Renal impairment and its impact on clinical outcomes in patients who are critically ill with COVID-19: a multicentre observational study

Renal impairment is common in patients who are critically ill with coronavirus disease-19 (COVID-19). We examined the association between acute and chronic kidney disease with clinical outcomes in 372 patients with coronavirus disease-19 admitted to four regional intensive care units between 10 March 2020 and 31 July 2020. A total of 216 (58%) patients presented with COVID-19 and renal impairment. Acute kidney injury and/or chronic kidney disease was associated with greater in-hospital mortality compared with patients with preserved renal function (107/216 patients (50%) (95%CI 44–57) vs. 32/156 (21%) (95%CI 15–28), respectively; p < 0.001, relative risk 2.4 (95%CI 1.7–3.4)). Mortality was greatest in patients with renal transplants (6/7 patients (86%) (95%CI 47–100)). Mortality rates increased in patients with worsening renal injury according to the Kidney Disease: Improving Global Outcomes classification: stage 0 mortality 33/157 patients (21%) (95%CI 15–28) vs. stages 1–3 mortality 91/186 patients (49%) (95%CI 42–56); p < 0.001, relative risk 2.3 (95%CI 1.7–3.3). Survivors were less likely to require renal replacement therapy compared with non-survivors (57/233 patients (24%) vs. 64/139 patients (46%), respectively; p < 0.001, relative risk 1.9 (95%CI 1.4–2.5)). One-fifth of survivors who required renal replacement therapy acutely in intensive care continued to require renal support following discharge. Our data demonstrate that renal impairment in patients admitted to intensive care with COVID-19 is common and is associated with a high mortality and requirement for on-going renal support after discharge from critical care. Our findings have important implications for future pandemic planning in this patient cohort.     

Insulin therapy and acute kidney injury in critically ill patients a systematic review.

BACKGROUND: Intensive insulin therapy has been found to reduce mortality in some critically ill patients. We performed a systematic review and meta-analysis to ascertain the effect of intensive insulin therapy on the incidence of acute kidney injury (AKI) in adult critically ill patients. METHODS: We searched MEDLINE, SCOPUS and the Cochrane Central Register of Controlled Trials for studies that compared 'conventional' vs 'intensive' insulin therapy in critically ill patients. Studies were combined with random effects model meta-analyses. RESULTS: Five studies, three of which were randomized controlled trials, reported AKI as a secondary outcome. Two of the studies were non-concurrent prospective cohort studies. All were single-centre studies conducted in intensive care unit settings. By meta-analysis across all studies, intensive insulin therapy reduced the incidence of AKI by 38% [risk ratio (RR) 0.62; 95% confidence interval (CI) 0.47, 0.83; P = 0.001]. The findings of the randomized and cohort studies were similar and the studies were not statistically heterogeneous. Three studies reported the effect of insulin therapy on dialysis requirement. Overall, intensive insulin therapy reduced the incidence of dialysis requirement by 35%, however, this was not statistically significant (RR 0.65; 95% CI 0.40, 1.05; P = 0.08). The overall rate of hypoglycaemia in the conventional insulin therapy group was 1.3% (range 0.3-3.4%). Intensive insulin therapy was associated with a >4-fold increase in the risk of hypoglycaemia (RR 4.5; 95% CI 2.4, 8.5; P < 0.00001) CONCLUSION: There is evidence that intensive insulin therapy initiated in critically ill adult patients is associated with a reduction in the incidence of AKI in medical and surgical settings. A large trial primarily designed to examine the effect of insulin on the prevention of AKI is needed to confirm this finding.     

A validation study of UCSD-Mayo risk score in predicting hospital-acquired acute kidney injury in COVID-19 patients

IntroductionAcute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort.MethodsFive hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records.ResultsOf all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84–0.91). Next, we determined the UCSD-Mayo risk score had good overall performance (Nagelkerke R² = 0.32) and calibration in our cohort. Further analysis showed that the UCSD-Mayo risk score performed well in subgroups defined by gender, age, and several chronic comorbidities. However, the discrimination of the UCSD-Mayo risk score in ICU patients and patients with mechanical ventilation was not good which might be resulted from different risk factors of these patients.ConclusionsWe validated the performance of UCSD-Mayo risk score in predicting hospital-acquired AKI in COVID-19 patients was excellent except for patients from ICU or patients with mechanical ventilation.     

Acute kidney injury and the critically ill

Acute renal failure is commonly encountered in the intensive care unit. It is associated with considerable morbidity and mortality. There are many possible aetiologies in the critically ill, including nephrotoxic agents, hypovolaemia and sepsis. While many classification systems for acute renal failure exist, the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria and the Acute Kidney Injury Network (AKIN) criteria are the most commonly utilized. Many supportive therapies are employed to minimize the degree of renal injury once recognized, such as fluid resuscitation, maintenance of an adequate mean arterial pressure (with the use of vasopressors in persistent hypotension despite fluid and treatment of the underlying aetiology). However, if renal failure becomes established, then renal replacement therapy (RRT) may be needed to maintain homeostasis. While there are no clear guidelines with respect to the ideal mode or timing of RRT, we will discuss pros and cons of the various options.     

Acute kidney injury and the critically ill

Acute renal failure is commonly encountered in the intensive care unit. It is associated with considerable morbidity and mortality. There are many possible aetiologies in the critically ill, including nephrotoxic agents, hypovolaemia and sepsis. While many classification systems for acute renal failure exist, the RIFLE (Risk, Injury, Failure, Loss, End-stage) criteria and the Acute Kidney Injury Network (AKIN) criteria are the most commonly utilized. Many supportive therapies are employed to minimize the degree of renal injury once recognized, such as fluid resuscitation and maintenance of an adequate mean arterial pressure (with the use of inotropes in persistent hypotension despite fluid and treatment of the underlying aetiology). However, if renal failure becomes established, then renal replacement therapy (RRT) may be needed to maintain homoeostasis. While there are no clear guidelines with respect to the ideal mode or timing of RRT, we will discuss pros and cons of the various bedside options.     

Altered kidney function induced by SARS-CoV-2 infection and acute kidney damage markers predict survival outcomes of COVID-19 patients: a prospective pilot study

BackgroundLiterature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage markers and their predictive value for survival among hospitalized subjects with COVID-19.MethodsForty-seven participants was included and grouped as: ‘COVID-19 patients before treatment’, ‘COVID-19 patients after treatment’, ‘COVID-19 patients under treatment in intensive care unit (ICU)’, and ‘controls’. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan–Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well.ResultsSerum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine–cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups ‘COVID-19 patients before treatment’ and ‘COVID-19 patients under treatment in ICU’. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22–30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00–2.52; p = 0.09).ConclusionsOur findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.     

Acute kidney injury after COVID-19 vaccines: a real-world study

BackgroundAcute kidney injury (AKI), a rare adverse event, cannot be ignored as millions of doses of coronavirus disease 2019 (COVID-19) vaccinations. We aimed to investigate the occurrence of post-vaccine AKI reported to the Vaccine Adverse Event Reporting System (VAERS).MethodsAfter data mapping from December 2020 to June 2021, we summarized demographic and clinical features and outcomes of reported cases from three vaccines (Pfizer-BNT, MODERNA, and JANSSEN). The Bayesian and nonproportional analyses explored the correlations between COVID-19 vaccines and AKI.ResultsWe identified 1133 AKI cases. Pfizer-BNT appeared to have a stronger AKI correlation than MODERNA and JANSSEN, based on the highest reporting odds ratio (ROR = 2.15, 95% confidence interval = 1.97, 2.36). We observed the differences in ages, comorbidities, current illnesses, post-vaccine AKI causes, and time to AKI onset (all p＜.05) among three vaccines. Most patients are elderly, with the highest age in MODERNA (68.41 years) and lowest in JANSSEN (59.75 years). Comorbidities were noticed in 58.83% of the cases and active infections in over 20% of cases. The leading cause of post-vaccine AKI was volume depletion (40.78%), followed by sepsis (11.74%). Patients in Pfizer-BNT had the worst outcome with 19.78% deaths, following 17.78% in MODERNA and 12.36% in JANSSEN (p = .217). The proportion of patients on dialysis was higher in JANSSEN than in Pfizer-BNT and MODERNA (14.61% vs. 6.54%, 10.62%, p = .008).ConclusionAKI could occur after the COVID-19 vaccines, predominantly in elderly patients. However, the causality needs further identification.     

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19

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Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis

ObjectivesHydroxychloroquine/chloroquine has been widely used as part of the standard treatment for patients with coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to determine whether hydroxychloroquine/chloroquine increases the risk of acute kidney injury (AKI) in COVID-19 patients.MethodsPubMed and Embase were searched for related publications from inception to Dec 31, 2021, including randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing the risk of AKI and/or increased creatinine in COVID-19 patients receiving hydroxychloroquine/chloroquine and other controls (active treatment and placebo). We conducted separate meta-analyses for RCTs and NRSIs based on fixed-effect model, with odds ratios (ORs) being considered as effect sizes.ResultsWe included 21 studies in the analysis, with 12 were RCTs. Based on the RCTs, compared to placebo, the OR was 1.19 (95% confidence interval [CI]: 0.86, 1.64; p = .30, n = 4, moderate quality) for AKI and 1.00 (95%CI: 0.64, 1.56; p = .99, n = 5, moderate quality) for increased creatinine for patients received hydroxychloroquine/chloroquine treatment; compared to active treatment, the odds was 1.28 (95%CI: 0.65, 2.53; p = .47, n = 2, low quality) for AKI and 0.64 (95%CI: 0.13, 3.20; p = .59, n = 1, low quality) for increased creatine. Evidence from NRSIs showed slightly increased odds of AKI, with low quality.ConclusionBased on current available studies which were graded as low to moderate quality, there is insufficient evidence to conclude that hydroxychloroquine/chloroquine use is associated with increased risk of AKI or raised creatinine. Abbreviations: AKI: acute kidney injury; COVID-19: Coronavirus Disease 2019; RCT: randomized controlled trials; NRSI: non-randomized studies of interventions; OR: odds ratios; ROBIS-I: Risk Of Bias In Non-randomized Studies – of Interventions     

Risk factors for the prognosis of acute kidney injury under the Acute Kidney Injury Network definition: a retrospective, multicenter study in critically ill patients

Aim: Despite significant advances in medical management and therapeutics, acute kidney injury (AKI) is still a common and serious complication with high morbidity and mortality in hospitalized patients, especially in patients admitted to the intensive care unit (ICU). The primary purpose of this study is to apply the definition proposed by the Acute Kidney Injury Network (AKIN) to investigate the incidence, 28‐day mortality and risk factors for the prognosis of AKI in ICU. Methods: In this retrospective study, data from a cohort of 4642 patients admitted to five ICUs were analyzed. Univariate and multivariate analyses were performed to investigate the risk factors for prognosis of AKI. Results: A total of 1036 patients were enrolled. AKI occurred in 353 of them (34.1%) under the AKIN criteria and the mortality was 54.4%. Multivariable analysis showed that variables related to the prognosis of AKI were: four or more (≥4) organ failed systems (odds ratio (OR) = 25.612), AKI III (OR = 14.441), AKI II (OR = 4.491), mechanical ventilation (OR = 7.201), sepsis (OR = 4.552), severe acute pancreatitis (OR = 3.299), base serum creatinine (OR = 1.004) and the length of stay in ICU (OR = 1.050). Conclusions: For critically ill patient, the ICU mortality of AKI was correlated with various independent risk factors, especially AKI II, AKI III, severe acute pancreatitis and multiple organ failed systems.     

AKI in Hospitalized Patients with COVID-19

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Hypophosphatemia is an independent risk factor for AKI among hospitalized patients with COVID-19 infection

BackgroundThis study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19.MethodsIn 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.ResultsIn 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.ConclusionThe 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.     

The role of kidney injury biomarkers in COVID-19

The coronavirus disease-2019 (COVID-19) outbreak has been declared a global pandemic. COVID-19-associated acute kidney injury (COVID-19 AKI) is related to a high mortality rate and serves as an independent risk factor for hospital death in patients with COVID-19. Early diagnosis would allow for earlier intervention and potentially improve patient outcomes. The goal of early identification of AKI has been the primary impetus for AKI biomarker research, and several kidney injury biomarkers have been demonstrated to be beneficial in predicting COVID-19 AKI as well as disease progression in COVID-19. Furthermore, such data provide valuable insights into the molecular mechanisms underlying this complex and unique disease and serve as a molecular phenotyping tool that could be utilized to direct clinical intervention. This review focuses on a number of kidney injury biomarkers, such as CysC, NAGAL, KIM-1, L-FABP, IL-18, suPAR, and [TIMP-2] • [IGFBP7], which have been widely studied in common clinical settings, such as sepsis, cardiac surgery, and contrast-induced AKI. We explore the role of kidney injury biomarkers in COVID-19 and discuss what remains to be learned.     

Outcomes from intensive care in patients with COVID-19: a systematic review and meta-analysis of observational studies

The emergence of coronavirus disease 2019 (COVID-19) has led to high demand for intensive care services worldwide. However, the mortality of patients admitted to the intensive care unit (ICU) with COVID-19 is unclear. Here, we perform a systematic review and meta-analysis, in line with PRISMA guidelines, to assess the reported ICU mortality for patients with confirmed COVID-19. We searched MEDLINE, EMBASE, PubMed and Cochrane databases up to 31 May 2020 for studies reporting ICU mortality for adult patients admitted with COVID-19. The primary outcome measure was death in intensive care as a proportion of completed ICU admissions, either through discharge from the ICU or death. The definition thus did not include patients still alive on ICU. Twenty-four observational studies including 10,150 patients were identified from centres across Asia, Europe and North America. In-ICU mortality in reported studies ranged from 0 to 84.6%. Seven studies reported outcome data for all patients. In the remaining studies, the proportion of patients discharged from ICU at the point of reporting varied from 24.5 to 97.2%. In patients with completed ICU admissions with COVID-19 infection, combined ICU mortality (95%CI) was 41.6% (34.0–49.7%), I² = 93.2%). Sub-group analysis by continent showed that mortality is broadly consistent across the globe. As the pandemic has progressed, the reported mortality rates have fallen from above 50% to close to 40%. The in-ICU mortality from COVID-19 is higher than usually seen in ICU admissions with other viral pneumonias. Importantly, the mortality from completed episodes of ICU differs considerably from the crude mortality rates in some early reports.     

Incidence and risk factors of acute kidney injury in COVID-19 patients with and without acute respiratory distress syndrome (ARDS) during the first wave of COVID-19: a systematic review and Meta-Analysis

BackgroundAcute kidney injury (AKI) is common among patients with COVID-19. However, AKI incidence may increase when COVID-19 patients develop acute respiratory distress syndrome (ARDS). Thus, this systematic review and meta-analysis aimed to assess the incidence and risk factors of AKI, need for kidney replacement therapy (KRT), and mortality rate among COVID-19 patients with and without ARDS from the first wave of COVID-19.MethodsThe databases MEDLINE and EMBASE were searched using relevant keywords. Only articles available in English published between December 1, 2019, and November 1, 2020, were included. Studies that included AKI in COVID-19 patients with or without ARDS were included. Meta-analyses were conducted using random-effects models.ResultsOut of 618 studies identified and screened, 31 studies met the inclusion criteria. A total of 27,500 patients with confirmed COVID-19 were included. The overall incidence of AKI in patients with COVID-19 was 26% (95% CI 19% to 33%). The incidence of AKI was significantly higher among COVID-19 patients with ARDS than COVID-19 patients without ARDS (59% vs. 6%, p < 0.001). Comparing ARDS with non-ARDS COVID-19 cohorts, the need for KRT was also higher in ARDS cohorts (20% vs. 1%). The mortality among COVID-19 patients with AKI was significantly higher (Risk ratio = 4.46; 95% CI 3.31–6; p < 0.00001) than patients without AKI.ConclusionThis study shows that ARDS development in COVID-19-patients leads to a higher incidence of AKI and increased mortality rate. Therefore, healthcare providers should be aware of kidney dysfunction, especially among elderly patients with multiple comorbidities. Early kidney function assessment and treatments are vital in COVID-19 patients with ARDS.     

The association between the duration of postoperative acute kidney injury and in-hospital mortality in critically ill patients after non-cardiac surgery: an observational cohort study

Abstract

Objectives: The severity of acute kidney injury (AKI) has been a well-known predictor for in-hospital mortality. Whether AKI duration could predict in-hospital mortality is not clear. This study determines the association between the in-hospital mortality and AKI duration in patients after non-cardiac surgery. Materials and methods: Surgical patients who were admitted to the ICU were enrolled. AKI cases were defined using KDIGO guidelines and categorized according to the tertiles of AKI duration (1st tertile: 2 days, 2nd tertile: 3–6 days and 3rd tertile: 7 days). The adjusted hazard ratios (HRs) for in-hospital mortality are compared to those without AKI. The predictability of mortality is accessed by calculating the area under the curve (AUC) for the receiver operating characteristic (ROC) curve. Results: From a total of 318 postoperative patients, 98 developed AKI (1st tertile: 34 cases, 2nd tertile: 30 cases and 3rd tertile: 34 cases) and 220 had no AKI. The in-hospital mortality rates are 6.8% (non-AKI), 50% (1st tertile), 46.7% (2nd tertile) and 47% (3rd tertile). The HR’s for in-hospital mortality are 7.92, 6.68 and 1.68, compared to the non-AKI group (p?=?0.006, 0.021 and 0.476). Cumulative in-hospital survival rates are significantly different for the non-AKI group and the AKI groups (p?<?0.001). The AUC for AKI duration and stage together (0.804) is higher than that for AKI stage and AKI duration alone (0.803 and 0.777) (both ps?<?0.001). Conclusion: In addition to severity, the duration of AKI may be a predictor of in-hospital mortality in patients, after non-cardiac surgery.     

Outcomes Among Patients Hospitalized With COVID-19 and Acute Kidney Injury

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A prospective cohort study of acute kidney injury and kidney outcomes,cardiovascular events,and death

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