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1.
Saudi J Kidney Dis Transpl ; 32(2): 504-509, 2021.
Article in English | MEDLINE | ID: covidwho-1622690

ABSTRACT

With the declaration of severe acute respiratory syndrome novel coronavirus-2019 as pandemic by the World Health Organization on March 11, 2020, there has been a steady rise in number of cases. Chronic kidney disease and dialysis population are risk factors for increased severity of illness. Literature about the coronavirus disease 2019 (COVID-19) in dialysis population is scarce. Management of COVID-19 patients in resource poor setting in a developing country does vary compared to developed nations. Nonavailability of the advanced laboratory facility and the newer medicines forces the treating team to manage the patients with available investigations and drugs. We aimed at analysis of clinical characteristics and outcomes of 84 patients on maintenance hemodialysis (HD). Data of all COVID-positive patients on maintenance HD, who were referred to our center were collected. All patients were given HD on NIKISSO machines. Outcomes of all the admitted patients were analyzed. Maintenance HD group formed majority of the kidney referrals (54%). Age group that was commonly affected was >50 years. Factors associated with mortality were age, diabetes, thrombocytopenia, prolonged baseline activated partial thromboplastin time, admission hypoxemia, high qSOFA score. Institutional Ethics Committee approval has been obtained for the study. Methodology of the study was in accordance with the Declaration of Helsinki. Verbal consent was obtained from patients/ attendants. In the ongoing COVID pandemic, in a developing nation where resources are constrained, it is difficult to salvage the critically ill patients. With the drugs available and the changing strategies, treatment was given to all the patients admitted with bedside renal replacement therapies. Our mortality rate was high compared to other studies due to delay in referral, admission hypoxemia, and late initiation of steroids.


Subject(s)
COVID-19/therapy , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/therapy , SARS-CoV-2/isolation & purification , Adult , Blood Coagulation Disorders , COVID-19/diagnosis , COVID-19/mortality , Female , Humans , Hypoxia/etiology , Kidney Function Tests , Male , Middle Aged , Pandemics , Reverse Transcriptase Polymerase Chain Reaction , Treatment Outcome
2.
Saudi J Kidney Dis Transpl ; 32(2): 377-386, 2021.
Article in English | MEDLINE | ID: covidwho-1622688

ABSTRACT

Coronavirus disease-2019 (COVID-19) is a global pandemic, also affecting Pakistan with its first case reported on February 26, 2020. Since then, it has been declared a pandemic by the World Health Organization. Our study aimed to evaluate the renal derangements associated with COVID-19 infection in our population. A retrospective, observational study was conducted to include all the admitted patients having COVID-19 positive, and evaluated those for derangements of renal function (n = 362). Out of the 362 patients, 229were admitted in the ward, 133 were in intensive care unit (ICU), 258 of them recovered, while 104 deaths reported. At admission, the renal profile was deranged in almost one-half of ICU admissions and mortalities which increased to two-third during the hospital stay, with around 80% of deaths reported with increased urea and creatinine levels. Among the deceased patients, around one-third of the mortalities developed renal profile derangements during the hospital stay although they were admitted with a normal renal profile. An estimated glomerular filtration rate showed a mean increase of 13.37 mL/min/1.73 m2 during the hospital stay of surviving patients, while a decline of 19.92 in nonsurviving patients. A hazard ratio of 3.293 (P <0.001) for admitting serum urea and 3.795 (P = 0.009) at discharge and for serum creatinine at 5.392 (P <0.001) on discharge was associated significantly with mortality. Kaplan-Meier plot showed a significant decline in days of survival with deranged urea and creatinine (P <0.001). The deranged renal function in COVID-19 patients is associated with an increased number of ICU admissions as well as mortalities.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , Hospital Mortality , Intensive Care Units/statistics & numerical data , SARS-CoV-2 , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , COVID-19/mortality , COVID-19 Nucleic Acid Testing , Creatinine/blood , Glomerular Filtration Rate , Humans , Incidence , Kidney Function Tests , Pakistan/epidemiology , Renal Dialysis , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Tertiary Healthcare , Urea/blood
3.
Inflammopharmacology ; 29(6): 1795-1805, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1505910

ABSTRACT

Hydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.


Subject(s)
Antimalarials/adverse effects , Antimalarials/blood , COVID-19/complications , Connective Tissue Diseases/complications , Hydroxychloroquine/adverse effects , Hydroxychloroquine/blood , Adult , Aged , Chromatography, High Pressure Liquid , Creatinine/blood , Electrocardiography , Erythrocyte Count , Female , Glomerular Filtration Rate/drug effects , Humans , Kidney Function Tests , Liver Function Tests , Long QT Syndrome/chemically induced , Male , Middle Aged , Tandem Mass Spectrometry , Young Adult
4.
J Am Soc Nephrol ; 32(3): 639-653, 2021 03.
Article in English | MEDLINE | ID: covidwho-1496657

ABSTRACT

BACKGROUND: CKD is a heterogeneous condition with multiple underlying causes, risk factors, and outcomes. Subtyping CKD with multidimensional patient data holds the key to precision medicine. Consensus clustering may reveal CKD subgroups with different risk profiles of adverse outcomes. METHODS: We used unsupervised consensus clustering on 72 baseline characteristics among 2696 participants in the prospective Chronic Renal Insufficiency Cohort (CRIC) study to identify novel CKD subgroups that best represent the data pattern. Calculation of the standardized difference of each parameter used the cutoff of ±0.3 to show subgroup features. CKD subgroup associations were examined with the clinical end points of kidney failure, the composite outcome of cardiovascular diseases, and death. RESULTS: The algorithm revealed three unique CKD subgroups that best represented patients' baseline characteristics. Patients with relatively favorable levels of bone density and cardiac and kidney function markers, with lower prevalence of diabetes and obesity, and who used fewer medications formed cluster 1 (n=1203). Patients with higher prevalence of diabetes and obesity and who used more medications formed cluster 2 (n=1098). Patients with less favorable levels of bone mineral density, poor cardiac and kidney function markers, and inflammation delineated cluster 3 (n=395). These three subgroups, when linked with future clinical end points, were associated with different risks of CKD progression, cardiovascular disease, and death. Furthermore, patient heterogeneity among predefined subgroups with similar baseline kidney function emerged. CONCLUSIONS: Consensus clustering synthesized the patterns of baseline clinical and laboratory measures and revealed distinct CKD subgroups, which were associated with markedly different risks of important clinical outcomes. Further examination of patient subgroups and associated biomarkers may provide next steps toward precision medicine.


Subject(s)
Renal Insufficiency, Chronic/classification , Adult , Aged , Algorithms , Bone Density , Cohort Studies , Disease Progression , Female , Heart Function Tests , Humans , Kaplan-Meier Estimate , Kidney Function Tests , Male , Middle Aged , Prognosis , Prospective Studies , Renal Insufficiency, Chronic/physiopathology , Risk Factors , Unsupervised Machine Learning , Young Adult
5.
J Am Soc Nephrol ; 32(2): 375-384, 2021 02.
Article in English | MEDLINE | ID: covidwho-1496655

ABSTRACT

BACKGROUND: Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood. METHODS: To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats. The 12-week-old animals underwent warm bilateral ischemia-reperfusion surgery involving clamping of both renal arteries for 45 minutes or sham surgery (control). Rats were allowed to recover for 1 month prior to mating. Recovery from ischemia-reperfusion injury was confirmed by measurements of plasma creatinine and urinary protein excretion. We assessed maternal and fetal outcomes during late pregnancy on gestational day 20. RESULTS: After recovery from ischemia-reperfusion injury, compared with healthy sham-surgery controls, dams exhibited pregnancy-induced renal insufficiency with increases in plasma creatinine and urea, along with increased urinary protein excretion. Additionally, recovered ischemia-reperfusion dams experienced worse fetal outcomes compared with controls, with intrauterine growth restriction leading to higher rates of fetal demise and smaller pups. CONCLUSIONS: In this rat model, despite biochemical resolution of ischemia-reperfusion injury, subsequent pregnancy resulted in maternal renal insufficiency and significant impairments in fetal growth. This mirrors findings in recent reports in the clinical population, indicating that this model may be a useful tool to further explore the alterations in kidney function after AKI in women.


Subject(s)
Acute Kidney Injury/etiology , Pregnancy Complications/etiology , Reperfusion Injury/etiology , Animals , Disease Models, Animal , Female , Kidney Function Tests , Ligation , Pregnancy , Rats , Rats, Sprague-Dawley , Renal Artery/surgery
6.
BMC Nephrol ; 22(1): 359, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1496153

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is common among patients hospitalised with COVID-19 and associated with worse prognosis. The aim of this study was to investigate the epidemiology, risk factors and outcomes of AKI in patients with COVID-19 in a large UK tertiary centre. METHODS: We analysed data of consecutive adults admitted with a laboratory-confirmed diagnosis of COVID-19 across two sites of a hospital in London, UK, from 1st January to 13th May 2020. RESULTS: Of the 1248 inpatients included, 487 (39%) experienced AKI (51% stage 1, 13% stage 2, and 36% stage 3). The weekly AKI incidence rate gradually increased to peak at week 5 (3.12 cases/100 patient-days), before reducing to its nadir (0.83 cases/100 patient-days) at the end the study period (week 10). Among AKI survivors, 84.0% had recovered renal function to pre-admission levels before discharge and none required on-going renal replacement therapy (RRT). Pre-existing renal impairment [odds ratio (OR) 3.05, 95%CI 2.24-4,18; p <  0.0001], and inpatient diuretic use (OR 1.79, 95%CI 1.27-2.53; p <  0.005) were independently associated with a higher risk for AKI. AKI was a strong predictor of 30-day mortality with an increasing risk across AKI stages [adjusted hazard ratio (HR) 1.59 (95%CI 1.19-2.13) for stage 1; p < 0.005, 2.71(95%CI 1.82-4.05); p < 0.001for stage 2 and 2.99 (95%CI 2.17-4.11); p < 0.001for stage 3]. One third of AKI3 survivors (30.7%), had newly established renal impairment at 3 to 6 months. CONCLUSIONS: This large UK cohort demonstrated a high AKI incidence and was associated with increased mortality even at stage 1. Inpatient diuretic use was linked to a higher AKI risk. One third of survivors with AKI3 exhibited newly established renal impairment already at 3-6 months.


Subject(s)
Acute Kidney Injury , COVID-19 , Renal Replacement Therapy , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Hospital Mortality , Humans , Incidence , Intensive Care Units/statistics & numerical data , Kidney Function Tests/methods , Male , Middle Aged , Outcome and Process Assessment, Health Care , Patient Acuity , Renal Replacement Therapy/methods , Renal Replacement Therapy/statistics & numerical data , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , United Kingdom/epidemiology
7.
Ren Fail ; 43(1): 1329-1337, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1493366

ABSTRACT

BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , Hypophosphatemia/complications , Pneumonia, Viral/complications , Acute Kidney Injury/epidemiology , COVID-19/epidemiology , China/epidemiology , Female , Hospitalization , Humans , Hypophosphatemia/epidemiology , Incidence , Intensive Care Units , Kidney Function Tests , Male , Middle Aged , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Retrospective Studies , Risk Factors , SARS-CoV-2
8.
Int J Antimicrob Agents ; 59(1): 106462, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1474605

ABSTRACT

OBJECTIVES: The use of antibiotics was common in some countries during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, but adequate evaluation remains lacking. This study aimed to evaluate the effect of early antibiotic use in patients with non-severe COVID-19 admitted without bacterial infection. METHODS: This multi-centre retrospective cohort study included 1,373 inpatients with non-severe COVID-19 admitted without bacterial infection. Patients were divided into two groups according to their exposure to antibiotics within 48 h of admission. The outcomes were progression to severe COVID-19, length of stay >15 days and mortality rate. A mixed-effect Cox model and random effect logistic regression were used to explore the association between early antibiotic use and outcomes. RESULTS: During the 30-day follow-up period, the proportion of patients who progressed to severe COVID-19 in the early antibiotic use group was almost 1.4 times that of the comparison group. In the mixed-effect model, the early use of antibiotics was associated with higher probability of developing severe COVID-19 and staying in hospital for >15 days. However, there was no significant association between early use of antibiotics and mortality. Analysis with propensity-score-matched cohorts displayed similar results. In subgroup analysis, patients receiving any class of antibiotic were at increased risk of adverse health outcomes. Azithromycin did not improve disease progression and length of stay in patients with COVID-19. CONCLUSIONS: It is suggested that antibiotic use should be avoided unless absolutely necessary in patients with non-severe COVID-19, particularly in the early stages.


Subject(s)
Anti-Bacterial Agents/therapeutic use , COVID-19 Drug Treatment , Adult , Aged , Antiviral Agents/therapeutic use , Bacterial Infections , COVID-19/etiology , COVID-19/mortality , Female , Fever/drug therapy , Fever/virology , Humans , Kidney Function Tests , Length of Stay , Liver Function Tests , Male , Middle Aged , Mortality , Retrospective Studies , Treatment Outcome
9.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166289, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1466061

ABSTRACT

To explore the recovery of renal function in severely ill coronavirus disease (COVID-19) survivors and determine the plasma metabolomic profile of patients with different renal outcomes 3 months after discharge, we included 89 severe COVID-19 survivors who had been discharged from Wuhan Union Hospital for 3 months. All patients had no underlying kidney disease before admission. At patient recruitment, renal function assessment, laboratory examination, chest computed tomography (CT) were performed. Liquid chromatography-mass spectrometry was used to detect metabolites in the plasma. We analyzed the longitudinally change in the estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin-c levels using the CKD-EPI equation and explored the metabolomic differences in patients with different eGFR change patterns from hospitalization to 3 months after discharge. Lung CT showed good recovery; however, the median eGFR significantly decreased at the 3-month follow-up. Among the 89 severely ill COVID-19 patients, 69 (77.5%) showed abnormal eGFR (<90 mL/min per 1.73 m2) at 3 months after discharge. Age (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.08-1.47, p = 0.003), body mass index (OR = 1.97, 95% CI = 1.20-3.22, p = 0.007), and cystatin-c level (OR = 1.22, 95% CI = 1.07-1.39, p = 0.003) at discharge were independent risk factors for post-discharge abnormal eGFR. Plasma metabolomics at the 3-months follow-up revealed that ß-pseudouridine, uridine, and 2-(dimethylamino) guanosine levels gradually increased with an abnormal degree of eGFR. Moreover, the kynurenine pathway in tryptophan metabolism, vitamin B6 metabolism, cysteine and methionine metabolism, and arginine biosynthesis were also perturbed in survivors with abnormal eGFR.


Subject(s)
COVID-19/complications , COVID-19/virology , Energy Metabolism , Glomerular Filtration Rate , Kidney Diseases/etiology , Kidney Diseases/metabolism , SARS-CoV-2 , Aged , COVID-19/diagnosis , Comorbidity , Female , Humans , Kidney Diseases/diagnosis , Kidney Function Tests , Male , Metabolic Networks and Pathways , Metabolome , Metabolomics/methods , Middle Aged , Odds Ratio , Patient Discharge , Severity of Illness Index , Symptom Assessment
10.
J Hepatol ; 75(2): 435-438, 2021 08.
Article in English | MEDLINE | ID: covidwho-1454287

ABSTRACT

BACKGROUND & AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p = 0.013) and mostly female (68%, p = 0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p <0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/ml vs. 200.5 AU/ml in controls, p <0.001). Predictors for negative response among LT recipients were older age, lower estimated glomerular filtration rate, and treatment with high dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group. CONCLUSION: LT recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. LAY SUMMARY: The Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine elicited substantially inferior immunity in liver transplant recipients. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were 2x less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine/immunology , Immunoglobulin G/blood , Immunosuppressive Agents/therapeutic use , Liver Transplantation/methods , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Humans , Immunosuppression Therapy/methods , Israel/epidemiology , Kidney Function Tests , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , Serologic Tests/methods , Serologic Tests/statistics & numerical data , Vaccination/adverse effects , Vaccination/methods
11.
Turk J Ophthalmol ; 51(4): 231-242, 2021 08 27.
Article in English | MEDLINE | ID: covidwho-1380043

ABSTRACT

Immunomodulatory agents are often used in the systemic treatment of non-infectious uveitis. These drugs consist of corticosteroids, conventional immunosuppressives, and biological agents. As it is known that they suppress the immune system, the most important concern associated with immunomodulatory therapy (IMT) is the increased risk of infection. The World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although severe acute respiratory distress syndrome secondary to SARS-CoV-2 infection may develop in all people, patients who receive IMT may be at higher risk in terms of both the transmission of the infection and more severe disease course. Therefore, guidelines on the management of patients receiving IMT due to uveitis during the pandemic are needed. In this review, we examined the immunomodulatory drugs used in the treatment of uveitis in terms of infectious complications and the data of patients who received IMT during the COVID-19 pandemic and discussed recommendations for the use of these drugs. According to the latest information, patients who receive IMT may continue their treatment as long as there are no disruptions in regular complete blood count (especially white blood cell count >4,000/µL) and liver and kidney function tests. Patients diagnosed with COVID-19 should be managed with a multidisciplinary approach.


Subject(s)
COVID-19/epidemiology , Glucocorticoids/therapeutic use , Immunomodulation , Immunosuppressive Agents/therapeutic use , SARS-CoV-2 , Uveitis/drug therapy , COVID-19/transmission , Clinical Decision-Making , Disease Transmission, Infectious/prevention & control , Humans , Kidney Function Tests , Leukocyte Count , Liver Function Tests , Ophthalmology , Risk Assessment
12.
Biomed Pharmacother ; 142: 111966, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330663

ABSTRACT

Since December 2019, the world was encountered a new disease called coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although SARS-CoV-2 initially causes lung damage, it also affects many other organs, including the kidneys, and on average, 5-23% of people with COVID-19 develop the symptoms of acute kidney injury (AKI), including elevated blood creatinine and urea, hematuria, proteinuria, and histopathological damages. The exact mechanism is unknown, but the researchers believe that SARS-CoV-2 directly and indirectly affects the kidneys. The direct pathway is by binding the virus to ACE2 receptor in the kidney, damage to cells, the renin-angiotensin system disturbances, activating coagulation pathways, and damaging the renal vascular endothelium. The initial evidence from studying the kidney tissue in postmortem patients is more in favor of the direct pathway. The indirect pathway is created by increased cytokines and cytokine storm, sepsis, circulatory disturbances, hypoxemia, as well as using the nephrotoxic drugs. Using renal tissue biopsy and autopsy in the patients with COVID-19, recent studies found evidence for a predominant indirect pathway in AKI induction by SARS-CoV-2. Besides, some studies showed that the degree of acute tubular injury (ATI) in autopsies from COVID-19 victims is milder compared to AKI degree. We review the mechanism of AKI induction and the renal side effects of the most common drugs used to treat COVID-19 after the overview of the latest findings on SARS-CoV-2 pathogenicity.


Subject(s)
Acute Kidney Injury , COVID-19 Drug Treatment , Kidney/pathology , SARS-CoV-2 , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/virology , COVID-19/complications , COVID-19/mortality , COVID-19/physiopathology , Humans , Kidney Function Tests/methods , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology
14.
Ren Fail ; 43(1): 1104-1114, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1303829

ABSTRACT

BACKGROUND: The clinical use of serum creatine (sCr) and cystatin C (CysC) in kidney function evaluation of critically ill patients has been in continuous discussion. The difference between estimated glomerular filtration rate calculated by sCr (eGFRcr) and CysC (eGFRcysc) of critically ill COVID-19 patients were investigated in this study. METHODS: This is a retrospective, single-center study of critically ill patients with COVID-19 admitted in intensive care unit (ICU) at Wuhan, China. Control cases were moderate COVID-19 patients matched in age and sex at a ratio of 1:1. The eGFRcr and eGFRcysc were compared. The association between eGFR and death were analyzed in critically ill cases. The potential factors influencing the divergence between eGFRcr and eGFRcysc were explored. RESULTS: A total of 76 critically ill COVID-19 patients were concluded. The mean age was 64.5 ± 9.3 years. The eGFRcr (85.45 (IQR 60.58-99.23) ml/min/1.73m2) were much higher than eGFRcysc (60.6 (IQR 34.75-79.06) ml/min/1.73m2) at ICU admission. About 50 % of them showed eGFRcysc < 60 ml/min/1.73 m2 while 25% showed eGFRcr < 60 ml/min/1.73 m2 (χ2 = 10.133, p = 0.001). This divergence was not observed in moderate group. The potential factors influencing the divergence included serum interleukin-6 (IL-6), tumor necrosis factor (TNF-α) level as well as APACHEII, SOFA scores. Reduced eGFRcr (<60 mL/min/1.73 m2) was associated with death (HR = 1.939, 95%CI 1.078-3.489, p = 0.027). CONCLUSIONS: The eGFRcr was generally higher than eGFRcysc in critically ill COVID-19 cases with severe inflammatory state. The divergence might be affected by inflammatory condition and illness severity. Reduced eGFRcr predicted in-hospital death. In these patients, we advocate for caution when using eGFRcysc.


Subject(s)
COVID-19/physiopathology , Creatine/blood , Cystatin C/blood , Glomerular Filtration Rate , Renal Insufficiency, Chronic/diagnosis , Aged , Biomarkers/blood , COVID-19/complications , COVID-19/mortality , China/epidemiology , Critical Illness/therapy , Female , Hospital Mortality , Humans , Kidney Function Tests , Male , Middle Aged , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/etiology , Retrospective Studies , Survival Analysis
15.
Nat Commun ; 12(1): 2506, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1216457

ABSTRACT

It is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human kidney, thus leading to acute kidney injury (AKI). Here, we perform a retrospective analysis of clinical parameters from 85 patients with laboratory-confirmed coronavirus disease 2019 (COVID-19); moreover, kidney histopathology from six additional COVID-19 patients with post-mortem examinations was performed. We find that 27% (23/85) of patients exhibited AKI. The elderly patients and cases with comorbidities (hypertension and heart failure) are more prone to develop AKI. Haematoxylin & eosin staining shows that the kidneys from COVID-19 autopsies have moderate to severe tubular damage. In situ hybridization assays illustrate that viral RNA accumulates in tubules. Immunohistochemistry shows nucleocapsid and spike protein deposits in the tubules, and immunofluorescence double staining shows that both antigens are restricted to the angiotensin converting enzyme-II-positive tubules. SARS-CoV-2 infection triggers the expression of hypoxic damage-associated molecules, including DP2 and prostaglandin D synthase in infected tubules. Moreover, it enhances CD68+ macrophages infiltration into the tubulointerstitium, and complement C5b-9 deposition on tubules is also observed. These results suggest that SARS-CoV-2 directly infects human kidney to mediate tubular pathogenesis and AKI.


Subject(s)
Acute Kidney Injury/etiology , COVID-19/complications , Kidney Tubules/virology , SARS-CoV-2/pathogenicity , Acute Kidney Injury/epidemiology , Acute Kidney Injury/pathology , Acute Kidney Injury/virology , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , Antigens, Viral/genetics , Antigens, Viral/metabolism , COVID-19/epidemiology , COVID-19/virology , China/epidemiology , Female , Humans , Immunity, Innate , Kidney Function Tests , Kidney Tubules/metabolism , Kidney Tubules/pathology , Male , Middle Aged , Pandemics , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viral Proteins/genetics , Viral Proteins/metabolism , Young Adult
16.
AIDS Res Hum Retroviruses ; 37(4): 292-296, 2021 04.
Article in English | MEDLINE | ID: covidwho-1207215

ABSTRACT

Advanced age is a high-risk factor for exacerbation of coronavirus disease 2019 (COVID-19), which causes a high rate of mortality. Therefore, it is important to strengthen the warning and monitoring of severe patients, and early identify the severe and critically severe types in time in the clinical treatment of COVID-19. Moreover, it is necessary to pay attention to the adverse reactions and damage to vital target organs caused by treatment drugs. This study reports the successful experience of diagnosis and treatment of an older patient with COVID-19 accompanied by progressive renal impairment, and pertinent literature was reviewed to help clinicians raise awareness of the disease.


Subject(s)
COVID-19/physiopathology , Kidney/physiopathology , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , COVID-19/virology , Female , Humans , Kidney Function Tests , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed
17.
Nephron ; 145(4): 386-387, 2021.
Article in English | MEDLINE | ID: covidwho-1158156
18.
Recenti Prog Med ; 112(3): 216-218, 2021 03.
Article in English | MEDLINE | ID: covidwho-1154141

ABSTRACT

We analysed RRI and other hemodynamic, re-spiratory and inflammation parameters in critically ill pa-tients affected by severe covid-19 with acute distress respi-ratory syndrome (ARDS) aiming at verifying their modifica-tions during supine and prone positioning and any mutual correlation or interplay with RRI.


Subject(s)
Blood Flow Velocity , COVID-19/physiopathology , Inflammation/physiopathology , Kidney/physiopathology , Lung/physiopathology , Renal Artery/physiopathology , Renal Circulation , Respiratory Distress Syndrome/physiopathology , SARS-CoV-2 , Biomarkers , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , Creatinine/blood , Diastole , Early Diagnosis , Female , Humans , Inflammation/blood , Inflammation/diagnosis , Kidney Function Tests , Male , Middle Aged , Oxygen/blood , Prone Position , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/etiology , Supine Position , Systole
19.
JAMA Netw Open ; 4(3): e211095, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1125117

ABSTRACT

Importance: Acute kidney injury (AKI) occurs in up to half of patients hospitalized with coronavirus disease 2019 (COVID-19). The longitudinal effects of COVID-19-associated AKI on kidney function remain unknown. Objective: To compare the rate of change in estimated glomerular filtration rate (eGFR) after hospital discharge between patients with and without COVID-19 who experienced in-hospital AKI. Design, Setting, and Participants: A retrospective cohort study was conducted at 5 hospitals in Connecticut and Rhode Island from March 10 to August 31, 2020. Patients who were tested for COVID-19 and developed AKI were screened, and those who survived past discharge, did not require dialysis within 3 days of discharge, and had at least 1 outpatient creatinine level measurement following discharge were included. Exposures: Diagnosis of COVID-19. Main Outcomes and Measures: Mixed-effects models were used to assess the association between COVID-19-associated AKI and eGFR slope after discharge. The secondary outcome was the time to AKI recovery for the subgroup of patients whose kidney function had not returned to the baseline level by discharge. Results: A total of 182 patients with COVID-19-associated AKI and 1430 patients with AKI not associated with COVID-19 were included. The population included 813 women (50.4%); median age was 69.7 years (interquartile range, 58.9-78.9 years). Patients with COVID-19-associated AKI were more likely to be Black (73 [40.1%] vs 225 [15.7%]) or Hispanic (40 [22%] vs 126 [8.8%]) and had fewer comorbidities than those without COVID-19 but similar rates of preexisting chronic kidney disease and hypertension. Patients with COVID-19-associated AKI had a greater decrease in eGFR in the unadjusted model (-11.3; 95% CI, -22.1 to -0.4 mL/min/1.73 m2/y; P = .04) and after adjusting for baseline comorbidities (-12.4; 95% CI, -23.7 to -1.2 mL/min/1.73 m2/y; P = .03). In the fully adjusted model controlling for comorbidities, peak creatinine level, and in-hospital dialysis requirement, the eGFR slope difference persisted (-14.0; 95% CI, -25.1 to -2.9 mL/min/1.73 m2/y; P = .01). In the subgroup of patients who had not achieved AKI recovery by discharge (n = 319), COVID-19-associated AKI was associated with decreased kidney recovery during outpatient follow-up (adjusted hazard ratio, 0.57; 95% CI, 0.35-0.92). Conclusions and Relevance: In this cohort study of US patients who experienced in-hospital AKI, COVID-19-associated AKI was associated with a greater rate of eGFR decrease after discharge compared with AKI in patients without COVID-19, independent of underlying comorbidities or AKI severity. This eGFR trajectory may reinforce the importance of monitoring kidney function after AKI and studying interventions to limit kidney disease after COVID-19-associated AKI.


Subject(s)
Acute Kidney Injury/metabolism , COVID-19/metabolism , Creatinine/metabolism , Acute Kidney Injury/complications , Acute Kidney Injury/epidemiology , Black or African American , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/epidemiology , Cohort Studies , Comorbidity , Female , Follow-Up Studies , Glomerular Filtration Rate , Hispanic or Latino , Humans , Hypertension/epidemiology , Kidney Function Tests , Longitudinal Studies , Male , Middle Aged , Patient Discharge , Proportional Hazards Models , Renal Insufficiency, Chronic/epidemiology , Retrospective Studies , SARS-CoV-2 , United States/epidemiology
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