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Results in Journal Kidney International: 22,710

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Camille Nicolas Frank, Xiaogang Hou, Astgik Petrosyan, Valentina Villani, Rui Zhao, Joshua R. Hansen, Geremy Clair, Fadi Salem, Roger E. De Filippo, Paolo Cravedi, et al.
Published: 22 September 2021
Abstract:
Progression of glomerulosclerosis is associated with loss of podocytes with subsequent glomerular tuft instability. It is thought that a diminished number of podocytes may be able to preserve tuft stability through cell hypertrophy associated with cell cycle re-entry. At the same time, reentry into the cell cycle risks podocyte detachment if podocytes cross the G1/S checkpoint and undergo abortive cytokinesis. In order to study cell cycle dynamics during chronic kidney disease (CKD) development, we used a FUCCI model (fluorescence ubiquitination-based cell cycle indicator) of mice with X-linked Alport Syndrome. This model exhibits progressive CKD and expresses fluorescent reporters of cell cycle stage exclusively in podocytes. With development of CKD, an increasing fraction of podocytes in vivo were found to be in G1 or later cell cycle stages. Podocytes in G1 and G2 were hypertrophic. Heterozygous female mice, with milder manifestations of CKD, showed G1 fraction numbers intermediate between wild-type and male Alport mice. Proteomic analysis of podocytes in different cell cycle phases showed differences in cytoskeleton re-organization and metabolic processes between G0 and G1 in disease. Additionally, in vitro experiments confirmed that damaged podocytes re-entered the cell cycle comparable to podocytes in vivo. Importantly, we confirmed upregulation of PDlim2, a highly expressed protein in podocytes in G1, in a patient with Alport Syndrome, confirming our proteomics data in the human setting. Thus, our data showed that in the Alport model of progressive CKD, podocyte cell cycle distribution is altered, suggesting that cell cycle manipulation approaches may have a role in treatment of various progressive glomerular diseases characterized by podocytopenia.
María Fernanda Zavala-Miranda, Samantha G. González-Ibarra, Abril A. Pérez-Arias, Norma O. Uribe-Uribe,
Published: 21 September 2021
, David Cherney, Douwe Postmus, Bergur V. Stefánsson, Glenn M. Chertow, Jamie P. Dwyer, Tom Greene, Mikhail Kosiborod, Anna Maria Langkilde, John JV. McMurray, et al.
Published: 21 September 2021
Abstract:
This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high risk patients based on having chronic kidney disease (CKD) and severe albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200–5000 mg/g and estimated glomerular filtration rate 25–75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function.
Kavita Gulati, Helena Edwards, Maria Prendecki, Thomas D. Cairns, Marie Condon, Jack Galliford, Megan Griffith, Jeremy B. Levy, Frederick W.K. Tam, Anisha Tanna, et al.
Published: 21 September 2021
Abstract:
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.
, Richard Furie, Y.K. Onno Teng, Gabriel Contreras, Ana Malvar, Xueqing Yu, Beulah Ji, Yulia Green, Tania Gonzalez-Rivera, Damon Bass, et al.
Published: 21 September 2021
Abstract:
We performed a post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). Add-on belimumab was found to be most effective in improving the primary efficacy kidney response and complete kidney response in patients with proliferative lupus nephritis and a baseline urine protein/creatinine ratio under 3 g/g. However, there was no observed improvement in the kidney response with belimumab treatment in patients with lupus nephritis and sub-epithelial deposits or with a baseline protein/creatinine ratio of 3 g/g or more. Belimumab significantly reduced the risk of kidney-related events or death, and lupus nephritis flare in the overall population. Belimumab reduced the risk of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) versus standard treatment alone and attenuated the annual rate of eGFR decline in patients who remained on-study. Thus, our data suggest that the addition of belimumab to standard therapy could attenuate the risk of lupus nephritis flare and eGFR decline in a broad spectrum of patients with lupus nephritis.
Fadi E. Salem, Laura Perin, Sargis Sedrakyan, Andrea Angeletti, Gianmarco Ghiggeri, Maria Cristina Coccia, Marty Ross, ,
Published: 20 September 2021
Abstract:
Analysis of the transcriptional profile of graft biopsies represents a promising strategy to study T cell mediated-rejection (TCMR), also known as acute cellular rejection. However, bulk RNA sequencing of graft biopsies may not capture the focal nature of acute rejection. Herein, we used the whole exome GeoMX Digital Space Profiling platform to study five tubular and three glomerular regions of interest in the kidney graft biopsy from a patient with a chronic-active TCMR episode and in analogous areas from two different normal kidney control biopsies. All kidney sections were from paraffin blocks. Overall, inflammatory genes were significantly upregulated in the tubular areas of the TCMR biopsy and showed an enrichment for gene-ontology terms associated with T cell activation, differentiation, and proliferation. Enrichment analysis of the 100 genes with the highest coefficient of variation across the TCMR tubular regions of interest revealed that these highly-variable genes are involved in kidney development and injury, and interestingly do not associate with the 2019 Banff classification pathology scores within the individual regions of interest. Spatial transcriptomics allowed us to unravel a previously unappreciated variability across different areas of the TCMR biopsy related to the graft response to the alloimmune attack, rather than to the immune cells. Thus, our approach has the potential to decipher clinically relevant, new pathogenic mechanisms, and therapeutic targets in acute cellular rejection and other kidney diseases with a focal nature.
Jakub Sikora, Tereza Kmochová, Dita Mušálková, Michal Pohludka, Petr Přikryl, Hana Hartmannová, Kateřina Hodaňová, Helena Trešlová, Lenka Nosková, Lenka Mrázová, et al.
Published: 20 September 2021
Abstract:
Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys being the most commonly and earliest affected organ. Previously described amyloid A amyloidosis is linked to increased production and deposition of serum amyloid A proteins secondary to inflammatory conditions arising from infectious, metabolic, or genetic causes. Here we describe a family with primary amyloid A amyloidosis due to a chr11:18287683 T>C (human genome version19) mutation in the SAA1 promoter linked to the amyloidogenic SAA1.1 haplotype. This condition leads to a doubling of the basal SAA1 promoter activity and sustained elevation of serum amyloid A levels that segregated in an autosomal dominant pattern in 12 genetically affected and in none of six genetically unaffected relatives, yielding a statistically significant logarithm of odds (LOD) score over 5. Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed specifically of the SAA1.1 isoform. Tocilizumab (a monoclonal antibody against the interleukin-6 receptor) had a beneficial effect when prescribed early in the disease course. Idiopathic forms represent a significant and increasing proportion (15-20%) of all diagnosed cases of amyloid A amyloidosis. Thus, genetic screening of the SAA1 promoter should be pursued in individuals with amyloid A amyloidosis and no systemic inflammation, especially if there is a positive family history.
, Line L. Bang, Ditte S. Tornby, Helene Kierkegaard, Anna C. Nilsson, Isik S. Johansen, Claus Bistrup, Thøger G. Jensen, Ulrik S. Justesen, Thomas E. Andersen
Published: 18 September 2021
Abstract:
Coronavirus disease 2019 (COVID-19)–vaccinated kidney transplant recipients (KTRs) display a lower-than-normal antibody (Ab) response toward severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), indicating a reduced humoral immune response against the virus.1Benotmane I. Gautier-Vargas G. Cognard N. et al.Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine.Kidney Int. 2021; 99: 1498-1500Abstract Full Text Full Text PDF PubMed Google Scholar A remaining question is to which extent this translates to lower the ability of KTRs to combat SARS-CoV-2.2Ikizler T.A. Coates P.T. Rovin B.H. Ronco P. Immune response to SARS-CoV-2 infection and vaccination in patients receiving kidney replacement therapy.Kidney Int. 2021; 99: 1275-1279Abstract Full Text Full Text PDF PubMed Google Scholar This capacity can be estimated by surrogate or pseudovirus neutralization assays or, optimally, the plaque reduction neutralization test (PRNT), in which live SARS-CoV-2 is challenged directly with patient blood plasma.3Rincon-Arevalo H. Choi M. Stefanski A.L. et al.Impaired humoral immunity to SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients and dialysis patients.Sci Immunol. 2021; 6eabj1031Crossref PubMed Google Scholar,4Pedersen R.M. Tornby D.S. Bistrup C. et al.Negative SARS-CoV-2 antibodies, T-cell response and virus neutralization following full vaccination in a renal transplant recipient: a call for vigilance.Clin Microbiol Infect. 2021; 27: 1371-1373Abstract Full Text Full Text PDF PubMed Google Scholar
Rosi Bissinger, Travis Nemkov, Angelo D´alessandro, Marijke Grau, Thomas Dietz, Bernhard N. Bohnert, Daniel Essigke, Matthias Wörn, Lina Schaefer, Mengyun Xiao, et al.
Published: 15 September 2021
Abstract:
Anemia is a common complication of chronic kidney disease, affecting the quality of life of patients. Among various factors, such as iron and erythropoietin deficiency, reduced red blood cell (RBC) lifespan has been implicated in the pathogenesis of anemia. However, mechanistic data on in vivo RBC dysfunction in kidney disease are lacking. Herein, we describe the development of chronic kidney disease-associated anemia in mice with proteinuric kidney disease resulting from either administration of doxorubicin or an inducible podocin deficiency. In both experimental models, anemia manifested at day 10 and progressed at day 30 despite increased circulating erythropoietin levels and erythropoiesis in the bone marrow and spleen. Circulating RBCs in both mouse models displayed altered morphology and diminished osmotic-sensitive deformability together with increased phosphatidylserine externalization on the outer plasma membrane, a hallmark of RBC death. Fluorescence-labelling of RBCs at day 20 of mice with doxorubicin-induced kidney disease revealed premature clearance from the circulation. Metabolomic analyses of RBCs from both mouse models demonstrated temporal changes in redox recycling pathways and Lands' cycle, a membrane lipid remodeling process. Anemic patients with proteinuric kidney disease had an increased proportion of circulating phosphatidylserine-positive RBCs. Thus, our observations suggest that reduced RBC lifespan, mediated by altered RBC metabolism, reduced RBC deformability, and enhanced cell death contribute to the development of anemia in proteinuric kidney disease.
Nicholas L. Li, P. Toby Coates, Brad H. Rovin
Published: 14 September 2021
Abstract:
To date over 4 billion doses of the various Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been administered worldwide in response to the Coronavirus Disease 2019 (COVID-19) pandemic. Even as widespread vaccination campaigns have contributed to declining case rates, adverse events are appearing beyond those originally reported in the clinical trials of vaccine efficacy and safety. Of particular relevance to the kidney is the increasing number of reports of de novo or reactivation of glomerular diseases (Table 1). The occurrence of glomerular disease after immunization against influenza, pneumococcus, and hepatitis B has been reported in the past26Gutierrez S. Dotto B. Petiti J.P. et al.Minimal change disease following influenza vaccination and acute renal failure: just a coincidence?.Nefrologia. 2012; 32: 414-415Google Scholar, 27Kikuchi Y. Imakiire T. Hyodo T. et al.Minimal change nephrotic syndrome, lymphadenopathy and hyperimmunoglobulinemia after immunization with a pneumococcal vaccine.Clin Nephrol. 2002; 58: 68-72Google Scholar, 28Ozdemir S. Bakkaloglu A. Oran O. Nephrotic syndrome associated with recombinant hepatitis B vaccination: a causal relationship or just a mere association?.Nephrol Dial Transplant. 1998; 13: 1888-1889Google Scholar. The reported patients developed acute onset nephrotic syndrome following vaccination, and kidney biopsies were consistent with a minimal change disease (MCD) pattern of injury. While temporal association (median onset of 12 days) with vaccination and disease onset suggested a vaccine-related induction of immune injury, the pathophysiologic mechanisms responsible have not been determined.Table 1Summary of reported cases of glomerular disease activation with COVID-19 vaccinationDiseaseAge (median and range)% FemaleVaccine TypeNumber of CasesDe Novo or Flare1Hanna C. Herrera Hernandez L.P. Bu L. et al.IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine.Kidney Int. 2021; 100: 705-706Google ScholarMaintenance Immune TherapyTemporal Association to VaccinationTreatmentOutcomeCOVID-IgG ResponseReferencesIgAN38 (13-52)58% (7/12)Pfizer-BioNTech, Moderna125 De Novo, 7 FlareNo, or Steroids, Mycophenolic acid, Calcineurin inhibitor in Transplant patient1-2 daysRASi, Steroids, CyclophosphamideSpontaneous resolution, renal response to immunotherapyPositive1Hanna C. Herrera Hernandez L.P. Bu L. et al.IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine.Kidney Int. 2021; 100: 705-706Google Scholar, 2Kudose S. Friedmann P. Albajrami O. et al.Histologic correlates of gross hematuria following Moderna COVID-19 vaccine in patients with IgA nephropathy.Kidney Int. 2021; 100: 468-469Google Scholar, 3Anderegg M.A. Liu M. Saganas C. et al.De novo vasculitis after mRNA-1273 (Moderna) vaccination.Kidney Int. 2021; 100: 474-476Google Scholar, 4Negrea L. Rovin B.H. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy.Kidney Int. 2021; 99: 1487Google Scholar, 5Perrin P. Bassand X. Benotmane I. et al.Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy.Kidney Int. 2021; 100: 466-468Google Scholar, 6Tan H.Z. Tan R.Y. Choo J.C.J. et al.Is COVID-19 vaccination unmasking glomerulonephritis?.Kidney Int. 2021; 100: 469-471Google Scholar, 7Rahim S.E.G. Lin J.T. Wang J.C. A case of gross hematuria and IgA nephropathy flare-up following SARS-CoV-2 vaccination.Kidney Int. 2021; 100: 238Google ScholarMCD61 (22-“early 80s”)36 (4/11)Pfizer-BioNTech, Moderna, Astra Zeneca117 De Novo, 4 FlareNo, or Steroids, Calcineurin inhibitor, Rituximab1-13 days (Median 7 days)Steroids, Calcineurin inhibitorRenal response to immunotherapy majority of casesPositive8Weijers J. Alvarez C. Hermans M.M.H. Post-vaccinal minimal change disease.Kidney Int. 2021; 100: 459-461Google Scholar, 9Morlidge C. El-Kateb S. Jeevaratnam P. et al.Relapse of minimal change disease following the AstraZeneca COVID-19 vaccine.Kidney Int. 2021; 100: 459Google Scholar, 10D'Agati V.D. Kudose S. Bomback A.S. et al.Minimal change disease and acute kidney injury following the Pfizer-BioNTech COVID-19 vaccine.Kidney Int. 2021; 100: 461-463Google Scholar, 11Schwotzer N. Kissling S. Fakhouri F. Letter regarding "Minimal change disease relapse following SARS-CoV-2 mRNA vaccine.Kidney Int. 2021; 100: 458-459Google Scholar, 12Holzworth A. Couchot P. Cruz-Knight W. et al.Minimal change disease following the Moderna mRNA-1273 SARS-CoV-2 vaccine.Kidney Int. 2021; 100: 463-464Google Scholar, 13Kervella D. Jacquemont L. Chapelet-Debout A. et al.Minimal change disease relapse following SARS-CoV-2 mRNA vaccine.Kidney Int. 2021; 100: 457-458Google Scholar, 14Leclerc S. Royal V. Lamarche C. et al.Minimal Change Disease With Severe Acute Kidney Injury Following the Oxford-AstraZeneca COVID-19 Vaccine: A Case Report.Am J Kidney Dis. 2021; Google Scholar, 15Komaba H. Wada T. Fukagawa M. Relapse of Minimal Change Disease Following the Pfizer-BioNTech COVID-19 Vaccine.Am J Kidney Dis. 2021; 78: 469-470Google Scholar, 16Maas R.J. Gianotten S. van der Meijden W.A.G. An Additional Case of Minimal Change Disease Following the Pfizer-BioNTech COVID-19 Vaccine.Am J Kidney Dis. 2021; 78: 312Google Scholar, 17Lebedev L. Sapojnikov M. Wechsler A. et al.Minimal Change Disease Following the Pfizer-BioNTech COVID-19 Vaccine.Am J Kidney Dis. 2021; 78: 142-145Google ScholarMN68 (66-70)50 (1/2)Pfizer-BioNTech, Sinovac21 De Novo (Anti-THSD7A+), 1 Flare (Anti-PLA2R+)No7-14 daysRASiNRPositive18Da Y. Goh G.H. Khatri P. A case of membranous nephropathy following Pfizer-BioNTech mRNA vaccination against COVID-19.Kidney Int. 2021; Google Scholar,19Aydin M.F. Yildiz A. Oruc A. et al.Relapse of primary membranous nephropathy after inactivated SARS-CoV-2 virus vaccination.Kidney Int. 2021; 100:...
Yuntao Bai, Ji Young Kim, Bijay Bisunke, Laura A. Jayne, Josie A. Silvaroli, Michael S. Balzer, Megha Gandhi, Kevin M. Huang, Veronika Sander, Jason Prosek, et al.
Published: 14 September 2021
Abstract:
A multitude of disease and therapy related factors drive the frequent development of kidney disorders in cancer patients. Along with chemotherapy, the newer targeted therapeutics can also cause kidney dysfunction through on and off-target mechanisms. Interestingly, among the small molecule inhibitors approved for the treatment of cancers that harbor BRAF-kinase activating mutations, vemurafenib can trigger tubular damage and acute kidney injury. BRAF is a proto-oncogene involved in cell growth. To investigate the underlying mechanisms, we developed cell culture and mouse models of vemurafenib kidney toxicity. At clinically relevant concentrations vemurafenib induces cell-death in transformed and primary mouse and human kidney tubular epithelial cells. In mice, two weeks of daily vemurafenib treatment causes moderate acute kidney injury with histopathological characteristics of kidney tubular epithelial cells injury. Importantly, kidney tubular epithelial cell-specific BRAF gene deletion did not influence kidney function under normal conditions or alter the severity of vemurafenib-associated kidney impairment. Instead, we found that inhibition of ferrochelatase, an enzyme involved in heme biosynthesis contributes to vemurafenib kidney toxicity. Ferrochelatase overexpression protected kidney tubular epithelial cells and conversely ferrochelatase knockdown increased the sensitivity to vemurafenib-induced kidney toxicity. Thus, our studies suggest that vemurafenib-associated kidney tubular epithelial cell dysfunction and kidney toxicity is BRAF-independent and caused, in part, by off-target ferrochelatase inhibition.
, Leon Fine
Published: 10 September 2021
Abstract:
Chuck’s classic textbook, co-edited with Morton Maxwell, Clinical Disorders of Fluid and Electrolyte Metabolism published first in 1962 and went through six editions. For those of our generation, then entering the new field of nephrology, that book today still reminds of the English romantic poet John Keats’s famous sonnet “On First Looking Into Chapman’s Homer”. Even sixty years later, its chapters on bone and mineral metabolism, and salt and water homeostasis, withstand critical reading. We owe much of our youthful enthusiasm for nephrology to Chuck and his inspired teaching. Many are the stories of those who heard him lecture for the first time and were entranced and captivated by the challenge of entering this new specialty of internal medicine. For, in Kleeman’s formative years, nephrology, endocrinology, and metabolism had not yet differentiated into distinct subspecialties, and his medical knowledge was broad and encyclopedic.
, Felix S. Seibert, Moritz Anft, Arturo Blazquez-Navarro, Sarah Skrzypczyk, Panagiota Zgoura, Toni L. Meister, Stephanie Pfaender, Julian Stumpf, Christian Hugo, et al.
Published: 9 September 2021
Abstract:
Renal transplant recipients (RTR) are at high risk for fatal Coronavirus disease 2019 (COVID-19) [1Council E.-E. Group E.W. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA.Nephrol Dial Transplant. 2021; 36: 87-94Crossref PubMed Google Scholar]. Vaccinations are indispensable to protect this vulnerable population. Unfortunately, >50% of solid organ recipients do not mount antibody responses after two doses of SARS-CoV-2-mRNA vaccines [2Sattler A. Schrezenmeier E. Weber U.A. Potekhin A. Bachmann F. Straub-Hohenbleicher H. Budde K. Storz E. Proß V. Bergmann Y. et al.Impaired humoral and cellular immunity after SARS-CoV2 BNT162b2 (Tozinameran) prime-boost vaccination in kidney transplant recipients.J Clin Invest. 2021 Jun 8; (Online ahead of print): 150175https://doi.org/10.1172/JCI150175Crossref Scopus (7) Google Scholar,3Miele M. Busà R. Russelli G. Sorrentino M.C. Di Bella M. Timoneri F. Mularoni A. Panarello G. Vitulo P. Conaldi P.G. Bulati M. Impaired anti-SARS-CoV-2 Humoral and Cellular Immune Response induced by Pfizer-BioNTech BNT162b2 mRNA Vaccine in Solid Organ Transplanted Patients.Am J Transplant. 2021 May 31; (Online ahead of print)https://doi.org/10.1111/ajt.16702Crossref PubMed Scopus (3) Google Scholar]. We hypothesized that a third vaccine dose elicits protective humoral and cellular immune response in primary non-responders. Ten RTR under immunosuppression (Suppl. Table 1) without measurable SARS-CoV-2 spike antibodies 4 weeks after a second dose of BNT162b2, received a third vaccine dose (mRNA-1273), which was well tolerated. The third vaccination induced seroconversion in 6 subjects (60%) with a median antibody titer concentration of 542 [IQR:478-923] U/mL and neutralizing capacity (Figure 1a,b). Correspondingly, a strong increase in the magnitude of SARS-CoV-2 Spike (S) protein-reactive T-cell immunity (median 0.08%) was observed in 9 subjects (90%) (Figure 1c,d, Suppl. Table 1) with T-cell frequencies comparable to healthy individuals [2Sattler A. Schrezenmeier E. Weber U.A. Potekhin A. Bachmann F. Straub-Hohenbleicher H. Budde K. Storz E. Proß V. Bergmann Y. et al.Impaired humoral and cellular immunity after SARS-CoV2 BNT162b2 (Tozinameran) prime-boost vaccination in kidney transplant recipients.J Clin Invest. 2021 Jun 8; (Online ahead of print): 150175https://doi.org/10.1172/JCI150175Crossref Scopus (7) Google Scholar]. Increased frequencies of cytokine-producing T-cells and follicular T-helper cells indicate a gain of anti-viral functionality (Figure 1e-i).Figure 1Humoral and cellular response following 3rd vaccination in kidney transplant recipient that failed the primary vaccination, Renal transplant recipients with failed seroconversion after BNT162b2 prime-boost vaccination were subjected to the third vaccination by mRNA-1273. Humoral and cellular immune responses before (red) and two weeks after (blue) the third vaccination are presented. ELISA was performed for the assessment of SARS-CoV-2 S-protein binding antibodies, neutralizing antibody capacity was assessed by pseudovirus system bearing the SRAS-COV-2 S-protein. S-protein-reactive T cells were analysed by flow cytometry following an overnight stimulation of PBMC with overlapping peptide pools (OPP) spanning the S-protein of SARS-CoV-2. Activation markers CD154 and CD137 were used for the assessment and quantification of S-protein-reactive T cells within CD3+ T cells. Expression of cytokines interferon(IFN)γ , tumor necrosis factor(TNF)α, and interleukin (IL)-2 as well as the effector molecule Granzyme(Grz)B were analyzed among activated CD4+ T cells by intracellular staining and flow cytometry after stimulation with OPP spanning the whole S-protein of SARS-CoV-2. Differences between the sub-cohorts were analyzed using the paired, two-sided t-test. Significance threshold was set at 0.05. Box plots depict the median, first and third quartile of a variable; the maximum length of the whiskers corresponds to 1.5 times the interquartile range. A) Titers of anti-Sars-CoV-2 spike-protein binding antibodies assessed by ELISA. B) Neutralizing antibody titers of for the SARS-CoV-2-S-protein. C) Frequencies of S-reactive CD4+ T cells as defined by CD154+CD137+ expression, D) Frequencies of S-reactive CD8+ T cells as defined by CD137 expression and cytokine production, E) Frequencies of S-reactive follicular CD4+Th cells as defined by the expression of CXCR5. F– I): Frequencies of S-reactive CD4+ T cells producing granzyme B (F), IFNγ (G), IL-2 (H), and TNFα (I)View Large Image Figure ViewerDownload Hi-res image Download (PPT)
Sam Kant,
Published: 6 September 2021
Abstract:
The advent of vaccines has resulted in mitigation of severe disease as a consequence of SARS-CoV-2. There is notable absence of humoral absence after two doses of mRNA vaccines in rheumatic and musculoskeletal diseases. 1Connolly CM, Boyarsky BJ, Ruddy JA, et al. Absence of humoral response after two-dose SARS-CoV-2 messenger RNA vaccination in patients with rheumatic and musculoskeletal diseases: A case series. Annals of internal medicine. 2021. https://search.proquest.com/docview/2532251579. doi: 10.7326/M21-1451.Google Scholar There has been evidence that administration of third dose of vaccine leads to augmentation of humoral response in kidney transplant recipients. 2Benotmane I, Gautier G, Perrin P, et al. Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients with minimal serologic response to 2 doses. JAMA : the journal of the American Medical Association. 2021. https://doi.org/10.1001/jama.2021.12339. doi: 10.1001/jama.2021.12339.Google Scholar In addition, there is increasing evidence that neutralizing antibody titers correlate with reduction in breakthrough infections in vaccinated individuals. 3Covid-19 breakthrough infections in vaccinated health care workers. The New England journal of medicine. 2021. https://search.proquest.com/docview/2556386530. doi: 10.1056/NEJMoa2109072.Google Scholar To further understand these aspects in patients with with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) on immunosuppression, we elucidated antibody response to booster doses of the COVID-19 vaccine; and sought to ascertain the effect of rituximab on SARS-CoV-2 antibody titers, given immunosuppression is known to alter immunogenicity of vaccine.
Yorg Azzi, Harith Raees, Tao Wang, Levi Cleare, Luz Liriano-Ward, Pablo Loarte-Campos, Cindy Pynadath, Maria Ajaimy, Omar Alani, Yi Bao, et al.
Published: 2 September 2021
Abstract:
The case fatality ratio of COVID-19 in kidney transplant recipients (KTR) is between 10-30%1Azzi Y. Parides M. Alani O. et al.COVID-19 infection in kidney transplant recipients at the epicenter of pandemics.Kidney international. 2020; https://doi.org/10.1016/j.kint.2020.10.004Abstract Full Text Full Text PDF Scopus (22) Google Scholar,2Azzi Y. Bartash R. Scalea J. Loarte-Campos P. Akalin E. COVID-19 and Solid Organ Transplantation: A Review Article.Transplantation. 2021; 105: 37-55https://doi.org/10.1097/TP.0000000000003523Crossref PubMed Scopus (21) Google Scholar, underscoring the importance of vaccination to prevent COVID-19. However, KTR have a reduced response to COVID-19 vaccines (18%-54%)3Boyarsky B.J. Werbel W.A. Avery R.K. et al.Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients.JAMA. 2021; 325: 2204-2206https://doi.org/10.1001/jama.2021.7489Crossref PubMed Scopus (54) Google Scholar,4Benotmane I. Gautier-Vargas G. Cognard N. et al.Weak anti-SARS-CoV-2 antibody response after the first injection of an mRNA COVID-19 vaccine in kidney transplant recipients.Kidney international. 2021; 99: 1487-1489https://doi.org/10.1016/j.kint.2021.03.014Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar. We determined SARS-CoV-2 spike IgG (anti-spike IgG) responses to COVID-19 vaccination in 65 KTRs who received BNT162b2, 29 who received mRNA-1273, and 4 who received Janssen Ad26.CoV2.S vaccines at a median of 4 years (range, 3 months-22 years) after transplantation (supplemental table and files). Twenty-one patients had prior COVID-19 infection and 11 (52%) had SARS-CoV-2 nucleocapsid IgG (anti-nucleocapsid IgG) before vaccination, of whom 20 (95%) generated anti-spike IgG. However, only 32% of 76 patients without a previous history of COVID-19 and a negative anti-nucleocapsid IgG before vaccination generated an anti-spike IgG response. The median anti-spike IgG level was significantly higher in those with prior COVID-19 (median S/CO 13.3 (7.59-16.20), vs. 6.3, (1.22-15.6), p < 0.01). African Americans, those on full dose anti-metabolite therapy, and with lower median CD3 and CD4 T cell and serum IgM levels had reduced responses (Table). Sixty-five% of those with CD4 counts > 400 and 57% with CD3 counts > 1,000 responded, but only 17% and 13%, respectively, of with CD4 counts < 400 and CD3 counts < 500 responded (Supplemental Figure 1 A and 1B). In summary, lack of response to COVID-19 vaccines was associated with African American race, being on high dose anti-metabolite therapy, and having lower pre-vaccination CD3, CD4 T cell and serum IgM levels.
Published: 1 September 2021
Kidney International, Volume 100, pp 493-495; https://doi.org/10.1016/j.kint.2021.07.010

, Hartmut H. Malluche, Vanda Jorgetti, Grahame J. Elder
Published: 1 September 2021
Kidney International, Volume 100, pp 502-505; https://doi.org/10.1016/j.kint.2021.05.024

Abstract:
Patients with chronic kidney disease–mineral and bone disorder (CKD-MBD) frequently have low bone formation rates. A recent review suggested that adynamic bone disease is not always associated with negative outcomes and therefore antiresorptive medications could be used more often. However, there is currently no evidence to support an improvement in fracture risk or mortality in patients with CKD-MBD and low bone turnover who are treated with antiresorptive medication. There is reasonable pathophysiological evidence suggesting that it may even be harmful.
Samira S. Farouk, ,
Published: 1 September 2021
Kidney International, Volume 100, pp 490-492; https://doi.org/10.1016/j.kint.2021.07.007

Abstract:
Barbara Therese Murphy, MD, MB, BAO, BCh, FRCPI, widely beloved and world-renowned transplant nephrologist, scientist, and visionary, passed away on June 30, 2021, at the age of 56. Barbara was born in 1964 in South Dublin, Ireland. After attending medical school at the Royal College of Surgeons in Ireland, she completed internship, residency, and clinical nephrology training at the Beaumont Hospital in Dublin. Presaging Barbara’s future of selfless devotion to helping those in need, while in medical school, she worked in a refugee camp near the border between Thailand and Cambodia. This area was dangerous due to threats from the Khmer Rouge, and Barbara narrowly escaped injury from an explosion in the local marketplace.
Allison L. Fisher,
Published: 1 September 2021
Kidney International, Volume 100, pp 505-508; https://doi.org/10.1016/j.kint.2021.06.023

Abstract:
Iron balance is tightly controlled to provide adequate amounts of this essential nutrient, but to limit the adverse effects of excess iron. Key mediators of systemic iron homeostasis are the iron regulatory hormone hepcidin and its receptor, the iron export protein ferroportin. A new study by Mohammad et al. demonstrates the functional role of the hepcidin-ferroportin axis in the kidney, and how this contributes to kidney iron levels and the systemic iron economy.
Zeenia Aga, , Sarah Delaney, Natalie Wong, Rachel Poley, Jeffrey Perl
Published: 1 September 2021
Kidney International, Volume 100, pp 711-712; https://doi.org/10.1016/j.kint.2021.05.020

Eibhlin Goggins,
Published: 1 September 2021
Kidney International, Volume 100, pp 508-510; https://doi.org/10.1016/j.kint.2021.05.039

Abstract:
Exosomes are emerging as a novel drug delivery system for the treatment of numerous diseases, including acute kidney injury. In this issue of Kidney International, Kim et al. use a novel optogenetically engineered exosome technology, "EXPLOR," to deliver the exosomal repressor of nuclear factor-κB into mice before and after renal ischemia-reperfusion. They report that these exosomes downregulated renal nuclear factor-κB signaling and ameliorated acute kidney injury. This study deserves attention for its significant scientific and potential clinical value in acute kidney injury.
Bernd Hoppe, Annelize Koch, Pierre Cochat, Sander F. Garrelfs, Michelle A. Baum, Jaap W. Groothoff, Graham Lipkin, Martin Coenen, Gesa Schalk, Aniruddha Amrite, et al.
Published: 1 September 2021
Abstract:
Primary hyperoxaluria (PH) is a family of ultra-rare autosomal recessive inherited disorders of hepatic glyoxylate metabolism characterized by oxalate overproduction. Nedosiran is an RNA interference agent that inhibits hepatic lactate dehydrogenase, the enzyme responsible for the common, final step of oxalate production in all three genetic subtypes of primary hyperoxaluria. Here, we assessed in a two-part, randomized, single-ascending-dose, phase 1 study (PHYOX1) the safety, pharmacokinetics, pharmacodynamics, and exposure-response of subcutaneous nedosiran in 25 healthy participants (Group A) and 18 patients with PH1 or PH2 (Group B). Group A received nedosiran (0.3, 1.5, 3.0, 6.0, then 12.0 mg/kg) or placebo, and Group B received open-label nedosiran (1.5, 3.0, or 6.0 mg/kg). No significant safety concerns were identified. Injection site reactions (four or more hours post dose) occurred in 13.3% participants in Group A and 27.8% participants in Group B. Mean maximum reduction in 24-hour urinary oxalate excretion from baseline to day 57 (end of study) across Group B dose cohorts was 55% (range: 22%–100%) after single-dose nedosiran, with 33% participants reaching normal 24-hour urinary oxalate excretion. Based on the available modeling and simulation data, a fixed monthly dose of nedosiran 160 mg (free acid; equivalent to 170 mg sodium salt) in adults was associated with the highest proportion of simulated individuals achieving normal or near-normal 24-hour urinary oxalate excretion and fewest fluctuations in urinary oxalate response. Thus, single-dose nedosiran demonstrated acceptable safety and evidence of a pharmacodynamic effect in both PH1 and PH2 subpopulations consistent with its mechanism of action.
Ana Huerta, Antonio F. Caballero Bermejo, Luis F. de Villa, Rosa Sedano, , Cristina Avendaño-Solá, José Portoles Pérez, Aranzazu Sancho-López
Published: 1 September 2021
Kidney International, Volume 100; https://doi.org/10.1016/j.kint.2021.05.010

Published: 1 September 2021
Kidney International, Volume 100, pp 511-513; https://doi.org/10.1016/j.kint.2021.06.022

Abstract:
The importance of kidney-gut crosstalk in driving kidney disease complications is increasingly being realized. However, little attention has been given to intestinal lymphatic changes in kidney disease. Zhong et al. report striking changes to intestinal lymphatic composition, structure, and function in proteinuric kidney injury models, including increased lymphangiogenesis, lymph flow, and transport of lipoproteins and proinflammatory mediators. These changes appear to be stimulated by isolevuglandin (IsoLG)-modified apolipoprotein AI (ApoAI). This intestinal lymphatic response may regulate systemic complications.
Hyung Ah Jo, Seung Hee Yang,
Published: 1 September 2021
Kidney International, Volume 100, pp 707-708; https://doi.org/10.1016/j.kint.2021.04.012

Published: 1 September 2021
Kidney International, Volume 100, pp 513-515; https://doi.org/10.1016/j.kint.2021.07.021

Abstract:
The biguanide metformin has been safely and widely used in the treatment of type 2 diabetes mellitus for decades. Preclinical studies have suggested that it may have a role in slowing disease progression in autosomal dominant polycystic kidney disease. In this issue, Perrone et al. report results from the Trial of Administration of Metformin in PKD (TAME PKD) study, a phase 2 randomized controlled trial investigating the safety and tolerability of metformin in patients in the early stages of autosomal dominant polycystic kidney disease. We discuss the implications of these findings and how they relate to a major phase 3 trial in autosomal dominant polycystic kidney disease that will start later in 2021.
Sofiane Salhi, David Ribes, Magali Colombat, Françoise Fortenfant,
Published: 1 September 2021
Kidney International, Volume 100, pp 708-709; https://doi.org/10.1016/j.kint.2021.04.011

, Luan D. Truong, Richard J. Johnson
Published: 30 August 2021
Abstract:
Although ACE2 is the receptor for SARS-CoV-2 entry into target cells, it has a major anti-inflammatory role by hydrolyzing angiotensin II, a pro-inflammatory mediator, to angiotensin 1-7, an anti-inflammatory molecule.
, Clarisse Kerleau, Claire Garandeau, Simon Ville, Diego Cantarovich, Maryvonne Hourmant, Delphine Kervella, Aurélie Meurette, Cécile Guillot-Gueguen, Irène Guihard, et al.
Published: 30 August 2021
Abstract:
Several reports have highlighted the poor humoral immune response of kidney transplant recipients following Covid mRNA vaccination compared to immunocompetent patients1Benotmane I. et al.Low immunization rates among kidney transplant recipients who received 2 doses of the mRNA-1273 SARS-CoV-2 vaccine.Kidney Int. 2021; (S0085253821003896)https://doi.org/10.1016/j.kint.2021.04.005Abstract Full Text Full Text PDF Scopus (16) Google Scholar, 2Marion O. et al.Safety and Immunogenicity of Anti–SARS-CoV-2 Messenger RNA Vaccines in Recipients of Solid Organ Transplants.Ann. Intern. Med. 2021; https://doi.org/10.7326/M21-1341Crossref Google Scholar, 3Müller L. et al.Age-dependent Immune Response to the Biontech/Pfizer BNT162b2 Coronavirus Disease 2019 Vaccination.Clin. Infect. Dis. 2021; https://doi.org/10.1093/cid/ciab381Crossref Google Scholar. Therefore, the French National Authority for Health has recommended the use of a third vaccine dose for immunosuppressed patients such as solid organ transplant recipients. We retrospectively assessed the humoral response of all kidney and pancreas transplant recipients vaccinated with BNT162b2 mRNA (Pfizer BioNTech) Covid-19 vaccine between January and May 2021 in our center. Patients with previous Covid-19 infection or positive pre-vaccination serology were excluded. The methods for detection of the anti-spike protein responses were dependent on laboratories’ practices and included, chemiluminescent microparticle immunoassay (Abbott Architect®), chemiluminescence immunoassay (Siemens Atellica®), and electrochemiluminescence immunoassay (Roche Elecsys®)). Anti-spike (IgG) responses were assessed one month after the second and third injection, patients were considered positive if their anti-spike level was above the laboratory threshold. 456 patients had a serological assessment one month after the second injection of whom 227 were positive representing 49.7% of our cohort (Table 1). 10.7% of these patients had a positive anti-spike protein one month after the first injection. Multivariate regression analysis (Table 2) revealed that there was an increased likelihood of being a non-responder after the second mRNA injection for patients treated with antimetabolite drugs (OR = 5.74, 95%CI [2.99;11.48], p < 0.0001) or steroids (OR = 3.68, 95%CI [2.10;6.66], p < 0.0001), older recipients (OR = 1.03, 95%CI [1.01;1.06], p = 0.0010), those with impaired allograft function (OR = 0.98, 95%CI [0.96;0.99], p = 0.0011) and those with a transplant ≤ 4 years (OR = 2.91, 95%CI [1.70;5.08], p = 0.0001). 136 patients had a serological assessment one month after the third injection (median of 30 days, quartile 1: 28 days, quartile 3: 32 days). The average time between the second and the third injection was 50 days. 94 patients were positive, representing a 69.2% serological conversion following the third mRNA injection (Figure 1A and Table 3). Among patients receiving a third dose, 85 had a serological assessment after both two and three injections, 34 of them (40%) became seropositive between the second and the third dose. Magnitude of immune response was investigated in 71 patients who had serological assessment using electrochemiluminescence immunoassay (Roche Elecsys®) after two and three injections (Figure 1B and 1C). Nearly all patients with a positive serology after the second mRNA vaccine had a very high titer of anti-spike antibody (> 250UI/l). Multivariate regression analysis (Table 4) determined that lymphocyte count < 1500/mm3 increased the likelihood of being a non-responder after the third mRNA injection (OR = 3.84, 95%CI [1.58;19.96], p = 0.0039), as impairment of allograft function (OR = 0.97, 95%CI [0.94;0.99], p = 0.0232). Of note, the use of antiproliferative drugs and steroids no longer seemed to significantly impact the serological conversion after the third mRNA vaccine injection. Male recipients were more likely to respond to the third mRNA vaccine injection in our cohort, without any clear explanation so far. Kidney transplant recipients respond poorly to Covid-19 mRNA vaccination, and whilst cellular responses to the vaccine seem better than humoral responses4Cucchiari D. et al.Cellular and humoral response after mRNA‐1273 SARS‐CoV‐2 vaccine in kidney transplant recipients.Am. J. Transplant. 2021; 16701 (ajt)https://doi.org/10.1111/ajt.16701Crossref Scopus (11) Google Scholar, severe Covid-19 pneumonia can occur following two mRNA vaccine injections5Caillard S. et al.Occurrence of severe COVID-19 in vaccinated transplant patients.Kidney Int. 2021; (S0085253821005093)https://doi.org/10.1016/j.kint.2021.05.011Abstract Full Text Full Text PDF Scopus (6) Google Scholar. Our data support the use of a third mRNA injection in order to improve the humoral response to vaccination from about 50% to 70%, reducing the negative impact of antimetabolite drugs and steroids on seroconversion. Moreover, for previously seropositive patients, the third mRNA vaccine largely improved the intensity of humoral response, reaching titers suggestive of neutralizing antibody activity. Indeed, seropositive assessment (especially weak titers in immunocompromised patients) is not constantly associated with protective antibodies titers5Caillard S. et al.Occurrence of severe COVID-19 in vaccinated transplant patients.Kidney Int. 2021; (S0085253821005093)https://doi.org/10.1016/j.kint.2021.05.011Abstract Full Text Full Text PDF Scopus (6) Google Scholar. However, severe lymphopenia and impaired graft function remained as risk factors for non-serological response. In this particular situation, a fourth dose, with or without immunomodulation, could be discussed in order to improve the humoral response of this highly immunosuppressed population. These data will need confirmation from other series.Table 1Characteristics associated with risk of non- humoral response to a second dose of mRNA Covid-19 vaccine after univariate...
Julien De Greef, , Imane Saad Albichr, Anais Scohy, Nada Kanaan, Hélène Georgery, Leila Belkhir, Benoit Kabamba, Jean Cyr Yombi, Eric Goffin
Published: 30 August 2021
Abstract:
Kidney transplant recipients (KTRs) are disproportionately affected by COVID-19. In addition to limited therapeutic options, concerns have arisen regarding poor vaccine efficacy in this population.(1)Georgery H, Devresse A, Yombi JC, et al. Disappointing Immunization Rate after two Doses of the BNT162b2 Vaccine in a Belgian Cohort of Kidney Transplant Recipients. Transplantation [Published online June 24, 2021]Google Scholar
Lorraine Gueguen, Charlotte Loheac, Nadia Saidani, Lydie Khatchatourian
Published: 19 August 2021
, Raja M. Kaja Kamal, James Fotheringham, Amanda Busby, Jocelyn Berdeprado, Ewa Kislowska, David Wellsted, Bassam Alchi, James O. Burton, Andrew Davenport, et al.
Published: 18 August 2021
Abstract:
Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3ml/min/1.73m2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Healthcare cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. 92% of incremental and 75% of standard arm patients had a urea clearance of 2ml/min/1.73m2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly higher compared to incremental hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.
, Claudia Torino, Francesca Mallamaci, Pantelis Sarafidis, Aikaterini Papagianni, Robert Ekart, Radovan Hojs, Marian Klinger, Krzysztof Letachowicz, Danilo Fliser, et al.
Published: 18 August 2021
Abstract:
Lung congestion, estimated by lung ultrasound is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis and may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled; 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study; 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk a treatment strategy guided by lung-ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.
, Francisco Díaz-Crespo, Ana Pérez de José, Úrsula Verdalles, Eduardo Verde, Fernando Almeida Ruiz, Adriana Acosta, Antonia Mijaylova, Marian Goicoechea
Published: 16 August 2021
Abstract:
Two cases of anti–neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis after SARS-CoV-2 vaccination have been reported to date, and both appeared after Moderna (mRNA) vaccination 1Sekar A, Campbell R, Tabbara J, Rastogi P. ANCA glomerulonephritis after the Moderna COVID-19 vaccination. Kidney Int. Published online May 31, 2021:S0085-2538(21)00555-X. doi:10.1016/j.kint.2021.05.017Google Scholar,2Anderegg MA, Liu M, Saganas C, et al. De novo vasculitis after mRNA-1273 (Moderna) vaccination. Kidney Int. Published online June 1, 2021:S0085-2538(21)00554-8. doi:10.1016/j.kint.2021.05.016Google Scholar.
Marc Ghannoum, Ingrid Berling, Valéry Lavergne, Darren M. Roberts, Tais Galvao, Robert S. Hoffman, Thomas D. Nolin, Andrew Lewington, Kent Doi, , et al.
Published: 3 August 2021
Abstract:
Baclofen toxicity results from intentional self-poisoning (acute baclofen poisoning) or accumulation of therapeutic dose in the setting of impaired kidney function. Standard care includes baclofen discontinuation, respiratory support and seizure treatment. Use of extracorporeal treatments (ECTRs) is controversial. To clarify this, a comprehensive review of the literature on the effect of ECTRs in baclofen toxicity was performed and recommendations following EXTRIP methods were formulated based on 43 studies (1 comparative cohort, 1 aggregate results cohort, 1 pharmacokinetic modeling, and 40 patient reports or series). Toxicokinetic data were available for 20 patients. Baclofen's dialyzability is limited by a high endogenous clearance and a short half-life in patients with normal kidney function. The workgroup assessed baclofen as "Moderately dialyzable" by intermittent hemodialysis for patients with normal kidney function (quality of evidence C) and "Dialyzable" for patients with impaired kidney function (quality of evidence C). Clinical data were available for 25 patients with acute baclofen poisoning and 46 patients with toxicity from therapeutic baclofen in kidney impairment. No deaths or sequelae were reported. Mortality in historical controls was rare. No benefit of ECTR was identified in patients with acute baclofen poisoning. Indirect evidence suggests a benefit of ECTR in reducing the duration of toxic encephalopathy from therapeutic baclofen in kidney impairment. These potential benefits were balanced against added costs and harms related to the insertion of a catheter, the procedure itself, and the potential of baclofen withdrawal. Thus, the EXTRIP workgroup suggests against performing ECTR in addition to standard care for acute baclofen poisoning and suggests performing ECTR in toxicity from therapeutic baclofen in kidney impairment, especially in the presence of coma requiring mechanical ventilation.
Katharina Tuschen, Jan Hinrich Bräsen, Jessica Schmitz, Martin Vischedyk,
Published: 2 August 2021
Abstract:
Several of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines use a mRNA lipid nanoparticle-encapsulated platform. In experimental models, the induced antibody titers are higher and T-and B-cell responses are enhanced compared to traditional vaccines. Possibly, due to this higher efficacy, more and more kidney specific side effects of mRNA vaccines related to immune-mediated glomerular disease are reported 1Negrea L. Rovin B.H. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy.Kidney International. 2021; 99https://doi.org/10.1016/j.kint.2021.03.002Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar, 2Tan HZ, Tan RY, Choo JCJ, et al. Is COVID-19 vaccination unmasking glomerulonephritis? Kidney International. Published online May 2021. doi:10.1016/j.kint.2021.05.009Google Scholar, 3Lebedev L. Sapojnikov M. Wechsler A. et al.Minimal Change Disease Following the Pfizer-BioNTech COVID-19 Vaccine.American Journal of Kidney Diseases. 2021; 78https://doi.org/10.1053/j.ajkd.2021.03.010Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar. Because of similar type I interferon and proinflammatory cytokine pathways in systemic lupus erythematodes and COVID-19, either potentiated or dysregulated immune responses to SARS-CoV-2 vaccines can be suspected to trigger disease activity in previously stable lupus 4Tang W. Askanase A.D. Khalili L. Merrill J.T. SARS-CoV-2 vaccines in patients with SLE.Lupus Science & Medicine. 2021; 8https://doi.org/10.1136/lupus-2021-000479Crossref Scopus (4) Google Scholar.
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