Tag: acute kidney injury

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Cast Nephropathy and plasmapheresis

Does removal of the light chains with plasmapharesis reduce the severity of cast nephropathy? We know that renal failure is a terrible prognostic factor in multiple myeloma so fixing acute renal failure is important.

Renal failure comes in many different flavors with myeloma:

  • Light chain deposition disease
  • Heavy chain deposition disease that I have never seen but Steve Rankin had a case as a fellow.
  • Amylloidosis
  • Hypercalcemia
  • Cast nephropathy
Only the last is amenable to plasmapheresis. Whether it works has been the subject of three prospective randomized studies:

  1. Zucchelli 1988
  2. Johnson 1990
  3. Clark  2005 (PDF)
UPDATE

Though not randomized this recent article from KI should be of interest (Thanks Kyste):

Leung et al. Improvement of cast nephropathy with plasma exchange depends on the diagnosis and on reduction of serum free light chains. Kidney Int (2008) vol. 73 (11) pp. 1282-8.

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How do you go from an EGD to acute kidney injury?

We had an interesting consult a few weeks ago.

The patient was an elderly gentleman who recently underwent an EGD for gastritis-like symptoms. A few days after the procedure he received a call from his gastroenterologist telling him that he had H. Pylori and needed to start an antibiotic. He was prescribed PrevPac for 10 days. He almost immediately began to feel worse. His wife ultimately stopped giving him the PrevPack after about four days of increasing weakness, lethergy and nausea. Despite stopping the new medicine the patient continued to deteriorate. He was admitted about 2 weeks after the EGD.

His creatinine had risen from a baseline of 1.2 mg/dL to 4.5 mg/dL. Our initial thought was that he was pre-renal. We prescribed 0.9% saline but the patient didn’t respond, and his creatine continued to rise.

One clinical pearl that I repeatedly teach fellows is not to under treat pre-renal azotemia. If you think the patient is volume depleted give enough fluid that the next day if the creatinine has not improved you will be convinced that the patient is no longer volume depleted. You want to fully rule-out volume depletion after the first day.

This patient didn’t respond to fluids so we reevaluated the history. PrevPac, what’s in that?

  • Lansoprazole
  • Amoxicillin
  • Clarithromycin
Clarithromycin is a potent inhibitor of CYP3A4 so it interacts with a lot of medications. Our patient was on simvastatin. Let’s check out what does Dr. Google has to say about that:
We check his CPK and its 8,000 almost a week after he stopped taking the Clarithro.

Rhabdo induced acute kidney injury due to a drug interaction.

Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin. Clarithromycin is a potent inhibitor of CYP3A4, the major enzyme responsible for simvastatin metabolism.

Effects of Clarithromycin on the Pharmacokinetics of Simvastatin. Compared with simvastatin alone, coadministration of clarythromycin and simvastatin significantly increased the peak concentration and the area under the curve for simvastatin by approximately 8-fold (p<0.0001). Levels of simvastatin acid were also significantly (about 14-fold) higher during clarythromycin treatment compared with simvastatin alone (p<0.0001).

If the figures on pharmacokinetics from that last article are to be believed then 500 mg of clarithromycin magnifies 80 mg of daily simvastatin to an equivalent daily dose of 640 to 1,120 mg.

Rhabdomyolysis induces acute kidney injury from myoglobin. Myoglobin can precipitate in the presence of acidic urine. The heme component of myoglobin can generate free-radicals which can damage lipid membranes. Patients develop vasoconstriction in response to rhabdomyolysis, both from the direct effect of the myoglobin on the renal vasculature and due to the movement of intravascular fluid into the damaged muscles. This gives a pre-renal picture on the fractional excretion of sodium.

Evaluating volume status can be tricky because patients will often have peripheral edema from the inflammation associated with the rhabdomyolysis. Additionally the BUN:Cr will often be low as the creatinine tends to rise quicker in rhabdomyolysis than in other forms of renal failure. This is usually explained by the release of intramuscular creatinine rather than just a failure to clear creatinine. The younger age and increased frequency of men suffering from rhabdomyolysis may also play a role in this observation.

The electrolyte abnormalities of rhabdomyolysis:

  • Hyperkalemia
  • Hyperphosphatemia
  • Hypocalcemia (early)
  • Hypercalcemia (late)
  • Hyperuricemia
  • Anion gap metabolic acidosis

 The NEJM recently did a nice review of rhabdomyolysis which presents the recent inconclusive data on alkalinization (not proven to be helpful but the animal/disease models make it look like the right thing to do), mannitol and diuretics and use of high flux dialyzers.

The Annals of Internal Medicine recently published a review of Statin-Related Myopathy. Here is what they had to say about drug interactions:

Because simvastatin, lovastatin, and atorvastatin are primarily metabolized through the cytochrome P450 3A4 (CYP3A4) isoenzyme (43), inhibitors of CYP3A4 could theoretically increase serum statin levels and exposure to susceptible tissues. Drugs known to interact with statins include protease inhibitors, cyclosporine, amiodarone, and fibrates (44, 45). Protease inhibitors are potent CYP3A4 inhibitors and thus can increase up to 30 times the plasma concentrations of certain statins (45, 46). Consequently, both simvastatin and lovastatin should be avoided in pa- tients receiving protease inhibitors (42, 45, 47). Cyclosporine is a potent inhibitor of not only CYP3A4 but also several membrane transporters, and it increases the phar- macokinetic area under the curve of statins by 2- to 25- fold, with many reported cases of rhabdomyolysis (44). Statin dosages in patients receiving cyclosporine have therefore been limited to 5 mg/d for rosuvastatin, 10 mg/d for simvastatin and atorvastatin, and 20 mg/d for lovastatin (42, 47–49).

Pravastatin is not metabolized by the P450 system but is excreted renaly. Fluvastatin and rosuvastatin are metabolized by an alternative enzyme, CYP2C9.

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My first two lectures to the IM Intern Class of 2012

On July first I gave a lecture on IV fluids, total body water and hyponatremia. This handout is similar to the lecture I give to the medical students titled sodium and water. It adds a half baked section on potassium but this handout really needs to have th sodium section tightened up and shortened, the potassium section finished and short sections on the treatment of phos, magnesium and calcium disorders.

  • Here is the PDF
  • Here is the native Pages documentin case you use Pages and are interested in finishing this work in progress.

On July 9th I gave a lecture on acute renal failure. The handout is 28 5.5 x 8.5 pages. The book is designed as a workshop with questions and points for discussion throughout.

  • Here is the PDF of the 28 page handout. It is very readable and one of the best handouts I have put together.
  • Here is the native Pages document in case you use Pages and are interested in editing my masterpiece.
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My philosophy of consult nephrology

If, on every consult for acute kidney injury, you limited your differential to pre-renal azotemia, obstruction and run-of-the-mill ischemic ATN you would be capable of reaching the right diagnosis 95% of the time. Common causes of renal failure are common. All the time we spend learning and teaching about glomerulonephritis, interstitial nephritis, vasculitis and the other zebras of acute renal failure is usually time wasted. However, your job as a consult nephrologist is to hunt down and flush these zebras. I strive to try and fit every clinical scenario into one of these alternative rare diagnosis. Because if you are not actively hunting a zebra, you will never find one.

When you see community acquired pneumonia and the ICU intern mentions that there was a lot of blood during the intubation your mind needs to starting thinking about pulmonary-renal syndromes. Ask the family about a history of sinusitis, pay extra-attention to the red cells on the U/A, fire off that ANCA and anti-GBM ab. It is the job of the nephrologist to consider this diagnosis, if you don’t no one will and a week later when the ICU and ID teams begin scratching their collective heads on why this patient is not behaving like a typical pneumonia you will have the reason and prevent a low yield and dangerous bronchoscopy because you will have the serologic evidence you need to get the renal biopsy for the win.

 The cryptic case of acute kidney injury starts off just like the banal case of acute renal failure, a rise in creatinine. If you open your eyes to the faint threads that don’t quite fit the standard narrative you will be more receptive to seeing the clues you need to make that rare diagnosis.

Stay vigilant and stay hungry
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How not to randomize a study

If you are designing a randomized study, make sure you actualize randomize your patients. Schiffl messed this up in his study of daily versus three days a week dialysis, for acute renal failure. Schiffl achieved randomization by alternating eligible patients to three days a week versus daily dialysis. One key aspect about randomization, especially in non-blinded studies, is that the investigators cannot know what arm of the study the patient will be in prior to enrolling the patient. With alternating patients every investigator knows which arm the next patient will end-up in and they can make subtle decisions on the appropriateness of the patient or in how they present the consent form to influence the composition of the study arms.

This comes up, because my fellow sent me a paper on prophylactic dialysis prior to CABG (PDF). From the paper comes this gem:

Repeat after me, “If you know what arm the patient will be in prior to enrolling the patient, you are not running a randomized trial.”

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Highest creatinine I have seen in acute kidney injury

We had a patient earlier this month who presented with a creatinine that was 20 mg/dL on admission and rose to 22 on the repeat. That is the highest creatinine I have ever seen in a patient with acute kidney injury. I have a seen two patients with advanced CKD with creatinines in the mid to high thirties. (34 and 37 mg/dL).

When my fellow described the patient I was sure this was going to be CKD until she mentioned, rather triumphantly, that when she examined the patient she palpated a large bladder. She had a Foley placed and the patient voided 1300 mL of urine in the next hour.
Obstructive uropathy in a woman is cervical cancer until proven otherwise. Sure enough, a subsequent CT scan of the pelvis revealed a pelvic mass which was diagnosed as cervical cancer.
The patient was discharged with a creatinine of 1.9 mg/dL.
A few aspects of the case were interesting and surprising:
  • Obstructive uropathy causes an electrogenic type 1 RTA (hyperkalemic type 1 RTA as opposed to the hypokalemic classic type 1 RTA). Because of the RTA, these patients often have hyperkalemia out of proportion to the degree of renal failure. She was not hyperkalemic and presented with a potassium of 4.6 mEq/L.
  • The patient had a pH of 7.2, bicarbonate of 4 and a pCO2 of 8, giving her a metabolic acidosis and a respiratory alkalosis (predicted pCO2 by Winter’s formula is 14±2). I had been taught that patients cannot blow off CO2 below 14 mmHG. I guess she had super lungs. As best we could tell, the respiratory alkalosis was due to anxiety and resolved the following day.
  • My fellow wanted to give bicarbonate for the metabolic acidosis, but I did not. The pH of 7.2 is fine and the patient was hemodynamically stable. Her total calcium was 4.6 and her phosphorous was 10. I was worried that giving bicarbonate would correct the acidosis which at the time was essential to prevent the hypocalcemia from causing tetany or worse. The acidosis shifts bound inactive calcium to the unbound and active ionized form.