Erythropoietin in Acute Kidney Injury (EAKI): a Pragmatic Randomized Clinical Trial

Background Treatment with erythropoietin is well established for anemia in chronic kidney disease patients but not well studied in acute kidney injury.MethodsThis is a multicenter, randomized, pragmatic controlled clinical trial. It included 134 hospitalized patients with anemia defined as hemoglobin <11 g/dL and acute kidney injury defined as an increase of serum creatinine of 0.3 mg/dL within 48 hours or 1.5 times baseline. One arm received recombinant human erythropoietin 4000 UI subcutaneously every other day (intervention; n=67) and the second received standard of care (control; n=67) during the hospitalization until discharge or death. The primary outcome was the need for transfusion; secondary outcomes were death, renal recovery, need for dialysis.ResultsThere was no statistically significant difference in transfusion need (RR=1.05, 95%CI 0.65,1.68; p=0.855), in renal recovery full or partial (RR=0.96, 95%CI 0.81,1.15; p=0.671), in need for dialysis (RR=11.00, 95%CI 0.62, 195.08; p=0.102) or in death (RR=1.43, 95%CI 0.58,3.53; p=0.440) between the erythropoietin and the control group. ConclusionsErythropoietin treatment had no impact on transfusions, renal recovery or mortality in acute kidney injury patients with anemia. The trial was registered on ClinicalTrials.gov (NCT03401710, 17/01/2018).

Association of persistent acute kidney injury and renal recovery with mortality in hospitalised patients

ObjectivesAcute kidney injury (AKI) affects up to one-quarter of hospitalised patients and 60% of patients in the intensive care unit (ICU). We aim to understand the baseline characteristics of patients who will develop distinct AKI trajectories, determine the impact of persistent AKI and renal non-recovery on clinical outcomes, resource use, and assess the relative importance of AKI severity, duration and recovery on survival.MethodsIn this retrospective, longitudinal cohort study, 156 699 patients admitted to a quaternary care hospital between January 2012 and August 2019 were staged and classified (no AKI, rapidly reversed AKI, persistent AKI with and without renal recovery). Clinical outcomes, resource use and short-term and long-term survival adjusting for AKI severity were compared among AKI trajectories in all cohort and subcohorts with and without ICU admission.ResultsFifty-eight per cent (31 500/54 212) had AKI that rapidly reversed within 48 hours; among patients with persistent AKI, two-thirds (14 122/22 712) did not have renal recovery by discharge. One-year mortality was significantly higher among patients with persistent AKI (35%, 7856/22 712) than patients with rapidly reversed AKI (15%, 4714/31 500) and no AKI (7%, 22 117/301 466). Persistent AKI without renal recovery was associated with approximately fivefold increased hazard rates compared with no AKI in all cohort and ICU and non-ICU subcohorts, independent of AKI severity.DiscussionAmong hospitalised, ICU and non-ICU patients, persistent AKI and the absence of renal recovery are associated with reduced long-term survival, independent of AKI severity.ConclusionsIt is essential to identify patients at risk of developing persistent AKI and no renal recovery to guide treatment-related decisions.

Short and Long-term Recovery after Moderate/Severe Acute Kidney Injury in patients with and without COVID-19

Introduction: Severe AKI is strongly associated with poor outcomes in COVID-19, but data on renal recovery is lacking. Methods: We retrospectively analyzed these associations in 3,299 hospitalized patients (1,338 with COVID-19 and 1,961 with acute respiratory illness but tested negative for COVID-19). Uni- and multi-variable analyses were used to study mortality and recovery after KDIGO Stage 2&3 AKI and Machine Learning (ML) for predicting AKI and recovery using admission data. Long-term renal function and other outcomes were studied in a sub-group of AKI-2/3 survivors. Results: Among the 172 COVID-19 negative patients with AKI-2/3, 74.4% had partial & 44.2% complete renal recovery, while 11.6% died. Among 255 COVID-19 positive patients with AKI-2/3, lower recovery and higher mortality were noted (50.6% partial, 24.7% complete renal recovery, 23.9% died). On multivariable analysis, ICU admission and ARDS were associated with non-recovery, and recovery was significantly associated with survival in COVID-19 positive patients. With ML, we were able to predict recovery from COVID-19-associated AKI-2/3 with an average precision of 0.62 and the strongest predictors of recovery were initial arterial paO2 & CO2, SCr, K, lymphocyte count, & CPK. At 12 months follow-up, among 52 survivors with AKI-2/3, 25.7% COVID-19 positive and 23.5% COVID-19 negative had incident or progressive CKD. Conclusions: Recovery from COVID-19-associated moderate/severe AKI, can be predicted using admission data and is associated with severity of respiratory disease and in-hospital death. The risk of CKD might be similar between COVID-19 positive and negative patients.

PREDICTORS IN-HOSPITAL MORTALITY OF SEPTIC VS NON-SEPTIC ACUTE KIDNEY INJURY PATIENTS: AN OBSERVATIONAL COHORT STUDY

Background: To compare the predictors In-hospital mortality of patients with septic Acute Kidney Injury (S-AKI) and non-septic AKI (NS-AKI). Methods: a cohort study of critically ill patients with AKI admitted to the emergency room at a tertiary hospital from January to June 2019. The primary outcome was hospital mortality. Results: There were 116 patients who met the inclusion criteria. Compared with NS-AKI, patients with S-AKI had significantly lower mean MAP, median eGFR, and urine output. (UO). S-AKI had higher mortality and vasopressor requirements and had a lower renal recovery than NS-AKI (63.2% vs 31.4%, p=0.001; 30.8% vs 13.7%, p=0.031, and 36.9% vs 60.8%, p=0.011, respectively). AKI stage 3 and vasopressor requirements were dependent risk factors for both S-AKI and NS-AKI mortality. Meanwhile, SOFA score > 7 and the need for dialysis are dependent and independent risk factors for mortality in S-AKI. Worsening and/or persistence in UO, serum urea and creatinine levels at 48 h after admission were predictors of mortality in S-AKI and NS-AKI. Improvement in UO in surviving patients was more pronounced in S-AKI than in NS-AKI (50% vs 17.1%, p=0.007). The surviving S-AKI patients had a longer hospital stay than surviving NS-AKI [8 (6-14.5) vs 5 (4 – 8), p=0.004]. S-AKI have higher mortality and vasopressor requirements and have lower renal recovery than NS-AKI. Conclusion: S-AKI have higher mortality and vasopressor requirements and a lower renal recovery than NS-AKI. Independent predictors of mortality in S-AKI were high SOFA scores and the need for dialysis.

Disease Severity Determines Timing of Initiating Continuous Renal Replacement Therapies: A Systematic Review and Meta-Analysis

Background: Timing of initiating continuous renal replacement therapies (CRRTs) among the patients with acute kidney injury (AKI) in intensive care units (ICU) has been discussed over decades, but the definition of early and late CRRT initiation is still unclear.Methods: The English language randomized controlled trials (RCTs) and cohort studies were searched through MEDLINE, EMBASE, and Cochrane Library on July 19, 2019, by the two researchers independently. The study characteristics; early and late definitions; outcomes, such as all-cause, in-hospital, 28- or 30-, 60-, 90-day mortality; and renal recovery were extracted from the 18 eligible studies. Pooled relative risk ratios (RRs) and 95% CIs were estimated with the fixed effects model and random effects model as appropriate. This study is registered with PROSPERO (CRD 42020158653).Results: Eighteen studies including 3,914 patients showed benefit in earlier CRRT (n = 1,882) over later CRRT (n = 2,032) in all-cause mortality (RR 0.78, 95% CI 0.66–0.92), in-hospital mortality (RR 0.81, 95% CI 0.67–0.99), and 28- or 30-day mortality (RR 0.81, 95% CI 0.74–0.88), but in 60- and 90-day mortalities, no significant benefit was observed. The subgroup analysis showed significant benefit in the disease-severity-based subgroups on early CRRT initiation in terms of in-hospital mortality and 28- or 30-day mortality rather than the time-based subgroups. Moreover, early CRRT was found to have beneficial effects on renal recovery after CRRT (RR 1.21, 95% CI 1.01–1.45).Conclusions: Overall, compared with late CRRT, early CRRT is beneficial for short-term survival and renal recovery, especially when the timing was defined based on the disease severity. CRRT initiation on Acute Kidney Injury Network (AKIN) stage 1 or Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE)-Risk or less may lead to a better prognosis.

Acute kidney injury in patients treated with immune checkpoint inhibitors

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

Platelet Decreases following Continuous Renal Replacement Therapy Initiation as a Novel Risk Factor for Renal Nonrecovery

<b><i>Background:</i></b> Continuous renal replacement therapy (CRRT) is a form of dialysis used in critically ill patients, and has recently been associated with renal nonrecovery. Decreases in platelets following CRRT initiation are common and are associated with mortality, but associations with renal recovery are unclear. Our objective was to determine if platelet nadir or the degree of platelet decrease following CRRT initiation was associated with renal nonrecovery. <b><i>Methods:</i></b> This is a secondary analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) trial. Primary predictors were platelet nadir discretized by median value and percent platelet decrease following CRRT initiation, with cut points evaluated by decile from 30 to 60%. The 2 primary outcomes were time to RRT-independence and RRT-free days. Secondary outcomes were 28-day mortality, 90-day mortality, intensive care unit (ICU)-free, and hospital-free days. <b><i>Results:</i></b> Time to RRT independence censored for death was achieved less frequently in patients with low platelet nadir (hazard ratio [HR] 0.77, confidence interval [CI] 0.66–0.91) and in those with &#x3e;50% platelet decrease (HR 0.84, CI 0.72–0.97). RRT-free days were lower in both low platelet nadir (odds ratio [OR] 0.94, CI 0.90–0.97) and &#x3e;50% platelet decrease (OR 0.91, CI 0.88–0.95). These groups also had higher rates of 28- and 90-day mortality and fewer ICU-free and hospital-free days. Thrombocytopenia at CRRT initiation was also associated with renal nonrecovery, although the clinical effect was small. <b><i>Conclusions:</i></b> Platelet nadir &#x3c;100 × 10³/µL and platelet decrease by &#x3e;50% following CRRT initiation were both associated with lower rates of renal recovery. Further research is needed to evaluate mechanisms-linking platelet changes and renal nonrecovery in CRRT.

Acute kidney injury prevalence, progression and long-term outcomes in critically ill patients with COVID-19: a cohort study

Background There are limited data on acute kidney injury (AKI) progression and long-term outcomes in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to describe the prevalence and risk factors for development of AKI, its subsequent clinical course and AKI progression, as well as renal recovery or dialysis dependence and survival in this group of patients. Methods This was a retrospective observational study in an expanded tertiary care intensive care unit in London, United Kingdom. Critically ill patients admitted to ICU between 1st March 2020 and 31st July 2020 with confirmed SARS-COV2 infection were included. Analysis of baseline characteristics, organ support, COVID-19 associated therapies and their association with mortality and outcomes at 90 days was performed. Results Of 313 patients (70% male, mean age 54.5 ± 13.9 years), 240 (76.7%) developed AKI within 14 days after ICU admission: 63 (20.1%) stage 1, 41 (13.1%) stage 2, 136 (43.5%) stage 3. 113 (36.1%) patients presented with AKI on ICU admission. Progression to AKI stage 2/3 occurred in 36%. Risk factors for AKI progression were mechanical ventilation [HR (hazard ratio) 4.11; 95% confidence interval (CI) 1.61–10.49] and positive fluid balance [HR 1.21 (95% CI 1.11–1.31)], while steroid therapy was associated with a reduction in AKI progression (HR 0.73 [95% CI 0.55–0.97]). Kidney replacement therapy (KRT) was initiated in 31.9%. AKI patients had a higher 90-day mortality than non-AKI patients (34% vs. 14%; p < 0.001). Dialysis dependence was 5% at hospital discharge and 4% at 90 days. Renal recovery was identified in 81.6% of survivors at discharge and in 90.9% at 90 days. At 3 months, 16% of all AKI survivors had chronic kidney disease (CKD); among those without renal recovery, the CKD incidence was 44%. Conclusions During the first COVID-19 wave, AKI was highly prevalent among severely ill COVID-19 patients with a third progressing to severe AKI requiring KRT. The risk of developing CKD was high. This study identifies factors modifying AKI progression, including a potentially protective effect of steroid therapy. Recognition of risk factors and monitoring of renal function post-discharge might help guide future practice and follow-up management strategies. Trial registration NCT04445259