Browsing by Subject "Acute kidney injury"
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Item A Randomized Control Trial of Ravulizumab for Treatment of Patients With COVID-19 Infection and Kidney Injury(Elsevier, 2022) Memon, Aliza A.; Ahmed, Hasban; Li, Yi; Wongboonsin, Janewit; Hundert, Joshua; Benoit, Stefanie; Chaudhari, Advika; Sher, Jawad; Ghimire, Pratima; Hopkins, Rebecca; Patel, Jay; Stegman, Melinda; Lim, Kenneth; Azzi, Jamil; Siedlecki, Andrew M.; Medicine, School of MedicineItem Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury(Springer Nature, 2019-09-12) Tang, Chengyuan; Han, Hailong; Liu, Zhiwen; Liu, Yuxue; Yin, Lijun; Cai, Juan; He, Liyu; Liu, Yu; Chen, Guochun; Zhang, Zhuohua; Yin, Xiao-Ming; Dong, Zheng; Pathology and Laboratory Medicine, School of MedicineAcute kidney injury (AKI) is a syndrome of abrupt loss of renal functions. The underlying pathological mechanisms of AKI remain largely unknown. BCL2-interacting protein 3 (BNIP3) has dual functions of regulating cell death and mitophagy, but its pathophysiological role in AKI remains unclear. Here, we demonstrated an increase of BNIP3 expression in cultured renal proximal tubular epithelial cells following oxygen-glucose deprivation-reperfusion (OGD-R) and in renal tubules after renal ischemia-reperfusion (IR)-induced injury in mice. Functionally, silencing Bnip3 by specific short hairpin RNAs in cultured renal tubular cells reduced OGD-R-induced mitophagy, and potentiated OGD-R-induced cell death. In vivo, Bnip3 knockout worsened renal IR injury, as manifested by more severe renal dysfunction and tissue injury. We further showed that Bnip3 knockout reduced mitophagy, which resulted in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and enhanced cell death and inflammatory response in kidneys following renal IR. Taken together, these findings suggest that BNIP3-mediated mitophagy has a critical role in mitochondrial quality control and tubular cell survival during AKI.Item Acute Kidney Injury and Fluid Overload in Pediatric Cardiac Surgery(Springer, 2019-12) Carlisle, Michael A.; Soranno, Danielle E.; Basu, Rajit K.; Gist, Katja M.; Pediatrics, School of MedicinePurpose of review: Acute kidney injury (AKI) and fluid overload affect a large number of children undergoing cardiac surgery, and confers an increased risk for adverse complications and outcomes including death. Survivors of AKI suffer long-term sequelae. The purpose of this narrative review is to discuss the short and long-term impact of cardiac surgery associated AKI and fluid overload, currently available tools for diagnosis and risk stratification, existing management strategies, and future management considerations. Recent findings: Improved risk stratification, diagnostic prediction tools and clinically available early markers of tubular injury have the ability to improve AKI-associated outcomes. One of the major challenges in diagnosing AKI is the diagnostic imprecision in serum creatinine, which is impacted by a variety of factors unrelated to renal disease. In addition, many of the pharmacologic interventions for either AKI prevention or treatment have failed to show any benefit, while peritoneal dialysis catheters, either for passive drainage or prophylactic dialysis may be able to mitigate the detrimental effects of fluid overload. Summary: Until novel risk stratification and diagnostics tools are integrated into routine practice, supportive care will continue to be the mainstay of therapy for those affected by AKI and fluid overload after pediatric cardiac surgery. A viable series of preventative measures can be taken to mitigate the risk and severity of AKI and fluid overload following cardiac surgery, and improve care.Item Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates(American Medical Association, 2023-08-01) Starr, Michelle C.; Griffin, Russell L.; Harer, Matthew W.; Soranno, Danielle E.; Gist, Katja M.; Segar, Jeffrey L.; Menon, Shina; Gordon, Lindsey; Askenazi, David J.; Selewski, David T.; Pediatrics, School of MedicineImportance: Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI. Objective: To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes. Design, setting, and participants: This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022. Exposure: Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]). Main outcomes and measures: The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models. Results: A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64). Conclusions and relevance: In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance.Item Acute kidney injury in critically Ill children and young adults with suspected SARS-CoV2 infection(Springer Nature, 2022-06) Basu, Rajit K.; Bjornstad, Erica C.; Gist, Katja M.; Starr, Michelle; Khandhar, Paras; Chanchlani, Rahul; Krallman, Kelli A.; Zappitelli, Michael; Askenazi, David; Goldstein, Stuart L.; Pediatrics, School of MedicineBackground: We aimed to study the association of suspected versus confirmed infection with the novel SARS-CoV2 virus with the prevalence of acute kidney injury (AKI) in critically ill children. Methods: Sequential point-prevalence study of children and young adults aged 7 days to 25 years admitted to intensive care units under investigation for SARS-CoV2 infection. AKI was staged in the first 14 days of enrollment using KDIGO creatinine-based staging. SARS-CoV2 positive (CONFIRMED) were compared to SUSPECTED (negative or unknown). Outcome data was censored at 28-days. Results: In 331 patients of both sexes, 179 (54.1%) were CONFIRMED, 4.2% (14) died. AKI occurred in 124 (37.5%) and severe AKI occurred in 63 (19.0%). Incidence of AKI in CONFIRMED was 74/179 (41.3%) versus 50/152 (32.9%) for SUSPECTED; severe AKI occurred in 35 (19.6%) of CONFIRMED and 28 (18.4%) of SUSPECTED. Mortality was 6.2% (n = 11) in CONFIRMED, but 9.5% (n = 7) in those CONFIRMED with AKI. On multivariable analysis, only Hispanic ethnicity (relative risk 0.5, 95% CI 0.3-0.9) was associated with less AKI development among those CONFIRMED. Conclusions: AKI and severe AKI occur commonly in critically ill children with SARS-CoV2 infection, more than double the historical standard. Further investigation is needed during this continuing pandemic to describe and refine the understanding of pediatric AKI epidemiology and outcomes. Trial registration: NCT01987921. Impact: What is the key message of the article? AKI occurs in children exposed to the novel SARS-CoV2 virus at high prevalence (~40% with some form of AKI and 20% with severe AKI). What does it add to the existing literature? Acute kidney injury (AKI) occurs commonly in adult patients with SARS-CoV2 (COVID), very little data describes the epidemiology of AKI in children exposed to the virus. What is the impact? A pediatric vaccine is not available; thus, the pandemic is not over for children. Pediatricians will need to manage significant end-organ ramifications of the novel SARS-CoV2 virus including AKI.Item Acute kidney injury in hospitalized children with sickle cell anemia(BMC, 2022-03-18) Batte, Anthony; Menon, Sahit; Ssenkusu, John; Kiguli, Sarah; Kalyesubula, Robert; Lubega, Joseph; Mutebi, Edrisa Ibrahim; Opoka, Robert O.; John, Chandy C.; Starr, Michelle C.; Conroy, Andrea L.; Pediatrics, School of MedicineBackground: Children with sickle cell anemia (SCA) are at increased risk of acute kidney injury (AKI) that may lead to death or chronic kidney disease. This study evaluated AKI prevalence and risk factors in children with SCA hospitalized with a vaso-occlusive crisis (VOC) in a low-resource setting. Further, we evaluated whether modifications to the Kidney Disease: Improving Global Outcomes (KDIGO) definition would influence clinical outcomes of AKI in children with SCA hospitalized with a VOC. Methods: We prospectively enrolled 185 children from 2 - 18 years of age with SCA (Hemoglobin SS) hospitalized with a VOC at a tertiary hospital in Uganda. Kidney function was assessed on admission, 24-48 h of hospitalization, and day 7 or discharge. Creatinine was measured enzymatically using an isotype-dilution mass spectrometry traceable method. AKI was defined using the original-KDIGO definition as ≥ 1.5-fold change in creatinine within seven days or an absolute change of ≥ 0.3 mg/dl within 48 h. The SCA modified-KDIGO (sKDIGO) definition excluded children with a 1.5-fold change in creatinine from 0.2 mg/dL to 0.3 mg/dL. Results: Using KDIGO, 90/185 (48.7%) children had AKI with 61/185 (33.0%) AKI cases present on admission, and 29/124 (23.4%) cases of incident AKI. Overall, 23 children with AKI had a 1.5-fold increase in creatinine from 0.2 mg/dL to 0.3 m/dL. Using the sKDIGO-definition, 67/185 (36.2%) children had AKI with 43/185 (23.2%) cases on admission, and 24/142 (16.9%) cases of incident AKI. The sKDIGO definition, but not the original-KDIGO definition, was associated with increased mortality (0.9% vs. 7.5%, p = 0.024). Using logistic regression, AKI risk factors included age (aOR, 1.10, 95% CI 1.10, 1.20), hypovolemia (aOR, 2.98, 95% CI 1.08, 8.23), tender hepatomegaly (aOR, 2.46, 95% CI 1.05, 5.81), and infection (aOR, 2.63, 95% CI 1.19, 5.81) (p < 0.05). Conclusion: These results demonstrate that AKI is a common complication in children with SCA admitted with VOC. The sKDIGO definition of AKI in children with SCA was a better predictor of clinical outcomes in children. There is need for promotion of targeted interventions to ensure early identification and treatment of AKI in children with SCA.Item Acute Kidney Injury in Neonatal Encephalopathy: An Evaluation of the AWAKEN Database(Springer, 2019-01) Kirkley, Megan J.; Boohaker, Louis; Griffin, Russell; Soranno, Danielle E.; Gien, Jason; Askenazi, David; Gist, Katja M.; Pediatrics, School of MedicineBackground: Acute kidney injury (AKI) is common in neonatal encephalopathy (NE) and is associated with worse outcomes. Our objectives were to determine the incidence, risk factors, and outcomes of AKI in infants with NE. Methods: We performed a retrospective analysis of infants ≥ 34 weeks' gestational age with a diagnosis of NE from the Analysis of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) database. AKI was defined using the modified Kidney Disease Improving Global Outcomes criteria. Perinatal and postnatal factors were evaluated. Multivariate logistic and linear regressions were performed. Results: One hundred and thirteen patients with NE were included. 41.6% (47) developed AKI. Being born outside the admitting institution (OR 4.3; 95% CI 1.2-14.8; p = 0.02), intrauterine growth restriction (OR 10.3, 95% CI 1.1-100.5; p = 0.04), and meconium at delivery (OR 2.8, 95% CI 1.04-7.7; p = 0.04) conferred increased odds of AKI. After controlling for confounders, infants with AKI stayed in the hospital an average of 8.5 days longer than infants without AKI (95% CI 0.79-16.2 days; p = 0.03). Conclusions: In this multi-national analysis, several important perinatal factors were associated with AKI and infants with both NE and AKI had longer length of stay than NE alone. Future research aimed at early AKI detection, renoprotective management strategies, and understanding the long-term renal consequences is warranted in this high-risk group of patients.Item Acute Kidney Injury Interacts With Coma, Acidosis, and Impaired Perfusion to Significantly Increase Risk of Death in Children With Severe Malaria(Oxford University Press, 2022) Namazzi, Ruth; Opoka, Robert; Datta, Dibyadyuti; Bangirana, Paul; Batte, Anthony; Berrens, Zachary; Goings, Michael J.; Schwaderer, Andrew L.; Conroy, Andrea L.; John, Chandy C.; Pediatrics, School of MedicineBackground: Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized. Methods: Between 2014 and 2017, 600 children aged 6-48 months to 4 years hospitalized with severe malaria were enrolled in a prospective clinical cohort study evaluating clinical predictors of mortality in children with severe malaria. Results: The mean age of children in this cohort was 2.1 years (standard deviation, 0.9 years) and 338 children (56.3%) were male. Mortality was 7.3%, and 52.3% of deaths occurred within 12 hours of admission. Coma, acidosis, impaired perfusion, AKI, elevated blood urea nitrogen (BUN), and hyperkalemia were associated with increased mortality (all P < .001). AKI interacted with each risk factor to increase mortality (P < .001 for interaction). Children with clinical indications for dialysis (14.4% of all children) had an increased risk of death compared with those with no indications for dialysis (odds ratio, 6.56; 95% confidence interval, 3.41-12.59). Conclusions: AKI interacts with coma, acidosis, or impaired perfusion to significantly increase the risk of death in severe malaria. Among children with AKI, those who have hyperkalemia or elevated BUN have a higher risk of death. A better understanding of the causes of these complications of severe malaria, and development and implementation of measures to prevent and treat them, such as dialysis, are needed to reduce mortality in severe malaria.Item Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria(Springer Nature, 2019-05-21) Conroy, Andrea L.; Opoka, Robert O.; Bangirana, Paul; Idro, Richard; Ssenkusu, John M.; Datta, Dibyadyuti; Hodges, James S.; Morgan, Catherine; John, Chandy C.; Pediatrics, School of MedicineBACKGROUND: Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown. METHODS: Ugandan children with cerebral malaria (CM, n = 260) and severe malaria anemia (SMA, n = 219) or community children (CC, n = 173) between 1.5 and 12 years of age were enrolled in a prospective cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD). Cognitive testing was conducted using the Mullen Scales of Early Learning in children < 5 and Kaufman Assessment Battery for Children (K-ABC) second edition in children ≥ 5 years of age. RESULTS: The prevalence of AKI was 35.1%, ranging from 25.1% in SMA to 43.5% in CM. In-hospital mortality was 11.9% in AKI compared to 4.2% in children without AKI (p = 0.001), and post-discharge mortality was 4.7% in AKI compared to 1.3% in children without AKI (p = 0.030) corresponding to an all-cause adjusted hazard ratio of 2.30 (95% CI 1.21, 4.35). AKI was a risk factor for short- and long-term neurocognitive impairment. At 1 week post-discharge, the frequency of neurocognitive impairment was 37.3% in AKI compared to 13.5% in children without AKI (adjusted odds ratio (aOR) 2.31 [95% CI 1.32, 4.04]); at 1-year follow-up, it was 13.3% in AKI compared to 3.4% in children without AKI (aOR 2.48 [95% CI 1.01, 6.10]), and at 2-year follow-up, it was 13.0% in AKI compared to 3.4% in children without AKI (aOR 3.03 [95% CI 1.22, 7.58]). AKI was a risk factor for CKD at 1-year follow-up: 7.6% of children with severe malaria-associated AKI had CKD at follow-up compared to 2.8% of children without AKI (p = 0.038) corresponding to an OR of 2.81 (95% CI 1.02, 7.73). The presenting etiology of AKI was consistent with prerenal azotemia, and lactate dehydrogenase as a marker of intravascular hemolysis was an independent risk factor for AKI in CM and SMA (p < 0.0001). In CM, AKI was associated with the presence and severity of retinopathy (p < 0.05) and increased cerebrospinal fluid albumin suggestive of blood-brain barrier disruption. CONCLUSIONS: AKI is a risk factor for long-term neurocognitive impairment and CKD in pediatric severe malaria.Item Acute Kidney Injury is Associated with Poor Lung Outcomes in Infants Born ≥32 Weeks of Gestational Age(Thieme, 2020-01) Starr, Michelle C.; Boohaker, Louis; Eldredge, Laurie C.; Menon, Shina; Griffin, Russell; Mayock, Dennis; Askenazi, David; Hingorani, Sangeeta; Pediatrics, School of MedicineObjective: This study aimed to evaluate the association between acute kidney injury (AKI) and lung outcomes in infants born ≥32 weeks of gestational age (GA). Study design: Secondary analysis of infants ≥32 weeks of GA in the assessment of worldwide acute kidney injury epidemiology in neonates (AWAKEN) retrospective cohort (n = 1,348). We used logistic regression to assess association between AKI and a composite outcome of chronic lung disease (CLD) or death at 28 days of age and linear regression to evaluate association between AKI and duration of respiratory support. Results: CLD occurred in 82/1,348 (6.1%) infants, while death occurred in 22/1,348 (1.6%); the composite of CLD/death occurred in 104/1,348 (7.7%). Infants with AKI had an almost five-fold increased odds of CLD/death, which remained after controlling for GA, maternal polyhydramnios, multiple gestations, 5-minute Apgar's score, intubation, and hypoxic-ischemic encephalopathy (adjusted odds ratio [OR] = 4.9, 95% confidence interval [CI]: 3.2-7.4; p < 0.0001). Infants with AKI required longer duration of respiratory support (count ratio = 1.59, 95% CI: 1.14-2.23, p = 0.003) and oxygen (count ratio = 1.43, 95% CI: 1.22-1.68, p < 0.0001) compared with those without AKI. Conclusion: AKI is associated with CLD/death and longer duration of respiratory support in infants born at ≥32 weeks of GA. Further prospective studies are needed to elucidate the pathophysiologic relationship.