New studies may help change views on hemodialysis with residual kidney function
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The benefits of residual kidney function in people treated with chronic hemodialysis cannot be overstated, according to Mariana Murea, MD, and include longer survival and fewer complications related to advanced kidney dysfunction and its treatment.
Photo courtesy Wake Forest University School of Medicine.
However, viewpoints vary on best practices and how to manage inclusion of residual kidney function (RKF) in the prescription of chronic hemodialysis, Murea, an associate professor of nephrology at Wake Forest University School of Medicine and a nephrologist at Atrium Health Wake Forest Baptist in Winston-Salem, North Carolina, told Healio | Nephrology News & Issues.
Murea’s dialysis clinic is one of six centers participating in the TwoPlus clinical trial funded by a $10.2 million grant from the Patient-Centered Outcomes Research Institute (PCORI). The trial will focus on adjusting hemodialysis treatments based on clinical manifestations and RKF in patients who elect in-center hemodialysis as their treatment modality for kidney dysfunction requiring dialysis.
“The goal of the study is to really change the way we deliver hemodialysis and respect dialysis modality choice,” Murea said. “By including RKF, when present, in an incremental-start hemodialysis prescription, not all patients need to jump-start on full-dose, three-times-per-week hemodialysis.”
While the viewpoint in the kidney community is that peritoneal dialysis is a better modality for preserving RKF, “there is no data to support this notion,” Murea said. “The community perceives that RKF declines faster with hemodialysis because it is neither monitored nor discussed with the patients who choose hemodialysis, giving the impression that these patients don’t have RKF or that it was already lost,” Murea said. “By not looking for and seeing RKF in patients on hemodialysis, however, it doesn’t mean they don’t have RKF. We want to show that patients who choose hemodialysis, for any reason, should receive the same attention to their ongoing levels of RKF — just as those who choose PD,” Murea said.
Likewise, the aim is not to suggest that incremental-start hemodialysis is better than home dialysis therapies. “We are not negating the option for home dialysis,” Murea said. “However, we do want to show that monitoring and including RKF can also be done for people treated with in-center hemodialysis. Our main objective is to show that incremental-start hemodialysis is safe in people who have RKF when in-center hemodialysis is started.”
The TwoPlus trial aims to enroll 350 patients who will be randomized, in a 1:1 ratio, to incremental-start twice-per-week hemodialysis vs conventional three-times-per-week hemodialysis. The study will also enroll caregivers to better understand how people cope with dialysis between the two different modes of hemodialysis initiation: incremental or full dose. The study is expected to last 5 years.
Other studies
“We need sound scientific evidence whether or not incremental-start hemodialysis is inferior, similar or superior to upfront three-times-per-week hemodialysis with respect to patient outcomes,” Peter Kotanko, MD, FASN, head of biomedical evidence generation at the Renal Research Institute and adjunct professor of medicine and nephrology at the Icahn School of Medicine at Mount Sinai, told Healio | Nephrology News & Issues. Kotanko, co-principal investigator with Murea on the TwoPlus trial, said he hopes funding will be available to include biobanking of samples from the two treatment groups. That can include measuring and documenting uremic toxins and other important indices to help researchers evaluate the impact of the frequency of the dialysis sessions. “The other things we should study are body composition and fluid overload using bioimpedance,” Kotanko said. “I think it will be important to see if patients treated with incremental-start hemodialysis have more, similar or less fluid overload than those treated with upfront three-times-per-week [hemodialysis].”
A second study under way by Veterans Affairs (VA) will compare the safety and efficacy of incremental hemodialysis to standard-of-care, three-times-per-week hemodialysis, similar to the PCORI-funded TwoPlus trial. The VA study, called Incremental Hemodialysis for Veterans in the First Year of Dialysis (IncHVets), will enroll 252 veterans with stage 5 CKD who need to start dialysis treatment and will take place at six VA medical centers.
“By conducting this study, the investigators hope to understand 1) whether starting dialysis with less frequency is safe, effective and can help veterans and their care partners to better cope with dialysis, and 2) if incremental dialysis can result in major cost benefits to the VA health care system, thus allowing more patients to stay in VA dialysis clinics vs. being transferred to outside clinics,” according to a description of the study on clinicaltrials.gov.
Kamyar Kalantar-Zadeh, MD, MPH, PhD, chief of the division of nephrology, hypertension and transplantation, vice chair for research and innovation in the department of medicine, Harbor-UCLA Medical Center and professor of medicine-in-residence at the UCLA David Geffen School of Medicine, told Healio | Nephrology News & Issues that the IncHVets trial will help determine the best approach for maintaining RKF.
“We are not able to create RKF, but we can preserve it longer,” Kalantar-Zadeh, the principal investigator on the VA study, said. “One of the ways to do that is to start patients on less dialysis when more dialysis is not needed.
“It is an interactive relationship,” Kalantar-Zadeh said. “If you make urine, you can do less dialysis; if you do less dialysis, you hopefully make urine longer,” he said.
Nutritional component
Modifications to a patient’s diet can have a positive impact on preserving RKF, Amanda Wetherington, RDN, LDN, a dietitian at DaVita Kidney Care, told Healio | Nephrology News & Issues. “In addition to modifying the quantity and type of protein in the diet, I identify what comorbid conditions patients have that would attribute to the acceleration of chronic kidney disease progression,” Wetherington said.
“I consider what other eating patterns and nutrition recommendations would benefit conditions such as hypertension and diabetes, and partner with the patient to determine where they identify room for improvement.
“Each individual has unique considerations when we take that information and look at how they can put it to use, with the goals being optimized glucose control, weight loss and consistent blood pressures in the therapeutic range,” Wetherington said. “Helping the patient connect these dots will ultimately help stabilize and slow CKD progression because they now have a better handle on the conditions that cause kidney damage.”
Practice guidelines
The kidney community does not offer many resources for clinicians interested in best practices for managing RKF. Anthony J. Bleyer, MD, MS, a professor of nephrology at Wake Forest University School of Medicine, was the lead author on a chapter in UptoDate that provides general guidance and best practices for preserving RKF.
“Many patients starting dialysis have significant RKF,” Bleyer and colleagues wrote. “According to the United States Renal Data System, only 15 [%] of individuals starting dialysis in 2020 had an [eGFR] [less than]5 mL/min/1.73 m2. Preservation of this RKF has been associated with improved outcomes, and nephrologists should try to preserve this RKF as long as possible,” the authors wrote. “However, while RKF is beneficial to patients on dialysis, patients should not be initiated on dialysis earlier to take advantage of more abundant RKF as this has not been associated with improved outcomes.”
Bleyer and colleagues cited several benefits to preserving RKF, including better quality of life, less inflammation, increased responsiveness to drugs to treat anemia, improved nutritional status with fewer dietary restrictions and decreased episodes of pruritus.
“RKF and urinary output are important and beneficial to patients on dialysis,” Bleyer and colleagues wrote. “Increased urinary output allows for more flexibility with fluid intake and less fluid removal with dialysis, resulting in lower rates of hypotension and cramping during hemodialysis. Importantly, among patients on peritoneal dialysis or hemodialysis, continued RKF is associated with improved survival. We therefore suggest the adoption of measures aimed at preserving RKF among patients on peritoneal dialysis and those on hemodialysis.”
Proving that both modality options can benefit from and incorporate RKF is an important step for management of kidney disease in the future, Kotanko said, but data gathering on the impact of the frequency of hemodialysis at its initiation in the PCORI and VA studies is key.
“In 8 to 10 years, we may see that long-term outcomes [from fewer dialysis sessions] are different, beyond those related to RKF. There may be a long-term effect of two- vs. three dialysis sessions,” Kotanko said. “We just don’t know.”
- References:
- Bleyer T, et al. Residual renal function in kidney failure. UptoDate. https://pro.uptodatefree.ir/Show/1941.
- Incremental hemodialysis for veterans in the first year of dialysis (IncHVets). https://classic.clinicaltrials.gov/ct2/show/NCT05465044.
- Okazaki M, et al. Kidney Int Rep. 2023;doi:10.1016/j.ekir.2023.07.020.
- For more information:
- Kamyar Kalantar-Zadeh, MD, PhD, can be reached at kkalantar@lundquist.org.
- Peter Kotanko, MD, FASN, can be reached at peter.kotanko@rriny.com.
- Mariana Murea, MD, can be reached at mariana.murea@wakeforesthealth.org.
- Amanda Wetherington, RDN, LDN, can be reached at amanda.wetherington@davita.com.
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