best predictive value was 4.87 (HR 6.32, 95% CI 3.30–12.11, P < 0.001). The risk of CVE gradually increased with higher TyG index (quartile 2, HR 1.71, 95% CI 0.84–5.20, P = 0.139; quartile 3, HR 3.12, 95% CI 1.61–6.02, P < 0.001; quartile 4, HR 7.46, 95% CI 4.03–13.80, P < 0.001, vs. quartile 1). TyG remained associated with CVE in multivariate analysis (HR 2.11, 95% CI 1.22–3.68, for each increase of 0.1 in TyG, P < 0.001).
Insulin resistance, as measured by the TyG index is strongly associated with CVE in KTRs. Improving insulin sensitivity seems to be a major issue to prevent CV morbidity and mortality in this high-risk population.
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