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Zununi Vahed S, Hosseiniyan Khatibi SM, Ardalan M. Canonical effects of cytokines on glomerulonephritis: A new outlook in nephrology. Med Res Rev 2025; 45:144-163. [PMID: 39164945 DOI: 10.1002/med.22074] [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: 11/08/2021] [Revised: 08/28/2022] [Accepted: 08/04/2024] [Indexed: 08/22/2024]
Abstract
Glomerulonephritis (GN) is an important cause of renal inflammation resulting from kidney-targeted adaptive and innate immune responses and consequent glomerular damage. Given the lack of autoantibodies, immune complexes, or the infiltrating immune cells in some forms of GN, for example, focal segmental glomerulosclerosis and minimal change disease, along with paraneoplastic syndrome and a special form of renal involvement in some viral infections, the likeliest causative scenario would be secreted factors, mainly cytokine(s). Since cytokines can modulate the inflammatory mechanisms, severity, and clinical outcomes of GN, it is rational to consider the umbrella term of cytokine GN as a new outlook to reclassify a group of previously known GN. We focus here, particularly, on cytokines that have the central "canonical effect" in the development of GN.
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Bach ML, Laftih S, Andresen JK, Pedersen RM, Andersen TE, Madsen LW, Madsen K, Hinrichs GR, Zachar R, Svenningsen P, Lund L, Johansen IS, Hansen LF, Palarasah Y, Jensen BL. ACE2 and TMPRSS2 in human kidney tissue and urine extracellular vesicles with age, sex, and COVID-19. Pflugers Arch 2025; 477:83-98. [PMID: 39382598 PMCID: PMC11711140 DOI: 10.1007/s00424-024-03022-y] [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: 06/10/2024] [Revised: 09/17/2024] [Accepted: 09/20/2024] [Indexed: 10/10/2024]
Abstract
SARS-CoV-2 virus infects cells by engaging with ACE2 requiring protease TMPRSS2. ACE2 is highly expressed in kidneys. Predictors for severe disease are high age and male sex. We hypothesized that ACE2 and TMPRSS2 proteins are more abundant (1) in males and with increasing age in kidney and (2) in urine and extracellular vesicles (EVs) from male patients with COVID-19 and (3) SARS-CoV-2 is present in urine and EVs during infection. Kidney cortex samples from patients subjected to cancer nephrectomy (male/female; < 50 years/˃75 years, n = 24; ˃80 years, n = 15) were analyzed for ACE2 and TMPRSS2 protein levels. Urine from patients hospitalized with SARS-CoV-2 infection was analyzed for ACE2 and TMPRSS2. uEVs were used for immunoblotting and SARS-CoV-2 mRNA and antigen detection. Tissue ACE2 and TMPRSS2 protein levels did not change with age. ACE2 was not more abundant in male kidneys in any age group. ACE2 protein was associated with proximal tubule apical membranes in cortex. TMPRSS2 was observed predominantly in the medulla. ACE2 was elevated significantly in uEVs and urine from patients with COVID-19 with no sex difference compared with urine from controls w/wo albuminuria. TMPRSS2 was elevated in uEVs from males compared to female. ACE2 and TMPRSS2 did not co-localize in uEVs/apical membranes. SARS-CoV-2 nucleoprotein and mRNA were not detected in urine. Higher kidney ACE2 protein abundance is unlikely to explain higher susceptibility to SARS-CoV-2 infection in males. Kidney tubular cells appear not highly susceptible to SARS-CoV-2 infection. Loss of ACE2 into urine in COVID could impact susceptibility and angiotensin metabolism.
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Affiliation(s)
- Marie Lykke Bach
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
| | - Sara Laftih
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Jesper K Andresen
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Rune M Pedersen
- Department of Clinical Microbiology, Odense University Hospital, and Research Unit for Clinical Microbiology, University of Southern Denmark, Odense, Denmark
| | - Thomas Emil Andersen
- Department of Clinical Microbiology, Odense University Hospital, and Research Unit for Clinical Microbiology, University of Southern Denmark, Odense, Denmark
| | - Lone W Madsen
- Department of Infectious Diseases, Odense University Hospital, and Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
- Unit for Infectious Diseases, Department of Medicine, Sygehus Lillebælt, Kolding, Denmark
| | - Kirsten Madsen
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
- Department of Pathology, Odense University Hospital, Odense, Denmark
| | - Gitte R Hinrichs
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
- Department of Nephrology, Odense University Hospital, Odense, Denmark
| | - Rikke Zachar
- Department of Nephrology, Odense University Hospital, Odense, Denmark
| | - Per Svenningsen
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Lars Lund
- Department of Urology, Odense University Hospital, Odense, Denmark
| | - Isik S Johansen
- Department of Infectious Diseases, Odense University Hospital, and Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
| | | | - Yaseelan Palarasah
- Unit of Inflammation and Cancer Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Boye L Jensen
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
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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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Baltu D, Kurt-Sukur ED, Tastemel Ozturk T, Gulhan B, Ozaltin F, Duzova A, Topaloglu R. COVID-19 vaccination among adolescents and young adults with chronic kidney conditions: a single-center experience. KLINISCHE PADIATRIE 2024. [PMID: 38821068 DOI: 10.1055/a-2319-2648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2024]
Abstract
BACKGROUND Following the pandemic of COVID-19, the main focus has been on COVID-19 vaccines and herd immunity. Although the safety of the COVID-19 vaccines has been shown in clinical trials, children with chronic diseases were not included. We investigated the side effect profile and safety of the COVID-19 vaccines in adolescents with kidney disease. METHODS A questionnaire including demographic information, history of COVID-19, vaccination status, and vaccine-related side effects was administered to the patients with chronic kidney disease (CKD) stage 2-5, glomerular disease treated with immunosuppression, and kidney transplant recipients. RESULTS Ninety-eight patients were vaccinated with CoronaVac-inactivated SARS-CoV-2 (n=16) or BNT162b2 messenger RNA (mRNA) COVİD-19 (n=82) vaccine. The mean age was 16.90±2.36 years. The most common side effects were local pain, fatigue, and fever. No serious side effects or renal disease flare were observed. There was no significant difference in the side effects reported after the BNT162b2 mRNA-RNA as compared to the Corona Vac-inactivated SARS-CoV-2 vaccine. No significant relationship was found between the frequency of side effects according to age, glomerular filtration rate, immunosuppressive treatments, CKD stage, and the underlying disease. CONCLUSION Although the reported data are subjective because they were obtained through a questionnaire and studies with long-term follow-up are needed, our early experience suggests that the vaccine is safe and adolescents and young adults should be encouraged to be vaccinated.
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Affiliation(s)
| | - Eda Didem Kurt-Sukur
- Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Tugba Tastemel Ozturk
- Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Bora Gulhan
- Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Fatih Ozaltin
- Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ali Duzova
- Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Rezan Topaloglu
- Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey
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Rakic JM, Pullinger CR, Van Blarigan EL, Movsesyan I, Stock EO, Malloy MJ, Kane JP. APOL1 Risk Variants Associate With the Prevalence of Stroke in African American Current and Past Smokers. J Am Heart Assoc 2023; 12:e030796. [PMID: 38084718 PMCID: PMC10863786 DOI: 10.1161/jaha.123.030796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 11/14/2023] [Indexed: 12/20/2023]
Abstract
BACKGROUND African American smokers have 2.5 times higher risk for stroke compared with nonsmokers (higher than other races). About 50% of the African American population carry 1 or 2 genetic variants (G1 and G2; rare in other races) of the apolipoprotein L1 gene (APOL1). Studies showed these variants may be associated with stroke. However, the role of the APOL1 risk variants in tobacco-related stroke is unknown. METHODS AND RESULTS In a cross-sectional study, we examined whether APOL1 risk variants modified the relationship between tobacco smoking and stroke prevalence in 513 African American adults recruited at University of California, San Francisco. Using DNA, plasma, and questionnaires we determined APOL1 variants, smoking status, and stroke prevalence. Using logistic regression models, we examined the association between smoking (ever versus never smokers) and stroke overall, and among carriers of APOL1 risk variants (1 or 2 risk alleles), and noncarriers, separately. Among participants, 41% were ever (current and past) smokers, 54% were carriers of the APOL1 risk variants, and 41 had a history of stroke. The association between smoking and stroke differed by APOL1 genotype (Pinteraction term=0.014). Among carriers, ever versus never smokers had odds ratio (OR) 2.46 (95% CI, 1.08-5.59) for stroke (P=0.034); OR 2.00 (95% CI, 0.81-4.96) among carriers of 1 risk allele, and OR 4.72 (95% CI, 0.62-36.02) for 2 risk alleles. Among noncarriers, smoking was not associated with a stroke. CONCLUSIONS Current and past smokers who carry APOL1 G1 and/or G2 risk variants may be more susceptible to stroke among the African American population.
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Affiliation(s)
- Jelena Mustra Rakic
- Cardiovascular Research InstituteUniversity of California, San FranciscoCAUSA
- Center for Tobacco Control Research and EducationUniversity of California, San FranciscoCAUSA
| | - Clive R. Pullinger
- Cardiovascular Research InstituteUniversity of California, San FranciscoCAUSA
- Department of Physiological NursingUniversity of California, San FranciscoCAUSA
| | - Erin L. Van Blarigan
- Department of Epidemiology and BiostatisticsUniversity of California, San FranciscoCAUSA
| | - Irina Movsesyan
- Cardiovascular Research InstituteUniversity of California, San FranciscoCAUSA
| | - Eveline Oestreicher Stock
- Cardiovascular Research InstituteUniversity of California, San FranciscoCAUSA
- Department of MedicineUniversity of California, San FranciscoCAUSA
| | - Mary J. Malloy
- Cardiovascular Research InstituteUniversity of California, San FranciscoCAUSA
- Department of MedicineUniversity of California, San FranciscoCAUSA
| | - John P. Kane
- Cardiovascular Research InstituteUniversity of California, San FranciscoCAUSA
- Department of MedicineUniversity of California, San FranciscoCAUSA
- Department of Biochemistry and BiophysicsUniversity of California, San FranciscoCAUSA
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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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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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Shabaka A, Rovirosa-Bigot S, Márquez CG, Alonso Riaño M, Fernández-Juárez G. Acute kidney failure and nephrotic syndrome secondary to COVID-19-associated focal segmental glomerulosclerosis. Nefrologia 2023; 42:727-729. [PMID: 36841681 PMCID: PMC9941307 DOI: 10.1016/j.nefroe.2020.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 10/29/2020] [Indexed: 02/23/2023] Open
Affiliation(s)
- Amir Shabaka
- Servicio de Nefrología, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
| | - Sofía Rovirosa-Bigot
- Servicio de Medicina Intensiva, Hospital Universitario Fundación Alcorcón, Madrid, Spain
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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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Muacevic A, Adler JR, Demarchi Foresto R, Machado Proença H, Medina-Pestana J. Two-Hit Kidney Allograft Injury by SARS-CoV-2. Cureus 2023; 15:e34603. [PMID: 36751573 PMCID: PMC9897707 DOI: 10.7759/cureus.34603] [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] [Accepted: 02/03/2023] [Indexed: 02/05/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) has been associated with acute kidney injury in kidney transplant recipients by several mechanisms. The authors report a case of acute kidney allograft dysfunction in a 48-year-old patient who presented in the emergency room with anasarca and nephrotic syndrome close after mild COVID-19 and no other clinical condition. Histopathology of the allograft biopsy revealed two distinct and simultaneous kidney lesions, collapsing glomerulopathy and thrombotic microangiopathy. Renal function persistently deteriorated, and definitive dialysis was initiated. After excluding other plausible causes for the findings, this case strengthens the hypothesis that the kidney allograft is also a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
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Lin L, Deng J, Tan W, Li J, Wu Z, Zheng L, Yang J. Pathogenesis and histological changes of nephropathy associated with COVID-19. J Med Virol 2023; 95:e28311. [PMID: 36377540 DOI: 10.1002/jmv.28311] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 11/01/2022] [Accepted: 11/10/2022] [Indexed: 11/16/2022]
Abstract
Coronavirus disease 2019 (COVID-19) can cause damage to multiple organ, not only to the lungs, but also to the kidneys. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute and chronic kidney disease through direct viral infection, indirect injury, and vaccination-related injury. Like lung injury, kidney injury is also an important aspect affecting the severity and prognosis of SARS-CoV-2. This article summarizes the pathogenesis, pathological manifestations, and clinical features of SARS-CoV-2 direct or indirect renal injury. Including direct injury, indirect injury, special comorbidities (receiving kidney transplantation and chronic kidney disease), and vaccine-related renal injury, and exploring the possible therapeutic effect of anti-SARS-CoV-2 therapy on renal injury. The purpose is to provide reference for understanding COVID-19-related renal injury, guiding clinical and pathological diagnosis and treatment, and evaluating prognosis.
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Affiliation(s)
- Lirong Lin
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Junhui Deng
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Wei Tan
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Jie Li
- Department of Nephrology, Yongchuan People's Hospital of Chongqing, Chongqing, China
| | - Zhifeng Wu
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Luquan Zheng
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
| | - Jurong Yang
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, China
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Nourmohammadi J, Akhondi M, Rajabiniat F, Vaeaz ZS, Nourmohammadi Z, Moghadam MH. Pharmacological evaluation of glomerulonephritis in Covid-19 patients. ROMANIAN JOURNAL OF MILITARY MEDICINE 2022. [DOI: 10.55453/rjmm.2022.125.4.14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
"Acute kidney injury (AKI) and glomerulonephritis can be complications in COVID-19 patients, which is announced with widely incidence rates in different investigations and is determined to have a major effect on the prognosis of the disease. There are considerable variations in AKI and glomerulonephritis rates between other countries. The rate is generally lower than in Western Europe and the United States in China. Heterogeneity in different racial and ethnic lines can be a potential explanation. This investigation systematically reviews the scientific resources regarding AKI and glomerulonephritis among hospitalized COVID-19 patients. Both observational and interventional investigations(including case reports) with English full-text provide essential data, with no limitation in release or peer-review. More evidence is required to assess the AKI, especially glomerulonephritis in Covid-19 patients, for better management of Covid-19."
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Sambharia M, Rastogi P, Thomas CP. Monogenic focal segmental glomerulosclerosis: A conceptual framework for identification and management of a heterogeneous disease. AMERICAN JOURNAL OF MEDICAL GENETICS. PART C, SEMINARS IN MEDICAL GENETICS 2022; 190:377-398. [PMID: 35894442 PMCID: PMC9796580 DOI: 10.1002/ajmg.c.31990] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/31/2022] [Accepted: 06/30/2022] [Indexed: 01/29/2023]
Abstract
Focal segmental glomerulosclerosis (FSGS) is not a disease, rather a pattern of histological injury occurring from a variety of causes. The exact pathogenesis has yet to be fully elucidated but is likely varied based on the type of injury and the primary target of that injury. However, the approach to treatment is often based on the degree of podocyte foot process effacement and clinical presentation without sufficient attention paid to etiology. In this regard, there are many monogenic causes of FSGS with variable presentation from nephrotic syndrome with histological features of primary podocytopathy to more modest degrees of proteinuria with limited evidence of podocyte foot process injury. It is likely that genetic causes are largely underdiagnosed, as the role and the timing of genetic testing in FSGS is not established and genetic counseling, testing options, and interpretation of genotype in the context of phenotype may be outside the scope of practice for both nephrologists and geneticists. Yet most clinicians believe that a genetic diagnosis can lead to targeted therapy, limit the use of high-dose corticosteroids as a therapeutic trial, and allow the prediction of the natural history and risk for recurrence in the transplanted kidney. In this manuscript, we emphasize that genetic FSGS is not monolithic in its presentation, opine on the importance of genetic testing and provide an algorithmic approach to deployment of genetic testing in a timely fashion when faced with a patient with FSGS.
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Affiliation(s)
- Meenakshi Sambharia
- Division of Nephrology, Department of Internal MedicineUniversity of IowaIowa CityIowaUSA
| | - Prerna Rastogi
- Department of PathologyUniversity of IowaIowa CityIowaUSA
| | - Christie P. Thomas
- Division of Nephrology, Department of Internal MedicineUniversity of IowaIowa CityIowaUSA,Department of PediatricsUniversity of IowaIowa CityIowaUSA,The Iowa Institute of Human GeneticsUniversity of IowaIowa CityIowaUSA,Medical ServiceVeterans Affairs Medical CenterIowa CityIowaUSA
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Cancarevic I, Nassar M, Medina L, Sanchez A, Parikh A, Hosna A, Devanabanda B, Vest M, Ayotunde F, Ghallab M, Omran I. Nephrotic Syndrome in Adult Patients With COVID-19 Infection or Post COVID-19 Vaccine: A Systematic Review. Cureus 2022; 14:e29613. [PMID: 36312654 PMCID: PMC9595350 DOI: 10.7759/cureus.29613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/26/2022] [Indexed: 11/05/2022] Open
Abstract
Nephrotic syndrome is a condition characterized by damage to podocytes that results in significant proteinuria, edema, hyperlipidemia, and hypercoagulability. Infections and malignancies are frequently associated with nephrotic syndrome. The COVID-19 virus has been associated with several atypical presentations of upper respiratory infections and acute kidney injury. Considering that COVID-19 causes systemic inflammatory changes, it seems plausible that it may also lead to nephrotic syndrome. This study aimed to investigate if an association between COVID-19 and the different types of nephrotic syndromes exists. Data were extracted into a spreadsheet. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS, IBM Corp., Armonk, NY, USA). We performed a systematic search of PubMed/Medline and Embase databases using both medical subject headings (MeSH) and regular keywords associated with COVID-19 and nephrotic syndrome, including different types of nephrotic syndromes. The search was performed on 17th December 2021. We included case reports and case series about adult patients who developed findings suggestive of nephrotic syndrome shortly after infection or vaccination. We excluded cases involving children, pregnant women, articles written in languages other than English, and those that were not retrievable. The relevance and quality of identified articles were assessed. We included 32 articles in the study, primarily case reports and case series. In our study, COVID-19 and the COVID-19 vaccine have been associated with the development of nephrotic syndrome, primarily a collapsing form of focal segmental glomerulosclerosis, although other forms have been observed as well. There was little consistency in patient histories, clinical presentations, clinical courses, or treatment regimens, although it appeared that most cases eventually resolved. More cases need to be reported and analyzed before more definitive conclusions can be reached. In conclusion, nephrotic syndrome is a possible complication of both COVID-19 infection and the COVD-19 vaccine and should be considered in patients exhibiting sudden onset edemas or deterioration in kidney function. While the majority of cases respond to standard treatment, clearer guidelines will need to be developed once more data is available.
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Affiliation(s)
- Ivan Cancarevic
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, USA
| | - Mahmoud Nassar
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, USA
| | - Luis Medina
- Internal Medicine, Queens Hospital Center, New York, USA
| | - Angelica Sanchez
- Internal Medicine, Universidad Autónoma de Santo Domingo, San Francisco de Macorís, DOM
| | - Avish Parikh
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, USA
| | - Asma Hosna
- Internal Medicine, Mount Sinai Hospital, New York , USA
| | - Bhavana Devanabanda
- Integrative Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, USA
| | - Mallorie Vest
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, USA
| | - Fatima Ayotunde
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, USA
| | - Muhammad Ghallab
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, USA
| | - Ismail Omran
- Internal Medicine, Icahn School of Medicine at Mount Sinai/NYC Health+Hospitals/Queens, New York, USA
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15
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Salvadori M, Tsalouchos A. COVID-19 and Kidney Transplantation: Epidemiology, Histopathological Presentation, Clinical Presentation and Outcomes, and Therapeutic Strategies. TRANSPLANTOLOGY 2022; 3:219-229. [DOI: 10.3390/transplantology3030023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
Abstract
Multiple case series of kidney transplant recipients with COVID-19 have shown increased mortality compared to nontransplant patients. To date, we do not have high-level evidence to inform immunosuppression minimization strategies in infected transplant recipients. Most centers, however, have adopted an early antimetabolite withdrawal in addition to other interventions. The epidemiological problem concerns also dialysis patients and waitlisted patients who have a higher COVID-19 infection diffusion with respect to kidney transplant recipients. Several factors influence mortality among kidney transplant recipients. Among these factors are the age, race, and comorbidity factors, such as hypertension, diabetes mellitus, obesity, and previous respiratory problems. Treatment is still limited. The only effective antiviral drug is remdesivir that should be administered before the development of the cytokine storm. Vaccination seems to be useful, but due to the concomitant immunosuppression limiting its efficacy, at least three or four doses should be administered.
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Affiliation(s)
- Maurizio Salvadori
- Department of Renal Transplantation, Careggi University Hospital, Viale Pieraccini 18, 50139 Florence, Italy
| | - Aris Tsalouchos
- Division of Nephrology, Santa Maria Annunziata Hospital, Via Antella 58, 50012 Florence, Italy
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16
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Daneshpajouhnejad P, Kopp JB, Winkler CA, Rosenberg AZ. The evolving story of apolipoprotein L1 nephropathy: the end of the beginning. Nat Rev Nephrol 2022; 18:307-320. [PMID: 35217848 PMCID: PMC8877744 DOI: 10.1038/s41581-022-00538-3] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2022] [Indexed: 01/13/2023]
Abstract
Genetic coding variants in APOL1, which encodes apolipoprotein L1 (APOL1), were identified in 2010 and are relatively common among individuals of sub-Saharan African ancestry. Approximately 13% of African Americans carry two APOL1 risk alleles. These variants, termed G1 and G2, are a frequent cause of kidney disease — termed APOL1 nephropathy — that typically manifests as focal segmental glomerulosclerosis and the clinical syndrome of hypertension and arterionephrosclerosis. Cell culture studies suggest that APOL1 variants cause cell dysfunction through several processes, including alterations in cation channel activity, inflammasome activation, increased endoplasmic reticulum stress, activation of protein kinase R, mitochondrial dysfunction and disruption of APOL1 ubiquitinylation. Risk of APOL1 nephropathy is mostly confined to individuals with two APOL1 risk variants. However, only a minority of individuals with two APOL1 risk alleles develop kidney disease, suggesting the need for a ‘second hit’. The best recognized factor responsible for this ‘second hit’ is a chronic viral infection, particularly HIV-1, resulting in interferon-mediated activation of the APOL1 promoter, although most individuals with APOL1 nephropathy do not have an obvious cofactor. Current therapies for APOL1 nephropathies are not adequate to halt progression of chronic kidney disease, and new targeted molecular therapies are in clinical trials. This Review summarizes current understanding of the role of APOL1 variants in kidney disease. The authors discuss the genetics, protein structure and biological functions of APOL1 variants and provide an overview of promising therapeutic strategies.
In contrast to other APOL family members, which are primarily intracellular, APOL1 contains a unique secretory signal peptide, resulting in its secretion into plasma. APOL1 renal risk alleles provide protection from African human trypanosomiasis but are a risk factor for progressive kidney disease in those carrying two risk alleles. APOL1 risk allele frequency is ~35% in the African American population in the United States, with ~13% of individuals having two risk alleles; the highest allele frequencies are found in West African populations and their descendants. Cell and mouse models implicate endolysosomal and mitochondrial dysfunction, altered ion channel activity, altered autophagy, and activation of protein kinase R in the pathogenesis of APOL1-associated kidney disease; however, the relevance of these injury pathways to human disease has not been resolved. APOL1 kidney disease tends to be progressive, and current standard therapies are generally ineffective; targeted therapeutic strategies hold the most promise.
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Affiliation(s)
- Parnaz Daneshpajouhnejad
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Pathology, University of Pennsylvania Hospital, Philadelphia, PA, USA
| | | | - Cheryl A Winkler
- Basic Research Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
| | - Avi Z Rosenberg
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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17
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Ning Q, Wu D, Wang X, Xi D, Chen T, Chen G, Wang H, Lu H, Wang M, Zhu L, Hu J, Liu T, Ma K, Han M, Luo X. The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication. Signal Transduct Target Ther 2022; 7:57. [PMID: 35197452 PMCID: PMC8863906 DOI: 10.1038/s41392-022-00907-1] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 01/10/2022] [Accepted: 01/17/2022] [Indexed: 02/06/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.
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Affiliation(s)
- Qin Ning
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Di Wu
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaojing Wang
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dong Xi
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Chen
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guang Chen
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongwu Wang
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huiling Lu
- National Medical Center for Major Public Health Events, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ming Wang
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lin Zhu
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Junjian Hu
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tingting Liu
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ke Ma
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Meifang Han
- National Medical Center for Major Public Health Events, Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Xiaoping Luo
- National Medical Center for Major Public Health Events, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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18
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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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19
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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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20
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Muehlig AK, Gies S, Huber TB, Braun F. Collapsing Focal Segmental Glomerulosclerosis in Viral Infections. Front Immunol 2022; 12:800074. [PMID: 35095882 PMCID: PMC8792967 DOI: 10.3389/fimmu.2021.800074] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 12/20/2021] [Indexed: 01/10/2023] Open
Abstract
Collapsing glomerulopathy represents a special variant of the proteinuric kidney disease focal segmental glomerulosclerosis (FSGS). Histologically, the collapsing form of FSGS (cFSGS) is characterized by segmental or global condensation and obliteration of glomerular capillaries, the appearance of hyperplastic and hypertrophic podocytes and severe tubulointerstitial damage. Clinically, cFSGS patients present with acute kidney injury, nephrotic-range proteinuria and are at a high risk of rapid progression to irreversible kidney failure. cFSGS can be attributed to numerous etiologies, namely, viral infections like HIV, cytomegalovirus, Epstein-Barr-Virus, and parvovirus B19 and also drugs and severe ischemia. Risk variants of the APOL1 gene, predominantly found in people of African descent, increase the risk of developing cFSGS. Patients infected with the new Corona-Virus SARS-CoV-2 display an increased rate of acute kidney injury (AKI) in severe cases of COVID-19. Besides hemodynamic instability, cytokine mediated injury and direct viral entry and infection of renal epithelial cells contributing to AKI, there are emerging reports of cFSGS associated with SARS-CoV-2 infection in patients of mainly African ethnicity. The pathogenesis of cFSGS is proposed to be linked with direct viral infection of podocytes, as described for HIV-associated glomerulopathy. Nevertheless, there is growing evidence that the systemic inflammatory cascade, activated in acute viral infections like COVID-19, is a major contributor to the impairment of basic cellular functions in podocytes. This mini review will summarize the current knowledge on cFSGS associated with viral infections with a special focus on the influence of systemic immune responses and potential mechanisms propagating the development of cFSGS.
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Affiliation(s)
- Anne K Muehlig
- III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,University Children's Research@Kinder-UKE, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sydney Gies
- III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tobias B Huber
- III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Fabian Braun
- III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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21
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Jefferis J, Kassianos AJ, Grivei A, Doucet B, Healy H, Francis L, Mon SY, John GT. SARS-CoV-2 vaccination-associated collapsing glomerulopathy in a kidney transplant recipient. Kidney Int 2022; 101:635-636. [PMID: 34995649 PMCID: PMC8731234 DOI: 10.1016/j.kint.2021.12.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/16/2021] [Accepted: 12/23/2021] [Indexed: 11/05/2022]
Affiliation(s)
- Julia Jefferis
- Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Andrew J Kassianos
- Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia; Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, Australia
| | - Anca Grivei
- Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Australia; Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, Australia
| | - Brian Doucet
- Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Helen Healy
- Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia; Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Brisbane, Australia
| | - Leo Francis
- Anatomical Pathology, Pathology Queensland, Health Support Queensland, Brisbane, Australia
| | - Saw Yu Mon
- Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - George T John
- Kidney Health Service, Royal Brisbane and Women's Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
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22
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Chen A, Yin L, Lee K, He JC. Similarities and Differences between COVID-19-Associated Nephropathy and HIV-Associated Nephropathy. KIDNEY DISEASES (BASEL, SWITZERLAND) 2022; 8:1-12. [PMID: 35127839 PMCID: PMC8805054 DOI: 10.1159/000520235] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 09/11/2021] [Indexed: 12/13/2022]
Abstract
Kidney disease is a major complication of viral infection, which can cause both acute and chronic kidney diseases via different mechanisms such as immune-mediated injury, kidney cell injury from a direct viral infection, systemic effects, and antiviral drug-induced nephrotoxicity. HIV-associated nephropathy (HIVAN), characterized by collapsing focal segmental glomerulosclerosis (cFSGS), has been described 2 decades ago as a major complication of acquired-immunodeficiency syndrome. The pathogenesis of HIVAN has been well studied, including viral entry, host response, and genetic factors. The incidence of this disease has been dramatically dropped with current antiretroviral therapy. In the recent severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic, acute kidney injury was also found to be a major complication in patients with (coronavirus disease) COVID-19. These patients also developed glomerular disease such as cFSGS in African Americans with apolipoprotein L1 risk alleles, similar to HIVAN. Whether SARS-CoV-2 can infect kidney cells locally remains controversial, but both local infection and systemic effects are likely involved in the pathogenesis of this disease. In this review, we present a comparison of the clinical presentations, pathological findings, disease mechanisms, and potential treatments between HIVAN and COVID-19. Leveraging the knowledge in HIVAN and experimental approaches used to study HIVAN will facilitate the exploration in the pathogenesis of COVID-19-associated kidney disease and improve our management of COVID-19 patients.
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Affiliation(s)
- Anqun Chen
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Lijun Yin
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Kyung Lee
- Division of Nephrology, Department of Medicine, Icahn School of Medicineat Mount Sinai, New York, New York, USA
| | - John Cijiang He
- Division of Nephrology, Department of Medicine, Icahn School of Medicineat Mount Sinai, New York, New York, USA
- Renal Program, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA
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23
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Daniel E, Sekulic M, Kudose S, Kubin C, Ye X, Shayan K, Patel A, Cohen DJ, E. Ratner L, Santoriello D, Barry Stokes M, Markowitz GS, Pereira MR, D’Agati VD, Batal I. Kidney allograft biopsy findings after COVID-19. Am J Transplant 2021; 21:4032-4042. [PMID: 34403563 PMCID: PMC8441660 DOI: 10.1111/ajt.16804] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/26/2021] [Accepted: 08/11/2021] [Indexed: 01/25/2023]
Abstract
COVID-19 has been associated with acute kidney injury and published reports of native kidney biopsies have reported diverse pathologies. Case series directed specifically to kidney allograft biopsy findings in the setting of COVID-19 are lacking. We evaluated 18 kidney transplant recipients who were infected with SARS-CoV-2 and underwent allograft biopsy. Patients had a median age of 55 years, six were female, and five were Black. Fifteen patients developed COVID-19 pneumonia, of which five required mechanical ventilation. Notably, five of 11 (45%) biopsies obtained within 1 month of positive SARS-CoV-2 PCR showed acute rejection (four with arteritis, three of which were not associated with reduced immunosuppression). The remaining six biopsies revealed podocytopathy (n = 2, collapsing glomerulopathy and lupus podocytopathy), acute tubular injury (n = 2), infarction (n = 1), and transplant glomerulopathy (n = 1). Biopsies performed >1 month after positive SARS-CoV-2 PCR revealed collapsing glomerulopathy (n = 1), acute tubular injury (n = 1), and nonspecific histologic findings (n = 5). No direct viral infection of the kidney allograft was detected by immunohistochemistry, in situ hybridization, or electron microscopy. On follow-up, two patients died and most patients showed persistent allograft dysfunction. In conclusion, we demonstrate diverse causes of kidney allograft dysfunction after COVID-19, the most common being acute rejection with arteritis.
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Affiliation(s)
- Emily Daniel
- Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, New York, USA
| | - Miroslav Sekulic
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Satoru Kudose
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Christine Kubin
- Department of Pharmacy, New York Presbyterian Hospital, New York, New York, USA
| | - Xiaoyi Ye
- Department of Medicine, Nephrology, Hartford Hospital, Hartford, Connecticut, USA
| | - Katayoon Shayan
- Department of Pathology, Rady Children’s Specialists of San Diego, California, USA
| | - Ankita Patel
- Department of Medicine, Nephrology, Hackensack University Medical Center, Hackensack, New Jersey, USA
| | - David J. Cohen
- Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, New York, USA
| | - Lloyd E. Ratner
- Department of Surgery, Renal and Pancreatic Transplantation, Columbia University Irving Medical Center, New York, New York, USA
| | - Dominick Santoriello
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - M. Barry Stokes
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Glen S. Markowitz
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Marcus R. Pereira
- Department of Medicine, Division of Infectious Disease, Columbia University Irving Medical Center, New York, New York, USA
| | - Vivette D. D’Agati
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Ibrahim Batal
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA,Correspondence Ibrahim Batal, Department of Pathology and Cell Biology, Renal Division, Columbia University Irving Medical Center, New York, NY, USA.
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24
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Jeyalan V, Storrar J, Wu HHL, Ponnusamy A, Sinha S, Kalra PA, Chinnadurai R. Native and transplant kidney histopathological manifestations in association with COVID-19 infection: A systematic review. World J Transplant 2021; 11:480-502. [PMID: 34868898 PMCID: PMC8603634 DOI: 10.5500/wjt.v11.i11.480] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/05/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in clinically significant multi-system disease including involvement in the kidney. The underlying histopathological processes were unknown at the start of the pandemic. As case reports and series have been published describing the underlying renal histopathology from kidney biopsies, we have started to gain an insight into the renal manifestations of this novel disease.
AIM To provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019 (COVID-19) infection.
METHODS A systematic review was performed by conducting a literature search in the following websites-‘PubMed’, ‘Web of Science’, ‘Embase’ and ‘Medline-ProQuest’ with the following search terms-“COVID-19 AND kidney biopsy”, “COVID-19 AND renal biopsy”, “SARS-CoV-2 AND kidney biopsy” and “SARS-CoV-2 AND renal biopsy”. We have included published data up until February 15, 2021, which includes kidney biopsies (native, transplant and postmortem) from patients with COVID-19. Data on clinical presentation, histopathological features, management and outcome was extracted from the reported studies.
RESULTS The total number of biopsies reported on here is 288, of which 189 are postmortem, 84 native and 15 transplants. The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury (ATI) to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy. There was variation in the specific treatment used for the various renal conditions, which included steroids, hydroxychloroquine, eculizumab, convalescent plasma, rituximab, anakinra, cyclophosphamide and renal replacement therapy, amongst others. The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others (for example, sepsis related hypoperfusion for ATI). It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease, and as such there may be inherent selection bias in the results described. Further work will be required to determine the pathogenetic link, if any, between COVID-19 and the other renal pathologies.
CONCLUSION This report has clinical relevance as certain renal pathologies have specific management, with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration, dependent upon the clinical presentation.
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Affiliation(s)
- Vishnu Jeyalan
- Department of Renal Medicine, Royal Preston Hospital, Preston PR2 9HT, United Kingdom
| | - Joshua Storrar
- Department of Renal Medicine, Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
| | - Henry H L Wu
- Department of Renal Medicine, Royal Preston Hospital, Preston PR2 9HT, United Kingdom
| | - Arvind Ponnusamy
- Department of Renal Medicine, Royal Preston Hospital, Preston PR2 9HT, United Kingdom
| | - Smeeta Sinha
- Department of Renal Medicine, Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
| | - Philip A Kalra
- Department of Renal Medicine, Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Salford Care Organisation, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, United Kingdom
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, United Kingdom
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25
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Wu J, Ma Z, Raman A, Beckerman P, Dhillon P, Mukhi D, Palmer M, Chen HC, Cohen CR, Dunn T, Reilly J, Meyer N, Shashaty M, Arany Z, Haskó G, Laudanski K, Hung A, Susztak K. APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis. Immunity 2021; 54:2632-2649.e6. [PMID: 34715018 PMCID: PMC9338439 DOI: 10.1016/j.immuni.2021.10.004] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/18/2021] [Accepted: 10/06/2021] [Indexed: 12/17/2022]
Abstract
The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endothelial-specific expression of RV APOL1 and in vitro studies demonstrated that RV APOL1 interfered with mitophagy, leading to cytosolic release of mitochondrial DNA and activation of the inflammasome (NLRP3) and the cytosolic nucleotide sensing pathways (STING). Genetic deletion or pharmacological inhibition of NLRP3 and STING protected mice from RV APOL1-induced permeability defects and proinflammatory endothelial changes in sepsis. Our studies identify the inflammasome and STING pathways as potential targets to reduce APOL1-associated health disparities in sepsis and COVID-19.
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Affiliation(s)
- Junnan Wu
- Renal, Electrolyte, and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Ziyuan Ma
- Renal, Electrolyte, and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Archana Raman
- Renal, Electrolyte, and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Pazit Beckerman
- Renal, Electrolyte, and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Poonam Dhillon
- Renal, Electrolyte, and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Dhanunjay Mukhi
- Renal, Electrolyte, and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Matthew Palmer
- Department of Pathology and Laboratory Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Hua Chang Chen
- Division of Nephrology & Hypertension, Tennessee Valley Healthcare System, Nashville Campus and Vanderbilt University Medical Centre, Nashville, TN, USA; Division of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Cassiane Robinson Cohen
- Division of Nephrology & Hypertension, Tennessee Valley Healthcare System, Nashville Campus and Vanderbilt University Medical Centre, Nashville, TN, USA; Division of Nephrology & Hypertension, Vanderbilt Precision Nephrology Program, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Thomas Dunn
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - John Reilly
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Nuala Meyer
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Michael Shashaty
- Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Zoltan Arany
- Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - György Haskó
- Department of Anesthesiology, Columbia University, New York, NY 10032, USA
| | - Krzysztof Laudanski
- Department of Anesthesiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Adriana Hung
- Division of Nephrology & Hypertension, Tennessee Valley Healthcare System, Nashville Campus and Vanderbilt University Medical Centre, Nashville, TN, USA; Division of Nephrology & Hypertension, Vanderbilt Precision Nephrology Program, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Katalin Susztak
- Renal, Electrolyte, and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
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26
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Hassler L, Reyes F, Sparks MA, Welling P, Batlle D. Evidence For and Against Direct Kidney Infection by SARS-CoV-2 in Patients with COVID-19. Clin J Am Soc Nephrol 2021; 16:1755-1765. [PMID: 34127485 PMCID: PMC8729421 DOI: 10.2215/cjn.04560421] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19-associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19-associated kidney disease.
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Affiliation(s)
- Luise Hassler
- Division of Nephrology and Hypertension, Northwestern University, Chicago, Illinois
| | - Fabiola Reyes
- Divison of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts
| | - Matthew A. Sparks
- Division of Nephrology, Duke University School of Medicine, Durham, North Carolina
- Renal Section, Durham Veterans Affairs Health Care System, Durham, North Carolina
| | - Paul Welling
- Departments of Medicine (Nephrology) and Physiology, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Daniel Batlle
- Division of Nephrology and Hypertension, Northwestern University, Chicago, Illinois
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27
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Kapp ME, Fogo AB, Roufouse C, Najafian B, Radhakrishnan J, Mohan S, Miller SE, D’Agati VD, Silberzweig J, Barbar T, Gopalan T, Srivatana V, Mokrzycki MH, Benstein JA, Ng YH, Lentine KL, Aggarwal V, Perl J, Salenger P, Koyner JL, Josephson MA, Heung M, Velez JC, Ikizler A, Vijayan A, William P, Thajudeen B, Slepian MJ. Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology. ASAIO J 2021; 67:1087-1096. [PMID: 34191753 PMCID: PMC8478105 DOI: 10.1097/mat.0000000000001530] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.
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Affiliation(s)
- Meghan E. Kapp
- From the Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Agnes B. Fogo
- From the Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Candice Roufouse
- Department of Immunology and Inflammation, Centre for Inflammatory Diseases, Imperial College, London, UK
| | - Behzad Najafian
- Department of Laboratory Medicine & Pathology, University of Washington Medicine, Seattle, Washington
| | - Jai Radhakrishnan
- Division of Nephrology, Columbia University Medical Center, New York, New York
| | - Sumit Mohan
- Division of Nephrology, Columbia University Medical Center, New York, New York
| | - Sara E. Miller
- Department of Pathology, Duke University School of Medicine, Durham, North Carolina
| | - Vivette D. D’Agati
- Department of Pathology and Cell Biology, Columbia University, New York, New York
| | | | - Tarek Barbar
- Division of Nephrology, Weill Cornell Medical College, New York, New York
| | - Tulasi Gopalan
- Division of Nephrology, Weill Cornell Medical College, New York, New York
| | - Vesh Srivatana
- Division of Nephrology, Weill Cornell Medical College, New York, New York
| | - Michele H. Mokrzycki
- Division of Nephrology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Judith A. Benstein
- Department of Medicine, New York University Tisch Hospital, New York, New York
| | - Yue-Harn Ng
- Division of Nephrology, University of Washington, Seattle, Washington
| | - Krista L. Lentine
- Division of Nephrology (9-FDT), Center for Abdominal Transplantation, St. Louis, Missouri
| | - Vikram Aggarwal
- Division of Nephrology, Northwestern Medicine, Chicago, Illinois
| | - Jeffrey Perl
- Division of Nephrology, University of Toronto, Toronto, Ontario, Canada
| | | | - Jay L. Koyner
- Department of Nephrology, University of Chicago, Chicago, Illinois
| | | | - Michael Heung
- Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, Michigan
| | - Juan Carlos Velez
- Department of Nephrology, Ochsner Health System, New Orleans, Louisiana
| | - Alp Ikizler
- Division of Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Anitha Vijayan
- Department of Medicine – Nephrology, Washington University School of Medicine in St Louis, St. Louis, Missouri
| | - Preethi William
- Division of Cardiology, Banner University of Arizona, Tucson, Arizona
| | - Bijin Thajudeen
- Division of Nephrology, Banner University of Arizona, Tucson, Arizona
| | - Marvin J. Slepian
- Departments of Medicine and Biomedical Engineering, Sarver Heart Center, University of Arizona, Tucson, Arizona
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28
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Quante M, Brake L, Tolios A, Della Penna A, Steidle C, Gruendl M, Grishina A, Haeberle H, Guthoff M, Tullius SG, Königsrainer A, Nadalin S, Löffler MW. SARS-CoV-2 in Solid Organ Transplant Recipients: A Structured Review of 2020. Transplant Proc 2021; 53:2421-2434. [PMID: 34551880 PMCID: PMC8364801 DOI: 10.1016/j.transproceed.2021.08.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 08/04/2021] [Accepted: 08/10/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging health systems all over the world. Particularly high-risk groups show considerable mortality rates after infection. In 2020, a huge number of case reports, case series, and consecutively various systematic reviews have been published reporting on morbidity and mortality risk connected with SARS-CoV-2 in solid organ transplant (SOT) recipients. However, this vast array of publications resulted in an increasing complexity of the field, overwhelming even for the expert reader. METHODS We performed a structured literature review comprising electronic databases, transplant journals, and literature from previous systematic reviews covering the entire year 2020. From 164 included articles, we identified 3451 cases of SARS-CoV-2-infected SOT recipients. RESULTS Infections resulted in a hospitalization rate of 84% and 24% intensive care unit admissions in the included patients. Whereas 53.6% of patients were reported to have recovered, cross-sectional overall mortality reported after coronavirus disease 2019 (COVID-19) was at 21.1%. Synoptic data concerning immunosuppressive medication attested to the reduction or withdrawal of antimetabolites (81.9%) and calcineurin inhibitors (48.9%) as a frequent adjustment. In contrast, steroids were reported to be increased in 46.8% of SOT recipients. CONCLUSIONS COVID-19 in SOT recipients is associated with high morbidity and mortality worldwide. Conforming with current guidelines, modifications of immunosuppressive therapies mostly comprised a reduction or withdrawal of antimetabolites and calcineurin inhibitors, while frequently maintaining or even increasing steroids. Here, we provide an accessible overview to the topic and synoptic estimates of expectable outcomes regarding in-hospital mortality of SOT recipients with COVID-19.
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Affiliation(s)
- Markus Quante
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Linda Brake
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Alexander Tolios
- Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria; Center for Physiology and Pharmacology, Institute of Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria; Center for Medical Statistics, Informatics, and Intelligent Systems, Institute of Artificial Intelligence, Medical University of Vienna, Vienna, Austria
| | - Andrea Della Penna
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Christoph Steidle
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Magdalena Gruendl
- Department of Epidemiology, Technical University Munich, Munich, Germany
| | - Anna Grishina
- Department of Pediatrics I, University Medicine Essen, Essen, Germany
| | - Helene Haeberle
- Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany
| | - Martina Guthoff
- Department of Diabetology, Endocrinology, Nephrology, Section of Nephrology and Hypertension, University Hospital Tübingen, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
| | - Stefan G Tullius
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alfred Königsrainer
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies," University of Tübingen, Tübingen, Germany
| | - Silvio Nadalin
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany
| | - Markus W Löffler
- Department of General, Visceral, and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies," University of Tübingen, Tübingen, Germany; Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Tübingen, Germany; Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany.
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29
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Basic-Jukic N, Coric M, Bulimbasic S, Dika Z, Juric I, Furic-Cunko V, Katalinic L, Kos J, Fistrek M, Kastelan Z, Jelakovic B. Histopathologic findings on indication renal allograft biopsies after recovery from acute COVID-19. Clin Transplant 2021; 35:e14486. [PMID: 34532893 PMCID: PMC8646844 DOI: 10.1111/ctr.14486] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/10/2021] [Accepted: 09/13/2021] [Indexed: 12/30/2022]
Abstract
Current knowledge on histopathological changes occurring after COVID‐19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID‐19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID‐19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID‐19, and all were diagnosed with imaging‐confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip‐lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody‐mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis‐dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS‐CoV‐2–infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.
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Affiliation(s)
- Nikolina Basic-Jukic
- Department of Nephrology, Arterial Hypertension and Dialysis, Klinički bolnički centar Zagreb, Zagreb, Croatia.,School of medicine, Sveučilište u Zagrebu Medicinski fakultet, Zagreb, Croatia
| | - Marijana Coric
- Department of pathology, Klinički bolnički centar Zagreb, Zagreb, Croatia
| | - Stela Bulimbasic
- Department of pathology, Klinički bolnički centar Zagreb, Zagreb, Croatia
| | - Zivka Dika
- Department of Nephrology, Arterial Hypertension and Dialysis, Klinički bolnički centar Zagreb, Zagreb, Croatia
| | - Ivana Juric
- Department of Nephrology, Arterial Hypertension and Dialysis, Klinički bolnički centar Zagreb, Zagreb, Croatia
| | - Vesna Furic-Cunko
- Department of Nephrology, Arterial Hypertension and Dialysis, Klinički bolnički centar Zagreb, Zagreb, Croatia
| | - Lea Katalinic
- Department of Nephrology, Arterial Hypertension and Dialysis, Klinički bolnički centar Zagreb, Zagreb, Croatia
| | - Jelena Kos
- Department of Nephrology, Arterial Hypertension and Dialysis, Klinički bolnički centar Zagreb, Zagreb, Croatia
| | - Margareta Fistrek
- Department of Nephrology, Arterial Hypertension and Dialysis, Klinički bolnički centar Zagreb, Zagreb, Croatia
| | - Zeljko Kastelan
- Department of Urology, University Hospital center Zagreb, Zagreb, Croatia
| | - Bojan Jelakovic
- Department of Nephrology, Arterial Hypertension and Dialysis, Klinički bolnički centar Zagreb, Zagreb, Croatia.,School of medicine, Sveučilište u Zagrebu Medicinski fakultet, Zagreb, Croatia
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30
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May RM, Cassol C, Hannoudi A, Larsen CP, Lerma E, Haun RS, Braga JR, Hassen SI, Wilson J, VanBeek C, Vankalakunti M, Barnum L, Walker PD, Bourne TD, Messias NC, Ambruzs JM, Boils CL, Sharma SS, Cossey LN, Baxi PV, Palmer M, Zuckerman J, Walavalkar V, Urisman A, Gallan A, Al-Rabadi LF, Rodby R, Luyckx V, Espino G, Santhana-Krishnan S, Alper B, Lam SG, Hannoudi GN, Matthew D, Belz M, Singer G, Kunaparaju S, Price D, Sauabh C, Rondla C, Abdalla MA, Britton ML, Paul S, Ranjit U, Bichu P, Williamson SR, Sharma Y, Gaspert A, Grosse P, Meyer I, Vasudev B, El Kassem M, Velez JCQ, Caza TN. A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19). Kidney Int 2021; 100:1303-1315. [PMID: 34352311 PMCID: PMC8328528 DOI: 10.1016/j.kint.2021.07.015] [Citation(s) in RCA: 98] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 07/14/2021] [Accepted: 07/23/2021] [Indexed: 12/12/2022]
Abstract
Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19) resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%) which associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19, demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.
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Affiliation(s)
- Rebecca M May
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Clarissa Cassol
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Andrew Hannoudi
- University of Michigan, 500 S State Street, Ann Arbor, MI USA 48109
| | - Christopher P Larsen
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Edgar Lerma
- University of Illinois at Chicago College of Medicine / Advocate Christ Medical Center, Department of Internal Medicine, 1853 W Polk St, Oak Lawn IL USA 60612
| | - Randy S Haun
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Juarez R Braga
- University of Arkansas for Medical Sciences, Nephrology Division, 4301 W Markham St, Little Rock, AR USA 72205
| | - Samar I Hassen
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Jon Wilson
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Christine VanBeek
- AmeriPath Laboratories, Pathology, 225 N.E. 97(th) St #600, Oklahoma City OK USA 73114
| | - Mahesha Vankalakunti
- Manipal Hospital - Bangalore, Department of Pathology, 98 HAL Old Airport Rd, Bangalore, Karnataka India 560017
| | - Lilli Barnum
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Patrick D Walker
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - T David Bourne
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Nidia C Messias
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Josephine M Ambruzs
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Christie L Boils
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Shree S Sharma
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - L Nicholas Cossey
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211
| | - Pravir V Baxi
- Rush University Medical Center, Nephrology Division, 1620 W. Harrison St, Chicago IL USA 60612
| | - Matthew Palmer
- University of Pennsylvania Perelman School of Medicine, Department of Pathology, 3400 Civic Center Blvd, Philadelphia PA USA 19104
| | - Jonathan Zuckerman
- University of California Los Angeles Health System, Department of Pathology and Laboratory Medicine, 140833 Le Conte Ave, Los Angeles, CA USA 90095
| | - Vighnesh Walavalkar
- UCSF Medical Center, Department of Pathology, 505 Panassus Avenue, CA USA 92103
| | - Anatoly Urisman
- UCSF Medical Center, Department of Pathology, 505 Panassus Avenue, CA USA 92103
| | - Alexander Gallan
- Medical College of Wisconsin, 9200 W. Wisconsin Avenue, WDL Building L73, Milkaukee, WI USA 53226
| | - Laith F Al-Rabadi
- University of Utah School of Medicine, 50 N Medical Drive, Salt Lake City UT 84132
| | - Roger Rodby
- Rush University Medical Center, Nephrology Division, 1620 W. Harrison St, Chicago IL USA 60612
| | - Valerie Luyckx
- University of Zurich, Department of Pathology and Molecular Biology, University Hospital Zurich, Schmelzberstrasse 8091, Zurich, Switzerland; Brigham and Women's Hospital, Renal Division, 75 Francis Street, Boston, MA USA 02115
| | - Gusavo Espino
- Albuquerque Nephrology Associates, 4333 Pan American Fwy NE, Albuquerque, NM USA 87107
| | | | - Brent Alper
- Tulane University School of Medicine, Tulane University Hypertension and Renal Center of Excellence, 6823 St. Charles Avenue, New Orleans, LA USA 70118; Tulane School of Medicine, 1430 Tulane Ave, New Orleans, LA USA 70112
| | - Son G Lam
- Nephrology and Hypertension Associated LTD, 1790 Barron Street, Oxford, MS USA 38655
| | - Ghadeer N Hannoudi
- Michigan Kidney Consultants, 44200 Woodward Ave, Suite 209, Pontiac, MI USA 48341
| | - Dwight Matthew
- Shoals Kidney & Hypertension Center, 422 East Dr Hicks Boulevard, Suite A, Florence, AL USA 35630
| | - Mark Belz
- Iowa Kidney Physicians PC, 1215 Pleasant Street, Suite 100, Des Moines, IA USA 50309
| | - Gary Singer
- Midwest Nephrology Associates, 70 Jungermann Circle, Suite 405, St. Peters, MO USA 63376
| | - Srikanth Kunaparaju
- Richmond Nephrology Associates, 7001 West Broad Street, Suite A, Richmond, VA USA 23294
| | - Deborah Price
- Nephrology Associates of NE Florida, 2 Shircliff Way DePaul Bldg Suite 700, Jacksonville, FL USA 32204
| | - Chawla Sauabh
- Northwest Indiana Nephrology, 6061 Broadway, Merrillville, IN USA 46410
| | - Chetana Rondla
- Georgia Nephrology, 595 Hurricane Shoals Road NW, Suite 100, Lawrenceville, GA USA 30046
| | - Mazen A Abdalla
- The Kidney Clinic, 2386 Clower Street, Suite C105, Snellville, GA USA 30078
| | - Marcus L Britton
- Nephrology & Hypertension Associates LTD, 1542 Medical Park Circle, Tupelo, MS USA 38801
| | - Subir Paul
- Shoals Kidney & Hypertension Center, 422 East Dr Hicks Boulevard, Suite A, Florence, AL USA 35630
| | - Uday Ranjit
- Nephrology Associates of Central Florida, 2501 N Orange Avenue #53, Orlando, FL USA 32804
| | - Prasad Bichu
- Nephrology Associates of Tidewater Ltd., Norfolk, VA USA 23510
| | | | - Yuvraj Sharma
- Henry Ford Hospital, 2799 W Grand Blvd, Detroit, MI USA 48202
| | - Ariana Gaspert
- Kantonal Hospital of Graubunden, Loestrasse 170, CH-7000, Chur, Switzerland
| | - Phillipp Grosse
- University of Zurich, Department of Pathology and Molecular Biology, University Hospital Zurich, Schmelzberstrasse 8091, Zurich, Switzerland
| | - Ian Meyer
- Mt Auburn Nephrology, 8260 Pine Road, Cincinnati OH USA 45236
| | - Brahm Vasudev
- Medical College of Wisconsin, 9200 W. Wisconsin Avenue, WDL Building L73, Milkaukee, WI USA 53226
| | - Mohamad El Kassem
- Mohamad El Kassem MD (private practice), Nephrology, Coral Springs, FL USA
| | - Juan Carlos Q Velez
- Ochsner Health System, Deparment of Nephrology, 1514 Jefferson Hwy, New Orleans LA USA 70121; Ochsner Clinical School, The University of Queensland (Australia), Department of Nephrology, St. Lucia, QLD, AUS
| | - Tiffany N Caza
- Arkana Laboratories, 10810 Executive Center Drive #100, Little Rock AR USA 72211.
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31
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Shimmel A, Shaikhouni S, Mariani L. Current Understanding of Clinical Manifestations of COVID-19 in Glomerular Disease. GLOMERULAR DISEASES 2021; 1:250-264. [PMID: 36747902 PMCID: PMC8450860 DOI: 10.1159/000518276] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 06/26/2021] [Indexed: 12/15/2022]
Abstract
Background The novel coronavirus disease (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an evolving pandemic with significant mortality. Information about the impact of infection on glomerular disease patients in particular has been lacking. Understanding the virus's effect in glomerular disease is constantly changing. This review article summarizes the data published thus far on COVID-19 and its manifestations in pre-existing and de novo glomerular disease. Summary While patients with glomerular disease may be at higher risk of severe COVID-19 due to their immunosuppressed status, some data suggest that a low amount of immunosuppression may be helpful in mitigating the systemic inflammatory response which is associated with high mortality rates in COVID-19. There have been a few case reports on COVID-19 causing glomerular disease relapse in patients. Multiple mechanisms have been proposed for kidney injury, proteinuria, and hematuria in the setting of COVID-19. More commonly, these are caused by direct tubular injury due to hemodynamic instability and hypoxic injury. However, the cytokine storm induced by COVID-19 may trigger common post-viral glomerular disease such as IgA nephropathy, anti-GBM, and ANCA vasculitis that have also been described in COVID-19 patients. Collapsing glomerulopathy, a hallmark of HIV-associated nephropathy, is being reported SARS-CoV-2 cases, particularly in patients with high-risk APOL1 alleles. Direct viral invasion of glomerular structures is hypothesized to cause a podocytopathy due to virus's affinity to ACE2, but evidence for this remains under study. Key Messages Infection with SARS-CoV-2 may cause glomerular disease in certain patients. The mechanism of de novo glomerular disease in the setting of COVID-19 is under study. The management of patients with existing glomerular disease poses unique challenges, especially with regard to immunosuppression management. Further studies are needed to inform clinician decisions about the management of these patients during the COVID-19 pandemic.
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Affiliation(s)
- Allison Shimmel
- College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio, USA
| | - Salma Shaikhouni
- Department of Nephrology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Laura Mariani
- Department of Nephrology, Michigan Medicine, Ann Arbor, Michigan, USA,*Laura Mariani,
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32
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Levenson E, Shepherd TN, Aviles D, Craver R, Ehlayel A, Love GL, Simms K, Straatmann C, Ashoor IF. De novo collapsing glomerulopathy in a pediatric kidney transplant recipient with COVID-19 infection. Pediatr Transplant 2021; 25:e14013. [PMID: 33773007 DOI: 10.1111/petr.14013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/17/2021] [Accepted: 03/09/2021] [Indexed: 12/24/2022]
Abstract
The negative impact of COVID-19 on adults with underlying chronic kidney disease, including kidney transplant recipients, has been well documented. Children have a less severe presentation and better prognosis compared to adults. However, little is known regarding the spectrum of COVID-19 infection in children and adolescents with underlying autoimmune disorders necessitating solid organ transplant and long-term immunosuppressive therapy. Case Report. An adolescent male developed end-stage kidney disease secondary to microscopic polyangiitis requiring a living-donor kidney transplant. Six years later, he developed antibody-mediated rejection of his kidney transplant. During his rejection treatment course, he contracted SARS-CoV-2 and developed new-onset nephrotic syndrome with severe acute kidney injury. Kidney transplant biopsy revealed de novo collapsing focal segmental glomerulosclerosis on a background of chronic active antibody mediated rejection. Immunostaining for SARS-CoV-2 on the biopsy specimen demonstrated positive staining of the proximal tubular epithelium consistent with intra-renal viral infection. Pulse corticosteroids, intravenous immunoglobulin, and temporary reduction of anti-metabolite therapy resulted in successful recovery with return of graft function back to pre-infection baseline. This case highlights the clinical conundrum of treating kidney transplant recipients with active rejection in the midst of the COVID-19 pandemic. Pediatric kidney transplant recipients can develop severe COVID-19-related kidney complications. Judicious immunosuppression modulation is necessary to balance infection and rejection risk.
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Affiliation(s)
- Emma Levenson
- Department of Pediatrics, LSU Health New Orleans, New Orleans, LA, USA
| | - Tara N Shepherd
- Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, USA
| | - Diego Aviles
- Division of Nephrology, Department of Pediatrics, LSU Health New Orleans, New Orleans, LA, USA
| | - Randall Craver
- Department of Pathology, LSU Health Science Center, New Orleans, LA, USA
| | - Abdulla Ehlayel
- Division of Nephrology, Department of Pediatrics, Children's Hospital, New Orleans, LA, USA
| | - Gordon L Love
- Department of Pathology, LSU Health Science Center, New Orleans, LA, USA
| | - K'Joy Simms
- Division of Nephrology, Department of Pediatrics, Children's Hospital, New Orleans, LA, USA
| | - Caroline Straatmann
- Division of Nephrology, Department of Pediatrics, LSU Health New Orleans, New Orleans, LA, USA
| | - Isa F Ashoor
- Division of Nephrology, Department of Pediatrics, LSU Health New Orleans, New Orleans, LA, USA
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33
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Hirsch JS, Ikizler TA, Sharma S, Mohammed A. Acute Kidney Injury and Advanced Kidney Disease in the COVID-19 Pandemic: Proceedings From a National Kidney Foundation Symposium. Kidney Med 2021; 3:426-432. [PMID: 33898966 PMCID: PMC8052503 DOI: 10.1016/j.xkme.2021.03.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented and historic public health crisis that continues to expand and evolve. The National Kidney Foundation held a 2-part continuing medical education live virtual symposium on July 16 and July 24, 2020, to address the multiple challenges of COVID-19 in the context of advanced chronic kidney disease. Faculty addressed the pathophysiology, impact, risks, and management of COVID-19 as it relates to advanced kidney disease. Testing, risk mitigation, and inpatient and outpatient management were also addressed. This concise review addresses major findings of the symposium along with certain updates regarding vaccinations since then. These findings include: (1) severe COVID-19 infection has been associated with acute kidney injury, (2) it is essential to prevent and actively manage acute kidney injury to decrease mortality in these critically ill patients, (3) management of patients with advanced kidney disease should be geared toward minimizing their risk for exposure while making sure they are receiving adequate treatments, and (4) patients with kidney disease, especially ones in advanced stages, should be prioritized for vaccination.
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Affiliation(s)
- Jamie S. Hirsch
- Division of Kidney Diseases and Hypertension, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY
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34
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de Oliveira P, Cunha K, Neves P, Muniz M, Gatto G, Salgado Filho N, Guedes F, Silva G. Renal Morphology in Coronavirus Disease: A Literature Review. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:258. [PMID: 33799854 PMCID: PMC7998438 DOI: 10.3390/medicina57030258] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/05/2021] [Accepted: 03/07/2021] [Indexed: 12/28/2022]
Abstract
Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and a variety of lesions are seen in the kidney tissue of coronavirus disease patients. This review is based on the morphological findings of patients described in case reports and a series of published cases. A search was conducted on MEDLINE and PubMed of case reports and case series of lesions in the presence of non-critical infection by SARS-CoV-2 published until 15/09/2020. We highlight the potential of the virus directly influencing the damage or the innate and adaptive immune response activating cytokine and procoagulant cascades, in addition to the genetic component triggering glomerular diseases, mainly collapsing focal segmental glomerulosclerosis, tubulointerstitial, and even vascular diseases. Kidney lesions caused by SARS-CoV-2 are frequent and have an impact on morbidity and mortality; thus, studies are needed to assess the morphological kidney changes and their mechanisms and may help define their spectrum and immediate or long-term impact.
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Affiliation(s)
- Patrick de Oliveira
- Nephrology Service, Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, Natal 59066-230, RN, Brazil; (P.d.O.); (F.G.)
| | - Kaile Cunha
- University Hospital of Federal University of Maranhão, São Luis 65020-070, MA, Brazil; (K.C.); (M.M.); (N.S.F.)
| | - Precil Neves
- Nephrology Division, University of São Paulo Medical School, São Paulo 05403-000, SP, Brazil;
| | - Monique Muniz
- University Hospital of Federal University of Maranhão, São Luis 65020-070, MA, Brazil; (K.C.); (M.M.); (N.S.F.)
| | - Giuseppe Gatto
- Nephrology Service, University Hospital of Brasília, Brasília 70840-901, DF, Brazil;
| | - Natalino Salgado Filho
- University Hospital of Federal University of Maranhão, São Luis 65020-070, MA, Brazil; (K.C.); (M.M.); (N.S.F.)
| | - Felipe Guedes
- Nephrology Service, Onofre Lopes University Hospital, Federal University of Rio Grande do Norte, Natal 59066-230, RN, Brazil; (P.d.O.); (F.G.)
| | - Gyl Silva
- Patology Department, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil
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35
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Sharma P, Ng JH, Bijol V, Jhaveri KD, Wanchoo R. Pathology of COVID-19-associated acute kidney injury. Clin Kidney J 2021; 14:i30-i39. [PMID: 33796284 PMCID: PMC7929005 DOI: 10.1093/ckj/sfab003] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/08/2021] [Indexed: 01/08/2023] Open
Abstract
Acute kidney injury (AKI) is common among hospitalized patients with coronavirus disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. An improved knowledge of the pathology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who develop AKI during COVID-19. In this review, we summarize the published cases and case series of various kidney pathologies seen with COVID-19. Both live kidney biopsies and autopsy series suggest acute tubular injury as the most commonly encountered pathology. Collapsing glomerulopathy and thrombotic microangiopathy are other encountered pathologies noted in both live and autopsy tissues. Other rare findings such as anti-neutrophil cytoplasmic antibody vasculitis, anti-glomerular basement membrane disease and podocytopathies have been reported. Although direct viral infection of the kidney is possible, it is certainly not a common or even widespread finding reported at the time of this writing (November 2020).
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Affiliation(s)
- Purva Sharma
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
- Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
| | - Jia H Ng
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
| | - Vanesa Bijol
- Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
- Department of Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
| | - Kenar D Jhaveri
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
- Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
| | - Rimda Wanchoo
- Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
- Glomerular Center at Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, USA
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36
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Toapanta N, Torres IB, Sellarés J, Chamoun B, Serón D, Moreso F. Kidney transplantation and COVID-19 renal and patient prognosis. Clin Kidney J 2021; 14:i21-i29. [PMID: 33815780 PMCID: PMC7995521 DOI: 10.1093/ckj/sfab030] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 01/27/2021] [Indexed: 02/07/2023] Open
Abstract
Coronavirus disease 2019 (COVD-19) emerged as a pandemic in December 2019. Infection has spread quickly and renal transplant recipients receiving chronic immunosuppression have been considered a population at high risk of infection, complications and infection-related death. During this year a large amount of information from nationwide registries, multicentre and single-centre studies have been reported. The number of renal transplant patients diagnosed with COVID-19 was higher than in the general population, but the lower threshold for testing may have contributed to its better identification. Major complications such as acute kidney injury and acute respiratory distress syndrome were very frequent in renal transplant patients, with a high comorbidity burden, but further studies are needed to support that organ transplant recipients receiving chronic immunosuppression are more prone to develop these complications than the general population. Kidney transplant recipients experience a high mortality rate compared with the general population, especially during the very early post-transplant period. Despite the fact that some studies report more favourable outcomes in patients with a kidney transplant than in patients on the kidney waiting list, the higher mortality described in the very early post-transplant period would advise against performing a kidney transplant in areas where the spread of infection is high, especially in recipients >60 years of age. Management of transplant recipients has been challenging for clinicians and strategies such as less use of lymphocyte-depleting agents for new transplants or anti-metabolite withdrawal and calcineurin inhibitor reduction for transplant patients with COVID-19 are not based on high-quality evidence.
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Affiliation(s)
- Néstor Toapanta
- Department of Nephrology, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
| | - Irina B Torres
- Department of Nephrology, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
| | - Joana Sellarés
- Department of Nephrology, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
| | - Betty Chamoun
- Department of Nephrology, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
| | - Daniel Serón
- Department of Nephrology, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
| | - Francesc Moreso
- Department of Nephrology, Hospital Universitari Vall d’Hebron, Barcelona, Spain
- Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain
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37
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Laboux T, Gibier JB, Pottier N, Glowacki F, Hamroun A. COVID-19-related collapsing glomerulopathy revealing a rare risk variant of APOL1: lessons for the clinical nephrologist. J Nephrol 2021; 34:373-378. [PMID: 33548053 PMCID: PMC7865108 DOI: 10.1007/s40620-020-00935-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 11/20/2020] [Indexed: 12/14/2022]
Affiliation(s)
- Timothée Laboux
- Kidney Transplantation and Dialysis Department, University of Lille, CHU Lille, 59037, Lille, France.
- RID-AGE, INSERM U1167, 59000, Lille, France.
| | - Jean-Baptiste Gibier
- Department of Pathology, Pathology Institute, Lille University, Regional and University Hospital Center of Lille, Lille, France
- INSERM UMR-S1172 Lille, JPARC-Jean-Pierre Aubert Research Center, Team Mucins, Epithelial Differentiation and Carcinogenesis, 59037, Lille, France
| | - Nicolas Pottier
- Toxicology and Genopathy Department, CHU Lille, 59000, Lille, France
- INSERM U1190, Translational Research for Diabetes, Lille, France
| | - François Glowacki
- Kidney Transplantation and Dialysis Department, University of Lille, CHU Lille, 59037, Lille, France
- CNRS, INSERM, Lille University, UMR9020- UMR-S 1277, F-59000, Lille, France
| | - Aghilès Hamroun
- Kidney Transplantation and Dialysis Department, University of Lille, CHU Lille, 59037, Lille, France
- Clinical Epidemiology Team, Center for Research in Epidemiology and Population Health, INSERM, Paris-Saclay University, Versailles Saint-Quentin University, CESP, 94807, Villejuif, France
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38
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Shabaka A, Rovirosa-Bigot S, Guerrero Márquez C, Alonso Riaño M, Fernández-Juárez G. Acute kidney injury and nephrotic syndrome secondary to COVID-19-associated focal segmental glomerulosclerosis. Nefrologia 2021; 42:S0211-6995(21)00007-2. [PMID: 33610371 DOI: 10.1016/j.nefro.2020.10.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Accepted: 10/29/2020] [Indexed: 12/28/2022] Open
Affiliation(s)
- Amir Shabaka
- Servicio de Nefrología. Hospital Universitario Fundación Alcorcón, Madrid, España.
| | - Sofía Rovirosa-Bigot
- Servicio de Medicina Intensiva. Hospital Universitario Fundación Alcorcón, Madrid, España
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39
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Convalescent plasma therapy for B-cell-depleted patients with protracted COVID-19. Blood 2020; 136:2290-2295. [PMID: 32959052 PMCID: PMC7702482 DOI: 10.1182/blood.2020008423] [Citation(s) in RCA: 242] [Impact Index Per Article: 48.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 08/25/2020] [Indexed: 02/07/2023] Open
Abstract
Anti-CD20 monoclonal antibodies are widely used for the treatment of hematological malignancies or autoimmune disease but may be responsible for a secondary humoral deficiency. In the context of COVID-19 infection, this may prevent the elicitation of a specific SARS-CoV-2 antibody response. We report a series of 17 consecutive patients with profound B-cell lymphopenia and prolonged COVID-19 symptoms, negative immunoglobulin G (IgG)-IgM SARS-CoV-2 serology, and positive RNAemia measured by digital polymerase chain reaction who were treated with 4 units of COVID-19 convalescent plasma. Within 48 hours of transfusion, all but 1 patient experienced an improvement of clinical symptoms. The inflammatory syndrome abated within a week. Only 1 patient who needed mechanical ventilation for severe COVID-19 disease died of bacterial pneumonia. SARS-CoV-2 RNAemia decreased to below the sensitivity threshold in all 9 evaluated patients. In 3 patients, virus-specific T-cell responses were analyzed using T-cell enzyme-linked immunospot assay before convalescent plasma transfusion. All showed a maintained SARS-CoV-2 T-cell response and poor cross-response to other coronaviruses. No adverse event was reported. Convalescent plasma with anti–SARS-CoV-2 antibodies appears to be a very promising approach in the context of protracted COVID-19 symptoms in patients unable to mount a specific humoral response to SARS-CoV-2.
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Yamada M, Rastogi P, Ince D, Thayyil A, Adela Mansilla M, Smith RJH, Kuppachi S, Thomas CP. Minimal Change Disease With Nephrotic Syndrome Associated With Coronavirus Disease 2019 After Apolipoprotein L1 Risk Variant Kidney Transplant: A Case Report. Transplant Proc 2020; 52:2693-2697. [PMID: 32972761 PMCID: PMC7440148 DOI: 10.1016/j.transproceed.2020.08.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 08/18/2020] [Indexed: 02/07/2023]
Abstract
Kidney injury is a well-known complication in people with coronavirus disease 2019 (COVID-19). In kidney transplant recipients with COVID-19, presentation with nephrotic syndrome has not been well described. We report on a 49-year-old black female kidney transplant recipient who presented 25 years after transplant with clinical features of nephrotic syndrome following a diagnosis of COVID-19. Histologic examination showed acute tubular injury with unremarkable glomeruli on light microscopy and diffuse foot process effacement of podocytes on electron microscopy, consistent with minimal change-like podocyte injury. Apolipoprotein L1 (APOL1) genetic testing confirmed 2 high-risk APOL1 alleles in the kidney donor. We speculate that COVID-19-induced systemic or local cytokine release could serve as a second hit in the presence of APOL1 risk alleles and mediate a podocytopathy manifesting as nephrotic syndrome. The presented case with minimal change-like disease, occurring in the context of the donor high-risk APOL1 genotype, extends the spectrum of clinical manifestations in COVID-19-associated nephropathy.
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Affiliation(s)
- Masaaki Yamada
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa; VA Medical Center, Iowa City, Iowa
| | - Prerna Rastogi
- Department of Pathology, University of Iowa, Iowa City, Iowa
| | - Dilek Ince
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa
| | - Abdullah Thayyil
- Department of Pathology, East Carolina University, Greenville, North Carolina; Department of Pathology, Vidant Medical Center, Greenville, North Carolina
| | - M Adela Mansilla
- Iowa Institute of Human Genetics, University of Iowa, Iowa City, Iowa
| | - Richard J H Smith
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa; Iowa Institute of Human Genetics, University of Iowa, Iowa City, Iowa
| | - Sarat Kuppachi
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa.
| | - Christie P Thomas
- Department of Internal Medicine, University of Iowa, Iowa City, Iowa; VA Medical Center, Iowa City, Iowa
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