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in category nephrology

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1: 2019 novel coronavirus disease in hemodialysis (HD) patients: Report from one HD center in Wuhan, China
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Posted 25 Feb 2020

2019 novel coronavirus disease in hemodialysis (HD) patients: Report from one HD center in Wuhan, China
13,579 downloads medRxiv nephrology

Yiqiong Ma, Bo Diao, Xifeng Lv, Jili Zhu, Wei Liang, Lei Liu, Wenduo Bu, Huiling Cheng, Sihao Zhang, Lianhua Yang, Ming Shi, Guohua Ding, Bo Shen, Huiming Wang

Importance: The outbreak of highly contagious COVID-19 has posed a serious threat to human health, especially for those with underlying diseases. However, Impacts of COVID-19 epidemic on HD center and HD patients have not been reported. Objective: To summery an outbreak of COVID-19 epidemic in HD center. Design, Setting, and Participants: We reviewed the epidemic course from the first laboratory-confirmed case of COVID-19 infection on January 14 to the control of the epidemic on March 12 in the HD center of Renmin Hospital of Wuhan University. Total 230 HD patients and 33 medical staff were included in this study Exposures: COVID-19. Main Outcomes and Measures: Epidemiological, clinical, laboratory, and radiological characteristics and outcomes data were collected and analyzed. 19 COVID-19 HD patients, 19 non-COVID-19 HD patients and 19 healthy volunteers were enrolled for further study about the effect of SARS-CoV-2 infection on host immune responses. Results: 42 out of 230 HD patients (18.26%) and 4 out of 33 medical staffs(12.12%) were diagnosed with COVID-19 from the outbreak to March 12, 2020. 13 HD patients (5.65%), including 10 COVID-19 diagnosed, died during the epidemic. Only 2 deaths of the COVID-19 HD patients were associated with pneumonia/lung failure. Except 3 patients were admitted to ICU for severe condition (8.11%), including 2 dead, most COVID-19 diagnosed patients presented mild or none-respiratory symptoms. Multiple lymphocyte populations in HD patients were significantly decreased. HD patients with COVID-19 even displayed more remarkable reduction of serum inflammatory cytokines than other COVID-19 patients. Conclusions and Relevance: HD patients are the highly susceptible population and HD centers are high risk area during the outbreak of COVID-19 epidemic. HD Patients with COVID-19 are mostly clinical mild and unlikely progress to severe pneumonia due to the impaired cellular immune function and incapability of mounting cytokines storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of COVID-19 epidemic on HD patients.

2: Kidney impairment is associated with in-hospital death of COVID-19 patients
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Posted 20 Feb 2020

Kidney impairment is associated with in-hospital death of COVID-19 patients
11,483 downloads medRxiv nephrology

Yichun Cheng, Ran Luo, Kun Wang, Meng Zhang, Zhixiang Wang, Lei Dong, Junhua Li, Ying Yao, Shuwang Ge, Gang Xu

BackgroundInformation on kidney impairment in patients with coronavirus disease 2019 (COVID-19) is limited. This study aims to assess the prevalence and impact of abnormal urine analysis and kidney dysfunction in hospitalized COVID-19 patients in Wuhan. MethodsWe conducted a consecutive cohort study of COVID-19 patients admitted in a tertiary teaching hospital with 3 branches following a major outbreak in Wuhan in 2020. Hematuria, proteinuria, serum creatinine concentration and other clinical parameters were extracted from the electronic hospitalization databases and laboratory databases. Incidence rate for acute kidney injury (AKI) was examined during the study period. Association between kidney impairment and in-hospital death was analyzed. ResultsWe included 710 consecutive COVID-19 patients, 89 (12.3%) of whom died in hospital. The median age of the patients was 63 years (inter quartile range, 51-71), including 374 men and 336 women. On admission, 44% of patients have proteinuria hematuria and 26.9% have hematuria, and the prevalence of elevated serum creatinine and blood urea nitrogen were 15.5% and 14.1% respectively. During the study period, AKI occurred in 3.2% patients. Kaplan-Meier analysis demonstrated that patients with kidney impairment have higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated serum creatinine, elevated urea nitrogen, AKI, proteinuria and hematuria was an independent risk factor for in-hospital death after adjusting for age, sex, disease severity, leukocyte count and lymphocyte count. ConclusionsThe prevalence of kidney impairment (hematuria, proteinuria and kidney dysfunction) in hospitalized COVID-19 patients was high. After adjustment for confounders, kidney impairment indicators were associated with higher risk of in-hospital death. Clinicians should increase their awareness of kidney impairment in hospitalized COVID-19 patients.

3: Impaired antigen-specific memory B cell and plasma cell responses including lack of specific IgG upon SARS-CoV-2 BNT162b2 vaccination among Kidney Transplant and Dialysis patients
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Posted 20 Apr 2021

Impaired antigen-specific memory B cell and plasma cell responses including lack of specific IgG upon SARS-CoV-2 BNT162b2 vaccination among Kidney Transplant and Dialysis patients
4,682 downloads medRxiv nephrology

Hector Rincon-Arevalo, Mira Choi, Ana-Luisa Stefanski, Fabian Halleck, Ulrike Weber, Franziska Szelinski, Bernd Jahrsdoerfer, Hubert Schrezenmeier, Carolin Ludwig, Arne Sattler, Katja Kotsch, Alexander Potekhin, Yidan Chen, Gerd-Ruediger Burmester, Kai-Uwe Eckardt, Gabriela Maria Guerra, Pawel Durek, Frederik Heinrich, Marta Ferreira-Gomes, Andreas Radbruch, Klemens Budde, Andreia C. Lino, Mir-Farzin Mashreghi, Eva Schrezenmeier, Thomas Doerner

Patients with kidney failure are at increased risk during the COVID-19 pandemic and effective vaccinations are needed. It is not known how efficient mRNA vaccines mount B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 25 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to 100% seroconversion in HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG positivity in 31 (70.5%) and anti-S1 IgA in 30 (68.2%) of 44, respectively. In contrast, KTR did not develop IgG response except one patient who had prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas these RBD+ B cells were enriched among pre-switch and naive B cells from DP and KTR. Single cell transcriptome and CITE-seq analyses found reduced frequencies of plasmablasts, TCF7+CD27+GZMK+ T cells and proliferating MKI67-expressing lymphocytes among KTR non-responders. Importantly, the frequency and absolute number of antigen-specific circulating plasmablasts in the whole cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, this data indicate that lack of T cell help related to immunosuppression results in impaired germinal center differentiation of B and plasma cell memory. There is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis.

4: Acute Kidney Injury in Hospitalized Patients with COVID-19
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Posted 08 May 2020

Acute Kidney Injury in Hospitalized Patients with COVID-19
4,592 downloads medRxiv nephrology

Lili Chan, Kumardeep Chaudhary, Aparna Saha, Kinsuk Chauhan, Akhil Vaid, Mukta Baweja, Kirk Campbell, Nicholas Chun, Miriam Chung, Priya Deshpande, Samira S Farouk, Lewis Kaufman, Tonia Kim, Holly Koncicki, Vijay Lapsia, Staci Leisman, Emily Lu, Kristin Meliambro, Madhav C Menon, Joshua L Rein, Shuchita Sharma, Joji Tokita, Jaime Uribarri, Joseph A Vassalotti, Jonathan Winston, Kusum S Mathews, Shan Zhao, Ishan Paranjpe, Sulaiman Somani, Felix Richter, Ron Do, Riccardo Miotto, Anuradha Lala, Arash Kia, Prem Timsina, Li Li, Matteo Danieletto, Eddye Golden, Patricia Glowe, Micol Zweig, Manbir Singh, Robert Freeman, Rong Chen, Eric Nestler, Jagat Narula, Allan C. Just, Carol Horowitz, Judith Aberg, Ruth JF Loos, Judy Cho, Zahi Fayad, Carlos Cordon-Cardo, Eric Schadt, Matthew Levin, David L Reich, Valentin Fuster, Barbara Murphy, John Cijiang He, Alexander Charney, Erwin P Bottinger, Benjamin S Glicksberg, Steven G Coca, Girish N Nadkarni

Importance: Preliminary reports indicate that acute kidney injury (AKI) is common in coronavirus disease (COVID)-19 patients and is associated with worse outcomes. AKI in hospitalized COVID-19 patients in the United States is not well-described. Objective: To provide information about frequency, outcomes and recovery associated with AKI and dialysis in hospitalized COVID-19 patients. Design: Observational, retrospective study. Setting: Admitted to hospital between February 27 and April 15, 2020. Participants: Patients aged [≥]18 years with laboratory confirmed COVID-19 Exposures: AKI (peak serum creatinine increase of 0.3 mg/dL or 50% above baseline). Main Outcomes and Measures: Frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aOR) with mortality. We also trained and tested a machine learning model for predicting dialysis requirement with independent validation. Results: A total of 3,235 hospitalized patients were diagnosed with COVID-19. AKI occurred in 1406 (46%) patients overall and 280 (20%) with AKI required renal replacement therapy. The incidence of AKI (admission plus new cases) in patients admitted to the intensive care unit was 68% (553 of 815). In the entire cohort, the proportion with stages 1, 2, and 3 AKI were 35%, 20%, 45%, respectively. In those needing intensive care, the respective proportions were 20%, 17%, 63%, and 34% received acute renal replacement therapy. Independent predictors of severe AKI were chronic kidney disease, systolic blood pressure, and potassium at baseline. In-hospital mortality in patients with AKI was 41% overall and 52% in intensive care. The aOR for mortality associated with AKI was 9.6 (95% CI 7.4-12.3) overall and 20.9 (95% CI 11.7-37.3) in patients receiving intensive care. 56% of patients with AKI who were discharged alive recovered kidney function back to baseline. The area under the curve (AUC) for the machine learned predictive model using baseline features for dialysis requirement was 0.79 in a validation test. Conclusions and Relevance: AKI is common in patients hospitalized with COVID-19, associated with worse mortality, and the majority of patients that survive do not recover kidney function. A machine-learned model using admission features had good performance for dialysis prediction and could be used for resource allocation.

5: Hemodialysis Patients Show a Highly Diminished Antibody Response after COVID-19 mRNA Vaccination Compared to Healthy Controls
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Posted 26 Mar 2021

Hemodialysis Patients Show a Highly Diminished Antibody Response after COVID-19 mRNA Vaccination Compared to Healthy Controls
3,951 downloads medRxiv nephrology

Benedikt Simon, Harald Rubey, Andreas Treipl, Martin Gromann, Boris Hemedi, Sonja Zehetmayer, Bernhard Kirsch

1. Abstract 1.1 Background and Objectives Hemodialysis patients are prone to infection with SARS-COV2 and show a high probability of a severe course of disease and high mortality when infected. In many countries hemodialysis patients are prioritised in vaccination programs to protect this vulnerable community. However, no hemodialysis patients were included in efficacy trials of SARS CoV-2 vaccines and therefore efficacy and safety data for this patient group are lacking. These data would be critical, since hemodialysis patients showed decreased responses against various other vaccines and this could mean decreased response to SARS CoV-2 vaccines. 1.2 Design, setting, participants, and measurements We conducted a prospective cohort study consisting of a group of 81 hemodialysis patients and 80 healthy controls who were vaccinated with mRNA vaccine BNT162b2 (BionTech/Pfizer, 2 doses with an interval of 21 days). Anti-SARS-COV-2 S antibody response in all participants was measured 21 days after the second dose. The groups were compared with univariate quantile regressions and a multiple analysis. Adverse events (AEs) of the vaccination were assessed with a standardized questionnaire. We also performed a correlation of HBs-Antibody response with the SARS-COV-2 antibody response in the hemodialysis patients. 1.3 Results Dialysis patients had significantly lower Anti-SARS-COV-2 S antibody titres than healthy control patients 21 days after vaccination with BNT162b2 (median dialysis Patients 171 U/ml versus median controls 2500 U/ml). Age also had a significant but less pronounced influence on antibody titres. Dialysis patients showed less AEs than the control group. No significant correlation was found for Hepatitis B vaccine antibody response and SARS CoV-2 vaccine antibody response. 1.4 Conclusions Hemodialysis patients exhibit highly diminished SARS-COV-2 S antibody titres compared to a cohort of controls. Therefore these patients could be much less protected by SARS CoV-2 mRNA vaccination than expected. Alternative vaccination schemes must be considered and preventive measures must be maintained after vaccination.

6: SARS-CoV-2 receptor networks in diabetic kidney disease, BK-Virus nephropathy and COVID-19 associated acute kidney injury
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Posted 13 May 2020

SARS-CoV-2 receptor networks in diabetic kidney disease, BK-Virus nephropathy and COVID-19 associated acute kidney injury
3,630 downloads medRxiv nephrology

Rajasree Menon, Edgar A. Otto, Rachel Sealfon, Viji Nair, Aaron K Wong, Chandra L Theesfeld, Xi Chen, Yuan Wang, Avinash Boppanna, Jinghui Luo, Yingbao Yang, Peter M Kasson, Jennifer A Schaub, Celine C Berthier, Sean Eddy, Chrysta C Lienczewski, Bradley Godfrey, Susan L Dagenais, Ryann Sohaney, John Hartman, Damian Fermin, Lalita Subramanian, Helen C Looker, Jennifer L Harder, Laura H. Mariani, Sangeeta R Hingorani, Jonathan Z. Sexton, Christiane E Wobus, Abhijit S Naik, Robert G Nelson, Olga G. Troyanskaya, Matthias Kretzler

COVID-19 morbidity and mortality is increased in patients with diabetes and kidney disease via unknown mechanisms. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Since ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease (DKD) and medications alter ACE2 receptor expression in kidneys. Single cell RNA profiling of healthy living donor (LD) and DKD kidney biopsies revealed ACE2 expression primarily in proximal tubular epithelial cells (PTEC). This cell specific localization was confirmed by in situ hybridization. ACE2 expression levels were unaltered by exposures to renin angiotensin aldosterone system inhibitors in DKD. Bayesian integrative analysis of a large compendium of public -omics datasets identified molecular network modules induced in ACE2-expressing PTEC in DKD (searchable at hb.flatironinstitute.org/covid-kidney) that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. The DKD ACE2-positive PTEC module overlapped with expression patterns seen in SARS-CoV-2 infected cells. Similar cellular programs were seen in ACE2-positive PTEC obtained from urine samples of 13 COVID-19 patients who were hospitalized, suggesting a consistent ACE2-coregulated PTEC expression program that may interact with the SARS-CoV-2 infection processes. Thus SARS-CoV-2 receptor networks can seed further research into risk stratification and therapeutic strategies for COVID-19 related kidney damage.

7: Analysis of early renal injury in COVID-19 and diagnostic value of multi-index combined detection
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Posted 10 Mar 2020

Analysis of early renal injury in COVID-19 and diagnostic value of multi-index combined detection
3,470 downloads medRxiv nephrology

Xu-wei Hong, Ze-pai Chi, Guo-yuan Liu, Hong Huang, Shun-qi Guo, Jing-ru Fan, Xian-wei Lin, Liao-zhun Qu, Rui-lie Chen, Ling-jie Wu, Liang-yu Wang, Qi-chuan Zhang, Su-wu Wu, Ze-qun Pan, Hao Lin, Yu-hua Zhou, Yong-hai Zhang

ObjectivesThe aim of the study was to analyze the incidence of COVID-19 with early renal injury, and to explore the value of multi-index combined detection in diagnosis of early renal injury in COVID-19. DesignThe study was an observational, descriptive study. SettingThis study was carried out in a tertiary hospital in Guangdong, China. Participants12 patients diagnosed with COVID-19 from January 20, 2020 to February 20, 2020. Primary and secondary outcome measuresThe primary outcome was to evaluate the incidence of early renal injury in COVID-19. In this study, the estimated glomerular filtration rate (eGFR), endogenous creatinine clearance (Ccr) and urine microalbumin / urinary creatinine ratio (UACR) were calculated to assess the incidence of early renal injury. Secondary outcomes were the diagnostic value of urine microalbumin (UMA), 1-microglobulin (A1M), urine immunoglobulin-G (IGU), urine transferring (TRU) alone and in combination in diagnosis of COVID-19 with early renal injury. ResultsWhile all patients had no significant abnormalities in serum creatinine (Scr) and blood urea nitrogen (BUN), the abnormal rates of eGFR, Ccr, and UACR were 66.7%, 41.7%, and 41.7%, respectively. Urinary microprotein detection indicated that the area under curve (AUC) of multi-index combined to diagnose early renal injury in COVID-19 was 0.875, which was higher than UMA (0,813), A1M (0.813), IGU (0.750) and TRU (0.750) alone. Spearman analysis showed that the degree of early renal injury was significantly related to C-reactive protein (CRP) and neutrophil ratio (NER), suggesting that the more severe the infection, the more obvious the early renal injury. Hypokalemia and hyponatremia were common in patients with COVID-19, and there was a correlation with the degree of renal injury. ConclusionsEarly renal injury was common in patients with COVID-19. Combined detection of UMA, A1M, IGU, and TRU was helpful for the diagnosis of early renal injury in COVID-19.

8: Hypokalemia in Patients with COVID-19
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Posted 16 Jun 2020

Hypokalemia in Patients with COVID-19
2,648 downloads medRxiv nephrology

Gaetano Alfano, Annachiara Ferrari, Francesco Fontana, Rossella Perrone, Giacomo Mori, Elisabetta Ascione, Magistroni Riccardo, Giulia Venturi, Simone Pederzoli, Gianluca Margiotta, Marilina Romeo, Francesca Piccinini, Giacomo Franceschi, Sara Volpi, Matteo Faltoni, Giacomo Ciusa, Erica Bacca, Marco Tutone, Alessandro Raimondi, marianna menozzi, Erica Franceschini, Gianluca Cuomo, Gabriella Orlando, Antonella Santoro, Margherita Di Gaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, Jovana Milic, Marianna Meschiari, Cristina Mussini, Gianni Cappelli, Giovanni Guaraldi

Patients with COVID-19 may experience multiple conditions (e.g., fever, hyperventilation, anorexia, gastroenteritis, acid-base disorder) that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder that may increase the susceptibility to various kinds of arrhythmia. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of non-critically ill patients. A retrospective analysis was conducted on 290 hospitalized patients with confirmed COVID-19 infection at the tertiary teaching hospital of Modena, Italy. Hypokalemia (<3.5 mEq/L) was detected in 119 patients (41%). The decrease of serum potassium level was of mild entity (3-3.4 mEq/L) and occurred in association with hypocalcemia (P=0.001) and lower level of serum magnesium (P=0.028) compared to normokaliemic patients. Urine K: creatinine ratio, measured in a small subset of patients (n=45; 36.1%), showed an increase of urinary potassium excretion in the majority of the cases (95.5%). Causes of kaliuria were diuretic therapy (53.4%) and corticosteroids (23.3%). In the remaining patients, urinary potassium loss was associated with normal serum magnesium, low sodium excretion (FENa< 1%) and metabolic alkalosis. Risk factors for hypokalemia were female gender (P=0.002; HR 0.41, 95%CI 0.23-0.73) and diuretic therapy (P=0.027; HR 1.94, 95%CI 1.08-3.48). Hypokalemia, adjusted for sex, age and SOFA score, resulted not associated with ICU admission (P=0.131, 95% CI 0.228-1.212) and in-hospital mortality (P=0.474; 95% CI 0,170-1,324) in our cohort of patients. Hypokalemia is a frequent disorder in COVID-19 patients and urinary potassium loss may be the main cause of hypokalemia. The disorder was mild in the majority of the patients and was unrelated to poor outcomes. Nevertheless, hypokalemic patients required potassium supplements to dampen the risk of arrhythmias.

9: Immunogenicity of SARS-CoV-2 Vaccine in Dialysis
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Posted 13 Apr 2021

Immunogenicity of SARS-CoV-2 Vaccine in Dialysis
1,995 downloads medRxiv nephrology

Eduardo Lacson, Christos Argyropoulos, Harold J Manley, Gideon Aweh, Andrew I Chin, Loay H Salman, Caroline M Hsu, Doug S Johnson, Daniel E Weiner

Abstract Importance: Patients receiving maintenance dialysis patients are at high risk for morbidity and mortality from COVID-19. The immunogenicity of SARS-CoV-2 mRNA vaccines is unknown in this vulnerable population where immune compromise is common. Objective: To determine seroresponse to vaccination against SARS-CoV-2 utilizing mRNA vaccines among patients receiving maintenance dialysis. Design: Retrospective observational study. Setting: Dialysis Clinic, Inc. (DCI) outpatient dialysis clinics in the United States. Participants: All patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with SARS-CoV-2 spike-antibody test results drawn at least 14 days after the second dose, as documented in the electronic health record through March 18, 2021. Exposure: Two doses of BNT162b2/Pfizer or of mRNA-1273/Moderna vaccines administered per manufacturer recommendations. Main Outcomes and Measures: Levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen (seropositive: 2 or greater) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G). The DCI clinical protocol for in-clinic administration included baseline and follow-up levels although initial administration of the vaccine occurred primarily elsewhere (e.g. long-term care facilities, hospitals, etc.) during the evaluation period. Hence, only post-vaccination antibody levels were reported. Results: Among 186 patients receiving maintenance dialysis from 32 clinics in 8 states tested an average of 23 days after receiving 2 vaccine doses, mean age was 68 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 history, seropositive rate was 38/38 (100%) with 97% at maximum titer. Conclusions and Relevance: Most patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 develop robust antibody response. These results support an equitable and aggressive vaccination strategy for all eligible patients receiving maintenance dialysis, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.

10: Justification, safety, and efficacy of a third dose of mRNA vaccine in maintenance hemodialysis patients: a prospective observational study
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Posted 06 Jul 2021

Justification, safety, and efficacy of a third dose of mRNA vaccine in maintenance hemodialysis patients: a prospective observational study
1,821 downloads medRxiv nephrology

Maxime Espi, Xavier Charmetant, Thomas Barba, Caroline Pelletier, Laetitia Koppe, Elodie Chalencon, Emilie Kalbacher, Virginie Mathias, Anne Ovize, Emmanuelle Cart-Tanneur, Christine Bouze, Laurence Pellegrina, Emmaunel Morelon, Laurent Juillard, Denis Fouque, Cecile Couchoud, Olivier Thaunat

Background: Patients on maintenance hemodialysis (MHD) are at high risk of infection with SARS-Cov-2 and death due to COVID-19. This vulnerable population has been prioritized for vaccination, but the level of protection achieved in these immunocompromised patients is unclear. Objectives: To evaluate the protection of MHD patients against COVID-19 after 2 doses (2D) of BNT162b2, and the safety and impact on immune responses of a 3rd dose (3D). Design: Prospective observational. Setting, Patients, intervention and measurements: REIN national registry was used to compare the severity of 1474 cases of COVID-19 diagnosed in MHD patients after 0, 1 or 2 doses of mRNA vaccine. Anti-spike receptor binding domain (RBD) IgG and interferon gamma-producing CD4+ and CD8+ specific-T cells were measured after 2D and 3D of BNT162b2 in a monocentric cohort of 75 MHD patients. Results: Vaccination reduced disease severity but 11% of MHD patients infected after 2D still died. Tolerance to 3D of BNT162b2 was excellent. MHD patients with humoral response similar to healthy volunteers after 2D did not generate more immune effectors after 3D and had more side effects. In contrast, 2/3 of MHD patients with suboptimal response after 2D reached optimal titer of anti-RBD IgG and/or developed spike-specific CD8+ T cells after 3D. Presence of spike-specific CD4+ T cells after 2D was associated with response to 3D in multivariate analysis (OR=4.80 [1.23-21.54]; p=0.029). Limitations: Limited number of patients injected with 3D. Conclusion: Standard scheme of vaccination provides insufficient protection to some MHD patients. Anti-RBD IgG and specific CD4+ T cells should be measured after 2D. Among patients with suboptimal humoral response, those with specific CD4+ T cells could benefit of a 3rd dose of vaccine.

11: Autoantibodies against nephrin elucidate a novel autoimmune phenomenon in proteinuric kidney disease
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Posted 02 Mar 2021

Autoantibodies against nephrin elucidate a novel autoimmune phenomenon in proteinuric kidney disease
1,807 downloads medRxiv nephrology

Andrew J.B. Watts, Keith H. Keller, Gabriel Lerner, Ivy Rosales, A. Bernard Collins, Miroslav Sekulic, Sushrut S. Waikar, Anil Chandraker, Leonardo V. Riella, Mariam P. Alexander, Jonathan P. Troost, Junbo Chen, Damian Fermin, Jennifer Lai Yee, Matthew Sampson, Laurence H. Beck, Joel M Henderson, Anna Greka, Helmut G. Rennke, Astrid Weins

Dysfunction of podocytes, cells critical for glomerular filtration, underlies proteinuria and kidney failure. Genetic forms of proteinuric kidney disease can be caused by mutations in several podocyte genes, including nephrin, a critical component of the kidney filter. In contrast, the etiology of acquired acute-onset nephrotic syndrome has remained elusive. Here we identify autoantibodies against nephrin in serum and glomeruli of a subset of adults and children with non-congenital acute nephrotic syndrome. Our findings align with published experimental animal studies and elucidate a novel autoimmune phenomenon in proteinuric kidney disease interfering with glomerular filter integrity.

12: Deep learning driven quantification of interstitial fibrosis in kidney biopsies
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Posted 04 Jan 2021

Deep learning driven quantification of interstitial fibrosis in kidney biopsies
1,688 downloads medRxiv nephrology

Yi Zheng, Clarissa A. Cassol, Saemi Jung, Divya Veerapaneni, Vipul C Chitalia, Kevin Ren, Shubha S. Bellur, Peter Boor, Laura M. Barisoni, Sushrut S. Waikar, Margrit Betke, Vijaya B. Kolachalama

Interstitial fibrosis and tubular atrophy (IFTA) on a renal biopsy are strong indicators of disease chronicity and prognosis. Techniques that are typically used for IFTA grading remain manual, leading to variability among pathologists. Accurate IFTA estimation using computational techniques can reduce this variability and provide quantitative assessment by capturing the pathologic features. Using trichrome-stained whole slide images (WSIs) processed from human renal biopsies, we developed a deep learning (DL) framework that captured finer pathological structures at high resolution and overall context at the WSI-level to predict IFTA grade. WSIs (n=67) were obtained from The Ohio State University Wexner Medical Center (OSUWMC). Five nephropathologists independently reviewed them and provided fibrosis scores that were converted to IFTA grades: <=10% (None or minimal), 11-25% (Mild), 26-50% (Moderate), and >50% (Severe). The model was developed by associating the WSIs with the IFTA grade determined by majority voting (reference estimate). Model performance was evaluated on WSIs (n=28) obtained from the Kidney Precision Medicine Project (KPMP). There was good agreement on the IFTA grading between the pathologists and the reference estimate (Kappa=0.622{+/-}0.071). The accuracy of the DL model was 71.8{+/-}5.3% on OSUWMC and 65.0{+/-}4.2% on KPMP datasets, respectively. Identification of salient image regions by combining microscopic and WSI-level pathological features yielded visual representations that were consistent with the pathologist-based IFTA grading. Our approach to analyzing microscopic- and WSI-level changes in renal biopsies attempts to mimic the pathologist and provides a regional and contextual estimation of IFTA. Such methods can assist clinicopathologic diagnosis. Translational statementPathologists rely on interstitial fibrosis and tubular atrophy (IFTA) to indicate chronicity in kidney biopsies and provide a prognostic indicator of renal survival. Although guidelines for evaluation of IFTA exist, there is variability in IFTA estimation among pathologists. In this work, digitized kidney biopsies were independently reviewed by five nephropathologists and majority voting on their ratings was used to determine the IFTA grade. Using this information, a deep learning model was developed that captured microscopic and holistic features on the digitized biopsies and accurately predicted the IFTA grade. The study illustrates that deep learning can be utilized effectively to perform IFTA grading, thus enhancing conventional clinicopathologic diagnosis.

13: Assessment of medication Dosage Adjustment in Hospitalized Patients with Chronic Kidney Disease
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Posted 08 May 2020

Assessment of medication Dosage Adjustment in Hospitalized Patients with Chronic Kidney Disease
1,455 downloads medRxiv nephrology

Zair Hassan, Iftikhar Ali, Arslan Rahat Ullah, Raheel Ahmad, Shakeel Rehman, Azizullah Khan

In patients with renal impairment, inappropriate medication dosing can develop adverse drug reactions (ADRs) or ineffective therapy due to declined renal function. This necessitates proper renal dosing adjustment. Using a retrospective analysis of medical records, this study was proposed to evaluate medication dosage adjustment in hospitalized chronic kidney disease (CKD) patients.This retrospective review of medical records was conducted at the Institute of Kidney Disease (IKD), Peshawar. It included all CKD patients hospitalized between June 01, 2019 and May 31, 2020 and receiving at least one medication that needed adjustment. Glomerular filtration rate was calculated using Renal Disease Diet Modification (RDDM) equation, and dose suitability was established by evaluating practice with relevant guidelines. Of the total 1537 CKD patients, 231(15.03%) had evidence of dosing error, which were considered for final analysis. Overall, 1549 drugs were prescribed, 480(30.99%) drugs required dose adjustment of which 196(40.42%) were adjusted properly and the remaining 286(59.58%) were unadjusted. The most common unadjusted drugs were meropenem, cefepime, ciprofloxacin and rosuvastatin, whereas captopril, aspirin, bisoprolol, pregabalin and levofloxacin had the highest percentage of adjusted drugs. On multivariate logistic regression, the number of drugs requiring dosing adjustments and obstructive nephropathy were found to be statistically significant factors that increased the likelihood of the medication dosing errors; A unit increase in the number of drugs requiring dose adjustment increases 5.241 times the likelihood of dosing error. Similarly the presence of obstructive nephropathy (Odds ratio (OR) 0.383, 95% confidence interval (Cl) [0.153-0.960] P= 0.041) was found to be significantly associated with dosing error after adjustment for potential confounding factors.The dosing of more than half of the prescribed drugs that required adjustment in CKD were not adjusted which showed that medication dosing errors were high. This highlights the importance of medication prescription according to guidelines in CKD patients to improve the outcomes of pharmacotherapy and patients quality of life.

14: Derivation and validation of a machine learning risk score using biomarker and electronic patient data to predict rapid progression of diabetic kidney disease
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Posted 02 Jun 2020

Derivation and validation of a machine learning risk score using biomarker and electronic patient data to predict rapid progression of diabetic kidney disease
1,420 downloads medRxiv nephrology

Lili Chan, Girish N Nadkarni, Fergus Fleming, James R McCullough, Patti Connolly, Gohar Mosoyan, Fadi El Salem, Michael W. Kattan, Joseph A Vassalotti, Barbara Murphy, Michael J. Donovan, Steven G Coca, Scott Damrauer

Importance: Diabetic kidney disease (DKD) is the leading cause of kidney failure in the United States and predicting progression is necessary for improving outcomes. Objective: To develop and validate a machine-learned, prognostic risk score (KidneyIntelXTM) combining data from electronic health records (EHR) and circulating biomarkers to predict DKD progression. Design: Observational cohort study Setting: Two EHR linked biobanks: Mount Sinai BioMe Biobank and the Penn Medicine Biobank. Participants: Patients with prevalent DKD (G3a-G3b with all grades of albuminuria (A1-A3) and G1 & G2 with A2-A3 level albuminuria) and banked plasma. Main outcomes and measures: Plasma biomarkers soluble tumor necrosis factor 1/2 (sTNFR1, sTNFR2) and kidney injury molecule-1 (KIM-1) were measured at baseline. Patients were divided into derivation [60%] and validation sets [40%]. A composite primary end point of rapid kidney function decline (RKFD) (estimated glomerular filtration rate (eGFR) decline of [&ge;]5 ml/min/1.73m2/year), [&ge;]40% sustained decline, or kidney failure within 5-years. A machine learning model (random forest) was trained and performance assessed using standard metrics. Results: In 1146 patients with DKD the median age was 63, 51% were female, median baseline eGFR was 54 ml/min/1.73 m2, urine albumin to creatinine ratio (uACR) was 61 mg/g, and follow-up was 4.3 years. 241 patients (21%) experienced RKFD. On 10-fold cross validation in the derivation set (n=686), the risk model had an area under the curve (AUC) of 0.77 (95% CI 0.74-0.79). In validation (n=460), the AUC was 0.77 (95% CI 0.76-0.79). By comparison, the AUC for an optimized clinical model was 0.62 (95% CI 0.61-0.63) in derivation and 0.61 (95% CI 0.60-0.63) in validation. Using cutoffs from derivation, KidneyIntelX stratified 47%, 37% and 16% of validation cohort into low-, intermediate- and high-risk groups, with a positive predictive value (PPV) of 62% (vs. 41% for KDIGO) in the high-risk group and a negative predictive value (NPV) of 91% in the low-risk group. The net reclassification index for events into high-risk group was 41% (p<0.05). Conclusions and Relevance: A machine learned model combining plasma biomarkers and EHR data improved prediction of adverse kidney events within 5 years over KDIGO and standard clinical models in patients with early DKD.

15: Antibody Response to COVID-19 vaccination in Patients Receiving Dialysis
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Posted 12 May 2021

Antibody Response to COVID-19 vaccination in Patients Receiving Dialysis
1,293 downloads medRxiv nephrology

Shuchi Anand, Maria E Montez-Rath, Jialin Han, Pablo Garcia, LinaCel Cadden, Patti Hunsader, Russell Kerschmann, Paul Beyer, Mary Dittrich, Geoffrey A Block, Scott D. Boyd, Julie Parsonnet, Glenn M Chertow

Background: Patients receiving dialysis may mount impaired responses to COVID19 vaccination. Methods: We report antibody response to vaccination from 1140 patients without, and 493 patients with pre-vaccination SARS-CoV-2 RBD antibody. We used commercially available assays (Siemens) to test remainder plasma monthly in association with vaccination date and type, and assess prevalence of absent total receptor binding antibody, and absent or attenuated (index value < 10) semiquantitative receptor binding domain IgG index values. We used Poisson regression to evaluate risk factors for absent or attenuated response to vaccination. Results: Among patients who were seronegative versus seropositive before vaccination, 62% and 56% were [&ge;]65 years old, 20% and 24% were Hispanic, and 22% and 23% were Black. Median IgG index values rose steadily over time, and were higher among the seropositive than in the seronegative patients after completing vaccination (150 [25th, 75th percentile 23.2, 150.0] versus 41.6 [11.3, 150.0]). Among 610 patients who completed vaccination (assessed [&ge;]14 days later, median 29 days later), the prevalence of absent total RBD response, and absent and attenuated semiquantitative IgG response was 4.4% (95% CI 3.1, 6.4%), 3.4% (2.4, 5.2%), and 14.3% (11.7, 17.3%) respectively. Risk factors for absent or attenuated response included longer vintage of end-stage kidney disease, and lower pre-vaccination serum albumin. Conclusions: More than one in five patients receiving dialysis had evidence of an attenuated immune response to COVID19 vaccination.

16: B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients
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Posted 12 Aug 2021

B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients
1,279 downloads medRxiv nephrology

Eva Schrezenmeier, Hector Rincon-Arevalo, Ana-Luisa Stefanski, Alexander Potekhin, Henriette Staub-Hohenbleicher, Mira Choi, Friederike Bachmann, Vanessa Pross, Charlotte Hammett, Hubert Schrezenmeier, Carolin Ludwig, Bernd Jahrsdoerfer, Andreia C. Lino, Kai-Uwe Eckardt, Katja Kotsch, Thomas Doerner, Klemens Budde, Arne Sattler, Fabian Halleck

Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

17: The Chronic Kidney Disease and Acute Kidney Injury Involvement in COVID-19 Pandemic: A Systematic Review and Meta-analysis
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Posted 02 May 2020

The Chronic Kidney Disease and Acute Kidney Injury Involvement in COVID-19 Pandemic: A Systematic Review and Meta-analysis
1,183 downloads medRxiv nephrology

Ya-Fei Liu, Zhe Zhang, Xiao-Li Pan, Guo-Lan Xing, Ying Zhang, Zhang-Suo Liu, Sheng-Hao Tu

Aim: The aim of this study was to uncover whether kidney diseases were involved in COVID-19 pandemic from a systematic review. Methods: The studies reported the kidney outcomes in different severity of COVID-19 were included in this study. Standardized mean differences or odds ratios were calculated by employing Review Manager meta-analysis software. Results: Thirty-six trials were included in this systematic review with a total of 6395 COVID-19 patients. The overall effects indicated that the comorbidity of chronic kidney disease (CKD) (OR = 3.28), complication of acute kidney injury (AKI) (OR = 11.02), serum creatinine (SMD = 0.68), abnormal serum creatinine (OR = 4.86), blood urea nitrogen (SMD = 1.95), abnormal blood urea nitrogen (OR = 6.53), received continuous renal replacement therapy (CRRT) (OR = 23.63) was significantly increased in severe group than that in nonsevere group. Additionally, the complication of AKI (OR = 13.92) and blood urea nitrogen (SMD = 1.18) were remarkably elevated in critical group than that in severe group. Conclusion: CKD and AKI are susceptible to occur in patients with severe COVID-19. CRRT is applied frequently in severe COVID-19 patients than that in nonsevere COVID-19 patients. The risk of AKI is higher in critical group than that in severe group.

18: Incidence, risk factors and mortality outcome in patients with acute kidney injury in COVID-19: a single-center observational study
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Posted 24 Jun 2020

Incidence, risk factors and mortality outcome in patients with acute kidney injury in COVID-19: a single-center observational study
1,172 downloads medRxiv nephrology

Gaetano Alfano, Annachiara Ferrari, Francesco Fontana, Giacomo Mori, Riccardo Magistroni, Meschiari Marianna, Franceschini Erica, Marianna Menozzi, Gianluca Cuomo, Gabriella Orlando, Antonella Santoro, Margherita Di Gaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, Jovana Milic, Paolo Raggi, Massimo Girardis, Cristina Mussini, Gianni Cappelli, Giovanni Guaraldi

Background Acute kidney injury (AKI) is a recently recognized complication of coronavirus disease-2019 (COVID-19). This study aims to evaluate the incidence, risk factors and case-fatality rate of AKI in patients with documented COVID-19. Methods We reviewed the health medical records of 307 consecutive patients hospitalized for symptoms of COVID-19 at the University Hospital of Modena, Italy. Results AKI was diagnosed in 69 out of 307 (22.4%) patients. The stages of AKI were stage 1 in 57.9%, stage 2 in 24.6% and stage 3 in 17.3%. Hemodialysis was performed in 7.2% of the subjects. AKI patients had a mean age of 74.7 {+/-} 9.9 years and higher serum levels of the main marker of inflammation and organ involvement (lung, liver, hearth and liver) than non-AKI patients. AKI events were more frequent in subjects with severe lung comprise. Two peaks of AKI events coincided with in-hospital admission and death of the patients. Kidney injury was associate with a higher rate of urinary abnormalities including proteinuria (0.448{+/-} 0.85 vs 0.18 {+/-} 0.29; P=<0.0001) and hematuria (P=0.032) compared to non-AKI patients. At the end of follow-up, 65.2% of the patients did not recover their renal function after AKI. Risk factors for kidney injury were age, male sex, CKD and non-renal SOFA. Adjusted Cox regression analysis revealed that AKI was independently associated with in-hospital death (hazard ratio [HR]=3.74; CI 95%, 1.34-10.46) compared to non-AKI patients. Groups of patients with AKI stage 2-3 and failure to recover kidney function were associated with the highest risk of in-hospital mortality. Lastly, long-hospitalization was positively associated with a decrease of serum creatinine, likely due to muscle depletion occurred with prolonged bed rest. Conclusions AKI was a dire consequence of patients with COVID-19. Identification of patients at high-risk for AKI and prevention of kidney injury by avoiding dehydration and nephrotoxic agents is imperative in this vulnerable cohort of patients.

19: Preprint server use in kidney disease research: a rapid review
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Posted 23 Mar 2020

Preprint server use in kidney disease research: a rapid review
1,143 downloads medRxiv nephrology

Caitlyn Vlasschaert, Cameron Giles, Swapnil Hiremath, Matthew B. Lanktree

Purpose of reviewPreprint servers including arXiv and bioRxiv have disrupted the scientific communication landscape by providing rapid access to pre--peer reviewed research. MedRxiv is a recently launched free online repository for preprints in the health sciences. We sought to summarize potential benefits and risks to preprint server use, from both the researcher and end--user perspective, and evaluate the uptake of preprint servers in the nephrology community. Sources of InformationWe performed a rapid review of articles describing preprint servers and their use. We approached the 20 highest impact nephrology journals regarding their policy towards the use of preprint servers. We evaluated the average time from study completion to publication of impactful articles in nephrology. Finally, we evaluated the number of nephrology articles submitted to preprint servers. FindingsTo date over 600 kidney--related articles have been uploaded to bioRxiv and medRxiv. The average time from study completion to publication was over 10 months. 16 of the top 20 nephrology journals currently accept research submitted to a preprint server. Transparency and collaboration, visibility and recognition, and rapid dissemination of results were identified as benefits of preprint servers. Concerns exist regarding the potential risk of non--peer reviewed medical research being publicly available. LimitationsPreprint servers remain a recent phenomenon in health sciences and their long-- term impact on the medical literature remains to be seen. ImplicationsThe quantity of research submitted to preprint servers is likely to continue to grow. The model for dissemination of research results will need to adapt to incorporate preprint servers.

20: Characterisation of Acute Kidney Injury in Critically Ill Patients with Severe Coronavirus Disease-2019 (COVID-19)
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Posted 10 May 2020

Characterisation of Acute Kidney Injury in Critically Ill Patients with Severe Coronavirus Disease-2019 (COVID-19)
1,103 downloads medRxiv nephrology

Sebastien RUBIN, Arthur Orieux, Renaud Prevel, Antoine Garric, Marie-Lise Bats, Sandrine Dabernat, Fabrice Camou, Olivier Guisset, Nahema Issa, Gaelle Mourissoux, Antoine Dewitte, Olivier Joannes-boyau, Catherine Fleureau, Hadrien Roze, Cedric Carrie, Laurent Petit, Benjamin Clouzeau, Charline Sazio, Hoang-Nam Bui, Odile Pillet, Claire Rigothier, Frederic Vargas, Christian Combe, Didier Gruson, Alexandre Boyer

Background: COVID19-associated acute kidney injury frequency, severity and characterisation in critically ill patients has not been reported. Methods: Single-center cohort performed from March 3, 2020, to April 14, 2020 in 4 intensive care units in Bordeaux University Hospital, France. All patients with COVID19 and pulmonary severity criteria were included. AKI was defined using KDIGO criteria. A systematic urinary analysis was performed. The incidence, severity, clinical presentation, biological characterisation (transient vs. persistent acute kidney injury; proteinuria, hematuria and glycosuria), and short-term outcomes was evaluated. Results: 71 patients were included, with basal serum creatinine of 69 +/- 21 micromol/L. At admission, AKI was present in 8/71 (11%) patients. Median follow-up was 17 [12-23] days. AKI developed in a total of 57/71 (80%) patients with 35% Stage 1, 35% Stage 2, and 30% Stage 3 acute kidney injury; 10/57 (18%) required renal replacement therapy. Transient AKI was present in only 4/55 (7%) patients and persistent AKI was observed in 51/55 (93%). Patients with persistent AKI developed a median urine protein/creatinine of 82 [54-140] (mg/mmol) with an albuminuria/proteinuria ratio of 0.23 +/- 20 indicating predominant tubulo-interstitial injury. Only 2 (4%) patients had glycosuria. At Day 7 onset of after AKI, six (11%) patients remained dependent on renal replacement therapy, nine (16%) had SCr > 200 micromol/L, and four (7%) died. Day 7 and day 14 renal recovery occurred in 28% and 52 % respectively. Conclusion: COVID19 associated AKI is frequent, persistent severe and characterised by an almost exclusive tubulo-interstitial injury without glycosuria

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