Intrinsic acute kidney injury (non-glomerular causes): Clinical sciences

Intrinsic acute kidney injury or AKI refers to a sudden decline in kidney function that results in electrolyte imbalances, extracellular dysregulation, and the accumulation of nitrogenous waste, such as ammonia and uric acid.

The underlying cause of intrinsic AKI can be glomerular, which involves damage to the glomerulus; and non-glomerular, which affects renal components like tubules or the interstitium.

If your patient presents with chief concerns suggesting AKI, first, perform an ABCDE assessment to determine if they’re unstable or stable.

If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access, which might include dialysis access, and put your patient on continuous vital sign monitoring and cardiac telemetry.

Finally, if you identify hyperkalemia, metabolic acidosis, volume overload, or symptomatic uremia, start emergent hemodialysis!

Now, let’s go back and take a look at stable patients.

First, obtain a focused history and physical exam, which usually reveals nonspecific signs and symptoms. For example, history might reveal reduced urine output, bloody urine, or systemic symptoms, like fatigue, malaise, and fever. Additionally, patients might report taking nephrotoxic medications or having chronic conditions, like systemic lupus erythematosus or malignancy.

Similarly, the physical exam is nonspecific and might reveal blood pressure abnormalities, rash, or periorbital and peripheral edema. In this case, suspect intrinsic AKI, so be sure to order a basic metabolic panel and urinalysis with microscopy, assess the patient’s urine output over time, and check renal ultrasound!

In all types of AKI, labs will reveal a rise in serum creatinine of 0.3 milligrams per deciliter or more over 48 hours; a rise of serum creatinine 1.5 times the baseline or more in the last 7 days, or urine output less than 0.5 milliliters per kilogram per hour for six hours.

However, with intrinsic AKI, the BUN-to-Cr ratio will be less than 20 to 1, and urine sodium will be greater than 20 milliequivalents per liter.

Next, calculate the fractional excretion of sodium, or FENa for short, to check the percentage of sodium filtered by kidneys into the urine. Divide the product of urinary sodium and serum creatinine by the product of urinary creatinine and serum sodium and multiply the dividend by 100.

In intrinsic AKI, kidneys fail to reabsorb the sodium from filtered urine, meaning more sodium gets excreted, so the FENa will be greater than 2 percent.

Now, here’s a clinical pearl! In contrast to intrinsic AKI, in prerenal AKI, the kidneys filter less sodium to maintain intravascular volume. In other words, the FENa will be below 1%. Remember, FENa is not reliable in oliguric individuals with chronic kidney disease because this condition is associated with an impaired ability to concentrate urine and varying baseline plasma sodium levels. In other words, FENa will not adequately reflect the changes in acute kidney injury. Similarly, FENa is not reliable in oliguric patients who are taking diuretics because these medications promote sodium excretion and can give falsely high FENa values.

Back to the lab results, where urinalysis and microscopy often reveal RBC-, WBC-, or tubular epithelial casts. Finally, if the renal ultrasound shows normal kidneys and parenchyma with no hydronephrosis diagnose intrinsic AKI, which can occur due to glomerular and non-glomerular causes.

Now, let’s focus on non-glomerular causes of intrinsic AKI, starting with acute tubular necrosis.

If the urinalysis with microscopy reveals muddy brown granular casts and renal tubular epithelial cells, diagnose acute tubular necrosis. Next, assess the type of acute tubular necrosis, which can be either ischemic or toxic.

Ischemic acute tubular necrosis occurs with inadequate renal perfusion and subsequent damage of renal tubular cells. This is common in conditions such as shock, severe blood loss, or with surgical interventions associated with the clamping of renal arteries. Also, bilateral renal artery stenosis and chronic conditions, like heart failure and cirrhosis, can affect renal perfusion and cause ischemic injury of renal tubular cells.

If history reveals any of these conditions, diagnose ischemic acute tubular necrosis, and begin supportive care for AKI.

If there’s hypovolemia, start intravenous hydration, and if there’s volume overload, stimulate diuresis with diuretics. In severe cases, initiate dialysis to manage potassium, urea, and acid-base balance until the kidneys recover. Also, correct any electrolyte disturbances and be sure to control blood pressure.

Finally, don’t forget to treat the underlying cause.

Now, here’s another clinical pearl! Since reduced renal perfusion can cause both prerenal AKI and acute tubular necrosis, sometimes it might be difficult to distinguish between the two. However, muddy brown casts, which represent tubular damage, are only seen in acute tubular necrosis!

In contrast to the ischemic type, in toxic acute tubular necrosis, there’s adequate renal perfusion, meaning there’s no ischemia. In this case, history will reveal exposure to nephrotoxic substances that can directly damage renal tubular cells.

These include nephrotoxic medications, like NSAIDs, aminoglycosides, vancomycin, and cisplatin, but also radiocontrast material.