Check this out.
My favorite part is “…this could lead to chronic renal failure and he could lose a kidney…”
Check this out.
My favorite part is “…this could lead to chronic renal failure and he could lose a kidney…”
Last July when I went to use UpToDate on the iPhone it used the traditional PC website so it was very slow and ill suited to the iPhone. I went to use it a few days ago and it had been reformatted to the iPhone and was fast and clean.
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.
Gave a lecture to the ID faculty and fellows today. That was the fourth lecture in 2 weeks. Done running the lecture gauntlet.
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.
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
I am trying to do a monthly lecture for the Providence internal medicine residents on electrolytes. I gave my second one last Friday. It was an interesting case we had of hypernatremia on the consult service last summer.
I did this lecture in Keynote and I am blown away by how good it presents through SlideShare. Really impressive.
Cool image from the lancet
I was playing around, I mean doing important work, and found out you don’t need to use a browser or an FTP client to move files on and off the iPhone.
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.
One of the coolest features of the iPhone is using it as a wireless USB drive. The iPhone can be used to carry all of your documents around so that you can use them on any convenient computer. One advantage over a thumbdrive is that you can not only transport these files from cvomputer-to-computer but you can view the files, right on the iPhone, as well.
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.
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).
Here are the instructional How-To videos from DataCase’s website.
MacOS X Leopard walkthrough:
Steven Fishbane, MD from The University of Pennsylvania, came to our fellowship program to discuss Fe and hemodialysis. He began by talking about hepcidin and then went on to discuss the iron targets in light of the DRIVE trial and then touched on IV Fe and proteinuria and finished with a discussion of platelets and mortality and its relationship to recent anemia trials.
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.
Ave TSAT 18, Ferritin 761, CRP 27, Hgb 10.3, ESA 34,000 U/wk
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
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.
This morning I woke to find this in my in-box:
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.