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Separate research groups offer two new methods for predicting which patients with chronic kidney disease are likely to progress to end-stage renal disease and other complications, according to studies published in the April 20 issue of JAMA.
Ultimately, the methods could help more accurately identify individuals who are at low and high risk for CKD progression, and allow for more appropriate use of health care resources for this population.
In the first report, a "triple-marker" approach using serum creatinine, serum cystatin C, and albuminuria levels yielded more accurate risk prediction than is achieved with current staging systems that are based primarily on creatinine-estimated glomerular filtration rates, said Dr. Carmen A. Peralta of the San Francisco VA Medical Center and her associates.
They assessed the triple-marker technique using a large, population-based cohort of adults (aged 45 years and older) who were participating in a stroke study. A subgroup of 26,643 of these subjects had undergone evaluation of kidney function as part of that study.
Patients in Dr. Peralta’s analysis had a mean age of 65 years. In all, 40% were black, more than half were women, 21% had diabetes, and 59% had hypertension. During a median follow-up of approximately 5 years, 177 subjects developed end-stage renal disease (ESRD) and 1,940 died of all causes.
Adding either the cystatin C or the albuminuria measures to creatinine-based estimated GFR greatly improved the ability to predict the development of ESRD as well as mortality. Using all three measures together improved it even further.
The rate of ESRD was 103-fold higher in subjects who were identified as being at risk via the triple-marker method than in those who were identified via creatinine level alone. Similarly, mortality was nearly eight times higher among those identified as being at risk via the triple-marker method than in those identified via creatinine level alone, the investigators said (JAMA 2011;305:1545-52).
Moreover, one in six subjects who were found to have CKD by the triple-marker method were not identified at all by creatinine level alone, suggesting that people could have occult CKD that would not be diagnosed according to standard methods.
In addition, 25% of subjects who were labeled as having CKD by creatinine-based GFR estimate alone were found not to have CKD when cystatin C and albuminuria levels were added into the risk stratification. This suggests that one-fourth of people screened by standard methods alone may be treated as though they’re at increased risk of ESRD or death when they are not.
Thus, using the triple-marker method "could both reduce unwarranted referrals and unnecessary work-ups for low-risk individuals and would prioritize specialty care and interventions to individuals at highest risk," Dr. Peralta and her colleagues said.
"Several groups are currently advocating new international guidelines that more accurately reflect prognosis of CKD and have proposed adding [albumin:creatinine ratio] to staging of CKD. Our results suggest that a triple-marker approach using both [albuminuria] and cystatin C to confirm CKD more accurately discriminates prognosis for death and progression to ESRD than creatinine and [albuminuria] alone," they added.
In the second report, investigators developed seven possible models for predicting CKD progression, using various combinations of more than 20 candidate variables that are known to affect renal function. To do so, they first assessed these variables in a Canadian cohort of 3,449 adults who were treated at nephrology clinics for stage 3-5 CKD.
These study subjects, who were followed from 2001 through 2008, helped determine which variables were best associated with CKD progression, said Dr. Navdeep Tangri of Tufts Medical Center, Boston, and his associates.
One of the seven models was particularly accurate at predicting CKD progression. It factored in patient age and sex, as well as the estimated GFR, albuminuria, serum calcium, serum phosphate, serum bicarbonate, and serum albumin levels. These are basic laboratory measurements "that are obtained routinely in patients with CKD," Dr. Tangri and his colleagues said (JAMA 2011;305:1553-9).
All seven models were tested in a validation cohort of 4,942 patients in a British Columbia registry who had stage 3-5 CKD. The same model was found to be the most accurate in predicting disease progression in that cohort.
"Using our models, lower-risk patients could be managed by the primary care physician without additional testing or treatment of CKD complications," whereas higher-risk patients could receive "more intensive testing, intervention, and early nephrology care," they said.
The models also could be used to triage patients with stage 4 CKD "regarding dialysis education, creation of vascular access, and preemptive transplantation"; to select stage 3 patients for public health interventions; and to select high-risk patients for enrollment in clinical trials, the researchers added.
Dr. Peralta’s study was supported by the National Institute of Neurological Disorders and Stroke, Amgen Corp., the National Institute of Diabetes and Digestive and Kidney Diseases, the Robert Wood Johnson Foundation, and the American Heart Association. Several associates also reported ties to Amgen. Dr. Tangri’s study was supported by a joint initiative of the Kidney Foundation of Canada, the Canadian Institute of Health Research, and the Canadian Society of Nephrology, as well as by the Change Foundation of Ontario. Dr. Tangri and associates reported no financial conflicts of interest.
The findings from both of these studies are "novel and important," but "much additional work is needed before these approaches can be recommended for routine clinical use," said Dr. Marcello Tonelli and Dr. Braden Manns.
Both studies provide proof of concept for two different methods that might enhance prognostic power, compared with the use of creatinine-estimated GFR alone.
However, it would be premature to introduce the triple-marker approach of Dr. Peralta and colleagues into clinical practice for three reasons: First, their study population was highly selected, so the findings cannot be generalized to other settings until further research is done. Second, current practice includes confirmation of estimated GFR with a second measurement to confirm CKD, and this repeat measurement was not addressed in this study. And third, the use of more stringent estimated GFR criteria to define CKD might attenuate the advantage of the triple-marker method.
It also would be premature to implement the prediction model of Dr. Tangri and colleagues because there were missing data in both the cohort used to develop the models and the validation cohort, and values were imputed for subjects who had incomplete information. More importantly, all the study subjects were already in the care of a nephrologist, so they are not representative of the general population.
"Careful consideration and research will be required to determine whether the benefits [of an eight-variable model] would outweigh its added complexity," they concluded.
Dr. Tonelli is at the University of Alberta, Edmonton. Dr. Manns is at the University of Calgary (Alta.). They were supported by the Alberta Heritage Foundation for Medical Research, by Alberta Health and Wellness, and by the University of Alberta. Dr. Tonelli also is supported by a Government of Canada Research Chair in the optimal treatment of CKD. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying the two reports (JAMA 2011:305:1593-5).
The findings from both of these studies are "novel and important," but "much additional work is needed before these approaches can be recommended for routine clinical use," said Dr. Marcello Tonelli and Dr. Braden Manns.
Both studies provide proof of concept for two different methods that might enhance prognostic power, compared with the use of creatinine-estimated GFR alone.
However, it would be premature to introduce the triple-marker approach of Dr. Peralta and colleagues into clinical practice for three reasons: First, their study population was highly selected, so the findings cannot be generalized to other settings until further research is done. Second, current practice includes confirmation of estimated GFR with a second measurement to confirm CKD, and this repeat measurement was not addressed in this study. And third, the use of more stringent estimated GFR criteria to define CKD might attenuate the advantage of the triple-marker method.
It also would be premature to implement the prediction model of Dr. Tangri and colleagues because there were missing data in both the cohort used to develop the models and the validation cohort, and values were imputed for subjects who had incomplete information. More importantly, all the study subjects were already in the care of a nephrologist, so they are not representative of the general population.
"Careful consideration and research will be required to determine whether the benefits [of an eight-variable model] would outweigh its added complexity," they concluded.
Dr. Tonelli is at the University of Alberta, Edmonton. Dr. Manns is at the University of Calgary (Alta.). They were supported by the Alberta Heritage Foundation for Medical Research, by Alberta Health and Wellness, and by the University of Alberta. Dr. Tonelli also is supported by a Government of Canada Research Chair in the optimal treatment of CKD. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying the two reports (JAMA 2011:305:1593-5).
The findings from both of these studies are "novel and important," but "much additional work is needed before these approaches can be recommended for routine clinical use," said Dr. Marcello Tonelli and Dr. Braden Manns.
Both studies provide proof of concept for two different methods that might enhance prognostic power, compared with the use of creatinine-estimated GFR alone.
However, it would be premature to introduce the triple-marker approach of Dr. Peralta and colleagues into clinical practice for three reasons: First, their study population was highly selected, so the findings cannot be generalized to other settings until further research is done. Second, current practice includes confirmation of estimated GFR with a second measurement to confirm CKD, and this repeat measurement was not addressed in this study. And third, the use of more stringent estimated GFR criteria to define CKD might attenuate the advantage of the triple-marker method.
It also would be premature to implement the prediction model of Dr. Tangri and colleagues because there were missing data in both the cohort used to develop the models and the validation cohort, and values were imputed for subjects who had incomplete information. More importantly, all the study subjects were already in the care of a nephrologist, so they are not representative of the general population.
"Careful consideration and research will be required to determine whether the benefits [of an eight-variable model] would outweigh its added complexity," they concluded.
Dr. Tonelli is at the University of Alberta, Edmonton. Dr. Manns is at the University of Calgary (Alta.). They were supported by the Alberta Heritage Foundation for Medical Research, by Alberta Health and Wellness, and by the University of Alberta. Dr. Tonelli also is supported by a Government of Canada Research Chair in the optimal treatment of CKD. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying the two reports (JAMA 2011:305:1593-5).
Separate research groups offer two new methods for predicting which patients with chronic kidney disease are likely to progress to end-stage renal disease and other complications, according to studies published in the April 20 issue of JAMA.
Ultimately, the methods could help more accurately identify individuals who are at low and high risk for CKD progression, and allow for more appropriate use of health care resources for this population.
In the first report, a "triple-marker" approach using serum creatinine, serum cystatin C, and albuminuria levels yielded more accurate risk prediction than is achieved with current staging systems that are based primarily on creatinine-estimated glomerular filtration rates, said Dr. Carmen A. Peralta of the San Francisco VA Medical Center and her associates.
They assessed the triple-marker technique using a large, population-based cohort of adults (aged 45 years and older) who were participating in a stroke study. A subgroup of 26,643 of these subjects had undergone evaluation of kidney function as part of that study.
Patients in Dr. Peralta’s analysis had a mean age of 65 years. In all, 40% were black, more than half were women, 21% had diabetes, and 59% had hypertension. During a median follow-up of approximately 5 years, 177 subjects developed end-stage renal disease (ESRD) and 1,940 died of all causes.
Adding either the cystatin C or the albuminuria measures to creatinine-based estimated GFR greatly improved the ability to predict the development of ESRD as well as mortality. Using all three measures together improved it even further.
The rate of ESRD was 103-fold higher in subjects who were identified as being at risk via the triple-marker method than in those who were identified via creatinine level alone. Similarly, mortality was nearly eight times higher among those identified as being at risk via the triple-marker method than in those identified via creatinine level alone, the investigators said (JAMA 2011;305:1545-52).
Moreover, one in six subjects who were found to have CKD by the triple-marker method were not identified at all by creatinine level alone, suggesting that people could have occult CKD that would not be diagnosed according to standard methods.
In addition, 25% of subjects who were labeled as having CKD by creatinine-based GFR estimate alone were found not to have CKD when cystatin C and albuminuria levels were added into the risk stratification. This suggests that one-fourth of people screened by standard methods alone may be treated as though they’re at increased risk of ESRD or death when they are not.
Thus, using the triple-marker method "could both reduce unwarranted referrals and unnecessary work-ups for low-risk individuals and would prioritize specialty care and interventions to individuals at highest risk," Dr. Peralta and her colleagues said.
"Several groups are currently advocating new international guidelines that more accurately reflect prognosis of CKD and have proposed adding [albumin:creatinine ratio] to staging of CKD. Our results suggest that a triple-marker approach using both [albuminuria] and cystatin C to confirm CKD more accurately discriminates prognosis for death and progression to ESRD than creatinine and [albuminuria] alone," they added.
In the second report, investigators developed seven possible models for predicting CKD progression, using various combinations of more than 20 candidate variables that are known to affect renal function. To do so, they first assessed these variables in a Canadian cohort of 3,449 adults who were treated at nephrology clinics for stage 3-5 CKD.
These study subjects, who were followed from 2001 through 2008, helped determine which variables were best associated with CKD progression, said Dr. Navdeep Tangri of Tufts Medical Center, Boston, and his associates.
One of the seven models was particularly accurate at predicting CKD progression. It factored in patient age and sex, as well as the estimated GFR, albuminuria, serum calcium, serum phosphate, serum bicarbonate, and serum albumin levels. These are basic laboratory measurements "that are obtained routinely in patients with CKD," Dr. Tangri and his colleagues said (JAMA 2011;305:1553-9).
All seven models were tested in a validation cohort of 4,942 patients in a British Columbia registry who had stage 3-5 CKD. The same model was found to be the most accurate in predicting disease progression in that cohort.
"Using our models, lower-risk patients could be managed by the primary care physician without additional testing or treatment of CKD complications," whereas higher-risk patients could receive "more intensive testing, intervention, and early nephrology care," they said.
The models also could be used to triage patients with stage 4 CKD "regarding dialysis education, creation of vascular access, and preemptive transplantation"; to select stage 3 patients for public health interventions; and to select high-risk patients for enrollment in clinical trials, the researchers added.
Dr. Peralta’s study was supported by the National Institute of Neurological Disorders and Stroke, Amgen Corp., the National Institute of Diabetes and Digestive and Kidney Diseases, the Robert Wood Johnson Foundation, and the American Heart Association. Several associates also reported ties to Amgen. Dr. Tangri’s study was supported by a joint initiative of the Kidney Foundation of Canada, the Canadian Institute of Health Research, and the Canadian Society of Nephrology, as well as by the Change Foundation of Ontario. Dr. Tangri and associates reported no financial conflicts of interest.
Separate research groups offer two new methods for predicting which patients with chronic kidney disease are likely to progress to end-stage renal disease and other complications, according to studies published in the April 20 issue of JAMA.
Ultimately, the methods could help more accurately identify individuals who are at low and high risk for CKD progression, and allow for more appropriate use of health care resources for this population.
In the first report, a "triple-marker" approach using serum creatinine, serum cystatin C, and albuminuria levels yielded more accurate risk prediction than is achieved with current staging systems that are based primarily on creatinine-estimated glomerular filtration rates, said Dr. Carmen A. Peralta of the San Francisco VA Medical Center and her associates.
They assessed the triple-marker technique using a large, population-based cohort of adults (aged 45 years and older) who were participating in a stroke study. A subgroup of 26,643 of these subjects had undergone evaluation of kidney function as part of that study.
Patients in Dr. Peralta’s analysis had a mean age of 65 years. In all, 40% were black, more than half were women, 21% had diabetes, and 59% had hypertension. During a median follow-up of approximately 5 years, 177 subjects developed end-stage renal disease (ESRD) and 1,940 died of all causes.
Adding either the cystatin C or the albuminuria measures to creatinine-based estimated GFR greatly improved the ability to predict the development of ESRD as well as mortality. Using all three measures together improved it even further.
The rate of ESRD was 103-fold higher in subjects who were identified as being at risk via the triple-marker method than in those who were identified via creatinine level alone. Similarly, mortality was nearly eight times higher among those identified as being at risk via the triple-marker method than in those identified via creatinine level alone, the investigators said (JAMA 2011;305:1545-52).
Moreover, one in six subjects who were found to have CKD by the triple-marker method were not identified at all by creatinine level alone, suggesting that people could have occult CKD that would not be diagnosed according to standard methods.
In addition, 25% of subjects who were labeled as having CKD by creatinine-based GFR estimate alone were found not to have CKD when cystatin C and albuminuria levels were added into the risk stratification. This suggests that one-fourth of people screened by standard methods alone may be treated as though they’re at increased risk of ESRD or death when they are not.
Thus, using the triple-marker method "could both reduce unwarranted referrals and unnecessary work-ups for low-risk individuals and would prioritize specialty care and interventions to individuals at highest risk," Dr. Peralta and her colleagues said.
"Several groups are currently advocating new international guidelines that more accurately reflect prognosis of CKD and have proposed adding [albumin:creatinine ratio] to staging of CKD. Our results suggest that a triple-marker approach using both [albuminuria] and cystatin C to confirm CKD more accurately discriminates prognosis for death and progression to ESRD than creatinine and [albuminuria] alone," they added.
In the second report, investigators developed seven possible models for predicting CKD progression, using various combinations of more than 20 candidate variables that are known to affect renal function. To do so, they first assessed these variables in a Canadian cohort of 3,449 adults who were treated at nephrology clinics for stage 3-5 CKD.
These study subjects, who were followed from 2001 through 2008, helped determine which variables were best associated with CKD progression, said Dr. Navdeep Tangri of Tufts Medical Center, Boston, and his associates.
One of the seven models was particularly accurate at predicting CKD progression. It factored in patient age and sex, as well as the estimated GFR, albuminuria, serum calcium, serum phosphate, serum bicarbonate, and serum albumin levels. These are basic laboratory measurements "that are obtained routinely in patients with CKD," Dr. Tangri and his colleagues said (JAMA 2011;305:1553-9).
All seven models were tested in a validation cohort of 4,942 patients in a British Columbia registry who had stage 3-5 CKD. The same model was found to be the most accurate in predicting disease progression in that cohort.
"Using our models, lower-risk patients could be managed by the primary care physician without additional testing or treatment of CKD complications," whereas higher-risk patients could receive "more intensive testing, intervention, and early nephrology care," they said.
The models also could be used to triage patients with stage 4 CKD "regarding dialysis education, creation of vascular access, and preemptive transplantation"; to select stage 3 patients for public health interventions; and to select high-risk patients for enrollment in clinical trials, the researchers added.
Dr. Peralta’s study was supported by the National Institute of Neurological Disorders and Stroke, Amgen Corp., the National Institute of Diabetes and Digestive and Kidney Diseases, the Robert Wood Johnson Foundation, and the American Heart Association. Several associates also reported ties to Amgen. Dr. Tangri’s study was supported by a joint initiative of the Kidney Foundation of Canada, the Canadian Institute of Health Research, and the Canadian Society of Nephrology, as well as by the Change Foundation of Ontario. Dr. Tangri and associates reported no financial conflicts of interest.
FROM JAMA
Major Finding: A triple-marker method incorporating serum creatinine, serum cystatin C, and albuminuria levels predicted CKD progression more accurately than did standard creatinine-estimated GFR alone. Another model incorporating seven patient variables also was more accurate at predicting disease progression than was standard creatinine-estimated GFR alone.
Data Source: The first study was a secondary analysis of a population-based cohort involving 26,643 adults. The second study was an analysis of CKD outcomes following the development and validation of seven models for predicting disease progression in adults with stage 3-5 CKD.
Disclosures: Dr. Peralta’s study was supported by the National Institute of Neurological Disorders and Stroke, Amgen Corp., the National Institute of Diabetes and Digestive and Kidney Diseases, the Robert Wood Johnson Foundation, and the American Heart Association. Several associates also reported ties to Amgen. Dr. Tangri’s study was supported by a joint initiative of the Kidney Foundation of Canada, the Canadian Institute of Health Research, and the Canadian Society of Nephrology, as well as by the Change Foundation of Ontario. Dr. Tangri and associates reported no financial conflicts of interest.