Dialysis Delay May Benefit Elderly CKD Patients

NATIONAL HARBOR, MD. – Contrary to current practice trends, evidence suggests that kidney dialysis can – and perhaps should – be delayed in older adults with chronic kidney disease.

"Older adults, like their younger counterparts, should not initiate dialysis on the basis of [estimated glomerular filtration] alone, but can wait to delay dialysis initiation until more traditional clinical indicators appear, such as fluid overload that can’t be managed with diuretics; uremic symptoms which interfere with quality of life; or electrolyte disturbances," said Dr. Manjula Kurella Tamura.

"An individualized approach to these decisions that accounts for the patient’s burden of symptoms and trajectory of kidney function decline is probably wise until more clinical trials are conducted in the older adult population," continued Dr. Tamura of the division of nephrology at Stanford (Calif.) University.

Two striking patterns have emerged over time. First, in all age groups, dialysis is being initiated at a higher estimated glomerular filtration rate (eGFR) today, compared with a decade ago, which is generally viewed as representing earlier initiation of dialysis over time (Kidney Int. 2009;76:257-61).

Secondl older patients are initiating dialysis earlier in the course of kidney disease than are younger patients. This was true one decade ago and is even more so today, when more than 50% of patients older than age 75 years begin dialysis with an eGFR greater than 10 mL/min per 1.73 m² (Arch. Intern. Med. 2011;171:1663-9).

One rationale often cited for starting older patients on dialysis sooner is that they have a lower tolerance for uremia. However, Dr. Tamura said, "I looked back through the literature to find out where this idea came from. It certainly has a lot of face validity, but is there evidence that it’s true? I couldn’t find it. I just kept seeing it repeated over and over, that older patients need to start sooner. But I couldn’t find an explanation."

And in fact, increasing evidence suggests that the opposite may be true. In one study of 112 adults older than age 75 with GFR of 5-7 mL/min, there were no differences in survival between those who were randomized to dialysis or those on a very low protein diet with delayed dialysis initiation (median follow-up, 26.5 months). There also were no differences between the two groups in the causes of death, and there were actually fewer hospitalizations and total hospital days in the diet group (Am. J. Kidney Dis. 2007;49:569-80).

That study excluded patients with diabetes, an ejection fraction less than 30%, urine protein excretion greater than 3 g/day, active malignancy, and uremic symptoms, she noted.

Subsequently, the multicenter IDEAL (Initiating Dialysis Early and Late) study was conducted in Australia and New Zealand, in which 828 adults (mean age, 60 years) with progressive chronic kidney disease were randomized to "early start" of dialysis, with planned initiation when eGFR was 10.0-14.0 mL/min, or "late start," at eGFR of 5.0-7.0 mL/min. Earlier initiation of dialysis was permitted based on the discretion of the treating physician (N. Engl. J. Med. 2010;363:609-19).

Owing to the development of symptoms, 75% of the "late start" group was initiated on dialysis with an eGFR of greater than 7.0 mL/min, with a mean of 9.8 mL/min and a median delay of 6 months, compared with the "early start" group, who initiated dialysis with a mean eGFR of 12 mL/min. There were no differences in survival between the early and late groups (median follow-up, 3.6 years). Subgroup analysis showed that there also were no differences between the early vs. late groups among patients older than 60 years, Dr. Tamura said.

The IDEAL authors concluded that "with careful clinical management, dialysis may be delayed until either the GFR drops below 7 mL/min or more traditional clinical indicators for the initiation of dialysis are present."

However, the question of whether the IDEAL findings can be applied to older patients prompted controversy, given that the patients included in the study were younger than the overall dialysis population and relatively healthy, and therefore less susceptible to the potential complications of later initiation of dialysis (N. Engl. J. Med. 2010;363:2368).

To address that issue, Dr. Tamura and her associates retrospectively examined the timing of initiation of dialysis in a population of 2,402 nursing home residents who initiated dialysis in 1998-2000. The median eGFR at the time of dialysis initiation was 9.8 mL/min. The likelihood of earlier dialysis initiation (eGFR of 15 mL/min or greater) was associated with having one or more signs and symptoms of volume overload, cognitive decline, increased dependence in activities of daily living, and weight loss. However, those factors altogether accounted for only 31% of the early dialysis initiations (Am. J. Kidney Dis. 2010;56:1117-26).

"Certainly, the factors that contribute to early dialysis initiation are complex and may not always be clinical. But again, it makes you think that perhaps some of these patients are not started early because they have symptoms, but for other reasons, and perhaps it’s just the nervousness of the nephrologist caring for a very frail patient," she commented.

Indeed, urgent indications accounted for just 10% of the patients in the late-start arm of the IDEAL study who ended up initiating dialysis at greater than the target eGFR, with "uremia" and "physician discretion" accounting for 80%. However, Dr. Tamura pointed out, the uremic syndrome can be difficult to diagnose in elderly patients with other chronic conditions. No biomarker is sufficiently specific, and symptoms of uremia can overlap with other conditions. For example, nausea may result from diabetic gastroparesis, fatigue may be from cardiopulmonary disease or depression, and cognitive impairment might be cause by medications or dementia.

Moreover, conditions commonly observed in advanced chronic kidney disease – such as malnutrition, low functional status, pruritis, and restless leg syndrome – not always improve with dialysis initiation.

Also complicating the decision of when to initiate dialysis in the elderly is the fact that estimated equations for GFR tend to be less accurate in the elderly due to sarcopenia and fluid retention, and that acute kidney injury is more common in older patients, she said.

Given all this, Dr. Tamura advises that it is appropriate to delay dialysis initiation in older asymptomatic adults with an eGFR greater than 10 mL/min. As for when it is appropriate to initiate dialysis, "there are still more questions than answers. Clinical judgment will continue to guide practice, but hopefully symptom burden and patient preferences will have a stronger influence."

Dr. Tamura reported having no conflicts of interest.

NATIONAL HARBOR, MD. – Contrary to current practice trends, evidence suggests that kidney dialysis can – and perhaps should – be delayed in older adults with chronic kidney disease.

"Older adults, like their younger counterparts, should not initiate dialysis on the basis of [estimated glomerular filtration] alone, but can wait to delay dialysis initiation until more traditional clinical indicators appear, such as fluid overload that can’t be managed with diuretics; uremic symptoms which interfere with quality of life; or electrolyte disturbances," said Dr. Manjula Kurella Tamura.

"An individualized approach to these decisions that accounts for the patient’s burden of symptoms and trajectory of kidney function decline is probably wise until more clinical trials are conducted in the older adult population," continued Dr. Tamura of the division of nephrology at Stanford (Calif.) University.

Two striking patterns have emerged over time. First, in all age groups, dialysis is being initiated at a higher estimated glomerular filtration rate (eGFR) today, compared with a decade ago, which is generally viewed as representing earlier initiation of dialysis over time (Kidney Int. 2009;76:257-61).

Secondl older patients are initiating dialysis earlier in the course of kidney disease than are younger patients. This was true one decade ago and is even more so today, when more than 50% of patients older than age 75 years begin dialysis with an eGFR greater than 10 mL/min per 1.73 m² (Arch. Intern. Med. 2011;171:1663-9).

One rationale often cited for starting older patients on dialysis sooner is that they have a lower tolerance for uremia. However, Dr. Tamura said, "I looked back through the literature to find out where this idea came from. It certainly has a lot of face validity, but is there evidence that it’s true? I couldn’t find it. I just kept seeing it repeated over and over, that older patients need to start sooner. But I couldn’t find an explanation."

And in fact, increasing evidence suggests that the opposite may be true. In one study of 112 adults older than age 75 with GFR of 5-7 mL/min, there were no differences in survival between those who were randomized to dialysis or those on a very low protein diet with delayed dialysis initiation (median follow-up, 26.5 months). There also were no differences between the two groups in the causes of death, and there were actually fewer hospitalizations and total hospital days in the diet group (Am. J. Kidney Dis. 2007;49:569-80).

That study excluded patients with diabetes, an ejection fraction less than 30%, urine protein excretion greater than 3 g/day, active malignancy, and uremic symptoms, she noted.

Subsequently, the multicenter IDEAL (Initiating Dialysis Early and Late) study was conducted in Australia and New Zealand, in which 828 adults (mean age, 60 years) with progressive chronic kidney disease were randomized to "early start" of dialysis, with planned initiation when eGFR was 10.0-14.0 mL/min, or "late start," at eGFR of 5.0-7.0 mL/min. Earlier initiation of dialysis was permitted based on the discretion of the treating physician (N. Engl. J. Med. 2010;363:609-19).

Owing to the development of symptoms, 75% of the "late start" group was initiated on dialysis with an eGFR of greater than 7.0 mL/min, with a mean of 9.8 mL/min and a median delay of 6 months, compared with the "early start" group, who initiated dialysis with a mean eGFR of 12 mL/min. There were no differences in survival between the early and late groups (median follow-up, 3.6 years). Subgroup analysis showed that there also were no differences between the early vs. late groups among patients older than 60 years, Dr. Tamura said.

The IDEAL authors concluded that "with careful clinical management, dialysis may be delayed until either the GFR drops below 7 mL/min or more traditional clinical indicators for the initiation of dialysis are present."

However, the question of whether the IDEAL findings can be applied to older patients prompted controversy, given that the patients included in the study were younger than the overall dialysis population and relatively healthy, and therefore less susceptible to the potential complications of later initiation of dialysis (N. Engl. J. Med. 2010;363:2368).

To address that issue, Dr. Tamura and her associates retrospectively examined the timing of initiation of dialysis in a population of 2,402 nursing home residents who initiated dialysis in 1998-2000. The median eGFR at the time of dialysis initiation was 9.8 mL/min. The likelihood of earlier dialysis initiation (eGFR of 15 mL/min or greater) was associated with having one or more signs and symptoms of volume overload, cognitive decline, increased dependence in activities of daily living, and weight loss. However, those factors altogether accounted for only 31% of the early dialysis initiations (Am. J. Kidney Dis. 2010;56:1117-26).

"Certainly, the factors that contribute to early dialysis initiation are complex and may not always be clinical. But again, it makes you think that perhaps some of these patients are not started early because they have symptoms, but for other reasons, and perhaps it’s just the nervousness of the nephrologist caring for a very frail patient," she commented.

Indeed, urgent indications accounted for just 10% of the patients in the late-start arm of the IDEAL study who ended up initiating dialysis at greater than the target eGFR, with "uremia" and "physician discretion" accounting for 80%. However, Dr. Tamura pointed out, the uremic syndrome can be difficult to diagnose in elderly patients with other chronic conditions. No biomarker is sufficiently specific, and symptoms of uremia can overlap with other conditions. For example, nausea may result from diabetic gastroparesis, fatigue may be from cardiopulmonary disease or depression, and cognitive impairment might be cause by medications or dementia.

Moreover, conditions commonly observed in advanced chronic kidney disease – such as malnutrition, low functional status, pruritis, and restless leg syndrome – not always improve with dialysis initiation.

Also complicating the decision of when to initiate dialysis in the elderly is the fact that estimated equations for GFR tend to be less accurate in the elderly due to sarcopenia and fluid retention, and that acute kidney injury is more common in older patients, she said.

Given all this, Dr. Tamura advises that it is appropriate to delay dialysis initiation in older asymptomatic adults with an eGFR greater than 10 mL/min. As for when it is appropriate to initiate dialysis, "there are still more questions than answers. Clinical judgment will continue to guide practice, but hopefully symptom burden and patient preferences will have a stronger influence."

Dr. Tamura reported having no conflicts of interest.

NATIONAL HARBOR, MD. – Contrary to current practice trends, evidence suggests that kidney dialysis can – and perhaps should – be delayed in older adults with chronic kidney disease.

"Older adults, like their younger counterparts, should not initiate dialysis on the basis of [estimated glomerular filtration] alone, but can wait to delay dialysis initiation until more traditional clinical indicators appear, such as fluid overload that can’t be managed with diuretics; uremic symptoms which interfere with quality of life; or electrolyte disturbances," said Dr. Manjula Kurella Tamura.

"An individualized approach to these decisions that accounts for the patient’s burden of symptoms and trajectory of kidney function decline is probably wise until more clinical trials are conducted in the older adult population," continued Dr. Tamura of the division of nephrology at Stanford (Calif.) University.

Two striking patterns have emerged over time. First, in all age groups, dialysis is being initiated at a higher estimated glomerular filtration rate (eGFR) today, compared with a decade ago, which is generally viewed as representing earlier initiation of dialysis over time (Kidney Int. 2009;76:257-61).

Secondl older patients are initiating dialysis earlier in the course of kidney disease than are younger patients. This was true one decade ago and is even more so today, when more than 50% of patients older than age 75 years begin dialysis with an eGFR greater than 10 mL/min per 1.73 m² (Arch. Intern. Med. 2011;171:1663-9).

One rationale often cited for starting older patients on dialysis sooner is that they have a lower tolerance for uremia. However, Dr. Tamura said, "I looked back through the literature to find out where this idea came from. It certainly has a lot of face validity, but is there evidence that it’s true? I couldn’t find it. I just kept seeing it repeated over and over, that older patients need to start sooner. But I couldn’t find an explanation."

And in fact, increasing evidence suggests that the opposite may be true. In one study of 112 adults older than age 75 with GFR of 5-7 mL/min, there were no differences in survival between those who were randomized to dialysis or those on a very low protein diet with delayed dialysis initiation (median follow-up, 26.5 months). There also were no differences between the two groups in the causes of death, and there were actually fewer hospitalizations and total hospital days in the diet group (Am. J. Kidney Dis. 2007;49:569-80).

That study excluded patients with diabetes, an ejection fraction less than 30%, urine protein excretion greater than 3 g/day, active malignancy, and uremic symptoms, she noted.

Subsequently, the multicenter IDEAL (Initiating Dialysis Early and Late) study was conducted in Australia and New Zealand, in which 828 adults (mean age, 60 years) with progressive chronic kidney disease were randomized to "early start" of dialysis, with planned initiation when eGFR was 10.0-14.0 mL/min, or "late start," at eGFR of 5.0-7.0 mL/min. Earlier initiation of dialysis was permitted based on the discretion of the treating physician (N. Engl. J. Med. 2010;363:609-19).

Owing to the development of symptoms, 75% of the "late start" group was initiated on dialysis with an eGFR of greater than 7.0 mL/min, with a mean of 9.8 mL/min and a median delay of 6 months, compared with the "early start" group, who initiated dialysis with a mean eGFR of 12 mL/min. There were no differences in survival between the early and late groups (median follow-up, 3.6 years). Subgroup analysis showed that there also were no differences between the early vs. late groups among patients older than 60 years, Dr. Tamura said.

The IDEAL authors concluded that "with careful clinical management, dialysis may be delayed until either the GFR drops below 7 mL/min or more traditional clinical indicators for the initiation of dialysis are present."

However, the question of whether the IDEAL findings can be applied to older patients prompted controversy, given that the patients included in the study were younger than the overall dialysis population and relatively healthy, and therefore less susceptible to the potential complications of later initiation of dialysis (N. Engl. J. Med. 2010;363:2368).

To address that issue, Dr. Tamura and her associates retrospectively examined the timing of initiation of dialysis in a population of 2,402 nursing home residents who initiated dialysis in 1998-2000. The median eGFR at the time of dialysis initiation was 9.8 mL/min. The likelihood of earlier dialysis initiation (eGFR of 15 mL/min or greater) was associated with having one or more signs and symptoms of volume overload, cognitive decline, increased dependence in activities of daily living, and weight loss. However, those factors altogether accounted for only 31% of the early dialysis initiations (Am. J. Kidney Dis. 2010;56:1117-26).

"Certainly, the factors that contribute to early dialysis initiation are complex and may not always be clinical. But again, it makes you think that perhaps some of these patients are not started early because they have symptoms, but for other reasons, and perhaps it’s just the nervousness of the nephrologist caring for a very frail patient," she commented.

Indeed, urgent indications accounted for just 10% of the patients in the late-start arm of the IDEAL study who ended up initiating dialysis at greater than the target eGFR, with "uremia" and "physician discretion" accounting for 80%. However, Dr. Tamura pointed out, the uremic syndrome can be difficult to diagnose in elderly patients with other chronic conditions. No biomarker is sufficiently specific, and symptoms of uremia can overlap with other conditions. For example, nausea may result from diabetic gastroparesis, fatigue may be from cardiopulmonary disease or depression, and cognitive impairment might be cause by medications or dementia.

Moreover, conditions commonly observed in advanced chronic kidney disease – such as malnutrition, low functional status, pruritis, and restless leg syndrome – not always improve with dialysis initiation.

Also complicating the decision of when to initiate dialysis in the elderly is the fact that estimated equations for GFR tend to be less accurate in the elderly due to sarcopenia and fluid retention, and that acute kidney injury is more common in older patients, she said.

Given all this, Dr. Tamura advises that it is appropriate to delay dialysis initiation in older asymptomatic adults with an eGFR greater than 10 mL/min. As for when it is appropriate to initiate dialysis, "there are still more questions than answers. Clinical judgment will continue to guide practice, but hopefully symptom burden and patient preferences will have a stronger influence."

Dr. Tamura reported having no conflicts of interest.