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

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Introduction 0:00–0:35

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.

Unstable patients 0:35–1:12

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 non-specific signs and symptoms.

Stable patients 1:12–2:06

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 erythematosis or malignancy.
Similarly, the physical exam is non-specific and might reveal BP 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 mg per deciliter or more over forty-eight hours.

Labs 2:06–4:19

A rise of serum creatinine 1.5 times the baseline or more in the last seven days, or urine output less than 0.5 mL per kilogram per hour for six hours.
However, with intrinsic AKI, the BUN to creatinine ratio will be less than 20:1, and urine sodium will be greater than 20 millequivalents per liter.
Next, calculate the fractional excretion of sodium, or FEINA 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 phenA will be greater than 2%.
Now, here's a clinical pearl. In contrast to intrinsic AKI in pre-renal AKI, the kidneys filter less sodium to maintain intravascular volume.
In other words, the PENA 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 PENA values.
Back to the lab results, where urinalysis and microscopy often reveal red blood cell, white blood cell, 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.
OK. Now, let's focus on non-glomerular causes of intrinsic AKI starting with acute tubular necrosis.

ATN 4:19–4:46

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.

Ischemic ATN 4:46–6:13

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 BP.
Finally, don't forget to treat the underlying cause. Now, here's another clinical pearl.
Since reduced renal perfusion can cause both pre-renal 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.

Toxic ATN 6:13–6:53

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.
These findings are suggestive of toxic acute tubular necrosis. So, immediately stop the nephrotoxic agent and initiate supportive care for AKI.
Now, switching gears and moving on to acute interstitial nephritis. In this case, the urinalysis with microscopy will reveal white blood cells and white blood cell casts, sometimes in combination with microscopic hematuria and eosinophiura.

AIN 6:53–7:18

With these findings, diagnose acute interstitial nephritis, and be sure to assess the type. First, let's focus on allergic acute interstitial nephritis, which is a type 4 hypersensitivity reaction.

Allergic AIN 7:18–8:19

In this condition, the immune system reacts to a specific medication and triggers tubular interstitial lymphocytic infiltration and subsequent interstitial edema.
This local edema compromises renal microvasculature, eventually decreasing the glomerular filtration rate and causing kidney injury.
Individuals with acute interstitial nephritis usually report rash and fever. Additionally, history will reveal exposure to antibiotics, including beta lactams and sulfonamides, NSAIDs, proton pump inhibitors, and anticonvulsants like phenytoin.
With these findings, diagnose allergic acute interstitial nephritis. Treatment involves removing the offending medication, supportive care for AKI, and glucocorticoids for refractory cases.
In non-allergic acute interstitial nephritis, on the other hand, infections such as streptococcal or HIV infection trigger the immune system and subsequent tubular interstitial lymphocytic infiltration.

Non-allergic AIN 8:19–9:06

Similarly, autoimmune conditions including systemic lupus erythematosis and Sjogren's syndrome can trigger interstitial inflammation.
Now, diagnose non-allergic acute interstitial nephritis. Then, initiate supportive care for AKI and be sure to treat the underlying cause.
Here's a clinical pearl to keep in mind. Both types of acute interstitial nephritis present with sterile pyuria, characterized by white blood cells on the urinalysis, and negative urine culture.
Next, let's discuss intrinsic AKI due to intratubular obstruction. Intratubular renal obstruction is associated with the physical blockage of tubules by substances like casts and crystals.

Intratubular obstruction 9:06–10:26

It is often seen in individuals with multiple myeloma or tumor lysis syndrome, which typically occurs as a result of cytotoxic therapy.
Your analysis with microscopy will reveal red blood cells and white blood cells, sometimes in combination with hematuria and proteinuria.
Also, you might notice specific plugs causing the obstruction. In multiple myeloma, urine microscopy will reveal light chain casts, while in tumor lysis syndrome, massive cell lysis will result in increased uric acid release and the formation of uric acid crystals.
With these findings, diagnose intratubular renal obstruction. Next, provide supportive care and be sure to address the underlying cause.
Here's one last clinical pearl. If you identify light chain casts, diagnose myeloma cast nephropathy, also known as light chain cast nephropathy.
On the flip side, if you identify uric acid crystals, diagnose acute urate nephropathy. Finally, let's take a look at extraglomerular vascular injury, which occurs when the renal vessels outside of the glomerulus are affected.

Extraglomerular vascular injury 10:26–11:31

In this case, history might reveal recent vascular instrumentation, such as cardiac catheterization, or conditions like malignant hypertension, sepsis, or severe trauma.
If your analysis with microscopy reveals hematuria and proteinuria, as well as red blood cells and white blood cells with no casts, you can diagnose extraglomerular vascular injury.
Examples of extraglomerular vascular injury include macrovascular conditions such as aortic dissection and renal vein thrombosis, but also conditions that can affect renal microvasculature, such as disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome.
Regarding treatment, provide supportive care for AKI and treat the underlying condition. All right, as a quick recap.

Review 11:31–12:19

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.
Non-glomerular causes include acute tubular necrosis, typically marked by muddy brown granular casts, acute interstitial nephritis, characterized by sterile pyuria, and intratubular obstruction, seen in conditions like multiple myeloma and hematological malignancies, and extraglomerular vascular injury, which includes conditions like aortic dissection or disseminated intravascular coagulation.
Treatment for intrinsic AKI primarily involves supportive care and management of the underlying cause.