musings of a salt whisperer
Third in the series of interesting fluid and electrolyte cases.
I would add a slide on where I was going in potassium before the anorexia section.
SlideSpace botches the torn paper frames I used through out the lecture so if you have Keynote, download and look at the native file.
Here is a link to the Keynote file.
feedback?
Effect of a very low protein diet on outcome: long-term follow-up.
The primary end-point was a composite of death or dialysis and just about every patient in both groups (95.7%) reached this end-point preventing a separation between the groups (p=0.5). Likewise there was no separation with regards to time to dialysis (p=0.4).
The surprising finding occurs when they looked at death after the initiation of dialysis. There were 34 deaths in the very low-protein group and 19 deaths in the low-protein group (p=0.01).
The separation begins around 15 months and grows over time. This difference was statistically significant and grew to a 2-fold increased risk of death after 6 years.
My take is this fits well with what I tell my patients when they ask me about protein restriction. I have always counseled patients against protein restriction. The two largest RCT were both negative trials (The Modification of Diet in Renal Disease and the Northern Italian Cooperative Study Group). Additionally my patients do not have the benefit of dedicated and repeated nutritional couseling that the patients in these trials receive. My fear is that with little therapeutic upside there is signifigent risk of malnutrition from overzealous protein restriction.
This study probably does not apply to my worry as I doubt patients would adhere to a very low-protein diet.
My other concearn regarding low-protein diets is patients need to get calories from somewhere. Calories can only come from protein, carbohydrates or fat. Considering that the vast majority of CKD patients are destined to die before dialysis I worry that my advice for protein restriction will result in increased carbohydrates (bad for diabetes and possibly CV disease, see Richard Johnson’s fructose hypertension research) and/or increased fats (bad for CV disease) and enhance the risk of death from the more likely outcome.
The chief resident at Providence asked me to do a board review class for the third-years. They have small sessions weekly (?) in the physician lounge. This afternoon we went over fluids, electrolytes and acid-base. We did the first 14 questions. Seems like it went pretty well.
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.
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.
This coming week is the 100th day of school.
As part of a school project all of the kids need to bring in a hundred of something. My son wanted a hundred paper airplanes. We made a couple of dozen and I had my lecture for the ER residents coming up. So passed out two sheets of paper for each resident when I passed out the handout and I asked each resident to make a couple of airplanes. It turned out great.
Thanks St John ER Residents.
Everything I learned in fellowship has turned out wrong. When I was a fellow I was taught:
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:
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:
Intensive strategy:
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:
Power analysis
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:
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:
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.
The Renal Fellow Network did a nice pocket review of Loin Pain Hematuria Syndrome recently. However they left off an important diagnosis which also presents with hematuria and unilateral pain, Nut Cracker Syndrome. This refers to impingement of the left renal vein between the aorta and superior mesenteric artery.
These patients usually come to the nephrology office with a history of mysterious kidney stones which have been difficult to visualize.
In Nut Cracker Syndrome the pain is always on the left side.
Nice review with imaging studies are found in this NDT article from 1995.
(a) MRI revealed a dilated left renal vein (black arrows) after passing between the aorta (A) and superior mesenteric artery (white arrowhead).
(b) MRA showed that the diameter of the left renal vein (black arrow) was larger in the left part adjacent to the aorta (A) compared with the right adjacent part. A prominent left ovarian vein (white arrow), implicating formation of a collateral circulation, was also noted. IVC = inferior vena cava.
(c) Digital subtraction MRA found the impingement of the left renal vein (LRV) between the aorta (A) and superior mesenteric artery (white arrowhead).
45 y.o. referred for 4+ proteinuria. Patient is asymptomatic without edema but the FLP shows total cholesterol to be pushing 300. The patient reports for one month he has seen bubbles in his urine. A 24-hour urine showed 2,500 mg of protein on an adequate specimen.
PMHx is significant for gout which has been treated with allopurinol without much improvement. Over the last couple of years he has gone from 100 mg to 300 mg, during this time his uric acid has stayed a midling 7-9 mg/dL. Two months ago he was started on probenecid, a uricosuric agent. This is appropriate as his renal function is great (S Cr of 0.9 in a male who works out).
His physical exam is benign.
No additional relevent data can be gleaned from his labs.
What’s the diagnosis?
Proteinuria due to probenecid. The patient stopped the offending agent and within ten days the U/A showed 1+ proteinuria and the PCR was 0.37.
In the exam room I told him it was a membranous nephropathy but according to this letter to NDT from 2007 the pathology is not typically membranous at all. This jives with the rapid recovery from proteinuria after the medicine is withdrawn.
Here is the mechanism of action of probenecid from UpToDate:
MECHANISM OF ACTION — Competitively inhibits the reabsorption of uric acid at the proximal convoluted tubule, thereby promoting its excretion and reducing serum uric acid levels; increases plasma levels of weak organic acids (penicillins, cephalosporins, or other beta-lactam antibiotics) by competitively inhibiting their renal tubular secretion
Cool case.
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.