Accounting for untreated in addition to treated kidney failure narrows the difference in kidney disease progression rates between older and younger adults, reported a retrospective cohort study of about 1.8 million participants in Alberta, Canada.
In the study, younger individuals were more likely to progress to treated kidney failure than older individuals were, as previous research had reported, but older participants were more likely than younger participants to develop untreated kidney failure, defined as estimated glomerular filtration rate (eGFR) less than 15 mL/min/1.73 m2 without renal replacement therapy. These results were published in the Journal of the American Medical Association (JAMA 2012;307:2507–2515).
The implications of reduced kidney function in older adults have been a source of debate in the nephrology field, and this analysis offers new data to inform the discussion and the way forward.
“Studies of the association among age, kidney function, and clinical outcomes have reported that elderly patients are less likely to develop end-stage renal disease compared with younger patients and are more likely to die than to progress to kidney failure, even at the lowest levels of estimated glomerular filtration rate,” said lead author Brenda R. Hemmelgarn, MD, PhD, Associate Professor at the University of Calgary in Calgary, Alberta.
“I think this study tells us that it is time to be aware that older adults can progress, and this presents an opportunity to undertake a shared decision-making process with the patient, the medical team, and the family. It's really about having an informed discussion about the potential treatment options.”
Treated vs. Untreated
Dr. Hemmelgarn has had a long-standing interest in kidney disease in older adults and was “a little bit surprised” by previous findings on disease progression in this population, she said. “I wanted to explore that in greater detail.”
In order to do that, Dr. Hemmelgarn and her team studied a cohort of 1,816,824 adults from Alberta who had at least one outpatient serum creatinine measurement between May 2002 and March 2008. Baseline eGFR was at least 15 mL/min/1.73 m2, and participants did not require renal replacement therapy at the beginning of the study.
The cohort members were divided into the following age categories: 18 to 44, 45 to 54, 55 to 64, 65 to 74, 75 to 84, and 85 and older. Estimated glomerular filtration rate was categorized as 90 or higher, 60 to 89, 45 to 59, 30 to 44, and 15 to 29 mL/min/1.73 m2.
The main outcome measures were adjusted rates of treated kidney failure, defined as initiation of long-term dialysis or receipt of a kidney transplant; untreated kidney failure, defined as progression to an eGFR less than 15 mL/min/1.73 m2 without dialysis therapy or a kidney transplant; and death.
During a median follow-up of 4.4 years, 97,451 (5.36%) of study participants died, 3,295 (0.18%) progressed to treated kidney failure, and 3,116 (0.17%) developed untreated kidney failure. Within each eGFR stratum, adjusted rates of death rose with increasing age.
Treated kidney failure, however, was more common among the youngest age group in each eGFR category. In the lowest eGFR stratum (15–29 mL/min/1.73 m2), rates of treated kidney failure were about 10-fold higher among the youngest (18–44) compared with the oldest (85 and older) age group, with adjusted rates of 24.00 and 1.53 per 1,000 person-years, respectively.
Untreated kidney failure, on the other hand, was seen consistently more often in older individuals. In the 15–29 mL/min/1.73 m2 eGFR category, the adjusted rates of untreated kidney failure were about fivefold higher among individuals 85 and older compared with those 18–44—19.95 versus 3.53 per 1,000 person-years.
Kidney failure rates showed less variation across age groups when treated and untreated patients were considered together.
Among participants with an eGFR 15–29 mL/min/1.73 m2, the adjusted rate of treated or untreated kidney failure per 1,000 person-years was 36.45 for those age 18 to 44 and 20.19 for those age 85 or older.
Untreated kidney failure specifically refers to the absence of renal replacement therapy, Dr. Hemmelgarn emphasized. “This does not mean that they weren't receiving other types of treatments,” she said.
The study was supported by the Canadian Institutes of Health Research and by an interdisciplinary team grant from Alberta Innovates–Health Solutions.
In an accompanying editorial, Manjula Kurella Tamura, MD, MPH, and Wolfgang C. Winkelmayer, MD, MPH, ScD, both from Stanford University School of Medicine, wrote, “In conclusion, the work by Hemmelgarn and colleagues highlights a potentially sizeable unmeasured burden of untreated kidney failure among older adults” (JAMA 2012;307:2545–2546).
The editorial authors agreed that the magnitude of untreated kidney failure among older adults does not necessarily imply inappropriate withholding of treatment. The study did not provide information on the alternative treatments patients might have received.
An important limitation of the analysis was the absence of details on why kidney failure went “untreated,” said Rebecca Schmidt, DO, of West Virginia University School of Medicine.
“When you use the word ‘untreated,’ it suggests that there is something volitional, whether on the part of the patient or a directive on the part of the nephrologist, and we just don't know from this paper.”
The best thing about the study, on the other hand, is that it brings to light the very important issue of how kidney failure is currently handled in older adults, she added.
“This study highlights the need to promote and recognize the importance of a shared decision-making process and that starting or not starting patients on dialysis needs to be a deliberate decision,” Dr. Schmidt said. “The study also highlights the need to have an age-attuned approach or an individualized, patient-centered approach for patients at this stage of the game with CKD [chronic kidney disease].”
Richard J. Glassock, MD, Emeritus Professor at the David Geffen School of Medicine at UCLA, praised the study because “it provides new data that were not previously available,” he said in an interview.
However, it may not be appropriate to apply these data from Canada directly to the experience in the United States, he added.
“It may be that the doctors in Canada have decided that dialysis doesn't really help people who are very old and who have end-stage renal failure, and they prefer to treat them conservatively, rather than with dialysis.
“There is substantial evidence that if you're frail, elderly, in a nursing home or receiving institutional care, and you happen to have end-stage renal failure, dialysis does very little to improve either your quality of life or your life expectancy, so it may be that the Canadian doctors have decided it's just not worth it even though the patients have access to it and it could be paid for.”
Striking the Right Balance
Other studies, such as a survey conducted by Sara N. Davison, MD, that also happened to focus on dialysis patients from Alberta (Clin J Am Soc Nephrol 2010;5:195–204), have shown that most patients with kidney failure prefer less aggressive treatment if it means decreased pain or discomfort, noted Daniel E. Weiner, MD, MS, a nephrologist at Tufts Medical Center. “The majority of the 584 patients surveyed regretted their decision to initiate dialysis,” he said, referring to Dr. Davison's study.
The nephrology community needs to better understand who is and who is not being offered dialysis, who is and is not electing dialysis, and the reasons behind these differences, Dr. Weiner suggested.
“Is there adequate patient and family education as patients progress across the stages of chronic kidney disease, or are these end-of-life discussions occurring for the first time in rushed and pressured situations?” he said.
“There are ample data that dialysis is not the optimal treatment of kidney failure for everyone with kidney failure, particularly in the elderly where both conservative therapy and also later start of kidney replacement therapy may be associated with better outcomes for many patients.”
It's time to refine the current understanding of what constitutes appropriate management of kidney failure, the editorial authors noted.
“Finding the right balance between overtreatment and undertreatment is challenging but necessary,” they wrote. “This important scientific and ethical debate can no longer be avoided, for both individual and societal good.”