Kidney Failure and Ultramarathoning

by Don Davis

Four days after winning the Seagate 100 km Ultramarathon in Toledo, Ohio, I was hospitalized for 11 days with Acute Kidney Failure, a direct consequence of the race, possibly exacerbated by the 2400 mg of ibuprofen that I took during the race. In this article, I will describe my race and my hospitalization, discuss similar experiences of two runners after the 1994 Western States (WS) 100 Mile Endurance Run, and tell what I have learned that might be of general interest.

I am 49 years old and have been running ultras regularly since 1979. My most memorable performances have included

The Seagate Ultras on November 26, 1994, included races of 60 km, 50 miles, and 100 km, each run on the same 1.1 mile loop. There were approximately 10, 10, and 6 runners, respectively, in these races, which were judged separately. My 9:29 time for 100 km was not very fast, but it won that race easily, and I also went through 60 km and 50 miles faster than anyone in those races. So I am not a novice.

The weather for the race was ideal by my standards, with temperatures in the 30s, light wind, and no precipitation. I was drinking water and/or Gatorade almost every lap, so I don't think dehydration was a cause of my problem. One unusual feature of the race is that I stopped to urinate at least 25 times, whereas usually I stop about 6 times in a race of that duration. I attributed that to the cool weather keeping me from sweating.

One factor which is probably significant is that three weeks before the race, during an easy run the day after an excellent 41-mile training run, I injured a calf muscle. I used electronic stimulation to promote healing, and ran very little during the three weeks preceding the race. This area bothered me frequently during the race, feeling as if it wanted to cramp. Whenever this happened, I would take two 200 mg ibuprofen and some salt (from pretzels). Six times during the race I took two of these pills. I had taken at least eight ibuprofen during some previous races, so I don't feel that the ibuprofen was the main thing that made this race different.

The race was on Saturday. On Sunday, I felt typical day-after soreness and disinterest in food. It was on Monday that my stomach really rebelled, and I vomited for the first time. On Tuesday, I could hold nothing down, and vomited three times, while still carrying on my normal professorial routine. I don't remember whether I was urinating on Monday and Tuesday. I know that on Saturday and Sunday my urine was discolored, but this has happened to me before. On Wednesday, I went to the doctor, and blood work indicated kidney failure, for which I was told to get to the hospital immediately.

Continuous intravenous saline solution and drugs to stimulate kidney function were administered. I was catheterized to facilitate urine collection. Friday night the doctors said that if I wasn't producing more urine by morning, I would have to undergo dialysis, in order to moderate the levels of toxicity in my blood. This threat must have jarred my kidneys into action, for the urine really started to flow that night, averting the dialysis. My weight peaked at 178, thirty pounds above its normal level, due to all the fluid being pumped into me. Some of this fluid went to my lungs, causing a temporary condition of congestive heart failure. My wife said I had the cheeks of a chipmunk and the neck of a football lineman. Once the urine was flowing at nearly 1 liter per hour, my weight dropped back to nearly its normal level. It was then a matter of adjusting the rate of intravenous intake so that my kidneys would produce urine at an appropriate rate.

In the meantime, I suffered continual nausea. The toxins in my blood upset my stomach's functioning. Various drugs, some given intravenously, some orally, and some by injections, eventually regulated this. I went nine days without really eating.

The explanation for how such a healthy sport can cause such a serious problem is quite well understood. It is explained in Noakes' "Lore of Running," as well as in many medical books which I consulted after leaving the hospital. Your muscles contain myoglobin, a protein which causes the red color of the muscles and helps the muscle use oxygen. Myoglobin is primarily contained in the slow-twitch muscles which are used in low-intensity exercise of long duration, and is particularly prevalent in trained athletes. When a muscle breaks down or is injured, some of this myoglobin is leaked into the bloodstream, which carries it to the kidney. There is not general agreement as to exactly how the myoglobin causes kidney failure. Probable factors are (1) tubular obstruction, (2) toxic reaction, and (3) decreased oxygen supply to the kidneys.

There is much evidence that kidney failure is exacerbated by ibuprofens and other nonsteroidal anti-inflammatory drugs (NSAIDs). There are substances in your body called prostaglandins which cause the blood vessels flowing into the kidney to dilate when necessary, increasing the blood flow to the kidney. The prostaglandins will ordinarily do this when the kidney is under attack from myoglobins. However, it is known that NSAIDs inhibit the action of the prostaglandins, thus allowing the myoglobins to do their nasty business unimpeded. Recent articles in medical journals have debated what constitutes a dangerous level of ibuprofen usage. My nephrologists agree that 2400 mg was too much for me, and was a definite contributor to my kidney failure. On the other hand, David Warady, in winning the 1992 Trans-America Footrace, took 7000 mg per day for 50 days with no problem.

Dr. Bob Lind, WS medical director, is skeptical about the role of NSAIDs in kidney failure. He has done some studies during recent WS races, and reported some preliminary findings in a November 1986 article in Ultrarunning. He has found no correlation between NSAID use and CPK (creatine phosphokinase) readings in the blood of runners immediately after the race. CPK is an enzyme leaked from the muscles into the blood along with myoglobin, and so it is an excellent indicator of rhabdomyolysis, which is injury of the muscle cell allowing its contents to escape. But the role of NSAIDs in promoting kidney failure is separate from the myoglobin and CPK leakage, and so this lack of correlation is not surprising.

My theory about what made this race different for me is that the pre- existing calf injury caused an unusually large amount of myoglobin to be leaked into the blood. Both Dr. Lind and one of my nephrologists speculate that racing after a 3-week near-layoff could have caused all the myoglobin leakage. There is ample evidence that tremendous exertion by an untrained person can cause myoglobin leakage; I wouldn't have thought that I would lose that much of my training edge in three weeks of relative inactivity.

To check whether you are a candidate for kidney failure, you might have blood work done after a race. An elevated CPK reading shortly after the race indicates a likelihood of kidney failure. An average CPK reading is 10 to 150. Dr. Lind reports that an average reading for a runner after WS is 17,000, that a reading of 25,000 to 50,000 is indicative of possible kidney failure, while a reading of 100,000 is a very dangerous signal. He has seen one or two kidney failures (out of 400 runners) after several WS races when the weather was hot.

I did not get a CPK reading until the fourth day after my race, and CPK readings generally drop after 24 to 48 hours. My doctors were most concerned about the creatinine in my blood. Creatinine is a waste product which the kidney is supposed to remove from your blood. It is an indicator that the kidney has already ceased to function. It does not achieve an elevated value as quickly as the CPK, but it stays elevated as long as your kidneys are not functioning properly. The normal range for creatinine is 0.7 to 1.5 mg/dL. My reading four days after the race was 6, and it increased to almost 8 after a few days in the hospital. A reading of 8 says that your kidneys are functioning at somewhat less than 1/8 of their capacity. I was released from the hospital when it got down to 1.7, and a week later it was down to 1.1. Several studies of runners after races of 26 or 62 miles have shown slight increases of creatinine shortly after the race, but nothing nearly comparable to the huge increases in CPK that Dr. Lind sees after WS.

CPK measures rhabdomyolysis, whereas creatinine is a direct measure of kidney malfunction. Although rhabdomyolysis and kidney failure are frequently linked, due to myoglobins, it is possible to have either one without the other. My nephrologists warn that heavy ibuprofen use during a race could cause kidney failure even without extremely high CPK readings if the prostaglandin- inhibiting effect were significant. A highly-publicized very recent study has also implicated acetaminophens such as Tylenol in kidney failure.

Subsequent to distributing preliminary versions of this article, I have talked to two runners who suffered Acute Kidney Failure as a consequence of the 1994 WS race. One of them, Greg Miller, 34, from California, fractured his ankle 5 miles into the race, but kept going until the 80-mile mark, using ibuprofen to reduce the pain. He started vomiting at the emergency room of the nearby hospital to which he was taken. His hospital stay was very similar to mine, lasting 10 days with a 25-pound weight gain due to fluid, a creatinine level of 9 which put him on the verge of dialysis, and much vomiting.

The other, Bill Fornoff, 51, from Maryland, had a more severe case of Acute Kidney Failure. He was in the hospital for 17 days, and had to undergo dialysis for five of those days. During each of those days, he was connected for four hours to a machine which performed the function of his kidneys, removing toxins from his blood. His peak creatinine level was 10, and he also gained 30 pounds of fluid temporarily. Like Greg and me, his main symptom was vomiting, which began the day after the race. After flying home the next day, he was told by two doctors that his vomiting was probably due to a bacterial infection that he had picked up during the race, and so it took several days for his kidney failure to be diagnosed. He finished the race six minutes before the 30-hour cutoff, and felt no particular injury that might have contributed to unusually large myoglobin leakage, except for an unprecedented amount of pain in his quadriceps, which he attributes to all the downhill running. He took one 500 mg Naprosyn during the race. His one lasting effect of this incident is high blood pressure, for which he still takes medication.

Both Miller and Fornoff ran respectable marathons six months after their bouts with kidney failure. My nephrologists have said that it is probably safe for me to race, provided I am well-trained and not injured, stay away from NSAIDs, hydrate adequately, and ingest plenty of potassium. They will also monitor my CPK after some long training runs. Dr. Lind adds that it is important to check that one is not losing weight during the race. Hot weather has also been implicated in many cases of kidney failure after long races, and I would try to avoid that. It is also known that kidney failure becomes more likely with increasing age, and so I will try to become younger. All ultramarathoners should consider these precautions, and if they start vomiting a day or two after a race, they should immediately have their blood tested for elevated CPK and creatinine levels. Be aware that this sport is capable of inflicting damage much more serious than the temporary injury to the musculo- skeletal system which occurs commonly to virtually all ultramarathoners.