Prerenal kidney injury is caused by a condition that diminishes blood flow to the kidneys, leading to hypoperfusion.

Hypoperfusion leads to hypoxemia, which can rapidly damage the kidney. The tubules are most susceptible to hypoxemia’s effect. The impaired blood flow results in decreased glomerular filtration rate (GFR) and increased tubular reabsorption of sodium and water. Life-threatening consequences include volume overload, hyperkalemia, and metabolic acidosis.

Intrarenal kidney injury, also called intrinsic or parenchymal renal failure, results from damage to the filtering structures of the kidneys. Nephrotoxicity or inflammation irreparably damages the delicate layer under the epithelium (basement membrane). Use of nephrotoxins also causes acute kidney injury because they accumulate in the renal cortex.

Postrenal kidney injury is a consequence of bilateral obstruction of urine outflow. The cause may be in the bladder, ureters, or urethra. Common causes include stones, blood clots, bladder tumors, pelvic malignancy, and prostatic hypertrophy.

When ischemic injury occurs, the tubular cells of the kidney suffer from cellular energy depletion, intracellular accumulation of calcium, and damage to the cell membranes. Patch necrosis results at multiple points in the tubules, the basement membrane may be ruptured, and the tubular lumen may become occluded by casts and debris. The occlusion is worsened by the inflammatory cells that produce casts and debris, contributing further to the urinary occlusion. Obstructed urine flow causes an increase tubular intraluminal pressure in the nephron, resulting in a decrease GFR. If the basement membrane is not severely destroyed or if the episode of acute tubular necrosis is not fatal, regeneration eventually will completely reverse the damage.

When nephrotoxic injury occurs, hemoglobin or myoglobin precipitates in the urine. Tubular cells are destroyed by direct toxic effects, lysis of red blood cells (RBCs), activating the cascade of the inflammatory mediators, intravascular coagulation, occlusion of tubules, and tissue hypoxia. In this form of acute tubular necrosis, most necrosis occurs in the proximal tubules.

Carcinogens are excreted in the urine, creating a medium for prolonged exposure to mucous membranes of the bladder. Bladder tumors can develop on the surface of the bladder wall (benign or malignant papillomas) or grow within the bladder wall (generally more virulent) and quickly invade underlying muscles. Ninety percent of bladder tumors are transitional cell carcinomas, arising from the transitional epithelium of mucous membranes. Less common are adenocarcinomas, epidermoid carcinomas, squamous cell carcinomas, sarcomas, tumors in bladder diverticula, and carcinoma in situ.

Infection results from a breakdown in local defense mechanisms in the bladder that allow bacteria to invade the bladder mucosa and multiply. The antibacterial features in the urine that aid in the prevention of bacterial growth are pH less than 5.5, urea concentration, and presence of organic acids. These factors create an unfavorable medium for bacterial growth due to the acidity. When the local defenses are changed, bacteria quickly grows if present.

Normally, a small amount of urine remains in the bladder after emptying without incident if the natural defenses are present. In cases when the urine is more alkanine, bacteria is allowed to germinate.

Another defense is the unidirectional flow of the urine. If the urine flow is decreased, a catheter or other instrumentation is inserted, or post sexual intercourse, bacteria travels more readily into the bladder. Without the natural defense mechanisms, bacteria can flourish resulting in a local infection.