Wednesday, January 28, 2009
Battlestar Galactica and wierd renal failure references
Check this out.
My favorite part is "...this could lead to chronic renal failure and he could lose a kidney..."
When did Up to Date get formatted for the iPhone?
I tap on the UpToDate icon to launch Safari and go straight to UpToDate. The icon is called a webclip. You can learn more about this at this Apple webpage.
Then I log in with my username and password.
Look at how simple the search page is. It loads nearly instantly.
The results load fast and are way easier to read than on the previous site.
You then get an outline of the subject. Burton Rose calls them "Cards."
Then you arrive at a manuscript that reads great on the iPhone screen.
Even foot notes pull up the reference and abstract.
Tuesday, January 27, 2009
HIV and the Kidney
Excellent website on HIV from the UCSF: HIV InSite Knowledge base
I though my lecture's section on HIVAN Therapy was little light here is InSite's monolog on therapy for HIVAN:
Clinical Course and Treatment
In the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, the U.S. Department of Health and Human Services now includes a diagnosis of HIVAN as an indication for ART, regardless of CD4 count.(94) Other treatment options that may influence the course of HIVAN include angiotensin-converting enzyme inhibitors (ACEIs) and corticosteroids administered before dialysis or kidney transplantation.
The original case reports of HIVAN described a rapid and inexorable progression to ESRD over a period of weeks to months.(2-4) However, after highly active ART came into use, several dramatic reports of renal recovery among these patients emerged in the medical literature. In one study, a patient with HIVAN and dialysis-dependent renal failure became dialysis free after 15 weeks of ART. Repeat renal biopsy revealed significant histologic recovery from fibrosis with only infrequent glomeruli showing mild collapse and minimal fibrosis.(65) Since then, a growing number of studies has helped establish ART as a first-line treatment for HIVAN.
The effect of ART on kidney disease progression has been characterized primarily by observational studies. A cohort of 53 patients with biopsy-proven HIVAN from the Johns Hopkins renal clinic was found to have better renal survival when treated with ART compared with patients who did not receive ART (adjusted hazard ratio: 0.30; 95% CI: 0.09-0.98).(95) In a retrospective study of 19 patients with a clinical diagnosis of HIVAN, after median follow-up of 16.6 months, the use of protease inhibitors was significantly associated with a slowing of the decline in creatinine clearance.(96)
In the Strategies for Management of Antiretroviral Therapy (SMART) study, 5,472 HIV-infected patients who had a CD4 count of >350 cells/µL were randomly assigned to continuous or episodic use of ART and were followed for a mean period of 16 months. Investigators found that, compared with continuous ART, planned treatment interruptions guided by CD4 counts significantly increased the risk of fatal or nonfatal ESRD (hazard ratio: 4.5; 95% CI: 1.0-20.9) in the treatment interruption arm. Although this study was not statistically powered to detect a difference in renal outcomes, the high incidence of ESRD in the treatment interruption group suggests that continuous therapy with antiretroviral medications is a key factor in preventing and slowing progression of kidney disease.(97)
Angiotensin-Converting Enzyme Inhibitors
Both ACEIs and angiotensin II receptor blockade have inhibited the development and progression of HIVAN in animal models.(98-100) Two prospective studies support the use of ACEI for the treatment of HIVAN. In a case-control study of 18 patients with HIVAN prior to the advent of ART, 9 were treated with captopril, and matched with 9 controls.(101) The captopril-treated group had improved renal survival, defined as time to ESRD, compared with controls (mean renal survival: 156 ± 71 days vs 37 ± 5 days; p < .002). In a single-center, prospective cohort study of 44 patients with HIVAN, 28 patients received fosinopril 10 mg/day, and 16 patients who refused treatment were followed as controls over 5.1 years.(102) The median renal survival of treated patients was 16.0 months, with only 1 patient developing ESRD. All untreated patients rapidly progressed to ESRD over a median period of 4.9 months. Despite the limitations of these studies, they suggest that ACEIs may be beneficial in curbing progression of HIVAN, and this class of drugs is a reasonable first choice as an antihypertensive agent for patients with HIVAN.
Evidence supporting the use of steroids for the treatment of HIVAN is also based on observational data.(95,103,104) In a single-center cohort study, 20 patients with HIVAN were prospectively enrolled to receive treatment with corticosteroids. Most patients (17 of 20) manifested improvements in kidney function and significant reductions in 24-hour urinary protein excretion. After steroid therapy, mean rates of protein loss declined from 9.1 ± 1.8 g per day to 3.2 ± 0.6 g per day (p < .005).(105) Another study of steroid therapy employed a control group and found similar results with no increased risk of infection in the steroid group.(104) Although these studies were generally limited by their nonrandomized designs, based on this evidence, steroids are considered second-line therapy for patients with HIVAN. The use of steroids should be considered for patients with a documented rapid deterioration in kidney function despite ART.
Monday, January 26, 2009
Melamine Crisis: The Death Penalty
Just as we saw in the contaminated pharmaceutical disaster the heavy hand of communist China comes down on Zhang Yujun and Geng Jinpin both who were sentenced to capital punishment for their roles in the Melamine Milk Contamination Tragedy. A third man, Gao Junjie, was sentenced to death for his role but received a two year reprieve so he still may escape the firing squad.
Good luck with that.
The chairwoman of Sanlu Group, Tian Wenhua, was sentenced to life in prison for her company's role in this. Can you imagine a CEO or Chairman of the Board getting that kind of sentence in the US? Of course I was equally shocked when they executed the head of the Chinese FDA for the pharmaceutical scandal.
China is different.
Source: New York Times
My previous posts on Melamine
Lecture at Providence Hospital on Electrolytes
I did this lecture in Keynote and I am blown away by how good it presents through SlideShare. Really impressive.
Wednesday, January 21, 2009
Tuesday, January 20, 2009
More information on DataCase and moving files to the iPhone from a Mac
This is for Mac OS X Leopard (10.5).
Press command-K from the finder to bring up the Connect to Server command.
Enter the afp address listed at the bottom of the DataCase screen. Then connect. You should click on guest at the next dialog box.
You will then be looking at a list of servers (folders) to mount on desktop.
Select the folder you want and then accept the connection on the iPhone.
Then you will have a new shared volume on the computer and you can upload, download or browse the files just like any hard drive.
Monday, January 19, 2009
How to carry PDFs around on your iPhone
In order to do this you must use a third party application. I will demonstrate the application that I use, DataCase (6.99 from the iTunes Store).
1. Start the application by tapping on it.
2. To browse documents that have been previously loaded, just tap on the file type at the bottom of the screen or tap on the folder icon in the center of the white donut.
3. You then can select the volume yoiu want to look at. Volumes are like folders on your computer.
3. To see the files on a PC or Mac, type in either the http or ftp address in the address bar of a internet browser or FTP client. The iPhone and the computer must be logged on to the same wireless network for this to work (I think).
When you select either of the above directories you will need to accept the connection on the iPhone. This provides some degree of security.
You can then download any file by simply clicking on it in the browser.
To upload the files, launch an FTP client. I use Transmit by Panic software. Enter the ftp address at the bottom of the DataCase home screen and drag the files you want over to the iPhone.
You can view any of the files you uploaded on the iPhone right in the DataCase application.
Here are the instructional How-To videos from DataCase's website.
MacOS X Leopard walkthrough:
Thursday, January 15, 2009
IV Iron in Hemodialysis
He started by talking about why Fe deficiency is so prevelant among CKD and dialysis. As an explanation he did a brief overview of Hepcidin.
Fe is a powerful growth factor for bacteria.
During an infection the body decides to withold Fe.
Inflammation leads to increases in hepcidin which increases ferritin.
Hepcidin decreases intestinal iron absorption and increases Fe sequestration in RE system. The end result is a decrease in serum Fe and TSAT.
DRIVE Study by Daniel Coin and Morin was designed to see if giving Fe in patients with a high ferritin and low TSAT was effective.
- Hgb less than 11
- ESA over 22,500 U/week
- Ferritin 500-1200
All patients had their ESA bumped 25% and randomized to either 1g of Fe or placebo.
The primary end-point was a change in hemoglobin over 6 weeks. The hemoglobin rose 10.2 to 11.3 in control and 10.4 to 11.9 in the Fe group over 6 weeks.
47% of the treatment group had an increase in hemoglobin of 2g versus 29% in the control group.
DRIVE-II by Kapoian
6 week follow-up after the randomized trial. Observational
Hgb increase was sustained despite the Fe group getting the Epo cut by 20% with no change in the in the epo dose of the control group.
Ferritin initially rose to 934 from 760+.
No different in responce in the patients with ferritin 500-800 vs 800-1200.
TSAT was not predictive of response low TSAT and high initial TSAT had the same response.
Prospectively studies cannot find link between IV Fe and infection.
Here is some criticism of the DRIVE study by the National Anemia Action Council:
The purpose of the DRIVE study and its six week extension, DRIVE II, was to determine the efficacy and safety of supplemental intravenous iron in anemic hemodialysis patients receiving recombinant erythropoietin who had a transferrin saturation <> 500 ng/mL. The intravenous iron group did increase their hemoglobin levels slightly more than control patients not given intravenous iron without additional toxicity, leading the authors to conclude that intravenous iron in this situation was both safe and effective. Unfortunately, the design and power of both studies were not sufficient for the investigators to reach these conclusions.
First, the decision to increase the dose of recombinant erythropoietin in each group by 25 % confuses the response to ESA and iron. In a chronic inflammatory state, such as chronic renal disease, the problem is not impaired iron availability but insufficient erythropoietin, which is required to mobilize iron and upregulate transferrin receptor expression. It is well recognized that erythropoietin trumps hepcidin in this situation and the authors merely confirmed that phenomenon.
Second, in the control groups of both DRIVE and DRIVE II, there were a disproportionate number of women, who are more likely to be iron deficient, and their response to recombinant erythropoietin proved this, reducing the effectiveness of comparisons.
Third, both DRIVE and DRIVE II were open label observational studies and in addition physician discretion was also allowed with respect to erythropoietin dosing and iron administration. This discretion can introduce significant bias, weakening the conclusions of the studies.
Fourth, no attempt to estimate blood loss, iatrogenic or otherwise, was made for either experimental group. Fifth, the difference in the hemoglobin level achieved with supplemental iron was not striking and also pushed the hemoglobin level above that currently recommended for safety reasons. Finally, since the serum ferritin and transferrin saturation increased in the iron-supplemented group, a state of iron overload was achieved that was unnecessary and the 12 week observation period was certainly not long enough to exclude the possibility of iron-induced organ toxicity.
It is clear that more data derived from larger prospective trials that are conducted for longer periods are needed. Until this data becomes available, anemic hemodialysis patients not responding to conventional doses of recombinant erythropoietin, in whom the serum ferritin is greater than 500 ng/mL, should first be evaluated for a source of blood loss or infection. Then the patient should be given a higher dose of recombinant erythropoietin for a minimum of 6 weeks with serial transferrin saturation and ferritin measurements before resorting to intravenous iron supplementation.
Fishbane then spoke about the possibility of proteinuria induced by iron sucrose. He showed the Agarwal data on proteinuria and IV iron. He stated that with out knowing how long the proteinuria lasted it was impossible to guess if this was important clinically.
Platelets in Nephrology
Fe deficiency causes reactive throbocytosis
ESAs raises platelets
ESAs cause fe deficiency
Increased RBC push platelets along the walls of the blood vessel. So treatment may cause a lot of atherothrombotic complications because they have both more platelets and red cells.
In DRIVE 20% drop in platelets with Fe treatment.
Streja Et al. used the Davita retrospective database to show a nice human association of TSAT and platelets with thrombosis. Importantly he showed no increase in mortality for Hgb over 13 when the data was controlled for the platelet count. Dr. Fishbane was unable to suggest a how one could design a prospective RCT to test this theory.
Wednesday, January 14, 2009
Hey my diabetic nephropathy lecture is in the spotlight
Your presentation Diabetic Nephropathy is currently being showcased on the 'Health & Medicine' page by our editorial team.
It's likely to be there for the next 16-20 hours...
- the SlideShare team
And here it is:
Here is the actual lecture. I would recommend going to the SlideShare website and downloading the lecture as it looks a lot better in PowerPoint than in the online presentation. You will need to establish a SlideShare account to download the presentation.
Tuesday, January 13, 2009
Has anybody seen this?
The urine electropheresis shows non-specific proteinuria.
- The first patient is an obese young African American woman with WHO type V lupus nephritis.
- The other patient is a thin young Caucasian woman with secondary FSGS due to chronic reflux. Her most recent PCR is 1.7, and her 24-hour urine from one week prior is 4.9 g.
Any ideas? What am I missing?
Monday, January 12, 2009
Nephrology Fellowship: by the numbers
The number of new nephrologists is just under 400 per year.
30% are woman and 51% are US medical graduates. This is a decrease in the number of foreign medical grads from 50% in 1999 to 40% in 2005.
757 applicants applied for 372 spots in at 135 accredited programs in 2007.
Nephrology is the fourth most popular internal medicine sub-specialty after cards, Heme/Onc and Pulmonary/Critical care (look at the bottom of the list and add that to the combined Pulm/Crit Care).
42 kidney transplant programs are available.
There are 19 programs in interventional nephrology however, only 6 are certified by the American Society of Diagnostic and Interventional Neophrology (ASDIN).
Sunday, January 11, 2009
What's going on with diabetes
That makes three negative trials in the last 12 months.
- ADVANCE trial: 11,140 people randomized to gliclazide in order to lower the A1c to 6.5, the control group achieved 7.3%. This lowered combined micro- and macrovascular complications by 10% 18.1% vs 20% after a median of 5 yrs (p=0.01). However the difference was entirely driven by a 21% reduction in nephropathy, with no reduction in retinopathy, macrovascular complications or reduction in CV death or death from any cause.
- ACCORD Trial: 10,251 people randomized to usual care (A1c 7.0-7.9) or intensive care (A1c under 6%). There was no difference in the primary composite outcome of non-fatal heart attack and strokes and CV mortality. Unfortunately there was a significant increase in total mortality (p=0.04) with high mortality in the intensive therapy group.
Unfortunately, this looks like a bust. Not one of the trials have shown any sign that improved glycemic control translates into reduced heart attacks or strokes.
Here is a powerpoint lecture on DM I gave a year ago. SlideShare kind of butchers the formatting so if you are really interested download it rather than whatch in the online viewer.
Thursday, January 8, 2009
2008 the year in Review
- ATN trial shows no benefit to high dose dialysis in acute kidney injury
- FDA finally validates concerns of oral sodium phosphorous solutions for colonoscopy prep
- Concerns with the COOPERATE trial
- Home blood pressure monitoring
- Reduction of proteinuria with aliskren
- No CERA for USA
- iPhone Medical Apps
- Lecture Seder Style
- Melamine Milk Poisoning
- Acid-Base Lecture
- IV Fluids Lecture
- PICARD Study
- iPhone medical applications
- Melamine milk poisoning and kidney stones
- Acid-base lecture for ER-residents
- Getting ready for fluids and electrolyte lecture
- Bumex same short pharmacokinetics of lasix with better bioavailability
- Bevacizumab and acute renal failure
- Melamine milk poisoning continues to make headlines
- Acid-base lecture for residents of St John
- Teaching on two-Ell: acute renal failure and GFR
- Teaching on two-Ell: anemia and ckd
Tuesday, January 6, 2009
Renal Revascularization: The Astral Trial
This shows that the 806 patients randomized to ASTRAL dwarves all of the previous work on the subject. (source)
ASTRAL was billed as the definitive study to determine if angioplasty and stent preserved renal function, improved blood pressure, prevented hospitalizations, or reduced CV mortality. Patients were followed for 27 months. The enrolled cohort is representative of that are typical candidates for renal revascularization. Here are the graphs from the Investigator Newsletter:
The bulk of patients had moderately severe renal disease. It is important that they did not select patients too late in the disease where revascularization may be too late to save the kidney. Similarly you wouldn't wat to intervene too early where the splay between the groups may take longer than 27 months to materialize.
The average GFR was 40 mL/min.
Of note: if you just looked at patients with an initial GFR<25, size="4">Length
The fact that the affected kidney size was pretty good goes against the potential criticism that they were revascularizing too late after permanent infarction and scarring has ocured.
Most of the patients had severe stenosis, a high grade that if found during a diagnostic angiogram would be followed by an intervention.
- 93% of interventions included use of a stent.
- The mean stenosis was 76%
At follow-up, no difference in creatinine, blood pressure, time to first renal event, or mortality (p = ns for all outcomes)
The authors emphasized that there was no benefit for the entire cohort but they feel that the therapy is likely helpful for some subset of the population. I agree, like every nephrologist, I have seen patients have dramatic improvements in renal function following angioplasty for RAS. With the immense ASTRAL database it will be exciting to see if the authors can tease out which subgroups benefit from this technology.
Despite having seen multiple patients benefit from renal artery angioplasty I have remained a skeptic of the technology. Part of this comes from the older flawed and small trials and partly due to the ineffectiveness of cardiac angioplasty to help patients except in regards to reducing angina (a condition that doesn't have a renal analog) or in patients having an active infarct.
Monday, January 5, 2009
Kidney Stones and Chronic Kidney Disease
The most important aspect of this is the question that was left unanswered: do kidney stones cause CKD. The association makes sence but causality would be much more important because we have good tools to prevent kidney stones and it would be wonderful if by preventing kidney stones we could also be preventing future kidney failure.
Hopefully this question will be answered in the near future.
[F-FC202] Kidney Stones Are Associated with an Increased Risk of Developing Chronic Kidney Disease
Andrew Rule, Eric Bergstralh, L. Joseph Melton, Xujian Li, Amy Weaver, John Lieske Nephrology, Mayo Clinic; Health Sciences Research, Mayo Clinic
Background: Kidney stones lead to chronic kidney disease (CKD) in patients with rare genetic diseases (e.g., primary hyperoxaluria), but it is less clear if kidney stones are an important risk factor for CKD in the general population.
Methods: A cohort of all Olmsted County, MN residents with incident kidney stones in the years 1984-2003 were matched 3:1 to controls in the general population based on index date (first stone diagnosis for stone formers and any clinic visit for controls), age, and sex. Diagnostic codes (yrs: 1935-2007) and serum creatinine levels (yrs: 1983-2006) were captured with the linkage infrastructure of the Rochester Epidemiology Project. Risk of incident chronic kidney disease was assessed using clinical diagnostic codes, end-stage renal disease (dialysis, transplant or death with CKD), sustained (>90 days) elevated serum creatinine (>1.3 mg/dl in men, >1.1 mg/dl in women), and sustained estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. Proportional hazards models adjusted for age, sex, and baseline and time-dependent co-morbidities (diabetes, obesity, gout, hypertension, hyperlipidemia, alcohol, tobacco, coronary artery disease, heart failure, cerebral infarct, and peripheral vascular disease).
Results: After excluding persons with prevalent CKD, 4424 stone formers and 10995 controls were identified with a mean follow-up of 8.4 and 8.8 years, respectively. Stone formers had an increased risk of developing a clinical diagnosis of CKD [hazard ratio (HR)=1.6, 95% CI: 1.4-1.8, see figure], end-stage renal disease (HR=1.4, 95% CI: 0.9-2.2), a sustained elevated serum creatinine (HR = 1.4, 95% CI: 1.2-1.7), and a sustained reduced eGFR (HR = 1.4, 95% CI: 1.2-1.6).
Conclusions: These data argue kidney stones to be an important risk factor for chronic kidney disease.