In the FLOW trial, semaglutide-treated patients had a significantly lower risk for the primary outcome (a composite of major kidney events* and death from kidney-related or cardiovascular causes) as well as a composite of just the kidney-specific components of the primary outcome and death from cardiovascular causes.
Risk Reduction With Semaglutide vs Placebo
BY JODY A. CHARNOW
Semaglutide reduces the likelihood of adverse kidney outcomes in patients at elevated risk for deterioration of renal function, according to findings from the phase 3 FLOW and SELECT trials presented at the 61st European Renal Association Congress in Stockholm, Sweden.
The FLOW trial demonstrated semaglutide’s beneficial effects on the kidneys in patients with type 2 diabetes and chronic kidney disease (CKD). Patients who received semaglutide, a glucagonlike peptide-1 receptor agonist (GLP1RA), experienced a significant 24% decreased risk for a composite of clinically important kidney disease events and death from kidney-related and
Iptacopan
Beneficial in C3G
Results from the phase 3 APPEAR-C3G trial show that iptacopan can significantly lower proteinuria in patients with complement 3 glomerulopathy (C3G), an extremely rare disease for which there are no approved therapies, according to an oral presentation at the 61st European Renal Association Congress in Stockholm, Sweden. The disease is caused by dysregulation of the alternative pathway of the complement system that leads to deposition of complement 3 (C3) protein in glomeruli, resulting in kidney inflammation and glomerular injury. Iptacopan is an oral proximal complement inhibitor that specifically binds to factor B and inhibits the alternative pathway.
The trial included 74 patients randomly assigned to receive iptacopan 200 mg twice daily (38 patients) or placebo (36 patients) in addition to standard of care. The primary outcome was a reduction in proteinuria as measured by 24-hour urinary protein-to-creatinine ratio (UPCR) at 6 months. The study also examined the effect of iptacopan on estimated glomerular filtration rate (eGFR) and a composite renal endpoint of a 50% or greater reduction in UPCR and a decrease in eGFR of no more than 15%.
Compared with baseline, the iptacopan group had a 30.2% reduction in 24-hour UPCR at month 6,
CKD Highly Prevalent in Gout Patients
Chronic kidney disease (CKD) is highly prevalent among patients with gout, especially those with the highest serum urate levels, according to data presented at the National Kidney Foundation’s 2024 Spring Clinical Meetings in Long Beach, California.
In a study of 18,253 patients with gout in a UK database, patients in the top quartile of serum urate levels had a 59.4% prevalence of CKD stages 3-5, Michael Garshick, MD, of NYU School of Medicine/NYU Langone Health in New York, New York, and colleagues reported in a poster presentation. By comparison, the prevalence was 47.9%, 43.9%, and 48.5% among patients in the first, second, and third quartiles, respectively. The investigators divided patients into quartiles based on mean serum urate values after the first gout diagnosis. For patients in the first, second, third, and fourth quartiles, the mean values were 5.53, 6.70, 7.47, and 8.74 mg/dL, respectively. continued
cardiovascular causes. The SELECT trial showed that semaglutide decreased the risk for major kidney events by a significant 22% in overweight or obese patients with preexisting cardiovascular disease (CVD) and no diabetes.
‘Fourth Pillar’ of Treatment
Treatments for CKD in patients with diabetes already include renin-angiotensin-system inhibitors, sodiumglucose co-transporter-2 (SGLT2) inhibitors, and the nonsteroidal mineralocorticoid antagonist finerenone, “and now we would posit that semaglutide can be the fourth pillar” of treatment, FLOW investigator Katherine R. Tuttle, MD, of the University of
continued on page 5
4 Iptacopan shown to decrease IgAN proteinuria
4 Low dietary manganese intake may raise CKD risk
NDAs for cancer drugs often lack PRO data
Stone surgery fails to lower UTI relapse risk
Hypertension is not more likely in living kidney donors
Editorial Advisory Board
MEDICAL DIRECTOR, UROLOGY
Robert G. Uzzo, MD, MBA, FACS
G. Willing “Wing” Pepper Chair in Cancer Research
Professor and Chairman Department of Surgery Fox Chase Cancer Center Temple University School of Medicine Philadelphia
UROLOGISTS
Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City
R. John Honey, MD
Head, Division of Urology, Endourology/Kidney Stone Diseases
St. Michael’s Hospital University of Toronto
Stanton Honig, MD Department of Urology
Yale University School of Medicine New Haven, CT
J. Stephen Jones, MD
Chief Executive Officer Inova Health System Falls Church, VA
Professor and Horvitz/Miller Distinguished Chair in Urologic Oncology (ret.)
Cleveland Clinic Lerner College of Medicine Cleveland
Jaime Landman, MD
Professor of Urology and Radiology Chairman, Department of Urology UC Irvine School of Medicine Orange, CA
James M. McKiernan, MD
John K. Lattimer Professor of Urology Chair, Department of Urology Director, Urologic Oncology Columbia University College of Physicians and Surgeons New York
Kenneth Pace, MD, MSc Assistant Professor, Division of Urology St. Michael’s Hospital University of Toronto Vancouver, Canada
NEPHROLOGISTS
Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, NC
David S. Goldfarb, MD Professor, Department of Medicine Clinical Chief New York University Langone Medical Center Chief of Nephrology NY Harbor VA Medical Center
Kamyar Kalantar-Zadeh, MD, MPH, PhD
Professor of Medicine, Pediatrics, and Public Health, and Chief of Nephrology, at the University of California-Irvine School of Medicine Orange, CA
Adjunct Professor of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA
Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center
Fred Hatch Professor of Medicine University of Tennessee Health Science Center Memphis, TN
Edgar V. Lerma, MD
Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine
University of Illinois at Chicago College of Medicine Chicago, IL
Allen Nissenson, MD
Emeritus Professor of Medicine
The David Geffen School of Medicine at UCLA Chief Medical Officer, DaVita Inc. Denver, CO
Rulan Parekh, MD, MS
Associate Professor of Pediatrics and Medicine University of Toronto
Robert Provenzano, MD
Associate Professor of Medicine
Wayne State University School of Medicine Detroit, MI
Vice President of Medical Affairs, DaVita Healthcare Denver, CO
Renal + Urology News Staff
Editor Jody A. Charnow
Digital content editor Natasha Persaud
Production editor Kim Daigneau
Group creative director Jennifer Dvoretz
Senior production manager Krassi Varbanov
Vice president, sales operations and production Louise Morrin Boyle
National accounts manager William Canning
Vice president, content, medical communications Lauren Burke
Chief commercial officer James Burke, RPh
President, medical communications Michael Graziani
Chairman & CEO, Haymarket Media Inc. Lee Maniscalco
Diet Remains a Pillar of CKD Management
Much has happened in recent years in terms of pharmacotherapies that slow progression of chronic kidney disease (CKD) in patients with and without diabetes. Most recently, semaglutide, a glucagon-like peptide-1 receptor agonist, demonstrated renoprotective effects in 2 clinical trials (see article on cover). In one trial, the therapy was significantly associated with a 22% decreased risk for major kidney events in overweight or obese patients with preexisting cardiovascular and no diabetes. The drug would be among the latest additions to an armamentarium for preventing kidney disease or its progression that already includes sodium-glucose cotransporter 2 (SGLT2) inhibitors, the nonsteroidal mineralocorticoid antagonist finerenone, and renin-angiotensin-system inhibitors. A growing number of pharmacologic options to slow CKD progression is good, but should not lead clinicians to relegate nutritional interventions to a position of lesser relevance.
Diet has a profound influence on kidney function in ways that may not be readily apparent. For example, in this issue’s Renal Nutrition Update column, renal dietitian Lindsey Zirker, MS, RD, emphasizes the importance of maintaining a healthy gut microbiome. An imbalance of beneficial and helpful bacteria in the intestines can lead to greater production of uremic toxins and, consequently, faster CKD progression, she writes. Plant-based, low-protein, high-fiber, and anti-inflammatory diets can correct this imbalance.
New study data underscoring how nutrition impacts outcomes in patients with kidney disease are presented regularly at conferences. At this year’s American Transplant Congress in Philadelphia, a transplant registered dietitian reported on a study demonstrating that malnutrition, especially muscle depletion, in patients prior to kidney transplantation increases the risk for early hospital readmission and delayed graft function after transplantation (see article on page 3). In another study presented at the congress, an investigator reported findings linking vitamin D deficiency to an increased risk for kidney graft failure. At the European Renal Association congress this year in Stockholm, Sweden, researchers presented data showing that pre-dialysis nutrition counseling and intervention significantly delayed dialysis initiation and decreased death risk among patients with advanced CKD.
The new pharmacotherapies that can slow CKD progression are a big step forward and have justifiably generated excitement in the nephrology community. Still, all clinicians involved in kidney care should not let the debut of better medicines diminish the importance of diet as a pillar of CKD management.
JODY A. CHARNOW Editor jody.charnow@haymarketmedia.com
Editor’s Picks
1 From the Editor
New drugs that slow CKD progression do not make dietary interventions less relevant.
3 News in Brief
Investigators have linked a rise in testicular cancer to in utero exposure.
4 Iptacopan Reduces IgAN Proteinuria
A potential therapy for immunoglobulin A nephropathy is the first to specifically target the alternative complement pathway.
4 Low Manganese Intake Increases CKD Risk
Each 20 µg/kg/d decrease in dietary manganese was significantly associated with a 13% increased risk for CKD in a fully adjusted model.
6 Patients’ Voices Absent from Many FDA Reviews of Cancer Drugs
A substantial proportion of New Drug Applications do not include patient-reported outcome data.
8 URS With Biopsy Improves High-Risk UTUC Outcomes
11 KT Candidate Death Rate High After Delisting
Half of the patients delisted from the kidney transplant waiting list from January 1, 2010 to September 2, 2020 died within 4 years, according to researchers.
12 New Data Support PCa Focal Cryoablation
The procedure is associated with good long-term oncologic control in well-selected men with localized tumors.
13 Abnormal Potassium Levels Before Radical Cystectomy Predict Worse Outcomes
Incorporating plasma potassium levels into preoperative assessments may allow for more tailored treatment planning.
14 Renal Nutrition Update
CLINICAL QUIZ
The federal Office for Civil Rights announced a HIPAA Final Rule for reproductive health care privacy. SUMMER
Investigators reported significantly longer 5-year overall and cancer-specific survival, but not metastasis-free survival.
A diet that promotes the growth of beneficial bacteria while suppressing harmful bacteria in the gut microbiome could help slow progression of chronic kidney disease.
15 Ethical Issues in Medicine
Shared decision-making balances patient autonomy and doctor beneficence.
16 Practice Management
Hyperkalemia in an Otherwise Healthy 28-Year-Old Woman
She had no significant medical history yet had persistent hyperkalemia on routine testing.
FEATURE: CHRONIC KIDNEY DISEASE
Plant-Based Diets Emphasized in 2024
KDIGO Guidelines for CKD
Latest recommendations include reduced intake of ultra-processed foods.
FEATURE: BLADDER CANCER
PROs Support First-Line Use of Enfortumab Vedotin+Pembrolizumab for Advanced UC Investigators report preserved or improved quality of life, especially with respect to pain.
Philadelphia, June 1-5, 2024
• Kidney Graft Loss Risk Not Increased If Only the Donor Has Diabetes
• Kidney Transplant Odds Increase for Older Patients After Bariatric Surgery
News in Brief
Stay
SHORT TAKES
First Living Recipient of a Pig Kidney Dies
The world’s first living recipient of a genetically modified pig kidney has died, according to the Massachusetts General Hospital in Boston, where the successful history-making transplant took place on March 16. He was discharged from the hospital on April 3.
The cause of death of Richard Slayman, 62, of Weymouth, Massachusetts, is not believed to be the result of the transplant, the hospital said in a press release.
“Mr. Slayman will forever be seen as a beacon of hope to countless transplant patients worldwide and we are deeply grateful for his trust and willingness to advance the field of xenotransplantation,” the hospital said.
PSMs After PN Increases RCC Recurrence Risk
Positive surgical margins (PSMs) following partial nephrectomy (PN), but not radical nephrectomy (RN), for renal cell carcinoma independently predict an increased risk for disease recurrence, Cesare Saitta, MD, of UC San Diego Health System in California, and colleagues reported in a poster presentation at the European Association of Urology’s 2024 congress in Paris.
The multi-institutional retrospective study included 5827 patients who underwent either PN or radical nephrectomy (RN) and had a median follow-up of 45 months. Of these, 251 (4.3%) had PSMs. On multivariable analysis, PSMs after PN were significantly associated with a 75% increased risk for recurrence, the study’s primary outcome.
AAV Ups Death Risk After Kidney Transplantation
Patients with ANCA-associated vasculitis (AAV) and end-stage kidney disease (ESKD) are at higher risk for death following kidney transplantation compared with patients who do not have AAV, according to a recent systematic review and metaanalysis. They also are more likely to experience post-transplant infection.
Jia Wu, MD, of Huzhou Traditional Chinese Medicine Hospital in Huzhou, China, and colleagues analyzed data from 23 retrospective studies that included 2503 patients with AAV. Of these, 18 were eligible for the meta-analysis. Patients with AAV had a significant 12-fold higher mortality rate and 53-fold higher rate of infections after transplantation compared with those without AAV, the investigators reported in Annals of Transplantation
CKD Prevalence Increasing in US
The prevalence of chronic kidney disease (CKD) in the United States increased by 28% from 1990 to 2019, investigators reported at the National Kidney Foundation’s 2024 Spring Clinical Meetings in Long Beach, California. Shown below are the places with the highest and lowest increases in prevalence.
Rise in Testicular Cancer Tied
to In Utero Exposure
Investigators in Finland have implicated in utero exposure as an underlying cause of an increased incidence of testicular cancer (TC) in that country, according to a presentation at the American Urological Association 2024 annual meeting in San Antonio, Texas.
Antti J. Kaipia, MD, of Tampere University Hospital in Finland, and colleagues followed up for development of TC among 1,342,996 men born in Finland from 1960-1999. The investigators identified 2542 cases of TC. The cumulative incidence increased in all municipalities, ranging from 85 to 201 per 100,000 men born in 1960-1969 to 209 to 314 per 100,000 men born in 1970-1979.
“Current evidence indicates that TC develops from germ cell neoplasia in situ that arises from embryogenesis,” the authors wrote in a study abstract. “Maternal environmental exposures are thus likely to play a role in the TC pathogenesis.”
They pointed out that environmental factors, especially exposure to estrogenmimicking and antiandrogenic compounds, have been postulated as risk factors.
ESKD Tied to Bicarbonate Use in Patients With CKD
Oral bicarbonate use by patients with incident chronic kidney disease (CKD) may increase the risk for end-stage kidney disease (ESKD), according to study findings presented at the National Kidney Foundation 2024 Spring Clinical Meetings in Long Beach, California.
The study included 50,540 US veterans with incident CKD (estimated glomerular filtration rate less than 60 mL/min/1.73 m2) who had up to 14 years of follow-up. Of these, 11,896 were incident bicarbonate users with a mean age of 65 years (97% male).
Bicarbonate use was significantly associated with a 1.5-fold increased risk of incident ESKD (initiation of kidney replacement therapy) compared with nonuse in a fully adjusted model, Diana Tran, MPH, of Tibor Rubin VA Medical Center in Long Beach and the Lundquist Institute in Torrance, California, and colleagues reported in a poster presentation. The incidence rate was 37.4 per 1000 patient-years.
Bicarbonate users were more likely to be Black and to have lower eGFR values, and greater use of renin-angiotensin-system inhibitors compared with nonusers.
PHILADELPHIA—Malnutrition, especially muscle depletion, prior to kidney transplantation is associated with adverse clinical outcomes following transplantation, including delayed graft function (DGF), an investigator reported at the 2024 American Transplant Congress.
“Inclusion of dietitians in the both the evaluation and selection of transplant recipients is important, with the goal of optimizing patients for kidney transplant,” said Jessa Engelken, MPH, RDN, a transplant registered dietitian nutritionist. She presented findings from a single-center study that included 367 kidney transplant recipients. Of these, 36 (10%) were malnourished—23 moderately and 13 severely—at pre-transplant evaluation. Muscle depletion was the most common criterion for malnutrition, present in all 36 recipients.
In adjusted models, pre-transplant malnutrition was significantly associated with approximately 2.9-fold increased odds for early readmission and 8.3-fold increased odds of DGF, Engelken reported. Muscle depletion by itself was significantly associated with 8.3-fold increased odds of DGF. She concluded that “malnutrition may be an important consideration for selection of recipients.”
Iptacopan Reduces IgAN Proteinuria
Potential therapy for the condition is the first to specifically target the alternative complement pathway
BY NATASHA PERSAUD
Treatment with the investigational drug iptacopan significantly reduces proteinuria in patients with IgA nephropathy (IgAN), according to the findings of a phase 3 trial presented at the National Kidney Foundation’s 2024 Spring Clinical Meetings in Long Beach, California.
Iptacopan is a factor B inhibitor of the alternative complement pathway that prevents the activity of C3 convertase. The APPLAUSE-IgAN trial is a phase 3 study that randomized participants to receive iptacopan 200 mg twice daily vs. placebo on top of optimized standard of care. Recruited patients had biopsy-confirmed IgAN, eGFR of 30 mL/min/1.73 m2 or higher, and proteinuria of 1 g/g or greater at baseline despite maximally tolerated stable renin-angiotensinsystem inhibition for at least 3 months. A prespecified interim analysis of the phase 3 APPLAUSE-IgAN study
showed that iptacopan plus supportive care significantly reduced proteinuria over 9 months by 38.3% compared with placebo, Dana Rizk, MD, professor of medicine at the University of Alabama at Birmingham, and colleagues reported. The analysis included 250 patients who had reached 9 months of follow-up.
In a phase 3 trial, the drug showed a 38.3% reduction in proteinuria over 9 months vs placebo.
Decreases in 24-hour urine protein-to-creatinine ratio (UPCR) were observed as early as week 2 and continued to decrease until month 9.
In a press release from Novartis, which is developing the drug, Dr Rizk noted that iptacopan “is the first
potential treatment for IgAN that specifically targets the alternative complement pathway.”
Nearly twice as many patients in the iptacopan than placebo group attained a reduction in 24-hour UPCR to a target of less than 1 g/g within 9 months: 42.5% vs 21.9%, Dr Rizk’s team reported. This is a key endpoint as up to 30% of patients with IgAN who have persistent proteinuria progress to kidney failure within 10 years.
Iptacopan was well tolerated. Treatment discontinuation due to adverse events occurred in 2.7% of patients in each arm and the infection rate was comparable, the investigators reported.
Iptacopan has received priority review from the FDA, according to Novartis. The trial is ongoing with results from the secondary efficacy endpoint — a reduction of the annualized total estimated glomerular filtration
Low Manganese Intake Increases CKD Risk
Decreasing consumption of dietary manganese, a trace element vital for various physiologic processes, is associated with an increasing risk for chronic kidney disease (CKD) in adults with normal kidney function, investigators concluded in a presentation at the 61st European Renal Association Congress in Stockholm, Sweden.
The finding is from a study of 135,577 participants enrolled in the UK Biobank who filled out 24-hour dietary recall questionnaires. Investigators used the information to calculate dietary manganese
intake and classify that intake by quartiles. They excluded patients with CKD.
The primary outcome was incident CKD diagnosis using ICD-10 and OPCS-4 codes.
During a median follow-up of 11.2 years, incident CKD developed in 4900 individuals (3.6%), Jung Tak Park, MD, and colleagues on Yonsei University College of Medicine in Seoul, Korea, reported.
The incidence of CKD decreased with increasing quartiles, from 4.2 per 1000 person-years among individuals in first quartile compared with 3.6, 3.0, and 2.3
per 1000 person-years among those in the second, third, and fourth quartiles, respectively, Dr Park’s team reported in a poster.
Compared with individuals in the fourth quartile (reference), those in the third, second, and first quartiles had a significant 12%, 22%, and 39% increased risk for CKD, respectively, in a fully adjusted model.
Each 20 µg/kg/d decrease in manganese intake was significantly associated with a 13% increased risk for CKD in a fully adjusted model. ■
High Albuminuria Ups Likelihood of Dementia
Elevated albuminuria levels are independently associated with a higher risk for all-cause, Alzheimer’s, and vascular dementia, investigators reported at the 61st ERA Congress in Stockholm, Sweden.
The finding is from a study of participants in the Stockholm Creatinine Measurement (SCREAM) project aged 65 years or older without a history of dementia. The main analyses included 138,688 individuals with at least a single urine albumin-creatinine ratio (ACR)
test. For sensitivity analyses, the investigators included 170,572 individuals who had at least 1 dipstick proteinuria test. During a median follow-up of 3.9 years, dementia developed in 9970 participants. After adjusting for multiple variables, including baseline estimated glomerular filtration rate, individuals with an ACR of 30-299 mg/g or 300 mg/g or higher had a significant 26% and 36% higher risk for all-cause dementia, respectively, compared with individuals who had an ACR less than 30 mg/g,
Li Luo, MD, of University Medical Center Groningen in the Netherlands, reported on behalf of her colleagues. Further, individuals with an ACR of 30-299 mg/g had a significant 9%, 35%, and 54% increased risk for Alzheimer’s, vascular, and unspecified dementia, respectively.
Dr Luo’s team observed no significant associations between albuminuria and the incidence of Lewy body dementia and Parkinson’s disease with dementia, frontotemporal demential, and other types of dementia. ■
rate (eGFR) slope over 24 months — expected in 2025.
Iptacopan was approved by the Food and Drug Administration in December 2023 for the treatment of adults with paroxysmal nocturnal hemoglobinuria, a rare blood disorder. The drug is under development for other rare kidney diseases, including complement 3 glomerulopathy (C3G), atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis, and lupus nephritis.
At the European Renal Association’s 2024 Congress, David Kavanagh, MB, ChB, PhD, of the Royal Victoria Infirmary in Newcastle, UK, reported findings from the phase 3 APPEAR-C3G trial showing that iptacopan treatment in addition to supportive care for C3G — a disease for which there are no approved therapies — achieved a clinically meaningful and statistically significant 35.1% reduction in proteinuria. ■
FDA Clears Novel Device to Treat SUI
The FDA has cleared Yōni.Fit® Bladder Support for the temporary management of urine leakage caused by stress urinary incontinence (SUI) in women 18 years of age and older.
Yōni.Fit is a self-administered, intravaginal insert that manages urinary incontinence without interfering with voluntary urination. The prescription device can be used during a specific activity or for up to 12 hours to control symptoms.
The FDA clearance was based on a study of 58 patients randomly assigned to use Yōni.Fit® or a comparator device. Compared with users of the comparator device, a significantly higher proportion of patients who used the Yōni.Fit device had a clinically meaningful reduction in 12-hour pad weights (53% vs 23.3%) and a greater than 50% reduction in SUI episodes from baseline (96.3% vs 27.2%). In addition, more patients using the Yōni.Fit reported their status as “much improved” or better vs those in the comparator group ■
Semaglutide
continued from page 1
Washington School of Medicine in Seattle, said in an oral presentation discussing the clinical implications of the trial, which was stopped early because of “clear positive efficacy.”
Helen M. Colhoun, MD, of the University of Edinburgh, UK, lead investigator for the SELECT trial, presented her study’s findings and discussed their relevance. “These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population [of overweight or obese individuals] in the absence of diabetes, and this is a population with a clearly increased need for renoprotection,” Dr Colhoun told attendees. SELECT results add to the growing body of evidence of the potential kidney benefit of semaglutide, including the findings from the FLOW trial, said.
The FLOW and SELECT results were published in the New England Journal of Medicine and Nature Medicine, respectively, on the same day they were presented at the congress.
The FLOW trial included 3533 patients with both type 2 diabetes and CKD randomly assigned to receive semaglutide (1767 patients) or placebo (1766 patients). The median follow-up duration was 3.4 years. The primary
Iptacopan in C3G
continued from page 1
whereas the placebo group had a 7.6% increase, a significant difference between study arms, investigator David Kavanagh, MB, ChB, PhD, Professor of Complement Therapeutics at Newcastle University in Newcastle upon Tyne, UK, reported.
“This study was to evaluate efficacy, safety, and tolerability compared to placebo over and above standard of care,” Dr Kavanagh told attendees. “It demonstrated a significant and clinically meaningful reduction [of
CKD in gout patients continued from page 1
outcome was a composite of major kidney disease events that included onset of kidney failure (initiation of dialysis or kidney transplantation), persistent estimated glomerular filtration rate (eGFR, in mL/min/1.73 m2) less than 15, at least a 50% reduction in eGFR from baseline, or death from kidney-related or cardiovascular causes.
If the trial confirmed superiority of semaglutide for the primary outcome, investigators evaluated confirmatory secondary outcomes in a prespecified
In the FLOW trial, semaglutide also lowered the risk for MACE and death from any cause.
hierarchical order: total eGFR slope, major adverse cardiovascular events (MACE), and all-cause mortality. MACE included nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes.
In addition to the significant 24% reduction in the risk for the primary outcome, semaglutide recipients had a significant 21% decreased risk for a composite of the kidney-specific components of the primary outcome and 29% decreased risk for death from cardiovascular causes, according to the investigators.
proteinuria] on top of that standard of care at 6 months.”
A significantly higher proportion of patients in the iptacopan arm compared with the placebo arm achieved the composite renal endpoint (29.7% vs 5.6%), with the difference driven primarily by proteinuria reduction, according to Dr Kavanagh. Iptacopan treatment was significantly associated with 7.1-fold increased odds of achieving the composite renal endpoint. The treatment substantially decreased the proportion of patients with nephroticrange proteinuria and led to a numerical, but not statistically significant,
Secondary Outcomes
The findings for all confirmatory secondary outcomes also favored semaglutide. Recipients of the drug had a mean annual eGFR slope that was significantly less steep compared with the placebo group (-2.19 vs -3.36). The semaglutide group also had a significant 18% lower risk for MACE and 20% lower risk for all-cause mortality compared with the placebo arm.
“FLOW has established clearly that semaglutide prevents major kidney outcomes, MACE, and all-cause mortality in people with type 2 diabetes and chronic kidney disease,” Dr Tuttle told attendees.
Lack of CKD Awareness
She added, however, that “we have a problem with going expeditiously from evidence generation to implementation, and it starts with the very low awareness of chronic kidney disease.” She cited statistics showing that 80% to 93% of individuals with CKD are unaware they have it. Dr Tuttle also pointed out that guideline-directed medical therapy for patients with diabetes and CKD is suboptimal. She presented findings from a study of 2019-2020 data from the CURE-CKD Registry published in Diabetes, Obesity and Metabolism showing that only 6.8% and 6.0% of patients with CKD and diabetes were prescribed GLP-1RAs and SGLT2 inhibitors, respectively.
improvement in eGFR at 6 months compared with placebo. Further, iptacopan treatment led to significant improvement in the trajectory of renal function function decline.
The SELECT trial included 17,604 overweight or obese patients with preexisting CVD but without diabetes. Investigators randomly assigned 8803 patients to receive once-weekly subcutaneous semaglutide 2.4 mg and 8801 to placebo. The main kidney endpoint was a prespecified 5-component composite of death from kidney disease, initiation of chronic kidney replacement therapy (dialysis or transplantation), onset of a persistent eGFR less than 15, persistent 50% or greater reduction in eGFR compared with baseline, or onset of persistent macroalbuminuria. By the end of follow-up, 1.8% of the semaglutide arm experienced the prespecified 5-component main kidney endpoint compared with 2.2% of the placebo arm, with semaglutide treatment associated with a significant 22% decreased risk compared with placebo, the researchers reported.
Positive Effect on eGFR
At 104 weeks, the eGFR had declined less in the semaglutide arm (-0.86) than in the placebo arm (-1.61). Among patients with a baseline eGFR less than 60, semaglutide recipients experienced a significantly greater increase in eGFR at 104 weeks compared with the placebo group (5.28 vs 3.09). The total eGFR slope was significantly less steep in the semaglutide than placebo arm (-0.78 vs -1.17). ■
Iptacopan was well tolerated and had a favorable safety profile, Dr Kavanagh reported.
In the APPEAR-C3G trial, iptacopan demonstrated a clinically meaningful reduction on proteinuria on top of standard of care at 6 months.
The historical trend in eGFR slope among all study participants before the trial was a 7.35 mL/min/1.73 m2 per year decline. Iptacopan treatment led to a 0.90 mL/ min/1.73 m2 per year increase in slope.
Iptacopan is currently in development for other rare kidney diseases including immunoglobulin A nephropathy, atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis, and lupus nephritis. ■
Findings from this study are not the first to link gout with CKD. For example, in a study of 76,309 individuals with gout and 1,623,304 without gout identified
Dr Garshick’s team observed that the prevalence of CKD stages 4 and 5 grew more slowly among patients in serum urate quartiles 1 and 2 and more rapidly among those in quartile 4. All-cause mortality prevalence was highest among patients in the top quartile of serum urate: 19.3% vs 10.0%, 8.6%, and 10.9% for those in the first, second, and third quartiles, respectively. Patients in the top quartile also had the highest prevalence of dysrhythmias, heart failure, cardiac valve disease, pulmonary circulation disease, and cardiomyopathies, according to the investigators.
in a 5% random sample of Medicare claims, CKD developed in 17,903 individuals with gout and 150,162 without gout. After adjusting for demographics, comorbidities, and use of cardiovascular and gout medications, gout was associated with a significant 3-fold higher risk for CKD, Jasvinder A. Singh, MD, MPH, and John D. Cleveland, MD, from the University of Alabama at Birmingham, reported in BMC Nephrology
Further, in a retrospective study that matched 41,446 new gout cases to the same number of patients without gout, UK investigators found that the absolute rate of CKD stage 3 or higher was higher in the gout group than non-gout group (28.6 vs 15.8 cases per 10,000 person-years). After adjusting for age, sex, comorbidities, and other variables, gout was associated with a significant 78% increased risk for CKD stage 3 or higher. ■
Patients’ Voices Absent from Many FDA Reviews of Cancer Drugs
A substantial proportion of New Drug Applications lack patient-reported outcomes
BY JODY A. CHARNOW
More and more clinical trials of cancer drugs involve assessments of patients’ views on how treatments are affecting them.
The US Food and Drug Administration (FDA) encourages the gathering and reporting of these patient-reported outcomes (PROs), which offer insight into the patient experience without biased interpretation by investigators. Still, PRO data for cancer drugs are frequently absent from marketing approval requests submitted to the FDA, or they are inadequate. Recent studies have found that the FDA approves many novel cancer drugs without PROs, so these medications reach the market without patients’ perspectives on how these products influenced their quality of life.
A study presented at the American Society of Clinical Oncology’s 2023 annual meeting by investigators at Howard University in Washington, DC, revealed that less than half of 420 pivotal trials leading to FDA cancer drug approvals from 2006 to 2022 included PRO assessments.1 Another study, published in 2023 in Supportive Care in Cancer , 2 showed that of 59 unique cancer drugs approved from 2013 to 2022 via the FDA’s accelerated approval pathway, only 59% included PRO assessments in the clinical trials. The investigators concluded that “PRO measurements are inconsistently utilized in trials leading to initial accelerated approvals of oncology drugs, and there seems to be a lack of harmonization of different PRO measurement tools across trials.”
In another study, investigators who reviewed transcripts from 27 meetings of the FDA’s Oncology Drugs Advisory Committee (ODAC) from 2016 to 2021
found that PRO-related topics were mentioned in only 12, according to a report in JCO Oncology Practice 3 Of those, ODAC reviewers were satisfied with PRO assessments in only 2.
PROs ‘Rarely Deemed Adequate’
“During ODAC meetings, committee members and FDA reviewers expressed frustration at the lack of PROs captured in clinical trials for cancer treatments,” authors Ari Gnanasakthy, MBA, MS, and colleagues concluded. “Less than
A recent study found that less than half of 420 pivotal trials leading to cancer drug approvals from 2006 to 2022 included PRO assessments.
half of evidence packages for cancer treatments submitted for FDA review included PROs. Even when PROs were included in evidence packages, the PROs were rarely deemed adequate for benefit-risk assessments.”
They added: “Lack of credible PRO data in oncology clinical trials prevents regulators from making comprehensive and accurate assessments of the benefits and risks of new cancer treatments. Clinicians and patients, therefore, are forced to choose among treatment options without understanding the experiences of patients who were treated with these options.”
Influence on Formularies
Lack of PROs could adversely affect decisions about which medications are placed on health plan formularies and thus covered by insurance. A survey of health plan representatives (90% pharmacists, 56% pharmacy administrators) found that 78% of the
106 respondents thought PRO evidence is useful for providing additional context for safety of oncology therapies. In addition, 47% suggested that formulary reviews would be at least somewhat influenced by a lack of PRO evidence from oncology clinical trials.
“US payers view PRO evidence from both clinical trials and real-world studies as useful for supplementing traditional clinical trial data when making oncology formulary decisions and for refining treatment pathways and care delivery models,” investigators Gary Oderda, PharmD, MPH, and coauthors concluded in a 2022 paper in the Journal of Managed Care & Specialty Pharmacy 4 “Manufacturers of oncology therapies should collect and consider leveraging PRO evidence from both settings when engaging with US payers.”
Primacy of Objective Data
Although PROs, which are subjective, can provide FDA reviewers with additional information to consider, objective data must be the foundation for evaluating a drug except in cases in which a drug’s effectiveness can only be evaluated using PROs, said Peter Lurie, MD, MPH, President and Executive Director at the Center for Science in the Public Interest in Washington, DC, and former Associate Commissioner for Public Health Strategy and Analysis at the FDA.
For example, in clinical trials of pain drugs, investigators have to rely on PROs to gauge effectiveness because changes in pain perception in response to treatment are subjective. This is not the case with diseases such as cancer for which objective measures are available, Dr Lurie said. Those measures,
Patients’ perspectives on how drugs affected them in clinical trials are often lacking in NDAs.
and not patient opinion, must provide the basis for approval. Cancer drugs “should not be coming onto the market because the majority of patients think the drugs work for them,” he said.
Dr Lurie asserted, “Encouraging assessment of PROs is definitely a good idea; making it a required part of the primary assessment of safety and efficacy probably is not.”
The American Society of Clinical Oncology said in an emailed statement that it “recommends that trialists consider including attributes of accessible and equitable research, such as patientreported outcomes, in the design and conduct of all clinical trials, as understanding how patients are affected by a therapy is paramount.”
FDA’s Efforts
Through its Patient-Focused Drug Development initiative established in 2012, FDA has been working to improve data collection and reporting in clinical trials. As part of that effort, the agency issued 2 guidance documents in November 2023: “Submitting Clinical Trial Datasets and Documentation for Clinical Outcome Assessments Using Item Response Theory” and “Submitting Patient-Reported Outcome Data in Cancer Clinical Trials.” The primary goal is to incorporate the patient’s voice in the drug development and evaluation.
“PROs play an important role in assessing the patient experience with a medical product, and can provide valuable evidence for regulators, payers, and health system administrators,” the agency said in an email. “FDA is working collaboratively to increase appropriate use and increase the value of PROs as evidence in regulatory decisions and for other, non-FDA purposes.”
The agency added, “In premarket studies, the patient perspective and experience are often complementary to clinical and other biological measures when evaluating the safety and effectiveness of candidate medical products.”
In the agency’s view, PROs are already having a positive impact on the product approval process. “The existence of well-established and researched PROs has benefited the ability to make regulatory decisions directly related to patient impact,” the agency wrote in
an email. “The development and continued research on PROs facilitated through FDA guidance efforts benefits FDA’s ability to include patient’s perspectives in meaningful ways.”
Studies demonstrate an increase in PRO assessments in clinical trials. The proportion of clinical trials registered with the ClinicalTrials.gov website that included use of 1 or more PRO measures rose from 14% during 20042007 to 27% in 2007 to 2013, according to separate studies.5,6 A review of PRO assessments in phase 1 oncology clinical trials registered in the same
A recent review found delays in the publication of patient-reported outcome data from numerous genitourinary cancer drug trials.
website found that the proportion of trials using 1 or more PRO measures rose from 0.6% of trials initiated prior to 2000 to 3.4% of trials initiated from 2015 to 2019, investigators reported in Oncology 7
PRO Reporting Issues
Amid the rise in PRO assessments in trials, shortcomings in PRO data reporting, such as delays in publication, have become apparent, as demonstrated in a review of 40 pivotal clinical trials leading to the approval of 40 genitourinary (GU) cancer drugs from February 2007 to July 2022. PRO data was published for 27 trials (67.5%). Of these, 4 (15%) included preliminary PRO results in the primary publication of clinical data, a team led by Jad Chahoud, MD, MPH, of H. Lee Moffitt Cancer Center in Tampa, Florida, concluded in a 2024 paper published in eClinicalMedicine 8 For 23 studies, PRO results were reported in a secondary dedicated paper. The median time from primary publication of results to publication of the corresponding secondary PRO data was 10.5 months.
Moreover, the investigators identified problems with the quality of PRO reporting as assessed using the PRO Endpoint
Analysis Score (PROEAS), a scale with 24 items describing some aspect of PRO reporting and analysis. A score of 1 is assigned to an item that is clearly reported, and a score of 0 is assigned to an item that is unclear or not reported. Of 30 randomized controlled trials in the study’s dataset, 20 reported PRO data in a dedicated secondary manuscript. The median PROEAS score for the 20 trials was 11.1 out of 24.
“Low overall PROEAS score and delays in PRO data publication in GU cancer drug trials conducted in the past decade emphasize the need for improvement in quality of design and conduct of PRO endpoint in future trials and accelerated publication of PRO endpoints, using standardized analysis, and prespecified hypothesis driven endpoint,” Dr Chahoud and colleagues wrote.
PROMIS
Many of the PRO measures used in clinical trials in recent years are products of the Patient-Reported Outcomes Measurement System (PROMIS) initiative launched in 2004 by the National Institutes of Health to develop and strengthen PRO measures for use in research and clinical settings. PROMIS has developed more than 300 measures of physical, mental, and social health designed to be relevant across all conditions for the assessment of symptoms and functions. “PROMIS is now the gold standard for patientreported outcome (PRO) measurement,” Edward Haksing Ip, PhD, of Wake Forest University in WinstonSalem, North Carolina, wrote in a 2021 editorial accompanying a special edition of Psychometrika focusing on lessons learned from PROMIS.
PROs Not Always Appropriate
Despite the potential usefulness of PROs in the drug approval process, efforts to assess them might not be relevant or appropriate for all clinical trials. “PROs have an important role and should be considered in most drug trials, but may not be appropriate in every setting,” medical oncologist Tomasz M. Beer, MD, who has participated in numerous clinical trials, said in an interview. He added that “while PROs are an invaluable tool to better understand the patient experience, like any important outcome measure, they should be used when clinically and
scientifically indicated. That is often, but not always.”
He pointed out that PRO assessments may be unwarranted when a trial is of insufficient size (as with a small pilot study) to enable meaningful measurement of PRO end points, or when the PRO effect of a particular drug treatment has been robustly evaluated and is well understood. “These are circumstances where a requirement for PROs may not add value,” said Dr Beer, Chief Medical Officer for Multi-Cancer Early Detection at Exact Sciences in Madison, Wisconsin, and adjunct professor of medicine at Oregon Health & Science University’s Knight Cancer Institute in Portland.
Limited Resources
Another consideration is limited resources. “It is also important to remember that adding elements to studies increases the burden on participants, study staff, and costs to sponsors,” Dr Beer explained. “We have a responsibility to be thoughtful about when an element adds value and when it does not add meaningful value. Adding cost, complexity, and burden can have undesirable consequences that are not always visible, for example, fewer resources for other important features of the study, for outreach, or even smaller study sample sizes than might otherwise have been possible.” ■
REFERENCES
1. Ojo AS, Ali A. The inclusion of health-related quality of life and other patient-reported outcomes in landmark trials for Food and Drug Administration oncology drug approvals: An analysis of cancer drug approvals between 2006 and 2022. Data presented at the 2023 annual meeting of the American Society of Clinical Oncology. Poster 163
2. Gnanasakthy A, Norcross L, Clark M, Fitzgerald K. A review of patient-reported outcomes considerations in oncology drugs advisory committee meetings (2016-2021). JCO Oncol Pract. 2023;19(5):e745-e762. doi:10.1200/OP.22.00774
3. Moore DC, Elmes JB, Strassels SA, Patel JN. Use of patientreported outcome measures for oncology drugs receiving accelerated approval. Support Care Cancer 2023;31(10):602. doi:10.1007/s00520-023-08068-9
4. Oderda G, Brixner D, Biskupiak J, et al. Payer perceptions on the use of patient-reported outcomes in oncology decision making. J Manag Care Spec Pharm 2022;28(2):188-195. doi:10.18553/ jmcp.2021.21223
5. Scoggins JF, Patrick DL. The use of patient-reported outcomes instruments in registered clinical trials: Evidence from ClinicalTrials.gov. Contemp Clin Trials. 2009;30:289-292. doi:10.1016/j.cct.2009.02.005
6. Vodicka E, Kim K, Gnanasakthy A, Scoggins JF, Patrick DL. Inclusion of patient-reported outcome measures in registered clinical trials: Evidence from ClinicalTrials.gov (2007-2013). Contemp Clin Trials. 2015;43:1-9. doi:10.1016/j.cct.2015.04.004
7. Coleman RL, Beck JT, Baranda JC, et al. The use of patientreported outcome measures in phase I oncology clinical trials. Oncology 2021;99:444-453. doi:10.1159/000514874
8. Paravathaneni M, Safa H, Joshi V, et al. 15 years of patientreported outcomes in clinical trials leading to GU cancer drug approvals: a systematic review on the quality of data reporting and analysis. eClinicalMedicine 2024;68:102413. doi:10.1016/j. eclinm.2023.102413
URS With Biopsy Improves High-Risk UTUC Outcomes
BY JOHN SCHIESZER
Diagnostic ureteroscopy (URS) with or without biopsy remains controversial in the management of high-risk upper tract urothelial carcinoma (UTUC). A recent retrospective multi-institutional study of patients with high-risk UTUC suggests that preoperative URS with biopsy can improve outcomes.
Preoperative URS was associated with significantly longer 5-year overall survival (OS) and cancer-specific survival (CSS), but did not improve 5-year recurrence-free survival (RFS) and metastasis-free survival (MFS), investigators reported in Urologic Oncology
“Preoperative URS with biopsy can significantly enhance patient selection for curative surgical treatment, leading to improved survival outcomes,” said first author Francesco Ditonno, MD, a urology resident at the University of Verona in Italy and a clinical research fellow at Rush University in Chicago. “However, the decision to use URS should be carefully considered, particularly in patients with larger tumors or locally advanced disease, where direct referral for radical nephroureterectomy may be more appropriate.”
Significantly longer cancer-specific and overall survival reported at 5 years.
Using the ROBUUST dataset, Dr Ditonno and colleagues studied patients who received preoperative URS and biopsy before curative surgery and compared them with those who did not. The study included 1,912 patients (1,035 with preoperative URS and biopsy and 877 without). Patients ranged in age from 64 to 78 years. The most common surgical procedure in both study arms was robotic-assisted radical nephroureterectomy (55.1%). The median follow-up duration was 24 months.
“We observed that patients undergoing preoperative URS had significantly prolonged overall survival and cancerspecific survival compared to those who did not undergo URS,”Dr Ditonno said. “Moreover, a high concordance between preoperative endoscopic biopsy and final histology was observed.”
The 5-year OS was 19 months in the URS arm compared with 13 months in the no-URS arm. The 5-year CSS was 37 months and 20 months, respectively.
The 5-year RFS was 7 months and 8 months in the URS and no-URS arm,
respectively, a nonsignificant difference. The 5-year MFS was 8 months in both groups.
Study results suggest that the additional diagnostic information obtained through URS may allow for a better selection of patients for appropriate surgical treatment, enhancing their prognosis.
“These findings were somewhat surprising, as the literature has been inconsistent regarding the impact of URS on oncological outcomes,” Dr Ditonno said.
The study included a large number of high-risk UTUC patients, which enhances the reliability and generalizability of the findings, according to the investigators.
“Data were collected from multiple institutions worldwide, providing a diverse patient population and reducing regional biases,” Dr Ditonno said. “However, variations in diagnostic and surgical techniques across different institutions might affect the consistency of the results, and the absence of a centralized review for
pathological assessments could introduce variability in tumor staging and grading.”
Multivariable logistic regression analysis showed that patients with a tumor size of 2 cm or more and those with suspected locally advanced disease (cT2 or higher) had significant 67% 51% reduced odds of undergoing a diagnostic URS, respectively.
Urologic surgeon Qiang Li, MD, PhD, who specializes in treating patients with
genitourinary malignancies at Roswell Park Comprehensive Cancer Center in Buffalo, New York, said the authors demonstrated an advantage in CSS and OS for patients undergoing preoperative URS. URS was not an independent factor, however, as the survival difference was attributed to a selection bias. “Better surgical candidates were chosen for preoperative URS,” Dr Li said. “Moreover, URS was not helpful for preoperative decision-making
regarding the use of neoadjuvant therapy and the type of definitive extirpative surgery. These results are expected because this is a descriptive study without defined criteria for preoperative URS.”
Dr Li said the finding may be clinically significant because the study had a large sample size of consecutive patients with comprehensive data variables and adequate follow-up. The authors demonstrated a real-world preoperative
URS experience, showing a low rate of non-diagnostic biopsies and a high concordance between URS biopsy and final pathology. “The main weakness is the lack of criteria for determining who needs preoperative URS,” Dr Li said. “A better study would pre-define the selection criteria and recommendations for preoperative URS and/or randomize all eligible patients to either undergo preoperative URS or not.” ■
Stone Surgery Fails to Lower UTI Relapse Risk
Surgical intervention for kidney stones in patients with a history of urinary tract infections (UTIs) does not significantly decrease the risk for UTI relapse, according to study data presented at the American Urological Association’s 2024 annual meeting in San Antonio, Texas.
Prior retrospective studies evaluating surgery for kidney stones in patients with recurrent UTIs found that infections resolve in approximately half of patients following stone removal, researchers noted. Connor M. Forbes, MD, and colleagues prospectively studied 82 patients with kidney stones and 3 symptomatic,
culture-confirmed UTIs in the preceding 12 months, or 2 in 6 months. Of these, 62 opted for surgery and 20 for observation. Follow-up data at 6 months were available for 37 and 11 patients in the intervention and observation arms, respectively. In the intervention group, 70% received their surgery and in the observation
group, 18% crossed over to surgery. In the intention-to-treat analysis, the surgery group was significantly more likely to be stone-free at 6 months (59% vs 0%). At 6 months, 5 patients (45%) in the observation group and 12 (32%) in the surgery group experienced 1 or more UTIs, a nonsignificant difference. ■
KT Candidate Death Rate High After Delisting
BY JODY A. CHARNOW
PHILADELPHIA—More than one-fifth of individuals on the kidney transplant waiting list in the United States are delisted, with approximately 50% of them dying within 4 years, according to data presented at the 2024 American Transplant Congress.
“Delisting of candidates from the kidney transplant waiting list is actually a more common outcome on the waiting list than death on the waiting list, and little has been published on the fate of these candidates after delisting,” investigator Douglas Keith, MD, of Ascension Sacred Heart Hospital
in Pensacola, Florida, told congress attendees.
Using data from the Scientific Registry of Transplant Recipients (SRTR), investigators identified 330,074 candidates who were removed from the kidney and kidney-pancreas waiting list for any reason from January 1,
2010 and September 2, 2020. Delisting accounted for 72,916 (21.9%) of them. The median time to delisting was 4.2 years. Death while on the waiting list accounted for 48,187 removals (14.6%). Of the remaining 208,971 patients (63.3%) removed from the list, 146,307 and 62,664 received a deceaseddonor kidney and living-donor kidney, respectively.
“The characteristics of candidates delisted were most similar to candidates who died on the list even though 50% of them were removed for reasons other than ‘too sick to transplant,’” Dr Keith said.
Among the 47% of candidates who were delisted because they were “too sick to transplant,” the median survival was only 3 years, he said.
The most important factors associated with death after delisting were increasing age, non-Latino White race, diabetes mellitus, and “too sick to transplant” given as a reason for delisting, he said.
Half of delisted kidney transplant candidates died within 4 years.
Dr Keith noted that “probably the majority of these people who are delisted are not likely to return to the list after delisting due to subsequent death.”
Waiting List Deaths Undercounted
In their study abstract, the investigators concluded: “Death on the waiting list vastly undercounts the true death rate among patients placed on the waiting list due to the high rate of death after delisting.”
Similar findings emerged from a study of 324,582 patients aged 18 years or older listed for a deceased-donor transplant from January 2003 to December 2013 who were identified using the SRTR. The study, led by Joel T. Adler, MD, of Brigham and Women’s Hospital in Boston, found that 18% of those patients were delisted, with “too sick” and “other” the most common reasons given. After delisting, 49.7% of patients had died by the end of follow-up, with a time to death after delisting of 5 years, according to findings published in Clinical Transplantation in 2021.
“These patients live a surprisingly long time after removal,” the authors concluded. ■
New Data Support PCa Focal Cryoablation
Investigators report good long-term oncologic control in well-selected men with localized tumors
Primary focal cryoablation can provide good long-term oncologic control in well-selected men with localized prostate cancer, investigators concluded in a presentation at the American Urological Association 2024 annual meeting in San Antonio, Texas.
Investigators led by Thomas J. Polascik, MD, of Duke Cancer Institute and Duke University Medical Center in Durham, North Carolina, identified 70 patients who underwent image-guided focal cryoablation from their prospectively maintained 2005-2020 database. The failure-free survival rate was 84% at 5 years and 58% at 10 years, Dr Polascik’s team reported. Failurefree survival was defined as the avoidance of salvage therapy. Metastasisfree, cancer-specific, and overall survival rates at 10 years were 94%, 98%, and 88%, respectively. The latter statistic suggests that these men died from causes other than prostate cancer, Dr Polascik said. He added that is the goal of focal therapy: to manage this disease without the attendant adverse lifealtering side effects often accompanying traditional whole gland treatments.
SURVIVAL OUTCOMES
Primary focal cryoablation for wellselected men with localized prostate cancer is associated with favorable 10-year metastasis-free, cancer-specific, and overall survival, according to a study.
Source: Deivasigamani S, et al. Long-term oncological and functional outcomes of focal cryoablation of localized prostate cancer with a median follow-up of 7 years: A single institution experience. Presented at the AUA 2024 Annual Meeting, May 3-6, San Antonio, Texas. Poster MP25-06.
With respect to functional outcomes at 12 months, 97% of men were continent without pad usage, and 73% of potent men were able to maintain erections sufficient for sexual intercourse.
“These study findings support favorable real-world outcomes of focal ablation of localized, image-visible cancer that can be targeted and treated,” Dr Polascik said in an interview. Functional outcomes partly depend on a good cancer location
that can be targeted, he noted, away from the neurovascular bundles or other important structures.
“Sound patient selection remains the foundation for successful focal therapy,” Dr Polascik emphasized. “Even older men, if deemed good candidates, may select image-guided focal therapy over conventional whole gland treatment options.”
The men in the study had a median age of 75 years and a median preoperative PSA of 6.5 ng/mL. D’Amico intermediate- and high-risk disease were diagnosed in 61% and 30%, respectively. Patients were followed up for a median 86 months.
Dr Polascik and colleagues made similar findings in a study of 282 patients in the international, multicenter Focal Therapy Society registry, which records patient data from 7 US centers and 1 South American center. The patients had a median follow-up of 24 months.
The investigators observed a failurefree survival rate of 74% at 5 years. Metastasis-free, cancer-specific, and overall survival rates at 5 years were 97%, 99%, and 96%, respectively.
Post-ablation biopsy was performed in 198 patients (70%), with results
showing a clinically significant in-field and out-field prostate cancer recurrence rate of 11% and 18%, respectively. Of 212 patients with a minimum of 1 year of follow-up, 209 (98%) were continent, requiring no pad use at 12 months post-procedure. Of 104 patients who were initially potent, 77 (74%) maintained erections sufficient for sexual intercourse.
The study population had a median preoperative PSA level of 6.8 ng/mL. Of the 282 patients, 217 (77%) and 45 (16%) had D’Amico intermediate- and highrisk disease, respectively.
Dr Polascik noted that “treatments will become more customized in the future, as preserving quality of life will need to be balanced with oncological outcomes. For some, this may convert prostate cancer management into one that is a chronic condition rather than simply surgically remove it and deal with the consequences for the remainder of one’s life.”
The study presents the first report of the oncologic and functional outcomes of focal cryotherapy in patients with organ-confined prostate cancer from the Focal Therapy Society registry. ■
Cretostimogene Promising for BCG-Unresponsive
Three-quarters of patients with highrisk nonmuscle-invasive bladder unresponsive to bacillus Calmette-Guérin (BCG) had a complete response to treatment with the investigational oncolytic immunotherapy cretostimogene grenadenorepvec, according to pivotal results from the phase 3 singlearm BOND-003 trial presented at the American Urological Association 2024 annual meeting in San Antonio, Texas. In many cases, patients maintained a complete response out to 12 months and even longer.
The immunotherapy, cretostimogene grenadenorepvec, is an intravesically administered adenovirus designed to replicate in and kill cancer cells, investigator Mark Tyson, MD, MPH, of Mayo Clinic in Rochester, Minnesota, explained in an oral presentation.
BOND-003 (NCT04452591) included a cohort of 112 patients who had BCGunresponsive high-risk NMIBC with carcinoma in situ. Patients received 6 sequential weekly instillations of cretostimogene followed by a repeat induction for nonresponders and maintenance for responders.
Dr Tyson presented findings from the first 105 patients with a cutoff date of April 1, 2024, which was an update of an earlier analysis. Of these, 79 (75.2%) had a complete response at any time during the study. Of the 35 complete responders who reached the 12-month time point, 29 (83%) maintained their complete response beyond 12 months, with 22 patients still pending. At 12 months, 92.4% of patients had not undergone a radical cystectomy. The treatment was well tolerated. “We observed no grade 3 or higher
treatment-related adverse events and no deaths,” Dr Tyson said.
Based on BOND-003 data, the FDA has granted cretostimogene monotherapy Fast Track and Breakthrough Therapy designations for BCG-unresponsive NMIBC with carcinoma in situ with or without papillary disease.
Overall complete response rate was 75.2%, according to investigators.
Recognizing that comparing across studies is difficult, Dr Tyson said cretostimogene “would at least compare favorably to the current nonsurgical costandards of care.” The 75% complete response rate at any time point with
NMIBC
cretostimogene compares favorably to the 62% observed for N-803 plus BCG combination therapy, the 51% observed for nadofaragene, and the 41% observed for pembrolizumab, he said.
Cretostimogene encodes the complementary DNA for GM-CSF, a potent cytokine inducer of anti-tumor immunity in animal models, Dr Tyson said. The primary receptor for cretostimogene is the coxsackie adenovirus receptor (CAR), which is expressed in all stages of bladder cancer. “After binding the CAR receptor, creto enters the malignant cell where viral replication leads to tumor cell lysis and release of viral- and tumor-specific antigens,” he explained. “These antigens are picked up by dendritic cells and presented to T-cells, which initiate the local anti-tumor response, thereby potentiating the immunotherapy effect.” ■
Abnormal Potassium Levels Before Radical Cystectomy Predict Worse Outcomes
Investigators report increased risk for cancer-specific and all-cause mortality
BY JOHN SCHIESZER
Findings from a recent retrospective study suggest that abnormal preoperative plasma potassium levels (PPLs) in patients undergoing radical cystectomy for bladder cancer increase the risk for adverse oncologic outcomes.
Preoperative PPLs could be a costeffective and easily obtainable biomarker to improve the accuracy of outcome predictions for treatment, investigators led by Jakob Klemm, MD, of University Medical Center HamburgEppendorf in Hamburg, Germany, concluded in a paper published in Clinical Genitourinary Cancer.
The study is the first to explore the influence of preoperative PPLs on oncologic outcomes and complications in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy, they noted.
More Adverse Pathology
The study included 501 patients from a single tertiary care center, of whom 63 (13%) had abnormal preoperative PPLs (less than 3.5 and greater than 4.6 mmol/L). The group included 50 patients (10%) with elevated PPLs
developed in 24 patients (39%). On multivariable Cox regression analyses adjusted for perioperative parameters, abnormal preoperative PPLs were significantly associated with 1.9-, 2.8- and 2.1-fold increased risks for all-cause mortality, cancer-specific mortality, and disease recurrence, respectively, Dr Klemm’s team reported. Elevated PPLs were significantly associated with 1.8-, 2.6-, and 2.0-fold increased risks for these outcomes, respectively. In models that included only preoperative factors, abnormal preoperative PPLs were not associated with overall, cancer-specific, and recurrence-free survival, according to investigators.
Better Patient Stratification
“Incorporating PPLs into preoperative assessments might aid in identifying patients at higher risk of adverse outcomes, allowing for more tailored treatment planning and closer postoperative monitoring,” the authors concluded. “If externally validated, this could lead to better patient stratification and potentially improved survival rates in UCB treatment through individualized management strategies.”
Incorporating plasma potassium levels into preoperative assessments may allow for more tailored treatment planning, researchers say.
(above 4.6 mmol/L) and 13 (2.5%) with decreased PPLs (less than 3.5 mmol/L). Patients with abnormal preoperative PPLs had a significantly higher prevalence of advanced tumor stage (pT3 or higher) and non-organ-confined disease compared with those who had normal preoperative PPLs.
After a median follow-up duration of 59 months, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) died from bladder cancer. Of the 63 patients with abnormal preoperative PPLs, 29 (46%) died, including 19 (30%) from UCB. Recurrence
The precise biological mechanisms underlying these findings are unknown, although a host of factors can impact electrolyte levels, according to the investigators. One hypothesis is that high PPLs stemming from tumor necrosis might suppress T-cell function, thereby decreasing the body’s immune response against the tumor. The authors acknowledged that their study was limited by its retrospective design, a relatively small sample size, its single-institution perspective, and the absence of neoadjuvant treatment in their cohort.
‘Huge Unmet Need’
“In this area of bladder cancer treatment, there is a huge unmet need to develop a biomarker that can help us predict how patients do after radical cystectomy, [and] this study aims to try to do this,” said Nitin Yerram, MD, Director of Urologic Research at Hackensack University Medical Center in New Jersey, who was not involved in the study. He cautioned about the applicability of the findings for clinical use. “Associations do not always have clinical meaning and should be used for hypothesis generation,” Dr Yerram said.
Douglas Scherr, MD, professor of urology and the Clinical Director of Urologic Oncology at the Weill Medical College of Cornell University in New York, New York, said the findings are not surprising. Low or high potassium levels are commonly a sign of other underlying disease states, including renal insufficiency, renal failure, heart disease, and thyroid and adrenal issues. “All of which will be harbingers of poor outcomes after radical cystectomy,” Dr Scherr said. “From a mechanistic standpoint, there is no rationale for potassium to dictate outcome of disease other than it reflects other underlying diseases.”
Michael Heung, MD, professor of medicine in the division of nephrology at the University of Michigan in Ann Arbor, said the findings overall were somewhat surprising. “It’s not clear to me why perioperative potassium abnormalities would be associated with adverse long-term outcomes,” Dr Heung said. “This certainly could be just an association, as I’m not sure what the biologic plausibility between isolated baseline potassium levels and long-term outcomes would be. This is not a particularly large study, especially when you consider that the exposure group (abnormal potassium levels) was only 63 patients. While the results are somewhat intriguing, further validation is needed before this can be adopted in clinical practice.” ■
Hypertension Is Not More Likely in LKDs
Living kidney donors (LKDs) are at no higher risk for hypertension or albuminuria compared with nondonors, investigators concluded.
The finding is from a prospective cohort study of 924 standard-criteria normotensive LKDs enrolled before nephrectomy and a concurrent sample of 396 nondonors. During a median follow-up of 7.3 years, hypertension developed in 17% of the LKDs and 17% of the nondonors, Amit X. Garg, MD, PhD, of Victoria Hospital in London, Ontario, Canada, and colleagues reported in JAMA. The donor and nondonor groups experienced comparable modest longitudinal
Finding is from a cohort study with a median 7.3 years of follow-up.
increases in blood pressure (BP), with a final mean systolic BP of 119 and 120 mm Hg, respectively.
Albuminuria developed in 15% of LKDs and 11% of nondonors, a nonsignificant difference after accounting for differences in baseline risk, according to investigators.
After an initial estimated glomerular filtration rate (eGFR) mean decline of 32 mL/min/1.73 m 2 from a mean baseline value of 100 mL/min/1.73 m2 , donors had a slower mean rate of eGFR decline compared with nondonors, but were more likely than nondonors to have an eGFR between 30 and 60 mL/ min/1.73 m2 at least once during follow-up (47% vs 5%), Dr Garg’s team reported. At final follow-up, donors had a lower eGFR compared with the nondonors (67 vs 91 mL/min/1.73 m2).
“After accounting for differences in baseline risk, living donors had a similar risk of hypertension as nondonors in the 7 years following donation and no significant difference in mean blood pressure,” the authors wrote.
The investigators defined hypertension as a systolic BP of 140 mm Hg or higher, a diastolic BP of 90 mm Hg or higher, or use of antihypertensive medications. ■
Renal Nutrition Update
Maintaining a healthy gut microbiome in CKD may help slow its progression
BY LINDSEY ZIRKER, MS, RD
The gut microbiome is an ecosystem containing trillions of bacterial cells. In healthy people, the gut microbiome is symbiotic and provides significant benefits. In patients with CKD, however, the gut microbiome is less synergistic. Compared with healthy individuals, patients with CKD, even in its early stages, have reduced levels of beneficial bacteria and increased levels of proinflammatory bacteria.1 This imbalance of bacteria (or dysbiosis) can lead to increased production of uremic toxins and increased intestinal permeability, thereby enabling these toxins to enter the bloodstream. This can result in a faster CKD progression, poor digestion and absorption of nutrients, food sensitivities, depression and other mental health issues, vascular damage, aortic calcification, atrial fibrillation, and autoimmune conditions, among other complications.2,3
Microbiome
Disrupters
An unhealthy gut microbiome may occur for a number of reasons, including buildup of uremic toxins, intestinal hypoperfusion from aggressive ultrafiltration, medications (such as omeprazole, phosphorus binders, and antibiotics), excessive protein intake, poor stress management, or low-fiber diets as the result of inappropriate potassium intake or other diet restrictions.3
Approaches to Support Gut Health
Plant-based, low-protein, high-fiber, and anti-inflammatory diets can promote the growth of beneficial bacteria while suppressing harmful bacteria and the production of toxins.4 These dietary patterns are in line with recent
CKD guidelines, despite gut health not necessarily being the focus. Recent recommendations can be found in Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, specifically guidelines 3.0.1 and 3.2.1 for type and amount of protein and 3.3.1 for dietary patterns.5
Different types of dietary supplements may have a place in supporting gut health, such as prebiotics (fiber that promotes the growth of beneficial bacteria), probiotics (supplements of beneficial bacteria) and synbiotics (supplements that include both).
In patients with CKD, prebiotics increase the levels of beneficial bacteria and reduce inflammatory factors such as indoxyl sulfate, p-cresyl
Patients with CKD, even in its early stages, have reduced levels of beneficial bacteria and increased levels of proinflammatory bacteria.
sulfate, and trimethylamine N-oxide. Probiotics, notably Renadyl™, can also help reduce uremic toxins. It is the only probiotic uniquely focused on breaking down uremic toxins. Probiotics can help improve gut barrier integrity, eliminate pathogens, and improve common digestive complaints in CKD patients.3,4,6
Stress has far-reaching effects on organs, and the gut is no exception. Helping patients find healthy ways to cope with stress, develop a resilient
mindset, support the vagus nerve, and engage in mindfulness activities are key to healing the gut. As with many interventions that attempt to address root issues, there are multiple benefits. Supporting patients’ mental health/ stress management can have a positive impact in other areas of their health, such as improved blood pressure, improved immunity, and better sleep.7 Therapists, social workers, and counselors can provide significant support in this area. Physical or massage therapists trained in vagus nerve activation can also provide support. Trained providers can be found at the Barral Institute website (www.barralinstitute.com).
Medications can be another source of microbiome disturbance, so providers should regularly review medication lists with patients. If they identify side effects that might adversely affect the gut, they can suggest alternative medications. It may also be helpful to have open discussions with other providers trained in gut health to know which medication adjustments are more likely to be helpful.3
Renal Dietitians’ Role
Nephrology providers need not be experts in gut health to maximize this opportunity to support kidney health. Renal dietitians are critical to helping patients shift their dietary patterns to support gut as well as kidney health. Dietitians can monitor and manage potential supplements to ensure the
patient is well nourished despite diet restrictions and poor digestion or absorption. Dietitians can also assess patient nutrient status to ensure adequate nutrition for healing the gut. Greater awareness of the kidneygut connection could give nephrology providers another way to provide holistic care to patients to slow progression of CKD. ■
Lindsey Zirker, MS, RD, is a renal dietitian who works with Kidney Nutrition Institute in Titusville, Florida. She specializes in autoimmune kidney disease and advanced practice medical nutrition therapy for patients with kidney disease.
REFERENCES
1. Voroneanu L, Burlacu A, Brinza C, et al. Gut microbiota in chronic kidney disease: From composition to modulation towards better outcomes—A systematic review. J Clin Med. 2023;12(5):1948. doi:10.3390/jcm12051948
2. Tang Z, Yu S, Pan Y. The gut microbiome tango in the progression of chronic kidney disease and potential therapeutic strategies. J Transl Med. 2023;21(1):689. doi:10.1186/s12967-023-04455-2.
3. Zirker L. Kidney-gut axis: The connection between kidney disease and the gut. Gonyea J, Phillips S, eds. Clinical Guide to Nutrition in Kidney Disease 3rd ed. Chicago, IL: Academy of Nutrition and Dietetics; 2023:443-453.
4. Lambert K, Rinninella E, Biruete A, et al. Targeting the gut microbiota in kidney disease: The future in renal nutrition and metabolism. J Ren Nutr. 2023;33(6S):S30-S39. doi:10.1053/j. jrn.2022.12.004
5. Ikizler TA, Burrowes J, Byham-Gray L, et al. KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update. Am J Kidney Dis. 2020;76(3 Suppl 1):S1-S107. doi:10.1053/j.ajkd.2020.05.006
6. Kiran MD, Gharat P, Vakharia M, Ranganathan N. Specific Probiotics for Chronic Kidney Disease: A Review. Indian Pract. 2019;72(2):22.
7. Bonaz B, Sinniger V, Pellissier S. Vagus nerve stimulation at the interface of brain-gut interactions. Cold Spring Harb Perspect Med 2019;9(8):a034199. doi:10.1101/cshperspect.a034199
Symbiotic intestinal bacteria have important implications for kidney health.
Ethical Issues in Medicine
How shared decision-making balances patient autonomy and doctor beneficence
BY DAVID J. ALFANDRE, MD, MSPH
Iremember the first time someone said to me, “It’s your world, I’m just living in it.” I was a Peace Corps volunteer serving as a health educator in a small village, living in a small concrete block home with a tin roof that when it rained sounded like the inside of a snare drum. I had never heard that unusual phrase before. I was tickled by the idea that a world could exist where I’m the center of it and other people simply revolve around me. It was probably the first time I gave the concept of autonomy some persistent thought.
No Undue Interference
For health care professionals, the concept of autonomy, or more accurately, respect for autonomy, is taught in every medical school as one of the central principles of Western medical ethics. Medical students learn early on that health care professionals are expected to respect the autonomy of patients because it helps to ensure that they can be self-determining. Stated simply, clinicians should not unduly interfere with allowing people to make informed decisions about their health and life consistent with their values, interests, and preferences.
Nonetheless, the principle of respect for autonomy does not exist in a vacuum, and leaving patients alone to navigate health care decisions would relinquish clinicians’ responsibility for promoting patients’ best interests. The tension over the ethical principles of autonomy and beneficence comes to mind here. However, even as patients are encouraged to be the ultimate decider on what is done to their body, it is the clinician who possesses the medical expertise to advise them on making that decision.
Clinicians can balance these professional obligations to patients by engaging them in shared decision-making (SDM), “an approach where clinicians and patients share the best available evidence when faced with the task of
People have innumerable sources for gathering medical and health information, but when they come for a medical evaluation, they generally want, and believe they will benefit from, clinician recommendations, not simply a laundry list of medical options. The SDM model advances clinicians as guides to the medically appropriate options while respecting and recognizing patients’ values and preferences.
Giving Patients Options
Sometimes, though, SDM is insufficient to maximize a patient’s autonomy, especially when they are facing a new illness or struggling about how to
Respect for the autonomy of patients does not mean leaving them to navigate health care decisions on their own.
making decisions, and where patients are supported to consider options, to achieve informed preferences.”1 This model recognizes both that the clinician possesses expert medical knowledge and should not be relegated to a bystander role, and that patients have expert knowledge of their own lives, values, and interests to help inform and guide the decision-making. This model is also designed to avoid the undesirable extremes of patients as completely passive participants and clinicians serving solely as information purveyors without any advisory role.
make a medical decision. For example, a patient with a new diagnosis of endstage kidney disease requiring kidney replacement therapy may believe that death is preferable to living with such an illness. These patients may be struggling with a range of emotions as they attempt to adjust to their new reality. They might feel grief, loss, anger, frustration, and fear, which might limit their ability to see a future where they continue to live well. An impoverished interpretation of autonomy would assert simply that patients have the right
to decline recommended treatment, even lifesaving treatment, provided they have been informed of and understand the risks, benefits, and alternatives.2 An expanded notion of autonomy could have the nephrology treatment team introduce the patient to other patients who are on different forms of kidney replacement therapy (eg, peritoneal dialysis, hemodialysis, home dialysis, transplantation), or they could suggest a time-limited trial of dialysis. This doesn’t deny patients their right to choose, but it can enhance autonomy by allowing patients to see beyond what they may be perceiving as terrible options, in this case dialysis or death. In fact, choosing death over dialysis could be considered a loss of autonomy if the patient believes their choices leave them with less control over their lives. That is, perhaps the only thing patients believe they could control at that moment was to decline lifesaving dialysis treatment. The psychiatrist Irv Yalom in his book The Gift of Therapy talks about his role with patients as helping to remove barriers to growth. This position is not unique to mental health professionals but indeed has relevance to any consultative medical professional. In the above example, persuading, gently pushing back, cajoling, and encouraging patients to consider other options can help to remove barriers to their potential growth rather than interfering with their ability to decide for themselves. In some ways, it’s the patient’s world: We’re just here to help. ■
David J. Alfandre, MD, MSPH, is a health care ethicist and an Associate Professor in the Department of Population Health at the NYU School of Medicine in New York. The views expressed in this article are those of the author and do not necessarily reflect the position or policy of the VA National Center for Ethics in Health Care or the US Department of Veterans Affairs.
REFERENCES
1. Elwyn G, Frosch D, Thomson R, et al. Shared decision making: A model for clinical practice. J Gen Intern Med 2012;27:1361-1367.
2. Kirschner K. Calling it quits: When patients or proxies request to withdraw or withhold life-sustaining treatment after spinal cord injury. Top Spinal Cord Inj Rehabil 2008;13:30-44.
Practice Management
Federal government announces HIPAA Final Rule for reproductive health care privacy
BY JOHN SCHIESZER
On April 22, the federal Office for Civil Rights (OCR) within the Department of Health and Human Services (HHS) announced a Final Rule called the “HIPAA Privacy Rule to Support Reproductive Health Care Privacy.” It strengthens the 1996 HIPAA Privacy Rule by prohibiting disclosure of protected health information (PHI) related to the provision of lawful reproductive health care.
Health care providers, health plans, and information clearinghouses are required to modify their Notice of Privacy Practices to support reproductive health care privacy.
It is hoped that the rule will bolster patient-provider confidentiality and promote trust and open communication between patients and their health care providers.
‘More Important Than Ever’ “Many Americans are scared their private medical information will be shared, misused, and disclosed without permission. This has a chilling effect on women visiting a doctor, picking up a prescription from a pharmacy, or taking other necessary actions to support their health,” HHS Secretary Xavier Becerra said in a department press release. “The BidenHarris Administration is providing stronger protections to people seeking lawful reproductive health care regardless of whether the care is in their home state or if they must cross state lines to get it. With reproductive health under attack by some lawmakers, these protections are more important than ever.”
Provisions of the new rule are important for clarifying how covered entities should protect reproductive health information, said Lara Cartwright-Smith, JD, MPH, an
associate professor in the Department of Health Policy and Management and program director for the MPH in Health Policy at the Milken Institute School of Public Health at George Washington University, Washington, DC. “This clarification was required
Cartwright-Smith said. “We all just scroll to the bottom and accept the terms and conditions. It’s also easier than ever to gather data from multiple sources that are not covered by HIPAA and use them to identify private information about individuals.”
FTC Makes Changes
The Federal Trade Commission (FTC) announced in April it has finalized changes to the Health Breach Notification Rule, which is designed to strengthen and modernize the rule by clarifying its applicability to health apps and other similar technologies.
The rule expands the information that covered entities must provide to
Provisions of the new rule are important for clarifying how covered entities should protect reproductive health information.
to help patients feel confident sharing information with their providers, even about care received in another state,” Cartwright-Smith said.
The OCR had previously issued guidance explaining that HIPAA rules do not protect the privacy or security of patients’ health information when they access or store it on personal cell phones or tablets.
“Individuals may input health information into apps that are not covered by HIPAA without realizing their information is not protected,”
consumers when notifying them of a breach of their health data.
“I think there need to be rules beyond HIPAA for settings other than health care because health information is reaching beyond the health care setting,” Cartwright-Smith said. “There is great value in sharing information to support patient engagement and selfmanagement, care coordination, quality improvement, public health, and other important goals.”
The rule modifies when the FTC must be notified. For breaches involving 500 or
more individuals, covered entities must notify the FTC at the same time they send notices to affected individuals. This must occur without unreasonable delay and in no case later than 60 calendar days after the discovery of a security breach.
“Patients, providers, and anyone using private health information should think about minimizing the risks to the subjects of that information, whether by minimizing the information collected, minimizing the risk of disclosure, or minimizing the potential harm that can result from disclosure,” Cartwright-Smith said.
HIPAA rules may need to be altered significantly over the next 12 to 24 months because of the potential that artificial intelligence (AI) tools could violate patient privacy. “I don’t think the privacy rights under HIPAA are greatly under threat, but I do think that AI and other tools that facilitate re-identification from large data sets, as well as tools that collect and share health data outside of health care settings, change the landscape so that HIPAA alone is not sufficient to ensure privacy of health information,” she said.
Josephine Wolff, PhD, associate professor of cybersecurity policy at Tufts University in Boston, Massachusetts, said there is a growing concern about augmented intelligence and patient privacy. “I think on the whole it will depend on whether health care institutions decide to use patient data to train models or otherwise use that data as inputs for these systems. If they do, then they will need to think carefully about who will have access to those models and what contexts they will be used to prevent potential privacy leaks,” Dr Wolff said. Lee Kim, JD, senior principal of Cybersecurity and Privacy at the Healthcare Information and Management Systems Society (HIMSS), a global advocate for digital health transformation, said the landscape is changing daily. “What we need to do is change the culture for better adherence to the rules,” Kim said. “Patient privacy should be acknowledged as a fundamental right. ■
John Schieszer is a medical journalist based in Seattle, Wash.
Learn about more ways to improve your day-to-day medical practice
