Contributions to nephrology
-
Hypoxia-inducible factor (HIF) stabilizers, also known as inhibitors of HIF prolyl hydroxylase domain (PHD) inhibitors enzymes, are novel small-molecule agents to treat renal anemia. They increase endogenous erythropoietin (EPO) production by stabilizing HIF. This review focuses on the mechanisms by which PHD inhibitors ameliorate anemia in chronic kidney disease (CKD) and summarizes the current clinical experience with and prospects for these drugs. ⋯ Anemia is a serious complication of CKD and is an independent risk factor for congestive heart failure. Appropriate treatment of anemia is important in the management of advanced stage CKD, as it might help to extend life expectancy and improve the physical function of patients with CKD. However, at present, adverse effects of treatment, such as thromboembolic events, as well as high therapeutic cost have a negative impact on society. PHD inhibitors stabilize the transcription factor HIF, increasing the expression of downstream target genes, including EPO and enzymes involved in iron metabolism, resulting in increased EPO production and improved iron utilization. Key Messages: The potential advantages of PHD inhibitors over conventional EPO-based therapies include a more physiologic response to renal anemia, noninvasive oral administration, and lower cost. Phase III trials of more than 5 PHD inhibitors are ongoing, with overall demonstration of success in increasing hemoglobin levels. In this review, we focus on the mechanisms of PHD inhibitors in improving renal anemia in CKD and summarize the current clinical findings regarding these drugs.
-
Recent large clinical trials have reported that despite the maintenance of target hemoglobin (Hb) levels, higher doses of erythropoiesis-stimulating agents (ESAs) and/or iron preparations are significantly associated with higher risks of adverse events and death in maintenance hemodialysis (MHD) patients. Higher doses of ESAs have been demonstrated to result in a higher risk for cardiovascular disease due to elevated blood pressure or increased thrombogenicity. In addition, a high dose of iron might enhance inflammatory responses to infection and impair the phagocytic function of neutrophils. ⋯ Patients with hyporesponsiveness to ESAs or dysutilization of iron for erythropoiesis tend to be treated with ESAs or iron at doses exceeding the physiological level. However, the optimal doses of ESAs and iron for maintaining target Hb levels in these patients are not well established. Thus, from the perspective of long-term survival in chronic kidney disease patients, it is necessary to treat anemia with appropriate doses of ESAs and an iron that can induce physiological erythropoiesis.
-
Acute kidney injury (AKI) is associated with both short- and long-term clinical consequences including progression to chronic kidney disease. Recovery of renal function has gained importance, as interventions to prevent or treat AKI are limited. Basing recovery on a return of serum creatinine values excludes mounting evidence that AKI, even when reversible, is a very serious clinical event that will result in a significant number of both renal and extra-renal complications such as late stage kidney disease, major cardiovascular events, and death. ⋯ Development of a definition for renal recovery is critical to organizing research in AKI treatment. Assessment of serum creatinine remains the primary measure of renal recovery despite known limitations. Patterns of renal recovery are highly associated with clinical outcomes including survival. Additional research in basic mechanisms of renal injury and repair is needed to help formulate a more comprehensive assessment of renal recovery. Novel biomarkers for assessment of AKI may also aid in the determination of renal recovery. Key Messages: (1) The concept of acute kidney disease (7-90 days post AKI) should direct clinicians as well as researchers to pay attention to a critical time period for renal recovery in which interventions may alter long-term outcomes. (2) Recent studies have evaluated AKI recovery patterns, or trajectories, and is an important step towards defining long-term prognosis. (3) Serum creatinine alone is not a reliable marker of recovery after AKI and is associated with poor clinical outcomes despite a return to baseline levels. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.
-
The acute reduction of kidney function in critically and noncritically ill patients (regardless of their age) is one of the deadliest clinical conditions ever reported in modern medicine. Acute kidney injury (AKI) symptoms are sneaky and potentially difficult to be identified at the right time at the bedside. One of the greatest efforts of the recent history of critical care nephrology has been to find a common classification for AKI definition and staging with the purpose of allowing a timely diagnosis and push forward epidemiologic research. ⋯ AKI is currently defined by the Kidney Disease Improving Global Outcomes (KDIGO) consensus classification that applies conventional serum creatinine and urine output (UO) criteria. According to a recent large epidemiologic study, this classification led to the confirmation that AKI occurs in about half of adult critically ill patients admitted to the intensive care unit and that a stepwise increase in mortality is associated with the severity of AKI along KDIGO stages. Both serum creatinine and UO have inherent limitations in accurately diagnosing abrupt decreases of renal function, but their common and easy application in routine clinical practice is currently considered the standard of care for AKI diagnosis. Pediatric and neonatal AKI have recently been described and specific staging with KDIGO modification has been proposed. Key Messages: AKI is frequent in critically ill patients and significantly affects intensive outcomes independent of other clinical factors. AKI can be diagnosed and its severity accurately staged by the KDIGO classification and its modification for pediatric patients. Serum creatinine and UO criteria are applied in order to diagnose and stage AKI. Despite some significant limitations of these commonly applied biomarkers, their application has made it possible to clearly appraise the importance of accurate AKI identification in clinical practice in several studies for prognostic and therapeutic purposes.
-
Patients who have undergone cardiac surgery are at high risk of acute kidney injury (AKI) and often associated with poor short- and long-term outcomes. It is considered that the burden of AKI can be reduced and the quality of care can be improved by raising the appropriate awareness and using the right tools for early prevention and better management, by (1) improving awareness by understanding the epidemiology and pathophysiology; (2) using tools for risk assessment for early prevention; (3) increasing the use of electronic screening for early diagnosis; and (4) developing right clinical strategies for better treatment. In this review, we will update some typical studies as well as some new concepts, which focus on the quality of care of CSA-AKI.