SARS-CoV-2-Associated Nephropathy: Direct Renal Infection and Damage

EMJ Nephrology ◽

10.33590/emjnephrol/20-00164 ◽

2020 ◽

Author(s):

Maurizio Salvadori

Keyword(s):

Kidney Injury ◽

Drug Induced ◽

Morphological Alterations ◽

Risk Alleles ◽

Haemostatic Factors ◽

Kidney Perfusion ◽

Immunohistochemical Evidence ◽

Renal Infection ◽

Cytopathic Action ◽

Apolipoprotein L1

Acute kidney injury is a frequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), principally because of hypotension and decreased kidney perfusion secondary to haemodynamic or haemostatic factors, drug-induced nephrotoxicity, and cytokine storm syndrome related to sepsis. Additionally, several factors support the existence of SARS-CoV-2-associated nephropathy, such as early, new-onset proteinuria and haematuria in many patients, the identification of SARS-CoV-2 viral load in precisely defined kidney compartments, ultrastructural and immunohistochemical evidence of direct viral infection of the kidneys, and, most importantly, morphological alterations associated with cytopathic action induced by the virus. In addition, collapsing glomerulopathy that has been reported in patients of African American descent with underlying apolipoprotein L1 (APOL1) kidney risk alleles and SARS-CoV-2 infection is evidence of a distinct form of SARS-CoV-2-associated nephropathy, the APOL1-SARS-CoV2-associated nephropathy.

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Nefropatia associata al SARS-CoV-2: cosa sappiamo finora

Giornale di Clinica Nefrologica e Dialisi ◽

10.33393/gcnd.2020.2166 ◽

2020 ◽

Vol 32 (1) ◽

pp. 102-106

Author(s):

Aris Tsalouchos ◽

Maurizio Salvadori

Keyword(s):

Kidney Injury ◽

Drug Induced ◽

Morphological Alterations ◽

Risk Alleles ◽

Collapsing Glomerulopathy ◽

Ultrastructural Evidence ◽

Hemostatic Factors ◽

Kidney Perfusion ◽

Cytopathic Action ◽

New Onset

Acute kidney injury (AKI) is a frequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attributable to i) hypotension and decreased kidney perfusion secondary to hemodynamic or hemostatic factors, ii) drug-induced nephrotoxicity, iii) cytokine storm syndrome related to sepsis. However: i) early new-onset proteinuria and hematuria in many patients, ii) the identification of SARS-CoV-2 viral load in precisely defined kidney compartments, iii) ultrastructural evidence of direct viral infection of the kidneys, and most importantly, iv) morphological alterations associated to cytopathic action induced by the virus support the existence of SARS-CoV-2 associated nephropathy. In addition, collapsing glomerulopathy reported in African American patients with underlying APOL1 kidney risk alleles and SARS-CoV-2 infection is the evidence of a distinct form of SARS-CoV-2 associated nephropathy, the APOL1-SARS-CoV2-associated nephropathy.

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Serial Quantification of Urinary Protein Biomarkers to Predict Drug-induced Acute Kidney Injury

Current Drug Metabolism ◽

10.2174/1389200220666190711114504 ◽

2019 ◽

Vol 20 (8) ◽

pp. 656-664 ◽

Cited By ~ 4

Author(s):

Yi Da ◽

K. Akalya ◽

Tanusya Murali ◽

Anantharaman Vathsala ◽

Chuen-Seng Tan ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cystatin C ◽

Calcineurin Inhibitors ◽

Kidney Injury ◽

Tubular Dysfunction ◽

Renal Tubular Dysfunction ◽

Protein Biomarkers ◽

Drug Induced ◽

Beta 2 ◽

Beta 2 Microglobulin

Background: : Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. Methods:: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. Results:: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. Conclusion: : Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.

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Acute interstitial nephritis and drug-induced systemic lupus erythematosus due to chlorthalidone and amiodarone: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x20910029 ◽

2020 ◽

Vol 8 ◽

pp. 2050313X2091002 ◽

Cited By ~ 1

Author(s):

Umut Selamet ◽

Ramy M Hanna ◽

Anthony Sisk ◽

Lama Abdelnour ◽

Lena Ghobry ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Interstitial Nephritis ◽

Lupus Erythematosus ◽

Kidney Biopsy ◽

Kidney Injury ◽

Acute Interstitial Nephritis ◽

Systemic Lupus ◽

Drug Induced ◽

Systemic Manifestations

Drug-induced lupus erythematosus has features distinct from primary systemic lupus erythematosus. It can occur with a wide variety of agents that result in the generation of anti-histone or other types of antibodies. Systemic manifestations of drug-induced systemic lupus erythematosus may include renal dysfunction due to circulating immune complexes or due to other immune reactions to the culprit medication(s). Acute interstitial nephritis occurs due to DNA–drug or protein–drug complexes that trigger an allergic immune response. We report a patient who developed acute kidney injury, rash, and drug-induced systemic lupus diagnosed by serologies after starting chlorthalidone and amiodarone. A renal biopsy showed acute interstitial nephritis and not lupus-induced glomerulonephritis. It is important to note that systemic lupus erythematosus and acute interstitial nephritis can occur together, and this report highlights the role of the kidney biopsy in ascertaining the pathological diagnosis and outlining therapy in drug-induced lupus erythematosus.

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Drug-Induced Acute Kidney Injury: A Study from the French Medical Administrative and the French National Pharmacovigilance Databases Using Capture-Recapture Method

Journal of Clinical Medicine ◽

10.3390/jcm10020168 ◽

2021 ◽

Vol 10 (2) ◽

pp. 168

Author(s):

Anne-Lise Rolland ◽

Anne-Sophie Garnier ◽

Katy Meunier ◽

Guillaume Drablier ◽

Marie Briet

Keyword(s):

Acute Kidney Injury ◽

Medical Information ◽

Significant Proportion ◽

Kidney Injury ◽

International Classification Of Diseases ◽

Administrative Databases ◽

Health Concern ◽

Medical Information System ◽

Drug Induced ◽

Capture Recapture

Background: Acute kidney injury (AKI) is a public health concern. Among the pathological situations leading to AKI, drugs are preventable factors but are still under-notified. We aimed to provide an overview of drug-induced AKI (DIAKI) using pharmacovigilance and medical administrative databases Methods: A query of the PMSI database (French Medical Information System Program) of adult inpatient hospital stays between 1 January 2017 and 31 December 2018 was performed using ICD-10 (International Classification of Diseases 10th revision) codes to identify AKI cases which were reviewed by a nephrologist and a pharmacovigilance expert to identify DIAKI cases. In parallel, DIAKIs notified in the French Pharmacovigilance Database (FPVDB) were collected. A capture-recapture method was performed to estimate the total number of DIAKIs. Results: The estimated total number of DIAKIs was 521 (95%CI 480; 563), representing 20.0% of all AKIs. The notification was at a rate of 12.9% (95%CI 10.0; 15.8). According to the KDIGO classification, 50.2% of the DIAKI cases were stage 1 and 49.8% stage 2 and 3. The mortality rate was 11.1% and 9.6% required hemodialysis. Conclusion: This study showed that drugs are involved in a significant proportion of patients developing AKI during a hospital stay and emphasizes the severity of DIAKI cases.

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Biomarkers of drug-induced acute kidney injury in the adult

Expert Opinion on Drug Metabolism & Toxicology ◽

10.1517/17425255.2015.1083011 ◽

2015 ◽

Vol 11 (11) ◽

pp. 1683-1694 ◽

Cited By ~ 18

Author(s):

Glenda C Gobe ◽

Jeff S Coombes ◽

Robert G Fassett ◽

Zoltan H Endre

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Drug Induced

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The Encapsulation of Lycopene in Nanoliposomes Enhances Its Protective Potential in Methotrexate-Induced Kidney Injury Model

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/2627917 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 12

Author(s):

Nenad Stojiljkovic ◽

Sonja Ilic ◽

Vladimir Jakovljevic ◽

Nikola Stojanovic ◽

Slavica Stojnev ◽

...

Keyword(s):

Oxidative Damage ◽

Structural Changes ◽

Corn Oil ◽

Kidney Tissue ◽

Kidney Injury ◽

Serum Urea ◽

Morphological Alterations ◽

Injury Model ◽

Serum Biochemical ◽

Degree Of Recovery

Methotrexate is an antimetabolic drug with a myriad of serious side effects including nephrotoxicity, which presumably occurs due to oxidative tissue damage. Here, we evaluated the potential protective effect of lycopene, a potent antioxidant carotenoid, given in two different pharmaceutical forms in methotrexate-induced kidney damage in rats. Serum biochemical (urea and creatinine) and tissue oxidative damage markers and histopathological kidney changes were evaluated after systemic administration of both lycopene dissolved in corn oil and lycopene encapsulated in nanoliposomes. Similar to previous studies, single dose of methotrexate induced severe functional and morphological alterations of kidneys with cell desquamation, tubular vacuolation, and focal necrosis, which were followed by serum urea and creatinine increase and disturbances of tissue antioxidant status. Application of both forms of lycopene concomitantly with methotrexate ameliorated changes in serum urea and creatinine and oxidative damage markers and markedly reversed structural changes of kidney tissue. Moreover, animals that received lycopene in nanoliposome-encapsulated form showed higher degree of recovery than those treated with free lycopene form. The findings of this study indicate that treatment with nanoliposome-encapsulated lycopene comparing to lycopene in standard vehicle has an advantage as it more efficiently reduces methotrexate-induced kidney dysfunction.

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Drug Induced Pneumonitis Secondary to Treatment with Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir (VIEKIRA PAK®) for Chronic Hepatitis C: Case Report of an Unexpected Life-Threatening Adverse Reaction

Case Reports in Medicine ◽

10.1155/2017/4895736 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 4

Author(s):

Shih Yea Sylvia Wu ◽

Bridget Faire ◽

Edward Gane

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Kidney Injury ◽

Complete Recovery ◽

Final Diagnosis ◽

Community Acquired Pneumonia ◽

Drug Induced ◽

First Case ◽

Life Threatening

VIEKIRA PAK (ritonavir-boosted paritaprevir/ombitasvir and dasabuvir) is an approved treatment for compensated patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection. This oral regimen has minimal adverse effects and is well tolerated. Cure rates are 97% in patients infected with HCV GT 1a and 99% in those with HCV GT 1b. We report the first case of life-threatening allergic pneumonitis associated with VIEKIRA PAK. This unexpected serious adverse event occurred in a 68-year-old Chinese female with genotype 1b chronic hepatitis C and Child-Pugh A cirrhosis. One week into treatment with VIEKIRA PAK without ribavirin, she was admitted to hospital with respiratory distress and acute kidney injury requiring intensive care input. She was initially diagnosed with community acquired pneumonia and improved promptly with intravenous antibiotics and supported care. No bacterial or viral pathogens were cultured. Following complete recovery, she recommenced VIEKIRA PAK but represented 5 days later with more rapidly progressive respiratory failure, requiring intubation and ventilation, inotropic support, and haemodialysis. The final diagnosis was drug induced pneumonitis.

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