High-altitude renal syndrome

Everyone knows the famous George Mallory answer to the question about why he was climbing Mount Everest , “because it’s there.” But I just learned that he continued after that mic drop and spoke about doing science on these mountain climbing missions:

Sometimes science is the excuse for exploration. I think it is rarely the reason.

The three primary causes of high altitude sickness:

  1. Acute mountain sickness (AMS): headache, gastrointestinal symptoms (anorexia, nausea, vomiting), sleep disturbances, dizziness, fatigue
  2. High altitude pulmonary edema (HAPE)
  3. High altitude cerebral edema (HACE)

Lake Louise Acute Mountain Sickness severity score for acute mountain score:

Preventing AMS is usually dependent on limiting altitude gain, avoiding alcohol and drinking a lot of water.  Acetazolamide 125-250 bid is also effective.

The headache of acute mountain sickness can be decreased or avoided with medications:

Aspirin 320 mg po q4-hours x 3 doses, starting 1 to 2 hours prior to arrival

Ibuprofen 600 mg po q8-hours for at least 3 doses, starting 6 to 24 hours before ascent.

Ginko Biloba has been used with variable success as prophylaxis. 160-240 mg in divided doses

Dexamethasone 8 mg daily in divided doses can also be used for prophylaxis.

Nice review of AMS treatments and prophylaxis can be found here.

In studies looking at the etiology of AMS and HAPE, Vascular Endothelial Growth Factor and its soluble receptor sFlt-1 were thought to play a role. However in a study of 51 Denali mountaineers, blood levels were not associated with AMS.

The body has a number of strategies to adapt to high altitude trekking. Among the changes is the observation that the density of capillaries per unit of muscle rises. This sounds cool until you read that some scientists believe this is primarly due to a loss of muscle mass rather than growth in new capillaries.

Other strategies for adaptation include

  • Hyperpnea and tachypnea leading to hypocapnia
  • Hypoxia may trigger several receptors, including airway chemoreceptors
  • Tissue hypoxia also induces the production of hypoxia-inducible factor (HIF) transcription factors
  • Changes in metabolic pathways including oxidative metabolism, cell cycle and diminished myogenesis
  • Changes in hemoglobin oxygen affinity that alter arterial oxygen saturation and release to tissues
  • Increase in mitochondria and cytochrome oxidase occur but only after 7-9 days at altitude

Renal changes.

High-altitude renal syndrome is an asymptomatic chronic condition of high-altitude dwellers defined as:

  • High-altitude polycythemia
  • Systemic hypertension
  • Microalbuminuria
  • Hyperuricemia
  • Relatively preserved glomerular filtration rate

High altitude renal syndrome is part of the complex adaptive response to altitude.

Creatinine based GFR is unaffected by increases in altitude, however a study that used cystatin c based GFR assessment found a 3ml/min drop in GFR for every 1,000 meters the mountaineers ascended.

Interestingly, AMS was associated with higher eGFR.

Most electrolytes fall:

The decrease in serum bicarbonate comes from hypoxia induced respiratory alkalosis. Arterial pH at the top of Everest is estimated to be 7.7 to 7.8. PaO2 was 35 mmHg!

Trekkers in the mountains have hypovolemia due to increased insensible losses, increased anorexia, and decreased thirst. Additionally there is altitude induced diuresis. This diuresis seems to be an obligatory early phase of adaptation to altitude. The diuresis can cause a 1-3 liter loss of body water resulting in a 38% increase in blood viscosity at 5,800 meters.

The diuresis has variably been explained by suppression of ADH, increases in ANP and increases in BNP. Increases in BNP are associated with increased risk of AMS.

This paragraph is very interesting:

It remains unknown whether the altitude-induced decrease in plasma volume is adaptive or potentially harmful. If adaptive, then less effort should be made to correct ‘dehydration’, and fluid intake should be limited to simply following the thirst mechanism and to offsetting insensible losses (admittedly difficult to estimate, much less measure, on the mountain). Indeed, as discussed above, fluid retention rather than dehydration is associated with AMS. Perhaps diminished plasma volume is part of the body’s effort to supply oxygen to the most vital organs, overriding the not insubstantial risks of hyperviscosity and thrombosis associated with hemoconcentration.
There could be two beneficial effects of high-altitude diuresis:
  1. Early hemoconcentration elevates the blood concentration of hemoglobin prior to the slower onset of EPO-stimulated erythropoiesis
  2. Volume depletion reduces intravascular pressure and volume load on the lungs and brain, and may decrease renal oxygen consumption (90% of which reflects renal sodium reabsorption) due to diminished filtration

This article is excellent.

Spooky Sodium 👻: The Grand Rounds

At Lankenau Medical Center in Philadelphia at 8:00 AM, January 12. I will be talking about Spooky Sodium 👻.

Here is the title slide

If you can’t make it, first of all, what’s wrong with you? But second of all don’t worry, you can get the high points from the man who discovered them in this 13 minute TedX Talk from Vanderbilt.

And from this article in the NYT

And don’t forget about the excellent NephJC coverage, including an editorial from Rodby.

I will eventually post a slidecast of my presentation.

Hypercalcemia from 1,25 vitamin D toxicity

I received an outpatient consult for acute kidney injury. One of the things that makes Saint Clair Nephrology a remarkable nephrology group is our ability to get patients in quickly. While competing practices in the area have a 3-month wait list to see new patients we get patients in within a week. This patient was seen two days after his doctor called.

The patient was frightened. He had previously been healthy and his doctor told him his kidneys were failing and that he needed to see a nephrologist. He arrived with a creatinine in the high 2s from a base line of 1.2 mg/dL. Along with the AKI his blood pressure was touching 180 systolic, out of character for him. Of note on the initial labs his calcium was 13.6 mg/dL.

The initial work-up showed suppressed PTH. SPEP and UPEP were normal.

On the next visit I checked the 1,25 vitamin D and it was 117 IU. I suspected lymphoma or sarcoidosis but the chest x-ray was unremarkable and the patient did not have any palpable lymph nodes or abnormalities on the CBC. No weight loss, night sweats, or fevers. ACE levels were unremarkable.

On further questioning on his third visit, the patient mentioned he was taking a generic knock off of Mega Red Fish Oil. Fish oils can have significant amounts of vitamin D and the supplement is famously lax with quality control. He stopped the fish oil, we started him on oral prednisone and the 1,25 vitamin D level quickly responded within a couple of weeks. The patient had a full recovery from the hypercalcemia, hypertension, and acute kidney injury.

 

 

Update

Some great comments from Twitter

 

 

#NephMadness Editorial in AJKD

Matt and I wrote an editorial on NephMadness. Last year was the fifth year of NephMadness and Matt and I felt it was time to pass the reigns to some new blood. Tim Yau came on board last year and got a lot of experience. Anna Burgner was added to the executive team this year. They are doing a cracking job.

As Matt and I move to lesser roles, Feldman, Dember, and Sterns invited us to review our experience with the first five years of NephMadness. It was very kind of them. The editorial is out now. Take a look.

My favorite part of this is that when you type NephMadness into PubMed, you will get two hits. (As of writing this, the new article is not indexed. Awkward.)

Cardiorenal conference in New York: #NephCards2018

You probably know Kenar Jhaveri. He is the founder of NephronPower and the first editor of AJKDblog. He is a professor of Medicine at Hofstra Northwell School of Medicine on Long Island. Kenar is a good friend and one of the great nephrology educators.

He is sponsoring a cardiorenal symposium in March. I’d love to go but I’ll be most of the way to Everest Basecamp at that time. If you have some spare conference time, you should check out The Heart-Kidney Connection.

There will be mad tweeting so in mid-March tune your Twitter machine to #nephcards2018

The Everest Itinerary

I am so excited to go to the Top of the World with MM4MM to help raise money and awareness for the multiple Myeloma Research Foundation. If you haven’t already, please take a look at my fundraising page.

The trip is being guided by Embark. They seem quite professional.

Here is the itinerary. From what I understand this is just provisional as all plans in the mountains must be.

 

Day 1. We meet in Kathmandu (4, 593 feet).

Day 2. We fly from Kathmandu to the world’s most dangerous airport in Lukla (9,383 feet).

Day 2. After landing in Lukla we hike to Phakding (8,563 feet).

Day 3. From Phakding we trek to Namche bazaar at 11,290 feet. Namche is in a bowl in the hill side, it is a commerce center. Will arrive in the afternoon and may need to climb up to our hotel.

Day 4. We have a rest day in Namche to help with acclimitization. We won’t go any higher to sleep but we will do day hikes. We should have the opportunity to go to Kumchong to see a Hillary School.

Day 5. The next day we will go to Tenboche (12,687 feet). This hike starts by going down and then up. We will be going to the Tanboche monastery, one of the largest in the area. Namche the crowd thins out and the villages are farther apart.

Day 6. The next day is at the Pheriche (14,340). We should get a view of Everest from here.

Day 7. Above Pheriche we encounter the glacier and go to Lobuche, 16,700 feet. We will be walking on the terminal moraine of the glacier.

Day 8. Biggest day is from Lobuche to Gorakshep. We will dump our gear and then climb up to the Everests Basecamp (17,598 feet). We will head back to Gorakshep to sleep (16,942 feet).

Day 9. The next morning we will get up early and head to the summit of Kalapathhar, the highest point of the trip (18,514 feet) and what should have a spectacular view of the glacier and Everest.

Day 10. We then go all the way to Pheriche (14,340 feet)  that night. Long day.

Day 11. The next day we go from from Pheriche to Namche where we will catch a helicopter to take us to Kathmandu.

I want to do some physiology testing on my climb to Everest Basecamp

This March, I am going to climb to Mt Everest Basecamp (EBC), altitude 17,900 feet. Actually I will be going a bit higher to Kalapathhar at 18,500 feet but no one knows what Kalapathhar is, so EBC it is. This is an 8-day trek and I want to do some physiology testing along the way. I am going to bring a pulse oximeter, a sphygmomanometer and some urine dipsticks to do serial urinalysis. I have a pretty strict weight limit. So careful choices need to be made with regard to equipment choices.

In terms of physiology testing I have multiple subjects willing to be part of my science fair.

My questions to the readers of PBF, is what questions can I answer?

I believe that everyone is going to be on acetazolamide.

I am interested in water intake, cramps and exercise fatigue. I could probably get that data with a daily survey and then I could correlate it with pulse oximetry and urine specific gravity at the end of the day’s hike.

I am also interested in peak specific gravity as we go up the mountain. Does it fall with increasing hypoxia? But this may be hopelessly obscured by the acetazolamide.

I would like to do some cognitive testing as we go up the mountain.

What other questions should I try to answer. What other medical instruments should I take? Bioelectrical impedance?

Also remember to donate to multiple myeloma research and my trip to EBC.

 

 

Resident lecture on NAGMA

One hour lecture on NAGMA. Just some small changes edits from the last time I gave it. It is one of the few lectures that is still in PowerPoint. It is due for a complete overhaul. It also needs a slide on the treatment of RTA that covers the amount of bicarbonate in a 650 mg tablet (8 mmol) and the fact that distal (type 1) RTA requires a limited amount of bicarbonate (at most 1 mmol/kg). This is appropriate for residents and medical students.

If you are interested in ward teaching and RTA, take a look at this post by Robert Centor.

Also this is a nice article on the issue of saline having a pH of 5.5, covering both the reason (its the PVC bag) and the implications (none).

NAGMA (PPT)