Early Dialysis Linked to Greater 1-Year Mortality

Although the use of early hemodialysis in relatively young and healthy end-stage renal disease patients has more than doubled since 1996, that practice may have increased their 1-year mortality risk, new research suggests.

The findings, together with those of several other studies of the issue, indicate that early hemodialysis – begun when the estimated glomerular filtration rate (eGFR) is still 10 mL/minute per 1.73 m

According to U.S. Renal Data System (USRDS) records, the proportion of patients initiating hemodialysis early rose from 20% to 52% between 1996 and 2008, even though there is no evidence of substantial benefit with the practice. In fact, nine recent studies have reported a survival disadvantage with early hemodialysis.

Critics of those studies say that earlier hemodialysis makes intuitive sense, and that the high rates of comorbidities and older age in most study subjects confounded the results. To “reduce or eliminate much of the selection biases and lessen the need for multiple adjustments for comorbid conditions that confounded earlier studies,” Dr. Rosansky and his colleagues undertook a large observational study restricted to the Medicare records of 81,176 relatively young ESRD patients (aged 20-64 years) who had no comorbidities other than hypertension.

In that healthy cohort, mortality in the first year after the start of hemodialysis was 9.4%, compared with an average 24% 1-year mortality in the entire USRDS population.

The investigators said that 1-year mortality was 20.1% in patients who started hemodialysis early, compared with 6.8% in those who started later.

Patients with the lowest albumin levels (less than 2.5 g/dL) were five times as likely to die in the first year of hemodialysis as were patients with the highest albumin levels (at least 3.5 g/dL), at 21% vs. 4.7%, respectively.

Among the healthiest group (albumin level at least 3.5 g/dL), those patients with an eGFR of at least 15 were 3.5 times as likely to die as were those with an eGFR of less than 5 (1-year mortality rates of 12.5% vs. 3.6%, respectively).

It is possible that the poorer survival might be related to fewer competing factors for mortality in those young and relatively healthy patients, the researchers noted.

Alternatively, relatively healthy patients with a higher eGFR at the start of hemodialysis “might have been more susceptible to potential harm from the hemodialysis procedure,” the investigators said.

The authors replicated their analyses using serum creatinine values rather than eGFR as a measure of kidney function, “and the results were the same; ostensibly, better kidney function … was associated with higher mortality,” they added.

A potential limitation of the study was the fact that it was based on registry data. Approximately one-third of the subjects in the study who were listed as having no comorbidities were missing one or more laboratory values corroborating that classification. However, separate analysis excluding that group produced the same result as with the entire study cohort.

The mechanism by which earlier hemodialysis may raise 1-year mortality is not yet known. “Possible mechanisms might include recurrent episodes of myocardial ischemia and 'stunning,' and eventual functional and structural changes with fixed systolic dysfunction induced by conventional thrice-weekly hemodialysis,” Dr. Rosansky and his associates said.

In addition, research has shown that endogenous renal function provides a survival benefit over hemodialytic clearance, and more than half of endogenous renal function can be lost during the first months of hemodialysis therapy, they noted.

The results of the study, together with those of other studies, “provide evidence questioning the trend to early start of hemodialysis,” the investigators said. “Initiation of hemodialysis should not be based on an arbitrary level of eGFR or serum creatinine level unless this measure is accompanied by definitive end-stage renal failure-related indications for hemodialysis.”

One of Dr. Rosansky's associates reported ties to numerous industry sources.

Although the use of early hemodialysis in relatively young and healthy end-stage renal disease patients has more than doubled since 1996, that practice may have increased their 1-year mortality risk, new research suggests.

The findings, together with those of several other studies of the issue, indicate that early hemodialysis – begun when the estimated glomerular filtration rate (eGFR) is still 10 mL/minute per 1.73 m

According to U.S. Renal Data System (USRDS) records, the proportion of patients initiating hemodialysis early rose from 20% to 52% between 1996 and 2008, even though there is no evidence of substantial benefit with the practice. In fact, nine recent studies have reported a survival disadvantage with early hemodialysis.

Critics of those studies say that earlier hemodialysis makes intuitive sense, and that the high rates of comorbidities and older age in most study subjects confounded the results. To “reduce or eliminate much of the selection biases and lessen the need for multiple adjustments for comorbid conditions that confounded earlier studies,” Dr. Rosansky and his colleagues undertook a large observational study restricted to the Medicare records of 81,176 relatively young ESRD patients (aged 20-64 years) who had no comorbidities other than hypertension.

In that healthy cohort, mortality in the first year after the start of hemodialysis was 9.4%, compared with an average 24% 1-year mortality in the entire USRDS population.

The investigators said that 1-year mortality was 20.1% in patients who started hemodialysis early, compared with 6.8% in those who started later.

Patients with the lowest albumin levels (less than 2.5 g/dL) were five times as likely to die in the first year of hemodialysis as were patients with the highest albumin levels (at least 3.5 g/dL), at 21% vs. 4.7%, respectively.

Among the healthiest group (albumin level at least 3.5 g/dL), those patients with an eGFR of at least 15 were 3.5 times as likely to die as were those with an eGFR of less than 5 (1-year mortality rates of 12.5% vs. 3.6%, respectively).

It is possible that the poorer survival might be related to fewer competing factors for mortality in those young and relatively healthy patients, the researchers noted.

Alternatively, relatively healthy patients with a higher eGFR at the start of hemodialysis “might have been more susceptible to potential harm from the hemodialysis procedure,” the investigators said.

The authors replicated their analyses using serum creatinine values rather than eGFR as a measure of kidney function, “and the results were the same; ostensibly, better kidney function … was associated with higher mortality,” they added.

A potential limitation of the study was the fact that it was based on registry data. Approximately one-third of the subjects in the study who were listed as having no comorbidities were missing one or more laboratory values corroborating that classification. However, separate analysis excluding that group produced the same result as with the entire study cohort.

The mechanism by which earlier hemodialysis may raise 1-year mortality is not yet known. “Possible mechanisms might include recurrent episodes of myocardial ischemia and 'stunning,' and eventual functional and structural changes with fixed systolic dysfunction induced by conventional thrice-weekly hemodialysis,” Dr. Rosansky and his associates said.

In addition, research has shown that endogenous renal function provides a survival benefit over hemodialytic clearance, and more than half of endogenous renal function can be lost during the first months of hemodialysis therapy, they noted.

The results of the study, together with those of other studies, “provide evidence questioning the trend to early start of hemodialysis,” the investigators said. “Initiation of hemodialysis should not be based on an arbitrary level of eGFR or serum creatinine level unless this measure is accompanied by definitive end-stage renal failure-related indications for hemodialysis.”

One of Dr. Rosansky's associates reported ties to numerous industry sources.

Although the use of early hemodialysis in relatively young and healthy end-stage renal disease patients has more than doubled since 1996, that practice may have increased their 1-year mortality risk, new research suggests.

The findings, together with those of several other studies of the issue, indicate that early hemodialysis – begun when the estimated glomerular filtration rate (eGFR) is still 10 mL/minute per 1.73 m

According to U.S. Renal Data System (USRDS) records, the proportion of patients initiating hemodialysis early rose from 20% to 52% between 1996 and 2008, even though there is no evidence of substantial benefit with the practice. In fact, nine recent studies have reported a survival disadvantage with early hemodialysis.

Critics of those studies say that earlier hemodialysis makes intuitive sense, and that the high rates of comorbidities and older age in most study subjects confounded the results. To “reduce or eliminate much of the selection biases and lessen the need for multiple adjustments for comorbid conditions that confounded earlier studies,” Dr. Rosansky and his colleagues undertook a large observational study restricted to the Medicare records of 81,176 relatively young ESRD patients (aged 20-64 years) who had no comorbidities other than hypertension.

In that healthy cohort, mortality in the first year after the start of hemodialysis was 9.4%, compared with an average 24% 1-year mortality in the entire USRDS population.

The investigators said that 1-year mortality was 20.1% in patients who started hemodialysis early, compared with 6.8% in those who started later.

Patients with the lowest albumin levels (less than 2.5 g/dL) were five times as likely to die in the first year of hemodialysis as were patients with the highest albumin levels (at least 3.5 g/dL), at 21% vs. 4.7%, respectively.

Among the healthiest group (albumin level at least 3.5 g/dL), those patients with an eGFR of at least 15 were 3.5 times as likely to die as were those with an eGFR of less than 5 (1-year mortality rates of 12.5% vs. 3.6%, respectively).

It is possible that the poorer survival might be related to fewer competing factors for mortality in those young and relatively healthy patients, the researchers noted.

Alternatively, relatively healthy patients with a higher eGFR at the start of hemodialysis “might have been more susceptible to potential harm from the hemodialysis procedure,” the investigators said.

The authors replicated their analyses using serum creatinine values rather than eGFR as a measure of kidney function, “and the results were the same; ostensibly, better kidney function … was associated with higher mortality,” they added.

A potential limitation of the study was the fact that it was based on registry data. Approximately one-third of the subjects in the study who were listed as having no comorbidities were missing one or more laboratory values corroborating that classification. However, separate analysis excluding that group produced the same result as with the entire study cohort.

The mechanism by which earlier hemodialysis may raise 1-year mortality is not yet known. “Possible mechanisms might include recurrent episodes of myocardial ischemia and 'stunning,' and eventual functional and structural changes with fixed systolic dysfunction induced by conventional thrice-weekly hemodialysis,” Dr. Rosansky and his associates said.

In addition, research has shown that endogenous renal function provides a survival benefit over hemodialytic clearance, and more than half of endogenous renal function can be lost during the first months of hemodialysis therapy, they noted.

The results of the study, together with those of other studies, “provide evidence questioning the trend to early start of hemodialysis,” the investigators said. “Initiation of hemodialysis should not be based on an arbitrary level of eGFR or serum creatinine level unless this measure is accompanied by definitive end-stage renal failure-related indications for hemodialysis.”

One of Dr. Rosansky's associates reported ties to numerous industry sources.