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1.
Clin Respir J ; 16(6): 441-449, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1853689

ABSTRACT

INTRODUCTION: Renal impairment is a common complication in coronavirus disease 2019 (COVID-19), although its prognostic significance remains unknown. OBJECTIVES: This study determines the impact of early renal impairment on the clinical outcome of COVID-19. METHODS: Patients diagnosed with COVID-19 and hospitalized in Xiaogan Central Hospital from 20 January to 29 February 2020 were retrospectively included and grouped into two cohorts (cohort with normal renal function and cohort with renal insufficiency) based on the renal function detected on admission. Records of clinical manifestation, laboratory findings and clinical outcome were collected and compared between these two cohorts. RESULTS: A total 543 COVID-19 patients were included. Among these patients, 70 patients developed early renal impairment, with an incidence of 12.89%. A significantly higher white blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatine (Cr), blood urine nitrogen (BUN) and brain natriuretic peptide (BNP) and a significantly lower blood platelet (PLT), lymphocyte count, prealbumin and albumin (ALB) were detected in the cohort with renal insufficiency (P < 0.05). Patients with early renal impairment were also associated with higher incidences of haematuria/proteinuria, higher incidences of mortality and prolonged hospitalization duration. The independent risk factors for in-hospital death included age >65 years old, complication of diabetes, renal impairment on admission (Cr > 73 µmol/L and eGFR < 60 ml/min 1.73 m2 ), WBC > 9.5 × 109 /L and ALB < 35 g/L. CONCLUSION: Early renal impairment is associated with higher risk of in-hospital death for patients with COVID-19. Risk stratification according to renal function can better guide the clinical management of COVID-19.


Subject(s)
COVID-19 , Renal Insufficiency , Aged , COVID-19/complications , COVID-19/epidemiology , Hospital Mortality , Humans , Renal Insufficiency/epidemiology , Retrospective Studies , SARS-CoV-2
3.
Kidney360 ; 3(2): 269-278, 2022 02 24.
Article in English | MEDLINE | ID: covidwho-1776878

ABSTRACT

Background: Remdesivir is not currently approved for patients with eGFR <30 ml/min per 1.73 m2. We aimed to determine the safety of remdesivir in patients with kidney failure. Methods: This study was a retrospective cohort study of patients with COVID-19 hospitalized between May 2020 and January 2021 with eGFR <30 ml/min per 1.73 m2 who received remdesivir and historical controls with COVID-19 hospitalized between March 1, 2020 and April 30, 2020 prior to the emergency use authorization of remdesivir within a large health care system. Patients were 1:1 matched by propensity scores accounting for factors associated with treatment assignment. Adverse events and hospital outcomes were recorded by manual chart review. Results: The overall cohort included 34 hospitalized patients who initiated remdesivir within 72 hours of hospital admission with eGFR<30 ml/min per 1.73 m2 and 217 COVID-19 controls with eGFR <30 ml/min per 1.73 m2. The propensity score-matched cohort included 31 remdesivir-treated patients and 31 nonremdesivir-treated controls. The mean age was 74.0 (SD=13.8) years, 57% were women, and 68% were white participants. A total of 26% had ESKD. Among patients who were not on dialysis prior to initiating remdesivir, one developed worsening kidney function (defined as ≥50% increase in creatinine or initiation of KRT) compared with three in the historical control group. There was no increased risk of cardiac arrythmia, cardiac arrest, altered mental status, or clinically significant anemia or liver function test abnormalities. There was a significantly increased risk of hyperglycemia, which may be partly explained by the increased use of dexamethasone in the remdesivir-treated population. Conclusions: In this propensity score-matched study, remdesivir was well tolerated in patients with eGFR <30 ml/min per 1.73 m2.


Subject(s)
COVID-19 , Renal Insufficiency , Adenosine Monophosphate/analogs & derivatives , Aged , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , COVID-19/drug therapy , Female , Humans , Kidney , Propensity Score , Renal Dialysis , Renal Insufficiency/drug therapy , Retrospective Studies , SARS-CoV-2
4.
J Am Soc Nephrol ; 33(4): 677-686, 2022 04.
Article in English | MEDLINE | ID: covidwho-1775517

ABSTRACT

BACKGROUND: Patients with kidney failure requiring KRT are at high risk of complications and death following SARS-CoV-2 infection, with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on the incidence of infection, hospitalization, and death from COVID-19 infection. METHODS: The study design was an observational data linkage cohort study. Multiple health care datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses, and vaccine effectiveness were calculated. RESULTS: As of September 19, 2021, 93% (n=5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness rates against infection and hospitalization were 33% (95% CI, 0 to 52) and 38% (95% CI, 0 to 57), respectively. Within 28 days of a SARS-CoV-2-positive PCR test, 9.2% of fully vaccinated individuals died (7% patients on dialysis and 10% kidney transplant recipients). This compares to <0.1% of the vaccinated general Scottish population admitted to the hospital or dying due to COVID-19 during that period. CONCLUSIONS: These data demonstrate that a primary vaccine course of two doses has limited effect on COVID-19 infection and its complications in patients with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required.


Subject(s)
COVID-19 , Renal Insufficiency , COVID-19/complications , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Testing , COVID-19 Vaccines/adverse effects , Cohort Studies , Humans , Incidence , SARS-CoV-2 , Scotland , Vaccination
5.
Nephrology (Carlton) ; 27(7): 551-565, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1707933

ABSTRACT

Dialysis withdrawal has become an accepted treatment option for patients with kidney failure and is one of the leading causes of death in patients receiving dialysis in high-income countries. Despite its increasing acceptance, dialysis withdrawal currently lacks a clear, consistent definition. The processes and outcomes of dialysis withdrawal have wide temporal and geographical variability, attributed to dialysis patient selection, influence from cultural, religious and spiritual beliefs, and availability of kidney replacement therapy and conservative kidney management. As a complex, evolving process, dialysis withdrawal poses an enormous challenge for clinicians and healthcare teams with various limitations precluding a peaceful and smooth transition between active dialysis and end-of-life care. In this review, we examine the current definitions of dialysis withdrawal, the temporal and geographical patterns of dialysis withdrawal, international barriers in the decision-making process (including dialysis withdrawal during the COVID-19 pandemic), and gaps in the current dialysis withdrawal recommendations for clinical consideration and future studies.


Subject(s)
COVID-19 , Kidney Failure, Chronic , Renal Insufficiency , Decision Making , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Pandemics , Renal Dialysis/adverse effects
6.
J Am Soc Nephrol ; 32(11): 2735-2742, 2021 11.
Article in English | MEDLINE | ID: covidwho-1690626

ABSTRACT

BACKGROUND: Patients receiving maintenance dialysis represent a high-risk, immune-compromised population with 15%-25% COVID-19 mortality rate who were unrepresented in clinical trials of mRNA vaccines. METHODS: All patients receiving maintenance dialysis who received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021, were included. Response was on the basis of levels of Ig-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike-antigen (seropositive ≥2 U/L) using an FDA-approved semiquantitative chemiluminescent assay (ADVIA Centaur XP/XPT COV2G). RESULTS: Among 186 patients on dialysis from 30 clinics in eight states tested 23±8 days after receiving two vaccine doses, there were 165 (88.7%) responders with 70% at maximum titer. There was no significant difference between BNT162b2/Pfizer (148 out of 168, 88.1%) and mRNA-1273/Moderna (17 out of 18, 94.4%), P=0.42. All 38 patients with COVID-19 history were responders, with 97% at maximum titer. Among patients without COVID-19, 127 out of 148 (85.8%) were responders, comparable between BNT162b2/Pfizer (113 out of 133) and mRNA-1273/Moderna (14 out of 15) vaccines (85.0% versus 93.3%, P=0.38). CONCLUSIONS: Most patients receiving maintenance dialysis responded after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine, suggesting the short-term development of antispike antibody is good, giving hope that most of these patients who are vulnerable, once immunized, will be protected from COVID-19. Longer-term evaluation is needed to determine antibody titer durability and if booster dose(s) are warranted. Further research to evaluate the approach to patients without a serologic response is needed, including benefits of additional dose(s) or administration of alternate options.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Immunogenicity, Vaccine , Renal Dialysis , Renal Insufficiency/immunology , Aged , Antibodies, Viral/blood , Female , Humans , Male , Middle Aged , Renal Insufficiency/blood , Renal Insufficiency/therapy , SARS-CoV-2/immunology
9.
J Clin Pharmacol ; 62(6): 777-782, 2022 06.
Article in English | MEDLINE | ID: covidwho-1589060

ABSTRACT

Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) drugs may modify risk associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we assessed whether baseline therapy with ACEIs or ARBs was associated with lower mortality, respiratory failure (noninvasive ventilation or intubation), and renal failure (new renal replacement therapy) in SARS-CoV-2-positive patients. This retrospective registry-based observational cohort study used data from a national database of emergency department patients tested for SARS-CoV-2. Symptomatic emergency department patients were accrued from January to October 2020, across 197 hospitals in the United States. Multivariable analysis using logistic regression evaluated end points among SARS-CoV-2-positive cases, focusing on ACEIs/ARBs and adjusting for covariates. Model performance was evaluated using the c statistic for discrimination and Cox plotting for calibration. A total of 13 859 (99.9%) patients had known mortality status, of whom 2045 (14.8%) died. Respiratory failure occurred in 2485/13 880 (17.9%) and renal failure in 548/13 813 (4.0%) patients with available data. ACEI/ARB status was associated with a 25% decrease in mortality odds (odds ratio [OR], 0.75; 95%CI, 0.59-0.94; P = .011; c = .82). ACEIs/ARBs were not significantly associated with respiratory failure (OR, 0.89; 95%CI, 0.78-1.06; P = .206) or renal failure (OR, 0.75; 95%CI, 0.55-1.04; P = .083). Adjusting for covariates, baseline ACEI/ARB was associated with 25% lower mortality in SARS-CoV-2-positive patients. The potential mechanism for ACEI/ARB mortality modification requires further exploration.


Subject(s)
COVID-19 , Renal Insufficiency , Respiratory Insufficiency , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Female , Humans , Male , Renal Insufficiency/drug therapy , Respiratory Insufficiency/drug therapy , Retrospective Studies , SARS-CoV-2
10.
Clin Microbiol Infect ; 28(6): 792-800, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1558736

ABSTRACT

OBJECTIVES: Viral reactivation is frequently detected in critically ill patients undergoing mechanical ventilation and is associated with worse outcomes. However, the efficacy and safety of antiviral therapy in these patients remain unknown. This review aims to assess the effects of antiviral therapy on mortality, viral reactivation, and adverse events in critically ill patients undergoing mechanical ventilation. METHODS: Data sources were Medline, Embase, the Cochrane Library, and reference lists. The study included randomized controlled trials that compared antiviral therapy with placebo, standard care, or no treatment. Participants were critically ill patients undergoing mechanical ventilation. Intervention was antiviral therapy. Assessment of risk of bias used the Cochrane risk of bias tool. For methods of data synthesis, risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model for meta-analysis with trial sequential analysis. RESULTS: Nine trials with a broad spectrum of critically ill patients were included. No association was found between antiviral therapy and all-cause mortality at the longest follow-up (nine trials, 1790 patients, RR 0.93, 95%CI 0.79-1.11, I2 3%). Trial sequential analysis showed that the cumulative Z curve crossed the futility boundary establishing sufficient evidence. No association was also found between antiviral therapy and 28-day mortality, in-hospital mortality, 60-day mortality, or 90-day mortality. However, antiviral therapy was associated with a reduction in viral reactivation (five trials, 644 patients, RR 0.23, 95%CI 0.14-0.37, I2 0%). Trial sequential analysis showed that the cumulative Z curve crossed the trial sequential monitoring boundary for benefit establishing sufficient evidence. Antiviral therapy was not associated with an increased risk of renal insufficiency (eight trials, 1574 patients, RR 0.88, 95%CI 0.73-1.05, I2 0%). CONCLUSIONS: No association between antiviral therapy and mortality was found, but antiviral therapy reduced viral reactivation without increasing the risk of renal insufficiency in critically ill patients with mechanical ventilation.


Subject(s)
Critical Illness , Renal Insufficiency , Antiviral Agents/adverse effects , Critical Illness/therapy , Humans , Randomized Controlled Trials as Topic , Renal Insufficiency/etiology , Respiration, Artificial/adverse effects
12.
J Am Soc Nephrol ; 32(11): 2958-2969, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1526711

ABSTRACT

BACKGROUND: The long-term outcome of COVID-19-associated collapsing glomerulopathy is unknown. METHODS: We retrospectively identified 76 native kidney biopsies from patients with history of COVID-19 between March 2020 and April 2021. Presenting and outcome data were obtained for all 23 patients with collapsing glomerulopathy and for seven patients with noncollapsing podocytopathies. We performed APOL1 genotyping by Sanger sequencing, immunostaining for spike and nucleocapsid proteins, and in situ hybridization for SARS-CoV-2. RESULTS: The 23 patients with COVID-19-associated collapsing glomerulopathy were median age 57 years (range, 35-72), included 16 men, and were predominantly (91%) Black. Severity of COVID-19 was mild or moderate in most (77%) patients. All but one patient presented with AKI, 17 had nephrotic-range proteinuria, and six had nephrotic syndrome. Fourteen (61%) patients required dialysis at presentation. Among 17 patients genotyped, 16 (94%) were high-risk APOL1. Among 22 (96%) patients with median follow-up at 155 days (range, 30-412), 11 (50%) received treatment for COVID-19, and eight (36%) received glucocorticoid therapy for podocytopathy. At follow-up, 19 (86%) patients were alive, and 15 (68%) were dialysis free, including seven of 14 who initially required dialysis. The dialysis-free patients included 64% (seven of 11) of those treated for COVID-19 and 75% (six of eight) of those treated with glucocorticoids for podocytopathy. Overall, 36% achieved partial remission of proteinuria, 32% had no remission, and 32% reached combined end points of ESKD or death. Viral infection of the kidney was not detected. CONCLUSIONS: Half of 14 patients with COVID-19-associated collapsing glomerulopathy requiring dialysis achieved dialysis independence, but the long-term prognosis of residual proteinuric CKD remains guarded, indicating a need for more effective therapy.


Subject(s)
COVID-19/complications , Kidney Glomerulus/pathology , Podocytes/pathology , Renal Insufficiency/pathology , Renal Insufficiency/virology , Adult , Aged , COVID-19/pathology , COVID-19/therapy , Female , Humans , Male , Middle Aged , Recovery of Function , Renal Dialysis , Renal Insufficiency/therapy , Retrospective Studies , Treatment Outcome
13.
PLoS One ; 16(11): e0260169, 2021.
Article in English | MEDLINE | ID: covidwho-1526694

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide, and several sociodemographic variables, comorbidities and care variables have been associated with complications and mortality. OBJECTIVE: To identify the factors associated with admission to intensive care units (ICUs) and mortality in patients with COVID-19 from 4 clinics in Colombia. METHODS: This was a follow-up study of a cohort of patients diagnosed with COVID-19 between March and August 2020. Sociodemographic, clinical (Charlson comorbidity index and NEWS 2 score) and pharmacological variables were identified. Multivariate analyses were performed to identify variables associated with the risk of admission to the ICU and death (p<0.05). RESULTS: A total of 780 patients were analyzed, with a median age of 57.0 years; 61.2% were male. On admission, 54.9% were classified as severely ill, 65.3% were diagnosed with acute respiratory distress syndrome, 32.4% were admitted to the ICU, and 26.0% died. The factors associated with a greater likelihood of ICU admission were severe pneumonia (OR: 9.86; 95%CI:5.99-16.23), each 1-point increase in the NEWS 2 score (OR:1.09; 95%CI:1.002-1.19), history of ischemic heart disease (OR:3.24; 95%CI:1.16-9.00), and chronic obstructive pulmonary disease (OR:2.07; 95%CI:1.09-3.90). The risk of dying increased in those older than 65 years (OR:3.08; 95%CI:1.66-5.71), in patients with acute renal failure (OR:6.96; 95%CI:4.41-11.78), admitted to the ICU (OR:6.31; 95%CI:3.63-10.95), and for each 1-point increase in the Charlson comorbidity index (OR:1.16; 95%CI:1.002-1.35). CONCLUSIONS: Factors related to increasing the probability of requiring ICU care or dying in patients with COVID-19 were identified, facilitating the development of anticipatory intervention measures that favor comprehensive care and improve patient prognosis.


Subject(s)
COVID-19/epidemiology , Hospital Mortality/trends , Intensive Care Units/statistics & numerical data , Patient Admission/statistics & numerical data , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , Colombia , Comorbidity , Female , Humans , Male , Middle Aged , Myocardial Ischemia/epidemiology , Pulmonary Disease, Chronic Obstructive/epidemiology , Renal Insufficiency/epidemiology , Sex Factors
14.
Int J Mol Sci ; 22(21)2021 Nov 03.
Article in English | MEDLINE | ID: covidwho-1502439

ABSTRACT

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin-angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.


Subject(s)
COVID-19/pathology , Endothelial Cells/metabolism , COVID-19/complications , COVID-19/virology , Cytokine Release Syndrome/etiology , Endothelial Cells/cytology , Endothelial Cells/virology , Heart Failure/etiology , Humans , Renal Insufficiency/etiology , Renin-Angiotensin System/physiology , SARS-CoV-2/isolation & purification , Thrombosis/etiology
15.
J Am Soc Nephrol ; 32(1): 99-114, 2021 01.
Article in English | MEDLINE | ID: covidwho-1496673

ABSTRACT

BACKGROUND: C3 glomerulopathy (C3G) is characterized by the alternative-pathway (AP) hyperactivation induced by nephritic factors or complement gene mutations. Mice deficient in complement factor H (CFH) are a classic C3G model, with kidney disease that requires several months to progress to renal failure. Novel C3G models can further contribute to understanding the mechanism behind this disease and developing therapeutic approaches. METHODS: A novel, rapidly progressing, severe, murine model of C3G was developed by replacing the mouse C3 gene with the human C3 homolog using VelociGene technology. Functional, histologic, molecular, and pharmacologic assays characterize the presentation of renal disease and enable useful pharmacologic interventions in the humanized C3 (C3hu/hu) mice. RESULTS: The C3hu/hu mice exhibit increased morbidity early in life and die by about 5-6 months of age. The C3hu/hu mice display elevated biomarkers of kidney dysfunction, glomerulosclerosis, C3/C5b-9 deposition, and reduced circulating C3 compared with wild-type mice. Administration of a C5-blocking mAb improved survival rate and offered functional and histopathologic benefits. Blockade of AP activation by anti-C3b or CFB mAbs also extended survival and preserved kidney function. CONCLUSIONS: The C3hu/hu mice are a useful model for C3G because they share many pathologic features consistent with the human disease. The C3G phenotype in C3hu/hu mice may originate from a dysregulated interaction of human C3 protein with multiple mouse complement proteins, leading to unregulated C3 activation via AP. The accelerated disease course in C3hu/hu mice may further enable preclinical studies to assess and validate new therapeutics for C3G.


Subject(s)
Complement C3/genetics , Disease Models, Animal , Glomerulonephritis, Membranoproliferative/genetics , Kidney Diseases/genetics , Animals , Complement C3/metabolism , Complement Pathway, Alternative/genetics , Exons , Gene Expression Regulation , Glomerulonephritis, Membranoproliferative/metabolism , Humans , Kidney Diseases/metabolism , Liver/metabolism , Male , Mice , Mice, Knockout , Microscopy, Fluorescence , Phenotype , Polymorphism, Single Nucleotide , Renal Insufficiency/genetics , Renal Insufficiency/metabolism
17.
Ann Clin Biochem ; 59(2): 110-115, 2022 03.
Article in English | MEDLINE | ID: covidwho-1480322

ABSTRACT

BACKGROUND: Ionized hypocalcemia is common in critically ill patients with COVID-19 and is associated with adverse outcomes. We previously developed a linear model that estimates ionized calcium (ICa) by adjusting total calcium (TCa) for the three components of the anion gap and albumin. On internal validation, it outperformed the popular method that corrects TCa for albumin alone (cTCa) in diagnosing low ICa. In this study, we sought to externally validate our ICa model in hospitalized COVID-19 positive patients. METHODS: We retrospectively studied all 200 patients with COVID-19 who were admitted to the State University of New York Downstate Medical Center between March 11th and April 30th 2020 and referred to the nephrology service for renal failure, and who had ICa measured on a venous blood gas within 25 min of a comprehensive metabolic panel. We compared the performance of the ICa model and cTCa in diagnosing low ICa by ROC analysis, and also examined the accuracy of the absolute values predicted by the two methods relative to measured ICa. RESULTS: On ROC analysis, the ICa model was better than cTCa (area under ROC curve: 0.872 [0.025] vs. 0.835 [0.028]; p = 0.045). The ICa model estimated ICa accurately, but the cTCa method seemed to overcorrect TCa, as a substantial number of patients with clearly normal cTCa values had low ICa. CONCLUSIONS: In an external validation cohort, the ICa model estimated ICa accurately and was better than cTCa in the diagnosis of low ICa. This finding can be useful in guiding direct ICa testing.


Subject(s)
COVID-19 , Hypocalcemia , Renal Insufficiency , Calcium , Humans , Hypocalcemia/diagnosis , Retrospective Studies , SARS-CoV-2
18.
Int J Mol Sci ; 22(12)2021 Jun 20.
Article in English | MEDLINE | ID: covidwho-1472414

ABSTRACT

Acute kidney injury (AKI) and chronic kidney disease (CKD) are rising in global prevalence and cause significant morbidity for patients. Current treatments are limited to slowing instead of stabilising or reversing disease progression. In this review, we describe mesenchymal stem cells (MSCs) and their constituents, extracellular vesicles (EVs) as being a novel therapeutic for CKD. MSC-derived EVs (MSC-EVs) are membrane-enclosed particles, including exosomes, which carry genetic information that mimics the phenotype of their cell of origin. MSC-EVs deliver their cargo of mRNA, miRNA, cytokines, and growth factors to target cells as a form of paracrine communication. This genetically reprograms pathophysiological pathways, which are upregulated in renal failure. Since the method of exosome preparation significantly affects the quality and function of MSC-exosomes, this review compares the methodologies for isolating exosomes from MSCs and their role in tissue regeneration. More specifically, it summarises the therapeutic efficacy of MSC-EVs in 60 preclinical animal models of AKI and CKD and the cargo of biomolecules they deliver. MSC-EVs promote tubular proliferation and angiogenesis, and inhibit apoptosis, oxidative stress, inflammation, the epithelial-to-mesenchymal transition, and fibrosis, to alleviate AKI and CKD. By reprogramming these pathophysiological pathways, MSC-EVs can slow or even reverse the progression of AKI to CKD, and therefore offer potential to transform clinical practice.


Subject(s)
Biological Therapy , Extracellular Vesicles/metabolism , Extracellular Vesicles/transplantation , Kidney Diseases/therapy , Mesenchymal Stem Cells/metabolism , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/therapy , Animals , Apoptosis/drug effects , Biological Therapy/methods , Cell Differentiation , Cell Proliferation/drug effects , Cell Self Renewal , Chemical Fractionation , Disease Management , Disease Susceptibility , Exosomes/metabolism , Humans , Kidney Diseases/etiology , Kidney Diseases/pathology , Mesenchymal Stem Cells/cytology , Protective Agents , Renal Insufficiency/diagnosis , Renal Insufficiency/etiology , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/therapy
20.
JAMA Netw Open ; 4(10): e2127369, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1453500

ABSTRACT

Importance: Persons with kidney failure require treatment (ie, dialysis or transplantation) for survival. The burden of the COVID-19 pandemic and pandemic-related disruptions in care have disproportionately affected racial and ethnic minority and socially disadvantaged populations, raising the importance of understanding disparities in treatment initiation for kidney failure during the pandemic. Objective: To examine changes in the number and demographic characteristics of patients initiating treatment for incident kidney failure following the COVID-19 pandemic by race and ethnicity, county-level COVID-19 mortality rate, and neighborhood-level social disadvantage. Design, Setting, and Participants: This cross-sectional time-trend study used data from US patients who developed kidney failure between January 1, 2018, and June 30, 2020. Data were analyzed between January and July 2021. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Number of patients initiating treatment for incident kidney failure and mean estimated glomerular filtration rate (eGFR) at treatment initiation. Results: The study population included 127 149 patients with incident kidney failure between January 1, 2018, and June 30, 2020 (mean [SD] age, 62.8 [15.3] years; 53 021 [41.7%] female, 32 932 [25.9%] non-Hispanic Black, and 19 835 [15.6%] Hispanic/Latino patients). Compared with the pre-COVID-19 period, in the first 4 months of the pandemic (ie, March 1 through June 30, 2020), there were significant decreases in the proportion of patients with incident kidney failure receiving preemptive transplantation (1805 [2.1%] pre-COVID-19 vs 551 [1.4%] during COVID-19; P < .001) and initiating hemodialysis treatment with an arteriovenous fistula (2430 [15.8%] pre-COVID-19 vs 914 [13.4%] during COVID-19; P < .001). The mean (SD) eGFR at initiation declined from 9.6 (5.0) mL/min/1.73 m2 to 9.5 (4.9) mL/min/1.73 m2 during the pandemic (P < .001). In stratified analyses by race/ethnicity, these declines were exclusively observed among non-Hispanic Black patients (mean [SD] eGFR: 8.4 [4.6] mL/min/1.73 m2 pre-COVID-19 vs 8.1 [4.5] mL/min/1.73 m2 during COVID-19; P < .001). There were significant declines in eGFR at initiation for patients residing in counties in the highest quintile of COVID-19 mortality rates (9.5 [5.0] mL/min/1.73 m2 pre-COVID-19 vs 9.2 [5.0] mL/min/1.73 m2 during COVID-19; P < .001), but not for patients residing in other counties. The number of patients initiating treatment for incident kidney failure was approximately 30% lower than projected in April 2020. Conclusions and Relevance: In this cross-sectional study of US adults, the COVID-19 pandemic was associated with a substantially lower number of patients initiating treatment for incident kidney failure and treatment initiation at lower levels of kidney function during the first 4 months, particularly for Black patients and people living in counties with high COVID-19 mortality rates.


Subject(s)
COVID-19 , Health Services Accessibility/trends , Healthcare Disparities/trends , Minority Groups , Renal Insufficiency/therapy , Social Class , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Cross-Sectional Studies , Female , Health Services Accessibility/economics , Healthcare Disparities/economics , Healthcare Disparities/ethnology , Humans , Kidney Transplantation/economics , Kidney Transplantation/trends , Male , Middle Aged , Pandemics , Poisson Distribution , Renal Dialysis/economics , Renal Dialysis/trends , Renal Insufficiency/economics , Renal Insufficiency/ethnology , Residence Characteristics , United States/epidemiology , Vulnerable Populations , Young Adult
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