Acute Kidney Injury

Today's case was of a middle-aged man with renal cell carcinoma. He was sent in for an acute rise in his serum creatinine following a nephrostomy change.

We talked about multiple valuable learning points:

-Acute kidney injury (formerly acute renal failure) is one of the most common inpatient referrals that we see as internists.  Although the approach is very rudimentary, it is quite helpful to at least entertain three categories of possible causes in your mind:

-Pre-renal causes: by definition, pre-renal causes will correct completely once circulating volume has been restored.  On history look for things like reduced PO intake, diarrhea, blood loss, etc.  Also, certain volume overloaded states like cardiorenal syndrome or hepatorenal syndrome behave as pre-renal AKI because as far as the kidney is concerned, there is reduced circulating volume.

-Post-renal causes: these relate to obstruction and back pressure on the collecting system of the kidney producing hydronephrosis and reduced urinary flow.  Keep in mind that most people have two functioning kidneys, meaning that severe AKI usually only occurs with lesions below the bladder (obstructing flow to both kidneys) or large retroperitoneal masses that directly compress both ureters.  Our patient has one kidney, so something like a stone or blocked nephrostomy tube would be sufficient to cause AKI.

-Intrinsic renal causes: The simplest way to divide these up is to think of the structures within the kidney.  Glomerular causes of AKI include things that cause acute glomerulonephritis (post-infectious, autoimmune/vasculitis, infectious/viral).  Tubular causes like acute tubular necrosis can occur because of drugs or insufficient circulating volume for sufficient time to induce injury/damage.  Interstitial causes of AKI can result from infection, autoimmune processes, or most commonly drugs (PPI’s are a common medication that can do this).  Finally, vascular causes in the microcirculation can also cause AKI (TTP, HUS, etc.).  Also, macrovascular complications like obstructive tumours or thrombi can lead to AKI through a variet of mechanisms.

-The approach to AKI is two-fold: firstly, you need to try to determine the cause.  Our usual assessment includes a history and physical examination focusing on volume status and indications for dialysis.  Almost every patient with AKI should have urine electrolytes (low urine sodium suggest a pre-renal cause), a urinalysis (blood suggests GN or ATN), a urine microscopy to look for casts, and an abdominal ultrasound or other imaging to exclude hydronephrosis.

-Once you’ve finished your assessment portion, you need to look at a few management things.  Always start with ABC’s (e.g. if the patient is in florid pulmonary edema, he probably requires respiratory support).  Following that, ensure that the patient is adequately volume replete – pre-renal AKI can cause a creatinine of 1000umol/L that corrects with fluid.  Then ensure that there are no medications causing the AKI (antibiotics, NSAIDS, chemotherapy, etc).  After that, ensure that there are no medications that can worsen the AKI (ACE inhibitors, ARBs, diuretics).  Finally, ensure that any medications that need to be adjusted or held in renal failure are examined (digoxin, antibiotics, etc.).

-We talked about indications for dialysis.  Briefly, they can be divided into the mnemonic AEIOU.

A = refractory acidosis

E = refractory electrolyte abnormalities (principally potassium or calcium)

I = intoxication (methanol, ethylene glycol, ASA, lithium)

O = refractory volume overload/heart failure

U = uremic pericarditis or uremic encephalopathy (asterixis)

For the most part, there is no survival advantage to early dialysis before one of these indications is met.  Furthermore, it is generally not advisable to use dialysis (or bicarbonate infusion for that matter) to treat lactic acidosis from hypoperfusion.  The best treatment is correcting the underlying cause (usually shock) because some of the physiologic changes associated with acidosis are actually adaptive.

-Finally, we talked a little bit about Septra®/Cotrimoxazole/Trimethoprim-Sulfamethoxazole.  There are a couple of things to recognize about this medication.  The spectrum that it has is actually quite broad, and it is on the common list of first-line agents for urinary tract infections.  This drug is highly bioavailable when taken orally, so there is almost never an indication to use the intravenous formulation.  The gram positive coverage is generally very good, and this drug can be used to treat infections with methicillin-resistant Staphylococcus Aureus (MRSA).

-That said, it is quite old and has a number of side effects.  Septra has been associated with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, it has many drug interactions because of its inhibition of cytochrome P450 hepatic enzymes, it can cause bone marrow suppression and cytopenias, and can cause AKI.  Additionally, the trimethoprim component actually behaves like a potassium-sparing diuretic leading to hyperkalemia independent of renal failure.  Furthermore, the sulfamethoxazole component behaves like a sulfonylurea secretagogue which can lead to hypoglycemia.  There have been associations between Septra and sudden death, presumably on the basis of hyperkalemia, in database studies.

Further Reading:

Fralick, M., Macdonald, E. M., Gomes, T., Antoniou, T., Hollands, S., Mamdani, M. M., & Juurlink, D. N. (2014). Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ, 349, g6196.

Star, R. A. (1998). Treatment of acute renal failure. Kidney international, 54(6), 1817-1831.