Acute Kidney Injury Recovery Research Articles

Assessment of Acute Kidney Injury and Longitudinal Kidney Function After Hospital Discharge Among Patients With and Without COVID-19

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. 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. 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. Diagnosis of COVID-19. 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. 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). 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.

Emerging roles for lymphatics in acute kidney injury: Beneficial or maleficent?

Acute kidney injury, a sudden decline in renal filtration, is a surprisingly common pathology resulting from ischemic events, local or systemic infection, or drug-induced toxicity in the kidney. Unchecked, acute kidney injury can progress to renal failure and even recovered acute kidney injury patients are at an increased risk for developing future chronic kidney disease. The initial extent of inflammation, the specific immune response, and how well inflammation resolves are likely determinants in acute kidney injury-to-chronic kidney disease progression. Lymphatic vessels and their roles in fluid, solute, antigen, and immune cell transport make them likely to have a role in the acute kidney injury response. Lymphatics have proven to be an attractive target in regulating inflammation and immunomodulation in other pathologies: might these strategies be employed in acute kidney injury? Acute kidney injury studies have identified elevated levels of lymphangiogenic ligands following acute kidney injury, with an expansion of the lymphatics in several models post-injury. Manipulating the lymphatics in acute kidney injury, by augmenting or inhibiting their growth or through targeting lymphatic-immune interactions, has met with a range of positive, negative, and sometimes inconclusive results. This minireview briefly summarizes the findings of lymphatic changes and lymphatic roles in the inflammatory response in the kidney following acute kidney injury to discuss whether renal lymphatics are a beneficial, maleficent, or a passive contributor to acute kidney injury recovery.

Effects of transient acute kidney injury, persistent acute kidney injury and acute kidney disease on the long-term renal prognosis after an initial acute kidney injury event.

To clarify the effects of the duration of acute damage and/or loss of renal function following an acute kidney injury event on the renal prognosis after recovery. We retrospectively reviewed data collected between 1995 and 2016 from the Kochi Medical School Hospital. Patients were stratified according to the time required for recovery with fluid therapy (expected to reflect the presence of renal dysfunction): ≤2 days after onset, transient injury group (n = 491); 3 to 7 days after onset, persistent injury group (n = 1076); and ≥ 8 days after onset, acute kidney disease group (n = 1046). The healthy group comprised 1000 randomly selected adult patients without acute kidney injury with at least two creatinine measurement results during the study. Survival time was defined as the time from recovery to a 30% decrease in the estimated glomerular filtration rate (primary endpoint). Kaplan-Meier and Cox proportional hazards analyses were conducted. Event incidence rates were higher for the transient injury, persistent injury and acute kidney disease groups than for the healthy group. Persistent injury and acute kidney disease presented a higher risk of renal function decline than transient injury following recovery. Transient acute kidney injury, persistent acute kidney injury and acute kidney disease resulted in functional decline and rapid chronic kidney disease progression risks despite recovery. Transient acute kidney injury recovery within 2 days could be associated with better long-term prognoses than persistent acute kidney injury and acute kidney disease persisting beyond 2 days.

Kidney Recovery From Acute Kidney Injury After Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis.

Patients with the recovery of kidney function after an episode of acute kidney injury (AKI) have better outcomes compared to those without recovery. The current systematic review is conducted to assess the rates of kidney function recovery among patients with AKI or severe AKI requiring kidney replacement therapy (KRT) within 100 days after hematopoietic stem cell transplant (HSCT).MethodsThe Ovid MEDLINE, EMBASE, and Cochrane databases were systemically searched from database inceptions through August 2019 to identify studies reporting the rates of recovery from AKI after HSCT. The random-effects and generic inverse variance methods of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies.ResultsA total of 458 patients from eight cohort studies with AKI after HSCT were identified. Overall, the pooled estimated rates of AKI recovery among patients with AKI and severe AKI requiring KRT within 100 days were 58% (95%CI: 37%-78%) and 10% (95%CI: 2%-4%), respectively. Among patients with AKI recovery, the pooled estimated rates of complete and partial AKI recovery were 60% (95%CI: 39%-78%) and 29% (95%CI: 10%-61%), respectively. There was no clear correlation between study year and the rate of AKI recovery (p=0.26).ConclusionThe rate of recovery from AKI after HSCT depends on the severity of AKI. While recovery is common, complete recovery is reported in about two-thirds of all AKI patients. The rate of recovery among those with AKI requiring renal replacement therapy (RRT) is substantially lower.

A Prospective Observational Study of Short-term Mortality Indicators in Acute Stroke Patients

Introduction: Stroke is the second leading cause of death worldwide, causing 6.2 million deaths in 2011. There is a lack of uniform consensus regarding the predicting factors for mortality associated with stroke. Aim: To determine the various factors which influence the mortality in acute stroke. Materials and Methods: This was a prospective study conducted between November 2017 to February 2020 at the hospitals attached to Bangalore Medical College and Research Institute, Bangalore, Karnataka, India. All the patients diagnosed with Cerebrovascular Accident (CVA) using neuroimaging of brain within 24 hours of a symptoms were enrolled and followed-up for 28 days. After obtaining informed consent, demographic, clinical, laboratory and radiological data was recorded. Patients were assessed using standardised data sheet containing different variables and treated appropriately for ischaemic and haemorrhagic stroke. Results: The study included 100 patients; 33 died during follow- up. The mean age of the patients was 55.35±15.78 years; there were 54 males and 46 females. Male gender (p-value <0.001), poor Glasgow Coma Scale (GCS) (p-value <0.001), severe neurodeficit (p-value <0.001), raised intracranial pressure (p-value <0.001) and complication like delayed recovery of GCS (p-value <0.001), aspiration pneumonia (p-value<0.001), Acute Kidney Injury (AKI) (p-value <0.001), fever (p-value <0.001), dysphagia (p-value <0.001), bedsore (p-value <0.001) and seizure (p-value <0.001) were the predictors of mortality in acute stroke. Conclusion: The factors like poor GCS, severe neurodeficit, raised intracranial pressure at the time presentation of patient and occurrence of complication like delayed recovery of GCS, aspiration pneumonia, AKI, fever, dysphagia, bedsore and seizure can be used as prognostic marker in acute stroke. Comprehensive neurological care wherever feasible involving neurologist, neurosurgeon, interventional radiologist, physiotherapist which take care of the immediate need and to prevent the long term complication would help to decrease mortality in acute stroke.

Renal involvement in sarcoidosis: histological patterns and prognosis, an Italian survey.

Background:Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI).Methods:This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU.Results:Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15–300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints.Conclusions:sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI.

The Risk Factors and Clinical Outcomes Associated with Acute Kidney Injury in Patients with COVID-19: Data from a Large Cohort in Iran

Introduction: Kidney involvement, ranging from mild hematuria and proteinuria to acute kidney injury (AKI) in patients with coronavirus disease-2019 (COVID-19), is a recent finding with various incidence rates reported among hospitalized patients with COVID-19. Given the various AKI rates and their associated risk factors, lack of AKI recovery in the majority of patients hospitalized with COVID-19, and limited data regarding AKI in patients with COVID-19 in Iran, we aim to investigate the potential risk factors for AKI development and its incidence in patients hospitalized with COVID-19. Methods: In this retrospective cohort study, we enrolled adult patients referred to the Sina Hospital, Iran, from February 20 to May 14, 2020, with either a positive PCR test or a highly susceptible chest computed tomography features consistent with COVID-19 diagnosis. AKI was defined according to the kidney disease improving global outcomes criteria, and patients were stratified based on their AKI staging. We evaluated the risk indicators associated with AKI during hospitalization besides in-hospital outcomes and recovery rate at the time of discharge. Results: We evaluated 516 patients with a mean age of 57.6 ± 16.1 years and a male-to-female ratio of 1.69 who were admitted with the COVID-19 diagnosis. AKI development was observed among 194 (37.6%) patients, comprising 61.9% patients in stage 1, 18.0% in stage 2, and 20.1% in stage 3. Out of all patients, AKI occurred in 58 (11.2%) patients during the hospital course, and 136 (26.3%) patients arrived with AKI upon admission. AKI development was positively associated with all of the in-hospital outcomes, including intensive care unit admissions, need for invasive ventilation, acute respiratory distress syndrome (ARDS), acute cardiac injury, acute liver injury, multiorgan damage, and mortality. Patients with stage 3 AKI showed a significantly higher mortality rate, ARDS, and need for invasive ventilation than other stages. After multivariable analysis, male sex (odds ratio [OR]: 11.27), chronic kidney disease (CKD) (OR: 6.89), history of hypertension (OR: 1.69), disease severity (OR: 2.27), and high urea levels (OR: 1.04) on admission were independent risk indicators of AKI development. Among 117 (28.1%) patients who experienced AKI and survived, only 33 (28.2%) patients made a recovery from the AKI, and 84 (71.8%) patients did not exhibit full recovery at the time of discharge. Discussion/Conclusion: We found that male sex, history of CKD, hypertension, disease severity, and high serum urea were independent risk factors associated with AKI in patients with COVID-19. Also, higher stages of AKI were associated with increased risk of mortality and in-hospital complications. Our results indicate a necessity for more precise care and monitoring for AKI during hospitalization in patients with COVID-19, and lack of AKI recovery at the time of discharge is a common complication in such patients.

1622. Outcomes of Colistin Weight-Based Dosing Versus The Non-Weight-Based Dosing

BackgroundThe use of colistin is currently the mainstay antimicrobial for several multi-drug resistant organisms (MDROs). New guidelines were recently published recommending non-weight-based (NWB) dosing of colistin. There is limited data on outcomes with this new dosing strategy. The purpose of this study was to investigate the outcomes of the new NWB dosing strategy in comparison to the previously used weight-based (WB) dosing strategy.MethodsA retrospective study was conducted at our quaternary care hospital between January 2016 and April 2020. Adults (≥ 18 years), who received intravenous (IV) colistin for ≥ 72 hours were included. Documented clinical cure was the primary endpoint, which was defined as having at least two of the following: normalization of white blood cell count or ≥ 25% reduction, defervescence, hemodynamic stability, normalization of inflammatory markers (C-reactive protein and procalcitonin values) or ≥ 25% reduction, or the resolution of signs and symptoms of infection by the end of the therapy. Secondary outcomes were microbiological cure, incidence of acute kidney injury (AKI), time to AKI, outcomes of AKI, time to AKI recovery, new infection while on IV colistin, recurrence of infection, and all-cause mortality.ResultsA total of 104 primarily male (57.7%) patients with a mean age of 63 ± 20.23 years and weight of 70.24 ± 19.46 kg met the inclusion criteria. At baseline for both groups, the estimated creatinine clearance was 74.23 ± 70.86 mL/min and renal replacement therapy was observed in 34.62%. There was no statistically significant difference observed in clinical cure rate in the WB was 77.03% while 83.33% in the NWB (p-value 0.48). However, a higher rate of AKI was observed in NWB was 84.21% while 53.33% in WB (p-value 0.02). Amongst those who had AKI, NWB had better AKI recovery status with 60.00% while 17.95% in WB (p-value 0.00). A higher all-cause mortality rate was observed in the WB group with 55.41% while 20.00% in NWB (p-value 0.02).ConclusionThe study showed no statistical difference in the primary outcome between the two groups, however, higher AKI rates, AKI recovery and all-cause mortality was observed in non-weight-based dosing when compared to the weight-based dosing. Our data needs to be validated in a larger study.Disclosures All Authors: No reported disclosures

Incidence and Recovery of Acute Kidney Injury in Diabetic and Nondiabetic Patients with Foot Infections.

The aim of this study was to evaluate the incidence and recovery of acute kidney injury (AKI) in patients admitted to the hospital with and without diabetes mellitus (DM) with foot infections. We retrospectively reviewed 294 patients with DM and 88 without DM admitted to the hospital with foot infections. The Kidney Disease: Improving Global Outcomes guidelines were used to define AKI. Recovery was divided into three categories: full, partial, and no recovery within 90 days of the index AKI. The AKI incidence was 3.0 times higher in patients with DM (DM 48.5% versus no DM 23.9%; 95% confidence interval [CI], 1.74-5.19; P < .01). Acute kidney injury incidence was similar at each stage in people with and without DM (stage 1, DM 58.1% versus no DM 47.6%; stage 2, DM 23.3% versus no DM 33.3%, and stage 3, DM 18.6% versus no DM 19.1%). Twenty-nine patients with diabetes had a second AKI event and four had a third event. In patients without DM, one patient had a second AKI. Cumulative AKI incidence was 4.7 times higher in people with DM (DM 60.9% versus no DM 25.0%; 95% CI, 2.72-8.03; P < .01). Patients with diabetes progressed to chronic kidney disease or in chronic kidney disease stage 39.4% of the time. Patients without diabetes progressed 16.7% of the time, but this trend was not significant (P = .07). Complete recovery was 3.8 times more likely in patients without diabetes (95% CI, 1.26-11.16; P = .02). Acute kidney injury incidence is higher in patients with diabetes, and complete recovery after an AKI is less likely compared to patients without diabetes.

New imaging techniques in AKI.

Acute kidney injury (AKI) is a common complication in critically ill patients. Understanding the pathophysiology of AKI is essential to guide patient management. Imaging techniques that inform the pathogenesis of AKI in critically ill patients are urgently needed, in both research and ultimately clinical settings. Renal contrast-enhanced ultrasonography (CEUS) and multiparametric MRI appear to be the most promising imaging techniques for exploring the pathophysiological mechanisms involved in AKI. CEUS and MRI can be used to noninvasively and safely evaluate renal macrocirculation and microcirculation and oxygenation in critical ill patients. These techniques show that a decrease in renal blood flow, particularly cortical blood flow, may be observed in septic AKI and may contribute to its development. MRI may be a valuable method to quantify long-term renal damage after AKI that cannot currently be detected using standard clinical approaches. CEUS and multiparametric renal MRI are promising imaging techniques but more evidence is needed to show how they can first be more widely used in a research setting to test key hypotheses about the pathophysiology and recovery of AKI, and then ultimately be adopted in clinical practice to guide patient management.

Intrarenal oxygenation determines kidney function during the recovery from an ischemic insult.

Acute kidney injury (AKI) is a significant clinical problem associated with poor outcome. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery, and intrarenal hypoxia is a hallmark of AKI and progression to chronic kidney disease. However, the role of intrarenal hypoxia per se in the recovery from an ischemic insult is presently unclear. The present study was designed to investigate 1) the role of systemic hypoxia in the acute progression and recovery of AKI and 2) whether increased intrarenal oxygenation improves recovery from an ischemic insult. Anesthetized male Sprague-Dawley rats were subjected to unilateral warm renal ischemia for 45 min followed by 2 h of reperfusion under systemic hypoxia (10% inspired oxygen), normoxia (21% inspired oxygen), or hyperoxia (60% inspired oxygen). Intrarenal oxygen tension was successfully manipulated by altering the inspired oxygen. Glomerular filtration rate (GFR) before the ischemic insult was independent of intrarenal oxygen tension. GFR during the recovery from the ischemic insult was significantly lower compared with baseline in all groups (3 ± 1%, 13 ± 1%, and 30 ± 11% of baseline for hypoxia, normoxia, and hyperoxia, respectively). However, GFR was significantly higher in hyperoxia than hypoxia (P < 0.05, hypoxia vs. hyperoxia). During recovery, renal blood flow was only reduced in hyperoxia, as a consequence of increased renal vascular resistance. In conclusion, the present study demonstrates that renal function during the recovery from an ischemic insult is dependent on intrarenal oxygen availability, and normobaric hyperoxia treatment has the potential to protect kidney function.

Acute kidney injury is a common complication in children and adolescents hospitalized for diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is associated with dehydration and which can cause acute kidney injury (AKI). The proportion of AKI in children and adolescents with DKA has not been reported in East Asian population. This study aimed to identify the prevalence of AKI and to determine whether there is an association between AKI severity and recovery time from metabolic acidosis in children and adolescents with DKA. Medical records of children and adolescents (aged <18 years) presenting with type 1 or type 2 diabetes mellitus and DKA between 2000–2017 at the MacKay Children’s Hospital were retrospectively reviewed. AKI was defined by an admission creatinine level >1.5 times the calculated expected baseline creatinine level. Patients were divided into three groups based on AKI severity: no AKI, mild AKI, and severe AKI. In total, 170 (56.5%) patients with DKA presented AKI (mild AKI, 116 [38.5%]; severe AKI, 54 [18.0%]). Heart rate and laboratory parameters related to dehydration, such as corrected sodium level and blood urea nitrogen, were strongly associated with AKI development (P<0.01). Blood pH, plasma glucose, and potassium levels were also associated with AKI. A negative correlation with borderline significance between the estimated glomerular filtration rate (eGFR) and recovery time from metabolic acidosis was observed in the severe AKI group. AKI was highly prevalent in children and adolescents with DKA. An association between AKI and biomarkers indicating dehydration was noted. The recovery time from metabolic acidosis following treatment may be longer in children with a decreased eGFR who present with severe AKI. AKI is a common complication in children with DKA.

Implementation of a care bundle for inpatient management of acute kidney injury among gynecologic oncology patients: Lessons learned from a quality improvement project

Objective: The aims of this study were to identify etiologies of acute kidney injury (AKI) occurring in gynecologic oncology patients admitted to the hospital and to determine factors associated with AKI recovery, including adherence to an inpatient AKI care bundle.

Regenerated nephrons in kidney cortices ameliorate exacerbated serum creatinine levels in rats with adriamycin nephropathy

Kidney regeneration could be classified into 2 groups: kidney generation and kidney repair. We have attempted in vivo nephron generation for kidney repair, as a therapy for chronic renal failure (CRF), by exploiting cellular interactions via conditioned media. In the previous report, we demonstrated the generation of rich nephrons in rat intact kidney cortices through percapsular injection of mesenchymal stem cell (MSC)-differentiated tubular epithelial cells (TECs) after pretreatment of 3-dimensional culture using a small amount of gel complex and condensed medium. In this study, to verify the amelioration of serum creatinine (sCr) levels by regenerated nephrons in rats with CRF, we first created damaged kidneys through systemic administration of adriamycin, and implanted the pretreated MSC-differentiated TECs into unilateral kidney cortices 2 weeks after adriamycin administration (A-2W, that is I–0W). After recovery of acute kidney injury, the control rats without cell implantation showed re-exacerbation of sCr levels, resulting in death within A-12W. Alternatively, the cell-implanted rats had a formation of mature nephrons in I–3W, and showed significant amelioration of sCr levels in I–7W. As a result, these rats could live until euthanization in I–12W or I–16W, indicating the utility of cell injection therapy into a kidney (K-CIT) for CRF. We expect that our K-CIT or the refined methods will be applied to patients with CRF.

Acute Kidney Injury in Pediatric Acute Respiratory Distress Syndrome.

To describe the incidence of and risk factors for acute kidney injury (AKI) in children with acute respiratory distress syndrome (ARDS) and study the effect of AKI on patient outcomes. A single-center retrospective study. A tertiary care children's hospital. All patients less than 18 years of age who received invasive mechanical ventilation (MV) and developed ARDS between July 2010 and July 2013 were included. Acute kidney injury was defined using p-RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria. None. One hundred fifteen children met the criteria and were included in the study. Seventy-four children (74/115, 64%) developed AKI. The severity of AKI was risk in 34 (46%) of 74, injury in 19 (26%) of 74, and failure in 21 (28%) of 74. The presence of AKI was associated with lower Pao 2 to Fio 2 (P/F) ratio (P = .007), need for inotropes (P = .003), need for diuretics (P = .004), higher oxygenation index (P = .03), higher positive end-expiratory pressure (PEEP; P = .01), higher mean airway pressure (P = .008), and higher Fio 2 requirement (P = .03). Only PEEP and P/F ratios were significantly associated with AKI in the unadjusted logistic regression model. Patients with AKI had a significantly longer duration of hospital stay, although there was no significant difference in the intensive care unit stay, duration of MV, and mortality. Recovery of AKI occurred in 68% of the patients. A multivariable model including PEEP, P/F ratio, weight, need for inotropes, and need for diuretics had a better receiver operating characteristic (ROC) curve with an AUC of 0.75 compared to the ROC curves for PEEP only and P/F ratio only for the prediction of AKI. Patients with ARDS have high rates of AKI, and its presence is associated with increased morbidity and mortality.

Combined use of GM2AP and TCP1-eta urinary levels predicts recovery from intrinsic acute kidney injury

Deficient recovery from acute kidney injury (AKI) has immediate and long-term health, clinical and economic consequences. Pre-emptive recovery estimation may improve nephrology referral, optimize decision making, enrollment in trials, and provide key information for subsequent clinical handling and follow-up. For this purpose, new biomarkers are needed that predict outcome during the AKI episode. We hypothesized that damage pattern-specific biomarkers are expected to more closely associate to outcome within distinct subpopulations (i.e. those affected by specific pathological processes determining a specific outcome), as biomarker pleiotropy (i.e. associated to phenomena unrelated to AKI) introduced by unselected, heterogeneous populations may blur statistics. A panel of urinary biomarkers was measured in patients with AKI and their capacity to associate to normal or abnormal recovery was studied in the whole cohort or after sub-classification by AKI etiology, namely pre-renal and intrinsic AKI. A combination of urinary GM2AP and TCP1-eta best associates with recovery from AKI, specifically within the sub-population of renal AKI patients. This two-step strategy generates a multidimensional space in which patients with specific characteristics (i.e. renal AKI patients with good or bad prognosis) can be identified based on a collection of biomarkers working serially, applying pathophysiology-driven criteria to estimate AKI recovery, to facilitate pre-emptive and personalized handling.

A pilot trial to evaluate the clinical usefulness of contrast-enhanced ultrasound in predicting renal outcomes in patients with acute kidney injury.

Contrast-enhanced ultrasound (CEUS) enables the assessment of real-time renal microcirculation. This study investigated CEUS-driven parameters as hemodynamic predictors for renal outcomes in patients with acute kidney injury (AKI). Forty-eight patients who were diagnosed with AKI were prospectively enrolled and underwent CEUS at the occurrence of AKI. Parameters measured were the wash-in slope (WIS), time to peak intensity, peak intensity (PI), area under the time-intensity curve (AUC), mean transit time (MTT), time for full width at half maximum, and rise time (RT). The predictive performance of the CEUS-driven parameters for Kidney Disease Improving Global Outcomes (KDIGO) AKI stage, initiation of renal replacement therapy (RRT), AKI recovery, and chronic kidney disease (CKD) progression was assessed. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of CEUS. Cortical RT (Odds ratio [OR] = 1.21) predicted the KDIGO stage 3 AKI. Cortical MTT (OR = 1.07) and RT (OR = 1.20) predicted the initiation of RRT. Cortical WIS (OR = 76.23) and medullary PI (OR = 1.25) predicted AKI recovery. Medullary PI (OR = 0.78) and AUC (OR = 1.00) predicted CKD progression. The areas under the ROC curves showed reasonable performance for predicting the initiation of RRT and AKI recovery. The sensitivity and specificity of the quantitative CEUS parameters were 60-83% and 62-77%, respectively, with an area under the curve of 0.69-0.75. CEUS may be a supplemental tool in diagnosing the severity of AKI and predicting renal prognosis in patients with AKI.

Serum Phosphate Kinetics in Acute Kidney Injury After Cardiac Surgery: An Observational Study

Acute kidney injury (AKI) is a common complication after cardiac surgery and may affect prognosis. Serum phosphate (SPh) elevation is well-known to occur after AKI but not well-documented. The aim of the present study was to describe SPh changes during AKI after cardiac surgery and to assess the accuracy for the diagnosis of AKI severity and recovery. Prospective, single center, observational study. Intensive care unit of a tertiary university hospital. All patients admitted consecutively to the intensive care unit between February 2015 and March 2016. AKI was defined according to Kidney Disease Improving Global Outcomes criteria and classified as nonsevere (stage 1) and severe (stages 2 and 3). Receiver operating characteristic curve analysis was conducted to test reliability of SPh for AKI severity and recovery. AKI occurred in 86 of the 260 patients included (33%) in the study; 58 (67%) experienced nonsevere AKI, and 28 (33%) experienced severe AKI. A significant elevation of SPh values was observed in AKI patients, which peaked at 48 hours. At this time, an SPh of 1.33 mmol/L demonstrated a good accuracy for AKI severity, with an area under the curve of 0.91 (95% confidence interval 0.82-1.00). For kidney recovery, a 25% SPh decrease 24 hours after the peak had a positive predictive value of 100%, and a 2.5% decrease allowed for the reclassification of patients when the serum creatinine had not decreased enough. The results showed that SPh changes closely follow AKI severity and kidney recovery after cardiac surgery. In addition to serum creatinine, this simple biological marker may help predict early favorable outcome.

Association Between Early Recovery of Kidney Function After Acute Kidney Injury and Long-term Clinical Outcomes

The severity of acute kidney injury (AKI) is usually determined based on the maximum serum creatinine concentration. However, the trajectory of kidney function recovery could be an additional important dimension of AKI severity. To assess whether the trajectory of kidney function recovery within 72 hours after AKI is associated with long-term risk of clinical outcomes. This prospective, multicenter cohort study enrolled 1538 adults with or without AKI 3 months after hospital discharge between December 1, 2009, and February 28, 2015. Statistical analyses were completed November 1, 2018. Participants with or without AKI were matched based on demographic characteristics, site, comorbidities, and prehospitalization estimated glomerular filtration rate. Participants with AKI were classified as having resolving or nonresolving AKI based on previously published definitions. Resolving AKI was defined as a decrease in serum creatinine concentration of 0.3 mg/dL or more or 25% or more from maximum in the first 72 hours after AKI diagnosis. Nonresolving AKI was defined as AKI not meeting the definition for resolving AKI. The primary outcome was a composite of major adverse kidney events (MAKE), defined as incident or progressive chronic kidney disease, long-term dialysis, or all-cause death during study follow-up. Among 1538 participants (964 men; mean [SD] age, 64.6 [12.7] years), 769 (50%) had no AKI, 475 (31%) had a resolving AKI pattern, and 294 (19%) had a nonresolving AKI pattern. After a median follow-up of 4.7 years, the outcome of MAKE occurred in 550 (36%) of all participants. The adjusted hazard ratio for MAKE was higher for patients with resolving AKI (adjusted hazard ratio, 1.52; 95% CI, 1.01-2.29; P = .04) and those with nonresolving AKI (adjusted hazard ratio 2.30; 95% CI, 1.52-3.48; P < .001) compared with participants without AKI. Within the population of patients with AKI, nonresolving AKI was associated with a 51% greater risk of MAKE (95% CI, 22%-88%; P < .001) compared with resolving AKI. The higher risk of MAKE among patients with nonresolving AKI was explained by a higher risk of incident and progressive chronic kidney disease. This study suggests that the 72-hour period immediately after AKI distinguishes the risk of clinically important kidney-specific long-term outcomes. The identification of different AKI recovery patterns may improve patient risk stratification, facilitate prognostic enrichment in clinical trials, and enable recognition of patients who may benefit from nephrology consultation.

Defining Early Recovery of Acute Kidney Injury.

Standardized systems for defining and staging AKI predict mortality in a stage-dependent manner. In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO) criteria unified the preceding RIFLE and AKIN classifications ([Figure 1A][1]) ([1][2]). However, AKI remains a syndrome with devastating