scholarly journals Proximal Tubular Oxidative Metabolism in Acute Kidney Injury and the Transition to Chronic Kidney Disease

Kidney360 ◽  
2020 ◽  
pp. 10.34067/KID.0004772020
Author(s):  
Jennifer A. Schaub ◽  
Manjeri A. Venkatachalam ◽  
Joel M. Weinberg
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Oxidative Metabolism ◽  
Tricarboxylic Acid Cycle ◽  
Kidney Injury ◽  
Therapeutic Interventions ◽  
Acid Oxidation ◽  
Atp Production

The proximal tubule relies on oxidative mitochondrial metabolism to meet its energy needs and has limited capacity for glycolysis, which makes it uniquely susceptible to damage during Acute Kidney Injury, especially after ischemia and anoxia. In that setting, mitochondrial ATP production is initially decreased by several mechanisms, including fatty acid-induced uncoupling and inhibition of respiration related to changes in the shape and volume of mitochondria. Glycolysis initially is insufficient as a source of ATP to protect the cells and mitochondrial function, but supplementation of tricarboxylic acid cycle intermediates, augments anaerobic ATP production and improves recovery of mitochondrial oxidative metabolism. Incomplete recovery is characterized by defects of respiratory enzymes and lipid metabolism. During the transition to Chronic Kidney Disease (CKD), tubular cells atrophy but maintain high expression of glycolytic enzymes and there is decreased fatty acid oxidation. These metabolic changes may be amenable to a number of therapeutic interventions.

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.

scholarly journals Developing better mouse models to study cisplatin-induced kidney injury

2017 ◽  
Vol 313 (4) ◽  
pp. F835-F841 ◽  
Author(s):  
Cierra N. Sharp ◽  
Leah J. Siskind
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Therapeutic Interventions ◽  
Low Doses ◽  
Dosing Regimen ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Novel Therapeutic

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury.

scholarly journals Sugar or Fat? Renal Tubular Metabolism Reviewed in Health and Disease

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1580
Author(s):  
Leslie S. Gewin
Keyword(s):  
Chronic Kidney Disease ◽  
Fatty Acid ◽  
Kidney Disease ◽  
Fatty Acid Oxidation ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Acid Oxidation ◽  
Renal Tubules ◽  
Solute Movement ◽  
Renal Tubular

The kidney is a highly metabolically active organ that relies on specialized epithelial cells comprising the renal tubules to reabsorb most of the filtered water and solutes. Most of this reabsorption is mediated by the proximal tubules, and high amounts of energy are needed to facilitate solute movement. Thus, proximal tubules use fatty acid oxidation, which generates more adenosine triphosphate (ATP) than glucose metabolism, as its preferred metabolic pathway. After kidney injury, metabolism is altered, leading to decreased fatty acid oxidation and increased lactic acid generation. This review discusses how metabolism differs between the proximal and more distal tubular segments of the healthy nephron. In addition, metabolic changes in acute kidney injury and chronic kidney disease are discussed, as well as how these changes in metabolism may impact tubule repair and chronic kidney disease progression.

scholarly journals Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

2021 ◽  
Author(s):  
John R. Prowle ◽  
Lui G. Forni ◽  
Max Bell ◽  
Michelle S. Chew ◽  
Mark Edwards ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Adverse Outcomes ◽  
Baseline Risk ◽  
Major Surgery ◽  
Increased Risk

AbstractPostoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

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