Way to go Blogger

It seems that Blogger, the service that hosts PBFluids and a number of other nephrology blogs including the Renal Fellow Network, usually gets disregarded and most serious bloggers elect to go with WordPress. I have been delighted with Blogger since beginning PBFluids almost three years ago and have been impressed with the regular updates they have introduced. Today, though they really blew me away. Take a look at the new Blogger Dynamic Views:

You can view any public Blogger website in the new views by adding "/views" to the end of the url.

Follow this link to see PBFluids in Mosaic. Sidebar is another do-not-miss view.

Blogger teased this in their recent ad they put together for South by Southwest:

Those pregnant patients with glomerulonephritis

I am still researching and writing up a monster post on membraous nephropathy and pregnancy (2,300 words and 7 images so far and I still have a handful of references to go). Researching this topic is like archeology. All the literature is from the early 90's and 80's. Almost none of the data is available as full text on the web. No PDFs. Its all scans of photocopies.

But I think the topic is important and having and the fact that the primary data is locked up in paper makes a comprehensive review indexible by google, all the more important.

The survey is also gaining data. So far it is showing definite equipoise on the questions. I am still looking for some more participants.

Nonhepatic hyperammonemias

A couple of months ago we had a patient with hyperammonemia from Depakote. Cool stuff. Dr. RW has the skinny.

Notes from Dr. RW: Nonhepatic hyperammonemias: "---may be underappreciated causes of encephalopathy in hospitalized patients. I recently blogged one example of a nonhepatic hyperammonemia..."

The types of doctor blogs

I guess PBFluids is part Dr. Boring and part Dr. Didactic.

From A Cartoon Guide to Becoming a Doctor

I guess thats better than being Dr. Product Placement.

Most depressing statistic in nephrology

The Scientific Registry of Transplant Recipients (SRTR) prepares an Annual Report in collaboration with the Organ Procurement and Transplantation Network (OPTN) on the state transplants in America. In 2008 there were fewer transplants done than in the previous year. Kidney transplants peaked in 2006 at 18,059 and have fallen for two straight years.

The total number of organs transplanted decreased from 27,586 in 2007 to 27,281 in 2008. This was an overall decrease of 305 organs transplanted (1.1 percent), including 91 (1.4 percent) fewer living donor transplants.

Here is the data on kidney transplants displayed graphically. Note the ever increasing demand for transplant as represented by the number of patients on the waiting list:

Here is the same data from the USRDS:

Increasing number of patients on the wait list, longer waiting times and fewer total transplants. Terrible.

Let's play "Would you biopsy this pregnant lady?"

At journal club this morning I mentioned my patient and polled the room to see who would have sent her for a kidney biopsy. Our fellowship director did his best Sarah Palin impersonation with, "Would I biopsy her? My answer isn't no, it's hell no."

Going around the room all 5 fellows and both of the attendings were in agreement that they would not do the biopsy. This is also in agreement with the first comment on Facebook. It seems that no one would biopsy this patient.

In the best traditions of Web 2.0, let's do an informal survey. Ill post the results next week along with a comprehensive summary of membranous nephropathy in pregnancy (the librarians are hard at work pulling articles as I type).

Would you biopsy this woman?

Today a woman came to see me who was 6 months pregnant. She was seeing me for a second opinion. During her first prenatal visit her OB discovered 4+ proteinuria and the patient was referred to nephrology. A 24-hour urine subsequently documented 7 grams of proteinuria with excellent renal function. She had a serum creatinine of 0.4 mg/dL.

The serologic work-up was negative. No ANA, negative ANCA, no viral hepatitis, compliments were not decreased, HIV was negative. Antiphospholipids were not checked.

The nephrologist then sent her for an ultrasound-guided renal biopsy, which  showed membranous nephropathy.

Now she is six months pregnant and doing well. She has a lot of lower extremity edema but no other symptoms. I advised no specific therapy at this time and close, continuous follow-up.

The whole time I'm seeing her I'm thinking would I have biopsied her? What are the indications for a kidney biopsy in a pregnant patient?

I love it when Dr. Google has just what you wanted to know:

And it's NDT, so hastle free PDFs. Yay!

From the introduction:

Indeed one group recommend no modification of the indication for renal biopsy in pregnancy and suggest that all pregnant women with abnormalities in urinalysis indicative of renal disease should undergo renal biopsy to guide treatment [4], but this is not standard practice. Although it has been established that there is no greater risk of complications of renal biopsy in pregnancy, the consequences to the mother and fetus of post-biopsy haemorrhage could be severe.

The article reviews 20 women who had kidney biopsies during pregnancy and 75 who had post-natal biopsies.

Biopsies during pregnancy (N=20)

• median age 28
• Gestation at biopsy: 20 weeks

Indications for the biopsy:

• 4 with previous diagnosis of lupus and new loss of renal function
• 4 with proteinuria and positive auto-immune serologies
• 4 with new nephrotic syndrome
• 3 in the first with proteinuria and decreased renal function
• 5 in the second trimester with worsening hypertension and proteinuria

The pregnancies resulted in 17 children, 2 miscarriages and one still birth. The average gestation at delivery was 34 weeks. The biopsies all went well with only one complication, mild hematuria that resolved spontaneously. The biopsy changed therapy in 9 of the patients.

Biopsies after pregnancy (N=75)

• median age 31

Indication for the biopsy:

• 50 presented with proteinuria during pregnancy
• 23 associated with pre-eclampsia
• 27 without pre-eclampsia
• 6 with nephrotic syndrome
• 6 with new renal impairment
• 4 with isolated hematuria
• 3 with acute renal failure

By my count that is only 69 patients, not sure what happened to the other 6.

The authors presented follow-up data on 47 patients who followed up within their hospital system. The patients who received follow-up tended to be patients with more severe disease, as patents with mild disease were discharged to primary care.

Grey is bad. Black is better.

The authors conclude that the modern kidney biopsy is generally safe during pregnancy and should be performed in the following circumstances:

In the first trimester
Structurally normal kidneys and:

• an active urinary sediment or
• nephrotic syndrome or
• unexplained CKD (with proteinuria and no evidence of scarring) or
• those with renal impairment and proteinuria in the context of systemic disease or positive autoimmune serology

We feel a diagnosis at this stage of pregnancy is of benefit to guide treatment and allow an informed discussion of the risks:benefit ratio of continuation of pregnancy.

In the second trimester
Renal biopsy should be reserved for those with:

• unexplained nephrotic range proteinuria
• progressive CKD and renal disease in the presence of active systemic disease

Interesting, so by these authors recommendations the biopsy was indicated (she has nephrotic syndrome), despite the fact that it didn't change her therapy. Good to know.

CJASN is not compatible with chrome? -Updated-

Crazy




I just received the following e-mail the ASN

On Tuesday, March 22, 2011, your HighWire sites began receiving a flood of unusual requests for PDFs. What we observed was that a single click to request a PDF of an article would result in multiple requests for the PDF being sent to your sites. In some cases a single request was being multiplied more than 100 times. This caused an overload on the systems responsible for serving PDFs. Early impacts, around 5:00 to 6:00 AM (PDT), were felt as slow response for PDF serving but as the day moved on and traffic on the sites rose the impacts increased until the whole sites were slow as the PDF requests backed up, in the 8:00-9:00 AM (PDT) hours.

Our first response was to turn off access to the PDFs so that the sites would continue to serve other pages well. This was effective and allowed us the breathing room to analyze the traffic more carefully, and we were able to localize the large majority of these multiple requests as coming from users of the most recent version of Google's Chrome browser, which was just updated in the last few days.

At approximately noon on Tuesday we blocked the use of the most recent version of Chrome from all H20 sites. We regretted taking this action (I use Chrome as my browser, too) but it was the way we could restore full service to more than 90 of your users and still allow the other 10 the option to choose a different browser and receive full service as well. Chrome was blocked from approximately noon until 5:15 PM, when we were able to deploy a fix for the Chrome bug.

During the time that Chrome was blocked we were able to perform diagnosis and to determine that for many PDFs, Chrome was requesting the file 32Kbytes at a time. What this mean is that for some large PDFs a single click of the mouse was generating 11,000 requests for the PDF. We were also able to determine how to prevent Chrome from making these requests and we built a fix that was deployed t0 all H20 sites at 5:15 PM.

At the time of this writing all sites have been restored to full function and all users are receiving full service. We have no reason to believe this problem will recur and we deeply regret the impact that the Chrome update had on you and your readers.

Wow, that's cool. Both that they fixed it so fast and that they cared enough to send a note. Go Team ASN!

Facebook

In February, for the first time, Facebook sent more readers to PBFluids than Google. I believe this is from the ASN Kidney News now linking to my posts on their Facebook page. It'll be interesting to see if the trend continues or if it was a one month aberration.

In response to the increasing importance of Facebook to my readership I have created a PBFluids facebook page. A new experiment with this medical blog unfolds. Exciting.

World Kidney Day: top ten list

Nephron Power has a fine post on the top ten reasons the kidney's are the best organs. Here is my riff:

1. A lot of organs can secrete hormones. The kidneys can turn water into stone.
2. Other organs have epithelial cells. Kidneys have podocytes.
3. Orthopods can cast bones. The kidneys can cast red cells, white cells, brown mud and hyalin!
4. Acute renal success!
5. Recombinant EPO causes thrombotic complications, erythropoietin from the kidney, pure gold.
6. The adrenal gland looks like a hat!
7. The lack of randomized controlled data means that all of the kidney's secrets are still, secret.
8. Technology can not duplicate the function of any other organ as well as the kidney. 
9. They are the key part of the machine that turns "the red wine of Shiraz into urine"
10. They have the best diss, "You got a problem with 'dis? Well you can just piss off."

No one could crystalizes the beauty of the kidneys and renal function better than Homer Smith:

The lungs serve to maintain the composition of the extracellular fluid with respect to oxygen and carbon dioxide, and with this their duty ends. The responsibility for maintaining the composition of this fluid in respect to other constituents devolves on the kidneys. It is no exaggeration to say that the composition of the body fluids is determined not by what the mouth takes in but what the kidneys keep: they are the master chemists of our internal environment. Which, so to speak, they manufacture in reverse by working it over some fifteen times a day. When among other duties, they excrete the ashes of our body fires, or remove from the blood the infinite variety of foreign substances that are constantly being absorbed from our indiscriminate gastrointestinal tracts, these excretory operations are incidental to the major task of keeping our internal environments in the ideal, balanced state.

That's not a gap, its the Grand Canyon!

When I talk about toxic alcohols causing anion gap metabolic acidosis I emphasize that these patients have large anion gaps. When you see an anion gap of 16 or 20 think uremia and lactic acid, not methanol. The cases I have seen have almost all had gaps greater than 25 and typically they run in the 30s.

But I have never heard of or seen a gap as big the one that came into the ICU this week-end:

To summarize the data from above. A patient was admitted with an anion gap of 65 that went up to 70 in the next 6.5 hours. I can visualize the ER doc reading the first chemistries, freaking out and re-ordering them, assuming that if the anion gap is greater than the chloride it must be a lab error, hence the repeat labs at 150 minutes after the first set.

Think about that, the anion gap was larger than the chloride concentration.

What kind of alien infestation causes numbers like that?

So when working up a large anion gap one tries to explain the anion gap. The lactic acid was only 34.5 mmol/L. So this patient has the highest lactic acid ever, yet it only covers half the gap. She also had serum ketones that remained positive at a 1:8 dilution and a creatinine of 14.

So is that it? Lactic acidosis, ketosis and uremia for an anion gap of 70? I sent off a D-lactic acid and a 5-oxoproline level, cause what the hell, when's the next time I'm going to see an anion gap of 70. A toxic alcohol screen was sent.

To compete the picture the ABG was: 6.95/13.4/187 with a measured bicarb of 3. With numbers this crazy a trip to the Henderson-Hasselbalch formula is probably not a bad idea:

MedCalc has a sweet HH calculator

So 6.97 is pretty close to the 6.95 measured, so no lab error at least in the ABG. Running Winter's formula (1.5 x HCO3) + 8 ±2 gives a predicted pCO2 of 13, so no respiratory component to the metabolic acidosis.

The next step is to look for toxic alcohols while waiting for the assay to come back from toxicology lab at Children's Hospital of Michigan. The osmolal gap calculation should be greater than 10 in the presence of methanol, isopropyl alcohol or ethylene glycol. The measured osmolality was 327.

MedCalc also has a sweet osmolar gap calculator

So no significant osmolal gap rules out a toxic alcohol. This was confirmed by the toxicology screens that eventually came back. Given the anuric renal failure, profound intractable acidosis and unknown anions still unaccounted for we initiated CVVHD. You can see the effect that had on her bicarbonate and creatinine.

The patient has since recovered and we have learned that she was on metformin so we are toying with metformin induced lactic acidosis as the etiology. Any other thoughts?

The cost of blogging

Michael Hyatt has an a good read about the costs of blogging and advises against getting bogged down in details about design, custom software and hosting. Find a way to cut through that BS inorder to start writing.

He recommends Wordpress.com, premium version for $12-17 a year. He doesn't say why he would choose that over Blogger (the host of PBFluids).

Today I received my bill for blogging for the next year here at PBFluids:

Blogging. Total bargain.

$10. That's all.

Here is Dr. Ves on Medical Blogging. He is actually quoting Seth Godin and Tom Peters. This best sums up my feelings on blogging:

It doesn’t matter if anyone reads it. What matters is the humility that comes from writing it. What matters is the metacognition of thinking about what you’re going to say.

No single thing in the last 15 years professionally has been more important to my life than blogging. It has changed my life, it has changed my perspective, it has changed my intellectual outlook, it’s changed my emotional outlook.

And it’s free.

And the baby with the baboon heart. Or It's an iPad world

I was giving my cardiorenal syndrome lecture on Friday and during the question and answer session one of the residents asked why furosemide drips were more effective than boluses. I explained about the results from this Cochrane review and this recent RCT. Unfortunately I had not read the table of contents from this weeks NEJM:

So of course one of the interns mentions the article and asked if I had read it. I copped to the truth but what happened next was incredible. Across the lecture room I could see dozens of iPads flick to life as nearly everyone started pulling up NEJM.org to check out the latest.

Medicine is magical and magical is art
The Boy in the Bubble
And the baby with the baboon heart

Cardiorenal syndrome

On the first Friday of every month I give a lecture to the residents at St. John Hospital and Medical Center. I like to do an electrolyte lecture but for March the chief resident asked me to talk about cardiorenal syndrome. In researching the lecture I came across this article by Claudio Ronco.

The article defines cardiorenal syndrome as any condition with simultaneous kidney and heart failure. He then goes on to subdivide cardiorenal syndrome into 5 types:

1. Acute heart failure causing acute renal failure
2. Chronic heart failure causing chronic kidney disease
3. Acute kidney injury causing any type of acute cardiac dysfunction (including arrhythmia)
4. Chronic kidney disease causing any chronic cardiac disease
5. Any systemic condition that causes renal and cardiac dysfuction (e.g. sepsis)

This is terrible. Cardiorenal syndrome used to signify the unique cause of acute kidney injury where the decrease in function is due to apparent volume depletion in a patient that obviously overloaded. It named the only scenario where acute kidney injury responded to diuresis. It was unique and specific. Ronco comes along and says, yes I like your version of cardiorenal syndrome so I will make it type 1 in my new all purpose definition of cardiorenal syndrome. Now whenever there is cardiac dysfunction and simultaneous kidney dysfunction we can just call it cardiorenal syndrome.

It doesn't have to be this way look at the example of hepatorenal syndrome. The syndrome does not refere to just any situation with simultaneous renal and liver dysfunction. It is a very specific diagnosis that only occurs with chronic liver disease and ascites. The patients must be oliguric, there is no non-oliguric HRS. Patients must be sodium avid and unresponsive to fluids and albumin. Additionally the patients cannot have laboratory or imaging evidence for an alternative cause of renal failure. Because of this definition hepatorenal syndrome identifies a very specific disorder, with a specific pathophysiology and unique prognosis and treatment options.

Ronco takes the beautiful and evocative name cardiorenal syndrome, strips it of all specificity and then tries to restore it by tacking on five different types. The fifth type 5 is the one that makes my brain explode. Sepsis, really? Acute kidney injury from sepsis that happens in the same patient who also suffers from sepsis induced cardiomyopathy should now be considered to have cardiorenal syndrome? Ronco is a man who has spent his life studying sepsis and acute renal failure, I can't believe he is actually referring to that condition as CRS type 5.

I'm not buying what Ronco's selling. Cardiorenal syndrome begins and ends with type 1 for me.

FYI: Here is the lecture (Keynote, PDF). It still needs some work. I'd like to add a section on ultrafiltration and I need to include the NEJM article on furosemide that was published yesterday.

Go green: recycle your organs

On of my patients, whose daughter had a kidney transplant, came into clinic wearing this T-shirt. Love it.

It says. "My child contains recycled parts. Be a hero, be a donor."