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American Journal of Physiology. Renal... Dec 2020Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has... (Review)
Review
Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has adverse consequences and could progress to renal fibrosis, which is the ultimate common pathway for various terminal kidney diseases. Thus, it is urgent to develop a strategy to hinder the transition from AKI to CKD. Some mechanisms of the AKI-to-CKD transition have been revealed, such as nephron loss, cell cycle arrest, persistent inflammation, endothelial injury with vascular rarefaction, and epigenetic changes. Previous studies have elucidated the pivotal role of mitochondria in acute injuries and demonstrated that the fitness of this organelle is a major determinant in both the pathogenesis and recovery of organ function. Recent research has suggested that damage to mitochondrial function in early AKI is a crucial factor leading to tubular injury and persistent renal insufficiency. Dysregulation of mitochondrial homeostasis, alterations in bioenergetics, and organelle stress cross talk contribute to the AKI-to-CKD transition. In this review, we focus on the pathophysiology of mitochondria in renal recovery after AKI and progression to CKD, confirming that targeting mitochondria represents a potentially effective therapeutic strategy for the progression of AKI to CKD.
Topics: Acute Kidney Injury; Animals; Disease Progression; Energy Metabolism; Humans; Kidney; Mitochondria; Mitochondrial Dynamics; Mitophagy; Renal Insufficiency, Chronic; Risk Factors
PubMed: 33073587
DOI: 10.1152/ajprenal.00285.2020 -
Nature Reviews. Nephrology May 2021Mitochondria are essential for the activity, function and viability of eukaryotic cells and mitochondrial dysfunction is involved in the pathogenesis of acute kidney... (Review)
Review
Mitochondria are essential for the activity, function and viability of eukaryotic cells and mitochondrial dysfunction is involved in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease, as well as in abnormal kidney repair after AKI. Multiple quality control mechanisms, including antioxidant defence, protein quality control, mitochondrial DNA repair, mitochondrial dynamics, mitophagy and mitochondrial biogenesis, have evolved to preserve mitochondrial homeostasis under physiological and pathological conditions. Loss of these mechanisms may induce mitochondrial damage and dysfunction, leading to cell death, tissue injury and, potentially, organ failure. Accumulating evidence suggests a role of disturbances in mitochondrial quality control in the pathogenesis of AKI, incomplete or maladaptive kidney repair and chronic kidney disease. Moreover, specific interventions that target mitochondrial quality control mechanisms to preserve and restore mitochondrial function have emerged as promising therapeutic strategies to prevent and treat kidney injury and accelerate kidney repair. However, clinical translation of these findings is challenging owing to potential adverse effects, unclear mechanisms of action and a lack of knowledge of the specific roles and regulation of mitochondrial quality control mechanisms in kidney resident and circulating cell types during injury and repair of the kidney.
Topics: Acute Kidney Injury; Animals; Humans; Mitochondria; Renal Insufficiency, Chronic
PubMed: 33235391
DOI: 10.1038/s41581-020-00369-0 -
Nephron 2023There is a pandemic of obesity worldwide and in Europe up to 30% of the adult population is already obese. Obesity is strongly related to the risk of CKD, progression of... (Review)
Review
There is a pandemic of obesity worldwide and in Europe up to 30% of the adult population is already obese. Obesity is strongly related to the risk of CKD, progression of CKD, and end-stage renal disease (ESRD), also after adjustment for age, sex, race, smoking status, comorbidities, and laboratory tests. In the general population, obesity increases the risk of death. In nondialysis-dependent CKD patients, the association between body mass index and weight with mortality is controversial. In ESRD patients, obesity is paradoxically associated with better survival. There are only a few studies investigating changes in weight in these patients and in most weight loss was associated with higher mortality. However, it is not clear if weight change was intentional or unintentional and this is an important limitation of these studies. Management of obesity includes life-style interventions, bariatric surgery, and pharmacotherapy. In the last 2 years, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist and GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist were shown to be effective in managing weight loss in non-CKD patients, but we are awaiting results of more definitive studies in CKD patients.
Topics: Adult; Humans; Renal Insufficiency, Chronic; Obesity; Kidney Failure, Chronic; Weight Loss; Glucagon-Like Peptide 1
PubMed: 37271131
DOI: 10.1159/000531379 -
The Annals of Pharmacotherapy Jan 2020To summarize current antibiotic dosing recommendations in critically ill patients receiving intermittent hemodialysis (IHD), prolonged intermittent renal replacement... (Review)
Review
Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update.
To summarize current antibiotic dosing recommendations in critically ill patients receiving intermittent hemodialysis (IHD), prolonged intermittent renal replacement therapy (PIRRT), and continuous renal replacement therapy (CRRT), including considerations for individualizing therapy. A literature search of PubMed from January 2008 to May 2019 was performed to identify English-language literature in which dosing recommendations were proposed for antibiotics commonly used in critically ill patients receiving IHD, PIRRT, or CRRT. All pertinent reviews, selected studies, and references were evaluated to ensure appropriateness for inclusion. Updated empirical dosing considerations are proposed for antibiotics in critically ill patients receiving IHD, PIRRT, and CRRT with recommendations for individualizing therapy. This review defines principles for assessing renal function, identifies RRT system properties affecting drug clearance and drug properties affecting clearance during RRT, outlines pharmacokinetic and pharmacodynamic dosing considerations, reviews pertinent updates in the literature, develops updated empirical dosing recommendations, and highlights important factors for individualizing therapy in critically ill patients. Appropriate antimicrobial selection and dosing are vital to improve clinical outcomes. Dosing recommendations should be applied cautiously with efforts to consider local epidemiology and resistance patterns, antibiotic dosing and infusion strategies, renal replacement modalities, patient-specific considerations, severity of illness, residual renal function, comorbidities, and patient response to therapy. Recommendations provided herein are intended to serve as a guide in developing and revising therapy plans individualized to meet a patient's needs.
Topics: Adult; Anti-Bacterial Agents; Continuous Renal Replacement Therapy; Critical Illness; Female; Humans; Intermittent Renal Replacement Therapy; Kidney Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Renal Dialysis; Renal Insufficiency
PubMed: 31342772
DOI: 10.1177/1060028019865873 -
Pediatric Nephrology (Berlin, Germany) Oct 2021Our aging population is growing and developing treatments for age-related diseases such as Alzheimer's and Parkinson's disease has taken on an increasing urgency and is... (Review)
Review
Our aging population is growing and developing treatments for age-related diseases such as Alzheimer's and Parkinson's disease has taken on an increasing urgency and is accompanied by high public awareness. The already high and rising incidence of acute kidney injury (AKI) in the elderly, however, has received relatively little attention despite the potentially fatal outcomes associated with an episode of AKI in this age group. When discussing AKI and aging, one should consider two aspects: first, elderly patients have an increased susceptibility to an AKI episode, and second, they have decreased kidney repair after AKI given the high incidence of progression to chronic kidney disease (CKD). It is unclear if the same factors that drive the increased susceptibility to AKI could be playing a role in the decreased repair capacity or if they are totally different and unrelated. This review will examine current knowledge on the risk factors for the increased susceptibility to AKI in the elderly and will also explore potential aspects that might contribute to a decreased kidney repair response in this age group.
Topics: Acute Kidney Injury; Aged; Aging; Disease Progression; Humans; Kidney; Renal Insufficiency, Chronic; Risk Factors
PubMed: 33411069
DOI: 10.1007/s00467-020-04849-0 -
Critical Care Clinics Apr 2021Acute kidney injury (AKI) is a syndrome of impaired kidney function associated with reduced survival and increased morbidity. International consensus criteria were... (Review)
Review
Acute kidney injury (AKI) is a syndrome of impaired kidney function associated with reduced survival and increased morbidity. International consensus criteria were developed based on changes in serum creatinine and urine output. Based on these definitions, epidemiologic studies have shown strong associations with clinical outcomes including death and dialysis. However, numerous limitations exist for creatinine and urine volume as markers of AKI and novel biomarkers have been developed to detect cellular stress or damage. Persistent AKI and acute kidney disease are relatively new concepts that explore the idea of AKI as a continuum with chronic kidney disease.
Topics: Acute Kidney Injury; Biomarkers; Creatinine; Humans; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 33752854
DOI: 10.1016/j.ccc.2020.11.001 -
Metabolism: Clinical and Experimental Jun 2022Acute kidney injury (AKI) is a global public health concern associated with high morbidity and mortality. Although advances in medical management have improved the... (Review)
Review
Acute kidney injury (AKI) is a global public health concern associated with high morbidity and mortality. Although advances in medical management have improved the in-hospital mortality of severe AKI patients, the renal prognosis for AKI patients in the later period is not encouraging. Recent epidemiological investigations have indicated that AKI significantly increases the risk for the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the future, further contributing to the economic burden on health care systems. The transition of AKI to CKD is complex and often involves multiple mechanisms. Recent studies have suggested that renal tubular epithelial cells (TECs) are more prone to metabolic reprogramming during AKI, in which the metabolic process in the TECs shifts from fatty acid β-oxidation (FAO) to glycolysis due to hypoxia, mitochondrial dysfunction, and disordered nutrient-sensing pathways. This change is a double-edged role. On the one hand, enhanced glycolysis acts as a compensation pathway for ATP production; on the other hand, long-term shut down of FAO and enhanced glycolysis lead to inflammation, lipid accumulation, and fibrosis, contributing to the transition of AKI to CKD. This review discusses developments and therapies focused on the metabolic reprogramming of TECs during AKI, and the emerging questions in this evolving field.
Topics: Acute Kidney Injury; Female; Fibrosis; Humans; Kidney; Kidney Failure, Chronic; Male; Renal Insufficiency, Chronic
PubMed: 35346693
DOI: 10.1016/j.metabol.2022.155194 -
American Journal of Nephrology 2022As one of the main complications of chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) in CKD patients is high. CVD risk is markedly increased... (Review)
Review
BACKGROUND
As one of the main complications of chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) in CKD patients is high. CVD risk is markedly increased even at early stages of CKD, and CVD deaths account for half of all known causes of mortality in end-stage renal disease patients. The alarming rate of CVD in CKD patients demands accurate risk prediction to identify individuals at greater risk and therefore needing intensive surveillance and treatment in order to improve their prognosis.
SUMMARY
Since the CVD risk prediction models used in general population did not perform well in CKD patients, novel CVD risk biomarkers and improved risk predictive models adapted to CKD are receiving increasing attention in recent years. In this article, we review the applicability and performance of some of the available cardiovascular risk prediction tools in CKD.
KEY MESSAGES
Cardiovascular risk prediction in CKD needs and deserves continued attention and in-depth research that helps clinicians set out timely and effective interventions.
Topics: Humans; Cardiovascular Diseases; Risk Factors; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Heart Disease Risk Factors; Chronic Disease
PubMed: 36481730
DOI: 10.1159/000528560 -
Kidney International Sep 2021Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease have been well defined and classified, leading to...
Kidney disease is an important public health problem. Both acute kidney injury (AKI) and chronic kidney disease have been well defined and classified, leading to improved research efforts and subsequent management strategies and recommendations. For those patients with abnormalities in kidney function and/or structure who meet neither the definition of AKI nor chronic kidney disease, there remains a gap in research, care, and guidance. The term acute kidney diseases and disorders, abbreviated to acute kidney disease (AKD), has been introduced as an important construct to address this. To expand and harmonize existing definitions and to ultimately better inform research and clinical care, Kidney Disease: Improving Global Outcomes (KDIGO) organized a consensus workshop. Multiple invitees from around the globe, representing both acute and chronic kidney disease researchers and experts, met virtually to examine existing data, and discuss key concepts related to AKD. Despite some remaining unresolved questions, conference attendees reached general consensus on the definition and classification of AKD, management strategies, and research priorities. AKD is defined by abnormalities of kidney function and/or structure with implications for health and with a duration of ≤3 months. AKD may include AKI, but, more importantly, also includes abnormalities in kidney function that are not as severe as AKI or that develop over a period of >7 days. The cause(s) of AKD should be sought, and classification includes functional and structural parameters. Management of AKD is currently based on empirical considerations. A robust research agenda to enable refinement and validation of definitions and classification systems, and thus testing of interventions and strategies, is proposed.
Topics: Acute Disease; Acute Kidney Injury; Consensus; Humans; Kidney; Renal Insufficiency, Chronic
PubMed: 34252450
DOI: 10.1016/j.kint.2021.06.028 -
Expert Opinion on Drug Safety Sep 2021Invasive fungal infections continue to be important causes of morbidity and mortality in severely ill and immunocompromised patient populations. The past three decades... (Comparative Study)
Comparative Study Review
INTRODUCTION
Invasive fungal infections continue to be important causes of morbidity and mortality in severely ill and immunocompromised patient populations. The past three decades have seen a considerable expansion in antifungal drug research, resulting in the clinical development of different classes of antifungal agents with different pharmacologic properties. Among drug-specific characteristics of antifungal agents, renal disposition and nephrotoxicity are important clinical considerations as many patients requiring antifungal therapy have compromised organ functions or are receiving other potentially nephrotoxic medications.
AREAS COVERED
The present article reviews incidence, severity and mechanisms of nephrotoxicity associated with antifungal agents used for prevention and treatment of invasive fungal diseases by discussing distribution, metabolism, elimination and drug-related adverse events in the context of safety data from phase II and III clinical studies.
EXPERT OPINION
Based on the available data amphotericin B deoxycholate has the highest relative potential for nephrotoxicity, followed by the lipid formulations of amphotericin B, and, to a much lesser extent and by indirect mechanisms, the antifungal triazoles.
Topics: Animals; Antifungal Agents; Drug Development; Drug Interactions; Humans; Immunocompromised Host; Incidence; Invasive Fungal Infections; Kidney; Renal Insufficiency; Severity of Illness Index
PubMed: 33896310
DOI: 10.1080/14740338.2021.1922667