Nephrology

MELBOURNE – Elevated total cholesterol and low-density lipoprotein cholesterol levels in patients with coronary heart disease were significantly associated with an increased risk of chronic kidney disease, according to a retrospective analysis of data from two large, randomized, controlled trials.

Data presented at the World Congress of Cardiology 2014 showed total cholesterol levels above 240 mg/dL were associated with a significant 78% increase in the risk of chronic kidney disease, while LDL cholesterol greater than 190 mg/dL was associated with a 72% increase in risk.

Elevated non–high-density lipoprotein cholesterol levels and the ratio of total cholesterol to HDL cholesterol were both associated with elevated risk of chronic kidney disease, but reduced HDL cholesterol and the ratio of apolipoprotein B/apolipoprotein A did not significantly affect risk.

Dyslipidemia is present in around 60% of patients with chronic kidney disease, noted presenter Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco. Previous studies in patients with coronary heart disease and chronic kidney disease also have shown that statins have a renoprotective effect.

However, Dr. Deedwania said there has been little exploration of the impact of baseline lipid parameters on renal function.

"We have found that there is a significant increase in not only the prevalence but also the morbidity and mortality in people with chronic kidney disease with coronary events and other cardiovascular events," Dr. Deedwania said in an interview.

Using data from the Treating to New Targets (TNT) study and Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study, in which patients were treated with either atorvastatin or simvastatin, researchers were able to examine the relationship between baseline lipoprotein parameters and kidney function in a combined cohort of more than 19,000 patients with coronary heart disease.

"That showed very good relationship between total cholesterol and LDL cholesterol with progressive decline in renal function, which then helped me explain what I had observed earlier in terms of improvement in kidney function in early-stage patients with statins," Dr. Deedwania said at the meeting, which was sponsored by the World Heart Federation.

The relationship between lipoprotein parameters and chronic kidney disease persisted even after adjustment for age, body mass index, smoking status, diabetes history and status, hypertension, and treatment assignment.

The study defined chronic kidney disease as an estimated glomerular filtration rate below 60 mL/min per 1.73 m². However, Dr. Deedwania said no patients achieved stage 4 kidney disease, and all eGFR measurements fell between 45 and 60 mL/min per 1.73 m².

The analysis used a relatively early definition of kidney disease as the outcome of interest, observed session chair Dr. Vlado Perkovic, professor of medicine at the University of Sydney (Australia).

Dr. Deedwania later said he believed the key was to focus on early-stage interventions rather than waiting until the disease progressed and suggested some interventional trials had failed to achieve an effect because they were done in more advanced patients.

The researchers declared a range of speakers fees, consultancies, and honoraria from the pharmaceutical industry; two of the authors were employees of Pfizer.

MELBOURNE – Elevated total cholesterol and low-density lipoprotein cholesterol levels in patients with coronary heart disease were significantly associated with an increased risk of chronic kidney disease, according to a retrospective analysis of data from two large, randomized, controlled trials.

Data presented at the World Congress of Cardiology 2014 showed total cholesterol levels above 240 mg/dL were associated with a significant 78% increase in the risk of chronic kidney disease, while LDL cholesterol greater than 190 mg/dL was associated with a 72% increase in risk.

Elevated non–high-density lipoprotein cholesterol levels and the ratio of total cholesterol to HDL cholesterol were both associated with elevated risk of chronic kidney disease, but reduced HDL cholesterol and the ratio of apolipoprotein B/apolipoprotein A did not significantly affect risk.

Dyslipidemia is present in around 60% of patients with chronic kidney disease, noted presenter Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco. Previous studies in patients with coronary heart disease and chronic kidney disease also have shown that statins have a renoprotective effect.

However, Dr. Deedwania said there has been little exploration of the impact of baseline lipid parameters on renal function.

"We have found that there is a significant increase in not only the prevalence but also the morbidity and mortality in people with chronic kidney disease with coronary events and other cardiovascular events," Dr. Deedwania said in an interview.

Using data from the Treating to New Targets (TNT) study and Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study, in which patients were treated with either atorvastatin or simvastatin, researchers were able to examine the relationship between baseline lipoprotein parameters and kidney function in a combined cohort of more than 19,000 patients with coronary heart disease.

"That showed very good relationship between total cholesterol and LDL cholesterol with progressive decline in renal function, which then helped me explain what I had observed earlier in terms of improvement in kidney function in early-stage patients with statins," Dr. Deedwania said at the meeting, which was sponsored by the World Heart Federation.

The relationship between lipoprotein parameters and chronic kidney disease persisted even after adjustment for age, body mass index, smoking status, diabetes history and status, hypertension, and treatment assignment.

The study defined chronic kidney disease as an estimated glomerular filtration rate below 60 mL/min per 1.73 m². However, Dr. Deedwania said no patients achieved stage 4 kidney disease, and all eGFR measurements fell between 45 and 60 mL/min per 1.73 m².

The analysis used a relatively early definition of kidney disease as the outcome of interest, observed session chair Dr. Vlado Perkovic, professor of medicine at the University of Sydney (Australia).

Dr. Deedwania later said he believed the key was to focus on early-stage interventions rather than waiting until the disease progressed and suggested some interventional trials had failed to achieve an effect because they were done in more advanced patients.

The researchers declared a range of speakers fees, consultancies, and honoraria from the pharmaceutical industry; two of the authors were employees of Pfizer.

MELBOURNE – Elevated total cholesterol and low-density lipoprotein cholesterol levels in patients with coronary heart disease were significantly associated with an increased risk of chronic kidney disease, according to a retrospective analysis of data from two large, randomized, controlled trials.

Data presented at the World Congress of Cardiology 2014 showed total cholesterol levels above 240 mg/dL were associated with a significant 78% increase in the risk of chronic kidney disease, while LDL cholesterol greater than 190 mg/dL was associated with a 72% increase in risk.

Elevated non–high-density lipoprotein cholesterol levels and the ratio of total cholesterol to HDL cholesterol were both associated with elevated risk of chronic kidney disease, but reduced HDL cholesterol and the ratio of apolipoprotein B/apolipoprotein A did not significantly affect risk.

Dyslipidemia is present in around 60% of patients with chronic kidney disease, noted presenter Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco. Previous studies in patients with coronary heart disease and chronic kidney disease also have shown that statins have a renoprotective effect.

However, Dr. Deedwania said there has been little exploration of the impact of baseline lipid parameters on renal function.

"We have found that there is a significant increase in not only the prevalence but also the morbidity and mortality in people with chronic kidney disease with coronary events and other cardiovascular events," Dr. Deedwania said in an interview.

Using data from the Treating to New Targets (TNT) study and Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study, in which patients were treated with either atorvastatin or simvastatin, researchers were able to examine the relationship between baseline lipoprotein parameters and kidney function in a combined cohort of more than 19,000 patients with coronary heart disease.

"That showed very good relationship between total cholesterol and LDL cholesterol with progressive decline in renal function, which then helped me explain what I had observed earlier in terms of improvement in kidney function in early-stage patients with statins," Dr. Deedwania said at the meeting, which was sponsored by the World Heart Federation.

The relationship between lipoprotein parameters and chronic kidney disease persisted even after adjustment for age, body mass index, smoking status, diabetes history and status, hypertension, and treatment assignment.

The study defined chronic kidney disease as an estimated glomerular filtration rate below 60 mL/min per 1.73 m². However, Dr. Deedwania said no patients achieved stage 4 kidney disease, and all eGFR measurements fell between 45 and 60 mL/min per 1.73 m².

The analysis used a relatively early definition of kidney disease as the outcome of interest, observed session chair Dr. Vlado Perkovic, professor of medicine at the University of Sydney (Australia).

Dr. Deedwania later said he believed the key was to focus on early-stage interventions rather than waiting until the disease progressed and suggested some interventional trials had failed to achieve an effect because they were done in more advanced patients.

The researchers declared a range of speakers fees, consultancies, and honoraria from the pharmaceutical industry; two of the authors were employees of Pfizer.

One in six patients with systemic lupus erythematosus was readmitted within 30 days after discharge in a multistate, administrative database study of more than 800 hospitals and 55,000 hospitalizations, and these readmissions occurred more often among black and Hispanic patients than whites.

"These findings suggest potential racial disparities in factors that are known to influence readmissions, such as the quality of care delivered in the hospital or during health care transitions to the outpatient settings," lead author Dr. Jinoos Yazdany, codirector of the lupus clinic at the University of California, San Francisco, said in an interview. "Poor access to high-quality care, both in the hospital and in the outpatient clinic, may be contributing, but further research is needed to prove this."

Patients with systemic lupus erythematosus (SLE) on Medicare or Medicaid also had higher readmission rates than those on private insurance, Dr. Yazdany and her associates reported Aug. 11 in Arthritis & Rheumatology.

Up to 25% of patients with SLE are hospitalized each year, and SLE has the sixth-highest readmission rate of any medical condition in the United States. To better characterize SLE readmissions, the researchers analyzed an administrative dataset representing 31,903 adult patients with SLE admitted at 810 hospitals in California, Florida, New York, Utah, and Washington during 2008-2009 (Arthritis Rheumatol. 2014 Aug. 11 [doi: 10.1002/art.38768]).

Of 55,936 total hospitalizations, 9,244 (16.5%) led to readmission within 30 days, the investigators reported. Patients were more likely to be readmitted if they were younger (odds ratio, 0.98 per year; 95% confidence interval, 0.98-0.98); black (OR, 1.18; 95% CI, 1.09-1.28); Hispanic (OR, 1.12; 95% CI, 1.02-1.22); or had Medicare or Medicaid versus private insurance (OR, 1.57; 95% CI, 1.45-1.69; and OR, 1.53; 95% CI, 1.40-1.67, respectively), the researchers added.

While SLE tends to be worse in younger patients, its greater prevalence and severity in minorities appears to be multifactorial, Dr. Yazdany said. "Environmental, psychosocial, biologic, and health care factors seem to all play a role," she noted. "This means that no one strategy will be enough to eliminate disparities in SLE."

Clinical features of SLE most often associated with readmission included lupus nephritis, serositis, and thrombocytopenia, the researchers added. New York hospitals had significantly lower risk-adjusted readmission rates than did those in California (OR, 0.77; 95% CI, 0.70-0.85), while hospitals in Florida had significantly higher rates (OR, 1.20; 95% CI, 1.11-1.32), compared with California, they reported.

"We should learn more about the systems that New York has in place for SLE patients, including whether the high concentration of dedicated SLE centers helps improve the quality of care," Dr. Yazdany said. Improving discharge planning, hospital transitions, coordination of care, and patient education are known to prevent avoidable hospitalizations in the overall population, she said. "To reduce readmissions in SLE, we need to investigate all of these strategies."

Notably, hospitals with high readmission rates for SLE did not also have higher rates for common chronic diseases such as heart disease or pneumonia, the researchers reported. "This tells us that it is important to look at SLE separately to properly target quality improvement initiatives," Dr. Yazdany said. "SLE requires highly coordinated, interdisciplinary care both in the hospital and during outpatient transitions, and our study implies that some hospital systems are doing a better job than others in caring for these patients."

Using readmissions to grade hospital quality is controversial, Dr. Yazdany noted. "However, readmissions can also serve as an outcome measure to help us identify disparities in care and to target quality improvement initiatives," she said. "Now that we know that there is significant unexplained variation in SLE readmission rates across states, the next step is to develop interventions to improve this outcome, particularly in high-risk patients."

Some states did not report whether admissions were planned, which could have led investigators to misclassify planned rehospitalizations as acute readmissions, they said. The dataset used in the study also had sparse clinical information, making it impossible to determine if readmissions were preventable, they added.

The study was partly funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors reported no conflicts of interest.

One in six patients with systemic lupus erythematosus was readmitted within 30 days after discharge in a multistate, administrative database study of more than 800 hospitals and 55,000 hospitalizations, and these readmissions occurred more often among black and Hispanic patients than whites.

"These findings suggest potential racial disparities in factors that are known to influence readmissions, such as the quality of care delivered in the hospital or during health care transitions to the outpatient settings," lead author Dr. Jinoos Yazdany, codirector of the lupus clinic at the University of California, San Francisco, said in an interview. "Poor access to high-quality care, both in the hospital and in the outpatient clinic, may be contributing, but further research is needed to prove this."

Patients with systemic lupus erythematosus (SLE) on Medicare or Medicaid also had higher readmission rates than those on private insurance, Dr. Yazdany and her associates reported Aug. 11 in Arthritis & Rheumatology.

Up to 25% of patients with SLE are hospitalized each year, and SLE has the sixth-highest readmission rate of any medical condition in the United States. To better characterize SLE readmissions, the researchers analyzed an administrative dataset representing 31,903 adult patients with SLE admitted at 810 hospitals in California, Florida, New York, Utah, and Washington during 2008-2009 (Arthritis Rheumatol. 2014 Aug. 11 [doi: 10.1002/art.38768]).

Of 55,936 total hospitalizations, 9,244 (16.5%) led to readmission within 30 days, the investigators reported. Patients were more likely to be readmitted if they were younger (odds ratio, 0.98 per year; 95% confidence interval, 0.98-0.98); black (OR, 1.18; 95% CI, 1.09-1.28); Hispanic (OR, 1.12; 95% CI, 1.02-1.22); or had Medicare or Medicaid versus private insurance (OR, 1.57; 95% CI, 1.45-1.69; and OR, 1.53; 95% CI, 1.40-1.67, respectively), the researchers added.

While SLE tends to be worse in younger patients, its greater prevalence and severity in minorities appears to be multifactorial, Dr. Yazdany said. "Environmental, psychosocial, biologic, and health care factors seem to all play a role," she noted. "This means that no one strategy will be enough to eliminate disparities in SLE."

Clinical features of SLE most often associated with readmission included lupus nephritis, serositis, and thrombocytopenia, the researchers added. New York hospitals had significantly lower risk-adjusted readmission rates than did those in California (OR, 0.77; 95% CI, 0.70-0.85), while hospitals in Florida had significantly higher rates (OR, 1.20; 95% CI, 1.11-1.32), compared with California, they reported.

"We should learn more about the systems that New York has in place for SLE patients, including whether the high concentration of dedicated SLE centers helps improve the quality of care," Dr. Yazdany said. Improving discharge planning, hospital transitions, coordination of care, and patient education are known to prevent avoidable hospitalizations in the overall population, she said. "To reduce readmissions in SLE, we need to investigate all of these strategies."

Notably, hospitals with high readmission rates for SLE did not also have higher rates for common chronic diseases such as heart disease or pneumonia, the researchers reported. "This tells us that it is important to look at SLE separately to properly target quality improvement initiatives," Dr. Yazdany said. "SLE requires highly coordinated, interdisciplinary care both in the hospital and during outpatient transitions, and our study implies that some hospital systems are doing a better job than others in caring for these patients."

Using readmissions to grade hospital quality is controversial, Dr. Yazdany noted. "However, readmissions can also serve as an outcome measure to help us identify disparities in care and to target quality improvement initiatives," she said. "Now that we know that there is significant unexplained variation in SLE readmission rates across states, the next step is to develop interventions to improve this outcome, particularly in high-risk patients."

Some states did not report whether admissions were planned, which could have led investigators to misclassify planned rehospitalizations as acute readmissions, they said. The dataset used in the study also had sparse clinical information, making it impossible to determine if readmissions were preventable, they added.

The study was partly funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors reported no conflicts of interest.

One in six patients with systemic lupus erythematosus was readmitted within 30 days after discharge in a multistate, administrative database study of more than 800 hospitals and 55,000 hospitalizations, and these readmissions occurred more often among black and Hispanic patients than whites.

"These findings suggest potential racial disparities in factors that are known to influence readmissions, such as the quality of care delivered in the hospital or during health care transitions to the outpatient settings," lead author Dr. Jinoos Yazdany, codirector of the lupus clinic at the University of California, San Francisco, said in an interview. "Poor access to high-quality care, both in the hospital and in the outpatient clinic, may be contributing, but further research is needed to prove this."

Patients with systemic lupus erythematosus (SLE) on Medicare or Medicaid also had higher readmission rates than those on private insurance, Dr. Yazdany and her associates reported Aug. 11 in Arthritis & Rheumatology.

Up to 25% of patients with SLE are hospitalized each year, and SLE has the sixth-highest readmission rate of any medical condition in the United States. To better characterize SLE readmissions, the researchers analyzed an administrative dataset representing 31,903 adult patients with SLE admitted at 810 hospitals in California, Florida, New York, Utah, and Washington during 2008-2009 (Arthritis Rheumatol. 2014 Aug. 11 [doi: 10.1002/art.38768]).

Of 55,936 total hospitalizations, 9,244 (16.5%) led to readmission within 30 days, the investigators reported. Patients were more likely to be readmitted if they were younger (odds ratio, 0.98 per year; 95% confidence interval, 0.98-0.98); black (OR, 1.18; 95% CI, 1.09-1.28); Hispanic (OR, 1.12; 95% CI, 1.02-1.22); or had Medicare or Medicaid versus private insurance (OR, 1.57; 95% CI, 1.45-1.69; and OR, 1.53; 95% CI, 1.40-1.67, respectively), the researchers added.

While SLE tends to be worse in younger patients, its greater prevalence and severity in minorities appears to be multifactorial, Dr. Yazdany said. "Environmental, psychosocial, biologic, and health care factors seem to all play a role," she noted. "This means that no one strategy will be enough to eliminate disparities in SLE."

Clinical features of SLE most often associated with readmission included lupus nephritis, serositis, and thrombocytopenia, the researchers added. New York hospitals had significantly lower risk-adjusted readmission rates than did those in California (OR, 0.77; 95% CI, 0.70-0.85), while hospitals in Florida had significantly higher rates (OR, 1.20; 95% CI, 1.11-1.32), compared with California, they reported.

"We should learn more about the systems that New York has in place for SLE patients, including whether the high concentration of dedicated SLE centers helps improve the quality of care," Dr. Yazdany said. Improving discharge planning, hospital transitions, coordination of care, and patient education are known to prevent avoidable hospitalizations in the overall population, she said. "To reduce readmissions in SLE, we need to investigate all of these strategies."

Notably, hospitals with high readmission rates for SLE did not also have higher rates for common chronic diseases such as heart disease or pneumonia, the researchers reported. "This tells us that it is important to look at SLE separately to properly target quality improvement initiatives," Dr. Yazdany said. "SLE requires highly coordinated, interdisciplinary care both in the hospital and during outpatient transitions, and our study implies that some hospital systems are doing a better job than others in caring for these patients."

Using readmissions to grade hospital quality is controversial, Dr. Yazdany noted. "However, readmissions can also serve as an outcome measure to help us identify disparities in care and to target quality improvement initiatives," she said. "Now that we know that there is significant unexplained variation in SLE readmission rates across states, the next step is to develop interventions to improve this outcome, particularly in high-risk patients."

Some states did not report whether admissions were planned, which could have led investigators to misclassify planned rehospitalizations as acute readmissions, they said. The dataset used in the study also had sparse clinical information, making it impossible to determine if readmissions were preventable, they added.

The study was partly funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors reported no conflicts of interest.

WASHINGTON – A large proportion of female triathletes who responded to a national Web-based survey have symptoms of pelvic floor disorders, and one in four screened positive for the female athlete triad.

These findings from women in the general population, with a median age range of 35-44 years, echo findings from studies of Olympic and professional athletes, and "show that even young, thin, and otherwise healthy endurance athletes [who are not professional athletes] have pelvic floor disorders," said Dr. Johnny Yi after presenting his findings in a press conference at the scientific meetings of the American Urogynecologic Society and the International Urogynecological Association.

© Fuse/Thinkstock

Currently, "these women may not get screened because they are not believed to be in a high-risk group," said Dr. Yi, a urogynecologist in group practice in Denver.

Of 311 women who responded to the survey, 37% reported symptoms of stress urinary incontinence, and 16% reported symptoms of urgency urinary incontinence. Anal incontinence was also a problem, with 37% reporting symptoms of this condition. Pelvic organ prolapse symptoms were reported by 5%.

Most of the participants were white (90%), nonsmokers (99%), and premenopausal (80%), and had a mean body mass index of 22 kg/m². About half had borne children, almost all of them had vaginal deliveries.

The women were invited to participate through a database of nationwide triathlon interest groups and a triathlete Internet forum. The survey included the Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ) and the Pelvic Girdle Pain Questionnaire (PGPQ), both of which are validated tools; the Female Athlete Triad Screening Questionnaire, which is endorsed by the National Collegiate Athletic Association; and various medical and demographic questions.

Approximately 18% of the women had pelvic girdle pain, although the mean score on the PGPQ (35.6) was relatively low. Respondents with various types of incontinence reported higher levels of pelvic girdle pain, Dr. Yi said.

Of the 75% of respondents who completed the triad questionnaire, 22% screened positive for low energy availability, 24% for menstrual irregularities, and 29% for abnormal bone strength. Eight percent screened positive for all three components of the female athlete triad, which is characterized by a hypoestrogenic state similar to menopause.

Dr. Yi said he is particularly interested in possible associations between the female athlete triad and pelvic floor disorders, and in the pelvic floor consequences of coupling high-impact, high-endurance activity with the potential for a hypoestrogenic state.

This study showed no significant association between the triad and pelvic floor disorders, but the findings emphasize that "both disorders are prevalent" and should be screened for and treated to avoid long-term sequelae and improve quality of life, he said.

Weekly training of the study participants consisted of running for a mean of 3.7 days, biking for a mean of 2.9 days, and swimming for a mean of 2.4 days. Training mileage and intensity were not associated with pelvic floor disorders. Not unexpectedly, parity was associated with a higher prevalence of stress urinary incontinence and pelvic organ prolapse.

Dr. Yi and his coinvestigators reported no disclosures.

WASHINGTON – A large proportion of female triathletes who responded to a national Web-based survey have symptoms of pelvic floor disorders, and one in four screened positive for the female athlete triad.

These findings from women in the general population, with a median age range of 35-44 years, echo findings from studies of Olympic and professional athletes, and "show that even young, thin, and otherwise healthy endurance athletes [who are not professional athletes] have pelvic floor disorders," said Dr. Johnny Yi after presenting his findings in a press conference at the scientific meetings of the American Urogynecologic Society and the International Urogynecological Association.

© Fuse/Thinkstock

Currently, "these women may not get screened because they are not believed to be in a high-risk group," said Dr. Yi, a urogynecologist in group practice in Denver.

Of 311 women who responded to the survey, 37% reported symptoms of stress urinary incontinence, and 16% reported symptoms of urgency urinary incontinence. Anal incontinence was also a problem, with 37% reporting symptoms of this condition. Pelvic organ prolapse symptoms were reported by 5%.

Most of the participants were white (90%), nonsmokers (99%), and premenopausal (80%), and had a mean body mass index of 22 kg/m². About half had borne children, almost all of them had vaginal deliveries.

The women were invited to participate through a database of nationwide triathlon interest groups and a triathlete Internet forum. The survey included the Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ) and the Pelvic Girdle Pain Questionnaire (PGPQ), both of which are validated tools; the Female Athlete Triad Screening Questionnaire, which is endorsed by the National Collegiate Athletic Association; and various medical and demographic questions.

Approximately 18% of the women had pelvic girdle pain, although the mean score on the PGPQ (35.6) was relatively low. Respondents with various types of incontinence reported higher levels of pelvic girdle pain, Dr. Yi said.

Of the 75% of respondents who completed the triad questionnaire, 22% screened positive for low energy availability, 24% for menstrual irregularities, and 29% for abnormal bone strength. Eight percent screened positive for all three components of the female athlete triad, which is characterized by a hypoestrogenic state similar to menopause.

Dr. Yi said he is particularly interested in possible associations between the female athlete triad and pelvic floor disorders, and in the pelvic floor consequences of coupling high-impact, high-endurance activity with the potential for a hypoestrogenic state.

This study showed no significant association between the triad and pelvic floor disorders, but the findings emphasize that "both disorders are prevalent" and should be screened for and treated to avoid long-term sequelae and improve quality of life, he said.

Weekly training of the study participants consisted of running for a mean of 3.7 days, biking for a mean of 2.9 days, and swimming for a mean of 2.4 days. Training mileage and intensity were not associated with pelvic floor disorders. Not unexpectedly, parity was associated with a higher prevalence of stress urinary incontinence and pelvic organ prolapse.

Dr. Yi and his coinvestigators reported no disclosures.

WASHINGTON – A large proportion of female triathletes who responded to a national Web-based survey have symptoms of pelvic floor disorders, and one in four screened positive for the female athlete triad.

These findings from women in the general population, with a median age range of 35-44 years, echo findings from studies of Olympic and professional athletes, and "show that even young, thin, and otherwise healthy endurance athletes [who are not professional athletes] have pelvic floor disorders," said Dr. Johnny Yi after presenting his findings in a press conference at the scientific meetings of the American Urogynecologic Society and the International Urogynecological Association.

© Fuse/Thinkstock

Currently, "these women may not get screened because they are not believed to be in a high-risk group," said Dr. Yi, a urogynecologist in group practice in Denver.

Of 311 women who responded to the survey, 37% reported symptoms of stress urinary incontinence, and 16% reported symptoms of urgency urinary incontinence. Anal incontinence was also a problem, with 37% reporting symptoms of this condition. Pelvic organ prolapse symptoms were reported by 5%.

Most of the participants were white (90%), nonsmokers (99%), and premenopausal (80%), and had a mean body mass index of 22 kg/m². About half had borne children, almost all of them had vaginal deliveries.

The women were invited to participate through a database of nationwide triathlon interest groups and a triathlete Internet forum. The survey included the Epidemiology of Prolapse and Incontinence Questionnaire (EPIQ) and the Pelvic Girdle Pain Questionnaire (PGPQ), both of which are validated tools; the Female Athlete Triad Screening Questionnaire, which is endorsed by the National Collegiate Athletic Association; and various medical and demographic questions.

Approximately 18% of the women had pelvic girdle pain, although the mean score on the PGPQ (35.6) was relatively low. Respondents with various types of incontinence reported higher levels of pelvic girdle pain, Dr. Yi said.

Of the 75% of respondents who completed the triad questionnaire, 22% screened positive for low energy availability, 24% for menstrual irregularities, and 29% for abnormal bone strength. Eight percent screened positive for all three components of the female athlete triad, which is characterized by a hypoestrogenic state similar to menopause.

Dr. Yi said he is particularly interested in possible associations between the female athlete triad and pelvic floor disorders, and in the pelvic floor consequences of coupling high-impact, high-endurance activity with the potential for a hypoestrogenic state.

This study showed no significant association between the triad and pelvic floor disorders, but the findings emphasize that "both disorders are prevalent" and should be screened for and treated to avoid long-term sequelae and improve quality of life, he said.

Weekly training of the study participants consisted of running for a mean of 3.7 days, biking for a mean of 2.9 days, and swimming for a mean of 2.4 days. Training mileage and intensity were not associated with pelvic floor disorders. Not unexpectedly, parity was associated with a higher prevalence of stress urinary incontinence and pelvic organ prolapse.

Dr. Yi and his coinvestigators reported no disclosures.

LAKE BUENA VISTA, FLA. – Renal ultrasound in infants under 2 months of age with febrile urinary tract infection can be used to rule out high-grade vesicoureteral reflux, according to findings from a retrospective cross-sectional study.

This is because renal ultrasound has a high negative predictive value for detecting high-grade vesicoureteral reflux (VUR) in neonates, and although it has poor sensitivity for detecting low-grade VUR, its sensitivity for detecting high-grade VUR is quite good in this population.

The findings could have important implications for the management of neonates with febrile urinary tract infection (UTI), who are not included in American Academy of Pediatrics guidelines for febrile UTI. A 2011 update to those guidelines calls for the use of screening renal and bladder ultrasound, but recommends against routine voiding cystourethrogram (VCUG) after an initial febrile UTI in young children unless indicated by sonographic findings; however, these guidelines apply to children aged 2 months to 2 years only.

Younger infants who present with febrile UTI differ from those over 2 months of age in that they are more likely to be male – a high percentage of whom are uncircumcised and prone to UTI because of colonization, they have a more immature immune system that can also contribute to greater likelihood of UTI, and they can have higher rates of reflux and anatomical anomalies, Dr. Sowdhamini S. Wallace, director of pediatric hospital medicine research at Texas Children’s Hospital, Houston, reported at the Pediatric Hospital Medicine 2014 meeting.

Although many studies have included older children, they have limited applicability to younger infants because of these differences, and those studies that have included infants less than 2 months of age have been of small size or questionable quality, Dr. Wallace noted.

"So the objective of our study was to determine the test properties of renal ultrasound for detecting VUR and high-grade VUR and obstructive uropathies in this [younger] age group," she said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, the AAP Section on Hospital Medicine, and the Academic Pediatric Association.

Of 200 eligible neonates with a mean age of 33 days, 30% had an abnormal renal ultrasound after presenting with febrile UTI. The most common reason for an abnormal finding was hydronephrosis.

Twenty-six percent of the neonates had reflux and 8% had high-grade reflux; 8% had obstructive uropathies or nonobstructive lower tract anomalies, Dr. Wallace said.

The sensitivity of renal ultrasound for all grades of VUR was 31% overall, but was 87% for high-grade VUR.

"For high-grade VUR, the negative predictive value was 99%, with a 95%-100% confidence interval. There were no obstructive uropathies that were diagnosed by VCUG in patients with a normal renal ultrasound," she said.

The number of patients with a normal ultrasound who would need to undergo VCUG to detect one case of high-grade VUR was 70; the number needed to test to detect one case of low-grade VUR was 4, she said.

The number needed to test "should be very helpful for physicians when they are deciding whether to get a VCUG on a neonate under 2 months if they have a normal renal ultrasound, Dr. Wallace said.

"Overall, I think you can see, with the number needed to test of 70, that you would have to test many babies with normal renal ultrasound to detect one case of high-grade VUR, so you may be able to spare many infants from VCUG," she concluded.

The infants presented to the emergency department during 2008-2011 with culture-proven UTI and fever of at least 100.4° F. They were identified through a microbiology database; those included in the study had urine collected through a catheterization or suprapubic aspiration, and those with a history of abnormal prenatal ultrasound, a previous diagnosis of genitourinary tract anomalies, or greater than 30 days between ultrasound and VCUG were excluded.

Imaging studies were reviewed independently by two radiologists who were blinded to the VCUG findings. Any discrepancies were resolved by a third radiologist.

Renal ultrasound was categorized as abnormal if it showed hydronephrosis and/or caliectasis, or if there was renal size discrepancy greater than 10%, findings of a duplicated collecting system, or urethral thickening, urethral dilatation, or bladder abnormalities.

VUR severity was determined by the standard classification system.

The study is limited by the fact that most renal ultrasounds were performed at the time of UTI diagnosis when inflammation is likely present. Inflammation may also be present in patients with VUR, thus the sensitivity of renal ultrasound in this study may have been higher than with renal ultrasound performed after a UTI has resolved. Also, in the absence of a standard definition for hydronephrosis in infants less than 2 months of age the prenatal parameter of 4 mL was used.

Dr. Wallace reported having no disclosures.

LAKE BUENA VISTA, FLA. – Renal ultrasound in infants under 2 months of age with febrile urinary tract infection can be used to rule out high-grade vesicoureteral reflux, according to findings from a retrospective cross-sectional study.

This is because renal ultrasound has a high negative predictive value for detecting high-grade vesicoureteral reflux (VUR) in neonates, and although it has poor sensitivity for detecting low-grade VUR, its sensitivity for detecting high-grade VUR is quite good in this population.

The findings could have important implications for the management of neonates with febrile urinary tract infection (UTI), who are not included in American Academy of Pediatrics guidelines for febrile UTI. A 2011 update to those guidelines calls for the use of screening renal and bladder ultrasound, but recommends against routine voiding cystourethrogram (VCUG) after an initial febrile UTI in young children unless indicated by sonographic findings; however, these guidelines apply to children aged 2 months to 2 years only.

Younger infants who present with febrile UTI differ from those over 2 months of age in that they are more likely to be male – a high percentage of whom are uncircumcised and prone to UTI because of colonization, they have a more immature immune system that can also contribute to greater likelihood of UTI, and they can have higher rates of reflux and anatomical anomalies, Dr. Sowdhamini S. Wallace, director of pediatric hospital medicine research at Texas Children’s Hospital, Houston, reported at the Pediatric Hospital Medicine 2014 meeting.

Although many studies have included older children, they have limited applicability to younger infants because of these differences, and those studies that have included infants less than 2 months of age have been of small size or questionable quality, Dr. Wallace noted.

"So the objective of our study was to determine the test properties of renal ultrasound for detecting VUR and high-grade VUR and obstructive uropathies in this [younger] age group," she said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, the AAP Section on Hospital Medicine, and the Academic Pediatric Association.

Of 200 eligible neonates with a mean age of 33 days, 30% had an abnormal renal ultrasound after presenting with febrile UTI. The most common reason for an abnormal finding was hydronephrosis.

Twenty-six percent of the neonates had reflux and 8% had high-grade reflux; 8% had obstructive uropathies or nonobstructive lower tract anomalies, Dr. Wallace said.

The sensitivity of renal ultrasound for all grades of VUR was 31% overall, but was 87% for high-grade VUR.

"For high-grade VUR, the negative predictive value was 99%, with a 95%-100% confidence interval. There were no obstructive uropathies that were diagnosed by VCUG in patients with a normal renal ultrasound," she said.

The number of patients with a normal ultrasound who would need to undergo VCUG to detect one case of high-grade VUR was 70; the number needed to test to detect one case of low-grade VUR was 4, she said.

The number needed to test "should be very helpful for physicians when they are deciding whether to get a VCUG on a neonate under 2 months if they have a normal renal ultrasound, Dr. Wallace said.

"Overall, I think you can see, with the number needed to test of 70, that you would have to test many babies with normal renal ultrasound to detect one case of high-grade VUR, so you may be able to spare many infants from VCUG," she concluded.

The infants presented to the emergency department during 2008-2011 with culture-proven UTI and fever of at least 100.4° F. They were identified through a microbiology database; those included in the study had urine collected through a catheterization or suprapubic aspiration, and those with a history of abnormal prenatal ultrasound, a previous diagnosis of genitourinary tract anomalies, or greater than 30 days between ultrasound and VCUG were excluded.

Imaging studies were reviewed independently by two radiologists who were blinded to the VCUG findings. Any discrepancies were resolved by a third radiologist.

Renal ultrasound was categorized as abnormal if it showed hydronephrosis and/or caliectasis, or if there was renal size discrepancy greater than 10%, findings of a duplicated collecting system, or urethral thickening, urethral dilatation, or bladder abnormalities.

VUR severity was determined by the standard classification system.

The study is limited by the fact that most renal ultrasounds were performed at the time of UTI diagnosis when inflammation is likely present. Inflammation may also be present in patients with VUR, thus the sensitivity of renal ultrasound in this study may have been higher than with renal ultrasound performed after a UTI has resolved. Also, in the absence of a standard definition for hydronephrosis in infants less than 2 months of age the prenatal parameter of 4 mL was used.

Dr. Wallace reported having no disclosures.

LAKE BUENA VISTA, FLA. – Renal ultrasound in infants under 2 months of age with febrile urinary tract infection can be used to rule out high-grade vesicoureteral reflux, according to findings from a retrospective cross-sectional study.

This is because renal ultrasound has a high negative predictive value for detecting high-grade vesicoureteral reflux (VUR) in neonates, and although it has poor sensitivity for detecting low-grade VUR, its sensitivity for detecting high-grade VUR is quite good in this population.

The findings could have important implications for the management of neonates with febrile urinary tract infection (UTI), who are not included in American Academy of Pediatrics guidelines for febrile UTI. A 2011 update to those guidelines calls for the use of screening renal and bladder ultrasound, but recommends against routine voiding cystourethrogram (VCUG) after an initial febrile UTI in young children unless indicated by sonographic findings; however, these guidelines apply to children aged 2 months to 2 years only.

Younger infants who present with febrile UTI differ from those over 2 months of age in that they are more likely to be male – a high percentage of whom are uncircumcised and prone to UTI because of colonization, they have a more immature immune system that can also contribute to greater likelihood of UTI, and they can have higher rates of reflux and anatomical anomalies, Dr. Sowdhamini S. Wallace, director of pediatric hospital medicine research at Texas Children’s Hospital, Houston, reported at the Pediatric Hospital Medicine 2014 meeting.

Although many studies have included older children, they have limited applicability to younger infants because of these differences, and those studies that have included infants less than 2 months of age have been of small size or questionable quality, Dr. Wallace noted.

"So the objective of our study was to determine the test properties of renal ultrasound for detecting VUR and high-grade VUR and obstructive uropathies in this [younger] age group," she said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, the AAP Section on Hospital Medicine, and the Academic Pediatric Association.

Of 200 eligible neonates with a mean age of 33 days, 30% had an abnormal renal ultrasound after presenting with febrile UTI. The most common reason for an abnormal finding was hydronephrosis.

Twenty-six percent of the neonates had reflux and 8% had high-grade reflux; 8% had obstructive uropathies or nonobstructive lower tract anomalies, Dr. Wallace said.

The sensitivity of renal ultrasound for all grades of VUR was 31% overall, but was 87% for high-grade VUR.

"For high-grade VUR, the negative predictive value was 99%, with a 95%-100% confidence interval. There were no obstructive uropathies that were diagnosed by VCUG in patients with a normal renal ultrasound," she said.

The number of patients with a normal ultrasound who would need to undergo VCUG to detect one case of high-grade VUR was 70; the number needed to test to detect one case of low-grade VUR was 4, she said.

The number needed to test "should be very helpful for physicians when they are deciding whether to get a VCUG on a neonate under 2 months if they have a normal renal ultrasound, Dr. Wallace said.

"Overall, I think you can see, with the number needed to test of 70, that you would have to test many babies with normal renal ultrasound to detect one case of high-grade VUR, so you may be able to spare many infants from VCUG," she concluded.

The infants presented to the emergency department during 2008-2011 with culture-proven UTI and fever of at least 100.4° F. They were identified through a microbiology database; those included in the study had urine collected through a catheterization or suprapubic aspiration, and those with a history of abnormal prenatal ultrasound, a previous diagnosis of genitourinary tract anomalies, or greater than 30 days between ultrasound and VCUG were excluded.

Imaging studies were reviewed independently by two radiologists who were blinded to the VCUG findings. Any discrepancies were resolved by a third radiologist.

Renal ultrasound was categorized as abnormal if it showed hydronephrosis and/or caliectasis, or if there was renal size discrepancy greater than 10%, findings of a duplicated collecting system, or urethral thickening, urethral dilatation, or bladder abnormalities.

VUR severity was determined by the standard classification system.

The study is limited by the fact that most renal ultrasounds were performed at the time of UTI diagnosis when inflammation is likely present. Inflammation may also be present in patients with VUR, thus the sensitivity of renal ultrasound in this study may have been higher than with renal ultrasound performed after a UTI has resolved. Also, in the absence of a standard definition for hydronephrosis in infants less than 2 months of age the prenatal parameter of 4 mL was used.

Dr. Wallace reported having no disclosures.

Fever, infection with organisms other than Escherichia coli, elevated C-reactive protein, and an abnormal ultrasonographic finding are significant predictors of a higher risk of renal scarring among children and adolescents with a first episode of urinary tract infection, a meta-analysis has found.

Urinary tract infection (UTI) is the most common serious bacterial infection in children, and studies have shown that in 10%-15% of cases it leads to renal scarring (Pediatrics 2010;126:1084-91). If the renal scarring is considerable and results in a reduction in kidney function, it may be associated with hypertension, preeclampsia, and end-stage renal disease in adult life, studies have found (J. Hypertens. 2000;18:485-91; Pediatr. Nephrol. 1996;10:139-42).

The analysis of patient data from 1,280 individuals in nine cohort studies also showed a polymorphonuclear cell count of greater than 60% nearly doubled the risk while the presence of grades IV-V vesicoureteral reflux was associated with a 22-fold increase in the likelihood of renal scarring, defined as presence of photopenia on a technetium Tc 99m succimer renal scan.

"Although our data confirm the importance of high-grade VUR’ [vesicoureteral reflux] as a risk factor for renal scarring, they do not resolve the difficult question of how to identify this important but small subgroup of children without subjecting all children to a VCUG [voiding cystourethrogram]," reported Dr. Nader Shaikh of the Children’s Hospital of Pittsburgh, and his colleagues in a paper published online in the Aug. 4 issue of JAMA Pediatrics.

Researchers used the data to generate a predictive model using the three variables of temperature, ultrasonographic findings, and etiologic organism, whereby children with a score of two or more had twice the baseline risk of scarring (JAMA Pediatrics 2014, Aug. 4 [doi:10.1001/jamapediatrics.2014.637]).

The investigators found that 78.3% of patients are at low or intermediate risk of renal scarring from their first diagnosed UTI. They have normal renal ultrasound findings and only one of two other findings: a temperature of at least 39° C or an organism other than E. coli. Children with all three of the findings have twice the risk of renal scarring and constitute 21.7% of patients. The latter group merit close clinical follow-up and possibly a technetium Tc 99m succimer renal scan. "But the potential merits of obtaining a late scan clearly need to be explored in future prospective studies before the scan can be recommended," Dr. Nader Shaikh of the Children’s Hospital of Pittsburgh, and his colleagues wrote.

In an accompanying editorial, Dr. Kenneth B. Roberts of the University of North Carolina, Chapel Hill, said the findings shift the focus from vesicoureteral reflux to renal scarring, and confirm the value of renal-bladder ultrasonogram as a predictor of renal damage.

"High fever and organisms other than E. coli are also predictors, but notably, adding a VCUG and serum inflammatory markers to the evaluation contributes very little," Dr. Roberts wrote (JAMA Pediatrics 2014, Aug. 4 [doi:10.1001/jamapediatrics.2014.1329]).

No conflicts of interest were reported for the study or editorial.

[email protected]

Fever, infection with organisms other than Escherichia coli, elevated C-reactive protein, and an abnormal ultrasonographic finding are significant predictors of a higher risk of renal scarring among children and adolescents with a first episode of urinary tract infection, a meta-analysis has found.

Urinary tract infection (UTI) is the most common serious bacterial infection in children, and studies have shown that in 10%-15% of cases it leads to renal scarring (Pediatrics 2010;126:1084-91). If the renal scarring is considerable and results in a reduction in kidney function, it may be associated with hypertension, preeclampsia, and end-stage renal disease in adult life, studies have found (J. Hypertens. 2000;18:485-91; Pediatr. Nephrol. 1996;10:139-42).

The analysis of patient data from 1,280 individuals in nine cohort studies also showed a polymorphonuclear cell count of greater than 60% nearly doubled the risk while the presence of grades IV-V vesicoureteral reflux was associated with a 22-fold increase in the likelihood of renal scarring, defined as presence of photopenia on a technetium Tc 99m succimer renal scan.

"Although our data confirm the importance of high-grade VUR’ [vesicoureteral reflux] as a risk factor for renal scarring, they do not resolve the difficult question of how to identify this important but small subgroup of children without subjecting all children to a VCUG [voiding cystourethrogram]," reported Dr. Nader Shaikh of the Children’s Hospital of Pittsburgh, and his colleagues in a paper published online in the Aug. 4 issue of JAMA Pediatrics.

Researchers used the data to generate a predictive model using the three variables of temperature, ultrasonographic findings, and etiologic organism, whereby children with a score of two or more had twice the baseline risk of scarring (JAMA Pediatrics 2014, Aug. 4 [doi:10.1001/jamapediatrics.2014.637]).

The investigators found that 78.3% of patients are at low or intermediate risk of renal scarring from their first diagnosed UTI. They have normal renal ultrasound findings and only one of two other findings: a temperature of at least 39° C or an organism other than E. coli. Children with all three of the findings have twice the risk of renal scarring and constitute 21.7% of patients. The latter group merit close clinical follow-up and possibly a technetium Tc 99m succimer renal scan. "But the potential merits of obtaining a late scan clearly need to be explored in future prospective studies before the scan can be recommended," Dr. Nader Shaikh of the Children’s Hospital of Pittsburgh, and his colleagues wrote.

In an accompanying editorial, Dr. Kenneth B. Roberts of the University of North Carolina, Chapel Hill, said the findings shift the focus from vesicoureteral reflux to renal scarring, and confirm the value of renal-bladder ultrasonogram as a predictor of renal damage.

"High fever and organisms other than E. coli are also predictors, but notably, adding a VCUG and serum inflammatory markers to the evaluation contributes very little," Dr. Roberts wrote (JAMA Pediatrics 2014, Aug. 4 [doi:10.1001/jamapediatrics.2014.1329]).

No conflicts of interest were reported for the study or editorial.

[email protected]

Fever, infection with organisms other than Escherichia coli, elevated C-reactive protein, and an abnormal ultrasonographic finding are significant predictors of a higher risk of renal scarring among children and adolescents with a first episode of urinary tract infection, a meta-analysis has found.

Urinary tract infection (UTI) is the most common serious bacterial infection in children, and studies have shown that in 10%-15% of cases it leads to renal scarring (Pediatrics 2010;126:1084-91). If the renal scarring is considerable and results in a reduction in kidney function, it may be associated with hypertension, preeclampsia, and end-stage renal disease in adult life, studies have found (J. Hypertens. 2000;18:485-91; Pediatr. Nephrol. 1996;10:139-42).

The analysis of patient data from 1,280 individuals in nine cohort studies also showed a polymorphonuclear cell count of greater than 60% nearly doubled the risk while the presence of grades IV-V vesicoureteral reflux was associated with a 22-fold increase in the likelihood of renal scarring, defined as presence of photopenia on a technetium Tc 99m succimer renal scan.

"Although our data confirm the importance of high-grade VUR’ [vesicoureteral reflux] as a risk factor for renal scarring, they do not resolve the difficult question of how to identify this important but small subgroup of children without subjecting all children to a VCUG [voiding cystourethrogram]," reported Dr. Nader Shaikh of the Children’s Hospital of Pittsburgh, and his colleagues in a paper published online in the Aug. 4 issue of JAMA Pediatrics.

Researchers used the data to generate a predictive model using the three variables of temperature, ultrasonographic findings, and etiologic organism, whereby children with a score of two or more had twice the baseline risk of scarring (JAMA Pediatrics 2014, Aug. 4 [doi:10.1001/jamapediatrics.2014.637]).

The investigators found that 78.3% of patients are at low or intermediate risk of renal scarring from their first diagnosed UTI. They have normal renal ultrasound findings and only one of two other findings: a temperature of at least 39° C or an organism other than E. coli. Children with all three of the findings have twice the risk of renal scarring and constitute 21.7% of patients. The latter group merit close clinical follow-up and possibly a technetium Tc 99m succimer renal scan. "But the potential merits of obtaining a late scan clearly need to be explored in future prospective studies before the scan can be recommended," Dr. Nader Shaikh of the Children’s Hospital of Pittsburgh, and his colleagues wrote.

In an accompanying editorial, Dr. Kenneth B. Roberts of the University of North Carolina, Chapel Hill, said the findings shift the focus from vesicoureteral reflux to renal scarring, and confirm the value of renal-bladder ultrasonogram as a predictor of renal damage.

"High fever and organisms other than E. coli are also predictors, but notably, adding a VCUG and serum inflammatory markers to the evaluation contributes very little," Dr. Roberts wrote (JAMA Pediatrics 2014, Aug. 4 [doi:10.1001/jamapediatrics.2014.1329]).

No conflicts of interest were reported for the study or editorial.

[email protected]

The Food and Drug Administration has approved once-daily oral empagliflozin for adults with type 2 diabetes, based on seven studies with nearly 4,500 patients.

Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels. It has been studied "as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylureas, pioglitazone, and insulin," according to an Aug. 1 FDA statement announcing the approval.

Boehringer Ingelheim Pharmaceuticals will market empagliflozin as Jardiance.

This is the third SGLT2 inhibitor approved by the FDA, following the approval of dapagliflozin (Farxiga) in January 2014 and canagliflozin (Invokana) in March 2013.

The most common side effects of treatment are genital infections in women and urinary tract infections, according to the FDA. Treatment can also cause dehydration resulting in hypotension, with dizziness and/or fainting, as well as reduced renal function. "The elderly, patients with impaired renal function, and patients on diuretics to treat other conditions appeared to be more susceptible to this risk," the FDA noted.

Empagliflozin should not be used to treat patients with severe renal impairment or end-stage renal disease, or who are on dialysis. The drug also should not be used in patients with diabetic ketoacidosis and those with type 1 diabetes.

Boehringer Ingelheim must conduct four postmarketing studies of empagliflozin: a cardiovascular outcomes trial, which is already underway; a pediatric pharmacokinetic/pharmacodynamic study; a pediatric safety and efficacy study (which will include evaluations of bone health and development); and a juvenile animal toxicity study. The animal study will have "a particular focus on renal development, bone development, and growth," the FDA statement said.

In May, the European Commission approved empagliflozin for treating adults with type 2 diabetes.

[email protected]

The Food and Drug Administration has approved once-daily oral empagliflozin for adults with type 2 diabetes, based on seven studies with nearly 4,500 patients.

Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels. It has been studied "as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylureas, pioglitazone, and insulin," according to an Aug. 1 FDA statement announcing the approval.

Boehringer Ingelheim Pharmaceuticals will market empagliflozin as Jardiance.

This is the third SGLT2 inhibitor approved by the FDA, following the approval of dapagliflozin (Farxiga) in January 2014 and canagliflozin (Invokana) in March 2013.

The most common side effects of treatment are genital infections in women and urinary tract infections, according to the FDA. Treatment can also cause dehydration resulting in hypotension, with dizziness and/or fainting, as well as reduced renal function. "The elderly, patients with impaired renal function, and patients on diuretics to treat other conditions appeared to be more susceptible to this risk," the FDA noted.

Empagliflozin should not be used to treat patients with severe renal impairment or end-stage renal disease, or who are on dialysis. The drug also should not be used in patients with diabetic ketoacidosis and those with type 1 diabetes.

Boehringer Ingelheim must conduct four postmarketing studies of empagliflozin: a cardiovascular outcomes trial, which is already underway; a pediatric pharmacokinetic/pharmacodynamic study; a pediatric safety and efficacy study (which will include evaluations of bone health and development); and a juvenile animal toxicity study. The animal study will have "a particular focus on renal development, bone development, and growth," the FDA statement said.

In May, the European Commission approved empagliflozin for treating adults with type 2 diabetes.

[email protected]

The Food and Drug Administration has approved once-daily oral empagliflozin for adults with type 2 diabetes, based on seven studies with nearly 4,500 patients.

Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor that blocks the reabsorption of glucose by the kidney, increases glucose excretion, and lowers blood glucose levels. It has been studied "as a stand-alone therapy and in combination with other type 2 diabetes therapies including metformin, sulfonylureas, pioglitazone, and insulin," according to an Aug. 1 FDA statement announcing the approval.

Boehringer Ingelheim Pharmaceuticals will market empagliflozin as Jardiance.

This is the third SGLT2 inhibitor approved by the FDA, following the approval of dapagliflozin (Farxiga) in January 2014 and canagliflozin (Invokana) in March 2013.

The most common side effects of treatment are genital infections in women and urinary tract infections, according to the FDA. Treatment can also cause dehydration resulting in hypotension, with dizziness and/or fainting, as well as reduced renal function. "The elderly, patients with impaired renal function, and patients on diuretics to treat other conditions appeared to be more susceptible to this risk," the FDA noted.

Empagliflozin should not be used to treat patients with severe renal impairment or end-stage renal disease, or who are on dialysis. The drug also should not be used in patients with diabetic ketoacidosis and those with type 1 diabetes.

Boehringer Ingelheim must conduct four postmarketing studies of empagliflozin: a cardiovascular outcomes trial, which is already underway; a pediatric pharmacokinetic/pharmacodynamic study; a pediatric safety and efficacy study (which will include evaluations of bone health and development); and a juvenile animal toxicity study. The animal study will have "a particular focus on renal development, bone development, and growth," the FDA statement said.

In May, the European Commission approved empagliflozin for treating adults with type 2 diabetes.

[email protected]

LAS VEGAS – Adult survivors of childhood cancer treated with high-dose cisplatin or high-dose ifosfamide are at markedly increased risk for chronic renal impairment, according to a large Dutch study with a median 18.3-year follow-up.

Long-term treatment-related nephrotoxicity was also seen in the adult survivors of childhood cancer who underwent unilateral nephrectomy combined with abdominal radiation therapy.

"This study is perhaps a warning to us when we’re seeing these adult survivors of childhood cancer in clinic, particularly if they have a history of ifosfamide or cisplatin use, to pay closer attention to the development of chronic kidney disease so they can be managed better in the future," Dr. Anushree C. Shirali said at a meeting sponsored by the National Kidney Foundation.

Drug-induced acute kidney injury is a common event during cancer therapy. Its mechanisms and treatments are well studied. In contrast, the long-term nephrotoxicity of the powerful therapies used in treating childhood cancers has received much less scrutiny. But it’s an increasingly relevant issue because childhood cancer survival rates have improved substantially. Indeed, as the Dutch investigators observed, today 1 in 570 young adults is a childhood cancer survivor (Clin. J. Am. Soc. Nephrol. 2013;8:922-9).

Dr. Shirali, a nephrologist at Yale University in New Haven, Conn., highlighted the Dutch study of 763 adult survivors of childhood cancer because of its unusually long and complete follow-up. The investigators included nearly 90% of all adult survivors treated at Erasmus University in Rotterdam, the Netherlands, during 1964-2005.

High-dose ifosfamide was associated with a 6.2-fold greater likelihood of an increased urinary beta₂-microglobulin/creatinine ratio indicative of persisting tubular dysfunction, compared with cancer survivors not receiving that therapy. High-dose cisplatin was associated with a 5.2-fold increased risk of albuminuria. The estimated glomerular filtration rate in adult survivors who had received high-dose ifosfamide was 88 mL/min per 1.73 m², significantly lower than the 98 mL/min per 1.73 m² in others. Similarly, patients who had received high-dose cisplatin had an average estimated glomerular filtration rate of 83 mL/min per 1.73 m², compared with 101 mL/min per 1.73 m² in survivors not treated with high-dose cisplatin.

In contrast to ifosfamide, its isomer cyclophosphamide was not associated with long-term nephrotoxicity; neither was carboplatin, a cisplatin analogue, or methotrexate. Although methotrexate is known to cause acute nephrotoxicity, this phenomenon appears to be completely reversible, since methotrexate-treated, long-term cancer survivors didn’t develop tubular or glomerular dysfunction.

This long-term study was supported by the Dutch Kidney Foundation. Dr. Shirali, who was not involved in the study, reported having no financial conflicts.

[email protected]

LAS VEGAS – Adult survivors of childhood cancer treated with high-dose cisplatin or high-dose ifosfamide are at markedly increased risk for chronic renal impairment, according to a large Dutch study with a median 18.3-year follow-up.

Long-term treatment-related nephrotoxicity was also seen in the adult survivors of childhood cancer who underwent unilateral nephrectomy combined with abdominal radiation therapy.

"This study is perhaps a warning to us when we’re seeing these adult survivors of childhood cancer in clinic, particularly if they have a history of ifosfamide or cisplatin use, to pay closer attention to the development of chronic kidney disease so they can be managed better in the future," Dr. Anushree C. Shirali said at a meeting sponsored by the National Kidney Foundation.

Drug-induced acute kidney injury is a common event during cancer therapy. Its mechanisms and treatments are well studied. In contrast, the long-term nephrotoxicity of the powerful therapies used in treating childhood cancers has received much less scrutiny. But it’s an increasingly relevant issue because childhood cancer survival rates have improved substantially. Indeed, as the Dutch investigators observed, today 1 in 570 young adults is a childhood cancer survivor (Clin. J. Am. Soc. Nephrol. 2013;8:922-9).

Dr. Shirali, a nephrologist at Yale University in New Haven, Conn., highlighted the Dutch study of 763 adult survivors of childhood cancer because of its unusually long and complete follow-up. The investigators included nearly 90% of all adult survivors treated at Erasmus University in Rotterdam, the Netherlands, during 1964-2005.

High-dose ifosfamide was associated with a 6.2-fold greater likelihood of an increased urinary beta₂-microglobulin/creatinine ratio indicative of persisting tubular dysfunction, compared with cancer survivors not receiving that therapy. High-dose cisplatin was associated with a 5.2-fold increased risk of albuminuria. The estimated glomerular filtration rate in adult survivors who had received high-dose ifosfamide was 88 mL/min per 1.73 m², significantly lower than the 98 mL/min per 1.73 m² in others. Similarly, patients who had received high-dose cisplatin had an average estimated glomerular filtration rate of 83 mL/min per 1.73 m², compared with 101 mL/min per 1.73 m² in survivors not treated with high-dose cisplatin.

In contrast to ifosfamide, its isomer cyclophosphamide was not associated with long-term nephrotoxicity; neither was carboplatin, a cisplatin analogue, or methotrexate. Although methotrexate is known to cause acute nephrotoxicity, this phenomenon appears to be completely reversible, since methotrexate-treated, long-term cancer survivors didn’t develop tubular or glomerular dysfunction.

This long-term study was supported by the Dutch Kidney Foundation. Dr. Shirali, who was not involved in the study, reported having no financial conflicts.

[email protected]

LAS VEGAS – Adult survivors of childhood cancer treated with high-dose cisplatin or high-dose ifosfamide are at markedly increased risk for chronic renal impairment, according to a large Dutch study with a median 18.3-year follow-up.

Long-term treatment-related nephrotoxicity was also seen in the adult survivors of childhood cancer who underwent unilateral nephrectomy combined with abdominal radiation therapy.

"This study is perhaps a warning to us when we’re seeing these adult survivors of childhood cancer in clinic, particularly if they have a history of ifosfamide or cisplatin use, to pay closer attention to the development of chronic kidney disease so they can be managed better in the future," Dr. Anushree C. Shirali said at a meeting sponsored by the National Kidney Foundation.

Drug-induced acute kidney injury is a common event during cancer therapy. Its mechanisms and treatments are well studied. In contrast, the long-term nephrotoxicity of the powerful therapies used in treating childhood cancers has received much less scrutiny. But it’s an increasingly relevant issue because childhood cancer survival rates have improved substantially. Indeed, as the Dutch investigators observed, today 1 in 570 young adults is a childhood cancer survivor (Clin. J. Am. Soc. Nephrol. 2013;8:922-9).

Dr. Shirali, a nephrologist at Yale University in New Haven, Conn., highlighted the Dutch study of 763 adult survivors of childhood cancer because of its unusually long and complete follow-up. The investigators included nearly 90% of all adult survivors treated at Erasmus University in Rotterdam, the Netherlands, during 1964-2005.

High-dose ifosfamide was associated with a 6.2-fold greater likelihood of an increased urinary beta₂-microglobulin/creatinine ratio indicative of persisting tubular dysfunction, compared with cancer survivors not receiving that therapy. High-dose cisplatin was associated with a 5.2-fold increased risk of albuminuria. The estimated glomerular filtration rate in adult survivors who had received high-dose ifosfamide was 88 mL/min per 1.73 m², significantly lower than the 98 mL/min per 1.73 m² in others. Similarly, patients who had received high-dose cisplatin had an average estimated glomerular filtration rate of 83 mL/min per 1.73 m², compared with 101 mL/min per 1.73 m² in survivors not treated with high-dose cisplatin.

In contrast to ifosfamide, its isomer cyclophosphamide was not associated with long-term nephrotoxicity; neither was carboplatin, a cisplatin analogue, or methotrexate. Although methotrexate is known to cause acute nephrotoxicity, this phenomenon appears to be completely reversible, since methotrexate-treated, long-term cancer survivors didn’t develop tubular or glomerular dysfunction.

This long-term study was supported by the Dutch Kidney Foundation. Dr. Shirali, who was not involved in the study, reported having no financial conflicts.

[email protected]

MELBOURNE – Elevated total cholesterol and low-density lipoprotein cholesterol levels in patients with coronary heart disease were significantly associated with an increased risk of chronic kidney disease, according to a retrospective analysis of data from two large, randomized, controlled trials.

Data presented at the World Congress of Cardiology 2014 showed total cholesterol levels above 240 mg/dL were associated with a significant 78% increase in the risk of chronic kidney disease, while LDL cholesterol greater than 190 mg/dL was associated with a 72% increase in risk.

Elevated non–high-density lipoprotein cholesterol levels and the ratio of total cholesterol to HDL cholesterol were both associated with elevated risk of chronic kidney disease, but reduced HDL cholesterol and the ratio of apolipoprotein B/apolipoprotein A did not significantly affect risk.

Dyslipidemia is present in around 60% of patients with chronic kidney disease, noted presenter Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco. Previous studies in patients with coronary heart disease and chronic kidney disease also have shown that statins have a renoprotective effect.

However, Dr. Deedwania said there has been little exploration of the impact of baseline lipid parameters on renal function.

"We have found that there is a significant increase in not only the prevalence but also the morbidity and mortality in people with chronic kidney disease with coronary events and other cardiovascular events," Dr. Deedwania said in an interview.

Using data from the Treating to New Targets (TNT) study and Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study, in which patients were treated with either atorvastatin or simvastatin, researchers were able to examine the relationship between baseline lipoprotein parameters and kidney function in a combined cohort of more than 19,000 patients with coronary heart disease.

"That showed very good relationship between total cholesterol and LDL cholesterol with progressive decline in renal function, which then helped me explain what I had observed earlier in terms of improvement in kidney function in early-stage patients with statins," Dr. Deedwania said at the meeting, which was sponsored by the World Heart Federation.

The relationship between lipoprotein parameters and chronic kidney disease persisted even after adjustment for age, body mass index, smoking status, diabetes history and status, hypertension, and treatment assignment.

The study defined chronic kidney disease as an estimated glomerular filtration rate below 60 mL/min per 1.73 m². However, Dr. Deedwania said no patients achieved stage 4 kidney disease, and all eGFR measurements fell between 45 and 60 mL/min per 1.73 m².

The analysis used a relatively early definition of kidney disease as the outcome of interest, observed session chair Dr. Vlado Perkovic, professor of medicine at the University of Sydney (Australia).

Dr. Deedwania later said he believed the key was to focus on early-stage interventions rather than waiting until the disease progressed and suggested some interventional trials had failed to achieve an effect because they were done in more advanced patients.

The researchers declared a range of speakers fees, consultancies, and honoraria from the pharmaceutical industry; two of the authors were employees of Pfizer.

MELBOURNE – Elevated total cholesterol and low-density lipoprotein cholesterol levels in patients with coronary heart disease were significantly associated with an increased risk of chronic kidney disease, according to a retrospective analysis of data from two large, randomized, controlled trials.

Data presented at the World Congress of Cardiology 2014 showed total cholesterol levels above 240 mg/dL were associated with a significant 78% increase in the risk of chronic kidney disease, while LDL cholesterol greater than 190 mg/dL was associated with a 72% increase in risk.

Elevated non–high-density lipoprotein cholesterol levels and the ratio of total cholesterol to HDL cholesterol were both associated with elevated risk of chronic kidney disease, but reduced HDL cholesterol and the ratio of apolipoprotein B/apolipoprotein A did not significantly affect risk.

Dyslipidemia is present in around 60% of patients with chronic kidney disease, noted presenter Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco. Previous studies in patients with coronary heart disease and chronic kidney disease also have shown that statins have a renoprotective effect.

However, Dr. Deedwania said there has been little exploration of the impact of baseline lipid parameters on renal function.

"We have found that there is a significant increase in not only the prevalence but also the morbidity and mortality in people with chronic kidney disease with coronary events and other cardiovascular events," Dr. Deedwania said in an interview.

Using data from the Treating to New Targets (TNT) study and Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study, in which patients were treated with either atorvastatin or simvastatin, researchers were able to examine the relationship between baseline lipoprotein parameters and kidney function in a combined cohort of more than 19,000 patients with coronary heart disease.

"That showed very good relationship between total cholesterol and LDL cholesterol with progressive decline in renal function, which then helped me explain what I had observed earlier in terms of improvement in kidney function in early-stage patients with statins," Dr. Deedwania said at the meeting, which was sponsored by the World Heart Federation.

The relationship between lipoprotein parameters and chronic kidney disease persisted even after adjustment for age, body mass index, smoking status, diabetes history and status, hypertension, and treatment assignment.

The study defined chronic kidney disease as an estimated glomerular filtration rate below 60 mL/min per 1.73 m². However, Dr. Deedwania said no patients achieved stage 4 kidney disease, and all eGFR measurements fell between 45 and 60 mL/min per 1.73 m².

The analysis used a relatively early definition of kidney disease as the outcome of interest, observed session chair Dr. Vlado Perkovic, professor of medicine at the University of Sydney (Australia).

Dr. Deedwania later said he believed the key was to focus on early-stage interventions rather than waiting until the disease progressed and suggested some interventional trials had failed to achieve an effect because they were done in more advanced patients.

The researchers declared a range of speakers fees, consultancies, and honoraria from the pharmaceutical industry; two of the authors were employees of Pfizer.

MELBOURNE – Elevated total cholesterol and low-density lipoprotein cholesterol levels in patients with coronary heart disease were significantly associated with an increased risk of chronic kidney disease, according to a retrospective analysis of data from two large, randomized, controlled trials.

Data presented at the World Congress of Cardiology 2014 showed total cholesterol levels above 240 mg/dL were associated with a significant 78% increase in the risk of chronic kidney disease, while LDL cholesterol greater than 190 mg/dL was associated with a 72% increase in risk.

Elevated non–high-density lipoprotein cholesterol levels and the ratio of total cholesterol to HDL cholesterol were both associated with elevated risk of chronic kidney disease, but reduced HDL cholesterol and the ratio of apolipoprotein B/apolipoprotein A did not significantly affect risk.

Dyslipidemia is present in around 60% of patients with chronic kidney disease, noted presenter Dr. Prakash Deedwania, professor of medicine at the University of California, San Francisco. Previous studies in patients with coronary heart disease and chronic kidney disease also have shown that statins have a renoprotective effect.

However, Dr. Deedwania said there has been little exploration of the impact of baseline lipid parameters on renal function.

"We have found that there is a significant increase in not only the prevalence but also the morbidity and mortality in people with chronic kidney disease with coronary events and other cardiovascular events," Dr. Deedwania said in an interview.

Using data from the Treating to New Targets (TNT) study and Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study, in which patients were treated with either atorvastatin or simvastatin, researchers were able to examine the relationship between baseline lipoprotein parameters and kidney function in a combined cohort of more than 19,000 patients with coronary heart disease.

"That showed very good relationship between total cholesterol and LDL cholesterol with progressive decline in renal function, which then helped me explain what I had observed earlier in terms of improvement in kidney function in early-stage patients with statins," Dr. Deedwania said at the meeting, which was sponsored by the World Heart Federation.

The relationship between lipoprotein parameters and chronic kidney disease persisted even after adjustment for age, body mass index, smoking status, diabetes history and status, hypertension, and treatment assignment.

The study defined chronic kidney disease as an estimated glomerular filtration rate below 60 mL/min per 1.73 m². However, Dr. Deedwania said no patients achieved stage 4 kidney disease, and all eGFR measurements fell between 45 and 60 mL/min per 1.73 m².

The analysis used a relatively early definition of kidney disease as the outcome of interest, observed session chair Dr. Vlado Perkovic, professor of medicine at the University of Sydney (Australia).

Dr. Deedwania later said he believed the key was to focus on early-stage interventions rather than waiting until the disease progressed and suggested some interventional trials had failed to achieve an effect because they were done in more advanced patients.

The researchers declared a range of speakers fees, consultancies, and honoraria from the pharmaceutical industry; two of the authors were employees of Pfizer.