Friday, February 27, 2009
Her pastor reads all the good report cards that the kids in her church bring to him. So she brought in her dialysis report card and her pastor read it on Sunday.
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.
Thursday, February 26, 2009
- Age: 18-70
- Abnormal Cr 1.2-7 women 1.4-7 in men.
- MAP of 125 or less (160/100)
- Proteinuria less than 10g per day
- No diabetics
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.
Wednesday, February 25, 2009
Tuesday, February 24, 2009
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.
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.
Sunday, February 22, 2009
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.
Saturday, February 21, 2009
- 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
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.
- Critically ill adult
- Age: 18 or older
- Renal failure plus at least one other organ system failure or sepsis
Patients were randomized to one of two dosing schemes:
- Stable: Intermittent hemodialysis: 3 days a week effluent
- Unstable: Continuous therapy: effluent of 20 mL/kg/hr
- Stable: Intermittent hemodialysis: 6 days a week effluent
- Unstable: Continuous therapy: effluent of 35 mL/kg/hr
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.
- 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.
- Estimated mortality with less-intensive strategy 55%
- Estimated mortality with intensive strategy 45%
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).
- 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
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
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.
Friday, February 13, 2009
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 secretionCool case.
Thursday, February 12, 2009
Wednesday, February 11, 2009
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
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.
Tuesday, February 10, 2009
Monday, February 9, 2009
Here is the handout. I added a couple of things since giving the lecture on Friday.
Update: I corrected a mistake in one of the delta bicarb questions. Sorry.
Acid Base Handout (Student)
Craig Langman (who has made a previous appearance on PBFluids) wrote an editorial for the Melamine article and pair of letters to The Journal (one from Wang et al. from Taiwan and the other from Ho et al. from Hong Kong).
He recommends the same advice I have been giving for Americans who have adopted Chinese infants:
How should physicians in other parts of the world care for Chinese infants who may have been exposed to melamine-contaminated powdered infant formula? The American Society of Pediatric Nephrology suggests a conservative approach in asymptomatic infants,PDF since stones presumed to have been induced by melamine ingestion appear to be passed easily after hydration, and there are currently no follow-up reports on the children studied by Guan et al. and Wang et al. Performance of abdominal ultrasonography in all potentially exposed Chinese children living in the United States would be likely to cost many millions of dollars, an expenditure difficult to justify, given that both unaffected and affected children may have no symptoms and that the meaning of a stone in an asymptomatic child is uncertain.
Langman emphasizes that each study is unable to estimate a true incidence because the populations studied were not representative of the population at risk.
He also teases the reader by mentioning that stones, which are increasing in frequency among adults, seem to be increasingly common among children. He states that this may be due to dietary and lifestyle issues but doesn't even entertain the possibility that melamine exposure here in the U.S. and around the world may be responsible. This possibility was first suggested in an insightful article in Slate. We know that melamine is found in the U.S., we don't know how long it has been here.
My personal sense is that the Slate article is just scaring people unnecessarily. if the increase in stones was do to melamine we would know it. We would know it because stones that are removed by interventions are always analyzed in a stone lab. The stones in China that were due to melamine were made of uric acid and melamine. If even a single stone in the U.S. was found to be melamine the whole medical world would go ape.
All of the children's parents were given a survey to establish demographic data and judge exposure. The investigators questioned parents on the brand and amount of formula ingested and matched it up to government data on the amount of melamine in each brand. Children were then put through varying degrees of biochemical and ultrasound testing.
All the children were under 36 months of age, the population most at risk of melamine stones.
- High melamine (over 500 ppm)
- Moderate melamine (less than 150 pm)
- Definite stones
- Suspected stones (increased sporadic, punctiform echogenicity in the kidneys or pyelocalyceal system)
- No stones
In 589 exams they found definite 50 stones, 112 suspected stones and 427 children were stone free.
Microalbuminuria was found in more of the children with stones (10%) or suspected of having stones (13.6%) compared to the stone free children (5.6%). Symptoms were not helpful in distinguishing stone formers from the stone free.
Fifty-six children had serum creatinine checked (22 with stones, 21 with suspected stones and 13 without). All of the creatinines were normal.
Interestingly 62 of 404 children had a calcium to creatinine ratio that exceeded age based targets. The 15% rate of hypercalciuria was not associated with stone risk in this study (p=0.34).
In multivariate analysis exposure to high-melamine milk (7x as likely) and pre-term birth (4.5x as likely) were significantly associated with stone formation.
The primary conclusion is that the physical and biochemical lab add nothiong to the evaluation of melamine stones. The birth history and the melamine exposure assessment are critical but need to be followed up by an ultra-sound.
The authors note that only 23 of 121 children exposed to high-melamine formula developed stones
Last week on the fellow education day we did the ESRD NephSAP. Dr. Bellovich showed me that the complete text is available through iTunes as a podcast. Sweet. I have started to listen to the NephSAP in the car. Seems like a pretty cool way to get the info.
Sunday, February 8, 2009
In India kidneys are widely available for purchse. This allows people with the means to get a kidney. The people with the means include Americans and Europeans as transplant tourists. organ tours.
JAMA published an article in 2002 showed that most of the donors are poor people in debt and a few years later they are still or again in debt and have experienced a decline in health. An essay in Lancet the following years details the global organ traffic and some of its negative consequences.
Despite these horrors they abysmal supply of organs makes the concept of buying and selling organs appealing. I have confidence that a well regulated market place for organs could improve the supply and avoid the horrors which result from the under-the-table, unregulated bazaar that currently exists.
Sally Satel outlines the pro argument in a couple of essays.
Wednesday, February 4, 2009
I would look at the March 2008 Seminars in Nephrology which is an entire issue devoted to nephrolithiasis.
The issue was guest edited by John Asplin, one of the best teachers I had during my fellowship. We co-authored a chapter on potassium and I tutored medical students for his renal physiology class. He is medical director of Litholink, a independent clinical lab which provides deep clinical information on the metabolic abnormalities found in patients with kidney stones. I use litholink for all of my stone patients and love it.
It also has multiple articles by Fred Coe and Elaine Worcester. Dr. Coe ran a weekly fluid and electrolyte conference that was one of the highlights of my fellowship experience. Every week a fellow would bring a set of electrolytes and Coe would tell you all about the patient simply from the numbers. It was uncanny how good he was.
My favorite quote from Dr. Coe was:
What you do is serious nephrology [he was referring to acute and chronic renal failure]. What I do is just civilian nephrology. [referring to nephrolithiasis]Elaine and I co-authored a chapter on calcium, magnesium and phosphorous. We had a great collegial relationship during my fellowship and only after I graduated did I realize how large she was in the field of nephrolithiasis.
Craig Langman also wrote one of the articles in this issue of Seminars in Nephrology. He is a pediatric nephrologist and I spent a couple of months with him at Children's Memorial during my second year of fellowship. He's a great teacher. He is now on the lecture circuit for Genzyme. If he comes to town, go. He's one of the great teachers in nephrology.
Update: Dr. Langman sent me a note stating that he is not "on the circuit." But my advice stands, if he comes to town, don't miss him.
Monday, February 2, 2009
When a patient needs a metabolic evaluation for kidney stones the twnety-four hour urine should include at minimum:
- Uric Acid
- Urea nitrogen
Urine oxalate over 90 mg/day should trigger an evaluation for enteric hyperoxaluria or primary hyperoxaluria.
Hypocitraturia is defined as a citrate below 325mg/day. Hypokalemia can trigger hypocitraturia (along with metabolic acidosis) so be careful when prescribing a thiazide for hypercalciuria, the resulting hypokalemia could surpress citrate and increase rather than lower the risk of developing a kidney stone.
While bowel disease is usually associated with calcium oxalate stones, patients often have decreased urine pH which predisposes them to uric acid stones.