Biomarkers and Mechanisms of Oxidative Stress-Last 20 Years of Research with an Emphasis on Kidney Damage and Renal Transplantation.

Oxidative stress is an imbalance between pro- and antioxidants that adversely influences the organism in various mechanisms and on many levels. Oxidative damage occurring concomitantly in many cellular structures may cause a deterioration of function, including apoptosis and necrosis. The damage leaves a molecular "footprint", which can be detected by specific methodology, using certain oxidative stress biomarkers. There is an intimate relationship between oxidative stress, inflammation, and functional impairment, resulting in various diseases affecting the entire human body. In the current narrative review, we strengthen the connection between oxidative stress mechanisms and their active compounds, emphasizing kidney damage and renal transplantation. An analysis of reactive oxygen species (ROS), antioxidants, products of peroxidation, and finally signaling pathways gives a lot of promising data that potentially will modify cell responses on many levels, including gene expression. Oxidative damage, stress, and ROS are still intensively exploited research subjects. We discuss compounds mentioned earlier as biomarkers of oxidative stress and present their role documented during the last 20 years of research. The following keywords and MeSH terms were used in the search: oxidative stress, kidney, transplantation, ischemia-reperfusion injury, IRI, biomarkers, peroxidation, and treatment.

Current Status of Novel Biomarkers for the Diagnosis of Acute Kidney Injury: A Historical Perspective.

Acute kidney injury (AKI) is a common and serious medical condition associated with significant increases in morbidity, mortality, and cost of care. Because of the high incidence and poor outcomes associated with AKI, there has been significant interest in the development of new therapies for the prevention and treatment of the disease. A lack of efficacy in drug trials led to the concern that AKI was not being diagnosed early enough for an effective intervention and that a rise in serum creatinine itself is not a sensitive-enough marker. Researchers have been searching for novel biomarkers that can not only assess a decline in kidney function but also demonstrate structural damage to the kidney and at time points earlier than increases in serum creatinine measurements allow. Over the past 10 years, there have been 3300 new publications and hundreds of new biomarkers investigated, yet concern still remains regarding AKI biomarker performance. The AKI biomarkers are yet to be widely utilized in clinical practice, leading some to question whether AKI biomarkers will ever reach their initial promise. However, we believe that biomarkers are an important part of current and future AKI research and clinical management. In this review, we compare the historical contexts of acute myocardial ischemia and AKI biomarker development to illustrate the progress that has been made within AKI biomarker research in a relatively short period of time and also to point out key differences between the disease processes that have been barriers to widespread AKI biomarker adoption. Finally, we discuss potential paths by which biomarkers can lead to appropriate AKI treatment responses that lower morbidity and mortality.

The priority of Antonino D'Antona in describing rhabdomyolysis with acute kidney injury, following the Messina earthquake (December 28, 1908). Commentary.

Following the Messina-Reggio Calabria earthquake (December 28, 1908) outstanding medical reports were published by Franz von Colmers (1875-1960), Antonino D'Antona (1842-1913), and Rocco Caminiti (1868-1940). The reports of D'Antona and Caminiti were heretofore neglected. Colmers, D'Antona and Caminiti described crush-syndrome. D'Antona who cured patients in shock also described two deaths due to uraemia. This gives him a priority in the description of crush syndrome with renal injury which has been traditionally attributed to Bywaters and Beall.

The Evolution of Critical Care Nephrology in Edmonton.

The University of Alberta (UofA) in Edmonton, Canada has a rich and productive history supporting the development of critical care medicine, nephrology and the evolving subspecialty of critical care nephrology. The first hemodialysis program for patients with chronic renal failure in Canada was developed at the University of Alberta Hospital. The UofA is also recognized for its early pioneering work on the diagnosis, etiology and outcomes associated with acute kidney injury (AKI), the development of a diagnostic scheme renal allograft rejection (Banff classification), and contributions to the Renal Disaster Relief Task Force. Edmonton was one of the first centers in Canada to provide continuous renal replacement therapy. This has grown into a comprehensive clinical, educational and research center for critical care nephrology. Critical care medicine in Edmonton now leads and participates in numerous critical care nephrology initiatives dedicated to AKI, renal replacement therapy, renal support in solid organ transplantation, and extracorporeal blood purification. Critical care medicine in Edmonton is recognized across Canada and across the globe as a leading center of excellence in critical care nephrology, as an epicenter for research innovation and for training a new generation of clinicians with critical care nephrology expertise.

[History of acute kidney injury, the early development of hemodialysis in France]. / Histoire de l'insuffisance rénale aiguë et des débuts de l'hémodialyse en France.

From the end of the 19th century to the 1950s, from mechanisms of disease and pathology to the first success of hemodialysis, the author depicts the history of acute kidney injury. These remarkable improvements of modern medicine led concurrently to the spread of hemodialysis for the replacement of end-stage renal disease.

An essential infusion for an essential organ.

Essential amino acid-based parenteral nutrition (PN) was found to be superior to hypertonic dextrose for patients with acute renal failure in a classical randomized trial that was published in 1973. However, subsequent trials were not able to duplicate this finding when this formulation was compared to hypertonic dextrose or to standard amino acid-based PN. As a result, this intervention has not been recommended in various guidelines for the nutrition support of patients with renal failure. However, all of these trials were relatively small, and none of them compared the intervention to a true control group-namely, patients who were not receiving any artificial nutrition. Because no trials have compared any form of artificial nutrition to no nutrition support in patients with acute renal failure, there really is no basis on which to make any level 1 evidence-based recommendation. Furthermore, a close look at all of the trials suggests that the essential amino acid-based formulation may be superior to the other types of intravenous nutrient supplementation to which it was compared. To determine whether this should be offered to patients with acute renal failure, we need data from one or more large, well-designed and executed, low risk of bias randomized trial(s) comparing essential amino acid-based PN to no nutrition therapy.

Emergence of the concept of acute kidney injury.

Acute kidney injury (AKI), a recently defined clinical entity, is an ailment that has afflicted humans from time immemorial. Its emergence as a disease follows by 50 years that of acute renal failure (ARF) after the Second World War. The medical model of ARF emerged as studies of the kidney in traumatic shock unraveled the pathophysiology of the disease and focused on its treatment with hemodialysis. ARF was reframed as AKI, based on the model that had been developed for chronic kidney disease, to incorporate the accrued epidemiologic data and present it as a public health model of disease that is potentially preventable and treatable at earlier stages of the disease.

Miguel de Cervantes: saberes médicos, enfermedades y muerte / Miguel de Cervantes: medical knowledges, ailments and death

Existe un reconocimiento generalizado de los amplios conocimientos médicos que Cervantes poseía para su época, hasta el punto de haberse afirmado que pudo ser médico. Parte de tales saberes pudieron serle trasmitidos por su padre que era cirujano-barbero y que le legó varios libros sobre materias médicas. Sin embargo, existe un desconocimiento casi total respecto a su patobiografía y las causas que originaron su muerte. Además de una posible malaria, tomando como base su propio testimonioy aceptando como síntomas cardinales la hidropesía y la sed incoercible, se le ha diagnosticado de cirrosis hepática con desarrollo final de una diabetes mellitus. No obstante, son también posibles otras alternativas como una insuficiencia cardiaca y existen ciertos argumentos a favor de que su dolencia final pudo ser una insuficiencia renal terminal

There is no doubt about the extensive medical knowledge of Cervantes at his time and some biographers affirm that he was a physician. Probably, part of these knowledges were the legacy of his father, a barber and surgeon, that bequeathed to him several medical books. However, there is an almost absolute ignorance related to his ailments and the cause of his death. Apart from a possible malaria, some authors have diagnosed him liver cirrhosis and diabetes mellitus, taking in account the Cervantes’s own testimony, with hydropsy and uncontrollable thirst as importants findings. However, some others explanations like heart failure are possible and certain data suggest terminal renal failure as his last illness

Jakub Penson and his studies on acute renal failure during typhus epidemics in Warsaw Ghetto.

In the Warsaw Ghetto established by the German Nazis as a special district for Polish Jews in 1940 there were two typhus epidemics. Many patients affected by this disease (1500 during the first and 6500 during second epidemic) were treated at The Department of Infectious Disease of Czyste Hospital headed by Dr Jakub Penson--a Polish physician of Jewish origin. A heroic group of 20 physicians not only treated patients in these tragic circumstances, but also performed in defiance of Nazi prohibition, scientific studies on the clinical course of typhus with special attention on hyperazotemia and renal complication. The results of their observations were presented in 1941-42 during clinical meetings in Czyste Hospital and later published by Penson in 1946 in the Polish Physicians Weekly. Among other clinical statements a description of acute renal failure of extrarenal origin, caused by dehydration and toxic influence of primary disease seems the most important one. It has to be taken into account that acute renal failure appearing during Crush Syndrome was described by Bywaters in 1941. Jakub Penson survived the German Nazi occupation and later become a head of the Internal Medicine Department in Gdansk Medical University and one of the precursors of clinical nephrology in Poland.

Emergence of the concept of acute renal failure.

Acute renal failure (ARF) is an ailment that has afflicted humans from time immemorial. Its recognition, however, was slow to emerge, hampered initially by the failure to consider it a diagnosis and, subsequently, by the disparity of its nomenclature in the different conditions in which it was observed and described. Further delay was due to the late recognition of the physiology of urine formation and the pathophysiology of acute injury to the kidney, which was to allow the final identification of the entity in the past century. The definition of "ischuria" as the suppression or retention of urine, and its classification to include "ischuria renalis" in the 17th century was a fundamental step that allowed diseases of the kidney to be grouped, studied and described. By the 18th century, the clinical course of ARF was well described, and by the 19th century its microscopic structural features were clearly detailed but continued to be given disparate names by various authors. During World War I, acute failure of kidney function due to trauma was reported as "war nephritis", which with the end of the war became a forgotten entity. In the interval between the two world wars, increased emphasis on experimental studies allowed major advances in the understanding of the hemodynamics of shock, volume homeostasis, kidney function and tubular epithelial cell injury and regeneration. As such, the reports of acute kidney failure in crush victims of the London air raids in 1941 prompted a series of clinical, pathological and experimental studies over the ensuing decade that were to lead to the full emergence of the concept of ARF in 1951.

Why did the 5th Earl of Derby die?

The unexpected death of Ferdinando Stanley, 5th Earl of Derby, on April 16, 1594 was an event of major political importance in the later years of Queen Elizabeth I of England. When he had succeeded his father at the age of 38 he became head of one of the most influential families in the country. He also had a claim to the throne if Elizabeth died without naming a successor. Yet within seven months of entering into his inheritance, this previously fit man was suddenly taken ill and died a fortnight later. His death was so significant that the historian John Stow recorded his illness in great detail (Fig. 1).(1) Stow's remarkable account is compatible with a sinister interpretation of the cause.