#NephJC this Tuesday, Jan 12 and Wednesday, Jan 13: SPLIT trial

We are going deep on this landmark RCT of saline versus balanced solutions.

JAMA has made the article open access for NephJC. Follow this link. JAMA is also going to offer prizes for the best tweet from the Jan 12th and Jan 13th discussions so warm up those twitter clients!

Spironolactone primer

Resistant hypertension is an important clinical problem. It is commonly defined as inadequate blood pressure control despite use of three antihypertensive agents of different classes at optimal dosages; one of the three should be an appropriately dosed diuretic. About 10-15% of hypertensive patients have resistant hypertension.

The magical powers of aldosterone antagonists first started to be publicized in the late 90's and in 2003 Calhoun showed a dramatic effect among patients with resistant hypertension:

“A total number of 76 subjects were included in the analysis, 34 of whom had biochemical primary aldosteronism. Low-dose spironolactone was associated with an additional mean decrease in BP of 21 ± 21 over 10 ± 14 mm Hg at 6 weeks and 25 ± 20 over 12 ± 12 mm Hg at 6-month follow-up. The BP reduction was similar in subjects with and without primary aldosteronism and was additive to the use of ACE inhibitors, ARBs, and diuretics.”

This was backed up by additional observational data as part of the ASCOT trial experience. The investigators found dramatic efficacy from modest doses of spironolactone among the 1,411 patients that received spironolactone as a fourth line agent:

“During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: ±18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; P<0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. ”

The first randomized, placebo controlled trial in resistant hypertension was published in 2011. The ASPIRANT trial (PDF) showed a more modest, but still clinically significant reduction blood pressure.

An important caution when looking at spironolactone data is that it appears that black patients  are more sensitive to increases in aldosterone, so one could predict more modest blood pressure improvements with spironolactone in a European population. See Tu et al. (Full text).

Another critical aspect of resistant hypertension is addressing non-adherence. 

“A mass spectrometry urine toxicology screening of antihypertensive drugs reported that 53% of patients with resistant hypertension were non-adherent to treatment. Of these, 70% were incompletely adherent and 30% were completely non-adherent. Reduced adherence was not attributed to a particular antihypertensive class. Another urine analysis study found that 23% of patients referred for renal denervation were completely non- adherent to their prescribed antihypertensive treatment.”

— From Rossignol et al. The double challenge of resistant hypertension and chronic kidney disease.

This is why PATHWAY-2's attempt to measure minimize non-adherence is so important.

This week's chat on PATHWAY-2 represents the first randomized controlled trial against an active control group. The fact that aldosterone rises above other fourth line agents to provide meaningful advantages in the treatment of resistant hypertension is important.

We are coming to a new age in hypertension management. On November 9, at 2:00 PM at the AHA meeting in Orlando the SPRINT Trial results will be released. This will almost certainly result in a wave of more aggressive blood pressure control. Almost simultaneously we now have access to the first of the next generation potassium binders, patiromer. This brings the hope of avoiding the most frightening of the side effects from aldosterone antagonists, hyperkalemia. These three seemingly unrelated events are going to be major influences on the treatment of hypertension going forward.

The IV versus PO iron conundrum for Tuesday and Wednesday

Joel said he would write the summary. Suzanne said she would write the summary and in the end wires got crossed and they both wrote the summary. Sigh. We are ardent conservationists and strongly believe that no part of the buffalo should go to waste so here is Dr. Norby's summary of this week's NephJC article:

A randomized trial of intravenous and oral iron in chronic kidney disease

Rajiv Agarwal, John W Kusek, and Maria K Pappas

Kidney International advance online publication 17 June 2015

doi: 10.1038/ki.2015.163

BACKGROUND

Anemia is common in patient with stages 3-5 chronic kidney disease (CKD) due to decreased erythropoietin production as well as iron deficiency, including the functional iron deficiency that can develop while using erythropoiesis-stimulating agents (ESA).

The KDIGO Clinical Practice Guideline for Anemia in CKD recommends (grade 2C) the use of IV iron in adult patients with CKD note yet on dialysis if 1) an increase in hemoglobin level is desired to avoid or minimize blood transfusions and ESA use and/or to alleviate symptoms potentially related to anemia and 2) TSAT is ≤30% and ferritin is ≤500 ng/ml. The Guideline also states that a 1-3 month trial of oral iron may be considered for patients not yet on dialysis.

Safety and risks of IV iron use in the non-dialysis CKD population are not fully understood although an author of the current study, Agarwal, along with other colleagues previously demonstrated that IV iron use can lead to increased oxidative stress, endothelial damage, and even renal injury.

The hypothesis of the current study, REVOKE (randomized trial to evaluate intravenous and oral iron in chronic kidney disease), was that IV iron would result in greater decrease in kidney function compared with oral iron in iron-deficient patients with moderate to severe CKD not yet on dialysis.

METHODS

Design: open-label, parallel-group, active-control, single-center randomized trial

Setting: A safety-net hospital and a VA Hospital, both in Indianapolis, IN; August 2008 – November 2014.

Inclusion criteria:

• ≥18 years old
• eGFR 21-60 ml/min/1.73 m2, not on dialysis
• Hemoglobin <12 g/dl
• Serum ferritin <100 ng/ml or serum transferring saturation <25%

Exclusion criteria:

• Pregnant or breast feeding females
• Known hypersensitivity to any intravenous iron, iothalamate meglumine (Conray 60, Malinckrodt) or iodine
• Severe anemia that required imminent red blood cell (RBC) transfusion (Hgb <8 g/dL) or the potential need for imminent RBC transfusion (e.g., active bleeding) 
• Persons with acute kidney injury
• History of intravenous iron use within the month prior to screening
• Iron overload (serum ferritin >800 ng/nl or transferrin saturation >50%)
• Anemia not caused by iron deficiency (e.g., sickle cell anemia)
• History of surgery or systemic or urinary tract infection within the past month
• Organ transplant recipients
• Persons currently being treated with immunosuppressive agents

Randomization and Blinding: 1:1 ratio, using computer generated permuted blocks, randomized to either oral iron or IV iron using concealed opaque envelopes

Primary outcome: 

• Difference between treatment groups in slope of mGFR decline from baseline to 2 years adjusted for the log of baseline urinary protein/creatinine ratio compared with baseline at 8 weeks, 6 months, 12 months, and 24 months after randomization.  

Secondary outcomes:

• further adjustment of the primary outcome for age, sex, race (Black vs. non-Black), angiotensin-converting enzyme/angiotensin receptor blocker use, and the presence or absence of cardiovascular disease (all determined at baseline)
• between-group % change in proteinuria from baseline to 8 weeks
• difference between hemoglobin response between treatment groups
• change in KDQOL

Statistical analysis:

• Intention-to-treat, if the participant received at least one dose of study medication
• Linear mixed model with GFR as outcome variable
• Assumptions: mean rate of decline in GFR of 4 ml/min per 1.73 m2 per year in the oral iron group and a 50% greater decline in the IV iron group and a cumulative rate of dropout of 25%
• Recruitment target of 100 patients for each treatment group with a minimum duration of follow-up of 2 years to achieve 82% power to detect hypothesized difference in decline in kidney function at the 5% level of significance
• 2-sided t-test considered significant for p<0.05

INTERVENTION

Participants were treated over 8 weeks beginning at the time of randomization. Those randomized to the IV iron group received iron sucrose 200 mg IV over 2 h at weeks 0, 2, 4, 6, and 8. Participants randomized to oral iron were counseled to take ferrous sulfate 325 mg three times daily for 8 weeks.

RESULTS

Trial was terminated early due to higher serious adverse event rate in IV iron group (199 per 100 patient years) compared with oral iron group (168.4 per 100 patient years); adjusted incidence rate ratio 1.60 (1.28–2.00), P<0.0001.  Statistically significant increases in infections and cardiovascular events were observed. In particular, the incidence of lung and skin infections was increased 3-4x and of hospitalization for heart failure was increased 2x in the IV iron group after adjusting for the more favorable baseline characteristics in that group.

Decrease in mGFR between groups was similar between both groups, -3.6 ml/min per 1.73 m2 per year for oral iron group and -4 ml/min per 1.73 m2 per year for IV iron group. 

Hemoglobin increase, change in proteinuria over time, ESA use, and need for blood transfusions were not significantly different in the 2 groups. KDQOL domain scores did not change over time in either group.

DISCUSSION

Since this study was limited to patients with stage 3-4 CKD not yet on dialysis, results cannot be generalized to patients already on dialysis. 

The primary outcome of comparing decline in mGFR between groups could not be evaluated due to early termination of the study due to safety concerns related to increased risk of infection and cardiovascular events.  While additional studies evaluating the long-term safety of IV iron use in this population are necessary, should the oral route be preferred when initiating iron supplementation in patients with stage 3-4 CKD?  Moreover, based on the time course of hemoglobin increase in patients in the oral iron group of this study, it would seem reasonable that a trial of oral iron be given to patients with CKD not yet on dialysis for a full 3 months, rather than at least 1 month and up to 3 months as suggested in the KDOQI guidelines.

Being Mortal: Chapter Seven

I did not like the Immortal Life of Henrietta Lacks. I thought the story of the HeLa cells and the story of Ms Lacks and her family was interesting and introduced me to a history of medicine that had previously been invisible. The story was fascinating but the book fell flat because of the way that the author, Rebecca Skloot, inserted herself into the story. Every chapter that was told from Ms. Skloot's point of view came across as having low stakes and was generally uninteresting. I finished the book with the belief that this point-of-view writing was a poor technique for non-fiction.

I was wrong. While it didn't work for the Immortal Life, Dr. Gawande uses it to dramatic effect in Being Mortal. Gawande is a recuring character in the book and the previous chapters we are taken on his journey from a doctor with conventional western medicine understanding about dying o a much deeper and richer understanding. In chapter seven, however, Gawande changes from a researcher to an active participant as his dad suffers a devastating illness and he needs to put his new found knowledge of hospice, assisted living, palliative care and end-of-life decisions to use.

“The scan revealed a tumor growing inside his spinal cord.
That was the moment when we stepped through the looking glass. Nothing about my father’s life and expectations for it would remain the same. Our family was embarking on its own confrontation with the reality of mortality. The test for us as parents and children would be whether we could make the path go any differently for my dad than I, as a doctor, had made it go for my patients. The No. 2 pencils had been handed out. The timer had been started. But we had not even registered that the test had begun.”

In 2006, Gawande's father, Dr. Atmaram Gawande, went for an MRI to diagnose a slowly progressive pain in his neck associated with numbness in his left hand. The scan revealed a spinal cord tumor.

The Gawande's then consulted a pair of neurosurgeons, one in Boston and one at the Cleveland Clinic. Gawande explains the bedside manner of both doctors by describing a paper by the medical ethicists Linda and Ezekiel Emmanuel that described the three type of relationships doctors could have with patients:

1. Paternalistic
2. Informative
3. Interpretive

Gawande describes all three types. The first is the doctor we read about from the 50's. The all knowing God-like figure that tells the patients what they should do and does not discuss options that the doctor does not think are optimal. We would like to think that we are past this but in reality it is more common than we care to admit. 

The second type, informative, is the opposite of the paternalistic relationship. The doctor informs the patient of the facts and figures needed to figure out the best option and then lets the patient make the decision. Gawked explains that this works best for for simple issues with clear choices and straightforward trade-offs. The more complex and emotional the issue the more this method breaks down.

The Emmanuels third option, interpretive, is a hybrid of the two earlier models. “Here the doctor’s role is to help patients determine what they want. Interpretive doctors ask, “What is most important to you? What are your worries?” Then, when they know your answers, they tell you about the red pill and the blue pill and which one would most help you achieve your priorities.”

The chapter winds its way through his father's illness and we see Gawande struggle to use the lessons he has learned to help his father. They make some excellent decisions, they make some mistakes, they meet some excellent physicians and some clunkers. The face decisions on hospice, medical decision making and hospice. Despite some missteps, by the end of the chapter his father is in hospice and living a surprisingly full life.

“But walking slowly, his feet shuffling, he went the length of a basketball floor and then up a flight of twenty concrete steps to join the families in the stands. I was almost overcome just witnessing it. Here is what a different kind of care—a different kind of medicine—makes possible, I thought to myself. Here is what having a hard conversation can do.”

Being Mortal: Chapter Five

Francesco Iannuzzella wrote the summary for chapter 5.

Chapter Five: A Better Life

In order to maintain the integrity of their social network, and enjoy a higher quality of life, most elderly people would prefer to remain in their homes as long as possible. Nevertheless, at some time during their life, many of them will be admitted to a nursing home.

Traditionally, nursing homes have been organized to provide an efficient medical care to frail and impaired individuals with little or no attention given to quality of life. Fortunately, the deepest changes usually start on a very small scale and one single successful experience can radically change the way of doing something. 

In the beginning of chapter five, Gawande describes the biography of one of these heroes, Bill Thomas, a man who rewrote the manual on how nursing homes operate.

Bill Thomas’s experience began in the early 1990s when he got a new job as medical director of Chase Memorial Nursing home in the town of New Berlin, NY. He was only thirty-one with little or no experience in eldercare. With his newcomer’s eyes, Bill began to question the basic assumptions all had taken for granted since then.

He identified “The Three Plagues” of nursing home existence:

1. boredom
2. loneliness, and
3. helplessness.

Then, he tried to fix them experimenting a new approach to eldercare. His aims were clear: he wanted to replace boredom with spontaneity, loneliness with companionship, and helplessness with a chance to become involved in caring for another being. At the beginning, he didn’t make a great change in everyday Chase Memorial healthcare practice, but he adopted an easy and effective approach to bring life to its inhabitants: he introduced a lot of pets, gardens and children to the nursing home.

“He said, “Now, what about cats?”
I said, “What about cats?” I said, “We’ve got two dogs down on the paper.”
He said, “Some people aren’t dog lovers. They like cats.”
I said, “You want dogs AND cats?”
He said, “Let’s put it down for discussion purposes.”
I said, “Okay. I’ll put a cat down.”
“No, no, no. We’re two floors. How about two cats on both floors?”
I said, “We want to propose to the health department two dogs and four cats?”
He said, “Yes, just put it down.”
I said, “All right, I’ll put it down. I think we’re getting off base here. This is not going to fly with them.”
He said, “One more thing. What about birds?”
I said that the code says clearly, “No birds allowed in nursing homes.”
He said, “But what about birds?”
I said, “What about birds?”
He said, “Just picture—look out your window right here. Picture that we’re in January or February. We have three feet of snow outside. What sounds do you hear in the nursing home?”
I said, “Well, you hear some residents moaning. You possibly hear some laughter. You hear televisions on in different areas, maybe a little more than we’d like them to be.” I said, “You’ll hear an announcement over the PA system.”
“What other sounds are you hearing?”
I said, “Well, you’re hearing staff interacting with each other and with residents.”
He said, “Yeah, but what are those sounds that are sounds of life—of positive life?”
“You’re talking birdsong.”
“Yes!”
I said, “How many birds are you talking to create this birdsong?”
He said, “Let’s put one hundred.”
“ONE HUNDRED BIRDS? IN THIS PLACE?” I said, “You’ve got to be out of your mind!”

Wilma and Libby

The results were extraordinary:

• The number of prescriptions halved
• With a particular reduction in the use of psychotropic drugs
• Mortality fell about 15%.

This was the starting point for a larger program, named Eden Alternative, which over the last 20-years de-institutionalized nursing homes and ultimately lead to the so-called Green House project. Since the first Green House was built in Tupelo, Mississipi, in the year 2000, more than 150 Green Houses have been built in twenty-five states. With no more than twelve residents each, all Green Houses are small and communal with a physical environment made to preserve quality of life, self-sufficiency, privacy, and dignity.

How to explain the Eden Alternative success?

To answer this question, Gawande cites an American philosopher, Josiah Royce (1855-1916), who believed that in order to live a worth living we need loyalty, i.e. a dedication to a cause beyond ourselves. It doesn’t matter if this cause is small (as small as the care for a pet) or large, what matters is that is such a cause provide meaning to one's life. We all need loyalty, and elderly people need it even more.

“The elderly need loyalty to give meaning to both their life and their death.”

They need loyalty to give meaning to both their life and their death. With aging, simple pleasures,  we all take for granted during our adulthood, may become a source of loyalty, a comfort to our pain. To testify to this truth, Gawande reports the interviews tof nursing home residents he met, whose quality of life strictly depends upon simple pleasures: living in a private room, going to the cinema, reading Fifty Shades of Grey, using a computer, preserving social interactions.

Gawande describes his experience visiting two different projects in the Boston area. The first one, it is a new human size retiring community called NewBridges on the Charles with great financial resources due to substantial philanthropic support.  The second project is a subsidized apartment building (Peter Sanbord Place) for low-income elderly people, whose director Jacquie Carson deeply changed to allow her residents to continue to live their own lives.

The chapter ends by returning to the story of Lou Sanders who has deteriorated to the point where he no longer can live in assisted living and is admitted to a nursing home. However, he enters a Green House with private rooms and a thoroughly de-institutionalized philosophy. He rapidly adapts and explains that he knew it was the place for him when he saw that all the rooms were single. Little things can make all the difference.

Being Mortal: Chapter Four

Swapnil Hiremath summarized chapter four, bringing us to the the halfway point. Remember the chat is next Tuesday and Wednesday, July 14 and 15.

Chapter 4: Assistance

“Life is pleasant. Death is peaceful. It’s the transition that’s troublesome.”

— Isaac Asimov

Atul Gawande continues in Chapter 4 with vignettes of frail elderly individuals facing loss of independence, and the difficult choices they face. This time it is the story of Lou Sanders, a gregarious ex-veteran living in a working class Boston neighbourhood. Lou's comfortable life starts unravelling soon after his wife’s passing. As an aside, it is notable how a ‘tipping point’ often is the death of a partner (and though there have been no stories so far of single/unattached individuals, I suspect they would be doing much worse at this stage). [note to self: buy flowers on the way home tonight]. Being a very social person, Lou is adamant in refusing to move to a nursing home ‘full of old people.’ He even forces his daughter to swear to never ship him off to a nursing home. After a heart attack, followed by Parkinson’s and additional falls, he agrees to move in with his daughter Shelley, an extraordinarily supportive and willing caregiver. The realities of the modern nuclear family however intrude, and this transition is not as smooth – unlike the story of the author’s grandfather Sitaram living in a large joint family. The toll of being a full time working professional, homemaker, and also caregiver for her father’s increasing needs proves to be too much for Shelley. Medical problems include hearing difficulty, prostatism, incontinence and continuing falls. The last is exacerbated with postural hypotension (likely due to the autonomic dysfunction common with Parkinson’s – and/or the drugs used to treat it). Lou continues to refuse moving to a nursing home, and is ultimately and unhappily transitioned into an assisted living facility.

The story of assisted living facilities, and how they came into being is one of the amazing stories that make Being Mortal such a compelling story. It is the story of Keren Brown Wilson, and her stroke-struck mother’s plaintive request to her, ‘Why don’t you do something to help people like me?’ Keren mother's request was a plea for autonomy and respect.

“She wanted a small place with a little kitchen and a bathroom. It would have her favorite things in it, including her cat, her unfinished projects, her Vicks VapoRub, a coffeepot, and cigarettes. There would be people to help her with the things she couldn’t do without help. In the imaginary place, she would be able to lock her door, control her heat, and have her own furniture. No one would make her get up, turn off her favorite soaps, or ruin her clothes. Nor could anyone throw out her “collection” of back issues and magazines and Goodwill treasures because they were a safety hazard. She could have privacy whenever she wanted, and no one could make her get dressed, take her medicine, or go to activities she did not like. She would be Jessie again, a person living in an apartment instead of a patient in a bed.”

So Keren and her husband, both academics, sketched out a plan for a new kind of place, and cleared endless bureaucratic and and financial  hurdles to open ‘Park Place’ in Portland, Oregon. It had many innovative, almost radical, components – one of the most important being that the residents were called ‘tenants’, not patients, and had many more rights – such as a locked front door to their apartments.  Despite this increased freedom, there was no trade-off with worsening safety as feared. The state of Oregon made Wilson track data – and it revealed improved outcomes (including satisfaction) with lower costs. In hindsight, much of this is now unsurprising, if we consider Maslow’s hierarchy of needs.

ource: https://en.wikipedia.org/wiki/Maslow's_hierarchy_of_needs#/media/File:MaslowsHierarchyOfNeeds.svg ; used under Creative Commons license.

Much of the research in this area is done by Laura Carstensen, now a Stanford Professor in Longevity, but once a high school educated almost single mother (read chapter 4 for the truly amazing story of how everything changed for her). Perspectives change as the end of life appears closer on the horizon, and comfort and companionship become valued over other ambitions. Unfortunately, the kind of assisted living started by Keren Brown Wilson has now morphed into something else entirely, with very few facilities including the core concepts from her original vision. The fate of Lou Sanders was in one such place. After initially coping and adjusting, the falls and more critical events force Shelley to ‘place’ him in a nursing home...

“a medically designed answer to unfixable problems, a life designed to be safe but empty of anything they care about.”

Being Mortal: Chapter Three

Graham Abra wrote this summary. 

Chapter 3: Dependence

The chapter begins with the stories of Bella Silversone and Alice Hobson who struggle and are unhappy with their experiences in assisted living and skilled nursing facilities. 

Gawande uses these narratives to set the stage for how society has handled the care of people as they age.  In the United States, in the early 1900s, if individuals did not have family or financial independence the only option once they were unable to care for themselves was a poorhouse or almshouse.  These institutions housed not just the elderly but also the mentally ill, young drunks, and out-of-luck immigrants.  Housing was provided in exchange for labor and conditions were generally poor. 

Although poorhouses have now disappeared as places of care for the elderly in the United States they have been replaced by institutions that often require us to give up most of the control of our lives.  How this happened is the story of the medicalization of natural aging. 

In 1946, the Hill-Burton Act provided large amounts of federal funding for communities to build hospitals.  Medicine was becoming more powerful and for the first time was actually curing previously fatal diseases.  Social security might have provided financial support but it didn’t “cure” infirmity and so the hospital became an attractive option for the elderly infirm.

Unfortunately medicine had no answer for the ravages of time and chronic illness so the hospitals began to fill with the elderly who were unable to care for themselves as the poorhouses emptied and closed through the 1950s.  As their beds overflowed hospitals lobbied for help and in 1954 funds were made available for custodial units that provided a place for patients in need of extended “recovery.”  Thus was born the “nursing” home.  

In 1965 the Medicare bill passed and payment for medical services for elderly Americans in facilities that met basic health and safety standards was available. Unfortunately many parts of the country lacked access to such places and so, fearing a political backlash, the concept of “substantial compliance” was created – allowing facilities that were “close” to the standards and trying to improve to qualify for payment. This opened the door to profit through underfunded service. With a belief in the power of medicine to cure and payment on hand, 13,000 nursing homes were built by 1970, many with substantial quality problems.

The quality problems have improved over time and have been replaced by a focus on control and safety in order to meet payment requirements.  The institutions where 50% of us will spend a year a more of lives were not designed to make life worth living at the end – they were designed to meet other goals.  

After losing her love for life and signing a DNR, the chapter ends with Alice’s death.

Being Mortal: Chapter Two

Edgar Lerma, [EL] Chicago nephrologist and father of #NephPearls worked with Joel on this summary of the second exciting chapter of Being Mortal.

Chapter Two: THINGS FALL APART

Chapter Two looks at how life and death have changed with modernity. Gawande describes how the lifespan has increased from around 60 in the 1930’s to somewhere in the 80’s today. But he goes on to emphasize that the life span does not quite capture how much the shape of mortality has changed. He points out that modern medicine has dramatically reduced childhood mortality. Please look at the story of John Leal and his role in reducing infant mortality by 74% by inventing the concept of chlorinating city water.

Gawande describes the change in the ‘trajectories of life.’ In the past, life appeared to be a continuum, curtailed by disease or injury. This could happen at anytime from infancy, to childhood, to adulthood to older age. The risk was relatively flat, one day you were alive and the next you were kicked by a horse, or infected with influenza, or had a heart attack, and the next day you were dead. Modern medicine has changed that trajectory in a couple of different patterns. The most successful medical practices delay or prevent acute deaths. Treatment of serious infections or trauma care are good examples. Even some cancer therapy is successful at delaying the onset of decline without changing the basic pattern of health until a final acute loss:

“People with incurable cancers, for instance, can do remarkably well for a long time after diagnosis. They undergo treatment. Symptoms come under control. They resume regular life. They don’t feel sick. But the disease, while slowed, continues progressing, like a night brigade taking out perimeter defenses. Eventually, it makes itself known, turning up in the lungs, or in the brain, or in the spine, as it did with Joseph Lazaroff. From there, the decline is often relatively rapid, much as in the past. Death occurs later, but the trajectory remains the same.”

But for others, including those with chronic and progressive diseases, the trajectory has ups and downs, and following every deterioration, any recovery is incomplete and the overall trend is accumulating burden of illness. A classic example is chronic kidney disease. It is a chronic and progressive disease marked with episodes of AKI that further reinforce and accelerate the decline. People become weaker and weaker with incomplete recovery.

The effect of medicine has also introduced (or made more prevalent) a new type of death, a third pattern, a pattern not influenced by acute or chronic disease but just a slow withering decline, death by old age. Gawande spends a few great paragraphs describing the normal deterioration of aging and medicines frustration in dealing with it. Some facts:

• By age 60, people in industrialized countries have lost on average a third of their teeth.
• “As we age, it’s as if the calcium seeps out of our skeletons and into our tissues.”
• More than half of people develop hypertension by age 65
• Peak cardiac output occurs at age 30 and deteriorates after that
• By age 85, 40% of people have textbook dementia

This resonates with my [EL] CKD practice. I am repeatedly explaining that from age 40 onwards kidney function deteriorates as pat of normal aging. Furthermore, uncontrolled diabetes, hypertension, along with acute illness, accelerates this decline. My job, all of our jobs, as kidney specialists, is to slow this inevitable decline.

Gawande emphasizes that this deterioration is normal and unavoidable. We hold up the exceptional 97-year old marathoner as something to strive for rather than a story of remarkable genetic luck.

He then describes various theories about aging and different models to explain why we age. He looks at models of aging from complex systems to genetics. He describes the cellular mechanics of aging in skin, hair, and the eyes. It is a fascinating trip through the biology of aging.

As part of this tour we are introduced to Dr. Felix Silverstone a senior geriatrician at Parker Jewish Institute in New York. He is introduced as an expert geriatrician with over a 100 publications. He is is however old and now experiencing what he spent a career studying.

These societal changes bring about two revolutions: a “biological transformation” of the course of one’s life and also a “cultural transformation” of how one thinks about that course.

One of the societal changes of modernity has been the ‘rectangularization’ of the pyramid of life.

n the past, the elderly tended to be outnumbered by the younger generation; however, as people tend to live longer, there are almost equal numbers represented by the young and the elderly. This has wide ranging implications. For one, the number of people supporting retirees is shrinking compared to the number of retirees. The time when a large working population is supporting a small number of retirees is gone.

The second issue that he brings up is that medicine has done a poor job preparing for the changing demographics. The number of geriatricians with the skill and experience in handling such patients is not keeping up with the need. Structural changes in medicine perversely are causing geriatric centers to close in the face of increasing need.

“Although the elderly population is growing rapidly, the number of certified geriatricians the medical profession has put in practice has actually fallen in the United States by 25 percent between 1996 and 2010.”

As a subspecialist, I [EL] tend to view my patients in a reno-centric point of view. I feel that I am very good at diagnosing and treating kidney related problems. However, I do realize that as I fix my patients’ kidney related issues, e.g., blood pressure control, diabetes control, etc., there are some on the problem list that won’t ever get resolved, e.g., the lower extremity edema of my CHF patient with LVEF ~ 10% or the salt intake of my patient who depends on Meals on wheels, etc.

Oftentimes, my untrained mind, wonders why is it that whenever I see elderly patients, it’s as if the primary care provider hasn’t adjusted their BP meds or checked their proteinuria, etc. Gawande addresses this by explaining that geriatricians have a unique point of view. An example is a story about Dr. Juergen Bludau, a geriatrician, who paid more attention to an elderly patient’s feet, and if she is able to bend over to clean them. It all boils down to the idea that this intensely practical approach translates into decreased falls. Dr Bludau said that “the job of any doctor is to support quality of life: as much freedom from the ravages of disease as possible, and retention of enough function for active engagement in the world.” Gawande describes how effective the work of geritricians is by explaining a landmark randomized controlled trial of geriatric versus usual care.

“Within eighteen months, 10 percent of the patients in both groups had died. But the patients who had seen a geriatrics team were a quarter less likely to become disabled and half as likely to develop depression. They were 40 percent less likely to require home health services.

These were stunning results. If scientists came up with a device—call it an automatic defrailer—that wouldn’t extend your life but would slash the likelihood you’d end up in a nursing home or miserable with depression, we’d be clamoring for it. We wouldn’t care if doctors had to open up your chest and plug the thing into your heart. We’d have pink-ribbon campaigns to get one for every person over seventy-five. Congress would be holding hearings demanding to know why forty-year-olds couldn’t get them installed. Medical students would be jockeying to become defrailulation specialists, and Wall Street would be bidding up company stock prices.

Instead, it was just geriatrics. The geriatric teams weren’t doing lung biopsies or back surgery or insertion of automatic defrailers. What they did was to simplify medications. They saw that arthritis was controlled. They made sure toenails were trimmed and meals were square. They looked for worrisome signs of isolation and had a social worker check that the patient’s home was safe.

How do we reward this kind of work? Chad Boult, the geriatrician who was the lead investigator of the University of Minnesota study, can tell you. A few months after he published the results, demonstrating how much better people’s lives were with specialized geriatric care, the university closed the division of geriatrics.”

The chapter closes by rejoining Felix Siverstone as he ages and enters a nursing home with his wife. He thrives in this environment and even starts a journal club for retired physicians (NephJC geriatric edition!)

The chapter is a great set up for the rest of the book, it informs the readers, sets the stage, raises the stakes. The tension is set.

Being Mortal: Chapter one

Suzanne Norby is a nephrologist and fellowship program director at the Mayo Clinic and recently joined the NephJC advisory board. She wrote the first of our eight (fingers crossed) chapter summaries of Atul Gawande's Being Mortal. 

Chapter one The Independent Self

In the first chapter of his book, Being Mortal – Medicine and What Matters in the End, Atul Gawande begins by introducing the reader to the dissimilar aging experiences of his grandmother-in-law, Alice Hobson, in Alexandria, VA and his own grandfather, Sitawan Gawande, in India.  He then explores several historical and cultural influences affecting how societies view elders and aging.

When Gawande first met his future grandmother-in-law, Alice was a vibrant 73-year-old widow living an active and independent life: residing in her own home, driving her own car, and even regularly going to the gym with a friend.  In contrast, his own grandfather was hard of hearing, walked with a cane, and lived in the home of one of his sons in India. He not only had assistance with activities of daily living but also occupied a place of honor. One fateful day, at age 109, he was traveling with a family member on a bus to take care of some of his own business at a courthouse.  He fell and hit his head, likely suffering a subdural hemorrhage. Several days later, he died at home, surrounded by family, as he would have wanted.

Next, Gawande explains that relationship between older and younger generations has evolved in multiple ways.  First, the exclusive position once held by elders has eroded. Throughout most of history, life expectancy was considerably shorter than it is now.  Those who lived to an advanced age were respected, even revered, for their wisdom, perspective, and knowledge of tradition.  Now, living to advanced age is commonplace. Contemporary means of communication have largely eliminated the need for oral transmission of precious information to the next generation.  Moreover, older people are less likely to embrace the most modern technology, and members of younger generations have become the experts in knowledge transmission, reducing the relative importance of elders.

In addition, older people no longer remain as heads of households, providing a basis for family stability until their death. Children follow their own paths, move out of the family home, secure their own property, and become economically independent. They don’t depend on inheriting parents’ money and property to sustain their own families.  At the same time, this phenomenon also has brought financial freedom to aging parents, along with the concept of enjoying retirement.  Gawande notes that “intimacy at a distance” occurs when elderly people have financial means of their own and can choose not to live with their children after they are no longer working.  The percentage of elderly people living alone is increasing not only in the U.S. but also in countries in which it had been previously regarded as “shameful” when an elderly parent is left to live alone.  In fact, he points out that it has become “acceptable and feasible” for elderly people, such as his grandmother-in-law Alice, to live autonomously.  Generational power differences have shifted, allowing both parents and children to have more freedom and control.  Rather than valuing elders or even the younger generations, society’s ideal has become the “independent self.”

“Alice’s unsteadiness is not something that can be fixed”

The problem with the independent self, Gawande explains, is that inexorably, the realities of life eventually render independence impossible.  He poses the question, “If independence is what we live for, what do we do when it can no longer be sustained?”  He then returns to the story of Alice, now 84 years old, exhibiting memory impairment while on a family vacation and sustaining multiple falls in her home. Her son takes her to the doctor, who diagnoses osteoporosis and changes her medications.  Ultimately, though, Alice’s unsteadiness is not something that can be fixed:  she would not be able to remain independent as she continued to decline.  Her doctor, however, “had no answers or direction or guidance” and couldn’t describe what to expect going forward.  With that statement, Gawande foreshadows the message of the next several chapters of his book.

The book club is coming!

On July 13th and 14th we will be doing the first NephJC book club on Atul Gawande's excellent Being Mortal.

Ugh! Chapter 3 is very depressing. More so because it seems true. Hope it gets better...#nephjc #bookclub pic.twitter.com/yA4VCec7bN

— Swapnil Hiremath, MD (@hswapnil) June 18, 2015

Don't lose hope the book has some supremely uplifting chapters like the story of Bill Thomas bringing life to a nursing home with pets, lots of pets:

@hswapnil buck up lil’gunner you’ll love the part about the nursing home with 2 dogs, 4 cats and a 100 birds! #NephJC pic.twitter.com/KuMB6OWWwX

— Joel Topf (@kidney_boy) June 19, 2015

To get ready for the book club I found this article about the twitter book club #1Book140. Pretty interesting. My favorite part of the article is

“But so what? For me, 1book140 was more enjoyable for its intimacy. Most of all, I liked how nice everyone was. So often the Internet is a place of derision and insult. But on 1book140, participants respected one another without having to be told to be nice.”

I would be so happy if the conclusion of people take away from NephJC is that the people are nice and the conversation civil.

Thoughts on tonight's #NephJC Social Media Chat

Last night I was reading John Weiner's personal reflection on social media in medicine. He posed the question of whether the definition of professionalism is fixed and we need to adapt our social media use to these standards or do we adopt our measure and expectations of professionalism to new tools and personal behaviors. His words:

For example, a joint initiative of the Australian Medical Association Council of Doctors-in-Training, the New Zealand Medical Association Doctors-in-Training Council, the New Zealand Medical Students’ Association and the Australian Medical Students’ Association has produced a document called ‘Social media and the medical profession’ (Mansfield et al., 2011). The advice includes, inter alia, this statement:

Our perceptions and regulations regarding professional behaviour must evolve to encompass these new forms of media.

I would argue that perceptions and regulations of professionalism, once properly espoused and documented, should be applied universally, in any day and age, and for any circumstance or technology. This is declared, for example, in the Royal Australian and New Zealand College of Psychiatrists Position Statement ‘Psychiatry, online presence and social media’ (RANZCP, 2012) where, although there are specific allusions to social media behaviour in the document, there is an over-riding clause that clearly states:

they must ensure their social media use and Internet presence upholds the ethical and practice standards required for Fellowship of the College. (RANZCP, 2012)

Others argue that social media is somehow different. After all, it has immediacy and reach and permanency. I cannot accept that a smart, well-educated student who has achieved entry to medical school does not know these properties of social media.

This question seems to be at the center of any discussion of professionalism in social media, we need to at least understand what we mean by professionalism. While at first blush it seems that standards are only standards because they do not change. But on deeper thought, it is clear society has evolved. Imagine 1985 Marty McFly driving his Delorean to 2015 Brooklyn. What would be his reaction to people:

• publicly share vacation photos for the world to see
• millions of public diaries open to the world
• restaurants full of people snapping and sharing pictures of their food
• people "checking in" to share their current location when they get to every social engagement

He would be shocked at this narcissistic hellscape. Our ideas of privacy have undergone radical changes in just a few decades. It seems to me that the codes of professionalism must evolve with the standards and behaviors of the time or they will lose relevancy and become just an exercise in conservatism.

Please join us for this chat tonight at 9PM Eastern or tomorrow at 8PM GMT (3PM Eastern/Noon Pacific), it should be great.

The AUA v ACP guidelines. Fight!

Tonight's and Wednesday's #NephJC is going to focus on the ACP guidelines. But it is important to recognize that a different group looked at the same data and came up with very different conclusions of what CPG should look like.

The systemic review that is the primary source...

...was the same in both clinical practice guidelines.

The American Urological Association Guideline (PDF) consists of 27 guidelines covering:

• Evaluation
• Diet therapy
• Pharmacologic therapy
• Follow-up

The AUA did consider 18 additional studies that were not part of the AHRQ analysis. The recommendations are graded and the authors interpreted the grades thusly:

1. Clinical Principle. This is a statement about a component of care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. My sense this is, that these recommendations are so woven into the fabric of stone care that people would not be able to get a study of these practices past an IRB.
2. Expert Opinion. This is a statement, achieved by consensus of the Panel, based on clinical training, experience, knowledge and judgment for which there is no or insufficient evidence.
3. A or B level evidence translated into Standards
4. C level evidence becomes Recommendations
5. Options are non-directive standards that may or may not be based on evidence. There is only one and it was evidence grade B

Background

• The prevalence of stones is increasing. It has gone from 5.2% in 1988-94 to 8.8% in 2007-2010.
   
• It is affecting more women so that it is much male dominated. The male:female ratio has slipped from 1.7:1 in 1997 to 1.3:1 in 2002.

• They looked at the diet studies that used stone formation as the outcome. Those studies found that increased water intake reduced stones. It found beneficial effect by avoiding cola. 
   
• They looked at multicomponent diets and described the ability of a low sodium, normal calcium, low animal protein to reduce stones more than a low calcium diet.
   
• Two other studies restricted animal protein as part of a multicomponent diet and was unable to find any advantage.
   
• The authors point out that changes to urinary stone risk factors has not been validated as an intermediate endpoint.

The authors are transparent about one of the primary gaps in the use of diagnostic information about the nature of a stone in the therapy for that stone.

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One caveat, all the RCTs diet studies were done in stone forming men.

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The Guidelines

The 27 guidelines themselves are pretty straight forward and read like a description of what takes place in a well run stone clinic. The authors are again transparent, labeling many of the guidelines as Clinical Principle and Expert Opinion. In terms of the final score it looks like this:

Well over half the guidelines are opinion or clinical principle (which is just an opinion in a new hat).

Here is the breakdown by section:

Not surprisingly, only pharmacologic therapy has received significant RCT attention.

The AUA and ACP guidelines are based on the same evidence but ultimately look very different. The ACP guidelines look at this evidence desert and provide guidelines so sparse they end up functionally useless. The AUA, on the other hand, hitches the evidence to common sense, scientific innuendo, and long-held medical habit to provide fairly comprehensive guidelines that primary care doctors and part-time stone-physicians can use to actually take care of patients. The AUA guidelines paired with the AHRQ evidence analysis are documents I would have every fellow add to their iPad library. The ACP guidelines? Not so much.

In the end the ACP guidelines read like political statement protesting the sorry state of stone evidence, while the AUA guidelines provide a practical manual guiding stone care while still being transparent about the poor state of evidence.

Joel Topf, MD