Kidney Disease

Kidney disease occurs when kidney function declines, disrupting the regulation of fluids, electrolytes, waste products, and acid-base balance. Acute kidney injury, or AKI, is a sudden decline in kidney function that’s typically reversible, whereas chronic kidney disease, or CKD, is kidney damage that is gradual and irreversible.

Now, the kidneys are the body’s natural blood filter. They regulate what’s in the blood, clearing it of metabolic waste and toxins and excreting them through urine. They’re essential in regulating fluids and electrolytes; maintaining acid-base balance; secreting hormones essential for regulating blood pressure and stimulating the production of red blood cells; and activating vitamin D.

Within each kidney, there are millions of tiny functional units called nephrons, which consist of a renal corpuscle and renal tubules. The renal corpuscle is where blood filtration occurs, and it includes a tiny bundle of capillaries called the glomerulus, and the glomerular capsule, or Bowman’s capsule, which is a cup-shaped structure that surrounds the glomerulus.

As blood flows through the glomerulus, an ultrafiltrate of blood is created, which is then collected by Bowman’s capsule. Then, as it moves into the renal tubules, the filtrate is modified according to the body’s needs and urine is produced, in which waste is eliminated. The rate at which filtration takes place is called glomerular filtration rate, or GFR for short, and it’s one of the main measures of kidney function.

Now, there are three different mechanisms that can cause kidney injury. First, prerenal kidney injury can occur when there’s decreased blood flow to the kidneys like from dehydration, hemorrhage, or shock. In certain individuals, medications like non-steroidal anti-inflammatory drugs, or NSAIDs; angiotensin-converting enzyme, or ACE, inhibitors; or angiotensin receptor blockers, or ARBs, can also cause prerenal kidney injury by altering the normal autoregulation of blood flow within the kidneys.

Next, intrinsic or intrarenal kidney injury occurs when there’s an ischemic or toxic insult that causes direct damage to the kidney tissue itself, including the tubules, glomeruli, and renal blood vessels. This can happen with nephrotoxic substances, like certain medications such as vancomycin or cytotoxic chemotherapy agents; or from ischemia, which can happen if either prerenal or postrenal kidney injury is prolonged.

Lastly, postrenal kidney injury is caused when the normal outflow of urine from the kidneys is obstructed, which can happen with benign prostatic hyperplasia; renal calculi, also called kidney stones; and even when there’s an obstructed or kinked indwelling urinary catheter.

Now, when it comes to CKD, it’s most often caused by conditions such as hypertension and diabetes mellitus. Additionally, AKI can progress into CKD if the cause is not resolved.

Risk factors for both AKI and CKD include pre-existing conditions that can affect normal kidney function; advanced age; family history; and exposure to potentially nephrotoxic substances.

Alright, so, the pathophysiology of AKI varies depending on the mechanism of injury. In prerenal AKI, inadequate kidney perfusion leads to decreased GFR. The kidney’s normal response to this low blood flow is to release renin, which activates the renin-angiotensin-aldosterone system, or RAAS, and antidiuretic hormone, or ADH, which are aimed at raising blood pressure, restoring renal perfusion, and preserving GFR. Injury occurs if perfusion isn’t restored.

Intrinsic AKI commonly involves damage to the renal tubules which triggers an inflammatory process that causes tubular epithelial cell damage in a patchy pattern of necrosis and apoptosis. Dead and damaged cells slough off and accumulate in the lumen of the tubules and combine with inflammatory cells and proteins in the filtrate, which then solidify into casts.