Deep in the Kidney: Gottschalk Lecture at #EB2013

Apr 23 2013 Published by under EB2013

The highest award of the APS Renal section went to Jeff Sands, MD, a clinician and physiologist and former editor of American Journal of Physiology Renal Physiology. My tweets from his lecture follow.

Share

No responses yet

A Starling Is Born: #EB2013

Apr 22 2013 Published by under Kidney Function

keep-calm-and-talk-science.pngMany awards in science give one the chance to deliver a lecture. These awards are usually named for famous dead guys, such as Ernest Starling. Here is his biography from the APS Website:

Ernest Starling (1866-1927) was pre-eminent in the golden age of British Physiology. His name is usually associated with his Law of the Heart, but his discovery of secretin (the first hormone whose mode of action was explained) and his work on capillaries were more important contributions. He coined the word 'hormone' one hundred years ago. His analysis of capillary function demonstrated that equal and opposite forces move across the capillary wall--an outward (hydrostatic) force and an inward (osmotic) force derived from plasma proteins. Starling was much more than a gifted scientist. He held passionate views on many subjects -- education, London University, Germany and the British Government, etc. -- and was not slow to voice them. Time has shown most of his views to be right, but their publication may have hampered his worldly success. Working on defense against poison gas during WWI, he crossed swords with the war officer. After resigning his commission as colonel, he became chairman of the committee supervising British nutrition and successfully introduced food rationing.

If he were around today, I just know he would have blogged. But on to an excellent presentation by Donald Kohan, MD, PhD, a professor at Utah who studies the role of the collecting duct in control of blood pressure. He has teased out the role of a number of substances by creating mice that overexpress or lack these substances only in the collecting duct cells. Just creating that many mice over a career blows my mind! His talk flowed so logically and told the story so clearly, I am afraid all subsequent lectures for the near future will falter in comparison.

I live-tweeted the session, and I have collected my thoughts below. Some abbreviations pop up now and then, including CD for collecting duct, AC for adenyl cyclase, and PRA for plasma renin activity. If something is unclear, ask in the comments.

I also enjoyed when he acknowledged the support of his spouse and family by pointing out how professionally-accomplished his wife was as well.

Share

No responses yet

Sweet 16 for #Nephmadness: My Thoughts

Mar 27 2013 Published by under [Medicine&Pharma]

The editors of eAJKD have narrowed the field from 32 to 16. Here are their picks:

Glomerulus

  • Medicare ESRD Benefit (1) vs PD First (14): Medicare ESRD Benefit (also my pick)
  • KDIGO (5) vs USRDS (7): KDIGO, the favorite, won, besting my pick of the USRDS.
  • Epigenetics (8) vs Propensity Scoring (6): Editors went with a bit of an upset here; I picked propensity scoring, a proven technique, over epigenetics, a promising but as yet unproven contender
  • Real Time PCR (4) vs Randomized Clinical Trial (2): RCT is the gold standard, and it wins. (also my pick)

Proximal Tubule

  • HEMO Trial (1) vs TREAT Trial (3): HEMO wins this one (also my pick)
  • ALLHAT Trial (5) vs IDEAL Trial (7): This was a tough choice, but I went with the underdog while the favorite, ALLHAT, moved on.
  • FGF23 (8) vs Anti-PLA(2)R (6): Anti-PLA(2)R is really important in membranous nephropathy, a common disease in adults. Not so common in pediatrics, so I missed this one as well.
  • HIVAN (13) vs APOL1 (2): I could not believe HIVAN won the first round; glad to see APOL1 take this match-up (also my pick)

Loop of Henle

  • Captopril (1) vs Mycophenolate Mofetil (3): ACE inhibitors rule nephrology; Captopril wipes the floor with MMF (also my pick)
  • Eculizumab (5) vs Tolvaptan (10): Seriously, what do these people see in Tolvaptan? I hope Captopril annihilates this newbie.
  • Renal Fellow Network (9) vs UpToDate (6): UpToDate takes it (also my pick)
  • ASN Kidney Week (4) vs NephSAP (2): Kidney Week for the win (also my pick)

Collecting Tubule

  • MDRD eGFR Equation (1) vs 24-hour Cr Cl (3): Equation beats collection is like the fast break taking down a half-court game, yet when in doubt we still get a 24-hour urine
  • Winter's Formula (5) vs FeNa (7): Glad to see FeNa take this round (also my pick)
  • Kidney Biopsy (8) vs Citrate Anticoagulation (11): Like anticoagulation could beat the ultimate diagnostic test (also my pick)
  • Scribner Shunt (4) vs Kidney Transplant (2): While the shunt was revolutionary and lifesaving in its time, we no longer use it. Kidney transplant, while not perfect remains the best form of renal replacement therapy and gets the win (also my pick).

The picture shows the Sweet 16 and my picks for the Elite 8, with rationale below:

Click to enlarge

Click to enlarge

  • Medicare ESRD Benefit vs KDIGO: No question in my mind; guaranteed coverage for end-stage therapy wins.
  • Epigenetics vs Randomized Clinical Trial: Unproven area of study vs the gold standard? Duh-RCT for the win!
  • HEMO Trial vs ALLHAT Trial: HEMO still guides dialysis therapy today. ALLHAT was important and affects alot of people, but the tip goes to HEMO in my mind.
  • Anti-PLA(2)R vs APOL1: The cause of membranous nephropathy vs the gene that explains the excess burden of kidney failure in African Americans can only mean one answer for me; APOL1 to the elite 8!
  • Captopril vs Tolvaptan: ACE inhibitors are the miracle drugs of nephrology. I cannot believe that Tolvaptan has hung around this long; it's time to retire that glass slipper!
  • UpToDate vs ASN Kidney Week: UpToDate clearly rules the reference rack these days, but for my specialty area I often want to know more, including recent research and the opinions of my colleagues. Kidney Week gives me all of that, as well as an excuse to hobknob with other nephrologists and talk about urine. It will be a battle, but I give Kidney Week the edge.
  • MDRD eGFR Equation vs FeNa: I did not have the eGFR equation advancing to the Sweet 16; nevertheless, I must favor it over FeNa for overall usefullness at this point in the competition.
  • Kidney Biopsy vs Kidney Transplant: Ah, the gold standard of diagnosis vs the gold standard of treatment.  I have to give the win to transplant. Even with biopsy, kidneys fail and require treatment...with transplant.

Head here to learn more about these teams and to vote for the Elite 8. Please allow my opinions to sway your vote; how has Tolvaptan made it this far, anyway???

Now for the state of my bracket:

  • Round 1:  27 out of 32
  • Round 2:  10 out of 16

What are you waiting for? Go vote!

Share

No responses yet

Bracket Fever

Mar 21 2013 Published by under Kidney Function

What more can I say?

Not just for basketball tournaments now, the beloved brackets of March feature all sorts of match-ups. My favorite is NephMadness (#Nephmadness), a battle among 64 drugs, formulas, studies, and other kidney milestones. Click over to the site and learn about these important milestones in nephrology. I promise, you will learn a lot of cool stuff.

You can also click here to see a brief discussion of my bracket. Yes, my final four feature no Cinderellas, but there are some upsets along the way.

Now I must go practice some nephrology, without the madness!

Share

No responses yet

Social Saturday: A New Page

Jan 05 2013 Published by under [Medicine&Pharma]

Astute readers may have noticed a new page here yesterday, highlighted in the image below:

CircledBanner

Latest Kidney Health News features a board created in ROCKZi, a service that aggregates content using the blekko search engine. In addition to the usual topic clusters, ROCKZi lets anyone with a Facebook account create a board about anything in less than a minute. The board can then be embedded on your own website, providing content for your readers even when a blog post cannot be contemplated. You can read more about using ROCKZi to embed social news at Problogger. The format allows direct social interaction via buttons that pop up when you mouse over an article, including comments and voting things up (rockz button). The service also provides a bookmark so that articles can be added from other sites to a board.

So far I have one complaint. When you create a new topic board, a list of RSS feeds is selected for you and shown in a column to the right of the board. You can delete feeds that seem off-topic, but I have found no way to add relevant feeds, nor any way to edit feeds after you accept a board. I suspect these functions may come on board in the future, but for now this is a bit frustrating. I know of some great kidney health feeds that should be added, but I cannot do so!

Go play with the new page and my Kidney Health Board. Let me know what you think of this addition to WhizBANG!

Share

2 responses so far

With a Grain of Salt

The biggest improvements in human health occur with systematic changes. Clean water systems make a huge differences. Wide-spread immunization requirements conquered illnesses.

Success of Back-to-Sleep
Click to Enlarge

For a more recent example, I present Back-to-Sleep, a recommendation from the American Academy of Pediatrics in 1992. Placing most infants on their backs for sleep seemed to reduce the risk of sudden infant death syndrome (SIDS), also known as crib death. In October, about the time  my son came into the world, they began a blast of public health announcements to put infants on their backs unless your pediatrician instructed otherwise. The risks of positioning infants this way seemed minimal, and the costs negligible. The effects have been impressive, with a 50% reduction in deaths over a decade (see graph).

The message was simple and easily followed. Statistical modeling suggested a major effect from the intervention, and we see it in the data. Unfortunately, preventative measures for other disorders do not meet these criteria.

A recent article examines salt and public health, an area of intense debate.

Ronald Bayer, Daveid Merritt Johns, and Sandro Galea. Salt and Public Health: Contested Science and the Challenge of Evidence-Based Decision Making. Health Affairs 31:2738, 2012 DOI:  10.1377/hlthaff.2012.0554

The authors describe the issue at hand:

 For more than four decades, starting in the late 1960s, a sometimes furious battle has raged among scientists over the extent to which elevated salt consumption has adverse implications for population health and contributes to deaths from stroke and cardiovascular disease.

...

In 2011 two authors involved in the conduct of systematic reviews on salt declared, “It is surprising that many countries have uncritically adopted sodium reduction, which probably is the largest delusion in the history of preventive medicine.”3 Concurrently, a group of scientists long associated with studies on the harmful consequences of salt consumption wrote, “Denial and procrastination about dietary salt reduction will be costly in terms of avoidable illness and costs; it will also be ethically irresponsible.”4

The article discusses the evidence regarding sodium and blood pressure over the past 40 years, including systematic reviews of these data. Weighing both quality and quantity of data, the Cochrane group reported in 2011:

The second 2011 Cochrane report went further. After examining the potential impact of salt reduction on hormones and lipids in people with normal blood pressure, it concluded that the available evidence did not permit a conclusion as to whether low-salt diets improved or worsened health. It was possible, the authors concluded, that further research might be able to detect the beneficial impact of salt reduction, but “after more than 150 RCTs and 13 population studies without an obvious signal in favor of sodium reduction, another position could be to accept that such a signal may not exist.”55(p18)

Click for source

Clearly, many people with hypertension have salt-sensitivity and could benefit from reduced sodium intake; however, we cannot see the benefits when large general populations are examined. Just as clinicians have to make decisions about individual patients despite scientific uncertainty, policy makers must do the same for large groups. Several considerations must be weighed:

  • What are the benefits of reducing salt intake?

Those who have salt-sensitive hypertension have received the most attention in this debate; however, the reduction in blood pressure from sodium restriction alone amounts to only 1-2 mmHg in most people. Other populations might also benefit from global reduction in food salt content. Chronic kidney disease rates are rising as our population ages, and high salt intake complicates treatment of this group. High sodium intake can also induce kidney stones, and may be a major factor in this condition in the US.

  • Are there risks to health of reducing salt intake?

The answer here is about as clear. Some studies have suggested that patients with a number of chronic disorders may not fare as well with severe salt restriction. Just as there are biologically plausible hypotheses for the benefits of salt restriction, the activation of the renin-angiotensin-aldosterone system by low salt intake provides fodder for the other side. As the authors note, "medicine and public health are replete with examples of seemingly sound ideas that had devastating unintended consequences. One hundred percent oxygen for newborns can cause blindness. Extensive use of x-rays for screening purposes is associated with greater risk of cancer. The risk of unintended consequences grows dramatically when interventions are translated to a populationwide scale."

  • What is the cost of reducing salt intake?

The short answer: I have no idea. Salt initially served a preservative function in our food, but we no longer need it for that reason. However, people's palates have grown accustomed to its presence. Try a can of no-salt green beans sometime; they taste wrong, even when salted at the table. Manufacturers could begin cutting salt out of their processes and slowly getting us accustomed to its absence; some have started to do this with a variety of products. However, I have no idea what this change may cost at the factory or in the store.

The authors of the Health Affairs article do not solve this big hairy dilemma for us; they wrote this piece to demonstrate  "the role that judgment and values must play in evidence-informed policy making."

 As Roger Chou, a central figure in the conduct of systematic reviews for the US Preventive Services Task Force, has stated, “The evidence can tell us the likely benefits and likely harms, burdens and costs, but it does not directly tell us how to weigh all of these factors.”60(p10) Policy makers must ask: Are the burdens of public health interventions too great, and for whom? Are the expected benefits sufficient given the potential costs? These are not questions that can be answered in the absence of normative judgments.

As a doctor whose patients must often restrict salt intake, I know it would be in their best interest to systematically reduce salt in foods in the US. I do not know if it would benefit the general population enough to be considered successful on the same level as Back-to-Sleep.

The debate rages on. More data will be published.

Share

3 responses so far

"Fluid Is a Drug"

Nov 02 2012 Published by under Pharmaceuticals

Kidney Week 2012 is in full swing. Earlier I tweeted from a session on acute kidney injury (AKI) in the pediatric population; the Storify of my brief notes follows down below. One quote from Stuart Goldstein of Cincinnati's Center for Acute Care Nephrology hit home with my nephro-tweeps, specifically the title of the post.

Like all drugs, fluids require a physician's order; nurses take off the order; the pharmacy fills the order; and the agent is administered to the patient. Why do we have a rather cavalier attitude to giving intravenous fluids?

He made another point I liked. We should treat kidney replacement therapy in the intensive care unit the way we do ventilators. You do not wait until the patient is pulseless to institute respiratory support; why do we wait until the kidney completely fails before supporting the patient's metabolic needs?

Of interest, his analysis shows that more than 15% volume overload {(liters of intake - output)/baseline weight in kg >0.15} produces higher mortality and longer length of stay. This is also the point where excess volume seems to complicate respiratory support.

The session provided a great review of the history of continuous filtration therapy and information on pediatric AKI (#PAKI) outside of the intensive care unit.

Share

No responses yet

That Special Time of Year

Oct 31 2012 Published by under [Medicine&Pharma]

Like Christmas on Halloween!

It's time to pack up the laptop and other gizmos and head to the West Coast.

It's Kidney Week! Thousands of us with interests in urine and all things related will invade San Diego for science and debate and fun.

I will be tweeting from this meeting through Saturday, when I leave for San Francisco and the meeting of the Association of American Medical Colleges.

By the way, with eight days of travel and a black-tie event, I'm checking a bag. Just a couple of totes for the gizmos and meds, both of which will fit under the seat in front of me.

I also mailed my absentee ballot last week. If you don't vote, you aren't allowed to complain. And I do so like to complain...

Share

No responses yet

One Less Reason to Drink Cosmopolitans

Oct 18 2012 Published by under [Medicine&Pharma]

Not a significant source of cranberry juice

Yesterday, the Cochrane Group released its latest analysis of studies of cranberry juice or supplements for urinary tract infection (UTI) prevention. When they first examined the evidence in 2008, 10 studies suggested that there might be benefits for women with recurrent UTIs. Now, with 14 more studies and over 4,000 patients, the evidence shows no benefit from cranberry juice in UTI prevention. Data on cranberry pill supplements remains unclear.

Part of the issue appears to be adherence to the juice schedule. Participants had to drink juice twice daily. For studies of supplements, the potency of the tablet or capsule often went unreported, making it more difficult to interpret these studies.  The group felt more studies of supplements might be in order.

I would be willing to sip a cosmo or two each evening to "support urinary health" as the supplements say. Since each drink includes only an ounce of cranberry juice, and I cannot have them for breakfast, they would seem to be of no documented benefit. Other than those provided by pink martinis, of course!

So ingest cranberries if you like them, but do not depend on them to prevent UTIs.

So drink cranberry

Share

2 responses so far

Journal Club Today: eGFR

Jul 10 2012 Published by under Journal Club

Glomerular filtration rate (GFR) measures the ability of the kidneys to clear wastes. Glomeruli are tiny clusters of blood vessels in the kidney. As the blood flows through them, the water and chemicals in it get squeezed out into the tubules of the kidney, leaving behind cells, proteins, and a tiny amount of water. As this filtered liquid goes through the tubules, most of it (95-98%) gets taken up by tubular cells and returned to the body. Under normal conditions, an adult produces 144 liters of filtrate each day, but puts out less than 2 liters of urine.

To measure GFR we need a substance that is freely filtered in the glomeruli and not altered by the tubules of the kidney. Inulin and other manufactured substances can measure GFR most accurately, but these methods require continuous intravenous drips. They are inconvenient and expensive. Doctors and scientists looked for a chemical within the body that met these criteria. They identified creatinine, a muscle protein now included on most routine biochemical panels.

Measuring clearance of creatinine requires a measurement of the blood level, a timed urine collection, and measurement of the creatinine in the urine. Collecting urine over a given period of time can be annoying. Thus began the search for a way to estimate GFR from just a blood test.

Click to enlarge: From J Am Soc Nephrol 23:995, 2012

Since muscles make creatinine, people with more muscle have higher levels regardless of kidney function. In pediatrics, where patients normally change size over time, these issues cause even more problems. The first pediatric formula, developed by Schwartz et al in the 1970s, used height as a proxy measure of muscle mass. Over time, this equation has been refined as our methodology to measure creatinine has improved. Several large studies of chronic kidney disease in adults led to other equations (see table).

The question remained when to switch from the pediatric formula to one of the adult equations. Selistre et al recently looked at correlation and agreement among these calculated values and measured inulin clearance (that gold standard) in adolescents and young adults from 10 to 25 years of age. Subjects had kidney function ranging from stage 1 (normal) to stage 4-5 (<20% of normal) in all age groups.

They found that the Schwartz 2009 equation provided the most accurate estimation of true GFR, across all age groups and all ranges of kidney function.  This formula tended to underestimate GFR in those with normal function, but provided good agreement in other categories. The adult equations tended to overestimate GFR by up to 30%.

As the population of patients with chronic kidney disease grows, we need convenient ways to track kidney function over time. This study fills a gap, telling us the best way to do this in adolescents and young adults.

At least for now.

Share

4 responses so far

Older posts »