Hundreds of Interlaced Fingers

by Vanessa Grubbs, M. D.

  I let them know that because the kidneys move up and down as we breathe, they will need to be awake in order to follow the radiologist’s instructions on when to hold their breath for the few seconds that we are taking the sample.

  Because many imagine we are removing big sections from each kidney, I let them know we will try to get two pieces from just one kidney. Each piece is about an inch long and about as thick as a pencil lead. To find out what is wrong, we need to get a sample of the kidney filters. A great sample is twenty filters. Each kidney has about a million filters.

  I tell them that the procedure itself usually takes no more than a half hour, with the bulk of the time spent setting everything up. Afterward we have the person lie on their back for six hours—because the weight of one’s own body will help prevent significant bleeding, and to monitor blood pressure and urine output. Finally we get a blood test for significant bleeding. If all is well, then we send them home to rest in bed until the next day and instruct them not to lift anything heavier than ten pounds for the next week or so.

  In spite of all the detail and attempts to reassure, the occasional patient can’t get past the fear of the possibilities. Or maybe not knowing what is happening in their kidneys is easier to cope with. They leave the clinic without making a follow-up appointment. Or they agree to the biopsy, we schedule and make all the arrangements—reserve the ultrasound suite, the radiologist, the recovery room bed—and then they don’t show up.

  When Robert had his biopsy done, computed tomography, aka the CAT scan, was used to visualize his kidney. He felt nervous when he went into the hospital that day. Not because he was afraid of needles—weekly shots for years had cured any needle phobia if one ever existed. Rather, it was the description he was given.

  “It’s like a controlled stab,” Gorman had told him. This was not just another test. Perhaps it was the power of suggestion that made it feel exactly like he had been stabbed. Or perhaps it was that third attempt to get tissue that made Robert’s lower half jerk that made it so.

  “Uh-oh,” said Gorman when Robert jerked side to side. I imagine most if not all doctors have thought “uh-oh” at some point in their training or practice. But to not be able to hold back speaking it? Never a good sign.

  “He nicked my colon!” Robert lamented. He had blood in his stool. The blood resolved in a day and Robert quickly forgave Gorman, but his fear of kidney biopsy would be permanent.

  My experience in doing kidney biopsies has been very different—at worst one patient had some nausea and bled enough to have temporary kidney injury but didn’t need a blood transfusion. Every other patient said some variation of “It wasn’t so bad” or “It wasn’t as bad as I thought it would be.”

  “The biopsy showed a condition we call F-S-G-S . . . focal . . . segmental . . . glomerulosclerosis,” Gorman said slowly to Robert and his mother in his clinic office about three weeks later.

  “What the hell is that?” Robert asked.

  Gorman went on to explain to him about how the glomerulus is the filter of the kidney, how the holes in his glomeruli were too big and that’s why so much protein was leaking into his urine, and how some of his glomeruli were scarred down.

  “What caused it?” Robert wanted to know next.

  “We don’t know. It could have been any number of things. An infection that was undertreated or maybe you just had it and it was never detected before.”

  Focal segmental glomerulosclerosis (FSGS) was first described in the 1970s. We have since learned that it accounts for 20 percent of heavy urine protein in children and 40 percent in adults. The vast majority of FSGS just is—a primary or idiopathic problem in how the interlacing fingers are made or work just springing up on its own (at least as far as we know). But it’s estimated that about one of every five cases of FSGS is secondary—caused by a number of things such as specific viruses, drugs, other diseases, and about twenty gene mutations that are passed on from parents to children, like the two recently discovered variations in the gene that makes apolipoprotein L1 (APOL1). Exactly how they cause FSGS remains unclear, but how the mutations came to be is an example of Nature hedging her bets.

  Normally APOL1 is a substance in the blood that can destroy Trypanosoma brucei brucei, a species of parasite that is spread by the tsetse fly of sub-Saharan Africa and causes sleeping sickness. Over time, two subspecies of the parasite that were resistant to APOL1’s effect evolved. Nature responded with two APOL1 variations that could destroy one of them. As a result, people whose gene carried the APOL1 variant were more likely to survive the deadly sleeping sickness—and pass it on to their children. This is akin to the sickle cell trait, in which a slight variation in the gene that makes blood creates protection against the deadliest form of malaria, which is spread by the anopheles mosquito found in sub-Saharan Africa, South America, the Caribbean, Central America, Saudi Arabia, India, and Mediterranean countries. The downside of nature’s response is that a child of parents who each carry one copy of the gene variant has a 25 percent chance of inheriting a copy from each parent. Two copies of the gene variant that protects against malaria is sickle cell disease, a form of severe anemia characterized by debilitating pain crises and a limited life expectancy, and two copies of an APOL1 variant and the child is at higher risk of developing FSGS (4.25 percent chance over their lifetime) than someone with just one copy (.3 percent) or none (.2 percent). But from Nature’s point of view, weighing the risk of having a child with sickle cell disease or FSGS against the risk of dying from malaria or sleeping sickness in days to months, the trade-off was well worth it. Researchers estimate that 51 percent of African Americans have at least one copy, but only 13 percent have two.

  While it is academically interesting and really kind of cool that we can pinpoint which of thousands and thousands of genes can cause a particular disease, a burn sprays through the pit of my stomach, my heartbeat quickens, and my body stiffens every time I read or hear race-specific data.

  When a gene is found to be more common in people of African ancestry, a series of assumptions and shortcuts takes place. African ancestry in the United States is renamed “African American,” and is applied to everyone labeled as such, regardless of individual ancestry. Suddenly African American takes on a precision, as if it is the gene itself. As if African American can be precisely located in our DNA.

  According to the Human Genome Project, which completed sequencing the entire human DNA in 2003, we humans are 99.9 percent identical. And the .1 percent difference does not fit in our defined race categories. Yet, amazingly, in spite of all that science, medicine can’t seem to shake the deep-seated belief that there are real biological differences defined by our made-up race categories.

  After this series of assumptions and shortcuts, one may arrive at the conclusion that an African American is an African American is an African American, when in truth African Americans include African, European, Native American, Asian, and Middle Eastern ancestries—and many within one body. This practice begs the same question that the medication BiDil, which was approved by the US Food and Drug Administration in 2005 for the treatment of congestive heart failure in Black patients, did—how Black does one have to be for race-specific data to apply? Where exactly do we draw the line?

  As late as the 1930s, states were adopting the “one drop rule” into law, which taught us that a person was Black if they had any sub-Saharan African ancestors because they embodied more than a single drop of “Black blood,” thus meeting the “one drop rule.” In modern US medicine, it appears that we employ a less scientific but more easily assessed version of the “brown paper bag test” (which was used by African Americans well into the twenty-first century to restrict elite organizations to light-skinned Blacks) to define “African American” instead: the “buff manila folder test,” where Blacks lighter than the folder are assumed to be of White or Other/not-exactly-sure-how-to-label-you race.

  This series of assumptions and shortcuts in medicine often restricts our
thinking, making it lazy at best. We use race as a diagnostic tool—like a fasting blood sugar or an echocardiogram. A fasting blood sugar above 126 is diabetes. A part of the heart not moving like the others is a heart attack. A lot of protein in the urine of an African American is FSGS. Maybe, but Black people get other things too.

  During my second year of nephrology fellowship, I remember telling the story of a young man with blood and protein in his urine before an audience of my peers and attending nephrologists that exemplified how race factors into our diagnostic reasoning. This was our “case conference,” a weekly half-hour meeting in which each of us fellows were scheduled to lead a discussion of a case of unknown diagnosis to most of the audience. Medical school trains us to begin each case the same—a however-many-year-old Black/White/Asian/Hispanic girl/boy/man/woman with a past medical history significant for blah blah blah presented to the clinic/emergency room with this, that, or the other.

  This day I purposely left out the race. A twenty-six-year-old man with no significant past medical history presented to clinic with proteinuria and microscopic hematuria.

  I couldn’t even get through the patient’s recent medical history, which might give clues to why my patient had protein and tiny amounts of blood in his urine, before the most brilliant of fellows in my group raised his hand.

  “What is his race?” he asked.

  “Green,” I said flippantly. “What difference does it make?”

  My brief attempt at social commentary completely lost on him, he launched into a thoroughly race-based litany of what the diagnosis could be. “Well if he is Asian, IgA nephropathy would be most likely. If he is African American, then FSGS would be most likely. . . .”

  For real? I thought. Would knowing his race make you not get a biopsy? I wanted to ask, but all other heads were nodding as if he were preaching what they believed. They too were all trained to believe knowing this patient’s race was as important to establishing the diagnosis as knowing how much protein was in his urine or if it hurt when he peed.

  My patient was White. I performed a biopsy. It showed IgA nephropathy.

  An earlier experience during my residency stood out as an example of how the sword of race-based generalization could cut more than one way. The noon conference lecturer was a renowned rheumatologist. He presented a case of a forty-something-year-old Black woman with a cough, shortness of breath, weight loss, and large tender bumps on her shins. A plain X-ray showed enlarged lymph nodes in the center of the chest. All were classic signs and symptoms of sarcoidosis, an inflammatory disease that can affect many organs in the body—and is more common in Blacks than Whites and more common in women than men. Even we Highland Hospital bald-headed notch below redheaded stepchildren of UCSF could figure that one out. Yet, the renowned rheumatologist disclosed, the patient’s diagnosis was delayed for years because he did not consider the diagnosis. He did not consider it because he was not really describing a forty-something-year-old Black woman. He—a sixty-something-year-old White man—was telling us his own medical history.

  I don’t know of a similar story in nephrology. But then again, we don’t biopsy everybody—especially if we don’t consider the possibility that the biopsy will show something different from the disease we have assumed.

  “We’re gonna keep an eye on it,” Gorman went on. He explained that though Robert’s glomeruli were damaged as evidenced by the protein in the urine, they were still working pretty well as evidenced by his creatinine blood test, used to estimate kidney function, which was still in the normal range—around 1.

  “What does it mean?” Robert asked. “Am I gonna have to be like those folks I saw by your office?” If I gotta do that, you might as well kill me, he thought again.

  “Not immediately, but eventually.”

  “What’s eventually?”

  “Ten to fifteen years.”

  To a teenager, ten to fifteen years was forever away. He wasn’t afraid because it wasn’t immediate.

  “How do I make sure it doesn’t happen to me?” He looked at Ginger now. He could tell she was thinking the same.

  Gorman handed Ginger prescriptions for a low-protein diet, an ACE inhibitor, and prednisone in hopes of lowering the amount of protein lost in Robert’s urine. How useful a low-protein diet may be goes in and out of favor like fashion trends. ACE inhibitor medications lower blood pressure, especially within the kidneys to help lower protein loss.

  Robert was able to tolerate the maximum dose of ACE inhibitor without the light-headedness from low blood pressure or the dry cough side effect that some people get with this class of medication, but he found the low-protein diet unsatisfying, and the prednisone gave him mood swings, a round face, and acne. The protein in Robert’s urine didn’t change very much up or down and his creatinine blood test stayed about the same after several months of treatment, so Gorman gradually tapered Robert off the prednisone and he was left with a chronic kidney problem.

  Today we also try to treat the treatable causes of FSGS—recommending antiretroviral medications for FSGS caused by HIV, weight loss for FSGS caused by morbid obesity, stopping the heroin for FSGS caused by it, and a few fancier medications—but the end result remains the same. While some treatments work better for some people than others, eventually—unless the person dies of something else first—almost all cases of FSGS and the other zebras share a common path where cure is not possible.

  They become plain old horses. Chronic kidney disease.

  13

  Horses

  It is hard for most people to wrap their minds around the reality that what they have is chronic—as in it ain’t never going away, never ever ever—kidney disease. They want me to prescribe the pill or shot that will make it go away. Tell them the food they should eat, the food they should stop eating to make it go away. Many look for a natural or non-Western approach to find their way out of the inevitable, assuming natural products are only safe and beneficial to health.

  Traditional Chinese medicine is often painted with this brush. In this holistic approach, the kidneys represent not just the organs themselves but rather the entire urinary system and the hormone-producing endocrine system. The kidneys house the body’s essence or life force (qi) and are the root of yin and yang for the entire body. While I appreciate the concepts of traditional Chinese medicine and am a big proponent of acupuncture for treating pain, for example, I am a bit leery of the herbal remedies central to it. I know it’s been around for a couple thousand years, but I still don’t know what’s in most of it.

  But what I do know is that plants containing aristolochic acid are commonly used in Chinese herbal medicine—and aristocholic acid can cause rapid scarring in the kidneys, often leading to end-stage kidney disease and cancers of the urinary system, making it one of the most dramatic examples of an herb that can damage the kidneys. And many other herbs can cause harm indirectly in those with or at risk for chronic kidney disease.

  Some dietary supplements contain herbs that increase blood pressure or blood sugar, which could potentially cause or worsen chronic kidney disease. Others contain herbs that cause low blood sugar or high potassium, particularly in people with advanced chronic kidney disease. Still others contain herbs that can cause diarrhea and vomiting bad enough to cause severe dehydration, which can cause sudden kidney failure or acute kidney injury, which in turn places a person at higher risk of chronic kidney disease. But since people are less likely to think that any badness can come from natural remedies, they often don’t tell their doctors they are taking them.

  “I’m feeling good, Doc,” Mr. Holly said as I sat down on my stool in the clinic exam room. He sat in the chair beside the computer table, his round freckled face beaming.

  I was not surprised. Most of my patients with chronic kidney disease tend to feel well until there is very little kidney function remaining because, like a woman losing herself because she is so focused on pleasing everyone else, She suffers in silence.

  “That’s great.
” I smiled back. But I had seen his lab results.

  Mr. Holly was in his mid-forties and had fairly advanced chronic kidney disease as a result of diabetes. The diabetes had also been taking a toll on his eyes and heart, leaving him nearly blind in one eye and in need of a heart bypass surgery. He had ignored his health until five years ago when diabetes symptoms took center stage. But since I met him three years ago, he had been doing the best he knew how to improve his health—except to stop smoking or lose weight. At least he knew his medicines, was taking them, and showed up to his appointments. Well, most of them anyway.

  I last saw him in clinic three months prior. His kidneys were filtering his blood at a rate of about 6 teaspoons per minute at that time, as it had been when I checked the visit before. Normal kidneys start out filtering about half a cup of blood per minute, or 25 teaspoons. At age forty, we lose about a teaspoon every five years (1 milliliter per minute every year) simply because parts don’t last forever, but we don’t really see evidence that She can’t keep up with her responsibilities until the estimated function drops below 12 teaspoons (60 milliliters) per minute. So at 6 teaspoons Mr. Holly’s kidney function was not good, but at least not worse than before.

  But the labs drawn just a couple of days ago showed that his kidney function was down to almost 4 teaspoons (21 milliliters) per minute. If it dropped any further, I would have to start the dreaded, tear-inducing “We need to talk about what you want to do when your kidneys fail completely” conversation.

  “What have you been up to?” I asked.

  “Oh, I’ve been drinking this health drink from Costco,” he said. “It’s called açaí berry juice and it’s natural and it’s got all kinds of antioxidants and stuff in it.”

  Açaí berry. Açaí berry. I searched the recesses of my mind to remember that açaí berry can have the same effects as NSAIDs—nonsteroidal anti-inflammatory drugs—like ibuprofen, Motrin, and Aleve. Taking a lot of NSAIDs for a long period of time can cause sudden—and sometimes irreversible—worsening of kidney function, especially in people who already have chronic kidney disease. And though açaí berry can help patients with diabetes lower their blood sugar a little, lowering blood sugar while kidney function is getting worse can be extremely dangerous, because it is the kidneys that remove most diabetes medicines from our bodies. And because sick kidneys aren’t so good at removing things, the medicines stick around longer—working to lower blood sugar.