Rituximab has shown encouraging results for the treatment of kidney transplantation recipients with focal segmental glomerulosclerosis (FSGS) recurrence. However, the correct, opportune, and safe use ...of rituximab for this indication remains to be determined.
This multicenter retrospective study reports on 19 new cases aged 35 (15-66) years who developed FSGS recurrence at 12 (1.5-27) days posttransplantation. Initial treatment consisted of plasma exchanges (PE), high doses of calcineurin inhibitors, and steroids. Rituximab was introduced either immediately (N = 6) or after failure of the initial treatment (N = 10) or failed attempted weaning from PE (N = 3).
Overall, we observed 9 of 19 complete remissions and 3 of 19 partial remissions. Estimated glomerular filtration rates (Modification of Diet in Renal Disease 4) were significantly higher in the responding patients than in nonresponding patients at month (M)12, M36, and M60. Overall, kidney survival at 5 years was 77.4% (95% range, 41.9-92.7). The 5-year graft survival rates in the responding patients and the nonresponding patients were 100% and 36.5%, respectively (P = 0.01). A further course of rituximab was required for 4 patients as a result of FSGS relapse, with good results. During the first year after renal transplantation, 14 patients developed severe infections (16 bacterial, 4 viral, 1 parasitic).
In kidney transplantation recipients with recurrent FSGS, rituximab therapy may be a recommended treatment for cases that have failed either the initial treatment or weaning from PE.
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.
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.
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.
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.
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.
Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle ...atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.400.26-0.55 mug/ml. Low muscle mass as defined by a lean tissue index (LTI) 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes.
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.
The clinical significance of early-onset acute kidney injury (EO-AKI) and recovery in severe COVID-19 intensive care unit (ICU) patients is poorly documented.
The aim of the study was to assess the ...epidemiology and outcome of EO-AKI and recovery in ICU patients admitted for SARS-CoV-2 pneumonia.
This was a retrospective single-centre study.
The study was carried out at the medical ICU of the university hospital of Clermont-Ferrand, France.
All consecutive adult patients aged ≥18 years admitted between 20 March 2020 and 31 August 2021 for SARS-CoV-2 pneumonia were enrolled. Patients with chronic kidney disease, referred from another ICU, and with an ICU length of stay (LOS) ≤72 h were excluded.
EO-AKI was defined on the basis of serum creatinine levels according to the Kidney Disease Improving Global Outcomes criteria, developing ≤7 days. Depending on renal recovery, defined by the normalization of serum creatinine levels, EO-AKI was transient (recovery within 48 h), persistent (recovery between 3 and 7 days) or AKD (no recovery within 7 days after EO-AKI onset).
Uni- and multivariate analyses were performed to determine factors associated with EO-AKI and EO-AKI recovery.
EO-AKI occurred in 84/266 (31.5%) study patients, of whom 42 (50%), 17 (20.2%) and 25 (29.7%) had EO-AKI stages 1, 2 and 3, respectively. EO-AKI was classified as transient, persistent and AKD in 40 (47.6%), 15 (17.8%) and 29 (34.6%) patients, respectively. The 90-day mortality was 87/244 (35.6%) and increased with EO-AKI occurrence and severity: no EO-AKI, 38/168 (22.6%); EO-AKI stage 1, 22/39 (56.4%); stage 2, 9/15 (60%); and stage 3, 18/22 (81.8%) (
< 0.01). The 90-day mortality in patients with transient or persistent AKI and AKD was 20/36 (55.6%), 8/14 (57.1%) and 21/26 (80.8%), respectively (
< 0.01). MAKE-90 occurred in 42.6% of all patients.
In ICU patients admitted for SARS-CoV-2 pneumonia, the development of EO-AKI and time to recovery beyond day 7 of onset were associated with poor outcome.
We report a case of multiorgan failure resulting from treatment with the antiviral foscarnet in a kidney transplant recipient. Precipitation of foscarnet crystals was confirmed histologically from a ...biopsy of the transplant using optical and infrared microscopy. In addition to kidney damage resulting from foscarnet crystal precipitation in the tubular lumen and glomerular capillaries, the patient presented with pancreatitis, pancolitis, and myocarditis with shock. Interruption of the treatment led to rapid improvement in her general condition, but did not prevent permanent loss of the kidney transplant. When faced with unexplained multiorgan failure in a patient treated with foscarnet, one should assume this substance to be toxic. A kidney biopsy can confirm this diagnosis.
The last decade has seen a steady increase worldwide in the prevalence of end-stage renal disease (ESRD). Hemodialysis is the major modality of renal replacement therapy (RRT) in 70% to 90% of ...patients, who require well-functioning vascular access for this procedure. The recommended access for hemodialysis is an arteriovenous fistula or a vascular graft. However, recourse to central venous catheters remains essential for patients whose chronic renal disease is diagnosed at the end stage or in whom an arteriovenous fistula cannot be created or maintained. Tunneled dialysis catheter (TDC) exposure can induce venous stenosis and occlusions and can result in superior vena cava syndrome and/or vascular access loss. Exhaustion of conventional vascular accesses is 1 of the greatest challenges that nephrologists and patients have to face. Several unconventional salvage-therapy routes for TDC placement in patients with exhausted upper body venous access have been reported in the literature.
We report 2 new cases of intra-atrial TDC placement for patients with exhausted vascular access and perform a meta-analysis of cases from the literature.
A total of 51 patients were included. The TDC was inserted by a cardiovascular surgeon in all cases. At the end of follow-up, 75% patients were alive. The median survival time was 25 months. Survival time of hemodialysis patients with intra-atrial TDC was lower than that observed with conventional TDC.
This unconventional technique is safe and functional for hemodialysis patients with exhausted venous access. Atrial vascular access for TDC placement is salvage therapy and is therefore potentially lifesaving.
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 (
= 193) and validation cohorts (
= 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), PaCO
(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.
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