Project description:BackgroundA population-based study would be useful to identify the association between chronic kidney disease (CKD) or acute kidney injury (AKI) and prognosis of coronavirus disease 2019 (COVID-19) patients.MethodsThis retrospective study utilized the claim data from Korea. Patients who underwent COVID-19 testing and were confirmed to be positive were included and divided into the following three groups based on the presence of CKD or requirement of maintenance dialysis: Non-CKD (participants without CKD), non-dialysis CKD (ND-CKD), and dialysis-dependent CKD (DD-CKD) patients. We collected data on the development of severe clinical outcomes and death during follow-up. Severe clinical outcomes were defined as the use of inotropics, conventional oxygen therapy, high-flow nasal cannula, mechanical ventilation, or extracorporeal membrane oxygenation and the development of AKI, cardiac arrest, myocardial infarction, or acute heart failure after the diagnosis of COVID-19. AKI was defined as the initiation of renal replacement therapy after the diagnosis of COVID-19 in patients not requiring maintenance dialysis. Death was evaluated according to survival at the end of follow-up.ResultsAltogether, 7,341 patients were included. The median duration of data collection was 19 (interquartile range, 11-28) days. On multivariate analyses, odds ratio (OR) for severe clinical outcomes in the ND-CKD group was 0.88 (95% confidence interval [CI], 0.64-1.20; P = 0.422) compared to the Non-CKD group. The DD-CKD group had ORs of 7.32 (95% CI, 2.14-33.90; P = 0.004) and 8.32 (95% CI, 2.37-39.21; P = 0.002) compared to the Non-CKD and ND-CKD groups, respectively. Hazard ratio (HR) for death in the ND-CKD group was 0.79 (95% CI, 0.49-1.26; P = 0.318) compared to the Non-CKD group. The DD-CKD group had HRs of 2.96 (95% CI, 1.09-8.06; P = 0.033) and 3.77 (95% CI, 1.29-11.06; P = 0.016) compared to the Non-CKD and ND-CKD groups, respectively. DD-CKD alone was associated with severe clinical outcomes and higher mortality. There was no significant difference in frequency of severe clinical outcomes or mortality rates between the Non-CKD and ND-CKD groups. In patients not requiring maintenance dialysis, AKI was associated with old age, male sex, and high Charlson's comorbidity index score but not with the presence of CKD. HRs for patients with AKI were 11.26 (95% CI, 7.26-17.45; P < 0.001) compared to those for patients without AKI in the multivariate analysis. AKI was associated with severe clinical outcomes and patient survival, rather than underlying CKD.ConclusionCKD requiring dialysis is associated with severe clinical outcomes and mortality in patients with COVID-19; however, the development of AKI is more strongly associated with severe clinical outcomes and mortality.
Project description:BackgroundNovel coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread, affecting >10 million cases worldwide. Caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and primarily manifesting as an acute respiratory failure with interstitial and alveolar pneumonia, it can also affect multiple organs. Kidney involvement was underestimated in early reports and its role remains controversial. The aim of this study was to analyse the role of kidney damage in COVID-19 outcome.MethodsThis is a prospective cohort study of 1603 consecutive patients admitted in a University Reference Hospital in the heart of the European outbreak.ResultsMedian age was 64 years, 40.4% were female, 15.2% presented diabetes mellitus, 35.7% hypertension and 20.3% obesity. On admission, the prevalence of elevated serum creatinine (sCr), proteinuria, leucocyturia and haematuria were 21.0, 37.8, 31.8 and 45.6%, respectively. In total, 43.5% of those with an elevated sCr had previous chronic kidney disease (CKD) and 11.4% of those with normal sCr developed an in-hospital acute kidney injury (AKI); 17 patients needed acute haemodialysis; and 197 patients died during hospitalization. Cox proportional hazard regression confirmed that elevated baseline sCr [hazard ratio (95% confidence interval) 2.40 (1.79-3.22)], previous CKD [1.59 (1.06-2.37)], haematuria [1 + 1.68 (0.92-3.06), 2-3 + 2.69 (1.49-4.87)] and in-hospital AKI [1.50 (0.92-2.44)] were independent risk factors for in-hospital death after adjusting for age, sex and comorbidity.ConclusionThe prevalence of acute and chronic kidney disease on admission and in-hospital AKI is higher than previously reported in Wuhan, and is associated with high in-hospital mortality. We should increase our awareness towards kidney involvement and design specific strategies for management of COVID-19 in these patients.
Project description:Coronavirus disease 2019 (COVID-19) caused by 2019 novel coronavirus (2019-nCoV) has caused significant mortality and has been declared as a global pandemic by the World Health Organization. The infection mainly presents as fever, cough, and breathing difficulty, and few patients develop very severe symptoms. The purpose of this review is to analyze the impact of the virus on the kidney. COVID-19 infection causes acute kidney injury (AKI) and is an independent risk factor for mortality. Angiotensin-converting enzyme 2 (ACE2) receptors, direct viral damage, and immune-mediated damage play important roles in the pathogenesis. AKI in COVID-19 infection could be from the synergistic effect of virus-induced direct cytotropic effect and cytokine-induced systemic inflammatory response. AKI caused in the viral infection has been analyzed from the available epidemiological studies. The proportion of patients developing AKI is significantly higher when they develop severe disease. Continuous renal replacement therapy (CRRT) is the most used blood purification technique when needed. The impact of COVID-19 infection on chronic kidney disease (CKD) and renal transplant patients is also discussed in the manuscript. No vaccine has been developed against the 2019-nCoV virus to date. The critical aspect of management is supportive care. Several investigative drugs have been studied, drugs approved for other indications have been used, and several clinical trials are underway across the globe. Recently remdesivir has received emergency use authorization by the Food and Drug Administration (FDA) in the USA for use in patients hospitalized with COVID-19. Prevention of the infection holds the key to management. The patients with underlying kidney problems and renal transplant patients are vulnerable to developing COVID-19 infection.
Project description:Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area. The study population included CKD patients recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within this PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015-19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. COVID-19 related mortality was about ten times higher than that of CKD patients without COVID. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.
Project description:BackgroundVaccination of patients with chronic kidney disease (CKD) and kidney transplants (KTs) may achieve a less robust immune response. Understanding such immune responses is crucial for guiding current and future vaccine dosing strategies.MethodsThis prospective, observational study estimated the immunogenicity of humoral and cellular responses of two SARS-CoV-2 vaccines in different patient groups with CKD compared with controls. Secondary outcomes included adverse events after vaccination and the incidence of COVID-19 breakthrough infection, including illness severity.ResultsIn total, 212 patients received ChAdOx1 nCoV-19 (89.62 %) or inactivated vaccines (10.38 %).The antibody response against the S protein was analyzed at T0 (before the first injection), T1 (before the second injection), and T2 (12 weeks after the second injection). Seroconversion occurred in 92.31 % of controls at T2 and in 100 % of patients with CKD, 42.86 % undergoing KT, 80.18 % of hemodialysis (HD), and 0 % of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) at T2 of the ChAdOx1 nCoV-19 vaccine. Neutralizing antibody levels by surrogate virus neutralization test were above the protective level at T2 in each group. The KT group exhibited the lowest neutralizing antibody and T cell response. Blood groups O and vaccine type were associated with good immunological responses. After the first dose, 14 individuals (6.6 out of the total population experienced COVID-19 breakthrough infection.ConclusionImmunity among patients with CKD and HD after vaccination was strong and comparable with that of healthy controls. Our study suggested that a single dose of the vaccine is not efficacious and delays may result in breakthrough infection. Some blood groups and types of vaccine can affect the immune response.
Project description:Renal involvement has been implicated in coronavirus disease 2019 (COVID-19), but the related prevalence and prognosis were largely unknown. In this meta-analysis, we searched the literature from PubMed, Embase, through bioRxiv, and medRxiv until April 26, 2020. Studies reporting chronic kidney diseases (CKDs) and/or acute kidney injury (AKI) were included. Demographics, relevant data of disease severity, and patient's prognosis were extracted and aggregated. Twenty-one thousand one hundred sixty-four patients from 52 peer-reviewed studies were included. Thirty-seven studies (n = 16,922) reported CKD in COVID-19 patients at diagnosis, and the pooled prevalence was 3.52% (95% CI, 1.98-5.48%; I 2 = 93%). Subgroup analysis showed that CKD prevalence was higher in severe cases [odds ratio (OR), 3.42; 95% CI 2.05-5.61; I 2 = 0%] compared to those with non-severe disease and deceased cases (6.46, 3.40-12.29; I 2 = 1%) compared with survivors. Pooled prevalence of CKD was lower in Chinese patients (2.56%; 95% CI, 1.79-3.47%; I 2 = 80%) compared to those outside of China (6.32%; 95% CI, 0.9-16.12%; I 2 = 93%) (p = 0.08). The summary estimates for AKI prevalence was 11.46% (95% CI, 6.93-16.94%). Patients with AKI had a higher prevalence of developing into severe cases (OR, 6.97; 95% CI, 3.53-13.75; I 2 = 0%) and mortality risk (45.79, 36.88-56.85; I 2 = 17%). The prevalence estimates of CKD or AKI were not significantly different from preprint publications (p > 0.05). Our study indicates that renal condition, either in CKD or AKI, is associated with COVID-19 prognosis, and taking care of such patients needs further awareness and investigations.
Project description:Antiviral drugs such as Remdesivir (Veklury), Nirmatrelvir with Ritonavir (Paxlovid), Azvudine, and Molnupiravir (Lagevrio) can reduce the risk for severe and fatal Coronavirus Disease (COVID)-19. Although chronic kidney disease is a highly prevalent risk factor for severe and fatal COVID-19, most clinical trials with these drugs excluded patients with impaired kidney function. Advanced CKD is associated with a state of secondary immunodeficiency (SIDKD), which increases the susceptibility to severe COVID-19, COVID-19 complications, and the risk of hospitalization and mortality among COVID-19 patients. The risk to develop COVID-19 related acute kidney injury is higher in patients with precedent CKD. Selecting appropriate therapies for COVID-19 patients with impaired kidney function is a challenge for healthcare professionals. Here, we discuss the pharmacokinetics and pharmacodynamics of COVID-19-related antiviral drugs with a focus on their potential use and dosing in COVID-19 patients with different stages of CKD. Additionally, we describe the adverse effects and precautions to be taken into account when using these antivirals in COVID-19 patients with CKD. Lastly, we also discuss about the use of monoclonal antibodies in COVID-19 patients with kidney disease and related complications.
Project description:BackgroundThe significance of chronic kidney disease on susceptibility to COVID-19 and subsequent outcomes remains unaddressed.ObjectiveTo investigate the association of estimated glomerular filtration rate (eGFR) on risk of contracting COVID-19 and subsequent adverse outcomes.MethodsRates of hospital-diagnosed COVID-19 were compared across strata of eGFR based on conditional logistic regression using a nested case-control framework with 1:4 matching of patients diagnosed with COVID-19 with controls from the Danish general population on age, gender, diabetes and hypertension. Risk of subsequent severe COVID-19 or death was assessed in a cohort study with comparisons across strata of eGFR based on adjusted Cox regression models with G-computation of results to determine 60-day risk standardized to the distribution of risk factors in the sample.ResultsEstimated glomerular filtration rate was inversely associated with rate of hospital-diagnosed COVID-19: eGFR 61-90 mL/min/1.73m2 HR 1.13 (95% CI 1.03-1.25), P = 0.011; eGFR 46-60 mL/min/1.73m2 HR 1.26 (95% CI 1.06-1.50), P = 0.008; eGFR 31-45 mL/min/1.73m2 HR 1.68 (95% CI 1.34-2.11), P < 0.001; and eGFR ≤ 30 mL/min/1.73m2 3.33 (95% CI 2.50-4.42), P < 0.001 (eGFR > 90 mL/min/1.73m2 as reference), and renal impairment was associated with progressive increase in standardized 60-day risk of death or severe COVID-19; eGFR > 90 mL/min/1.73m2 13.9% (95% CI 9.7-15.0); eGFR 90-61 mL/min/1.73m2 16.1% (95% CI 14.5-17.7); eGFR 46-60 mL/min/1.73m2 17.8% (95% CI 14.7-21.2); eGFR 31-45 mL/min/1.73m2 22.6% (95% CI 18.2-26.2); and eGFR ≤ 30 mL/min/1.73m2 23.6% (95% CI 18.1-29.1).ConclusionsRenal insufficiency was associated with progressive increase in both rate of hospital-diagnosed COVID-19 and subsequent risk of adverse outcomes. Results underscore a possible vulnerability associated with impaired renal function in relation to COVID-19.
Project description:Kidney function is affected in COVID-19, while kidney itself modulates the immune response. Here, hypothesize if COVID-19 urine biomarkers level can assess immune activation vs. clinical trajectory. Considering the kidney's critical role in modulating the immune response, we sought to analyze activation markers in patients with pre-existing dysfunction. This was a cross-sectional study of 68 patients. Blood and urine were collected within 48 h of hospital admission (H1), followed by 96 h (H2), seven days (H3), and up to 25 days (H4) from admission. Serum level ferritin, procalcitonin, IL-6 assessed immune activation overall, while the response to viral burden was gauged with serum level of spike protein and αspike IgM and IgG. 39 markers correlated highly between urine and blood. Age and race, and to a lesser extend gender, differentiated several urine markers. The burden of pre-existing conditions correlated with urine DCN, CAIX and PTN, but inversely with IL-5 or MCP-4. Higher urinary IL-12 and lower CAIX, CCL23, IL-15, IL-18, MCP-1, MCP-3, MUC-16, PD-L1, TNFRS12A, and TNFRS21 signified non-survivors. APACHE correlated with urine TNFRS12, PGF, CAIX, DCN, CXCL6, and EGF. Admission urine LAG-3 and IL-2 predicted death. Pre-existing kidney disease had a unique pattern of urinary inflammatory markers. Acute kidney injury was associated, and to a certain degree, predicted by IFNg, TWEAK, MMP7, and MUC-16. Remdesavir had a more profound effect on the urine biomarkers than steroids. Urinary biomarkers correlated with clinical status, kidney function, markers of the immune system activation, and probability of demise in COVID-19.
Project description:BackgroundCurrently, the SARS-CoV-2 promptly spread across China and around the world. However, there are controversies about whether preexisting chronic kidney disease (CKD) and acute kidney injury complication (AKI) are involved in the COVID-19 pandemic.MeasurementsStudies reported the kidney outcomes in different severity of COVID-19 were included in this study. Standardized mean differences or odds ratios were calculated by employing Review Manager meta-analysis software.ResultsThirty-six trials were included in this systematic review with a total of 6395 COVID-19 patients. The overall effects indicated that preexisting CKD (OR = 3.28), complication of AKI (OR = 11.02), serum creatinine (SMD = 0.68), abnormal serum creatinine (OR = 4.86), blood urea nitrogen (SMD = 1.95), abnormal blood urea nitrogen (OR = 6.53), received continuous renal replacement therapy (CRRT) (OR = 23.63) were significantly increased in severe group than that in nonsevere group. Additionally, the complication of AKI (OR = 13.92) and blood urea nitrogen (SMD = 1.18) were remarkably elevated in the critical group than that in the severe group.ConclusionsCKD and AKI are susceptible to occur in patients with severe COVID-19. CRRT is applied frequently in severe COVID-19 patients than that in nonsevere COVID-19 patients. The risk of AKI is higher in the critical group than that in the severe group.