Chronic kidney disease is a broad term that includes subtle decreases in kidney function that develop over a minimum of three months. In contrast, acute kidney injury refers to any deterioration in kidney function that happens in less than three months. Now the kidney’s job is to regulate what’s in the blood, so they might remove waste, or make sure electrolyte levels are steady, or regulate the overall amount of water, and even make hormones - the kidneys do a lot of stuff! Blood gets into the kidney through the renal artery, and once inside it goes gets into tiny clumps of arterioles called glomeruli where it’s initially filtered, and the filtrate which is the stuff that gets filtered out, moves into the renal tubule. The rate at which this filtration takes place is known as glomerular filtration rate or GFR. In a normal healthy person, this is somewhere around 100-120 milliliter of fluid filtered per minute per 1.73 m2 of body surface area. The value is slightly less in women than men and it decreases slowly in all of us as we grow older. One of the most common causes of chronic kidney disease is hypertension. In hypertension, the walls of arteries supplying the kidney begin to thicken in order to withstand the pressure, and that results in a narrow lumen. A narrow lumen means less blood and oxygen gets delivered to the kidney, resulting in ischemic injury to the nephron’s glomerulus. Immune cells like macrophages and fat-laden macrophages called foam cells slip into the damage glomerulus and start secreting growth factors like Transforming Growth Factor ß1 or TGF-ß1. These growth factors cause the mesangial cells to regress back to their more immature stem cell state known as mesangioblasts and secrete extracellular structural matrix. This excessive extracellular matrix leads to glomerulosclerosis, hardening and scarr, and diminishes the nephron’s ability to filter the blood - over time leading to chronic kidney disease. The most common cause of CKD is diabetes, excess glucose in the blood starts sticking to proteins in the blood — a process called non-enzymatic glycation because no enzymes are involved. This process of glycation particularly affects the efferent arteriole and causes it to get stiff and more narrow - a process called hyaline arteriosclerosis. This creates an obstruction that makes it difficult for blood to leave the glomerulus, and increases pressure within the glomerulus leading to hyperfiltration. In response to this high-pressure state, the supportive mesangial cells secrete more and more structural matrix expanding the size of the glomerulus. Over many years, this process of glomerulosclerosis, once again, diminishes the nephron’s ability to filter the blood and leads to chronic kidney disease. Although diabetes and hypertension are responsible for the vast majority of CKD cases, there are other systemic diseases like lupus and rheumatoid arthritis, can also cause glomerulosclerosis. Other causes of chronic kidney disease include infections like HIV, as well as long-term use of medications like NSAIDs, and toxins like the ones in tobacco. Now, normally urea in the body gets excreted in the urine, but when there’s a decreased glomerular filtration fate, less urea get filtered out, and therefore it accumulates in the blood, a condition called azotemia, which can cause general symptoms like It nausea and a loss of appetite. As the toxin levels really build up, they can affect the functioning of the central nervous system - causing encephalopathy. This results in asterixis, a tremor of the hand that kind of resembles a bird flapping its wings and is best seen when the person attempts to extend their wrists. Further accumulation of these toxins in the brain can even progress to coma and death. The buildup of toxins can also cause pericarditis which is inflammation of the lining of the heart. In addition, there can be increased tendency for bleeding, since excess urea in the blood makes platelets less likely to stick to each other, and so there’s less clot formation. Finally, in some cases, someone can develop uremic frost, where urea crystals can deposit in the skin and they look like powdery snowflakes. In addition to getting rid of waste, the kidneys play an important role in electrolyte balance. Potassium levels are particularly important, and normally the kidney helps with potassium excretion. In chronic kidney disease, just like with urea, less potassium is excreted and more builds up in the blood, and it leads to hyperkalemia, which is worrisome because it can cause cardiac arrhythmias. Another key role of the kidneys relates to balancing calcium levels. Normally, the kidney helps to activate vitamin D which helps to increase absorption of calcium from the diet. In chronic kidney disease, there’s less activated vitamin D, so less calcium is absorbed into the blood, resulting in hypocalcemia