Cardiorenal Syndrome. Revised

I gave the cardiology fellows at St John Hospital and Medical Center a lecture on cardiorenal syndrome this morning. I revised and expanded the lecture I used for the residents:

• I added my rant regarding the Ronco's codification of cardiorenal syndrome
• I added the latest NEJM article on diuretic strategies 
• I included a section on extracorporeal ultrafiltration and the UNLOAD trial.

It could still use a slide or two on the various loop diuretics and their uses.

We also had an interesting discussion on the data suggesting that loop diuretics maybe harmful in acute decompensated heart failure. I should include a couple of slides on that.

Overall a significant upgrade. You can find the lecture in the usual place.

Cardiorenal syndrome

On the first Friday of every month I give a lecture to the residents at St. John Hospital and Medical Center. I like to do an electrolyte lecture but for March the chief resident asked me to talk about cardiorenal syndrome. In researching the lecture I came across this article by Claudio Ronco.

The article defines cardiorenal syndrome as any condition with simultaneous kidney and heart failure. He then goes on to subdivide cardiorenal syndrome into 5 types:

1. Acute heart failure causing acute renal failure
2. Chronic heart failure causing chronic kidney disease
3. Acute kidney injury causing any type of acute cardiac dysfunction (including arrhythmia)
4. Chronic kidney disease causing any chronic cardiac disease
5. Any systemic condition that causes renal and cardiac dysfuction (e.g. sepsis)

This is terrible. Cardiorenal syndrome used to signify the unique cause of acute kidney injury where the decrease in function is due to apparent volume depletion in a patient that obviously overloaded. It named the only scenario where acute kidney injury responded to diuresis. It was unique and specific. Ronco comes along and says, yes I like your version of cardiorenal syndrome so I will make it type 1 in my new all purpose definition of cardiorenal syndrome. Now whenever there is cardiac dysfunction and simultaneous kidney dysfunction we can just call it cardiorenal syndrome.

It doesn't have to be this way look at the example of hepatorenal syndrome. The syndrome does not refere to just any situation with simultaneous renal and liver dysfunction. It is a very specific diagnosis that only occurs with chronic liver disease and ascites. The patients must be oliguric, there is no non-oliguric HRS. Patients must be sodium avid and unresponsive to fluids and albumin. Additionally the patients cannot have laboratory or imaging evidence for an alternative cause of renal failure. Because of this definition hepatorenal syndrome identifies a very specific disorder, with a specific pathophysiology and unique prognosis and treatment options.

Ronco takes the beautiful and evocative name cardiorenal syndrome, strips it of all specificity and then tries to restore it by tacking on five different types. The fifth type 5 is the one that makes my brain explode. Sepsis, really? Acute kidney injury from sepsis that happens in the same patient who also suffers from sepsis induced cardiomyopathy should now be considered to have cardiorenal syndrome? Ronco is a man who has spent his life studying sepsis and acute renal failure, I can't believe he is actually referring to that condition as CRS type 5.

I'm not buying what Ronco's selling. Cardiorenal syndrome begins and ends with type 1 for me.

FYI: Here is the lecture (Keynote, PDF). It still needs some work. I'd like to add a section on ultrafiltration and I need to include the NEJM article on furosemide that was published yesterday.

That's a really low fractional excretion of sodium

Patient with acute renal failure and constipation. Normal saline to the rescue.
That's a low FeNa, but not the lowest I have ever seen.

- Posted using BlogPress from my iPhone

second lecture of the year: acute kidney injury

AKI Lecture 2010

View more presentations from Joel Topf.

This is a significant upgrade from the version I posted a couple of years ago. I put the lecture together right before the ATN trial was published. I finally got around to updating the presentation to include that data. I also updated the NGAL section and added some data on avoiding volume overload.

I used a number of the posts on the blog to allow me to rapidly update the presentation. I was pleased with how well my ATN commentary/review stood up.

Volume, a new target for dialysis and acute renal failure?

One of the major advancements in nephrology in the first decade of the 21ast century was the rejection of Kt/V as a treatment target in dialysis. In a field that is lacking in randomized clinical trials we had three well done randomized clinical trials designed to verify the mounds of observational data. In all three Kt/V as an expression of dose failed.

Chronic hemodialysis: HEMO

• eKt/V of 1.05 vs 1.45 (or a spKt/V of 1.2 vs 1.6) 

Peritoneal dialysis: ADEMEX

• Increase in PD dose such that they move from less than 40% at Kt/V of 2.0 to 83% at Kt/V of 2.0

Dialytic support for acute renal failure: VA/NIH ATN trial

• 3 days a week dialysis versus 6 days a week all at a single-pool Kt/V of 1.2 to 1.4 per session
• Hemodynamicly unstable patients were randomized to one of two levels of CVVH 20 or 35 ml/kg/hour of total CRT effluent

All three looked at variations on Kt/V tuned to the individual clinical scenario. Varying Kt/V in each of these clinical scanrio made not a whif of difference to the patients.

In the aftermath of such intellectual carnage nephrology is desperately seeking a replacement. My experience with nocturnal dialysis and the amazing work coming out of Canada makes home hemo look like the most appealing option. Getting results comparable to transplant makes it look like an entirely new modality compared to traditional in-center hemo.

One of the aspects that made Kt/V so appealing was how it was a useful in any situation involving dialysis. (The lessons from NCDS study on chronic in-center hemodialysis guided the definition of adequate dialysis for ARF in the ATN trial)

What lessons does home hemo have to teach acute renal failure in the ICU? What lessons does it have for peritoneal dialysis. One could argue that one of the central problems in modern dialysis is fluid management. Too many of my patients are chronically fluid overloaded leading to hypertension and over worked hearts. Home hemo corrects hypertension. Is solving that cardiovascular problem accounting for much of the improved clinical outcomes?

If that is the case, then there is a clear lesson that we can take from home hemo and apply to the ICU. 

Don't let your patients get volume overloaded

We covered this in journal club last thursday: Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy

The study is a retrospective interpretation of registry data on children with acute renal failure receiving continuous renal replacement therapy. Each patient was given a fluid overload score by calculating a percentage overload:

They divided patients into three strata:

1. <10% overload
2. 10-20% overload
3. ≥20% overload

They also used percentage overload as a continuous variable for the primary multivariate analysis.

The primary data is shown in table 2.

It should be immediatly obvious that the patients with more volume overload were sicker, they had signifigantly:

• longer ICU stay
• higher mortality
• more multi-organ dysfunction
• more likely to be intubated
• more inotropes
• more sepsis
• higher PRISM score

For that reason I am not going to spend time discussing the univariate analysis and go straight to the multivariate analysis:

Worse fluid overload severity remained independently associated with mortality (OR, 1.03; 95% CI, 1.01-1.05). The relationship was satisfactorily linear and the OR suggests a 3% increase in mortality for each 1% increase in degree of fluid overload at CRRT initiation.

That is impressive. If the results hold up and aplies to adults it should scare the crap out of anyone who regularly rounds in the ICU. Think of a typical 80 kg adult who has total input of 2,400 mL (100 mL/hr) and has 1,600 mL of urine output, 67 mL/hour. That is a positive balance of 800 mL or 1% of body weight. If that goes on for 3 days and then the patient becomes oliguric with only 400 mL of urine output for two days (2,000 mL positive per day) before initiating CRT. That patient would be up 6,400 mL or 8% of bodyweight: Those relatively innocuous seeming numbers would represent a 24% increase in mortality compared to someone with matched ins and outs. Yowsa!

This is an observational study and it is important not to accept he results as truth but it is certainly a suggestive lead.

lowest FeNa I have ever seen

I was consulted on a patient with autoimmune hepatitis and acute kidney injury. The patient has ascites and was admitted with a small bowel obstruction.

I'm not sure if it is actually the lowest but it is remarkably low:

serum Na 147 mmol/L
serum Creatinine 1.77 mg/dL

urine Na <10
urine Cr 148

I assumed a urine sodium of 5 mmol/L

FENa= 0.04%

This is 4 molecules of sodium excreted for every 10,000 filtered. Amazing.

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.

Highest urine urea ever

Just saw a urine urea of 1,019 mg/dL. I can't remember ever seeing one over 1,000 before. The FE Urea was 55% in a urosepsis induced AKI.

Today we did the recent NEJM CRT dosing article in journal club

The article is here.

Three of our attendings and fellows raved about Dr. Tolwani's AKI in the ICU lecture from Renal Week.

Here is the slide deck.

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.

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.
  

Acute renal failure links from the NEJM

Abuelo. Normotensive ischemic acute renal failure. N Engl J Med (2007) vol. 357 (8) pp. 797-805 (Pubmed)

Schrier and Wang. Acute renal failure and sepsis. N Engl J Med (2004) vol. 351 (2) pp. 159-69 (Pubmed)

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

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."

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.

Cryptogenic acute renal failure and emboli

Image from WebPath

Acute renal failure with the creatinine doubling everyday.
AKIN 3 on hospital day three.
Past medical history: a-fib

HPI: includes flank pain, but no hematuria.
PE: fluid overload
Low FEUrea

U/S is unremarkable, Mag3, LDH pending.

This study is afoot.

Monday was the highest traffic day on this site. Ever.

My post on Everything I learned in fellowship is wrong was featured on the home page of renalWEB.

It feels weird that my post was listed at the top under "News Headlines." The ATN article came out in July and I just got around to writing about it six months later. I wrote it so that when I discuss the findings on rounds, I have a way to quickly find an abstract of the study with my personal observations. And I will discuss it with the fellows because even though the study was a negative study it is a benchmark study in nephrology. The article is a negative study but it is negative in the way that HEMO was negative, not the way that DCOR was.

• HEMO is usually listed as a disappointing study because we were not able to help patients by ratcheting up their dose of dialysis from 1.16 to 1.53 (eKt/V).
  But as Glen Chertow argued persuasively, the HEMO trial was a triumph of evidence based medicine. We were able to definitively argue against the desire to incrementally enhance three-times a week day-time dialysis. The increasing evidence for daily and in-center nocturnal dialysis are by-products of the failure of HEMO. If HEMO had been a positive trial we would probably be focusing on a HEMO II with a targetted eKt/V of 1.8. The negative result has sparked innovation and a search for novel ideas.

• DCOR on the other hand has almost nothing definitive to show despite being "the largest outcomes study ever done in the hemodialysis population." The failure of DCOR can be attributed to a low event rate, a high but undefined cross-over rate and a 50% drop-out rate. All of these conspired to produce an under-powered study and clinicians are left in a sea of phosphorous binder marketing without near term hope for better guidance.

So the negative finding of the ATN group advances the science of nephrology, removes an important question and will allow us to move on to new strategies to help patients with acute kidney injury.

A final note to the editor of RenalWEB, my bullet on the dose of dialysis referred to the HEMO trial, which did not look at frequency of dialysis or radical increases in dose. The jury is still out on those techniques but I'm with you. Those two strategies seem right and beneficial.

Dose of DIalysis

Everything I learned in fellowship has turned out wrong. When I was a fellow I was taught:

• Higher Kt/V were beneficial for patients
• Increasing the hemoglobin reduced LVH and improved outcomes in CKD
• Using non-calcium based binders saved lives
• and most importantly: increasing the dose of dialysis in AKI improved survival
  

The last point was an area that was emphasized in my education. I heard Dr. Murray spend so much time going over the preliminary evidence that I was honed to proselytize the gospel of early and often dialysis for acute kidney injury. I loved working with Murray, he's a great speaker, a great teacher and the only man with more board certifications than years in middle school (internal medicine, nephrology, critical care, clinical pharmacology).

Since finishing fellowship it has been humbling watching each of these truths fall to the blade of the RCT (though I still believe that calcium based binders are harmful).

The results of the ATN Trial this past summer has been especially heartfelt because I was so invested in the outcome. I had argued and fought so many times to get an access and initiate dialysis, to get an extra-treatment, all this time being smugly self confident that I was helping the patient. Confident that I was fighting the good fight. Ughh.

So here it is, a review of the article that kicked me in the chest...
The objective was to determine if more intensive dialysis for acute kidney injury would improve survival in critically ill people. Unique to this trial, the protocol allowed patients to get either conventional hemodialysis or hemofiltration depending on the hemodynamic status of the patient at any time during the trial. This innovation allows the trial to better track actual practice. Additionally, it allows the trial to get past the eternal debate of which modality is better, and answer the question of what dose to target regardless of the modality.

The study was conducted from 2003 to 2007.

The trial was run at 27 institutions.

Enrollment criteria:

• Critically ill adult
• Age: 18 or older
  
• Renal failure plus at least one other organ system failure or sepsis
  

Patients who were hemodynamically stable were provided hemodialysis (prescribed Kt/V 1.2-1.4). If they were unstable, CVVH or SLED was provided. The decision between CVVH and SLED was determined by individual site preference.

Patients were randomized to one of two dosing schemes:

Less-intensive strategy:

• Stable: Intermittent hemodialysis: 3 days a week effluent
• Unstable: Continuous therapy: effluent of 20 mL/kg/hr

Intensive strategy:

• Stable: Intermittent hemodialysis: 6 days a week effluent
• Unstable: Continuous therapy: effluent of 35 mL/kg/hr

These definitions for dose come from Ronco's paper (continuous therapy) and Schiffl's paper (intermittent therapy) two studies which are (were?) frequently invoked as support for high dose dialysis in acute kidney injury.

Dialysis was continued until recovery of renal function, discharge from the ICU or 28-days of therapy or death. Recovery of renal function was defined by 6-hour CrCl of >12 mL/min and investigator discretion or >20 mL/min.

Primary Endpoint: All-cause mortality at day 60.

Secondary endpoints:

• In-hospital death
• Recovery of renal function (CrCl>20). Recovery was defined as complete if Cr was <0.5>0.5 over the baseline creatinine.
• Duration of renal replacement therapy
• Dialysis free at 60 days
• Duration of ICU stay
• Return to previous home at day 60.

Power analysis

• Estimated mortality with less-intensive strategy 55%
• Estimated mortality with intensive strategy 45%

The authors estimated 10% loss to follow-up and all patients lost were assigned to "alive" for analysis. 90% power with a sample size of 1164.

Enrollment was below the power analysis goal of 1164 at 1124 but the study had better retention with 29 being lost for various reasons and 5 being lost and analyzed as "alive." The power analysis anticipated 112 people being lost.


The all important table 1. shows a cohort that looks similar to the patients I take care of. 60% sepsis and 80% ventilated. Appache 26. All and all, a sick cohort.

The protocol was adhered to extremely well with extra treatments occurring on 0.5% of days in the high dose group and .5% of days with less-intensive strategy. Missed treatments occurred on 1.9% of days in the intensive strategy and 1.1% in less-intensive strategy. Surprisingly, the delivered dose of dialysis with intermittent therapy was a Kt/V of 1.3, right in the middle of the prescribed target. ICU patients are classically difficult to dialyze and previous analysis of delivered dose have shown it to lag well behind prescribed dose.

With continuous therapy the delivered dose like-wise correlated well with prescribed dose: 36.2 mL/kg with intensive strategy and 21.5 mL/kg with less-intensive strategy.

Primary outcome: 53.6% 60-day mortality with less-intensive strategy and 51.5% mortality with intensive strategy (p=0.47).

Secondary outcomes:

• In-hospital mortality: 48.0% less-intensive strategy, 51.2% intensive strategy
• Complete recovery of renal function (day 28): 18.4% less-intensive strategy, 15.4% intensive strategy
• Return to home by day 60: 16.4% less-intensive strategy, 15.7% intensive strategy

Complications: Patients on the intensive strategy required vasopressor support during renal-replacement therapy more often, 14.4% vs 10.0% (p=0.02) and required interventions for hypotension more often, 37.7% vs 30.0% (p=0.006). However, in intermittent dialysis both groups reported similar rates of dialysis associated hypotension 18.5% with intensive vs 18.0% with less-intensive) and similar drops in blood pressure (MAP from 86 to 75 with intensive and from 86 to 74 with less-intensive). The increase in dialysis associated events maybe related to the increased frequency of dialysis (more exposures to dialysis) with intensive strategy.

Hypophosphatemia (17.6% vs 10.9%, p=0.001) and hypokalemia (7.5% vs 4.5%, p=0.03) were both more common with intensive therapy than with less-intensive therapy.

The editorial by Bonventre that was published with the article was okay. I would re-direct interested readers to the Hume, et al. editorial in AJKD which was better.

Some points from the Bonventre article include:

• Increased numbers of men in the study
• Lack of CKD patients
• Questions about the changing of modalities allowed by the protocol
• Increased amount of SLED in the intensive therapy group compared to the less-intensive strategy

Some choice quotations from the Hume article:

This report currently should be viewed as the definitive study defining dialysis dosing in critically ill patients with AKI.

During the maintenance phase of AKI, while hemodialysis/hemofiltration techniques are being utilized, the patient dies from multi-organ failure while in exquisite electrolyte and fluid balance.

Our group has focused on 2 major areas of evaluation. The first is the recognition that current renal substitution therapy only provides the small-solute clearance function of the kidney but not the metabolic and endocrine functions of the kidney. Similar to the clinical evidence that kidney transplantation markedly prolongs survival and improves health related quality of life compared to dialysis, the replacement of renal parenchymal cell functions in AKI may change the natural history of this disorder.

Acute renal failure talk for the ED residents

The same talk I gave to the internal medicine residents but I have further polished it. Added some AIN data and put an answer section at the end.

ARF Handout

Publish at Scribd or explore others: Academic Work acute kidney injury acute renal failure

Articles that changed the way I practice: Gonzalez and Steroids for AIN

Acute interstitial nephritis (AIN) is a drug induced renal failure.

Patients classically have fever, rash and eosinophilia.

During my fellowship there was little data to support the use of steroids and I came down opposed to steroids. Last year Gonzales Et al. published a retrosprective analysis of 61 patients with biopsy proven AIN. 9 were not given steroids and the remiander were given a hodge-podge of different steroid protocols.

In addition to providing data on the question of steroids the article is a goldmine of data regarding AIN.

The culprit was usually an antibiotic:

• Antibiotic in 34 cases
• Cephalosporin in 15 cases
• Quinolone in 12 cases
• Penicillin in 7 cases
• NSAID in 23 cases
• Allopurinol in 1 case
• Ranitidine in 1 case
• Omeprazole in 1 case
• Pimozide in 1 case

Only 8 patients (13%) had the classic triad of fever, rash and eosinophilia. Table 1:

The key result was a signifigant difference in the need for long-term dialysis and a reduction in the final creatinine with steroids.


The data is not the most compelling (It's retrospective, the control group was tiny compared to the intervention group) but it is by far best we have on the subject and it changed the way I treat AIN.