Chronic kidney disease - causes, symptoms, diagnosis, treatment, pathology #kidney #kidneydisease # kidneycauses #kidneysymptoms

 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, make sure electrolyte levels are steady, 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 the 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 to withstand the pressure, resulting 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 damaged 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 matrices 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, that 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 gets 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 build-up of toxins can also cause pericarditis which is inflammation of the lining of the heart. 

In addition, there can be an 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 on the skin and 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, which 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 the 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 - low calcium levels. As calcium levels in the blood falls, parathyroid hormone is released, causing the bones to lose calcium. Over time, this resorption of calcium from the bones leaves them weak and brittle, a condition known as renal osteodystrophy. The kidneys also release key hormones. For example, normally when the kidneys start sensing a lower than normal amount of fluid getting filtered, they respond by releasing the hormone renin to increase the blood pressure. In chronic kidney disease, the falling glomerular filtration rate leads to more and more renin secretion which leads to hypertension. 

Now, remember that hypertension is a cause of chronic kidney disease itself, so this creates quite the vicious cycle. The kidney also secretes the hormone erythropoietin which stimulates the production of red blood cells from the bone marrow. In chronic kidney disease, erythropoietin levels fall and this leads to a lowered production of red blood cells, and ultimately anemia. Ultimately the diagnosis of chronic kidney disease comes down to looking at changes in the glomerular filtration rate over time. Chronic kidney disease might be suspected with a GFR of less than 90 ml/min/1.73 m2, and irreversible kidney damage might happen with a GFR below 60 ml/min/1.73 m2. To confirm the diagnosis a kidney biopsy can be done to look for changes like glomerulosclerosis.

Treatment for chronic kidney disease often involves managing the underlying cause. In severe situations, dialysis or a kidney transplant might be needed.