Patients on nocturnal hemodialysis (NHD) lived just about as long as those who had received a deceased-donor kidney transplant, reported a matched-cohort study published early online by Nephrology Dialysis Transplantation.
“This is the first time that anyone has really been able to demonstrate that a dialysis modality is potentially similar to having received a deceased-donor kidney transplant,” said lead author Robert P. Pauly, MD, MSc, Medical Director of the Home Hemodialysis Program at the University of Alberta, in a phone interview. “That's a huge outcome.”
Robert Lockridge, MD, a clinical ne-phrologist whose Lynchburg, VA, practice has the largest nocturnal home hemodialysis program in the United States, agreed.
“Can you believe it's been since 1991 or ‘2 that…the gold standard [renal replacement therapy] has been transplant, and there's something equal for patients who are not transplanted and for older people who have comorbid issues?…This is really an exciting article,” said Dr. Lockridge, who is also Associate Clinical Professor at the University of Virginia (UVa) and Medical Director of Dialysis Facilities and Home Dialysis Facilities at UVa Lynchburg Dialysis, in a phone interview.
Transplant Recipients Highly Selected
Just because a difference wasn't demonstrated, though, doesn't necessarily mean one doesn't exist, Dr. Pauly cautioned.
Treatment assignment was not random, and follow-up was relatively short, he and colleagues wrote.
“Notwithstanding the fact that we've been able to collect a cohort that is the largest cohort to date worldwide to be applied to this particular problem, and certainly the cohort of the longest duration, there is still a statistical weakness that a difference may exist that we were not able to demonstrate,” Dr. Pauly said.
There is reason to be optimistic about the validity of the results, though. The nocturnal hemodialysis patients were also compared with recipients of a living-donor kidney transplant as an internal control, and the results of that analysis were reassuring, Dr. Pauly noted.
“We thought well we need to at least make sure that the people who receive living donation do better than everybody else because that's what we would all expect to happen. So one important outcome is we confirmed in the context of our study that patients who received a living-donor kidney do better.
“That was an important issue for us. It sort of said we were on the right track—we had some good internal consistency in our data.”
The high level of scrutiny with which the health of transplant candidates is evaluated lends additional credibility to the data, Dr. Lockridge said.
“Every transplant [candidate] has a cardiac evaluation, a colonoscopy, a PSA [prostate-specific antigen test], and if they have any type of coronary artery disease or any risk factors—which they do the longer they are on dialysis—they have all of that repeated.”
In the study, more patients on nocturnal hemodialysis had a history of cancer, peripheral vascular disease, and ischemic heart disease compared with the transplant recipients.
“One of the things that people have said about us doing nocturnal dialysis is we're selecting the people out,” Dr. Lockridge said. “The most selected group is cadaver transplants, so that makes it even better that people [on nocturnal dialysis] are doing equal to cadaver transplants, which suggests the outcomes are equal if not better.”
The study cohort included all 177 patients who were treated between January 1, 1994, and December 31, 2006, in one of two Toronto nocturnal home hemodialysis programs—the program at the Toronto General Hospital or the one at Humber River Regional Hospital—and had never received a kidney transplant.
“For the most part our patients received between four and six nights of dialysis per week, each session lasting between six and eight hours,” Dr. Pauly said.
Demographic and clinical information on these patients were taken from paper and electronic records, as well as from the Toronto Region Dialysis Registry.
Those on nocturnal hemodialysis were randomly matched in a 1:3:3 ratio to patients from the United States Renal Data System (USRDS) who had received a first standard-criteria deceased-donor kidney transplant (n=531) or a living-donor kidney transplant (n=531) during the same time period.
“Some might argue that there may be some minor differences in terms of US versus Canadian patients, and there's really just no other way in which to address that limitation,” Dr. Pauly said. “There are debates as to whether that's a serious limitation or not.”
Patients in the study were matched according to race, diabetic status, and length of time they were treated with conventional dialysis before the initiation of nocturnal dialysis or the receipt of a transplant.
Recipients of a living-donor kidney were slightly younger than those who had received a deceased-donor organ or were on nocturnal dialysis, and fewer women were treated with nocturnal dialysis than with either form of transplantation. The majority of the study patients were white—68%—and 14% had diabetes.
“You're not probably looking at as great a cross-sectional analysis of diabetes and heart disease and race and sex—in the nocturnal group women are not as well represented—so it's a more of a select group in that way, but you're selecting everybody in a fairly large geographical area, so maybe that equals out,” Dr. Lockridge said.
The mean duration of conventional dialysis was 2.5 years for the patients on nocturnal dialysis, 2.4 years for deceased-donor transplant recipients, and 2.2 years for living-donor transplant recipients.
In each group, 14.1% of patients were never on conventional dialysis—they went right on nocturnal dialysis or were preemptively transplanted—and 14.7% of patients in each group were on conventional dialysis for longer than 60 months.
The median duration of follow-up was 3.77 years for nocturnal hemodialysis patients, 4.62 years for deceased-donor transplant recipients, and 4.30 years for living-donor transplant recipients.
Bridge to Transplant
Among patients on nocturnal dialysis, there were 26 deaths (14.7%), compared with 76 deaths (14.3%) among deceased-donor transplant recipients and 45 deaths (8.5%) among living-donor transplant recipients.
In a multivariable analysis, there was no significant difference in risk of death between patients on nocturnal dialysis and recipients of a deceased-donor transplant, while recipients of a living-donor transplant had a significantly higher survival rate.
“We know that patients who are on conventional dialysis do worse in terms of survival than patients who get transplanted,” Dr. Pauly said.
“We also know that the longer you're on conventional dialysis before you ultimately receive a transplant, the worse your outcome is from the transplant, and so one of the kind of tangential implications of this study is that possibly nocturnal dialysis may be a better bridge to transplantation than conventional dialysis.”
The results can also be used to aid medical decision-making, he added.
“It provides more information for patients and their caregivers to make a balanced decision between different treatment modalities.
“We always tend to say you should get a transplant; that would be great. But the reality is not everybody is a good transplant candidate, and this just gives a little more information about a very good alternative for patients who may not be ideal transplant candidates or who may not be transplantable because maybe they've had a history of cancer or they may have other prohibitive medical comorbidities or because they're highly sensitized.”
Other recently published studies in the nephrology literature help to put these findings into context.
“I think it's a very important study for two reasons,” Dr. Lockridge said. “Dr. Kjellstrand presented a year ago his data that goes back into the 80s and had 400 and some odd patients looking at short-daily [dialysis] and at different vintages and at different times [Nephrol Dial Transplantation 2008;23: 3283–3289].
“It showed a similar result, but this study [by Pauly et al] was done quite well, really trying to match people with the same cohort in the [USRDS] database, so I think it's a much cleaner study in a sense.”
Another recent study projected that 46% of patients older than 60 who went on the deceased-donor kidney transplant waiting list between 2006 and 2007 will die while they're waiting, Dr. Lockridge noted [Schold J et al: Clin J Am Soc Nephrol 2009;4:1239–1245].
“I would think that we really should be targeting people who are on a transplant list to do nocturnal dialysis, and I think the paper did suggest that, but it also would suggest that we really should consider or think about even a broader spectrum of people who could do as well as transplant but may have more comorbid events.”
Compare with ECD Transplants
In terms of further research, Dr. Pauly and his colleagues are interested in comparing outcomes for nocturnal dialysis with those for different categories of organ donors, such as extended-criteria donors (ECD).
“That may actually impact the types of decisions that people make if they had on the one hand the possibility of remaining on nocturnal dialysis with a good survival and good quality of life versus considering accepting an extended-criteria donor where we know that the outcomes are not as favorable as compared with receiving a standard–criteria donor,” Dr. Pauly said.
Registries also should be set up in a way that allows patient outcomes to be tracked according to renal replacement modality, Dr. Lockridge said.
“I think that we'll never have enough money and time to do a randomized study. What we've got is what we've got that's going to come out of the NIH [National Institutes of Health] randomized study.” (The Frequent Hemodialysis Network [FHN] is currently conducting two parallel randomized, controlled trials, one in in-center short-daily hemodialysis and one in nocturnal home hemodialysis, sponsored by the NIH's National Institute of Diabetes and Digestive and Kidney Diseases.)
“If we identify those who are doing this we should be able to have some better handle on cost and outcomes,” Dr. Lockridge said.
Real Issue: Uptake
Beyond research, steps also must be taken to increase availability of nocturnal hemodialysis, Dr. Lockridge said.
“I still think that the real issue is uptake. There are about 2,000 people doing three-times-a-week nocturnal dialysis in-center in this country, and there are probably less than 200 people doing the kind of treatment I do in Lynchburg, which is five or more times a week at home doing nocturnal dialysis, so you're really talking about a very small population.
“So is the reason people don't do it even though it may be as good as a transplant…because of fear of going at home? Is it because of technology? I think it's all of the above, but I think that if people are given informed consent I'm finding more and more people are willing to undertake the burden to ultimately end up with a benefit….
“We've got to figure out a way to offer this modality,” Dr. Lockridge said, noting that the dialysis mortality rate in the United States, where 91% of patients are receiving in-center treatment, has only gone down by 2.1% over the last 10 years and still exceeds 20% per year. “I think we've got to realize that there's got to be a better approach than what we're doing.”