A 36-year-old female presents in moderate respiratory distress, following a night of sleeplessness, nausea, vomiting and diarrhea. Speaking in short sentences, she denies chest pain, but is experiencing abdominal discomfort. She is hypertensive and tachycardic. Upon physical exam you note diminished lung sounds in the bases of both lungs. Her abdomen is soft and tender to the touch. You also notice signs of edema in her ankles, which the patient describes as a new onset, about one to two days ago. She has just started chemotherapy for ovarian cancer and was given an intraperitoneal injection of carboplatin.

What might be causing these signs and symptoms?

For most EMS providers, renal failure would not be the first medical condition that would come to mind. However, this patient is experiencing an acute, potentially life-threatening kidney injury that is the result of acute poisoning associated with the potent anti-cancer medication she had just received. Let's take a look at renal complications that are less commonly seen, but can present to prehospital providers.

Kidney injury: How big is the problem?

The rate of diagnosed kidney injuries (KI), formerly known as renal failure, is on the rise. While experts debate whether better, more consistent definitions of KI is contributing to the dramatic increase, there seems to be consensus that overall the percentage of people in the United States with KI has increased.[1] 

Acute kidney injuries, or acute renal failure (ARF), is also increasing among patients who are hospitalized for non-renal specific conditions.[3] It can worsen the ability of these patients to recover from their original medical problem or condition.

Kidney anatomy and pathophysiology: A quick overview

There are two kidneys in the human body; each is roughly the size of a clenched fist. They are located in the retroperitoneal space, behind the much larger abdominal cavity. One of the kidney's main functions is to filter waste by-products and toxins from the blood as it passes through the kidney.

The filtration process is complex, and changes according to the demands of the body. The primary functional unit of the kidney is called a nephron; on average, there are an estimated 1 million nephrons within each kidney. Blood enters the first part of the nephron called the glomerulus. Much of the blood's liquid plasma is forced out of the glomerulus and into the surrounding space called the Bowman's capsule, carrying with it waste and toxins, along with nutrients and necessary electrolytes like potassium.

The fluid is collected in the second part of the nephron known as the renal tubules. The tubules selectively reabsorb water, nutrients and electrolytes back into the capillaries carrying the blood cells. As the process continues, the plasma containing mostly waste is concentrated in the renal tubule.

Toward the end of this process, the nephron will secrete any last toxins or excess substances out of the capillaries and into the final part of the renal tubule, such as medications. The now highly concentrated plasma is eventually dumped into collecting ducts, forming urine that is drained from each kidney via its ureter into the urinary bladder.

To summarize, there are three steps to how the nephron clears the bloodstream:

1. Filtration in the glomerulus
2. Reabsorption of water and needed materials in the beginning segment of the tubule
3. Secretion of final waste products at the end of the tubule.

Kidney injury: What is it?

Kidney injuries can be broadly classified into two categories, chronic and acute. An acute kidney injury (AKI) is defined as an sudden decline in renal function that occurs over a few hours to a few days.[4] Patients with AKI rapidly lose their ability to filter blood, resulting in an increasingly toxic blood stream and fluid overload.

Conditions that lead to AKI can be categorized into three areas:

1. Prerenal causes are mostly related to blood flow to the kidney. Hypotension secondary to decreased cardiac output, blood volume or massive vasodilation is the most common prerenal cause of AKI.
2. Postrenal problems are usually related to the inability to remove urine from the body, either due to an obstruction somewhere in the excretion apparatus, such as a kidney stone in the ureter, or problems with the bladder retaining urine.
3. Intrinsic problems happen within the kidney itself. There can be damage to the glomerulus, renal tubules or the tissue containing the nephrons.

Diseases such as lupus erythematosus, streptococcal or viral infections, or increasingly, medications such as antibiotics, nonsteroidal anti-inflammatory drugs (ibuprofen is an example) can cause the kidney to suddenly lose function. The patient in the case study, the 36-year-old female, has an intrinsic problem.

There are several signs and symptoms that are associated with AKI. They include:

• Sudden changes in mental status or mood
• Nausea, vomiting and/or diarrhea
• Rapid onset of numbness or tingling, especially around the hands and feet
• Sudden onset of edema to the feet and/or hands
• Rapid onset of hypertension
• Rapid decrease in urine output
• Seizures, muscle twitching as a result of increasing potassium levels (hyperkalemia)
• Changes in the electrocardiogram such as elevated or peaked T waves associated with hyperkalemia

Recall that in AKI these signs and symptoms will occur over just a few hours or days. As fluid rapidly builds up, it will begin to shift to other areas of the body, including the lungs. This will result in shortness of breath. Patients may experience chest pain as a result of fluid overload placing additional workload on the heart.

Compared to AKI, chronic kidney injuries occur much more slowly. Diseases such as hypertension and diabetes are considered risk factors for developing chronic kidney failure.

There may be few signs of failure during the evolution of the disease; the kidneys may be down to 25 percent of normal function by the time symptoms become noticeable.[5] Many patients report a slow, steady onset of fatigue, general weakness, slow onset of pedal edema, and decreasing urine output. Resting blood pressure rises as fluid slowly builds up in the body.

Over time, even with aggressive medical management, end-stage renal disease (ESRD) may develop. At this point the kidney's ability to perform is insufficient to maintain normal blood volume and composition. Patients with ESRD require their blood to be artificially dialyzed, either through hemodialysis or peritoneal dialysis. Certain patients may become eligible for kidney transplants. Efforts are underway to develop artificial kidneys that can be implanted[6] or worn on a belt.[7]

Assessment of kidney injury

An initial impression of an acute kidney injury may be hard to determine at first glance. EMS providers will likely consider more common causes of respiratory distress, chest pain or seizures. Pay close attention to the history of the illness and the timing of the physical findings. The patient, family or caregiver may describe an unusual sign or symptom occurring within the past few days, such as swelling of the feet or hands, or a sudden change in the patient's level of alertness.

Consider possible AKI if there is an introduction of a medication described above. Ask about urinary habits; has there been a decrease in output? Has the color of urine become darker, more concentrated? Especially in the absence of a fever or infection history, these may be signs of renal impairment.

Remember that kidney failure may be the result of another problem that is causing decreased blood flow. Patients with sepsis are at high risk for developing AKI.[8]

Treatment of kidney injury

Out of hospital treatment is mainly supportive. Preserve the patient's airway patency if necessary and ensure adequate ventilation and oxygenation. Monitoring oxygen saturation via pulse oximetry (SpO2) and carbon dioxide levels during exhalation using waveform capnography (ETCO2) will guide the EMS provider in appropriate ventilation rates and volume.

If hypotension exists, volume expansion may be required for both kidney and overall perfusion needs. In severe sepsis, a vasopressor may also be needed for increasing cardiac output.

On the other hand, hypertensive states require careful restriction of fluid delivery. If pulmonary edema exists, consider a diuretic such as furosemide. Nitrate therapy may help reverse fluid shifts by reducing hypertension temporarily through vasodilatation. Continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) can force pulmonary interstitial fluid overload back into the vasculature, increasing gas exchange effectiveness.

There may be other causes for altered mental status that might be present. Remember to check blood glucose levels and treat as necessary.

Encounters with patients experiencing an acute kidney injury may occur rarely for EMS providers, and remain hidden behind other more common causes of medical emergencies. Paying attention to specific signs and symptoms and how quickly they arise might provide a clue to the actual cause of the patient's presentation.

References

1. Slew ED and Davenport A. The growth of acute kidney injury: a rising tide or just closer attention to detail? Kidney International (2015) 87, 46–61.

2. Centers for Disease Control and Prevention. National chronic kidney disease fact sheet, 2014. http://www.cdc.gov/diabetes/pubs/pdf/kidney_factsheet.pdf; retrieved 20 April 2015.

3. Waikar SS et al. Diagnosis, Epidemiology and Outcomes of Acute Kidney Injury. Clinical Journal of the American Society of Nephrology. 2008. vol. 3 no. 3844-861.

4. Hughes PS. Classification systems for acute kidney injury. Medscape 16 October 2014. http://emedicine.medscape.com/article/1925597-overview. Retrieved 20 April 2015.

5. Nordqvist C. What is chronic renal failure? Medical News Today. 10 September 2014. http://www.medicalnewstoday.com/articles/172179.php retrieved 21 April 2015.

6. University of California, San Francisco. The Kidney Project. http://pharm.ucsf.edu/kidney. Retrieved 25 April 2015.

7. Barbor M. New Wearable Artificial Kidney Improves Mobility. Medscape Medical News. 9 February 2015. http://www.medscape.com/viewarticle/839462. Retrieved 25 April 2015.

8. Majumbar A. Sepsis-induced kidney injury. Indian Journal of Critical Care Medicine. 2010:  Jan-Mar; 14(1): 14–21.

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