Lead time bias

As I go through the literature on early nephrology referral, I am troubled by the possibility of lead time bias. This was a large issue in the debate surrounding the optimal time to initiate dialysis. The problem comes from measuring survival from the initiation of dialysis.

Patients with good nephrologic care regularly get started on dialysis earlier than their counterparts with poor or non-existent CKD care. This is evidenced by the lower creatinines at the time of initiation of dialysis in patients with early referral seen in multiple studies.

This is consistent with my practice where I tell my patients that we “…want to delay dialysis as long as possible, but not longer than possible…” because if they have profound malnutrition or advanced heart disease due to the delay of dialysis they will do poorly once they transition to dialysis.

Because of this skew in the initiation of dialysis it is important to account for that in any analysis of survival on dialysis. I hope this short slide show makes this clear.

Note: I do not know if lead time bias is responsible for the prolonged survival with early referral to nephrology I just know that it needs to be accounted for and most literature ignores this potential source of error.

Fluid and Electrolyte lecture at Providence from Friday

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.

HIV and the Kidney

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.

Antiretroviral Therapy

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.

Steroids

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.

Lecture at Providence Hospital on Electrolytes

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.

Hey my diabetic nephropathy lecture is in the spotlight

This morning I woke to find this in my in-box:

Hi nephron!

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…

Cheers,

– 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.

What’s going on with diabetes

VADT is yet another negative trial showing a lack of benefit from controlling blood sugars.

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.

All three of these trials were looking to prove that better glycemic control could reduce strokes and heart attacks. We have known since the early nineties that good glycemic control prevents or delays microvascualr complications (kidney disease, blindness, neuropathy) but the data on cardiovascular disease was lacking. This is important because relatively few diabetics develop ESRD and most patients die of heart disease, a macrovascular complication. For example in type 1 diabetics the 20 year risk of developing ESRD is only 2.2%, while the risk of death is four times that at around 10%.

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.

Fluid and Electrolyte lecture at Providence from Tuesday Dec 16

I did a lecture at Providence last week.

I was scheduled to just give a electrolyte lecture without any further guidance. I pulled out two interesting cases I had seen in the last few weeks. Both patients have a non-anion gap metabolic acidosis, but one is hypokalemic and the other is hyperkalemic.

Here is the native Powerpoint files for you to use or edit.

Here is the SlideShare for online viewing

July first lecture on IVF, Diuretics and dysnatremia


Today I gave the first lecture of the ’08-’09 Academic Year. This was morning report for internal medicine. I did a lecture on IVF, diuretics, total body water and dysnatremia. It was a good lecture but Powerpoint only. I am about half-way done with the killer handout I am working on and am disapointed that I didn’t finish it. Hopefully will have it done for the next lecture in two weeks.

Fluids And Electrolytes July1

View SlideShare presentation or Upload your own. (tags: diuretics sodium)