Living with PKD: A PKD Survivor in Palo Alto; PKD Research: bardoxolone Phase 2 study shows improvement for ADPKD; Kidney Transplant Wait List Issues

Living with PKD

From The Almanac, Palo Alto, CA

A health scare, then a new restaurant

Two months after getting a kidney transplant she was never supposed to survive, Maria Neal opened her first restaurant.

It might sound like a recipe for chaos or, at the very least, excessive stress for someone recovering from a serious surgery. But for Neal, a 36-year-old mother of four from Peru, it was a change that she says has saved her life.

Neal, who lives in Menlo Park, opened Caffe Machiavello in the ground floor of Park Plaza Apartments at 195 Page Mill Road in Palo Alto in early August. The idea for the restaurant was born three years ago, when Neal, who was born with polycystic kidney disease, fell and harmed her kidneys. Her nephrologist told her she had a 14 percent chance of making it to her kidney transplant surgery -- not to survive the surgery, but simply to the day of, she said. She prepared for the worst.

"I had accepted that I was going to die," she said.

But survive she did, with a new kidney from her mother and a new outlook on what's most important to her. She left her job as a real estate agent to spend more time with her three sons and daughter, 16, 14, 8 and 6 years old.

Post-surgery, however, Neal's diet became extremely restricted and eating out with her children became near-impossible. Things were "chaotic," she said.

"I spent the last few years searching for stability ... to leave my kids something behind that they can actually remember mommy by, and for them to know that I was not going to just disappear," Neal said, sitting at a table inside Caffe Machiavello on a recent afternoon. "So I decided to build this restaurant."

Neal was encouraged by a mentor, an older local restaurant owner who had survived cancer twice. (He did not wish to be named.) He is like a father figure for Neal, who lost her father to the same kidney disease when she was a teenager.

He "pushed me to see life in a different way and to not believe what the doctors say necessarily," Neal said, "but to fight."

At Caffe Machiavello (Neal's maiden name), there is a high emphasis on quality of ingredients, largely due to the owner's dietary restrictions. In Neal's words, she doesn't use anything "that I can't pronounce." The bread for sandwiches, the pizza dough and the complimentary cookies brought to every table are all made in house. The kitchen uses a 50-year-old family recipe for the bread, Neal said, and imports flour from Italy for the pizza. They serve thin-crusted, Roman-style pinsa pizza made from Italian flour, olive oil and water.

The kitchen also has to be impeccably clean. Neal's kidney medications lower her immune defenses, making her extremely susceptible to any kind of illness.

The menu is global, with bruschetta and pizza next to hamburgers and chicken wings. Peruvian dishes include lomo saltado, steak flambe with onions, tomatoes, cilantro and rice or quinoa; pollo a la brasa, rotisserie chicken seasoned by Neal nightly with spices and aji panca, a Peruvian red pepper; and a quinoa bowl with roasted rocoto, a spicy Peruvian pepper. A deli section sells packaged international foods like Italian salami and Mediterranean spreads.

The wide culinary range is purposeful, meant to serve large families with different tastes and customers with dietary restrictions. Customers who want the kitchen to make them something special only need to ask, Neal said.

It's also reflective of a diverse staff, whom Neal refers to as her "family." She said she plans to give employees a portion of the restaurant's profit as it grows.

"You have food from around the world and people cooking from around the world. That's kind of what we want. Under this one roof, you can feel a little piece of what America used to be -- a humongous, beautiful, happy melting pot," she said.

Her family helps out frequently. Her husband DJs on a patio during happy hour, while her oldest son works at the restaurant after school.

Running the large, airy restaurant, and all the ups and downs that come with it, has become a welcome respite for Neal.

"This is not allowing me to feel weak or sick. I have not been able to rest ever since I left the hospital," she said. "I think that it helps me a lot. I'm very happy and very energetic, something that I didn't have before."

PKD Research

From Healio, Nephrology News & Issues

Phase 2 data show bardoxolone improves kidney function in patients with CKD

Results from a phase 2 study of bardoxolone methyl in patients with either IgA nephropathy or chronic kidney disease-associated type 1 diabetes showed improvement in eGFR after 12 weeks of therapy, according to a press release from Reata Pharmaceuticals Inc.

Improved kidney function in both cohorts was the primary endpoint of the PHOENIX study, which was conducted by the biopharmaceutical company.

“With these data, bardoxolone has improved kidney function in multiple rare forms of CKD, including Alport syndrome, autosomal dominant polycystic kidney disease, IgA nephropathy and type 1 diabetic CKD,” said Reata’s chief medical officer Colin Meyer, MD, in a press release. “The absence of drug-related serious adverse events and the eGFR improvements observed in the rare forms of CKD that we have studied suggest that bardoxolone has the potential to become an effective therapy for multiple rare forms of CKD.”

In the program, patients received bardoxolone orally once a day for 12 weeks. The primary efficacy endpoint was change from baseline in eGFR after 12 weeks of treatment.

In the IgA nephropathy cohort, patients treated with bardoxolone experienced an increase in eGFR of 8 mL/min/1.73 m2 (n=26) at Week 12 compared to baseline. Reata collected historical eGFR data for 23 of these patients, which demonstrated their kidney function was declining at an average annual rate of 1.2 mL/min/1.73 m2prior to study entry, the company said. The observed improvement after 12 weeks of treatment with bardoxolone represents a recovery of approximately 6 years of average eGFR loss, Reata reported.

In the type 1 diabetes cohort, patients treated with bardoxolone experienced a significant increase in eGFR of 5.5 mL/min/1.73 m2 (n=28) at Week 12 compared to baseline. Historical eGFR data for 22 of these patients showed kidney function was declining at an average annual rate of 1.9 mL/min/1.73 m2 prior to study entry. The observed improvement after 12 weeks of treatment with bardoxolone represents a recovery of approximately 3 years of average eGFR loss, the company said.

No treatment-related serious adverse events were reported in either cohort, and the reported adverse events were generally mild to moderate in intensity, Reata reported.

Reata said in its press release that the FDA has granted orphan designation to bardoxolone for the treatment of Alport syndrome and pulmonary arterial hypertension, and the European Commission has granted orphan designation to bardoxolone for the treatment of Alport syndrome. In addition to PHOENIX, bardoxolone is being studied in CARDINAL, a phase 3 study for the treatment of Alport syndrome; in CATALYST, a phase 3 study for the treatment of connective tissue disease-associated pulmonary arterial hypertension; and in AYAME, a phase 3 study for the treatment of diabetic kidney disease in Japan, the company said.

Kidney Transplant

From Healio, Nephrology News & Issues

Disparities seen in access to preemptive transplant listing
The new Kidney Allocation System has not solved inequities that low-income and minority patients with kidney disease face when seeking the benefits of preemptive waitlisting for a transplant, Drexel University College of Medicine researchers reported in a study published in the Journal Clinical Transplantation.

Preemptive waitlisting allows patients with kidney disease to be listed for a kidney transplant before requiring dialysis.

“The goal of this study was to examine whether the new [Kidney Allocation System] KAS was associated with differences in pre-transplant dialysis durations for (deceased donor kidney transplant) recipients with and without preemptive waiting time,” wrote study lead author Meera Nair Harhay, MD, a nephrologist and associate professor of medicine at Drexel University College of Medicine, and colleagues. “We performed a retrospective pre-post cohort study to examine whether average pre-transplant dialysis durations differed among kidney transplant recipients before and after KAS implementation based on the recipient’s preemptive listing status and by race/ethnicity.”

Getting on a waitlist for a transplant – and avoiding dialysis – has for some time “been skewed toward patients with a higher socioeconomic status, access to better health insurance and primary care,” wrote Lauren Ingeno in a summary of the study for the newsletter Drexel Now. “Low-income and minority patients, by contrast, are disproportionately less likely to receive care for their disease early, and therefore spend much longer on dialysis.”

Harhay and colleagues performed a retrospective study of deceased donor kidney transplant (DDKT) recipients between Dec. 4, 2011 and Dec. 3, 2014, prior to the implementation of the KAS, and between Dec. 4, 2014 to Dec. 3, 2017, post-KAS. Among 65,385 DDKT recipients, “preemptively listed recipients (21%, n = 13,696) were more likely to be white (59% vs. 34%, P < 0.001) and have private insurance (64% vs. 30%, P < 0.001),” the authors wrote. “In the pre- and post-KAS periods, average adjusted pretransplant dialysis durations for preemptively listed recipients were [less than] 2 years in all racial groups. Compared to recipients who were listed after starting dialysis, preemptively listed recipients experienced 3.85 (95% Confidence Interval [CI] 3.71-3.99) and 4.53 (95% CI 4.32-4.74) fewer average years of pretransplant dialysis in the pre- and post-KAS periods, respectively (P < 0.001 for all comparisons).”

“You would expect that this new system would reshuffle the deck a bit and narrow this gap - so that someone who had been on dialysis for 2 or 3 years might get a kidney transplant before someone who has not started dialysis,” said Harhay in Drexel Now. “But we did not find that to be the case. The gap between those who were listed early and listed late is still quite wide.”

KAS also gives the highest-quality kidneys to those who have had the least years on dialysis, opening the door to further disparities based on the timing of waitlisting, Leone wrote.

“[This] study found that among kidney transplant recipients of all races and ethnicities, preemptive wait-listing continues to confer a large benefit with respect to minimizing pre-transplant dialysis duration compared to listing after dialysis under the new KAS,” Harhay and colleagues wrote. “Future studies should be directed at mitigating persistent drivers of disparate access to preemptive waitlisting.”

PKD Research: T Cells, Gift of Life: Cape Town

PKD Research

From Kidney International: Official Journal of the International Society of Nephrology

CD8+ T cells modulate autosomal dominant polycystic kidney disease progression

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent inherited nephropathy. To date, therapies alleviating the disease have largely focused on targeting abnormalities in renal epithelial cell signaling. ADPKD has many hallmarks of cancer, where targeting T cells has brought novel therapeutic interventions. However, little is known about the role and therapeutic potential of T cells in ADPKD. Here, we used an orthologous ADPKD model, Pkd1 p.R3277C (RC), to begin to define the role of T cells in disease progression. Using flow cytometry, we found progressive increases in renal CD8+ and CD4+ T cells, correlative with disease severity, but with selective activation of CD8+ T cells. By immunofluorescence, T cells specifically localized to cystic lesions and increased levels of T-cell recruiting chemokines (CXCL9/CXCL10) were detected by qPCR/in situ hybridization in the kidneys of mice, patients, and ADPKD epithelial cell lines. Importantly, immunodepletion of CD8+ T cells from one to three months in C57Bl/6 Pkd1RC/RC mice resulted in worsening of ADPKD pathology, decreased apoptosis, and increased proliferation compared to IgG-control, consistent with a reno-protective role of CD8+ T cells. Thus, our studies suggest a functional role for T cells, specifically CD8+T cells, in ADPKD progression. Hence, targeting this pathway using immune-oncology agents may represent a novel therapeutic approach for ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common, potentially lethal monogenic nephropathy caused predominantly by mutations to either PKD1 or PKD2.1, 2, 3, 4ADPKD accounts for 8% to 10% of patients receiving renal replacement therapy for end-stage renal disease (ESRD) worldwide5 and affects roughly 1:400 to 1:1000 people.6, 7 The disease is characterized by dysregulated growth of renal epithelial cells leading to progressive, bilateral fluid-filled renal cysts and resulting in ESRD in about 50% of patients by middle age.8, 9Extrarenal manifestations, such as liver and pancreatic cysts or cardiovascular abnormalities, further decrease quality of life and increase morbidity and mortality.10, 11 Previous research focused on targeting pathways central to cyst pathology, such as cyclic adenosine monophosphate/protein kinase A, epidermal growth factor, and mammalian target of rapamycin,12 have provided positive data in murine preclinical trials, but their efficacy in humans was modest at best.13, 14, 15, 16, 17 Hence the number of US Food and Drug Administration (FDA)–approved compounds for the treatment of ADPKD are limited, and ESRD is managed by either dialysis or kidney transplant.18 Thus an urgent need exists to explore new treatment options that can slow the progression of ADPKD and prevent advancement to ESRD.

Whereas mutations in PKD1 or PKD2 mediate ADPKD initiation and progression,19, 20 observed intra- and interfamilial phenotypic heterogeneity, ranging from in utero onset21, 22 to adequate renal function at old age,23 exceeds genic effects,3, 24 suggesting that additional, nongenetic factors contribute to disease progression. Further, the functional role of the PKD1 and PKD2proteins, polycystin-1 and polycystin-2, while extensively studied, remains elusive, leaving many open questions regarding the mechanisms that drive cystogenesis.25, 26, 27, 28

Although ADPKD historically has been considered a “neoplasia in disguise,”29 the significant similarities between ADPKD and cancer have been rediscovered more recently.30 In fact, many of the cancer hallmarks as defined by Hanahan and Weinberg31 are applicable to ADPKD (e.g., sustained proliferation,12, 30, 32 genomic instability,33, 34, 35 deregulated cellular energetics,36, 37and inflammation/avoiding immune destruction38, 39, 40, 41, 42, 43, 44, 45, 46, 47). Importantly, interstitial inflammation has been reported in human patients with ADPKD, as well as in animal models of the disease.40 In concordance with an inflammatory response, increased levels of pro-inflammatory cytokines, such as monocyte chemoattractant protein-1 and tumor necrosis factor–α, were detected in cyst fluid of patients with ADPKD, and anti-inflammatory therapies have been shown to attenuate disease progression in animal models.38, 39, 40 Furthermore, macrophage infiltration can be observed in orthologous and nonorthologous ADPKD models at advanced disease stage,41, 42, 43 and a few reports show CD4+ T cells, mast cells, and neutrophils in the interstitium of patients with ADPKD.44, 45, 46 Additionally, historic data showed that murine PKD models raised in germ-free environments present with milder cystic disease,47 suggesting a role for the immune system in PKD. In fact, it was shown that M2-like macrophages can promote cyst growth in murine models of autosomal recessive PKD (ARPKD) and ADPKD and that their depletion slows renal and hepatic cystogenesis.41, 42, 48 However, to date, no research in the literature addresses the role of the adaptive immune system in ADPKD initiation and progression.

Targeting adaptive immunity has become a central focus in developing new therapeutic approaches in multiple malignancies.49, 50 In many cancers, increased numbers of tumor-infiltrating T cells are associated with better prognosis,51 consistent with a role for these cells in inhibiting tumor progression. However, the role of different T-cell subtypes is complex because of their heterogeneity.52 As such, different populations have either pro-tumorigenic (e.g., regulatory T cells [Tregs]) or antitumorigenic (e.g., CD8+ T cell) roles. Additionally, cancers have developed multiple cellular and molecular pathways to suppress T-cell functions. Strategies targeting the interaction of specific T cells with cancer cells have shown recent clinical success, leading to FDA approval of checkpoint inhibitors that target the interactions of programmed cell death protein-1 (PD-1) with its ligand PD-L1, resulting in reactivation of antitumor CD8+ T cells.53, 54 The progress made in the field of cancer research, specifically the function of T cells in tumorigenesis, may yield new ideas and avenues for ADPKD research. Thus, an essential first step forward is to understand the role of T cells in ADPKD progression.

Here, we characterized T-cell subpopulations in an orthologous mouse model of ADPKD that reproduces critical features of the human disease, including a slow rate of progression. We found that T cells increase in correlation with disease severity and localize specifically to cystic lesions. Importantly, our results define a functional role for CD8+ T cells in inhibiting ADPKD progression, highlighting the potential to adapt cancer immunotherapy strategies to ADPKD.

Results

Renal T-cell numbers are increased in the C57Bl/6 Pkd1RC/RC model compared with wild type

The homozygous Pkd1 p.R3277C (Pkd1RC/RC)55 model genetically and physiologically mimics human ADPKD. It harbors a knock-in mutation that mimics a hypomorphic allele identified in ADPKD families56 and presents over time in the C57Bl/6 background with slowly progressive disease with moderate increases in percent kidney weight/body weight (%KW/BW), renal cystic/fibrotic area (index), chronic inflammation (increased renal interleukin-6/decreased interleukin-10 levels), as well as mild renal function decline (Supplementary Figure S1; Supplementary Table S1). To evaluate how the cystic microenvironment (CME), specifically T cells, differ between C57Bl/6 wild type (WT) and Pkd1RC/RC mice and to correlate changes in the adaptive immune system profile with cystogenesis progression, we used flow cytometry analysis of renal single cell suspensions and analyzed mice at 3, 6, and 9 months of age. In Pkd1RC/RCC57Bl/6 mice at 3 and 6 months, when the cystic disease is mild/moderate, respectively, we detected a statistically significant increase in immune cells (CD45+) and T cells (T-cell receptor β+[TCRβ+]) in Pkd1RC/RC compared with WT mice, but the most striking increase occurred at 9 months of age, the investigated time point at which PKD is most severe (Figure 1a and b; Supplementary Figure S1; Supplementary Table S1). The same pattern was observed for both cytotoxic T cells (CD8+) and helper T cells (CD4+, Figure 1c and d; Supplementary Table S1). Importantly, as shown by immunofluorescence, T cells (CD3+, CD4+, CD8+) specifically localized around cystic lesions even at mild stages of cystogenesis (3 months) when the global increase of T-cell number in the kidney was modest (Figure 1e and f; Supplementary Figure S2). At 9 months a more diffuse increase of T cells was notable by immunofluorescence, characterized by increased localization to noncystic areas, likely accounting for the striking increase in T-cell number at 9 months observed by flow cytometry (Figure 1b and e). This finding likely reflects the adaptive immune system’s response to increasing tubular atrophy and interstitial expansion/inflammation that can be observed in 9-month-old Pkd1RC/RC C57Bl/6 mice, despite the slowly progressive/mild disease (Supplementary Figure S1C). Importantly, the increase in T-cell numbers between C57Bl/6 WT and Pkd1RC/RC mice was specific to kidney disease, as no changes were observed in spleens (Supplementary Figure S3).  Read More...

Gift of Life

From News24, Cape Town, South Africa

Dad in desperate need of kidney saved by daughter’s teachers

A dad in desperate need of a kidney has been saved by two teachers at his daughter's school – sparking a donor chain reaction that saw eight more lives being saved.

Dad-of-two Neil Emmott was diagnosed with polycystic kidney disease (PKD) – which causes cysts to grow on the kidneys – in 2001, and over the next 15 years his vital organs began to fail.

In 2016 the usually shy and private Neil, from Fort Lauderdale in Florida in the US, was forced to make his plight public as his search for a suitable kidney became more desperate.

By the beginning of 2017, the 56-year-old’s kidney functionality was down to just 11%, leaving a single percentage of function before he’d need to be put on emergency dialysis.

When Neil’s wife, Lisa (44), and his brother, Gordon, were ruled out as potential donors because of minor health issues, Lisa – a kindergarten teaching assistant – broke down in front of one her colleagues, Allison Malouf (40), while explaining the family’s dire situation.

Allison, who teaches the couple's youngest daughter, Mackenzie (9), didn't hesitate in offering a kidney to Neil after her husband had donated a kidney to save a stranger eight years prior.

Unbeknown to the family, another teacher at the school, Britani Atkinson (44), had also registered as a potential donor for Neil in secret – hoping to save the family further disappointment if she was rejected.

“The diagnosis came as a huge shock to us – we were just enjoying our first year of marriage,” Lisa said.

“When I was denied [the chance] to donate a kidney, panic, fear and sheer anger all made me a prisoner of my own mind.

“The only thing I wanted to do in my life was to give a piece of myself to save my husband – but I couldn’t.”

She says she knew that she had only one other option: to find a donor for her Neil.

“I knew that Allison’s husband had donated a kidney eight years [before], and I wanted to tell her about it all because I knew she’d understand the donor process and the emotions that accompany the journey,” Lisa said.

“Her immediate response was, ‘I want to donate my kidney. Let’s get me tested for Neil.’ I was so shocked and politely declined her offer – but she insisted.”

Allison was approved as a donor in May last year, and soon after Britani was also approved.

But because of conflicting blood types and kidney sizes, neither of the pair could directly donate to Neil so they registered with the National Kidney Registry.

Allowing incompatible donor-patient pairs from all over the country to set up four-person “chains”, where donors can swop compatible organs. Britani’s universal blood type allowed her to find a match quickly – and, in turn, by September Neil was undergoing surgery.

Despite her initial designated recipient receiving a life-saving intervention, Allison remained inspired to donate a kidney, and after beginning a chain of her own, four others were saved – including a 14-year-old boy.

Now enjoying Neil’s renewed health, Lisa is hoping her story helps to comfort others desperately in search of a kidney.

Within 24 hours of Neil receiving a kidney, his health drastically improved.

“For 15 years, I had watched a downward trajectory in his [kidney] function. It seemed too good to be true that in just a matter of moments the numbers were climbing.”

“I’d seen him so grey and sullen for so many years, but now the colour had come rushing back to his face. It’s nearly impossible to express the gratitude we feel.”

Britani and Allison don’t see their actions as heroic, instead asking why they wouldn’t donate their kidneys as they each have two and only need one.

“I believe people can learn from Britani and Allison’s courage and selflessness by recognizing that any greatness worth achieving usually happens outside your comfort zone, Lisa said.

Living with PKD: Neil Simon, Walk for PKD: Portland, Dialysis Politics in California

Living with PKD

From Villages News, By Gabe Mirkin
Neil Simon’s kidney transplant contributed to later dementia

Neil Simon was America’s premier play and movie writer. His more than 30 plays and 30 movies won a Pulitzer Prize, three Oscars, three Tony awards, 17 Tony nominations and four Academy Award nominations. He once had four successful plays running at the same time on Broadway, and in 1983, he became the only living person to have a Broadway theater named after him.

On August 26, 2018, Simon died at age 91 of pneumonia, probably caused by food aspirated into his lungs, which often occurs with dementia (brain damage), associated with immune suppression from the drugs given to him so he would not reject the kidney transplant he received 14 years ago, to replace his kidneys that were destroyed by a genetic condition called polycystic kidney disease.

He Wrote About What He Lived

He became America’s greatest playwright by writing about his own experiences. He was born in the Bronx in 1927 and grew up during the Great Depression of the 1930s. His early upbringing and poverty had a marked effect on his own life, his many marriages and the characters he wrote about in his plays and movies. His father was a garment salesman and his mother worked in a department store. Their constant screaming and fighting and his father’s frequent absences from their home hurt Simon greatly. Money was so tight that he and his brother often had to live with relatives so his parents could earn money by taking in boarders. He was very shy in high school and spent much of his youth watching comedy acts in movie theaters. He said that he became a comedy writer in an effort to block out his painful childhood. At age 15, he received his first writing paycheck for doing funny sketches for a department store party. To obtain money for college, he enlisted in the Army Air Force Reserve at New York University. He was sent to Lowry Air Force Base in Colorado, where he wrote pieces primarily about sports.

After college he worked as a mailroom clerk for two years and then his brother invited him to join him in writing radio and television scripts. In his late twenties, he was hired to write for the television comedies Your Show of Shows and The Phil Silvers Show. He wrote scripts with Carl Reiner, Howie Morris, Mel Brooks and Woody Allen. In 1961, at age 34, his first Broadway play, Come Blow Your Horn with Frank Sinatra, ran for 678 performances. This was followed by two smash hits, Barefoot in the Park (1963) and The Odd Couple (1965), which made him the most sought after playwright on Broadway. In his late fifties, he wrote plays about himself growing up in working-class New York neighborhoods: Brighton Beach Memoirs, Biloxi Blues andBroadway Bound.

His Characters and His Marriages

He wrote mostly about himself and his neighbors and friends, so his characters were usually white middle-class Americans, mostly New Yorkers and Jewish, and his themes were strongly influenced by his painful childhood and his first marriage. He wrote comedies about fading love that often causes separation, divorce and child custody battles. In Lost in Yonkers, which won the Pulitzer Prize, he showed that marriages full of strife can deprive children of love that can damage them so much that they themselves end up with emotional disease and failed marriages. However, he often tried to save his characters by having them end up reconciling and staying together. He constantly preached monogamy as a means of stabilizing society and made infidelity a source of suffering.

He himself was married five times, twice to the same woman. At age 26 he married dancer Joan Baim, and they were together until she died of bone cancer 20 years later. That same year he married actress Marsha Mason, and stayed with her for 10 years. At age 60 he married actress Diane Lander, divorced her one year later, and at age 63 married her a second time for eight more years. At age 72 he married actress Elaine Joyce, who carried him through his kidney transplant at age 76 and his later years of suffering from dementia.

Polycystic Kidney Disease

Polycystic Kidney Disease is primarily a genetic disorder in which normal kidney tissue is replaced by sacs of fluid. It affects more than 600,000 Americans and causes about 10 percent of all end-stage kidney disease that requires dialysis and often requires kidney transplants. Symptoms can include back or belly pain, high blood pressure, headaches, and bloody and excessive urination. There is no FDA-approved treatment, but calorie restriction and avoidance of obesity may slow the disease’s progression (J Am Soc of Neph, Nov 4, 2015)

His Kidney Transplant

His wife, Elaine, said that he was already having kidney problems when she married him when he was 72, and that his disease progressed dramatically in the early years of their marriage. By age 75, his kidneys failed completely and he required dialysis. He suffered from exhaustion, severe muscle cramps, nausea, vomiting and worst of all, memory loss. He was now unable to write clearly. He was waiting for a donated kidney and matching donors are hard to find. One day he mentioned his need for a kidney to his friend and publicist, Bill Evans. In 1976, Simon had taken a chance when he hired Evans, who was just getting started as a publicist, and they continued working together up until 2006 on more than 20 plays. Simon recalled that he told Evans, “‘I just need to get a kidney somewhere.’ Evans replied, ‘Well, I’ll give you one.’ ‘You would?’ ‘Let me think about it,’ and he called the next day and said he would.”

Transplants and Dementia

Seventeen percent of people over 75 who receive kidney transplants develop dementia within 10 years, often because the immune-suppressing drugs that are used to prevent the body from rejecting the transplanted kidney can damage the brain (J Am Soc of Nephrology, December 15, 2016). Those who develop dementia have a 43 percent chance of rejecting their kidneys within 10 years and almost a 90 percent chance of dying within 10 years. The average survival time for people diagnosed with dementia is about four and a half years. After kidney transplantation, the most common causes of death are heart disease (36 percent), infection (24 percent) and brain death (12 percent), with smaller numbers from brain aneurism, brain hemorrhage or ischemic stroke (J Am Soc of Neph, June 1, 1995;5(12):2048-2056).

Everything You Do to Prevent Heart Attacks Also Helps to Prevent Dementia

About 35 percent of people over 85 suffer from dementia and being brilliant does not protect you from developing this condition. Other notable people who have suffered dementia include Aaron Copland, Abe Burrows, Alfred Van Vogt, Arlene Francis, Barry Goldwater, Burgess Meredith, Charles Bronson, Charlton Heston, Molly Picon, Norman Rockwell, Otto Preminger, Perry Como, Peter Falk, Rita Hayworth, Ronald Reagan, Sugar Ray Robinson and many others.

You can reduce your risk for suffering from dementia by 70 percent when you follow the same healthful habits that help to prevent heart attacks (JAMA, Aug 21, 2018;320(7):657-664). See my report on this study in Risk for Dementia Goes Down with Steps to Prevent Heart Attacks.

Dr. Gabe Mirkin is a Villager. Learn more at www.drmirkin.com

Dialysis Politics

From The Fiscal Times, By Yuval Rosenberg

California Assembly Passes Bill Cracking Down on Dialysis Reimbursement

The California State Assembly on Wednesday passed a landmark bill cracking down on the prices and payment practices of dialysis centers, delivering a win to insurers who backed the bill and potentially threatening the profits of large dialysis chains like DaVita and Fresenius.

The bill places limits on third-party groups like the American Kidney Fund, a not-for-profit organization that subsidizes premiums for dialysis patients with commercial insurance. The bill also caps some commercial dialysis payments at lower Medicare rates.

DaVita and Fresenius are large contributors to the American Kidney Fund, and insurers and labor groups including the Service Employees International Union of California have argued that the charity’s payments are used to game the system and direct patients to insurers that provide higher reimbursement rates — and more profit — for the dialysis companies.

The American Kidney Fund has said that the bill “would cause profound harm” to many dialysis patients. It called the legislation “nothing more than a thinly-veiled attempt by large health insurance companies to kick kidney patients off their insurance plans.”

The state assembly’s vote means the bill now will likely head to the desk of Gov. Jerry Brown, who has until the end of next month to act on it.

Why it matters: “This is a giant win for the SEIU, health insurers and employers and a huge blow to dialysis companies and the American Kidney Fund,” writes Axios’ Caitlin Owens, adding that “there will be a fierce lobbying blitz” by the dialysis companies to get Brown to kill the bill. If the legislation does get signed into law, Modern Healthcare’s Susannah Luthi writes, it could have a major impact on DaVita and Fresenius, which have about 70% of California's market share of just under 600 dialysis clinics and nearly 70,000 dialysis patients.”

Walk for PKD

From KATU, Channel 2, Portland, OR

Polysistic Kidney Disease Foundation Walk

Imagine having a disease that can cause your kidney to grow to the size of a football and that ultimately requires a kidney transplant. That's the reality for people with Polycystic kidney disease (PKD). PKD is a chronic, genetic disease causing uncontrolled growth of cysts in the kidney, often leading to kidney failure. It affects all racial and ethnic groups equally. The Herman Family--Rob, Linda, Kaley & Journey--joined us to share how their family is handling life with PKD.

The PKD Foundation has been leading the fight against PKD for more than 35 years through research, education, advocacy, support and awareness. 5h3y are the only organization in the U.S. dedicated solely to finding treatments and a cure for PKD. To help raise funds, they're holding walks across the country:

PKD Walk
Saturday, September 8, 2018
Registration: 8:30 a.m. | Penny Kids Dash: 9:15 a.m. | Walk start: 9:30 a.m.

Howard M. Terpenning Recreation Complex
15707 SW Walker Road, Beaverton

For more information, visit the website.