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Sevcan K, Özlem D. Evaluation of the Effect of Care Package Application on Urinary Catheter-Related Infections and Incontinence in Female Patients Hospitalized in Intensive Care Units. Nurs Health Sci 2025; 27:e70108. [PMID: 40273953 PMCID: PMC12021455 DOI: 10.1111/nhs.70108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 03/18/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025]
Abstract
The study was carried out to determine the effect of the application of the Urinary Infections and Incontinence Prevention Care Package (UII-PCP) on incontinence and infections in female patients. This was an experimental pilot study with nonrandomized application and a control group design. The study was conducted with 52 female patients in the adult ICU. A patient identification form and patient follow-up form were completed with the intervention and control groups, and the Overactive Bladder Questionnaire (OAB-V8) was completed with both of the groups on the day of discharge and 1 month after discharge. The incidence of catheter-associated urinary tract infections (CA-UTI) symptoms after catheterization was significantly higher in the intervention group (42.3%) compared to the control group (15.4%; p < 0.05). Although there were signs of CA-UTI in the intervention group, no significant correlation was found with the urine culture growth results (p < 0.05). UI and CA-UTI status when applying UII-PCP were examined, and no significant results were identified. However, since this represents the first study on this topic, further studies are warranted.
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Affiliation(s)
- Kutlug Sevcan
- Institute of Health Sciences, NursingSakarya UniversitySakaryaTurkey
| | - Dogu Özlem
- Faculty of Health Sciences, Fundamentals of NursingSakarya UniversitySakaryaTurkey
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Nandula SR, Brichacek B, Sen S. Podocyte-Specific Protein Expression in Urine Exosome Acts as a Marker for Renal Injury in Post-COVID State. Metab Syndr Relat Disord 2025; 23:205-210. [PMID: 40100769 DOI: 10.1089/met.2024.0199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2025] Open
Abstract
Introduction: Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) has been associated with the development of COVID-19. COVID-19 may cause endothelial cell dysfunction (ECD), which can lead to cardiometabolic diseases and podocytopathy. In this study, we explored whether presence of hyperglycemia predisposes to SARS-CoV-2 infection, in vitro, and whether COVID-19 can put an individual at a higher risk of persistent renal damage in the long-term following acute COVID infection. To estimate renal damage, we evaluated albuminuria and podocytopathy. Podocytopathy was estimated by measuring podocyte-specific protein levels in urine-derived exosomes from patients who were admitted with acute COVID-19 at 10 days, 6 months, and 12 months post-acute SARS-CoV-2 infection. Methods: Blood and urine samples from patients with SARS-CoV-2 post-infection were procured from the George Washington University COVID repository. Peripheral blood mononuclear cells and urine exosomes were isolated. Podocyte-specific proteins Podocalyxin (PODXL) and Nephrin (NEPH) were identified from urine exosomes. Results: Urine exosomal podocalyxin levels were significantly high at 10 week (n = 18; P = 0.001), 6 month (n = 25; P = 0.003) and 12 month (n = 14; P = 0.0001) time points. Nephrin levels were also noted to be high at 10 week (n = 18; P = 0.001) and 12 month (n = 14; P = 0.007) time points, compared with urine samples obtained from type 2 diabetes subjects who never had COVID-19. Though urinary podocyte-specific proteins were high, compared to control, there were no significant differences noted on urine albumin:creatinine ratios (UACR) between the groups. Conclusion: Persistent high levels of podocyte-specific proteins noted in urinary exosomes even at 12 months post-Covid may lead to the development of chronic kidney disease.
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Affiliation(s)
- Seshagiri Rao Nandula
- Department of Medicine and Biochemistry, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
| | - Beda Brichacek
- Department of Medicine and Biochemistry, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
| | - Sabyasachi Sen
- Department of Medicine and Biochemistry, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
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Shyong O, Alfakhri N, Bates SV, Carroll RW, Gallagher K, Huang L, Madhavan V, Murphy SA, Okrzesik SA, Yager PH, Yonker LM, Lok J. Multisystem Inflammatory Syndrome in Children: A Comprehensive Review Over the Past Five Years. J Intensive Care Med 2025:8850666251320558. [PMID: 40096057 DOI: 10.1177/08850666251320558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Multisystem Inflammatory Syndrome in Children: A Comprehensive Review over the Past Five Years This review explores many facets of Multisystem Inflammatory Syndrome in Children (MIS-C) over the previous 5 years. In the time since the COVID 19 pandemic gripped our medical systems, we can now explore the data that has been collected from the previous years. The literature has allowed us to better understand the impact of COVID 19 and the post illness occurrence of a severe systemic inflammatory disease on our youngest patient populations. This paper will outline the pathophysiology of MIS-C, the treatments utilized, short and long-term patient outcomes including epidemiological factors.
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Affiliation(s)
- Olivia Shyong
- Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Nora Alfakhri
- Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Sara V Bates
- Harvard Medical School, Boston, MA, USA
- Department of Pediatrics, Newborn Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Ryan W Carroll
- Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Krista Gallagher
- Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Lena Huang
- Touro University Nevada, College of Osteopathic Medicine, Henderson, NV, USA
| | - Vandana Madhavan
- Harvard Medical School, Boston, MA, USA
- Department of Pediatrics, Pediatric Infectious Disease, Massachusetts General Hospital, Boston, MA, USA
| | - Sarah A Murphy
- Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Sylvia A Okrzesik
- Department of Pharmacy, Massachusetts General Hospital, Boston, MA, USA
| | - Phoebe H Yager
- Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Lael M Yonker
- Harvard Medical School, Boston, MA, USA
- Department of Pediatrics, Pediatric Pulmonary Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Josephine Lok
- Department of Pediatrics, Pediatric Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
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Olabisi OA, Barrett NJ, Lucas A, Smith M, Bethea K, Soldano K, Croall S, Sadeghpour A, Chakraborty H, Wolf M. Design and Rationale of the Phase 2 Baricitinib Study in Apolipoprotein L1-Mediated Kidney Disease (JUSTICE). Kidney Int Rep 2024; 9:2677-2684. [PMID: 39291185 PMCID: PMC11403079 DOI: 10.1016/j.ekir.2024.06.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 06/06/2024] [Accepted: 06/17/2024] [Indexed: 09/19/2024] Open
Abstract
Introduction Individuals of recent West African ancestry develop focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (HTN-ESKD) at 4 times the rate of White Americans. Two protein-coding variants of the Apolipoprotein L1 (APOL1) gene, G1 and G2, explain 50% to 70% of the excess risk of HTN-ESKD and FSGS among this group. Increased expression of G1 and G2 in the kidney, mediated by Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling, drive pathogenesis of these kidney diseases. Baricitinib is an orally active inhibitor of JAK1/2 that blocks APOL1 synthesis. The Janus kinase-STAT Inhibition to Reduce APOL1-Associated Kidney Disease (JUSTICE) trial is evaluating the antiproteinuric efficacy and safety of baricitinib in patients with APOL1-associated FSGS and HTN-attributed chronic kidney disease (HTN-CKD). Methods JUSTICE is a single-center, randomized, double-blind, placebo-controlled, pilot phase 2 trial of baricitinib in patients with proteinuria, APOL1-associated FSGS or APOL1-associated HTN-CKD without diabetes. A total of 75 African American patients with APOL1-associated CKD, including 25 with FSGS and 50 with HTN-CKD, aged 18 to 70 years will be randomized 2:1 to daily treatment with baricitinib or placebo, respectively. Results The primary efficacy end point will be percent change in urine albumin-to-creatinine ratio (UACR) from baseline to end of month 6. The primary safety end point will be incidence of clinically significant decreases in hemoglobin of ≥ 1g/dl. Conclusion The phase 2 JUSTICE study will characterize the antiproteinuric efficacy and safety of JAK1/2 inhibition with baricitinib in patients with APOL1-associated FSGS and APOL1-associated HTN-CKD.
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Affiliation(s)
- Opeyemi A Olabisi
- Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Nadine J Barrett
- Atrium Health/Wake Forest Comprehensive Cancer Center and Maya Angelo Center for Health Equity, Wake Forest School of Medicine, Wake Forest, North Carolina, USA
- Department of Social Science and Health Policy, Division of Population Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
- Maya Angelo Center for Health Equity, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Anika Lucas
- Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Maurice Smith
- Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Kenisha Bethea
- Duke Clinical and Translational Science Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Karen Soldano
- Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA
- Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA
| | - Stephanie Croall
- Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Azita Sadeghpour
- Duke Precision Medicine Program, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | | | - Myles Wolf
- Division of Nephrology, Duke University School of Medicine, Durham, North Carolina, USA
- Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA
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Fisher M, Ross M, DiFranza L, Reidy K. An Update on Viral Infection-Associated Collapsing Glomerulopathy. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:317-325. [PMID: 39084757 PMCID: PMC11296492 DOI: 10.1053/j.akdh.2023.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 11/14/2023] [Accepted: 12/14/2023] [Indexed: 08/02/2024]
Abstract
The COVID-19 era has been a reminder to clinicians around the world of the important role that viral infections play in promoting glomerular disease. Several viral infections including human immunodeficiency virus (HIV), severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, cytomegalovirus, and parvovirus B19 can cause podocyte injury and present with a collapsing glomerulopathy (CG) variant of focal segmental glomerulosclerosis or minimal change disease. CG associated with COVID-19 has been termed COVID-19-associated nephropathy due to its striking resemblance to HIV-associated nephropathy. Host susceptibility is a major determinant of viral infection-associated CG, and the presence of two APOL1 risk variants explains most of the racial predilection to viral-associated CG observed in individuals of African ancestry. Interactions between APOL1 risk variants, viral genes, and the systemic inflammatory response to viral infection all contribute to kidney injury. This review will summarize our current knowledge of viral infection-associated CG, focusing primarily on the clinical presentation, histological features, mechanisms, and disease course of HIV-associated nephropathy and COVID-19-associated nephropathy.
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Affiliation(s)
- Molly Fisher
- Division of Nephrology, Albert Einstein College of Medicine, Montefiore Health System, Bronx, NY.
| | - Michael Ross
- Division of Nephrology, Albert Einstein College of Medicine, Montefiore Health System, Bronx, NY; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY
| | - Lanny DiFranza
- Department of Pathology, Albert Einstein College of Medicine, Montefiore Health System, Bronx, NY
| | - Kimberly Reidy
- Division of Pediatric Nephrology, The Children's Hospital at Montefiore/Albert Einstein College of Medicine, Bronx, NY
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Özdemir BH, Ok Atılgan A, Akyüz Özdemir A, Haberal M. Unmasking the Silent Threat: COVID-19's Pervasive Impact on Renal Allografts. EXP CLIN TRANSPLANT 2024; 22:522-530. [PMID: 39223810 DOI: 10.6002/ect.2023.0352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
OBJECTIVES Growing evidence has highlighted the substantial effects of COVID-19 on kidneys, ranging from mild proteinuria to severe acute kidney injury. However, comprehensive assessments of histopathological features in renal allograft biopsies are lacking. MATERIALS AND METHODS Seventeen kidney transplant recipients with COVID-19 between March 2020 and November 2022 were evaluated. Clinical characteristics, pathological findings, and outcomes were studied. RESULTS Six kidney transplant recipients (35.3%) developed acute kidney injury, leading to the requirement for hemodialysis. COVID-19 severity, as indicated by pneumonia (P = .028) and hospitalization (P = .002), was significantly associated with development of acute kidney injury. Most patients with COVID-19 (82.4%) showed considerably increased proteinuria levels (82.4%), along with presence of new-onset microscopic hematuria (35.3%) and nephrotic syndrome (58.8%). Tubular viral inclusionlike changes were detected in 47.1% of cases and were associated with a higher risk of graft loss (75%). Thrombotic microangiopathy and endothelial cell swelling in glomeruli were prevalent, highlighting extensive endothelial cell injury. Most recipients (88.2%) experienced rejection after COVID-19, with graft loss occurring in 46.7% of these cases. Biopsies revealed collapsing (n = 5), noncollapsing (n = 3), and recurrent (n = 2) focal segmental glomerulosclerosis, as well as acute tubulointerstitial nephritis (n = 3), crescentic glomerulonephritis with immunoglobulin A nephropathy (n = 1), and membranoproliferative glomerulonephritis (n = 1), in 129.7 ± 33 days. Eight patients experienced graft loss (8.2 ± 2 mo posttransplant). Hospitalization (P = .044) and viralinclusion-like nuclear changes in tubules (P = .044) significantly influenced graft survival. Collapsing (60%) and noncollapsing (66.7%) focal segmental glomerulosclerosis increased the risk of graft loss. CONCLUSIONS COVID-19 has had a multifaceted and enduring effect on renal allografts, urging the need for meticulous monitoring and tailored management strategies to mitigate the risk of severe kidney-related complications and graft loss in this vulnerable population.
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Affiliation(s)
- B Handan Özdemir
- >From the Pathology Department, Faculty of Medicine, Baskent University, Ankara, Türkiye
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Tabachnikov O, Skorecki K, Kruzel-Davila E. APOL1 nephropathy - a population genetics success story. Curr Opin Nephrol Hypertens 2024; 33:447-455. [PMID: 38415700 PMCID: PMC11139250 DOI: 10.1097/mnh.0000000000000977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
PURPOSE OF REVIEW More than a decade ago, apolipoprotein L1 ( APOL1 ) risk alleles designated G1 and G2, were discovered to be causally associated with markedly increased risk for progressive kidney disease in individuals of recent African ancestry. Gratifying progress has been made during the intervening years, extending to the development and clinical testing of genomically precise small molecule therapy accompanied by emergence of RNA medicine platforms and clinical testing within just over a decade. RECENT FINDINGS Given the plethora of excellent prior review articles, we will focus on new findings regarding unresolved questions relating mechanism of cell injury with mode of inheritance, regulation and modulation of APOL1 activity, modifiers and triggers for APOL1 kidney risk penetrance, the pleiotropic spectrum of APOL1 related disease beyond the kidney - all within the context of relevance to therapeutic advances. SUMMARY Notwithstanding remaining controversies and uncertainties, promising genomically precise therapies targeted at APOL1 mRNA using antisense oligonucleotides (ASO), inhibitors of APOL1 expression, and small molecules that specifically bind and inhibit APOL1 cation flux are emerging, many already at the clinical trial stage. These therapies hold great promise for mitigating APOL1 kidney injury and possibly other systemic phenotypes as well. A challenge will be to develop guidelines for appropriate use in susceptible individuals who will derive the greatest benefit.
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Affiliation(s)
- Orly Tabachnikov
- Department of Nephrology, Rambam Healthcare Campus, Haifa, Israel
| | - Karl Skorecki
- Department of Nephrology, Rambam Healthcare Campus, Haifa, Israel
- Departments of Genetics and Developmental Biology and Rappaport Faculty of Medicine and Research Institute, Technion—Israel Institute of Technology, Haifa, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Etty Kruzel-Davila
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
- Department of Nephrology, Galilee Medical Center, Nahariya, Israel
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Dogan M, Watkins C, Ingram H, Moore N, Rucker GM, Gower EG, Eason JD, Bhalla A, Talwar M, Nezakatgoo N, Eymard C, Helmick R, Vanatta J, Bajwa A, Kuscu C, Kuscu C. Unveiling APOL1 haplotypes in a predominantly African-American cohort of kidney transplant patients: a novel classification using probe-independent quantitative real-time PCR. Front Med (Lausanne) 2024; 11:1325128. [PMID: 38660426 PMCID: PMC11039853 DOI: 10.3389/fmed.2024.1325128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 03/20/2024] [Indexed: 04/26/2024] Open
Abstract
Introduction Apolipoprotein-L1 (APOL1) is a primate-specific protein component of high-density lipoprotein (HDL). Two variants of APOL1 (G1 and G2), provide resistance to parasitic infections in African Americans but are also implicated in kidney-related diseases and transplant outcomes in recipients. This study aims to identify these risk variants using a novel probe-independent quantitative real-time PCR method in a high African American recipient cohort. Additionally, it aims to develop a new stratification approach based on a haplotype-centric model. Methods Genomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. A quantitative PCR assay with modified forward primers and a common reverse primer enabled us to quantitatively identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion. Additionally, we used Sanger sequencing to verify our QPCR findings. Results Our novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletions, and homozygous SNPs/deletions, with at least 4-fold differences. A high prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, no significant impact of recipient APOL1 variants on transplant outcomes was observed up to 12-month of follow-ups. Ongoing research will encompass more time points and a larger patient cohort, allowing for a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding. Conclusion Our cost-effective and rapid qPCR technique facilitates APOL1 genotyping within hours. Prospective and retrospective studies will enable comparisons with long-term allograft rejection, potentially predicting early/late-stage transplant outcomes based on haplotype evaluation in this diverse group of kidney transplant recipients.
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Affiliation(s)
- Murat Dogan
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Christine Watkins
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Holly Ingram
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Nicholas Moore
- Transplant Research Institute, Memphis, TN, United States
| | - Grace M. Rucker
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | | | | | - Anshul Bhalla
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Methodist Hospital, Memphis, TN, United States
| | - Manish Talwar
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Methodist Hospital, Memphis, TN, United States
| | - Nosratollah Nezakatgoo
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Methodist Hospital, Memphis, TN, United States
| | - Corey Eymard
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Methodist Hospital, Memphis, TN, United States
| | - Ryan Helmick
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Methodist Hospital, Memphis, TN, United States
| | - Jason Vanatta
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
- Methodist Hospital, Memphis, TN, United States
| | - Amandeep Bajwa
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Canan Kuscu
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Cem Kuscu
- Transplant Research Institute, Memphis, TN, United States
- Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
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Al Otaibi T, Nagib A, Nair P, Halim MA, Khaled M, Hammad MA, Mahmoud TS, Sobhy I, Zakaria Z, Atta A, Deraz A, Mostafa A, Abuelmagd M, Shaker M, Alserwy N, Fyyad Z, Rida S, Aboatya H, Adel M, Balaha M, Atea K, Gheith O. Acute Kidney Injury Among COVID-19-Positive Patients Is Associated With Higher Mortality: A Single-Center Experience. EXP CLIN TRANSPLANT 2024; 22:290-298. [PMID: 38385415 DOI: 10.6002/ect.mesot2023.p98] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2024]
Abstract
OBJECTIVES Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes. MATERIALS AND METHODS We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury. RESULTS Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%). CONCLUSIONS We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.
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Marzoog BA. Gastrointestinal Tract and Kidney Injury Pathogenesis in Post-COVID-19 Syndrome. Curr Diabetes Rev 2024; 20:e051023221787. [PMID: 37815187 DOI: 10.2174/0115733998250889230919185305] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 06/20/2023] [Accepted: 07/18/2023] [Indexed: 10/11/2023]
Abstract
COVID-19 is a global health emergency that requires worldwide collaboration to control its spread. The scientific community is working to understand the different aspects of the post-COVID-19 syndrome and potential treatment strategies. Interestingly, there have been reports of gastrointestinal tract (GIT) involvement in the post-COVID-19 syndrome, suggesting the presence of both severe and mild GIT disorders. The development of the post-COVID-19- GIT syndrome involves various factors, such as impaired GIT mucosa cells, disruptions in the feeling of satiety, reduced blood supply due to the formation of small blood clots, and increased prostaglandin secretion caused by an excessive immune response. GIT symptoms have been observed in around 16% of COVID-19 patients. Other complications include kidney damage and prolonged impairment in the filtration and excretion functions of the glomeruli and tubules. The pathogenesis of post-COVID-19 renal syndrome involves factors, like an overactive immune response, reduced lung perfusion and oxygenation, viral infection in kidney tissues, endothelial dysfunction, and decreased blood volume. Roughly 20% of hospitalized patients experience renal manifestations after recovering from COVID-19.
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Affiliation(s)
- Basheer Abdullah Marzoog
- World-Class Research Center, Digital Biodesign and Personalized Healthcare, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
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11
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Mir TH, Zargar PA, Sharma A, Jabeen B, Sharma S, Parvaiz MO, Bashir S, Javeed R. Post COVID-19 AA amyloidosis of the kidneys with rapidly progressive renal failure. Prion 2023; 17:111-115. [PMID: 37055928 PMCID: PMC10114959 DOI: 10.1080/19336896.2023.2201151] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 12/15/2022] [Accepted: 01/22/2023] [Indexed: 04/15/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) pandemic has taken the world by a storm, posing a gruelling challenge to the medical fraternity globally. Besides its very high infectivityinfectivity, significant organ dysfunction occurs in critically ill COVID-19 patients, leading to severe morbidity and mortality. Pulmonary involvement is the leading cause of death in these patients to be followed by the cardiovascular involvement. Kidney involvement due to COVID-19 is becoming more discernible with AKI adversely affecting the outcome. Besides AKI, a few cases of collapsing FSGS in genetically vulnerable patients and thrombotic microangiopathies have been reported as well. We report a case of AA amyloidosis of the kidney with a rapidly progressive renal failure and congestive heart failure with preserved left ventricular functions, which complicated a moderate COVID-19 pneumonia providing some clues to a possible association of this novel virus disease with this complication, which needs to be confirmed in future studies.
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Affiliation(s)
- Tajamul H. Mir
- Department of Nephrology, Government Medical College, Srinagar, Jammu and Kashmir, India
- Department of Nephrology, Khyber Medical Institute Nowpora, Srinagar, Jammu and Kashmir, India
| | - Parvaiz A Zargar
- Department of Cardiology, Government Medical College, Srinagar, Jammu and Kashmir, India
| | - Alok Sharma
- Department of Renal Pathology, Dr. Lal Path lab/National Reference lab, New Delhi, India
| | - Bushra Jabeen
- Department of Radiology, SMHS Hospital, Srinagar, Jammu and Kashmir, India
| | - Shephali Sharma
- Department of Renal Pathology, Dr. Lal Path lab/National Reference lab, New Delhi, India
| | - M. Omar Parvaiz
- Department of Medicine, Holy Family Red Crescent Medical College, Dhaka, Bangladesh
| | - Sabah Bashir
- Department of Nephrology, Khyber Medical Institute Nowpora, Srinagar, Jammu and Kashmir, India
| | - Reem Javeed
- Department of Nephrology, Government Medical College, Srinagar, Jammu and Kashmir, India
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12
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Hu J, Raina M, Mehta I, Sethi SK, Soundararajan A, Bansal SB. AKI in Adults with COVID-19 Infection: Mechanisms of Development and Role of Blood Filtration Devices in Treatment. Indian J Nephrol 2023; 33:411-419. [PMID: 38174296 PMCID: PMC10752394 DOI: 10.4103/ijn.ijn_51_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 04/09/2023] [Accepted: 04/22/2023] [Indexed: 01/05/2024] Open
Abstract
During the coronavirus disease 2019 (COVID-19) pandemic, acute kidney injury (AKI) was a common sequela of COVID-19 infection and predicted disease severity and mortality. Extracorporeal blood purification techniques involving blood filtration devices are an emerging treatment for AKI in the setting of severe COVID-19 infections. In this review, we discuss potential mechanisms for the development of AKI in COVID-19 patients as well as the various available blood filtration devices and the role they may play in managing the AKI in COVID-19 patients. A total of seven blood filters currently available were compared based on their potential in treating AKI in COVID-19 patients. Blood filtration devices show potential as an emerging treatment modality for COVID-19-induced AKI, but further clinical trials are necessary before their widespread adoption and usage.
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Affiliation(s)
- Jieji Hu
- Northeast Ohio Medical University, Rootstown, Ohio, USA
| | | | - Ira Mehta
- Lake Ridge Academy, North Ridgeville, Ohio, USA
| | - Sidharth K. Sethi
- Department of Pediatric Nephrology and Pediatric Kidney Transplantation, Kidney and Urology Institute, Medanta, The Medicity Hospital, Gurugram, India
| | - Anvitha Soundararajan
- Akron Nephrology Associates/Cleveland Clinic Akron General Medical Center, Akron, Ohio, USA
| | - Shyam Bihari Bansal
- Department of Nephrology and Kidney Transplant Medicine, Kidney Institute, Medanta, The Medicity, Gurugram, Haryana, India
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13
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Dogan M, Watkins C, Ingram H, Moore N, Rucker GM, Gower EG, Eason JD, Bhalla A, Talwar M, Nezakatgoo N, Eymard C, Helmick R, Vanatta J, Bajwa A, Kuscu C, Kuscu C. Unveiling APOL1 Haplotypes: A Novel Classification Through Probe-Independent Quantitative Real-Time PCR. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.10.16.562539. [PMID: 37905084 PMCID: PMC10614821 DOI: 10.1101/2023.10.16.562539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2023]
Abstract
Introduction Apolipoprotein-L1 (APOL1) is a primate-specific protein component of high- density lipoprotein (HDL). Two variants of APOL1 (G1 and G2), provide resistance to parasitic infections in African Americans but are also implicated in kidney-related diseases and transplant outcomes in recipients. This study aims to identify these risk variants using a novel probe- independent quantitative real-time PCR method in a high African American recipient cohort. Additionally, it aims to develop a new stratification approach based on haplotype-centric model. Methods Genomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. Quantitative PCR assay with modified forward primers and a common reverse primer enabled us to identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion quantitatively. Additionally, we used sanger sequencing to verify our QPCR findings. Results Our novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletion, and homozygous SNPs/deletion, with at least 4-fold differences. High prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, up to 12-month follow-up revealed no significant impact of recipient APOL1 variants on transplant outcomes. Ongoing research will encompass more time points and a larger patient cohort, allowing a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding. Conclusions Our cost-effective and rapid qPCR technique facilitates APOL1 genotyping within hours. Prospective and retrospective studies will enable comparisons with long-term allograft rejection, potentially predicting early/late-stage transplant outcomes based on haplotype evaluation in this diverse group of kidney transplant recipients.
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14
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Pokharel A, Anderson JD, Deebajah M, Blatt NB, Reddy G, Garlapaty V, Li W, Kanaan HD, Zhang PL. Podocytopathies related to either COVID-19 infection or its vaccination, our experience and literature review. Ultrastruct Pathol 2023; 47:373-381. [PMID: 37463165 DOI: 10.1080/01913123.2023.2237565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 06/13/2023] [Accepted: 07/13/2023] [Indexed: 07/20/2023]
Abstract
Coronavirus disease 2019 (COVID-19) affects several organs including the kidney resulting in acute kidney injury (AKI) and variants of podocytopathies. From the beginning to the middle period of the COVID-19 pandemic, we have collected eight renal biopsies with various renal diseases including 4 podocytopathies. In addition, from the middle period to the near end of the COVID-19 pandemic, we have seen two of the patients who developed nephrotic syndrome following COVID-19 vaccination. Three of 4 podocytopathies were collapsing glomerulopathy (also called collapsing focal segmental glomerulosclerosis) and the fourth was a minimal change disease (MCD). Two of three collapsing glomerulopathy were found in African American patients, one of who was tested positive for having the high-risk allele APOL-1 G1. In addition, the two renal biopsies showed either MCD or replaced MCD following COVID-19 vaccination. MCD can be a rare complication following COVID-19 infection and COVID-19 vaccination, raising the question if there are similar antigens induced by the infection or by the vaccination that trigger the MCD. This article reports our experience of diagnosing podocytopathies related to either COVID-19 infection or its vaccination and provides a literature review regarding the incidence and potential pathophysiology in the field.
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Affiliation(s)
- Ashbita Pokharel
- Department of Pathology, Corewell Health (East), Royal Oak, MI, USA
| | | | - Mustafa Deebajah
- Department of Pathology, Corewell Health (East), Royal Oak, MI, USA
| | - Neal B Blatt
- Division of Pediatric Nephrology, Corewell Health (East), Royal Oak, MI, USA
| | - Gampala Reddy
- Division of Nephrology, Corewell Health (East), Royal Oak, MI, USA
| | - Vamshi Garlapaty
- Division of Nephrology, Corewell Health (East), Royal Oak, MI, USA
| | - Wei Li
- Department of Pathology, Corewell Health (East), Royal Oak, MI, USA
| | - Hassan D Kanaan
- Department of Pathology, Corewell Health (East), Royal Oak, MI, USA
| | - Ping L Zhang
- Department of Pathology, Corewell Health (East), Royal Oak, MI, USA
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15
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Marasa M, Ahram DF, Rehman AU, Mitrotti A, Abhyankar A, Jain NG, Weng PL, Piva SE, Fernandez HE, Uy NS, Chatterjee D, Kil BH, Nestor JG, Felice V, Robinson D, Whyte D, Gharavi AG, Appel GB, Radhakrishnan J, Santoriello D, Bomback A, Lin F, D’Agati VD, Jobanputra V, Sanna-Cherchi S. Implementation and Feasibility of Clinical Genome Sequencing Embedded Into the Outpatient Nephrology Care for Patients With Proteinuric Kidney Disease. Kidney Int Rep 2023; 8:1638-1647. [PMID: 37547535 PMCID: PMC10403677 DOI: 10.1016/j.ekir.2023.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 05/01/2023] [Accepted: 05/22/2023] [Indexed: 08/08/2023] Open
Abstract
Introduction The diagnosis and management of proteinuric kidney diseases such as focal segmental glomerulosclerosis (FSGS) are challenging. Genetics holds the promise to improve clinical decision making for these diseases; however, it is often performed too late to enable timely clinical action and it is not implemented within routine outpatient nephrology visits. Methods We sought to test the implementation and feasibility of clinical rapid genome sequencing (GS) in guiding decision making in patients with proteinuric kidney disease in real-time and embedded in the outpatient nephrology setting. Results We enrolled 10 children or young adults with biopsy-proven FSGS (9 cases) or minimal change disease (1 case). The mean age at enrollment was 16.2 years (range 2-30). The workflow did not require referral to external genetics clinics but was conducted entirely during the nephrology standard-of-care appointments. The total turn-around-time from enrollment to return-of-results and clinical decision averaged 21.8 days (12.4 for GS), which is well within a time frame that allows clinically relevant treatment decisions. A monogenic or APOL1-related form of kidney disease was diagnosed in 5 of 10 patients. The genetic findings resulted in a rectified diagnosis in 6 patients. Both positive and negative GS findings determined a change in pharmacological treatment. In 3 patients, the results were instrumental for transplant evaluation, donor selection, and the immunosuppressive treatment. All patients and families received genetic counseling. Conclusion Clinical GS is feasible and can be implemented in real-time in the outpatient care to help guiding clinical management. Additional studies are needed to confirm the cost-effectiveness and broader utility of clinical GS across the phenotypic and demographic spectrum of kidney diseases.
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Affiliation(s)
- Maddalena Marasa
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Dina F. Ahram
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | | | - Adele Mitrotti
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | | | - Namrata G. Jain
- Division of Pediatric Nephrology, Department of Pediatrics, Columbia University, New York, USA
| | - Patricia L. Weng
- Division of Pediatric Nephrology, Department of Pediatrics, UCLA Medical Center and UCLA Medical Center-Santa Monica, Los Angeles, California, USA
| | - Stacy E. Piva
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Hilda E. Fernandez
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Natalie S. Uy
- Division of Pediatric Nephrology, Department of Pediatrics, Columbia University, New York, USA
| | - Debanjana Chatterjee
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Byum H. Kil
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Jordan G. Nestor
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | | | | | - Dilys Whyte
- Pediatric Specialty Center of Good Samaritan Hospital Medical Center, Babylon, New York, USA
| | - Ali G. Gharavi
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Gerald B. Appel
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Jai Radhakrishnan
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Dominick Santoriello
- Department of Pathology and Cell Biology, Renal Pathology Division, Columbia University Medical Center, New York, USA
| | - Andrew Bomback
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
| | - Fangming Lin
- Division of Pediatric Nephrology, Department of Pediatrics, Columbia University, New York, USA
| | - Vivette D. D’Agati
- Department of Pathology and Cell Biology, Renal Pathology Division, Columbia University Medical Center, New York, USA
| | - Vaidehi Jobanputra
- The New York Genome Center, New York, USA
- Department of Pathology and Cell Biology, Columbia University, New York, USA
| | - Simone Sanna-Cherchi
- Division of Nephrology, Department of Medicine, Columbia University, New York, USA
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16
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Volbeda M, Jou-Valencia D, van den Heuvel MC, Zijlstra JG, Franssen CFM, van der Voort PHJ, Moser J, van Meurs M. Acute and chronic histopathological findings in renal biopsies in COVID-19. Clin Exp Med 2023; 23:1003-1014. [PMID: 36396750 PMCID: PMC9672628 DOI: 10.1007/s10238-022-00941-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 11/03/2022] [Indexed: 11/19/2022]
Abstract
The dominant ICU admission diagnosis of COVID-19 patients is respiratory insufficiency, but 32-57% of hospitalized COVID-19 patients develop acute kidney injury (COVID-AKI). The renal histopathological changes accompanying COVID-AKI are not yet fully described. To obtain a detailed insight into renal histopathological features of COVID-19, we conducted a review including all studies reporting histopathological findings of diagnostic and postmortem kidney biopsies from patients with COVID-19 published between January 1, 2020, and January 31, 2021. A total of 89 diagnostic and 194 postmortem renal biopsies from individual patients in 39 published studies were investigated and were included in the analysis. In the diagnostic biopsy group, mean age was 56 years and AKI incidence was 96%. In the postmortem biopsy group, mean age was 69 years and AKI incidence was 80%. In the diagnostic biopsy group, the prevalence of acute glomerular diseases was 74%. The most common glomerular lesions were collapsing focal segmental glomerulosclerosis (c-FSGS) in 54% and thrombotic microangiopathy (TMA) in 9% of patients. TMA was also found in 10% of patients in the postmortem biopsy group. The most common acute tubular lesions was acute tubular necrosis (ATN) which was present in 87% of patients in the diagnostic and in 77% of patients in the postmortem biopsy group. Additionally, we observed a high prevalence of preexisting chronic lesions in both groups such as atherosclerosis and glomerulosclerosis. Histopathological changes in renal biopsies of COVID-19 patients show a heterogeneous picture with acute glomerular lesions, predominantly c-FSGS and TMA, and acute tubular lesions, predominantly ATN. In many patients, these lesions were present on a background of chronic renal injury.
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Affiliation(s)
- Meint Volbeda
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
| | - Daniela Jou-Valencia
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Marius C van den Heuvel
- Department of Pathology and Medical Biology, Pathology Section, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jan G Zijlstra
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Casper F M Franssen
- Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Peter H J van der Voort
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Jill Moser
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Department of Pathology and Medical Biology, Medical Biology Section, Laboratory for Endothelial Biomedicine and Vascular Drug Targeting Research, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Matijs van Meurs
- Department of Critical Care, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
- Department of Pathology and Medical Biology, Medical Biology Section, Laboratory for Endothelial Biomedicine and Vascular Drug Targeting Research, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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17
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Balan C, Ciuhodaru T, Bubenek-Turconi SI. Kidney Injury in Critically Ill Patients with COVID-19 - From Pathophysiological Mechanisms to a Personalized Therapeutic Model. J Crit Care Med (Targu Mures) 2023; 9:148-161. [PMID: 37588184 PMCID: PMC10425930 DOI: 10.2478/jccm-2023-0023] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 07/28/2023] [Indexed: 08/18/2023] Open
Abstract
Acute kidney injury is a common complication of COVID-19, frequently fuelled by a complex interplay of factors. These include tubular injury and three primary drivers of cardiocirculatory instability: heart-lung interaction abnormalities, myocardial damage, and disturbances in fluid balance. Further complicating this dynamic, renal vulnerability to a "second-hit" injury, like a SARS-CoV-2 infection, is heightened by advanced age, chronic kidney disease, cardiovascular diseases, and diabetes mellitus. Moreover, the influence of chronic treatment protocols, which may constrain the compensatory intrarenal hemodynamic mechanisms, warrants equal consideration. COVID-19-associated acute kidney injury not only escalates mortality rates but also significantly affects long-term kidney function recovery, particularly in severe instances. Thus, the imperative lies in developing and applying therapeutic strategies capable of warding off acute kidney injury and decelerating the transition into chronic kidney disease after an acute event. This narrative review aims to proffer a flexible diagnostic and therapeutic strategy that recognizes the multi-faceted nature of COVID-19-associated acute kidney injury in critically ill patients and underlines the crucial role of a tailored, overarching hemodynamic and respiratory framework in managing this complex clinical condition.
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Affiliation(s)
- Cosmin Balan
- Prof. Dr. C. C. Iliescu Emergency Cardiovascular Diseases Institute, Bucharest, Romania
| | - Tudor Ciuhodaru
- Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iași, Romania
| | - Serban-Ion Bubenek-Turconi
- Prof. Dr. C. C. Iliescu Emergency Cardiovascular Diseases Institute, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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18
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Yazdanparast S, Bakhtiyaridovvombaygi M, Mikanik F, Ahmadi R, Ghorbani M, Mansoorian MR, Mansoorian M, Chegni H, Moshari J, Gharehbaghian A. Spotlight on contributory role of host immunogenetic profiling in SARS-CoV-2 infection: Susceptibility, severity, mortality, and vaccine effectiveness. Life Sci 2023:121907. [PMID: 37394094 DOI: 10.1016/j.lfs.2023.121907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 06/29/2023] [Accepted: 06/29/2023] [Indexed: 07/04/2023]
Abstract
BACKGROUND The SARS-CoV-2 virus has spread continuously worldwide, characterized by various clinical symptoms. The immune system responds to SARS-CoV-2 infection by producing Abs and secreting cytokines. Recently, numerous studies have highlighted that immunogenetic factors perform a putative role in COVID-19 pathogenesis and implicate vaccination effectiveness. AIM This review summarizes the relevant articles and evaluates the significance of mutation and polymorphism in immune-related genes regarding susceptibility, severity, mortality, and vaccination effectiveness of COVID-19. Furthermore, the correlation between host immunogenetic and SARS-CoV-2 reinfection is discussed. METHOD A comprehensive search was conducted to identify relevant articles using five databases until January 2023, which resulted in 105 total articles. KEY FINDINGS Taken to gather this review summarized that: (a) there is a plausible correlation between immune-related genes and COVID-19 outcomes, (b) the HLAs, cytokines, chemokines, and other immune-related genes expression profiles can be a prognostic factor in COVID-19-infected patients, and (c) polymorphisms in immune-related genes have been associated with the effectiveness of vaccination. SIGNIFICANCE Regarding the importance of mutation and polymorphisms in immune-related genes in COVID-19 outcomes, modulating candidate genes is expected to help clinical decisions, patient outcomes management, and innovative therapeutic approach development. In addition, the manipulation of host immunogenetics is hypothesized to induce more robust cellular and humoral immune responses, effectively increase the efficacy of vaccines, and subsequently reduce the incidence rates of reinfection-associated COVID-19.
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Affiliation(s)
- Somayeh Yazdanparast
- Student Research Committee, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Bakhtiyaridovvombaygi
- Student Research Committee, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mikanik
- Student Research Committee, Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Reza Ahmadi
- Department of Infectious Diseases, School of Medicine, Infectious Diseases Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Mohammad Ghorbani
- Laboratory Hematology and Transfusion Medicine, Department of Pathology, Faculty Medicine, Gonabad University of Medical Sciences, Gonabad, Iran.
| | | | - Mozhgan Mansoorian
- Nursing Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Hamid Chegni
- Department of Immunology, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jalil Moshari
- School of Medicine, Gonabad University of Medical Science, Gonabad, Iran
| | - Ahmad Gharehbaghian
- Department of Hematology and Blood Bank, School of Allied Medical Science, Shahid Beheshti University of Medical Science, Tehran, Iran; Pediatric Congenital Hematologic Disorders Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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19
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Yousefi P, Soltani S, Siri G, Rezayat SA, Gholami A, Zafarani A, Razizadeh MH, Alborzi E, Mokhtary‐Irani G, Abedi B, Karampoor S, Tabibzadeh A, Farahani A. Coagulopathy and thromboembolic events a pathogenic mechanism of COVID-19 associated with mortality: An updated review. J Clin Lab Anal 2023; 37:e24941. [PMID: 37431777 PMCID: PMC10431412 DOI: 10.1002/jcla.24941] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 05/24/2023] [Accepted: 06/26/2023] [Indexed: 07/12/2023] Open
Abstract
During 2019, the SARS-CoV-2 emerged from China, and during months, COVID-19 spread in many countries around the world. The expanding data about pathogenesis of this virus could elucidate the exact mechanism by which COVID-19 caused death in humans. One of the pathogenic mechanisms of this disease is coagulation. Coagulation disorders that affect both venous and arterial systems occur in patients with COVID-19. The possible mechanism involved in the coagulation could be excessive inflammation induced by SARS-CoV-2. However, it is not yet clear well how SARS-CoV-2 promotes coagulopathy. However, some factors, such as pulmonary endothelial cell damage and some anticoagulant system disorders, are assumed to have an important role. In this study, we assessed conducted studies about COVID-19-induced coagulopathy to obtain clearer vision of the wide range of manifestations and possible pathogenesis mechanisms.
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Affiliation(s)
- Parastoo Yousefi
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
| | - Saber Soltani
- Department of Virology, School of Public HealthTehran University of Medical SciencesTehranIran
| | - Goli Siri
- Department of Internal Medicine, Amir Alam HospitalTehran University of Medical SciencesTehranIran
| | - Sara Akhavan Rezayat
- Department of Health Care Management and Economics, School of Public HealthTehran University of Medical SciencesTehranIran
| | - Ali Gholami
- School of MedicineArak University of Medical SciencesArakIran
| | - Alireza Zafarani
- Department of Hematology and Blood Banking, Faculty of Allied MedicineIran University of Medical SciencesTehranIran
| | | | - Ehsan Alborzi
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
| | - Golnaz Mokhtary‐Irani
- Department of Virology, Faculty of MedicineAhvaz Jondishapur University of Medical SciencesAhvazIran
| | - Behnam Abedi
- Department of Medical Laboratory SciencesKhomein University of Medical SciencesKhomeinIran
| | - Sajad Karampoor
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
- Gastrointestinal and Liver Diseases Research CenterIran University of Medical SciencesTehranIran
| | - Alireza Tabibzadeh
- Department of Virology, School of MedicineIran University of Medical SciencesTehranIran
| | - Abbas Farahani
- Department of Medical Laboratory SciencesKhomein University of Medical SciencesKhomeinIran
- Molecular and Medicine Research CenterKhomein University of Medical SciencesKhomeinIran
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20
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Anand A, Aoyagi H. Understudied Hyperphosphatemia (Chronic Kidney Disease) Treatment Targets and New Biological Approaches. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:959. [PMID: 37241191 PMCID: PMC10221414 DOI: 10.3390/medicina59050959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/19/2023] [Accepted: 04/28/2023] [Indexed: 05/28/2023]
Abstract
Hyperphosphatemia is a secondary disorder of chronic kidney disease that causes vascular calcifications and bone-mineral disorders. As per the US Centers for Disease Control and Prevention, renal damage requires first-priority medical attention for patients with COVID-19; according to a Johns Hopkins Medicine report, SARS-CoV-2 can cause renal damage. Therefore, addressing the research inputs required to manage hyperphosphatemia is currently in great demand. This review highlights research inputs, such as defects in the diagnosis of hyperphosphatemia, flaws in understanding the mechanisms associated with understudied tertiary toxicities, less cited adverse effects of phosphate binders that question their use in the market, socioeconomic challenges of renal treatment and public awareness regarding the management of a phosphate-controlled diet, novel biological approaches (synbiotics) to prevent hyperphosphatemia as safer strategies with potential additional health benefits, and future functional food formulations to enhance the quality of life. We have not only introduced our contributions to emphasise the hidden aspects and research gaps in comprehending hyperphosphatemia but also suggested new research areas to strengthen approaches to prevent hyperphosphatemia in the near future.
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Affiliation(s)
- Ajeeta Anand
- Institute of Life Sciences and Bioengineering, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
| | - Hideki Aoyagi
- Institute of Life Sciences and Bioengineering, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
- Institute of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan
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21
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Sahrai H, Hemmati-Ghavshough M, Shahrabi M, Jafari-Rouhi AH, Solduzian M. Thromboprophylaxis for Coagulopathy Related to COVID-19 in Pediatrics: A Narrative Review. Paediatr Drugs 2023:10.1007/s40272-023-00566-x. [PMID: 37142896 PMCID: PMC10158690 DOI: 10.1007/s40272-023-00566-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/27/2023] [Indexed: 05/06/2023]
Abstract
In addition to harming the respiratory system, COVID-19 can affect multiple organs. Children may develop a specific complication of COVID-19 called multisystem inflammatory syndrome in children (MIS-C) which could influence the vascular system of children and cause multiple coagulopathies in the body. Information on the use of thromboprophylaxis in this condition was collected via the review of various articles. In general, different factors in immune system responses can trigger the initiation of thrombotic events. Studies have shown that starting anticoagulant prophylaxis, which contributes to decreased thrombotic events, is dependent on the patient's condition and D-dimer levels. However, further studies on pediatric populations are needed to establish the role of anticoagulants in children with this condition.
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Affiliation(s)
- Hadi Sahrai
- Student research committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Marzieh Shahrabi
- Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Solduzian
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
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22
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Medina E, Rueda C, Batlle D. FSGS and COVID-19 in Non-African American Patients. KIDNEY360 2023; 4:687-699. [PMID: 37229730 PMCID: PMC10371264 DOI: 10.34067/kid.0000000000000104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 02/10/2023] [Indexed: 05/27/2023]
Abstract
Collapsing Focal Segmental Glomerulosclerosis (FSGS) has been reported relatively frequently in African American (AA) patients with coronavirus disease 2019 (COVID-19), and it is associated almost always with Apolipoprotein L gen 1 (APOL1) high-risk variants. We reviewed the published literature from April 2020 to November 2022 searching for non-African American (non-AA) patients with FSGS associated with COVID-19 (eight White patients, six Hispanic patients, three Asian patients, one Indian patient, and one Asian Indian patient). The following histologic patterns were found: collapsing (n=11), not otherwise specified (n=5), tip (n=2), and perihilar (n=1). Fifteen of the 19 patients had AKI. The APOL1 genotype was reported in only six of the 19 non-AA patients. Three of them (two Hispanic patients and one White patient) with collapsing FSGS had high-risk APOL1 variants. The other three patients (two White patients and one Hispanic patient with the collapsing variant, tip variant, and not otherwise specified) had low-risk APOL1 variants. Among 53 African American patients with collapsing FSGS associated with COVID-19, 48 had high-risk APOL1 variants and five had low-risk APOL1 variants. We conclude that in non-AA patients, FSGS is a rare complication of COVID-19. FSGS associated with COVID-19 can occur rarely with low-risk APOL1 variants in non-AA and AA patients. Non-AA patients reported to be associated with high-risk APOL1 variants possibly reflect inaccuracy of self-reported race with AA admixture because of unknown ancestry. Given the importance of APOL1 in the pathogenesis of FSGS associated with viral infection and to avoid racial bias, it seems appropriate that APOL1 testing be considered in patients with FSGS associated with COVID-19, regardless of self-reported race.
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Affiliation(s)
- Elba Medina
- Division of Nephrology, General Hospital of México, Eduardo Liceaga, México City, México
- Master's and PhD Program in Dental and Health Medical Sciences, Universidad Nacional Autónoma de México, México City, México
| | - Carlos Rueda
- Division of Nephrology/Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Daniel Batlle
- Division of Nephrology/Hypertension, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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23
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Dhillon VS, Alkashash A, Viquez-Beita K. Coronavirus disease 2019-associated nephropathy in an African American patient: a case report and review of the literature. J Med Case Rep 2023; 17:153. [PMID: 37024977 PMCID: PMC10079329 DOI: 10.1186/s13256-023-03888-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 03/14/2023] [Indexed: 04/08/2023] Open
Abstract
BACKGROUND Acute kidney injury is now recognized as a common complication of coronavirus disease 2019, affecting up to 46% of patients, with acute tubular injury as the most common etiology. Recently, we have seen an increase in cases of collapsing glomerulonephritis in patients with coronavirus disease 2019, also known as coronavirus disease 2019-associated nephropathy. It has been noted to be seen with a higher incidence in African American patients who are carriers of the APOL1 variant allele. CASE PRESENTATION A 47-year-old African American male with a past medical history of asthma presented to the emergency department with complaints of intermittent chest pain, shortness of breath, and worsening confusion. On admission, he was found to be hemodynamically stable, but labs were significant for elevated creatinine and blood urea nitrogen, signifying acute kidney injury. He was admitted and taken for emergent dialysis. During his hospitalization, he was found to be positive for coronavirus disease 2019. Renal biopsy was done, which showed collapsing glomerulopathy, and the patient continues to require outpatient dialysis after discharge. CONCLUSION Collapsing glomerulonephritis has emerged as a complication in patients with coronavirus disease 2019. This condition should be particularly suspected in African American patients who present with acute kidney injury, nephrotic-range proteinuria, and who are positive for coronavirus disease 2019. Current treatment options are limited to supportive treatment and renal replacement therapy. More clinical cases and trials are needed to better understand and improve therapeutic outcomes in these patients.
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Affiliation(s)
- Vijaypal S Dhillon
- Internal Medicine, Indiana University School of Medicine Muncie, Muncie, USA.
| | - Ahmad Alkashash
- Department of Pathology, Indiana University, Indianapolis, USA
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24
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Abstract
COVID (Coronavirus disease)-19 is a systemic disease and the kidney is one of the target organs of infection. Kidney injury is common and can occur in up to 40% of patients. Several glomerular diseases have been reported in association with COVID-19. Some are likely related to COVID-19 whereas many are likely coincidental. Glomerular diseases that are frequently reported in COVID-19 and have a plausible mechanistic explanation, are likely to be related to COVID-19. On the other hand, glomerular diseases that are seldom reported and have no known plausible mechanism, are likely to be unrelated. Collapsing glomerulopathy (CG) is by far the most prevalent. Its association with COVID-19, resembling human immunodeficiency virus (HIV) and CG, led to the newly proposed term “COVID-19 associated nephropathy” or “COVAN”. High-risk APOL1 genotypes are the major risk factor in COVAN patients. Podocytopathy, membranous nephropathy, pauci-immune crescentic glomerulonephritis, and thrombotic microangiopathy are also reported. In kidney allografts, CG remains the most common glomerular pathology. Patients typically present with acute kidney injury (AKI) or abnormal urinary findings at the time of or shortly after COVID-19 diagnosis. Treatment of glomerular disease in COVID-19 patients is challenging. Providers should cautiously consider balancing risks and benefit of immunosuppression, particularly in patients with active diseases. Short-term outcomes vary but generally remain poor with high morbidity and mortality. Future study of long-term outcomes is needed to improve our understanding of glomerular disease associated with COVID-19.
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25
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Qamar MA, Kogut LM, Tebha SS, Arif A, Ninmol J, Abdul Razzaque MR, Qamar K, Yosufi A. Collapsing focal segmental glomerulosclerosis secondary to COVID-19: A systematic review and meta-analysis. Ann Med Surg (Lond) 2023; 85:92-101. [PMID: 36845824 PMCID: PMC9949810 DOI: 10.1097/ms9.0000000000000107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 12/22/2022] [Indexed: 02/28/2023] Open
Abstract
The renal system manifestations of coronavirus disease-2019 have been documented extensively; however, scientific literature remains scarce regarding collapsing glomerulopathy hence the need for this investigation. Methods A comprehensive review was conducted covering a timeline from 1 January 2020 to 5 February 2022 without any restrictions. The data extraction was conducted independently, and articles were assessed for the risk of bias. Data analysis was conducted using Comprehensive Meta-Analysis version 3.3.070 and RevMan version 5.4 for pooled proportions and risk ratio (RR) between dialysis-dependent and independent treatment groups with a P-value less than 0.05 considered significant. Results A total of 38 studies were included in this review, including 74 (65.9%) males. The mean age was 54.2 years old. The most common symptoms reported were related to the respiratory system (59.6%, 95% CI: 50.4-68.2%) and hematuria (34.2%, 95% CI: 26.1-43.4). Antibiotics (25.9%, 95% CI: 12.9-45.3%) was the commonest management used. Proteinuria was the most reported laboratory finding at 89.5% (95% CI: 82.4-93.9%), while the commonest microscopic finding was acute tubular injury (77.2%, 95% CI: 68.6-84.0%). An increased risk of the presence of symptoms (P=0.005) and microscopic findings (P=0.0003) related to collapsing glomerulopathy in dialysis-dependent group was noted with increased management (P=0.01) used in this group for coronavirus disease-2019 infection. Conclusion The findings of this study portray the prognostic value of the variables (symptoms and microscopic findings, etc.) reported in the analysis. Hence this study serves as a foundation for future investigations that minimize the study's limitations to provide a more robust conclusion.
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Affiliation(s)
| | - Lucas M. Kogut
- Department of Nephrology, Hope Medical Institute, Newport News, Virginia, USA
| | - Sameer S. Tebha
- Department of Neurosurgery and Neurology, Jinnah Medical and Dental College
| | | | - Jesse Ninmol
- Department of Public Health, University of California, Berkeley, California
| | - Muhammad R. Abdul Razzaque
- Department of Medicine, Section of Nephrology, Jinnah Medical and Dental College, Karachi, Sindh, Pakistan
| | | | - Abubakr Yosufi
- Medical School, Kabul University of Medical Sciences, Kabul, Afghanistan
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26
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Hassan MO, Balogun RA. The Effects of Race on Acute Kidney Injury. J Clin Med 2022; 11:5822. [PMID: 36233687 PMCID: PMC9573379 DOI: 10.3390/jcm11195822] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/16/2022] [Accepted: 09/27/2022] [Indexed: 12/03/2022] Open
Abstract
Racial disparities in incidence and outcomes of acute kidney injury (AKI) are pervasive and are driven in part by social inequities and other factors. It is well-documented that Black patients face higher risk of AKI and seemingly have a survival advantage compared to White counterparts. Various explanations have been advanced and suggested to account for this, including differences in susceptibility to kidney injury, severity of illness, and socioeconomic factors. In this review, we try to understand and further explore the link between race and AKI using the incidence, diagnosis, and management of AKI to illustrate how race is directly related to AKI outcomes, with a focus on Black and White individuals with AKI. In particular, we explore the effect of race-adjusted estimated glomerular filtration rate (eGFR) equation on AKI prediction and discuss racial disparities in the management of AKI and how this might contribute to racial differences in AKI-related mortality among Blacks with AKI. We also identify some opportunities for future research and advocacy.
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Affiliation(s)
- Muzamil Olamide Hassan
- Department of Medicine, Obafemi Awolowo University, Ile-Ife 220005, Nigeria
- Division of Nephrology, Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
| | - Rasheed Abiodun Balogun
- Division of Nephrology, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA
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27
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Storrar J, Kudose S, Woywodt A. Have we missed AINything? Acute interstitial nephritis in SARS-CoV-2 infection and vaccination. Clin Kidney J 2022; 15:1643-1652. [PMID: 35999962 PMCID: PMC9213847 DOI: 10.1093/ckj/sfac147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Indexed: 11/14/2022] Open
Abstract
Acute interstitial nephritis (AIN), defined by the presence of interstitial inflammation accompanied by tubulitis, is an often overlooked cause of acute kidney injury (AKI). It is now well established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause a wide variety of kidney injuries, most commonly acute tubular injury and collapsing glomerulopathy. In comparison, AIN is rarely documented in association with SARS-CoV-2 both anecdotally and in larger series of autopsy or biopsy studies. In this issue of the Journal, León-Román describe five cases of AIN in patients with a history of coronavirus disease 2019 (COVID-19) and highlight AIN as a possibly under-reported or ignored facet of renal disease associated with SARS-CoV-2. They describe three scenarios in which AIN can be seen: (i) SARS-CoV-2 infection after diagnosis of AIN, (ii) AIN followed by SARS-CoV-2 infection in the same admission and (iii) Severe SARS-CoV-2 and AIN possibly associated with SARS-CoV-2 itself. Overall, AIN remains rare in SARS-CoV-2 and causality is difficult to ascertain. Interestingly, AIN is not only seen in association with the disease itself but also with SARS-CoV-2 vaccination. This scenario is equally rare and causality is no less difficult to prove. A history of preceding SARS-CoV-2 infection and vaccination should be actively sought when patients present with otherwise unexplained AIN.
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Affiliation(s)
- Joshua Storrar
- Department of Nephrology, Northern Care Alliance NHS Foundation Trust, Salford Royal Hospital, Salford, UK
| | - Satoru Kudose
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, NY, NY, USA
| | - Alexander Woywodt
- Department of Nephrology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK
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28
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Gnanenthiran SR, Borghi C, Burger D, Caramelli B, Charchar F, Chirinos JA, Cohen JB, Cremer A, Di Tanna GL, Duvignaud A, Freilich D, Gommans DHF, Gracia-Ramos AE, Murray TA, Pelorosso F, Poulter NR, Puskarich MA, Rizas KD, Rothlin R, Schlaich MP, Schreinlecher M, Steckelings UM, Sharma A, Stergiou GS, Tignanelli CJ, Tomaszewski M, Unger T, van Kimmenade RRJ, Wainford RD, Williams B, Rodgers A, Schutte AE. Renin-Angiotensin System Inhibitors in Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials Led by the International Society of Hypertension. J Am Heart Assoc 2022; 11:e026143. [PMID: 36000426 PMCID: PMC9496439 DOI: 10.1161/jaha.122.026143] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin‐angiotensin system inhibitors (RASi) in adults with COVID‐19. We therefore performed a meta‐analysis to assess the safety and efficacy of RASi in adults with COVID‐19. Methods and Results MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID‐19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all‐cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow‐up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all‐cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID‐19 severity or trial type. Network meta‐analysis identified no difference between angiotensin‐converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05–3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. Conclusions This meta‐analysis of randomized controlled trials evaluating angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID‐19 found no difference in all‐cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID‐19.
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Affiliation(s)
- Sonali R Gnanenthiran
- The George Institute for Global Health University of New South Wales Sydney NSW Australia
| | - Claudio Borghi
- Department of Medical and Surgical Sciences University of Bologna Italy
| | - Dylan Burger
- Department of Cellular and Molecular Medicine, Kidney Research Centre, Ottawa Hospital Research Institute University of Ottawa Canada
| | - Bruno Caramelli
- Interdisciplinary Medicine in Cardiology Unit, InCor University of Sao Paulo Brazil
| | - Fadi Charchar
- School of Health and Life Sciences Federation University Australia Ballarat VIC Australia
| | - Julio A Chirinos
- Division of Cardiovascular Medicine University of Pennsylvania Perelman School of Medicine Philadelphia PA
| | - Jordana B Cohen
- Renal-Electrolyte and Hypertension Division and Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Perelman School of Medicine Philadelphia PA
| | - Antoine Cremer
- Department of Cardiology and Hypertension, Hypertension Excellence Center Hôpital Saint André, Centre Hospitalier Universitaire de Bordeaux & University Bordeaux Bordeaux France
| | - Gian Luca Di Tanna
- The George Institute for Global Health University of New South Wales Sydney NSW Australia
| | - Alexandre Duvignaud
- Department of Infectious Diseases and Tropical Medicine, Division of Tropical Medicine and Clinical International Health Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux & University Bordeaux Bordeaux France
| | | | - D H Frank Gommans
- Department of Cardiology Radboud University Medical Center Nijmegen The Netherlands.,Netherlands Heart Institute Utrecht The Netherlands
| | - Abraham E Gracia-Ramos
- Departamento de Medicina Interna, Hospital General, Centro Médico Nacional "La Raza" Instituto Mexicano del Seguro Social Mexico City Mexico.,Departamento de Medicina Interna Hospital Regional de Alta Especialidad de Zumpango Estado de Mexico Mexico
| | - Thomas A Murray
- Division of Biostatistics, School of Public Health University of Minnesota Minneapolis MN
| | - Facundo Pelorosso
- Asociacion Argentina de Medicamentos Ciudad Autonoma de Buenos Aires Argentina.,Servicio de Anatomía Patologica, Hospital de Alta Complejidad El Calafate SAMIC Santa Cruz Argentina
| | - Neil R Poulter
- Imperial Clinical Trials Unit Imperial College London London UK
| | - Michael A Puskarich
- Department of Emergency Medicine Hennepin County Medical Center University of Minnesota Minneapolis MN
| | - Konstantinos D Rizas
- Medizinische Klinik und Poliklinik I Ludwig Maximilian University Hospital Munich Munich Germany
| | - Rodolfo Rothlin
- Asociacion Argentina de Medicamentos Ciudad Autonoma de Buenos Aires Argentina.,Sociedad Argentina de Farmacología Clínica, Asociacion Medica Argentina Buenos Aires Argentina
| | - Markus P Schlaich
- Dobney Hypertension Centre, Medical School, Royal Perth Hospital Unit-Royal Perth Hospital Medical Research Foundation University of Western Australia Perth Australia
| | - Michael Schreinlecher
- Department of Internal Medicine III, Cardiology and Angiology Medical University of Innsbruck Innsbruck Austria
| | | | - Abhinav Sharma
- Division of Cardiology McGill University Health Centre Montreal Quebec Canada
| | - George S Stergiou
- Hypertension Center STRIDE-7, School of Medicine, Third Department of Medicine, Sotiria Hospital National and Kapodistrian University of Athens Athens Greece
| | | | - Maciej Tomaszewski
- Division of Cardiovascular Sciences, Faculty of Medicine, Biology and Health University of Manchester Manchester UK.,Manchester Academic Health Science Centre Manchester University National Health Service Foundation Trust Manchester Manchester UK
| | - Thomas Unger
- Cardiovascular Research Institute Maastricht-School for Cardiovascular Diseases Maastricht University Maastricht The Netherlands
| | - Roland R J van Kimmenade
- Department of Cardiology Radboud University Medical Center Nijmegen The Netherlands.,Netherlands Heart Institute Utrecht The Netherlands
| | - Richard D Wainford
- Department of Pharmacology and Experimental Therapeutics and the Whitaker Cardiovascular Institute Boston University School of Medicine Boston MA
| | - Bryan Williams
- Institute of Cardiovascular Science University College London and National Institute for Health Research University College London Hospitals Biomedical Research Centre London UK
| | - Anthony Rodgers
- The George Institute for Global Health University of New South Wales Sydney NSW Australia
| | - Aletta E Schutte
- The George Institute for Global Health University of New South Wales Sydney NSW Australia
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29
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Rasmi Y, Hatamkhani S, Naderi R, Shokati A, Nayeb Zadeh V, Hosseinzadeh F, Farnamian Y, Jalali L. Molecular signaling pathways, pathophysiological features in various organs, and treatment strategies in SARS-CoV2 infection. Acta Histochem 2022; 124:151908. [PMID: 35662001 PMCID: PMC9130726 DOI: 10.1016/j.acthis.2022.151908] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 05/19/2022] [Indexed: 01/08/2023]
Abstract
Cytokine storms and extra-activated cytokine signaling pathways can lead to severe tissue damage and patient death. Activation of inflammatory signaling pathways during Cytokine storms are an important factor in the development of acute respiratory syndrome (SARS-CoV-2), which is the major health problem today, causing systemic and local inflammation. Cytokine storms attract many inflammatory cells that attack the lungs and other organs and cause tissue damage. Angiotensin-converting enzyme 2 (ACE2) are expressed in a different type of tissues. inhibition of ACE2 activity impairs renin-angiotensin (RAS) function, which is related to the severity of symptoms and mortality rate in COVID-19 patients. Different signaling cascades are activated, affecting various organs during SARS-CoV-2 infection. Nowadays, there is no specific treatment for COVID-19, but scientists have recognized and proposed several treatment alternatives, including applying cytokine inhibitors, immunomodulators, and plasma therapy. Herein, we have provided the detailed mechanism of SARS-CoV-2 induced cytokine signaling and its connection with pathophysiological features in different organs. Possible treatment options to cope with the severe clinical manifestations of COVID-19 are also discussed.
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Affiliation(s)
- Yousef Rasmi
- Cellular and Molecular Research Center,Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Shima Hatamkhani
- Experimental and Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran; Department of Clinical Pharmacy, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
| | - Roya Naderi
- Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of Physiology, school of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ameneh Shokati
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | | | - Faezeh Hosseinzadeh
- Department of Tissue Engineering, Qom University of Medical Sciences, Qom, Iran
| | - Yeganeh Farnamian
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Ladan Jalali
- Cellular and Molecular Research Center,Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
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30
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Amin S, Rahim F, Noor M, Wahab A, Qureshi SA. COVID-19 Associated Illnesses From Alveoli to Glomeruli: A Case Report. Cureus 2022; 14:e25670. [PMID: 35812531 PMCID: PMC9256007 DOI: 10.7759/cureus.25670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2022] [Indexed: 11/11/2022] Open
Abstract
Hypoxemic respiratory failure is the most frequent complication of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infection. Coronavirus disease-19 (COVID-19) is no longer considered a standalone respiratory infection. It can involve other organs, including kidneys by direct invasion or indirectly through immune activation, cytokine storm, microthrombi and hemodynamic instability. Multiorgan involvement carries a worse prognosis in COVID-19. Tubulopathy is the most frequently reported renal pathology, followed by glomerulopathies. Among the glomerulopathies, immunoglobulin A (IgA) nephropathy is less often reported. Differentiating tubulopathy from glomerulopathy is important from the management and prognostic point of view. Laboratory investigations, including urine microscopy, cannot predict glomerulopathy as a cause of renal involvement. Therefore, it is important to proceed with renal biopsy early to make a definite diagnosis. We report a case of a 33-year-old male who presented three weeks after recovery from COVID-19 with proteinuric acute kidney injury. Subsequent renal biopsy revealed IgA nephropathy.
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Affiliation(s)
- Said Amin
- Internal Medicine, Khyber Girls Medical College, Peshawar, PAK
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Fawad Rahim
- Internal Medicine, Khyber Girls Medical College, Peshawar, PAK
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Mohammad Noor
- Internal Medicine, Khyber Girls Medical College, Peshawar, PAK
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Azhar Wahab
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
| | - Sobia A Qureshi
- Internal Medicine, Hayatabad Medical Complex Peshawar, Peshawar, PAK
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31
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Paidas MJ, Sampath N, Schindler EA, Cosio DS, Ndubizu CO, Shamaladevi N, Kwal J, Rodriguez S, Ahmad A, Kenyon NS, Jayakumar AR. Mechanism of Multi-Organ Injury in Experimental COVID-19 and Its Inhibition by a Small Molecule Peptide. Front Pharmacol 2022; 13:864798. [PMID: 35712703 PMCID: PMC9196045 DOI: 10.3389/fphar.2022.864798] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 04/20/2022] [Indexed: 12/11/2022] Open
Abstract
Severe disease from SARS-CoV-2 infection often progresses to multi-organ failure and results in an increased mortality rate amongst these patients. However, underlying mechanisms of SARS- CoV-2-induced multi-organ failure and subsequent death are still largely unknown. Cytokine storm, increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs contribute to the pathogenesis of COVID-19. One potential consequence of immune/inflammatory events is the acute progression of generalized edema, which may lead to death. We, therefore, examined the involvement of water channels in the development of edema in multiple organs and their contribution to organ dysfunction in a Murine Hepatitis Virus-1 (MHV-1) mouse model of COVID-19. Using this model, we recently reported multi-organ pathological abnormalities and animal death similar to that reported in humans with SARS-CoV-2 infection. We now identified an alteration in protein levels of AQPs 1, 4, 5, and 8 and associated oxidative stress, along with various degrees of tissue edema in multiple organs, which correlate well with animal survival post-MHV-1 infection. Furthermore, our newly created drug (a 15 amino acid synthetic peptide, known as SPIKENET) that was designed to prevent the binding of spike glycoproteins with their receptor(s), angiotensin- converting enzyme 2 (ACE2), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (SARS-CoV-2 and MHV-1, respectively), ameliorated animal death and reversed altered levels of AQPs and oxidative stress post-MHV-1 infection. Collectively, our findings suggest the possible involvement of altered aquaporins and the subsequent edema, likely mediated by the virus-induced inflammatory and oxidative stress response, in the pathogenesis of COVID- 19 and the potential of SPIKENET as a therapeutic option.
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Affiliation(s)
- Michael J. Paidas
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
- *Correspondence: Michael J. Paidas, ; Arumugam R. Jayakumar,
| | - Natarajan Sampath
- School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India
| | - Emma A. Schindler
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Daniela S. Cosio
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Chima Obianuju Ndubizu
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | | | - Jaclyn Kwal
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Suset Rodriguez
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Anis Ahmad
- Department of Radiation Oncology, Sylvester Cancer Center, University of Miami School of Medicine, Miami, FL, United States
| | - Norma Sue Kenyon
- Microbiology & Immunology and Biomedical Engineering, Diabetes Research Institute, University of Miami, Miami, FL, United States
| | - Arumugam R. Jayakumar
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL, United States
- *Correspondence: Michael J. Paidas, ; Arumugam R. Jayakumar,
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Wishahi M, Kamal NM. Multidisciplinary basic and clinical research of acute kidney injury with COVID-19: Pathophysiology, mechanisms, incidence, management and kidney transplantation. World J Nephrol 2022; 11:105-114. [PMID: 35733654 PMCID: PMC9160708 DOI: 10.5527/wjn.v11.i3.105] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/04/2022] [Accepted: 04/30/2022] [Indexed: 02/06/2023] Open
Abstract
Acute kidney injury (AKI) linked to coronavirus disease 2019 (COVID-19) has been identified in the course of the disease. AKI can be mild or severe and that is dependent on the presence of comorbidities and the severity of COVID-19. Among patients who had been hospitalized with COVID-19, some were admitted to intensive care unit. The etiology of AKI associated with COVID-19 is multifactorial. Prevention of severe AKI is the prime task in patients with COVID-19 that necessitates a battery of measurements and precautions in management. Patients with AKI who have needed dialysis are in an increased risk to develop chronic kidney disease (CKD) or a progression of their existing CKD. Kidney transplantation patients with COVID-19 are in need of special management to adjust the doses of immunosuppression drugs and corticosteroids to guard against graft rejection but not to suppress the immune system to place the patient at risk of developing a COVID-19 infection. Immunosuppression drugs and corticosteroids for patients who have had a kidney transplant has to be adjusted based on laboratory results and is individualized aiming at the protection of the transplanted from rejection.
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Affiliation(s)
- Mohamed Wishahi
- Department of Urology, Theodor Bilharz Research Institute, Cairo 12411, Egypt
| | - Nabawya M Kamal
- Department of Anaesthesia and Surgical Intensive Care, Theodor Bilharz Research Institute, Cairo 12411, Egypt
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Savedchuk S, Raslan R, Nystrom S, Sparks MA. Emerging Viral Infections and the Potential Impact on Hypertension, Cardiovascular Disease, and Kidney Disease. Circ Res 2022; 130:1618-1641. [PMID: 35549373 DOI: 10.1161/circresaha.122.320873] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Viruses are ubiquitous in the environment and continue to have a profound impact on human health and disease. The COVID-19 pandemic has highlighted this with impressive morbidity and mortality affecting the world's population. Importantly, the link between viruses and hypertension, cardiovascular disease, and kidney disease has resulted in a renewed focus and attention on this potential relationship. The virus responsible for COVID-19, SARS-CoV-2, has a direct link to one of the major enzymatic regulatory systems connected to blood pressure control and hypertension pathogenesis, the renin-angiotensin system. This is because the entry point for SARS-CoV-2 is the ACE2 (angiotensin-converting enzyme 2) protein. ACE2 is one of the main enzymes responsible for dampening the primary effector peptide Ang II (angiotensin II), metabolizing it to Ang-(1-7). A myriad of clinical questions has since emerged and are covered in this review. Several other viruses have been linked to hypertension, cardiovascular disease, and kidney health. Importantly, patients with high-risk apolipoprotein L1 (APOL1) alleles are at risk for developing the kidney lesion of collapsing glomerulopathy after viral infection. This review will highlight several emerging viruses and their potential unique tropisms for the kidney and cardiovascular system. We focus on SARS-CoV-2 as this body of literature in regards to cardiovascular disease has advanced significantly since the COVID-19 pandemic.
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Affiliation(s)
- Solomiia Savedchuk
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC (S.S., S.N., M.A.S.)
| | - Rasha Raslan
- Internal Medicine, Virginia Commonwealth University, Richmond (R.R.)
| | - Sarah Nystrom
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC (S.S., S.N., M.A.S.)
| | - Matthew A Sparks
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC (S.S., S.N., M.A.S.)
- Renal Section, Durham VA Health Care System, NC (M.A.S.)
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Kesiena O, Papadopoulos P, Amakye D, Hama E, Mackay R. COVID-19 associated collapsing glomerulopathy presenting as acute kidney injury on chronic kidney disease: a case report and review of the literature. CEN Case Rep 2022; 11:273-277. [PMID: 34825347 PMCID: PMC8616717 DOI: 10.1007/s13730-021-00667-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 11/17/2021] [Indexed: 02/06/2023] Open
Abstract
Traditionally collapsing glomerulopathy (CG) is associated with medications, autoimmune disease, viral infection and the APOL1 gene variant seen in blacks/African Americans. Most reported cases of acute kidney injury (AKI) in COVID-19 infected individuals have been in individuals without prior CKD. In this report, we present a 49-year-old African American female with a past medical history of chronic kidney disease (CKD) stage 4, hypertension, type 2 diabetes mellitus, recent COVID-19 infection, and a repeat positive blood test for COVID-19 more than 21 days after the initial result, who presented with an AKI on CKD. Renal biopsy revealed a collapsing glomerulopathy. She was started on hemodialysis and did not receive immunosuppressive therapy due to the advanced scaring seen on the renal biopsy. Concerning the pathophysiology of COVID-19-associated CG, researchers have postulated different mechanisms such as a direct cytopathic effect of the virus on podocytes, immune dysregulation, and fluid imbalance. This is one of a few cases of AKI on CKD due to CG related to COVID-19. The mechanism of CG was, however, unclear. Currently, there is no specific interventions to prevent the development of CG in patients with COVID-19 infection. Further studies should investigate measures to prevent the development of CG.
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Affiliation(s)
- Onoriode Kesiena
- Department of Internal Medicine, Piedmont Athens Regional Medical Center, 1199 Prince Avenue, Athens, GA, 30606, USA.
| | - Pia Papadopoulos
- Department of Internal Medicine, Piedmont Athens Regional Medical Center, 1199 Prince Avenue, Athens, GA, 30606, USA
| | - Dominic Amakye
- Department of Internal Medicine, Piedmont Athens Regional Medical Center, 1199 Prince Avenue, Athens, GA, 30606, USA
| | - Eunice Hama
- Department of Internal Medicine, Piedmont Athens Regional Medical Center, 1199 Prince Avenue, Athens, GA, 30606, USA
| | - Rene Mackay
- Department of Nephrology, Piedmont Athens Regional Medical Center, Athens, GA, USA
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Mallela SK, Merscher S, Fornoni A. Implications of Sphingolipid Metabolites in Kidney Diseases. Int J Mol Sci 2022; 23:ijms23084244. [PMID: 35457062 PMCID: PMC9025012 DOI: 10.3390/ijms23084244] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/08/2022] [Accepted: 04/10/2022] [Indexed: 12/18/2022] Open
Abstract
Sphingolipids, which act as a bioactive signaling molecules, are involved in several cellular processes such as cell survival, proliferation, migration and apoptosis. An imbalance in the levels of sphingolipids can be lethal to cells. Abnormalities in the levels of sphingolipids are associated with several human diseases including kidney diseases. Several studies demonstrate that sphingolipids play an important role in maintaining proper renal function. Sphingolipids can alter the glomerular filtration barrier by affecting the functioning of podocytes, which are key cellular components of the glomerular filtration barrier. This review summarizes the studies in our understanding of the regulation of sphingolipid signaling in kidney diseases, especially in glomerular and tubulointerstitial diseases, and the potential to target sphingolipid pathways in developing therapeutics for the treatment of renal diseases.
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Affiliation(s)
- Shamroop kumar Mallela
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA;
- Peggy and Harold Katz Family Drug Discovery Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Sandra Merscher
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA;
- Peggy and Harold Katz Family Drug Discovery Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
- Correspondence: (S.M.); (A.F.); Tel.: +1-305-243-6567 (S.M.); +1-305-243-3583 (A.F.); Fax: +1-305-243-3209 (S.M.); +1-305-243-3506 (A.F.)
| | - Alessia Fornoni
- Katz Family Division of Nephrology and Hypertension, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136, USA;
- Peggy and Harold Katz Family Drug Discovery Center, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
- Correspondence: (S.M.); (A.F.); Tel.: +1-305-243-6567 (S.M.); +1-305-243-3583 (A.F.); Fax: +1-305-243-3209 (S.M.); +1-305-243-3506 (A.F.)
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Arrestier R, Gendreau S, Mokrani D, Bastard JP, Fellahi S, Bagate F, Masi P, d’Humières T, Razazi K, Carteaux G, De Prost N, Audard V, Mekontso-Dessap A. Acute Kidney Injury in Critically-Ill COVID-19 Patients. J Clin Med 2022; 11:jcm11072029. [PMID: 35407639 PMCID: PMC8999255 DOI: 10.3390/jcm11072029] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/25/2022] [Accepted: 03/31/2022] [Indexed: 02/04/2023] Open
Abstract
Purpose: Acute kidney injury (AKI) is common in patients with COVID-19, however, its mechanism is still controversial, particularly in ICU settings. Urinary proteinuria profile could be a non-invasive tool of interest to scrutinize the pathophysiological process underlying AKI in COVID-19 patients. Material and Methods: We conducted a retrospective study between March 2020 and April 2020. All patients with laboratory-confirmed COVID-19 and without end-stage kidney disease requiring renal replacement therapy before ICU admission were included. Our objectives were to assess the incidence and risk factors for AKI and to describe its clinical and biological characteristics, particularly its urinary protein profile. Results: Seventy patients were included; 87% needed mechanical ventilation and 61% needed vasopressor during their ICU stay; 64.3% of patients developed AKI and half of them needed dialysis. Total and tubular proteinuria on day 1 were higher in patients with AKI, whereas glomerular proteinuria was similar in both groups. The main risk factor for AKI was shock at admission (OR = 5.47 (1.74−17.2), p < 0.01). Mortality on day 28 was higher in AKI (23/45, 51.1%) than in no-AKI patients (1/25, 4%), p < 0.001. Risk factors for 28-days mortality were AKI with need for renal replacement therapy, non-renal SOFA score and history of congestive heart failure. Conclusions: AKI is common in COVID-19 patients hospitalized in ICU; it seems to be related to tubular lesions rather than glomerular injury and is related to shock at ICU admission.
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Affiliation(s)
- Romain Arrestier
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
- GRC CARMAS, Faculté de Médecine de Créteil, Université Paris Est Créteil, 94010 Creteil, France
- Correspondence: ; Tel.: +33-01-4981-2399; Fax: +33-01-4981-2542
| | - Ségolène Gendreau
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
- GRC CARMAS, Faculté de Médecine de Créteil, Université Paris Est Créteil, 94010 Creteil, France
| | - David Mokrani
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
| | - Jean-Philippe Bastard
- Département de Biochimie-Pharmacologie-Biologie Moléculaire-Génétique Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (J.-P.B.); (S.F.)
- Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris Est Créteil, 94010 Creteil, France;
| | - Soraya Fellahi
- Département de Biochimie-Pharmacologie-Biologie Moléculaire-Génétique Médicale, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (J.-P.B.); (S.F.)
- Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-Métabolisme et Nutrition (ICAN), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S938, Sorbonne Université, 75006 Paris, France
| | - François Bagate
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
- GRC CARMAS, Faculté de Médecine de Créteil, Université Paris Est Créteil, 94010 Creteil, France
| | - Paul Masi
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
- GRC CARMAS, Faculté de Médecine de Créteil, Université Paris Est Créteil, 94010 Creteil, France
| | - Thomas d’Humières
- Service de Physiologie Explorations Fonctionnelles, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France
| | - Keyvan Razazi
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
- GRC CARMAS, Faculté de Médecine de Créteil, Université Paris Est Créteil, 94010 Creteil, France
| | - Guillaume Carteaux
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
- GRC CARMAS, Faculté de Médecine de Créteil, Université Paris Est Créteil, 94010 Creteil, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris Est Créteil, 94010 Creteil, France;
| | - Nicolas De Prost
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
- GRC CARMAS, Faculté de Médecine de Créteil, Université Paris Est Créteil, 94010 Creteil, France
| | - Vincent Audard
- Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris Est Créteil, 94010 Creteil, France;
- Service de Néphrologie et Transplantation, Centre de Référence Maladie Rare Syndrome Néphrotique Idiopathique, Assistance Publique-Hôpitaux de Paris (AP-HP), Fédération Hospitalo-Universitaire Innovative Therapy for Immune Disorders, Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France
| | - Armand Mekontso-Dessap
- Service de Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, 94010 Creteil, France; (S.G.); (D.M.); (F.B.); (P.M.); (K.R.); (G.C.); (N.D.P.); (A.M.-D.)
- GRC CARMAS, Faculté de Médecine de Créteil, Université Paris Est Créteil, 94010 Creteil, France
- Institut National de la Santé et de la Recherche Médicale (INSERM) U955, Institut Mondor de Recherche Biomédicale (IMRB), Université Paris Est Créteil, 94010 Creteil, France;
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Kirtipal N, Kumar S, Dubey SK, Dwivedi VD, Gireesh Babu K, Malý P, Bharadwaj S. Understanding on the possible routes for SARS CoV-2 invasion via ACE2 in the host linked with multiple organs damage. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2022; 99:105254. [PMID: 35217145 PMCID: PMC8863418 DOI: 10.1016/j.meegid.2022.105254] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 01/12/2022] [Accepted: 02/19/2022] [Indexed: 02/07/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accountable for causing the coronavirus diseases 2019 (COVID-19), is already declared as a pandemic disease globally. Like previously reported SARS-CoV strain, the novel SARS-CoV-2 also initiates the viral pathogenesis via docking viral spike-protein with the membranal angiotensin-converting enzyme 2 (ACE2) - a receptor on variety of cells in the human body. Therefore, COVID-19 is broadly characterized as a disease that targets multiple organs, particularly causing acute complications via organ-specific pathogenesis accompanied by destruction of ACE2+ cells, including alveolus, cardiac microvasculature, endothelium, and glomerulus. Under such circumstances, the high expression of ACE2 in predisposing individuals associated with anomalous production of the renin-angiotensin system (RAS) may promote enhanced viral load in COVID-19, which comparatively triggers excessive apoptosis. Furthermore, multi-organ injuries were found linked to altered ACE2 expression and inequality between the ACE2/angiotensin-(1-7)/mitochondrial Ang system (MAS) and renin-angiotensin-system (RAS) in COVID-19 patients. However, the exact pathogenesis of multi-organ damage in COVID-19 is still obscure, but several perspectives have been postulated, involving altered ACE2 expression linked with direct/indirect damages by the virus-induced immune responses, such as cytokinin storm. Thus, insights into the invasion of a virus with respect to ACE2 expression site can be helpful to simulate or understand the possible complications in the targeted organ during viral infection. Hence, this review summarizes the multiple organs invasion by SARS CoV-2 linked with ACE2 expression and their consequences, which can be helpful in the management of the COVID-19 pathogenesis under life-threatening conditions.
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Affiliation(s)
- Nikhil Kirtipal
- School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
| | - Sanjay Kumar
- School of Biotechnology, Jawaharlal Nehru University, New Delhi, India; Centre for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation, Greater Noida, India
| | | | - Vivek Dhar Dwivedi
- Centre for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation, Greater Noida, India.
| | - K Gireesh Babu
- Department of Life Sciences, Parul Institute of Applied Sciences, Parul University, Limda, Vadodara, India.
| | - Petr Malý
- Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences v.v.i., BIOCEV Research Center, Vestec, Czech Republic.
| | - Shiv Bharadwaj
- Laboratory of Ligand Engineering, Institute of Biotechnology of the Czech Academy of Sciences v.v.i., BIOCEV Research Center, Vestec, Czech Republic.
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Atari M, Ambruzs JM, Saqqa O, Simon EE. Collapsing glomerulopathy in a patient with mixed connective tissue disease. Am J Med Sci 2022; 364:99-105. [DOI: 10.1016/j.amjms.2022.04.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 12/07/2021] [Accepted: 04/08/2022] [Indexed: 01/19/2023]
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Association of severity and mortality of Covid-19 cases among acute kidney injury and sexual dimorphism. Mol Biol Rep 2022; 49:6753-6762. [PMID: 35249167 PMCID: PMC8898193 DOI: 10.1007/s11033-022-07308-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 02/24/2022] [Indexed: 11/26/2022]
Abstract
Introduction The outbreak of coronavirus disease 2019 (Covid-19) severely impacted global health and economic status. The native receptor-ligand interaction of Angiotensin-converting enzyme 2 (ACE2) and S protein induces host cell pathogenesis via immunosuppression. Material and Methods The emerging evidence reports the sex disparity in Covid-19 induced mortality rate which affects abundantly men population. Although the biological interaction of Covid-19 with receptor upregulates the viral genome protein interactions and initiates the predictive multiorgan failure followed by acute kidney injury (AKI) in Covid-19 infected male population. Conclusion Besides, the knowledge and lessons learned from the study depict that cellular and molecular links may explain the risk and severity of Covid-19 and AKI in the male population and lead to management of Covid-19 induced AKI. Therefore, this review explored the pathways associated with the pathogenesis of two diseased conditions with sex disparity.
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Turner-Stokes T, Edwards H, Lightstone L. COVID-19 in patients with glomerular disease. Curr Opin Nephrol Hypertens 2022; 31:191-198. [PMID: 34923542 DOI: 10.1097/mnh.0000000000000769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Managing patients with glomerular disease during the COVID-19 pandemic has been challenging, as the infection risk associated with immunosuppression must be balanced against the need to control severe glomerular disease that can lead to kidney failure. This review provides an overview of COVID-19 and the effectiveness of SARS-CoV-2 vaccination in patients with glomerular disease. RECENT FINDINGS Registry data, although biased towards outcomes of hospitalized patients, suggest that the mortality from COVID-19 is higher in patients with glomerular disease than in the general population. Glucocorticoid use prior to SARS-CoV-2 infection is associated with adverse outcomes from COVID-19. Rituximab significantly attenuates serological responses to both natural infection and vaccination against SARS-CoV-2, although it is not clear whether this leads to adverse outcomes. Case reports of disease flares occurring after vaccination have been reported, but causality in any of these cases has yet to be proven and the absolute risk remains very small. SUMMARY Patients with glomerular disease represent an at-risk group for severe COVID-19 disease and vaccination is key to reducing this risk. As immunosuppressed patients demonstrate an attenuated response to vaccination, the efficacy of a third primary dose followed by a subsequent booster is being investigated.
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Affiliation(s)
- Tabitha Turner-Stokes
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London
- Imperial College Renal and Transplant Centre, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
| | - Helena Edwards
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London
- Imperial College Renal and Transplant Centre, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
| | - Liz Lightstone
- Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London
- Imperial College Renal and Transplant Centre, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
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Thorburn CA, Samarapungavan D, Kanaan HD, Cohn S, Jabbar KJ, Li W, Bedi D, Suliman ST, Patel PJ, Putchakayala K, Singh A, Zhang PL. Focal Segmental Glomerulosclerosis (FSGS) Progressing to Collapsing Glomerulopathy in Renal Transplant Recipients with and without COVID-19 Infection. Transplant Proc 2022; 54:1465-1470. [DOI: 10.1016/j.transproceed.2022.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 10/19/2022]
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Long JD, Strohbehn I, Sawtell R, Bhattacharyya R, Sise ME. COVID-19 Survival and its impact on chronic kidney disease. Transl Res 2022; 241:70-82. [PMID: 34774843 PMCID: PMC8579714 DOI: 10.1016/j.trsl.2021.11.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/31/2021] [Accepted: 11/03/2021] [Indexed: 12/16/2022]
Abstract
Up to 87% of patients hospitalized with coronavirus disease 2019 (COVID-19) experience chronic sequelae following infection. The long-term impact of COVID-19 infection on kidney function is largely unknown at this point in the COVID-19 pandemic. In this review, we highlight the current understanding of the pathophysiology of COVID-19-associated kidney injury and the impact COVID-19 may have on long-term kidney function. COVID-19-induced acute kidney injury may lead to tubular injury, endothelial injury, and glomerular injury. We highlight histopathologic correlates from large kidney biopsy and autopsy series. By conducting a comprehensive review of published literature to date, we summarize the rates of recovery from COVID-19-associated-AKI. Finally, we discuss how certain genetic differences, including APOL1 risk alleles (a risk factor for collapsing glomerulopathy), coupled with systemic healthcare disparities, may lead to a disproportionate burden of post-COVID-19-kidney function decline among racial and ethnic minority groups. We highlight the need for prospective studies to determine the true incidence of chronic kidney disease burden after COVID-19.
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Key Words
- aki, acute kidney disease
- aor, adjusted odds ratio
- atn, acute tubular necrosis
- covan, covid-19-associated-nephropathy
- covid-19, coronavirus disease 2019
- ckd, chronic kidney disease
- egfr, estimated glomerular filtration rate
- eskd, end-stage kidney disease
- hr, ratio
- tma, thrombotic microangiopathy
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Affiliation(s)
- Joshua D Long
- Massachusetts General Hospital, Department of Medicine, Division of Nephrology, Boston, Massachusetts
| | - Ian Strohbehn
- Massachusetts General Hospital, Department of Medicine, Division of Nephrology, Boston, Massachusetts
| | - Rani Sawtell
- Massachusetts General Hospital, Department of Medicine, Division of Nephrology, Boston, Massachusetts
| | - Roby Bhattacharyya
- Massachusetts General Hospital, Department of Medicine, Division of Infectious Diseases, Boston, Massachusetts
| | - Meghan E Sise
- Massachusetts General Hospital, Department of Medicine, Division of Nephrology, Boston, Massachusetts.
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Alawad MJ, Subahi EA, Al-Ani HA, Taha NM, Kamal I. A case of crescentic glomerulonephritis in a patient with COVID-19 infection: A case report and literature review. Medicine (Baltimore) 2022; 101:e28754. [PMID: 35363164 PMCID: PMC9282030 DOI: 10.1097/md.0000000000028754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 01/17/2022] [Indexed: 01/04/2023] Open
Abstract
RATIONALE Kidney involvement with COVID-19 infection is a well-known complication, and the majority of kidney involvement is related to ischemic injury/acute tubular injury. However, there are some cases of glomerulonephritis, the etiology of which is not yet known, but an immune process is likely to be the trigger. PATIENT CONCERNS A 27-year-old man presented to our hospital with facial puffiness and lower-limb swelling. DIAGNOSIS Laboratory assessment revealed features of impaired kidney function with proteinuria and hematuria; COVID-19 polymerase chain reaction was positive, which was consistent with pauci-immune crescentic focal segmental glomerulonephritis. INTERVENTION After renal biopsy, the patient was started on methylprednisolone and rituximab. Due to worsening kidney parameters, he underwent intermittent hemodialysis as needed. OUTCOME Kidney function tests partially improved; he was discharged on oral steroids with follow-up in the nephrology clinic to observe for the need for further hemodialysis. LESSONS We conducted a literature review of cases of glomerulonephritis associated with COVID-19 and described numerous types of glomerulonephritis. This report highlights the importance of recognizing emerging glomerulonephritis with COVID-19, the different pathological patterns of renal biopsies, and management interventions and responses.
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Affiliation(s)
- Mouhammad J. Alawad
- Department of Medical Education, Internal Medicine Residency Program, Hamad Medical Corporation, Doha, Qatar
| | - Eihab A. Subahi
- Department of Medical Education, Internal Medicine Residency Program, Hamad Medical Corporation, Doha, Qatar
| | - Haneen A. Al-Ani
- Department of Medical Education, Internal Medicine Residency Program, Hamad Medical Corporation, Doha, Qatar
| | - Noheir M. Taha
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
| | - Ijaz Kamal
- Department of Internal Medicine, Hamad Medical Corporation, Doha, Qatar
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Teixeira JP, Barone S, Zahedi K, Soleimani M. Kidney Injury in COVID-19: Epidemiology, Molecular Mechanisms and Potential Therapeutic Targets. Int J Mol Sci 2022; 23:2242. [PMID: 35216358 PMCID: PMC8877127 DOI: 10.3390/ijms23042242] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/07/2022] [Accepted: 02/08/2022] [Indexed: 01/08/2023] Open
Abstract
As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.
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Affiliation(s)
- J. Pedro Teixeira
- Department of Internal Medicine, Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; (S.B.); (K.Z.)
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
| | - Sharon Barone
- Department of Internal Medicine, Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; (S.B.); (K.Z.)
- Research/Medicine Services, New Mexico Veterans Healthcare Medical Center, Albuquerque, NM 87108, USA
| | - Kamyar Zahedi
- Department of Internal Medicine, Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; (S.B.); (K.Z.)
- Research/Medicine Services, New Mexico Veterans Healthcare Medical Center, Albuquerque, NM 87108, USA
| | - Manoocher Soleimani
- Department of Internal Medicine, Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; (S.B.); (K.Z.)
- Research/Medicine Services, New Mexico Veterans Healthcare Medical Center, Albuquerque, NM 87108, USA
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Gambella A, Barreca A, Biancone L, Roccatello D, Peruzzi L, Besso L, Licata C, Attanasio A, Papotti M, Cassoni P. Spectrum of Kidney Injury Following COVID-19 Disease: Renal Biopsy Findings in a Single Italian Pathology Service. Biomolecules 2022; 12:298. [PMID: 35204798 PMCID: PMC8961620 DOI: 10.3390/biom12020298] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/09/2022] [Accepted: 02/10/2022] [Indexed: 02/04/2023] Open
Abstract
The onset of coronavirus disease (COVID-19) as a pandemic infection, has led to increasing insights on its pathophysiology and clinical features being revealed, such as a noticeable kidney involvement. In this study, we describe the histopathological, immunofluorescence, and ultrastructural features of biopsy-proven kidney injury observed in a series of SARS-CoV-2 positive cases in our institution from April 2020 to November 2021. We retrieved and retrospectively reviewed nine cases (two pediatric and seven adults) that experienced nephrotic syndrome (six cases), acute kidney injury (two cases), and a clinically silent microhematuria and leukocyturia. Kidney biopsies were investigated by means of light microscopy, direct immunofluorescence, and electron microscopy. The primary diagnoses were minimal change disease (four cases), acute tubular necrosis (two cases), collapsing glomerulopathy (two cases), and C3 glomerulopathy (one case). None of the cases showed viral or viral-like particles on ultrastructural analysis. Novel and specific histologic features on kidney biopsy related to SARS-CoV-2 infection have been gradually disclosed and reported, harboring relevant clinical and therapeutic implications. Recognizing and properly diagnosing renal involvement in patients experiencing COVID-19 could be challenging (due to the lack of direct proof of viral infection, e.g., viral particles) and requires a proper integration of clinical and pathological data.
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Affiliation(s)
- Alessandro Gambella
- Pathology Unit, Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy; (A.G.); (A.A.)
| | - Antonella Barreca
- Pathology Unit, “Città della Salute e della Scienza di Torino” University Hospital, Via Santena 7, 10126 Turin, Italy;
| | - Luigi Biancone
- Division of Nephrology Dialysis and Transplantation, AOU Città della Salute e della Scienza di Torino, Department of Medical Sciences, University of Turin, 10126 Turin, Italy;
| | - Dario Roccatello
- CMID, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, Nephrology and Dialysis Unit (ERK-Net Member), San Giovanni Bosco Hub Hospital, University of Turin, 10144 Turin, Italy;
| | - Licia Peruzzi
- Pediatric Nephrology Unit, Regina Margherita Department, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy;
| | - Luca Besso
- Division of Nephrology and Dialysis, AO S. Croce e Carle di Cuneo, 12100 Cuneo, Italy;
| | - Carolina Licata
- Division of Nephrology and Dialysis, ASL TO4, 10073 Ciriè, Italy;
| | - Angelo Attanasio
- Pathology Unit, Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy; (A.G.); (A.A.)
| | - Mauro Papotti
- Pathology Unit, Department of Oncology, University of Turin, Via Santena 7, 10126 Turin, Italy;
| | - Paola Cassoni
- Pathology Unit, Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy; (A.G.); (A.A.)
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Wiley Z, Kubes JN, Cobb J, Jacob JT, Franks N, Plantinga L, Lea J. Age, Comorbid Conditions, and Racial Disparities in COVID-19 Outcomes. J Racial Ethn Health Disparities 2022; 9:117-123. [PMID: 33415702 PMCID: PMC7790329 DOI: 10.1007/s40615-020-00934-0] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/24/2020] [Accepted: 11/25/2020] [Indexed: 11/29/2022]
Abstract
BACKGROUND Black patients are disproportionately affected by COVID-19. The purpose of this study was to compare risks of hospitalization of Black and non-Black COVID-19 patients presenting to the emergency department and, of those hospitalized, to compare mortality and acute kidney injury. METHODS A retrospective cohort of 831 adult COVID-19 patients (68.5% Black) who presented to the emergency departments of four academic hospitals, March 1, 2020-May 31, 2020. The primary outcome was risk of hospitalization among Blacks vs. non-Blacks. Secondary outcomes were mortality and acute kidney injury, among hospitalized patients. RESULTS The crude odds of hospitalization were not different in Black vs. non-Black patients; however, with adjustment for age, Blacks had 55% higher odds of hospitalization. Mortality differed most in the model adjusted for age alone. Acute kidney injury was more common in the Black hospitalized patients, regardless of adjustment. Stratified analyses suggested that disparities in the risk of hospitalization and of in-hospital acute kidney injury were highest in the youngest patients. CONCLUSIONS Our report shows that Black and non-Black patients presenting to the emergency department with COVID-19 had similar risks of hospitalization and, of those who were hospitalized, similar mortality when adjusted for multiple factors. Blacks had higher risk of acute kidney injury. Our results suggest that examination of disparities without exploration of the individual effects of age and comorbidities may mask important patterns. While stratified analyses suggest that disparities in outcomes may differ substantially by age and comorbid conditions, further exploration among these important subgroups is needed to better target interventions to reduce disparities in COVID-19 clinical outcomes.
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Affiliation(s)
- Zanthia Wiley
- Division of Infectious Diseases - Emory University Hospital Midtown, Emory University School of Medicine, 550 Peachtree Street, 7th floor of Medical Office Tower, Atlanta, GA, 30308, USA.
| | - Julianne N Kubes
- Office of Quality and Risk, Emory Healthcare - Emory University Hospital Midtown, 550 Peachtree Street, Orr Building 8th floor, Atlanta, GA, 30308, USA
| | - Jason Cobb
- Division of Renal Medicine - Emory University Hospital Midtown, Emory University School of Medicine, 550 Peachtree Street, 7th floor of Medical Office Tower, Nephrology Clinic, Atlanta, GA, 30308, USA
| | - Jesse T Jacob
- Division of Infectious Diseases - Emory University Hospital Midtown, Emory University School of Medicine, 550 Peachtree Street, 7th floor of Medical Office Tower, Atlanta, GA, 30308, USA
| | - Nicole Franks
- Department of Emergency Medicine - Emory University Hospital Midtown, Emory University School of Medicine, 550 Peachtree Street, Orr Building 11th Floor, Atlanta, GA, 30308, USA
| | - Laura Plantinga
- Division of Geriatrics and Gerontology - WWHC, Emory University School of Medicine, 552, 1841 Clifton Road, Atlanta, GA, 30329, USA
| | - Janice Lea
- Division of Renal Medicine - Emory University Hospital Midtown, Emory University School of Medicine, 550 Peachtree Street, 7th floor of Medical Office Tower, Nephrology Clinic, Atlanta, GA, 30308, USA
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Mohamed RAE, Abdelsalam EM, Maghraby HM, Al Jedaani HS, Rakha EB, Hussain K, Sultan I. Performance features and mortality prediction of the 4C Score early in COVID-19 infection: a retrospective study in Saudi Arabia. J Investig Med 2022; 70:421-427. [PMID: 34836890 PMCID: PMC8635889 DOI: 10.1136/jim-2021-001940] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2021] [Indexed: 01/28/2023]
Abstract
The ISARIC4C consortium developed and internally validated the 4C Score for prediction of mortality only in hospitalized patients. We aimed to assess the validity of the 4C Score in mortality prediction of patients with COVID-19 who had been home isolated or hospitalized.This retrospective cross-sectional study was performed after the first wave of COVID-19. Data of all PCR-positive COVID-19 patients who had been discharged, hospitalized, or died were retrospectively analyzed. Patients were classified into four risk groups according to the 4C Mortality Score. A total of (506) patients were classified as follows: low (57.1%), intermediate (27.9%), high (13%), and very high (2%) risk groups. Clinical, radiological, and laboratory data were significantly more severe in the high and very high-risk groups compared with other groups (p<0.001 for all). Mortality rate was correctly estimated by the model with 71% sensitivity, 88.6% specificity, and area under the curve of 0.9. The mortality rate was underestimated among the very high-risk group (66.2% vs 90%). The odds of mortality were significantly greater in the presence of hypoxia (OR 2.6, 95% CI 1.5 to 4.6, p<0.001) and high respiratory rate (OR 5.3, 95% CI 1.6 to 17.9, p<0.007), C reactive protein (CRP) (OR 3.5, 95% CI 1.8 to 6.8, p<0.001), and blood urea nitrogen (BUN) (OR 1.9, 95% CI 1.3 to 3.1, p<0.002). Other components of the model had non-significant predictions. In conclusion, the 4C Mortality Score has good sensitivity and specificity in early risk stratification and mortality prediction of patient with COVID-19. Within the model, only hypoxia, tachypnea, high BUN, and CRP were the independent mortality predictors with the possibility of overlooking other important predictors.
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Affiliation(s)
- Rehab Abd Elfattah Mohamed
- Internal Medicine Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
- Internal Medicine Department, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
| | - Eman Mahmoud Abdelsalam
- Internal Medicine Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Hend Maghraby Maghraby
- Internal Medicine Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| | - Huda Shali Al Jedaani
- Obs/Gyn Department, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
| | - Ehab Badran Rakha
- Clinical Pathology Department, Mansoura University, Faculty of Medicine, Mansoura, Egypt
| | - Khamrunissa Hussain
- Quality Department, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
| | - Intessar Sultan
- Internal Medicine Department, Ibn Sina National College for Medical Studies, Jeddah, Saudi Arabia
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48
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Al-Khafaji ZA, Abady NR, Al-Kafaji HA. Epidemiological and Clinical Comparative Study for COVID-19 Patients in Babylon Province, Iraq. ARCHIVES OF RAZI INSTITUTE 2022; 77:111-115. [PMID: 35891720 PMCID: PMC9288599 DOI: 10.22092/ari.2021.356550.1869] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 11/10/2021] [Indexed: 06/15/2023]
Abstract
A respiratory illness outbreak caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) began in China and spread to other nations. Typically, the real-time reverse transcriptase polymerase chain reaction of nasopharyngeal swabs has been utilized to confirm the clinical diagnosis. However, it is uncertain if the virus is found in specimens from other places, and therefore, possibly transmitted in methods other than respiratory droplets. Patients with coronavirus disease 2019 (COVID-19) were identified based on symptoms, and SARS-CoV-2 detection confirmed the diagnosis. Pharyngeal swabs were obtained from August to September 2020. Individuals with obtained samples based on clinical indications from hospitals in Marjan City and a public health laboratory in Babylon Province, Iraq, were included in this retrospective study. The findings of the clinical symptoms and their intensity were provided in the chart, which revealed that all indications were equal in both male and female patients, with no obvious differences, especially given that all patients' ages ranged from 30 to 70 years. High temperature, sore throat, and shortness of breath were shown to be the most common symptoms, in comparison to other symptoms in the chart.
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Affiliation(s)
- Z A Al-Khafaji
- Department of Microbiology, College of Medicine, Babylon University, Babylon, Iraq
| | - N R Abady
- Department of Microbiology, Al-Qasim Green University, Babylon, Iraq
| | - H A Al-Kafaji
- Department of Microbiology, College of Medicine, Babylon University, Babylon, Iraq
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Cryer MJ, Farhan S, Kaufmann CC, Jäger B, Garg A, Krishnan P, Mehran R, Huber K. Prothrombotic Milieu, Thrombotic Events and Prophylactic Anticoagulation in Hospitalized COVID-19 Positive Patients: A Review. Clin Appl Thromb Hemost 2022; 28:10760296221074353. [PMID: 35068227 PMCID: PMC8793375 DOI: 10.1177/10760296221074353] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality worldwide. Although initial reports concentrated on severe respiratory illness, emerging literature has indicated a substantially elevated risk of thromboembolic events in patients with COVID-19 disease. Pro-inflammatory cytokine release has been linked to endothelial dysfunction and activation of coagulation pathways, as evident by elevated D-dimer levels and deranged coagulation parameters. Both macrovascular and microvascular thromboses have been described in observational cohort and post-mortem studies. Concurrently, preliminary data have suggested the role of therapeutic anticoagulation in preventing major thromboembolic complications in moderately but not critically ill patients. However, pending results from randomized controlled trials, clear guidance is lacking regarding the intensity and duration of anticoagulation in such patients. Herein, we review the existing evidence on incidence and pathophysiology of COVID-19 related thromboembolic complications and guide anticoagulation therapy based on current literature and societal consensus statements.
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Affiliation(s)
- Michael Joseph Cryer
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
- Tucson Medical Center/Tucson Hospitals Medical Education Program, Tucson, Arizona, USA
| | - Serdar Farhan
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | - Bernhard Jäger
- Wilhelminenhospital, Vienna, Austria
- Sigmund Freud University, Medical School, Vienna, Austria
| | - Aakash Garg
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Prakash Krishnan
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Roxana Mehran
- The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Kurt Huber
- Wilhelminenhospital, Vienna, Austria
- Sigmund Freud University, Medical School, Vienna, Austria
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50
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Dugbartey GJ, Alornyo KK, Ohene BO, Boima V, Antwi S, Sener A. Renal consequences of the novel coronavirus disease 2019 (COVID-19) and hydrogen sulfide as a potential therapy. Nitric Oxide 2022; 120:16-25. [PMID: 35032641 PMCID: PMC8755416 DOI: 10.1016/j.niox.2022.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 01/06/2022] [Accepted: 01/10/2022] [Indexed: 12/14/2022]
Abstract
The novel coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global pandemic which is primarily considered a respiratory illness. However, emerging reports show that the virus exhibits both pulmonary and extra-pulmonary manifestations in humans, with the kidney as a major extra-pulmonary target due to its abundant expression of angiotensin-converting enzyme 2 and transmembrane protease serine 2, which facilitate entry of the virus into cells. Acute kidney injury has become prevalent in COVID-19 patients without prior any history of kidney dysfunction. In addition, the virus also worsens kidney conditions and increases mortality of COVID-19 patients with pre-existing chronic kidney disease, renal cancer, diabetic nephropathy, end-stage kidney disease as well as dialysis and kidney transplant patients. In the search for antiviral agents for the treatment of COVID-19, hydrogen sulfide (H2S), the third established member of gasotransmitter family, is emerging as a potential candidate, possessing important therapeutic properties including antiviral, anti-inflammatory, anti-thrombotic and antioxidant properties. A recent clinical study revealed higher serum H2S levels in survivors of COVID-19 pneumonia with reduced interleukin-6 levels compared to fatal cases. In this review, we summarize the global impact of COVID-19 on kidney conditions and discuss the emerging role of H2S as a potential COVID-19 therapy.
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Affiliation(s)
- George J Dugbartey
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
| | - Karl K Alornyo
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Bright O Ohene
- Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Vincent Boima
- Department of Medicine and Therapeutics, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Accra, Ghana
| | - Sampson Antwi
- Department of Child Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology and Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Alp Sener
- Department of Surgery, Division of Urology, London Health Sciences Center, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, Western University, London, Ontario, Canada; Multi-organ Transplant Program, London Health Sciences Center, Ontario, Canada; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada
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