Angiopoietins as Prognostic Markers for Future Kidney Disease and Heart Failure Events After Acute Kidney Injury

2022 ◽  
pp. ASN.2021060757
Author(s):  
Sherry Mansour ◽  
Pavan Bhatraju ◽  
Steven Coca ◽  
Wassim Obeid ◽  
Francis Wilson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Lower Risk ◽  
Kidney Injury ◽  
Early Response ◽  
Secondary Outcome ◽  
Ckd Progression ◽  
Angiopoietin 2 ◽  
Vessel Stability

Background The mechanisms underlying long-term sequelae following acute kidney injury (AKI) remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for chronic kidney disease (CKD) and heart failure. Methods To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure, as well as the secondary outcome of all-cause mortality 3 months after discharge or later. Results Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [95% CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression. Conclusions A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.

scholarly journals HMOX1 and Acute Kidney Injury in Sickle Cell Anemia

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 686-686
Author(s):  
Santosh L. Saraf ◽  
Maya Viner ◽  
Ariel Rischall ◽  
Binal Shah ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Risk Factor ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Kidney Injury ◽  
Ckd Progression ◽  
Kdigo Guidelines

Abstract Acute kidney injury (AKI) is associated with tubulointerstitial fibrosis and nephron loss and may lead to an increased risk for subsequently developing chronic kidney disease (CKD). In adults with sickle cell anemia (SCA), high rates of CKD have been consistently observed, although the incidence and risk factors for AKI are less clear. We evaluated the incidence of AKI, defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a rise in serum creatinine by ≥0.3mg/dL within 48 hours or ≥1.5 times baseline within seven days, in 158 of 299 adult SCA patients enrolled in a longitudinal cohort from the University of Illinois at Chicago. These patients were selected based on the availability of genotyping for α-thalassemia, BCL11A rs1427407, APOL1 G1/G2, and the HMOX1 rs743811 and GT-repeat variants. Median values and interquartile range (IQR) are provided. With a median follow up time of 66 months (IQR, 51-74 months), 137 AKI events were observed in 63 (40%) SCA patients. AKI was most commonly observed in the following settings: acute chest syndrome (25%), an uncomplicated vaso-occlusive crisis (VOC)(24%), a VOC with pre-renal azotemia determined by a fractional excretion of sodium <1% or BUN-to-creatinine ratio >20:1 (14%), or a VOC with increased hemolysis, defined as an increase in serum LDH or indirect bilirubin level >1.5 times over the baseline value at the time of enrollment (12%). Compared to individuals who did not develop AKI, SCA adults who developed an AKI event were older (AKI: median and IQR age of 35 (26-46) years, no AKI: 28 (23 - 26) years; P=0.01) and had a lower estimated glomerular filtration rate (eGFR) (AKI: median and IQR eGFR of 123 (88-150) mL/min/1.73m2, no AKI: 141 (118-154) mL/min/1.73m2; P=0.02) by the Kruskal-Wallis test at the time of enrollment. We evaluated the association of a panel of candidate gene variants with the risk of developing an AKI event. These included loci related to the degree of hemolysis (α-thalassemia, BCL11A rs1427407), to chronic kidney disease (APOL1 G1/G2 risk variants), and to heme metabolism (HMOX1) . Using a logistic regression model that adjusted for age and eGFR at the time of enrollment, the risk of an AKI event was associated with older age (10-year OR 2.6, 95%CI 1.4-4.8, P=0.002), HMOX1 rs743811 (OR 3.1, 95%CI 1.1-8.7, P=0.03), and long HMOX1 GT-repeats, defined as >25 repeats (OR 2.5, 95%CI 1.01-6.1, P=0.04). Next, we assessed whether AKI is associated with a more rapid decline in eGFR and with CKD progression, defined as a 50% reduction in eGFR, on longitudinal follow up. Using a mixed effects model that adjusted for age and eGFR at the time of enrollment, the rate of eGFR decline was significantly greater in those with an AKI event (β = -0.51) vs. no AKI event (β = -0.16) (P=0.03). With a median follow up time of 66 months (IQR, 51-74 months), CKD progression was observed in 21% (13/61) of SCA patients with an AKI event versus 9% (8/88) without an AKI event. After adjusting for age and eGFR at the time of enrollment, the severity of an AKI event according to KDIGO guidelines (stage 1 if serum creatinine rises 1.5-1.9 times baseline, stage 2 if the rise is 2.0-2.9 times baseline, and stage 3 if the rise is ≥3 times baseline or ≥4.0 mg/dL or requires renal replacement therapy) was a risk factor for CKD progression (unadjusted HR 1.6, 95%CI 1.1-2.3, P=0.02; age- and eGFR-adjusted HR 1.6, 95%CI 1.1-2.5, P=0.03). In conclusion, AKI is commonly observed in adults with sickle cell anemia and is associated with increasing age and the HMOX1 GT-repeat and rs743811 polymorphisms. Furthermore, AKI may be associated with a steeper decline in kidney function and more severe AKI events may be a risk factor for subsequent CKD progression in SCA. Future studies understanding the mechanisms, consequences of AKI on long-term kidney function, and therapies to prevent AKI in SCA are warranted. Disclosures Gordeuk: Emmaus Life Sciences: Consultancy.

scholarly journals Clinical Usefulness of Urinary Liver Fatty Acid-Binding Protein Excretion for Predicting Acute Kidney Injury during the First 7 Days and the Short-Term Prognosis in Acute Heart Failure Patients with Non-Chronic Kidney Disease

2017 ◽  
Vol 7 (4) ◽  
pp. 301-315 ◽  
Author(s):  
Akihiro Shirakabe ◽  
Noritake Hata ◽  
Nobuaki Kobayashi ◽  
Hirotake Okazaki ◽  
Masato Matsushita ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Fatty Acid Binding Protein ◽  
Kidney Injury ◽  
Liver Fatty Acid ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Background: The clinical significance of urinary liver fatty acid-binding protein (u-LFABP) in acute heart failure (AHF) patients remains unclear. Methods and Results: The u-LFABP levels on admission of 293 AHF patients were analyzed. The patients were divided into 2 groups according to the u-LFABP quartiles (Q1, Q2, and Q3 = low u-LFABP [L] group vs. Q4 = high u-LFABP [H] group). We evaluated the diagnostic and prognostic value of u-LFABP and compared the findings between the chronic kidney disease (CKD; n = 165) and non-CKD patients (n = 128). Acute kidney injury (AKI) during the first 7 days was evaluated based on the RIFLE criteria. In the non-CKD group, the number of AKI patients during the first 7 days was significantly greater in the H group (70.0%) than in the L group (45.6%). A multivariate logistic regression model indicated that the H group (odds ratio: 3.850, 95% confidence interval [CI] 1.128-13.140) was independently associated with AKI during the first 7 days. The sensitivity and specificity of u-LFABP for predicting AKI were 63.6 and 59.7% (area under the ROC curve 0.631) at 41.9 ng/mg × cre. A Cox regression model identified the H group (hazard ratio: 13.494, 95% CI 1.512-120.415) as an independent predictor of the 60-day mortality. A Kaplan-Meier curve, including all-cause death within 60 days, showed a significantly poorer survival rate in the H group than in the L group (p = 0.036). Conclusions: The u-LFABP level is an effective biomarker for predicting AKI during the first 7 days of hospitalization and an adverse outcome in AHF patients with non-CKD.

MO378WHAT LIES BENEATH ANTICOAGULATION-RELATED ACUTE KIDNEY INJURY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hernando Trujillo ◽  
Justo Sandino Pérez ◽  
Teresa Cavero Escribano ◽  
Eduardo Gutierrez ◽  
Angel Sevillano ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Iga Nephropathy ◽  
Kidney Biopsy ◽  
Vitamin K Antagonists ◽  
Immunosuppressive Treatment ◽  
Kidney Injury ◽  
Secondary Outcome ◽  
Biopsy Specimens

Abstract Background and Aims Acute kidney injury (AKI) secondary to glomerular hemorrhage in the context of overanticoagulation, commonly known as anticoagulant-related nephropathy (ARN), is a relatively novel recognized entity. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to examine underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Method Spanish retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. The main outcome was to describe pathologic findings in kidney biopsy specimens of patients with clinical suspicion of ARN. The secondary outcome was to assess kidney outcomes during follow-up. Results Twenty-four patients were included with a median age of 76 years (interquartile range [IQR] 64-81) and a follow-up period of 10.1 (IQR 1.3-41.1) months. 79% were male, 22 (91%) had hypertension and 9 (37%) were diabetic. Most cases (91%) were on anticoagulation with vitamin K antagonists. At admission, 87% of cases presented gross hematuria with a median serum creatinine (SCr) of 4.2 mg/dl and a median INR of 2.3. During follow-up, median highest (peak) SCr was 6.3 mg/dl and 11 (45%) patients required acute dialysis. Kidney biopsy showed that all patients except one had an underlying nephropathy (confirmed IgA nephropathy in 16 [66.7%], probable IgA nephropathy in 2, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1). Tubules filled with red cells and red cell casts were observed in 66.7% of the cases and acute tubular necrosis in 70.8%. Management included anticoagulation withdrawal in 14 cases (58.3%) and immunosuppressive treatment with corticosteroids (n = 17 [70.8%]) and mycophenolic acid (n = 5 [20.8%]). At 12 weeks after discharge, 11 patients had >50% decrease in SCr (with respect to peak SCr), 6 had <50% decrease and 5 were on chronic dialysis. Conclusion IgA nephropathy was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

scholarly journals P0547THE DELETION OF AKT1 ATTENUATES RENAL FIBROSIS AND TUBULAR EPITHELIAL-MESENCHYMAL TRANSITION DURING ACUTE KIDNEY INJURY TO CHRONIC KIDNEY DISEASE PROGRESSION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Byung Min Ye ◽  
Il Young Kim ◽  
Min Jeong Kim ◽  
Soo Bong Lee ◽  
Dong Won Lee ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Injury ◽  
Wild Type ◽  
Ckd Progression ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background and Aims Acute kidney injury (AKI) is an underestimated, yet important risk factor for the development of chronic kidney disease (CKD), which is characterized by the tubulointerstitial fibrosis and tubular epithelial-mesenchymal transition (EMT). Akt has been reported to be involved in renal fibrosis and EMT. Thus, we investigated the role of Akt1, one of the three Akt isoforms, in the murine model of AKI to CKD progression. Method We subjected the wild type and Akt1−/− mice to unilateral ischemia-reperfusion injury (UIRI). UIRI was induced by clamping the left renal artery for 30 min followed by reperfusion. After 6 weeks of UIRI, the renal fibrosis and EMT were assessed by histology, immunohistochemistry, and western blot. Results After 6 weeks after UIRI, we found that Akt1, not Akt2 or Akt3, was activated in UIRI-kidney. The tubulointerstitial fibrosis was significantly alleviated in Akt1−/− mice compared with the wild type (WT) mice. Besides, the deletion of Akt1 decreased the expression of the vimentin and α-SMA and increased the expression of E-cadherin, indicating the suppression of tubular EMT. However, there was no difference in the activity of TGF-β1/Smad signalling, which is the potent inducer of renal fibrosis and EMT, between WT mice and Akt1−/− mice. The deletion of Akt1 also increased the GSK-3β activity and decreased the expression of β-catenin, Snail, and twist1. Conclusion Our findings demonstrate that the deletion of Akt1 attenuates the renal fibrosis and tubular EMT independently of TGF-β1/Smad signalling during the AKI to CKD progression. Akt1 may be the therapeutic target against the AKI to CKD progression.

scholarly journals Clinical significance of frusemide stress test in predicting the severity of acute kidney injury

2021 ◽  
Author(s):  
Arun Gokul Pon ◽  
Raveendran Vairakkani ◽  
Edwin Fernando Mervin ◽  
Nagalakshmi Dhanapal Srinivasaprasad ◽  
Thirumalvalavan Kaliaperumal
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Clinical Significance ◽  
Urine Output ◽  
Primary Outcome ◽  
Stress Test ◽  
Kidney Injury ◽  
Secondary Outcome ◽  
Operating Characteristics ◽  
Roc Curve Analysis

Abstract Introduction: The outcomes of Acute Kidney Injury (AKI) remain dismal even today, owing in part due to the lack of an ideal biomarker for detecting renal damage early enough. We conducted this pilot study to determine the clinical significance of Frusemide Stress Test (FST) to predict the severity of AKI. Methods: A total of 80 patients with AKI-KDIGO (Kidney Disease: Improving Global Outcomes) stage 1 or stage 2 underwent FST by administering a bolus dose of frusemide (1mg/kg for frusemide naïve and 1.5mg/kg for prior frusemide exposure in the past week), and urine output was then measured for the next two hours with volume replacement as desirable. The progression to AKI-KDIGO stage 3 within 14 days of FST was studied as the primary outcome. The composite end point of achieving AKI-KDIGO stage 3 or death within 14 days of FST was studied as the secondary outcome. Results: Out of 80 patients, 28(35%) patients met the primary outcome, and 34(42.5%) patients met the secondary composite outcome. Except for baseline Chronic Kidney Disease (CKD) status (p=0.018), other demographic characteristics were comparable between progressors and non-progressors group. Using receiver operating characteristics (ROC) curve analysis, a cumulative 2-hour post-FST urine output of ≤300 mL predicted progression to stage 3 AKI with 82.14% sensitivity, 82.69% specificity, and AUC of 0.89±0.03 (p<0.0001). Conclusion: The FST showed promising results as a novel tubular biomarker to identify progression to severe AKI with good predictive ability.

scholarly journals Association of Acute Kidney Injury with Cardiovascular Events and Death in Systolic Blood Pressure Intervention Trial

2019 ◽  
Vol 49 (5) ◽  
pp. 359-367
Author(s):  
Brad P. Dieter ◽  
Kenn B. Daratha ◽  
Sterling M. McPherson ◽  
Robert Short ◽  
Radica Z. Alicic ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Systolic Blood Pressure ◽  
Cardiovascular Events ◽  
Kidney Injury ◽  
Secondary Outcome ◽  
Intervention Trial ◽  
Major Cardiovascular Events

Rationale and Objective: In the Systolic Blood Pressure Intervention Trial, the possible relationships between acute kidney injury (AKI) and risk of major cardiovascular events and death are not known. Study Design: Post hoc analysis of a multicenter, randomized, controlled, open-label clinical trial. Setting and Participants: Hypertensive adults without diabetes who were ≥50 years of age with prior cardiovascular disease, chronic kidney disease (CKD), 10-year Framingham risk score > 15%, or age > 75 years were assigned to a systolic blood pressure target of < 120 mm Hg (intensive) or < 140 mm Hg (standard). Predictor: AKI episodes. Outcomes: The primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or cardiovascular death. The secondary outcome was death from any cause. Analytical Approach: AKI was defined using the Kidney Disease: Improving Global Outcomes modified criteria based solely upon serum creatinine. AKI episodes were identified by serious adverse events or emergency room visits. Cox proportional hazards models assessed the risk for the primary and secondary outcomes by AKI status. Results: Participants were 68 ± 9 years of age, 36% women (3,332/9,361), and 30% Black race (2,802/9,361), and 17% (1,562/9,361) with cardiovascular disease. Systolic blood pressure was 140 ± 16 mm Hg at study entry. AKI occurred in 4.4% (204/4,678) and 2.6% (120/4,683) in the intensive and standard treatment groups respectively (p < 0.001). Those who experienced AKI had higher risk of cardiovascular events (hazard ratio [HR] 1.52, 95% CI 1.05–2.20, p = 0.026) and death from any cause (HR 2.33, 95% CI 1.56–3.48, p < 0.001) controlling for age, sex, race, baseline systolic blood pressure, body mass index, number of antihypertensive medications, cardiovascular disease and CKD status, hypotensive episodes, and treatment assignment. Limitations: The study was not prospectively designed to determine relationships between AKI, cardiovascular events, and death. Conclusions: Among older adults with hypertension at high cardiovascular risk, intensive treatment of blood pressure independently increased risk of AKI, which substantially raised risks of major cardiovascular events and death.

Extended Mortality and Chronic Kidney Disease After Septic Acute Kidney Injury

2018 ◽  
Vol 35 (6) ◽  
pp. 527-535 ◽  
Author(s):  
Horng-Ruey Chua ◽  
Weng-Kin Wong ◽  
Venetia Huiling Ong ◽  
Dipika Agrawal ◽  
Anantharaman Vathsala ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Simplified Acute Physiology Score ◽  
Cardiac Events ◽  
Ckd Progression ◽  
Septic Acute Kidney Injury ◽  
Adverse Cardiac Events ◽  
Kidney Disease Progression

Purpose: To evaluate 1-year mortality in patients with septic acute kidney injury (AKI) and to determine association between initial AKI recovery patterns ( reversal within 5 days, beyond 5 days but recovery, or nonrecovery) and chronic kidney disease (CKD) progression. Methods: Prospective observational study, with retrospective evaluation of initial nonconsenters, of critically ill patients with septic AKI. Results: We studied 207 patients (age, mean [SD]: 64 [16] years, 39% males), of which 56 (27%), 18 (9%), and 9 (4%) died in intensive care unit (ICU), post-ICU in hospital, and posthospitalization, respectively. Infections (including pneumonia) and major adverse cardiac events accounted for 64% and 12% of deaths, respectively. Factors independently associated with 1-year mortality include older age, ischemic heart disease, higher Simplified Acute Physiology Score II, central nervous system or musculoskeletal primary infections, higher daily fluid balance (FB), and frusemide administration during ICU stay (all P < .05). Among 63 patients receiving renal replacement therapy (RRT), hospital mortality was higher with cumulative median FB >8 L versus ≤8 L at RRT initiation (57% vs 24%; P = .009); there was trend for less ICU- and RRT-free days at day 28 in patients with higher FB pre-RRT ( P = NS). Chronic kidney disease progression over 1 year developed in 21%, 30%, and 79% of 105 initial survivors with AKI reversal, recovery, and nonrecovery, respectively ( P < .001). Acute kidney injury nonrecovery during hospitalization independently predicted CKD progression ( P = .001). Conclusions: Patients with septic AKI had 40% 1-year mortality, mainly associated with infections. High FB and frusemide administration were modifiable risk factors. Risk of CKD progression is high especially with initial AKI nonrecovery.

scholarly journals The Management of Heart Failure in Kidney and Urinary Tract Syndromes

2017 ◽  
Vol 10 ◽  
Author(s):  
Yuri Lopatin ◽  
Andrew JS Coats
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Urinary Tract ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Kidney Dysfunction ◽  
Co Morbidity ◽  
The Common

Kidney dysfunction and other related abnormalities are extremely common in all HF syndromes, both because of the similarity of risk factors and the similarity of demography of the two types of patients but also because of the common renal effects of agents used for the treatment of HF. Important renal syndromes for the HF patient include including chronic kidney disease, acute kidney injury, cardio-renal syndrome, and prostatic obstruction. In HF (all types including  HFrEF, HFmrEF and especially HFpEF) chronic kidney disease (CKD) frequently co-exists and almost as frequently complicates the HF management. The two groups of syndromes share many risk factors (diabetes, hypertension, hyperlipidaemia) and often interact to worsen the prognosis of each other in a way that makes the patient with combined HF and renal disease at extremely high risk. This article reviews this common co-morbidity and how to manage it.

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