Parental recovered acute kidney injury causes prenatal renal dysfunction and fetal growth restriction with sexually dimorphic implications for adult offspring.

Introduction: Acute kidney injury (AKI) is rapidly increasing in global incidence and a healthcare burden. Prior maternal AKI diagnosis correlates with later pregnancy complications. As pregnancy influences developmental programming, we hypothesized that recovered parental AKI results in poor pregnancy outcomes, impaired fetal growth, and adult offspring disease. Methods: Using a well-characterized model of rhabdomyolysis-induced acute kidney injury (RIAKI), a form of AKI commonly observed in young people, we confirmed functional renal recovery by assessing glomerular filtration rate (GFR) 2 weeks following RIAKI. We bred sham and recovered RIAKI sires and dams in timed, matched matings for gestational day (GD) 16.5 and offspring (birth-12 weeks, 6 months) study. Results: Despite a normal GFR pre-pregnancy, recovered RIAKI dams at GD16.5 had impaired renal function, resulting in reduced fetoplacental ratios and offspring survival. Pregnant RIAKI dams also had albuminuria and less renal megalin in the proximal tubule brush border than shams, with renal subcapsular fibrosis and higher diastolic blood pressure. Growth-restricted offspring had a reduced GFR as older adults, with evidence of metabolic inefficiency in male offspring; this correlated with reduced renal AngII levels in female offspring from recovered RIAKI pairings. However, the blood pressures of 6-month-old offspring were unaffected by parental RIAKI. Conclusions: Our mouse model demonstrated a causal relationship among RIAKI, gestational risk, and developmental programming of the adult-onset offspring GFR and metabolic dysregulation despite parental recovery.

Legal Performance-enhancing Drugs Alter Course and Treatment of Rhabdomyolysis-induced Acute Kidney Injury.

INTRODUCTION: Rhabdomyolysis-induced acute kidney injury (RIAKI) can interrupt physical training and increase mortality in injured warfighters. The legal performance-enhancing drugs caffeine and ibuprofen, which can cause renal injury, are widely used by service members. Whether caffeine or ibuprofen affects RIAKI is unknown. Cilastatin treatment was recently identified as an experimental treatment to prevent RIAKI at injury. To determine potential interacting factors in RIAKI treatment, we test the hypothesis that caffeine and ibuprofen worsen RIAKI and interfere with treatment. MATERIALS AND METHODS: In mice, RIAKI was induced by glycerol intramuscular injection. Simultaneously, mice received caffeine (3 mg/kg), ibuprofen (10 mg/kg), or vehicle. A second cohort received volume resuscitation (PlasmaLyte, 20 mL/kg) in addition to caffeine or ibuprofen. In a third cohort, cilastatin (200 mg/kg) was administered concurrently with drug and glycerol administration. Glomerular filtration rate (GFR), blood urea nitrogen (BUN), urine output (UOP), renal pathology, and renal immunofluorescence for kidney injury molecule 1 were quantified after 24 hours. RESULTS: Caffeine did not worsen RIAKI; although BUN was modestly increased by caffeine administration, 24-hour GFR, UOP, and renal histopathology were similar between vehicle-treated, caffeine-treated, and caffeine + PlasmaLyte-treated mice. Ibuprofen administration greatly worsened RIAKI (GFR 14.3 ± 19.5 vs. 577.4 ± 454.6 µL/min/100 g in control, UOP 0.5 ± 0.4 in ibuprofen-treated mice vs. 2.7 ± 1.7 mL/24 h in control, and BUN 264 ± 201 in ibuprofen-treated mice vs. 66 ± 21 mg/dL in control, P < .05 for all); PlasmaLyte treatment did not reverse this effect. Cilastatin with or without PlasmaLyte did not reverse the deleterious effect of ibuprofen in RIAKI. CONCLUSIONS: Caffeine does not worsen RIAKI. The widely used performance-enhancing drug ibuprofen greatly worsens RIAKI in mice. Standard or experimental treatment of RIAKI including the addition of cilastatin to standard resuscitation is ineffective in mice with RIAKI exacerbated by ibuprofen. These findings may have clinical implications for the current therapy of RIAKI and for translational studies of novel treatment.

Molecular Mechanisms of Rhabdomyolysis-Induced Kidney Injury: From Bench to Bedside.

Rhabdomyolysis-induced acute kidney injury (RIAKI) occurs following damage to the muscular sarcolemma sheath, resulting in the leakage of myoglobin and other metabolites that cause kidney damage. Currently, the sole recommended clinical treatment for RIAKI is aggressive fluid resuscitation, but other potential therapies, including pretreatments for those at risk for developing RIAKI, are under investigation. This review outlines the mechanisms and clinical significance of RIAKI, investigational treatments and their specific targets, and the status of ongoing research trials.

Harm! foul! How acute kidney injury SHReDDs patient futures.

PURPOSE OF REVIEW: Transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is increasingly accepted. Less well recognized, but supported by very similar data, is development of disease of other organ systems after AKI. Awareness of other-organ sequelae of AKI may inform efforts to improve the care of patients after AKI. RECENT FINDINGS: Stroke, hypertension, reproductive risk, dementia, and death (SHReDD) are sequelae, which occur with increased risk relative to that of non-AKI within 6 months-3 years after AKI diagnosis, and which are supported by preclinical/mechanistic study. Adjusted hazard ratios for these sequelae are strikingly similar to that of AKI-CKD, ranging from 1.2 to 3.0. Mechanistic studies suggest kidney-centric mechanisms including sodium regulation, volume status regulation, and the renin-angiotensin system are drivers of long-term, extra-renal, change. SUMMARY: Further clinical characterization and mechanistic insight is necessary, and may have considerable translational impact. Programs which screen or follow post-AKI patients may increase clinical utility if focus is expanded to include the SHReDD complications.

Experimental models of acute kidney injury for translational research.

Preclinical models of human disease provide powerful tools for therapeutic discovery but have limitations. This problem is especially apparent in the field of acute kidney injury (AKI), in which clinical trial failures have been attributed to inaccurate modelling performed largely in rodents. Multidisciplinary efforts such as the Kidney Precision Medicine Project are now starting to identify molecular subtypes of human AKI. In addition, over the past decade, there have been developments in human pluripotent stem cell-derived kidney organoids as well as zebrafish, rodent and large animal models of AKI. These organoid and AKI models are being deployed at different stages of preclinical therapeutic development. However, the traditionally siloed, preclinical investigator-driven approaches that have been used to evaluate AKI therapeutics to date rarely account for the limitations of the model systems used and have given rise to false expectations of clinical efficacy in patients with different AKI pathophysiologies. To address this problem, there is a need to develop more flexible and integrated approaches, involving teams of investigators with expertise in a range of different model systems, working closely with clinical investigators, to develop robust preclinical evidence to support more focused interventions in patients with AKI.

Renal injury in cardiorenal syndrome type 1 is mediated by albumin.

Cardiorenal syndrome type 1 (CRS-1) acute kidney injury (AKI) is a critical complication of acute cardiovascular disease but is poorly understood. AKI induces acute albuminuria. As chronic albuminuria is associated with worsening kidney disease and albumin has been implicated in tubular epithelial injury, we investigated whether albumin participates in CRS-1, and whether CRS-1 alters renal albumin handling. We report the role of albumin in in vivo and in vitro CRS-1 models. An established translational model, cardiac arrest and cardiopulmonary resuscitation (CA/CPR) induced severe acute albuminuria which correlated with tubular epithelial cell death. In vivo microscopy demonstrated CA/CPR-induced glomerular filtration of exogenous albumin, while administration of exogenous albumin after CA/CPR worsened AKI compared to iso-oncotic control. Increased albumin signal was observed in the proximal tubules of CA/CPR mice compared to sham. Comparison of albumin flux from tubular lumen to epithelial cells revealed saturated albumin transport within minutes of albumin injection after CA/CPR. In vitro, HK2 cells (human kidney tubular epithelial cells), exposed to oxygen-glucose deprivation were injured by albumin in a dose dependent fashion. This interference was unchanged by the tubular endocytic receptor megalin. In conclusion, CRS-1 alters albumin filtration and tubular uptake, leading to increased tubular exposure to albumin, which is injurious to tubular epithelial cells, worsening AKI. Our findings shed light on the pathophysiology of renal albumin and may guide interventions such as albumin resuscitation to improve CRS-1 outcomes. This investigation may have important translational relevance for patients that receive exogenous albumin as part of their CRS-1 treatment regimen.

Soluble ACE2 Is Filtered into the Urine.

Background: ACE2 is a key enzyme in the renin-angiotensin system (RAS) capable of balancing the RAS by metabolizing angiotensin II (AngII). First described in cardiac tissue, abundance of ACE2 is highest in the kidney, and it is also expressed in several extrarenal tissues. Previously, we reported an association between enhanced susceptibility to hypertension and elevated renal AngII levels in global ACE2-knockout mice. Methods: To examine the effect of ACE2 expressed in the kidney, relative to extrarenal expression, on the development of hypertension, we used a kidney crosstransplantation strategy with ACE2-KO and WT mice. In this model, both native kidneys are removed and renal function is provided entirely by the transplanted kidney, such that four experimental groups with restricted ACE2 expression are generated: WT→WT (WT), KO→WT (KidneyKO), WT→KO (SystemicKO), and KO→KO (TotalKO). Additionally, we used nanoscale mass spectrometry-based proteomics to identify ACE2 fragments in early glomerular filtrate of mice. Results: Although significant differences in BP were not detected, a major finding of our study is that shed or soluble ACE2 (sACE2) was present in urine of KidneyKO mice that lack renal ACE2 expression. Detection of sACE2 in the urine of KidneyKO mice during AngII-mediated hypertension suggests that sACE2 originating from extrarenal tissues can reach the kidney and be excreted in urine. To confirm glomerular filtration of ACE2, we used micropuncture and nanoscale proteomics to detect peptides derived from ACE2 in the Bowman's space. Conclusions: Our findings suggest that both systemic and renal tissues may contribute to sACE2 in urine, identifying the kidney as a major site for ACE2 actions. Moreover, filtration of sACE2 into the lumen of the nephron may contribute to the pathophysiology of kidney diseases characterized by disruption of the glomerular filtration barrier.

Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice.

BACKGROUND: Rhabdomyolysis, the destruction of skeletal muscle, is a significant cause of AKI and death in the context of natural disaster and armed conflict. Rhabdomyolysis may also initiate CKD. Development of specific pharmacologic therapy is desirable because supportive care is nearly impossible in austere environments. Myoglobin, the principal cause of rhabdomyolysis-related AKI, undergoes megalin-mediated endocytosis in proximal tubule cells, a process that specifically injures these cells. METHODS: To investigate whether megalin is protective in a mouse model of rhabdomyolysis-induced AKI, we used male C57BL/6 mice and mice (14-32 weeks old) with proximal tubule-specific deletion of megalin. We used a well-characterized rhabdomyolysis model, injection of 50% glycerol in normal saline preceded by water deprivation. RESULTS: Inducible proximal tubule-specific deletion of megalin was highly protective in this mouse model of rhabdomyolysis-induced AKI. The megalin knockout mice demonstrated preserved GFR, reduced proximal tubule injury (as indicated by kidney injury molecule-1), and reduced renal apoptosis 24 hours after injury. These effects were accompanied by increased urinary myoglobin clearance. Unlike littermate controls, the megalin-deficient mice also did not develop progressive GFR decline and persistent new proteinuria. Administration of the pharmacologic megalin inhibitor cilastatin to wild-type mice recapitulated the renoprotective effects of megalin deletion. This cilastatin-mediated renoprotective effect was dependent on megalin. Cilastatin administration caused selective proteinuria and inhibition of tubular myoglobin uptake similar to that caused by megalin deletion. CONCLUSIONS: We conclude that megalin plays a critical role in rhabdomyolysis-induced AKI, and megalin interference and inhibition ameliorate rhabdomyolysis-induced AKI. Further investigation of megalin inhibition may inform translational investigation of a novel potential therapy.

Critical care and ventilatory management of deceased organ donors impact lung use and recipient graft survival.

Current risk-adjusted models for donor lung use and lung graft survival do not include donor critical care data. We sought to identify modifiable donor physiologic and mechanical ventilation parameters that predict donor lung use and lung graft survival. This is a prospective observational study of donors after brain death (DBDs) managed by 19 Organ Procurement Organizations from 2016 to 2019. Demographics, mechanical ventilation parameters, and critical care data were recorded at standardized time points during donor management. The lungs were transplanted from 1811 (30%) of 6052 DBDs. Achieving ≥7 critical care endpoints was a positive predictor of donor lung use. After controlling for recipient factors, donor blood pH positively predicted lung graft survival (OR 1.48 per 0.1 unit increase in pH) and the administration of dopamine during donor management negatively predicted lung graft survival (OR 0.19). Tidal volumes ≤8 ml/kg predicted body weight (OR 0.65), and higher positive end-expiratory pressures (OR 0.91 per cm H2 O) predicted decreased donor lung use without affecting lung graft survival. A randomized clinical trial is needed to inform optimal ventilator management strategies in DBDs.

Meta-analysis of AKI to CKD transition in perioperative patients.

BACKGROUND: Recent research shows AKI increases the risk of incident CKD. We hypothesized that perioperative AKI may confer increased risk of subsequent CKD compared to nonperioperative AKI. METHODS: A MEDLINE search was performed for "AKI, CKD, chronic renal insufficiency, surgery, and perioperative" and related terms yielded 5209 articles. One thousand sixty-five relevant studies were reviewed. One thousand six were excluded because they were review, animal, or pediatric studies. Fifty-nine studies underwent full manuscript review by two independent evaluators. Seventeen met all inclusion criteria and underwent analysis. Two-by-two tables were constructed from AKI +/- and CKD +/- data. The R package metafor was employed to determine odds ratio (OR), and a random-effects model was used to calculate weighted ORs. Leave-1-out, funnel analysis, and structured analysis were used to estimate effects of study heterogeneity and bias. RESULTS: Nonperioperative studies included studies of oncology, percutaneous coronary intervention, and myocardial infarction patients. Perioperative studies comprised patients from cardiac surgery, vascular surgery, and burns. There was significant heterogeneity, but risk of bias was overall assessed as low. The OR for AKI versus non-AKI patients developing CKD in all studies was 4.31 (95% CI 3.01-6.17; p < 0.01). Nonperioperative subjects demonstrated OR 3.32 for developing CKD compared to non-AKI patients (95% CI 2.06-5.34; p < 0.01) while perioperative patients demonstrated OR 5.20 (95% CI 3.12-8.66; p < 0.01) for the same event. CONCLUSIONS: We conclude that studies conducted in perioperative and nonperioperative patient populations suggest similar risk of development of CKD after AKI.

The CAT-1 is out of the bag: endothelial Cationic Amino Acid Transporter-1 is a critical player in cardiorenal syndrome type 2.

Although the numbers of patients affected by cardiorenal syndrome keeps increasing, we lack a complete understanding of the molecular pathways involved in its development and progression. Nitric oxide synthase (NOS) may play a role in cardiorenal syndrome, particularly cardiorenal syndrome type 2 (CRS2). However, complexities and paradoxical clinical findings have limited translation. In the current Clinical Science, Giam et al. (Clinical Science (2020) 134, 2755-2769) highlight the role of a key NOS substrate transporter, the cationic amino acid transporter-1, in preserving renal function in CRS2. In this commentary, we introduce the cardiorenal syndrome and the putative role that nitric oxide (NO) may play in the development of this disease and discuss the exciting findings of Giam et al. (Clinical Science (2020) 134, 2755-2769) and their tantalizing translational implications.

Acute Cardiorenal Syndrome: Models and Heart-Kidney Connectors.

Cardiorenal syndrome type 1 (CRS-1) is an acute kidney injury (AKI) due to acute worsening of cardiac function. More than 20% of patients with acute heart failure develop AKI, and AKI predicts poor outcome. Although a number of potential pathways have been suggested as heart-kidney connectors which might drive the syndrome, there are significant barriers to investigation, such as a paucity of animal models, a lack of specific biomarkers, and an inconsistent temporal and causal relationship between changes in cardiac flow and development of renal dysfunction. Thus, mechanisms of heart-kidney interaction are still unclear, and there is no specific or effective therapy for CRS-1. This review, therefore, focuses on mitigating these challenges in the investigation of CRS-1. We review the available models and focus on mechanistic insights gained from those models. In particular, we focus on non-flow and endocrine mediators of CRS-1 such as heart-derived messengers which alter renal function and which may represent targetable pathways in this syndrome. As precise connectors of heart-kidney interaction remain unclear, the establishment of animal and relevant cell-culture models and further investigation are required.

Vasopressor selection during critical care management of brain dead organ donors and the effects on kidney graft function.

BACKGROUND: Delayed graft function (DGF), the need for dialysis in the first week following kidney transplant, affects approximately one quarter of deceased-donor kidney transplant recipients. Donor demographics, donor serum creatinine, and graft cold ischemia time are associated with DGF. However, there is no consensus on the optimal management of hemodynamic instability in organ donors after brain death (DBDs). Our objective was to determine the relationship between vasopressor selection during donor management and the development of DGF. METHODS: Prospective observational data, including demographic and critical care parameters, were collected for all DBDs managed by 17 organ procurement organizations from nine Organ Procurement and Transplantation Network Regions between 2012 and 2018. Recipient outcome data were linked with donor data through donor identification numbers. Donor critical care parameters, including type of vasopressor and doses, were recorded at three standardized time points during donor management. The analysis included only donors who received at least one vasopressor at all three time points. Vasopressor doses were converted to norepinephrine equivalent doses and analyzed as continuous variables. Univariate analyses were conducted to determine the association between donor variables and DGF. Results were adjusted for known predictors of DGF using binary logistic regression. RESULTS: Complete data were available for 5,554 kidney transplant recipients and 2,985 DBDs. On univariate analysis, donor serum creatinine, donor age, donor subtype, kidney donor profile index, graft cold ischemia time, phenylephrine dose, and dopamine dose were associated with DGF. After multivariable analysis, increased donor serum creatinine, donor age, kidney donor profile index, graft cold ischemia time, and phenylephrine dose remained independent predictors of DGF. CONCLUSION: Higher doses of phenylephrine were an independent predictor of DGF. With the exception of phenylephrine, the selection and dose of vasopressor during donor management did not predict the development of DGF. LEVEL OF EVIDENCE: Prognostic study, Level III.

The acute kidney injury to chronic kidney disease transition in a mouse model of acute cardiorenal syndrome emphasizes the role of inflammation.

Acute cardiorenal syndrome is a common complication of acute cardiovascular disease. Studies of acute kidney injury (AKI) to chronic kidney disease (CKD) transition, including patients suffering acute cardiovascular disease, report high rates of CKD development. Therefore, acute cardiorenal syndrome associates with CKD, but no study has established causation. To define this we used a murine cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) model or sham procedure on male mice. CA was induced with potassium chloride while CPR consisted of chest compressions and epinephrine eight minutes later. Two weeks after AKI was induced by CA/CPR, the measured glomerular filtration rate (GFR) was not different from sham. However, after seven weeks the mice developed CKD, recapitulating clinical observations. One day, and one, two, and seven weeks after CA/CPR, the GFR was measured, and renal tissue sections were evaluated for various indices of injury and inflammation. One day after CA/CPR, acute cardiorenal syndrome was indicated by a significant reduction of the mean GFR (649 in sham, vs. 25 µL/min/100g in CA/CPR animals), KIM-1 positive tubules, and acute tubular necrosis. Renal inflammation developed, with F4/80 positive and CD3-positive cells infiltrating the kidney one day and one week after CA/CPR, respectively. Although there was functional recovery with normalization of GFR two weeks after CA/CPR, deposition of tubulointerstitial matrix proteins α-smooth muscle actin and fibrillin-1 progressed, along with a significantly reduced mean GFR (623 in sham vs. 409 µL/min/100g in CA/CPR animals), proteinuria, increased tissue transforming growth factor-ß, and fibrosis establishing the development of CKD seven weeks after CA/CPR. Thus, murine CA/CPR, a model of acute cardiorenal syndrome, causes an AKI-CKD transition likely due to prolonged renal inflammation.

Renal clearable nanochelators for iron overload therapy.

Iron chelators have been widely used to remove excess toxic iron from patients with secondary iron overload. However, small molecule-based iron chelators can cause adverse side effects such as infection, gastrointestinal bleeding, kidney failure, and liver fibrosis. Here we report renal clearable nanochelators for iron overload disorders. First, after a singledose intravenous injection, the nanochelator shows favorable pharmacokinetic properties, such as kidney-specific biodistribution and rapid renal excretion (>80% injected dose in 4 h), compared to native deferoxamine (DFO). Second, subcutaneous (SC) administration of nanochelators improves pharmacodynamics, as evidenced by a 7-fold increase in efficiency of urinary iron excretion compared to intravenous injection. Third, daily SC injections of the nanochelator for 5 days to iron overload mice and rats decrease iron levels in serum and liver. Furthermore, the nanochelator significantly reduces kidney damage caused by iron overload without demonstrating DFO's own nephrotoxicity. This renal clearable nanochelator provides enhanced efficacy and safety.

Glomerular filtrate proteins in acute cardiorenal syndrome.

Acute cardiorenal syndrome (CRS-1) is a morbid complication of acute cardiovascular disease. Heart-to-kidney signals transmitted by "cardiorenal connectors" have been postulated, but investigation into CRS-1 has been limited by technical limitations and a paucity of models. To address these limitations, we developed a translational model of CRS-1, cardiac arrest and cardiopulmonary resuscitation (CA/CPR), and now report findings from nanoscale mass spectrometry proteomic exploration of glomerular filtrate 2 hours after CA/CPR or sham procedure. Filtrate acquisition was confirmed by imaging, molecular weight and charge distribution, and exclusion of protein specific to surrounding cells. Filtration of proteins specific to the heart was detected following CA/CPR and confirmed with mass spectrometry performed using urine collections from mice with deficient tubular endocytosis. Cardiac LIM protein was a CA/CPR-specific filtrate component. Cardiac arrest induced plasma release of cardiac LIM protein in mice and critically ill human cardiac arrest survivors, and administration of recombinant cardiac LIM protein to mice altered renal function. These findings demonstrate that glomerular filtrate is accessible to nanoscale proteomics and elucidate the population of proteins filtered 2 hours after CA/CPR. The identification of cardiac-specific proteins in renal filtrate suggests a novel signaling mechanism in CRS-1. We expect these findings to advance understanding of CRS-1.

Impact of Isolyte Versus 0.9% Saline on Postoperative Event of Acute Kidney Injury Assayed by Urinary [TIMP-2] × [IGFBP7] in Patients Undergoing Cardiac Surgery.

OBJECTIVE: Administration of excess chloride in 0.9% normal saline (NS) decreases renal perfusion and glomerular filtration rate, thereby increasing the risk for acute kidney injury (AKI). In this study, the effect of NS versus Isolyte use during cardiac surgery on urinary levels of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor-binding protein 7 [TIMP-2] × [IGFBP7] and postoperative risk of AKI were examined. DESIGN: Prospective, randomized, and single-blinded trial. SETTING: Single university medical center. PARTICIPANTS: Thirty patients over 18 years without chronic renal insufficiency or recent AKI undergoing elective cardiac surgery. INTERVENTIONS: Subjects were randomized to receive either NS or Isolyte during the intraoperative period. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in urinary levels of [TIMP2] × [IGFBP7] from before surgery to 24 hours postoperatively. Secondary outcomes included serum creatinine pre- and postoperatively at 24 and 48 hours, serum chloride pre- and postoperatively at 24 and 48 hours, need for dialysis prior to discharge, and arterial pH measured 24 hours postoperatively. Sixteen patients received NS and 14 patients received Isolyte. Three patients developed AKI within the first 3 postoperative days, all in the NS group. The authors found increases in [TIMP-2] × [IGFBP7] in both groups. However, the difference in this increase between study arms was not significant (p = 0.92; -0.097 to 0.107). CONCLUSION: The authors observed no change in urinary [TIMP-] × [IGFBP7] levels in patients receiving NS versus Isolyte during cardiac surgery. Future larger studies in patients at higher risk for AKI are recommended to evaluate the impact of high- versus lower-chloride solutions on the risk of postoperative AKI after cardiac surgery.

Right Ventricular Systolic Performance Determined by 2D Speckle-Tracking Echocardiography and Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: An association between central venous pressure and acute kidney injury (AKI) has been observed following cardiac surgery, but it is unknown whether this reflects intravascular volume status or impaired right ventricular (RV) myocardial performance. This study was performed to test the hypothesis that decreased RV peak longitudinal strain (PLSS), as measured by 2-dimensional speckle-tracking echocardiography, is associated with AKI following cardiac surgery. DESIGN: Retrospective observational cohort study. SETTING: Cardiovascular intensive care unit in a 576-bed referral hospital. PARTICIPANTS: Adult patients having undergone cardiac surgery in whom a transthoracic echocardiogram (TTE) was performed within 48 hours after chest closure. INTERVENTIONS: This was a retrospective study. Urine output and serum creatinine values were recorded at baseline and for 48 hours after surgery. Statistical analysis was performed to identify differences in baseline demographic and echo-derived values between patients with and without postoperative AKI criteria. MEASUREMENTS AND MAIN RESULTS: One hundred ninety-nine subjects had postprocessing of TTE performed. AKI was observed in 87% of patients (173 of 199). Age, body mass index, and preoperative serum creatinine were higher in the AKI group. The mean PLSS was -17.2% ± 4.3% versus -17.1% ± 3.7% in patients with AKI versus those without (p = 0.95). The calculated RV systolic pressure was elevated in the AKI group compared to the non-AKI group (38.9 ± 9.9 v 34.6 ± 7.9 mmHg, p = 0.02). CONCLUSION: In this cohort of cardiac surgery patients, speckle-tracking analysis of RV myocardial performance was feasible. Elevated RV systolic pressure associated with AKI, while speckle tracking-derived echocardiography measurements did not.