Acute Kidney Injury

General information

The theme of SensUs 2024 is Kidney failure also referred to as acute kidney injury (AKI). 10% of the population globally is affected by chronic kidney disease, with over 750,000 people in the US alone. Kidney failure is characterized by one or both kidneys losing their renal function, namely, the ability to filter waste matter from the blood. This results in an accumulation of waste in the bloodstream, altering the ionic homeostasis of the blood. There are 5 stages of kidney failure depending on glomerular filtration rate (GFR) which measures the blood filtration rates of the kidneys (in (mL/min), with the preliminary signs advancing to kidney failure including fatigue, nausea, swelling, etc. Generally, the clearance of substances that are freely filtered but not secreted or reabsorbed by the kidneys is used to estimate the GFR in clinical settings, with creatinine meeting the criteria. Creatinine is a product of the metabolism of creatine, which is produced in the liver from three amino acids, methionine, arginine, and glycine, and stored in muscle to be used as a source of energy once phosphorylated. Creatinine is normally excreted through the kidneys. Healthy kidneys are responsible for filtering creatinine out of the bloodstream, as it is a freely filtered metabolite that is not secreted or reabsorbed. Consequently, during kidney failure when the GFR reduces, there is a buildup of high levels of creatinine in the blood. A standard range of serum creatinine levels (SCr) for healthy men is 0.7 - 1.3 mg/dL (61.9 - 114.9 µmol/L), and for healthy women is 0.6 – 1.1 mg/dL (53 – 97.2 µmol/L). As diet and hydration has a negligible impact on serum creatinine levels, it serves as a reliable indicator of renal function. There is no cure for chronic kidney disease (CKD), although maintaining a proper diet and medications can slow the progression of the disease. A person with kidney failure needs to undergo dialysis treatment or kidney transplantation. These two treatments allow the normal, healthy functioning of the kidneys.

History of Acute Kidney Injury

Some of the earliest knowledge about kidney and urinary diseases dates all the way back to 9000BC. It comes from the cradle of Western civilization, Mesopotamia, from the cuneiform clay tablets of Acadia, Assyria, and Babylon that contain references to urinary obstruction, stone, cysts, urethritis, stricture, and urethral discharge. In ancient Babylon physicians made diagnoses depending on the appearance of the urine. They treated symptoms with remedies derived from plants or minerals. Drugs were administered by blowing them through a tube into the urethra, most likely also to relieve urinary obstruction, and using alcohol as an anaesthetic. Much of the medical information generated in Mesopotamia was later transported to the Mediterranean, especially to Greece. Except for infections which cause symptoms such as pyuria, pain and fever, at the time (about 450BC), most diseases of the renal parenchyma were unknown in Greek and Roman antiquity. Treatments for uraemia included the use of hot baths, sweating therapies, bloodletting and enemas. First records of urinary diseases are found in the Hippocratic Corpus, a collection of some 60 studies that are believed to represent the work of several medical writers. How much was written by Hippocrates himself remains uncertain. Nevertheless, Hippocrates of Cos (460–377 BCE) is regarded as the father of medicine, and many of the aphorisms attributed to him refer to diseases of the kidney. Even in the Renaissance renal diseases were still not being properly identified and oedema was generally thought to be related to liver disease. In 1827, Richard Bright provided the first, almost complete clinical description of the various forms of acute and chronic glomerulonephritis and showed that they were accompanied by macroscopic changes in the kidneys. Between 1850 and 1885, Frerichs, Klebs and Langhans described the primary glomerular lesions. Scottish chemist Thomas Graham first described dialysis in 1854. He used osmosis to separate dissolved substances and remove water through semi-permeable membranes, although he did not apply the method to medicine. The first human dialysis machine was constructed in 1943 by Dr Willem Kolff. His work to create an artificial kidney began in the late 1930s when he was working in a small ward at the University of Groningen Hospital in the Netherlands. Kolff’s machine is considered the first modern drum dialyzer. The first patient in the world to be treated by repeated haemodialysis was Clyde Shields in 1960 in Seattle. After the early successes in Seattle, haemodialysis established itself as the treatment of choice worldwide for chronic and acute kidney failure. Membranes, dialyzers and dialysis machines were continuously improved and manufactured industrially in ever-increasing numbers. A major step forward was the development of the first hollow-fibre dialyzer in 1964. This technology replaced the until-then traditional membranous tubes and flat membranes with a number of capillary-sized hollow membranes. This procedure allowed for the production of dialyzers with a surface area large enough to fulfil the demands of efficient dialysis treatment. Over the years that followed, thanks to the development of appropriate industrial manufacturing technologies, it became possible to produce large numbers of disposable dialyzers at a reasonable price. Today, dialyzers are made from entirely synthetic polysulfone, a plastic that exhibits exceptionally good filtering efficiency and tolerability for patients.