From Renal and Urology News, Jody A. Charnow, Editor
Tolvaptan Offers Sustained Slowing of Renal Function Decline in ADPKD
Tolvaptan treatment has a sustained disease-modifying effect on estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD), but the effects of five compared to two years of treatment on total kidney volume (TKV) were not significantly different, according to a new study.
The open-label extension trial, TEMPO (Tolvaptan Efficacy and safety in Management of Polycystic kidney disease and its Outcomes) 4:4, provided an additional 2 years of data on the long-term safety and efficacy of tolvaptan on TKV and eGFR among patients completing the pivotal TEMPO 3:4 trial. In TEMPO 3:4, tolvaptan, a vasopressin V2 receptor antagonist, slowed TKV growth by 49.2% and eGFR decline by 26% compared with placebo.
Of 1445 patients randomized to TEMPO 3:4, 871 (60.3%) enrolled in TEMPO 4:4. The group included 557 patients who received prior tolvaptan (early-treated group) and 314 who received prior placebo (delayed-treated group) in TEMPO 3:4.
From TEMPO 3:4 baseline to TEMPO 4:4 Month 24, TKV increased by 29.9% in early-treated patients and 31.6% in delayed-treated patients, a between-group difference that was not statistically significant, Vicente E. Torres, MD, of Mayo Clinic in Rochester, Minnesota, and colleagues reported in a paper published online ahead of print in Nephrology Dialysis Transplantation. TKV increases in both early- and delayed-treated patients were less than the increase estimated to have occurred without treatment (approximately 40%). The inability to demonstrate that the early treatment advantage on TKV achieved during TEMPO 3:4 was maintained at the end of TEMPO 4:4 may be accounted for by randomization imbalances that developed in the transition from TEMPO 3:4 to TEMPO 4:4 and by the fact that the tolvaptan effect on TKV is greatest during the first year of treatment, according to the investigators. Adjusting for baseline covariates improved the TKV treatment difference at month 24 in TEMPO 4:4 from 1.70% to 4.15% between the groups, a statistically significant difference.
Slopes of TKV growth during TEMPO 4:4 were higher in early- versus delayed-treatment groups (6.16% vs 4.96% per year).
Data showed that the effect of tolvaptan on slowing renal function decline in TEMPO 3:4 was maintained for an additional 2 years in TEMPO 4:4. The eGFR slopes in TEMPO 4:4 were similar in early and delayed-treated patients (−3.26 and −3.14 mL/min/1.73 m2 per year, respectively) compared with placebo.
The tolvaptan safety profile in TEMPO 4:4 was similar to that in TEMPO 3:4, Dr Torres' team reported.
PKD Research
From Yale News, Yale University, By Ziba Kashef
Yale researchers are studying kidney and liver diseases to determine which genes are involved in the formation of cysts.
In order to diagnose and find treatments for a genetic disorder, scientists need to identify which gene mutations cause the disease. A common and often devastating genetic disease known as polycystic kidney disease (PKD) results in cysts in both the kidney and liver. Cysts are pockets of fluid in an organ that develop over time and crowd out the normal functioning parts. The more common form of PKD that affects adults and approximately half of their children, typically leads to kidney failure by the sixth decade of life. It is caused by mutations in the genes PKD1 or PKD2. The more rare juvenile form is caused by mutations inherited from both parents in a gene called PKHD1.
Researchers in the lab of Yale nephrologist Dr. Stefan Somlo have found that some patients have only liver cysts, not kidney cysts, and thus don’t get kidney failure. This disease, known as isolated polycystic liver disease (PCLD), is typically benign but can lead to symptoms in rare cases where the liver becomes very large. Nonetheless cysts form due to a dysregulation of the same disease process as those in the kidney, the details of which are an important area of investigation. To deepen understanding of why liver and kidney cysts form, a Yale-led research team examined the genes of patients with liver cysts.
Through sequencing of patient genomes and computer analyses, the researchers identified four additional genes associated with PLCD. This discovery demonstrated that many different genes are involved in the process of cyst formation. Interestingly, one of the identified genes was PKHD1, suggesting that a subset of carriers of PKHD1 mutations (parents of children with the juvenile form of PKD) can present with PCLD.
This finding supports a common mechanism of disease between both the adult and juvenile PKD and PCLD. Researchers, such as first author Whitney Besse, a clinical fellow in medicine, hope that through improving understanding of the genes involved in cyst formation, an effective treatment can be developed. It could be hypothesized now that blocking a single pathway could cure all of these diseases, said Besse. She and her colleagues plan to further study the underlying mechanisms of these diseases and how they might interact.
Read the fully study, published in the Journal of Clinical Investigation.
Living with PKD
Terrence Marks, 55, of West Gardiner, talks about his kidney disease and retirement case during an interview on Thursday in his West Gardiner home. Staff photo by Joe Phelan
AUGUSTA — Terrence “Terry” Marks has kidneys that are twice the normal size and are doing less than a quarter of the work they should be doing to filter toxins from his system.
Symptoms of his polycystic kidney disease — now at stage 4 — forced the West Gardiner man from his job in November 2015 as part of a state highway maintenance crew that plowed roads in winter and did other jobs in the summer.
Marks, 55, has seen his disability retirement application rejected by the Maine Public Employees Retirement System, has been declared ineligible to collect a military retirement because his wife earns $29,000 as a clerk for the Town of West Gardiner, and is ineligible for Social Security disability benefits.
He went to the State House Friday morning to speak in favor L.D. 176, a bill that he hopes will change the laws regarding state disability retirement benefits.
However, the Legislature’s Appropriations and Financial Affairs Committee only briefly considered the bill before agreeing to carry it over to the next session. Marks was out of the hearing room when the public was invited to comment, and he missed the opportunity. In fact, no one spoke about the bill, which is a concept only and lacks specific language.
But he and his wife, Tina Marks, still plan to support a law change so others don’t run into similar problems.
“There’s no help in the state system,” Terry Marks said on Thursday as he considered what he wanted to tell the committee. “My money is sitting in the state retirement system. My money’s there. I’m getting nothing. My future retirement money’s sitting there.”
Marks was terminated in November 2015 because he was no longer physically able to perform his job after 19 years and 11 months working for the state.
For a year, the family was OK financially because he had purchased income protection insurance, but that support ended in November 2016. Now things are much tighter.
While he has medical insurance through his wife’s job, he said, “There’s lots of bills coming in that aren’t covered by insurance. I have an old junked-out pickup truck. There’s the phone, lights, heating. Once there’s no paycheck, we’re scrimping, downsizing, everything you can imagine we’re trying to streamline.”
They feel powerless.
“This isn’t my master plan,” Marks said. “We were going to retire and venture out and do the day trips. We were going to enjoy our retirement. Our plan was not to be sick. We were going to buy a camper and go camping on weekends and travel around the state of Maine. My retirement has been altered. My plan wasn’t to get sick and end up suffering in end-stage kidney failure.”
He got news of his latest denial from the Maine Public Employees Retirement System on Wednesday.
According to Michael Colleran, general counsel for MainePERS, Marks’ case now will be considered by the system’s board of trustees. If the board upholds the hearing officer’s denial, then Marks’ only appeal would be to a superior court judge.
Data from MainePERS indicates that 82 of the 121 disability applications handled in 2016 were denied initially. It also shows that of the 73 appeals completed that year, 23 were granted.
State Sen. Shenna Bellows, D-Manchester, who is not on the committee but who attempted to aid the Marks, said afterward, “It strains credibility to me that 62 percent of the applicants for disability can be denied.”
She said she worries about how the families can survive.
“I would like to see something done that will try to make the system work for the people it’s designed to serve,” she said.
Just prior to the committee’s consideration of L.D. 176, introduced by state Rep. Robert A. Foley, R-Wells, the MainePERS system and the MainePERS Disability Retirement Task Force made presentations to the committee that appeared to address some of the concerns that Marks and others face.
Sandy Matheson, executive director of MainePERS, noted that 1,300 of 38,500 retirement member are on disability; the others are on service retirement. Another 51,000 are active members, paying into the plan.
She noted that members of MainePERS “experience varying levels of difficulty and frustration when applying for disability retirement.”
Specifically, Matheson said, the statute limits the MainePERS benefit to permanent disability.
“We know there’s a misperception of what our program is that really causes a lot of hardship and heartache for people,” Matheson told the committee.
She said that the task force looked into the costs for long-term disability insurance, which would fill in when the short-term income protection ends.
“We’re hoping to make it an opt-out, so people are aware there could be a gap in income and don’t think of our plans as disability insurance,” she said.
State Rep. Brian Hubbell, D-Bar Harbor, who serves on the committee, said, “I’m convinced we need to do that. We have to have some system to tell employees what our disability retirement program is and isn’t.”
Matheson said later that MainePERS is trying to refine its internal process to educate members and employers that the retirement system is not for long-term disability.
“You retire because you’re permanently disabled,” she said.
She told the committee that problems arise when members essentially apply too soon, when they find work difficult but are not yet permanently disabled.
Matheson also indicated that Foley’s bill is a placeholder should the agency need changes in the law.
State Sen. Roger Katz, R-Augusta, also presented a bill to give state disability retirement benefits to someone who becomes disabled after leaving state service, who is ineligible for social security disability and who prevails in or settles a claim under the state’s Whistleblowers’ Protection Act.
The first person to testify in favor of the bill was Sharon Leahy-Lind of Portland, who meets all those requirements.
In 2013, Leahy-Lind, who was director of the CDC’s Division of Local Public Health, disclosed that she was ordered by her superiors to shred documents related to competitive grant awards in the Healthy Maine Partnerships program. The documents shed light on irregularities and possible illegal activity in the way certain grants were awarded.
She later filed a whistle-blower complaint in federal court alleging retaliation for refusing to shred the documents. The lawsuit was settled.
Leahy-Lind said bonafide whistleblowers should not be denied benefits. She told the committee she had been diagnosed with pancreatic cancer after leaving state service and that the bill could potentially benefit her and protect future whistle-blowers.
“I’m not here today to seek your sympathy,” she told them. “What I’m afraid of is to live with no income, continue to liquidate my assets and leave my daughters with debt.”
Friends and former coworkers of Leahy-Lind spoke in support of the bill as well.
Betty Adams — 621-5631
No comments:
Post a Comment