Kidney disease coupled with heart disease common problem in elderly

Chronic kidney disease (CKD) is common and linked with heart disease in the very elderly, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN).

25 april 2011--CKD is a major public health problem that disproportionately affects the elderly. Shani Shastri, MD, Mark Sarnak, MD (Tufts Medical Center), and their colleagues examined kidney and heart disease in octogenarians. The researchers assessed the prevalence of CKD by using different formulas based on different kidney function markers (serum creatinine and cystatin C) in 1,028 octogenarians enrolled in the Cardiovascular Health Study All Stars, a study of adults aged 65 years and older that examined subclinical and clinical risk factors for cardiovascular disease.

The prevalence of CKD was very high in the elderly individuals in this study. However, the study revealed that different formulas used to assess prevalence provide different pictures of CKD in the elderly. Prevalence differed from 33% to 51% depending on the equation used, even though there is a strong correlation between creatinine- and cystatin C-based estimates of kidney function. According to Dr. Sarnak, the study emphasizes that using different formulas to estimate kidney function in octogenarians results in different estimates of the prevalence of CKD. "Unfortunately, there is no gold standard estimating equation that has been developed or validated in octogenarians," he said.

Regardless of which equation researchers used to estimate kidney function, CKD in the elderly was associated with cardiovascular disease. Elderly individuals with CKD were approximately one-and-a-half to two times as likely to suffer from coronary heart disease, heart failure, or stroke as those without CKD. "Therefore, even in the very old, kidney function appears to be a marker of vascular disease," said Dr. Sarnak.

More information: The article entitled, "Chronic Kidney Disease in Octogenarians" will appear online at doi 10.2215/CJN.08801010

Provided by American Society of Nephrology

Coronary Angiography Found Safe in Chronic Kidney Disease


Procedure does not reduce kidney function in high-risk patients awaiting a transplant

24 oct 2009-- Screening coronary angiography does not reduce renal function in high-risk patients with advanced chronic kidney disease awaiting a kidney transplant, according to a study published online Oct. 15 in the Clinical Journal of the American Society of Nephrology.

Nicola Kumar, from the Imperial College Kidney and Transplant Institute in London, and colleagues retrospectively determined the risk of contrast nephropathy in 76 high-risk patients with advanced chronic kidney disease (stages IV or V) who underwent screening coronary angiography.

The researchers found that the glomerular filtration rate was similar six months before and after coronary angiography. Cumulative dialysis-free survival was 89.1 percent six months after angiography, and 32.9 percent of patients received a kidney transplant, of which 88.0 percent were performed before the need for dialysis. Flow-limiting coronary artery disease was present in 30.3 percent of patients.

"The data suggest coronary angiography screening does not accelerate the decline in renal function for patients with advanced chronic kidney disease, facilitating a safe preemptive transplant program," Kumar and colleagues conclude. "If the procedure is performed appropriately with small volumes of contrast, biplane angiography using N-Acetylcysteine, and adequate hydration around the time of the procedure, then the risk of contrast exposure can be minimized in this population."

Abstract
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Cardiac Score Predicts Death in Chronic Kidney Disease

TIMI score effective in patients with kidney dysfunction and chest pain or a heart attack

09 june 2009-- A risk stratification score is effective in predicting mortality risk across a range of kidney function in patients with chest pain or a heart attack, according to a study in the June 1 issue of the American Journal of Cardiology.

Usman Baber, M.D., and colleagues from Mount Sinai Hospital in New York City examined the prognostic value of the Thrombolysis In Myocardial Infarction (TIMI) risk score in 6,940 patients with moderate to advanced kidney disease and unstable angina pectoris or non-ST elevation myocardial infarction.

During a median follow-up of 3.2 years, the researchers observed 813 deaths. The adjusted mortality hazard ratio for the highest TIMI scores compared with lower scores was as high as 4.26 in patients with an estimated glomerular filtration rate (eGFR) of 60 or greater, as high as 1.77 for patients with an eGFR of 30 to 59, as high as 2.83 for patients with an eGFR less than 30, and as high as 3.67 for patients on dialysis.

"Our study demonstrates that the TIMI risk score, a conventional algorithm that does not include nontraditional risk factors, discriminates mortality risk in patients with advanced chronic kidney disease and on dialysis," Baber and colleagues conclude.

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Impaired kidney function raises risk of heart problems in the elderly

21 jan 2009--A study published next week in the open access journal PLoS Medicine suggests that elderly people with damaged kidneys are at greater risk of cardiovascular disease, such as heart failure and stroke, and other causes of mortality. The findings indicate that greater efforts should be made to encourage elderly people who have impaired kidney function alongside other risk factors—such as high blood cholesterol and high blood pressure, which are often a result of smoking and diet—to make lifestyle changes to avoid developing cardiovascular problems.
Most countries face increasing rates of cardiovascular disease and it is the single leading cause of death in the United States and many European countries. It has already been established that young and middle-aged people with a reduced estimated glomerular filtration rate (eGFR)—the measurement of the movement of waste and excess fluid through the kidneys—are more likely to develop cardiovascular disease than those with healthy kidneys. To establish how at risk elderly people with impaired kidney function were, Ian Ford of the University of Glasgow and colleagues analysed existing data from a three year clinical trial conducted among men and women aged between 70 and 82 in Scotland, Ireland and the Netherlands.
The trial—known as the Prospective Study of Pravastatin in the Elderly at Risk, or PROSPER trial—had been designed to test the effect of the statin pravastatin on the development of cardiovascular disease. Dividing the trial participants into four groups based on their eGFR at the start of the study, Ian Ford and colleagues established that the patients with a low eGFR—those with the most impaired kidney function—were twice as likely to die from any cause as those with healthier kidneys. They also established that the patients with the most damaged kidneys were three times more likely to have non-fatal heart failure or disease and were more likely to die as a result of heart disease or failure.
The data also showed that treatment with the drug pravastatin reduced the number of fatal and non-fatal heart problems more effectively amongst the group of patients with the most damaged kidneys—although the researchers warn that this finding is statistically borderline and say the most that can be concluded is that there is no reason to exclude elderly people with damaged kidneys from treatment with statins, the drugs that reduce blood cholesterol levels in those at risk of cardiovascular disease.
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Citation: Ford I, Bezlyak V, Stott DJ, Sattar N, Packard CJ, et al. (2009) Reduced glomerular filtration rate and its association with clinical outcome in older patients at risk of vascular events: Secondary analysis. PLoS Med 6(1): e1000016.

Weight Gain Increases Risk to Kidneys

By Michael Smith
SEOUL, South Korea, 23 june 2008 -- Gaining weight, even while remaining within the normal range, increases a patient's risk of chronic kidney disease, researchers here said.
In a four-year prospective cohort study, men who gained more than 0.75 kilograms a year (about 1.65 pounds) were more than four times as likely to develop kidney disease as those who gained less than 0.25 kilograms, according to Seungho Ryu, M.D., of Kangbuk Samsung Hospital, and colleagues.
Although obesity is associated with an increased risk of chronic kidney disease, the findings in this study held true whether participants were of normal weight, overweight, or obese, Dr. Ryu and colleagues reported online in the Journal of the American Society of Nephrology.
The curve was actually U-shaped, the researchers said, with a loss of more than 0.75 kilograms a year also associated with an increased risk of kidney disease.
But that finding "should be interpreted with caution," the researchers said, because it contradicts most other research. It's possible, they said, that participants who lost large amounts of weight were more overweight and less healthy to start with.
The researchers studied 8,792 men who were followed for an average of 4.13 years, as they took part in government-mandated annual or biennial comprehensive health exams.
During the 35,927 person-years of follow-up, there were 427 incident cases of chronic kidney disease, defined by an estimated glomerular filtration rate of less than 64 millimeters per minute per 1.73 meters squared.
Cox proportional hazards analysis, adjusted for a range of factors including age, baseline BMI, incident hypertension, regular exercise, and HDL cholesterol levels, showed increased risk with respect to those whose weight changed minimally during follow-up.
Specifically, with participants who gained or lost less than 0.25 kilograms a year (about 0.55 pounds) as the reference group, the analysis showed:
For those who gained 0.75 kilograms or more, the hazard ratio for chronic kidney disease was 4.29, with a 95% confidence interval from 3.20 to 5.76.
Those who lost 0.75 kilograms or more had a hazard ratio for chronic kidney disease of 3.40, with a 95% confidence interval from 2.44 to 4.75.
Those who gained or lost between 0.25 and 0.75 kilograms a year also had increased risk, but the confidence intervals crossed unity.
The trend was significant at P<0.001.
The study had a large sample size, wrote the researchers, which allowed them to stratify participants by baseline BMI and to find that a gain of 0.75 kilograms a year predicted kidney disease even in those whose weight remained in the normal range.
One limitation of the study, they said, is that they used an estimated rather than a measured glomerular filtration rate. On the other hand, such estimates are widely used in epidemiological studies and clinical practice to evaluate renal function.
They also pointed out that "ethnic factors that are characteristic of the Asian population are not well established with respect to using equations that estimate GFR; therefore, these equations need to be validated in large Asian cohorts with additional studies."
The researchers also noted that they had no information on family history of chronic kidney disease, although such a history is associated with increased risk, and loss to follow-up may have biased the results.
The researchers did not report any external support for the study. Dr. Ryu said he had no disclosures.
Primary source: Journal of the American Society of NephrologySource reference:Ryu S, et al "Changes in body weight predict CKD in healthy men" J Am Soc Nephrol 2008; DOI: 10.1681/ASN.2007121286.

Subclinical Hypothyroidism Common with Chronic Kidney Disease

By Charles Bankhead
DENVER, 12 june 2008-- Almost 20% of patients with chronic kidney disease have subclinical primary hypothyroidism, according to data from a large cohort of outpatients.
About 10% of unselected patients had subclinical primary hypothyroidism, Michel Chonchol, M.D., of the University of Colorado Health Sciences Center, and colleagues reported online in the Clinical Journal of the American Society of Nephrology.
However, patients with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 had a prevalence of 18%.
"Future clinical and experimental studies should explore potential causal mechanisms linking subclinical primary hypothyroidism and chronic kidney disease," the authors concluded.
"The possible adverse effects of subclinical hypothyroidism on cardiovascular risk associated with chronic kidney disease are presently unknown. Whether adult patients with chronic kidney disease should be routinely screened for subclinical hypothyroidism requires further investigation."
An improved capability to detect subtle changes in thyroid function has led to the emergence of the concept of subclinical primary hypothyroidism, defined as elevated serum thyrotropin levels but normal free thyroxine levels.
Subclinical primary hypothyroidism has been associated with markers of cardiovascular risk and impaired cardiac function, the authors said. Moreover, subclinical primary hypothyroidism is an independent predictor of all-cause mortality in dialysis patients and is a risk factor for nephropathy and cardiovascular events in patients with type 2 diabetes.
The prevalence of subclinical primary hypothyroidism in the general population and by different levels of estimated GFR has not been studied extensively. Dr. Chonchol and colleagues performed a cross-sectional analysis of a large database from a clinical chemistry laboratory in Verona, Italy.
The study involved 3,089 adults, 293 (9.5%) of them meeting the laboratory definition for subclinical primary hypothyroidism and 277 (9%) who had an estimated GFR of lower than 60 mL/min/1.73 m2.
The prevalence of subclinical primary hypothyroidism increased from 7% in patients with an estimated GFR ≥90 mL/min/1.73 m2 to 17.9% in patients with an estimated GFR <60 mL/min/1.73 m2 (P<0.0001 for trend).
After adjustment for age, sex, fasting glucose, total cholesterol, and triglycerides, an estimated GFR of lower than 60 mL/min/1.73 m2 increased the likelihood of subclinical hypothyroidism by almost 75% compared with patients who had higher estimated GFR values (OR 1.73, 95% CI 1.20 to 2.48, P=0.003).
"With progressively lower estimated GFR, there was graded increased likelihood of subclinical primary hypothyroidism," the authors said.
The authors noted several limitations of the study. "Because this study is cross-sectional, the present analysis is limited in its ability to establish causal or temporal relationships between subclinical primary hypothyroidism and kidney disease."
"Nonthyroidal (e.g., low T3 syndrome, which is typically seen in some ill patients, including those with end-stage renal disease) and thyroidal causes of subclinical hypothyroidism were not identified."
Dr. Chonchol and colleagues reported no disclosures.

Primary source: Clinical Journal of the American Society of NephrologySource reference:Chonchol M, et al "Prevalence of subclinical hypothyroidism in patients with chronic kidney disease" Clin J Am Soc Nephrol 2008; DOI: 10.2215/cjn.00800208.

Raloxifene (Evista) No Hazard to Women with Chronic Kidney Disease

MINNEAPOLIS, April 9, 2008-- Postmenopausal women with chronic kidney disease can take raloxifene (Evista) to prevent osteoporosis without the risk of exacerbating their renal conditions, according to investigators here.
Raloxifene, a selective estrogen receptor modulator, significantly improved bone mineral density and reduced the risk of vertebral fracture versus placebo, irrespective of a patient's baseline kidney function, Areef Ishani, M.D., of the University of Minnesota, and colleagues reported online in advance of the July issue of the Journal of the American Society of Nephrology.
The rate of adverse events and associated discontinuation did not differ between treatment groups across the range of kidney function included in the study.
"We found that the effect of raloxifene on rates of spinal bone loss, risk for fractures, and rates of adverse events was consistent across all risk subgroups defined by baseline [creatinine clearance or estimated glomerular filtration rate]," the authors concluded.
The prevalence of low bone mineral density and osteoporosis increases with greater severity of chronic kidney disease. Even so, most randomized clinical trials evaluating pharmacologic agents to prevent fractures in postmenopausal women have excluded patients with serum creatinine levels >2.0 mg/dL, the authors noted.
In an effort to clarify the impact of osteoporosis therapies in postmenopausal women with chronic kidney disease, Dr. Ishani and colleagues performed a post hoc analysis of data from the Multiple Outcomes of Raloxifene Evaluation (MORE). The trial involved 7,705 postmenopausal women, who were randomized to placebo or to one of two doses of raloxifene. The primary objective was to evaluate raloxifene's effect on the risk of vertebral fracture in women with established osteoporosis.
Dr. Ishani and colleagues limited their analysis to 7,316 MORE participants who had baseline serum creatinine measurements. The data were stratified by creatinine clearance values as estimated using the Cockcroft-Gault formula: <45 mL/min/1.732, 45 to 59 mL/min/1.732, and ≥60 mL/min/1.732.
For each category of kidney function, patients assigned to raloxifene had a net gain in bone mineral density during follow-up, compared with a loss in the placebo group. Statistically significant differences were observed for the femoral neck (P=0.012) and lumbar spine (P<0.001). Use of raloxifene also was associated with a 43% reduction in the incidence of vertebral fractures (OR 0.57, 95% CI 0.47 to 0.69) but had no effect on the risk of nonvertebral fracture (OR 0.94, 95%CI: 0.80 to 1.11).

NKF: Chronic Kidney Disease Often Missed in Primary Care

By Charles Bankhead
DALLAS, April 7 -- Chronic kidney frequently goes undiagnosed by primary care physicians, even in patients with clear risk factors, according to a study from the VA healthcare system.Medical records of two-thirds of patients with chronic kidney disease by estimated glomerular filtration rate had no evidence that the disease had been recognized, Grady Wick, M.D., of the University of Illinois at Chicago, reported at the National Kidney Foundation meeting here.Recognition improved with worsening kidney function.White patients and women had the lowest rates of detection.
"We found that recognition was pretty poor overall," said Dr. Wick. "Obviously, as [glomerular filtration rate] went down, the recognition rate went up. In the diagnostically nebulous area of a GFR of 50 or 60, recognition was only 18%."
To determine how often the condition is recognized in VA patients, he and his colleagues reviewed medical records of 354,468 patients seen at VA primary care clinics during 2002. They found that 78,563 patients had at least two estimated glomerular filtration rate values during the review period.
Chronic kidney disease was defined as an estimated rate <60 mL/min/1.732 on two occasions at least 90 days apart. Disease recognition was defined as the presence of a diagnostic code related to kidney disease or evidence of care by a nephrologist.
Of the patients with two estimated glomerular filtration rate measurements, 20,923 (26.6%) had chronic kidney disease. The investigators found evidence of disease recognition in 35.4% of cases.
The rate of recognition increased from 18.4% among patients with an estimated rate between 50 and 60 mL/min/1.732 to 92.2% for patients with an estimated rate <15 mL/min/1.732.
A separate analysis of disease recognition by serum creatinine level showed that the rate of recognition increased from 15.7% in patients with serum creatinine levels between 1.0 and 1.5 mg/dL to 90% among patients with creatinine levels ≥3.5 mg/dL.
Among patients with diabetes (25% of the population) or hypertension (50%), chronic kidney disease was recognized in 39% and 37%, respectively.
Recognition rates were 37% to 45% in patients with cardiovascular disease, peripheral vascular disease, a history of stroke, and chronic obstructive pulmonary disease.
Recognition rates differed substantially by race and sex. Primary care providers recognized chronic kidney disease in 55.7% of nonwhite patients versus 33.3% of white patients and in 35.9% of men versus 15.9% of women.
The rate of recognition did not differ between patients younger than 65 (37.6%) versus 65 or older (34.8%).
After adjustment for confounders, Dr. Wick and colleagues found that women were 66% less likely than men to have chronic kidney disease recognized by their primary care providers (OR 0.34, 95% CI 0.27 to 0.43). White patients were 57% less likely than black patients to have documentation of chronic kidney disease in medical records (OR 0.43, 95% CI: 0.39 to 0.47).
Dr. Wick said findings from a VA patient population might not be generalizable to other patient populations, but he acknowledged that that issue was beyond the scope of the study.
Dr. Wick reported no disclosures.
Primary source: National Kidney Foundation Meeting 2008Source reference:Fischer M, et al "Chronic kidney disease is significantly underrecognized among VA primary care users" NKF Meeting 2008; Abstract 218.

ACE Inhibitors or ARBs in Hypertension? In Chronic Kidney Disease?

Steve Stiles
January 17, 2008 — A pair of articles in the January 1, 2008 Annals of Internal Medicine brings together the existing literature to address issues that have persisted since the introduction of angiotensin-receptor blockers (ARBs): namely, when and how these drugs might be advantageous in conditions long served by angiotensin-converting enzyme (ACE) inhibitors.
A meticulous survey of studies found that the two drug classes are about equally safe and effective at managing high blood pressure and have similar effects on other risk factors and clinical outcomes in patients with essential hypertension [1]. It also confirmed that ARBs are less likely to cause coughing, but suggested that the side effect might be less common with ACE inhibitors than randomized trials indicate.
In the setting of chronic kidney disease (CKD), concludes the other study, which is a meta-analysis, ACE inhibitor and ARB monotherapy are similarly effective at reducing proteinuria, but a combination of the two angiotensin-2-suppressing drugs works better than either agent individually [2]. But a blanket recommendation to combine them would be premature, according to the authors, because there is little evidence that the combination would improve clinical outcomes over monotherapy, and the safety of such combination therapy is largely undefined.
The authors of both analyses acknowledge that they have major limitations, particularly the heterogeneity of the combined studies, their limited follow-up times, and spotty data on adverse effects.
"The most important contribution of these systematic reviews is that they tell us what we do not know," notes an accompanying editorial [3]. They suggest that the two drug classes are comparably effective as antihypertensive and antiproteinuric agents, writes Dr Patrick S Parfrey (Memorial University of Newfoundland, St John's), but "we know far too little about their long-term safety, especially with combination therapy of ACE inhibitors plus ARBs in stage 3 or 4 chronic kidney disease."
No "clinically meaningful difference" in hypertension
"With the exception of rates of cough, the available evidence does not strongly support the hypothesis that ACE inhibitors and ARBs have clinically meaningful differences in benefits or harms for individuals with essential hypertension," according to the report's authors, led by Dr David B Matchar (Duke Center for Clinical Health Policy Research, Durham, NC).
He and his colleagues analyzed 69 reports based on 61 randomized and observational studies that lasted at least three months and directly compared an ACE inhibitor and an ARB in adults with essential hypertension and evaluated meaningful end points like blood pressure control, treatment compliance, and adverse events.
The strength of evidence was considered high for the observation that the two drug classes are similarly effective at controlling blood pressure. They were comparable in 37 of the 50 studies evaluated for that outcome; 47 of those 50 studies were randomized controlled trials (RCTs).
Also similar were the associated rates of death and cardiovascular (CV) events, quality-of-life measures, successful use of the ACE inhibitor or ARB as the only antihypertensive agent, effects on lipid levels and left ventricular (LV) mass, and risk of dysglycemia or renal dysfunction.
Mortality and CV-event outcomes were available for only nine studies, most of which excluded patients with clinically significant CV disease or comorbidities, the group reported. Few of the studies followed patients for even as long as a year, and "there were really very limited data about major events, such as heart attack and stroke," Matchar told heartwire.
The two drug classes showed similar risks of headache and dizziness, but ACE inhibitors were about three times more likely to have cough as a side effect, regardless of whether the study was cohort-based or an RCT. But the rates of cough were "dramatically higher" in the RCTs, probably because in RCTs, in contrast to cohort-based studies, patients are more likely to be queried specifically for that side effect, Matchar said.
Other evidence suggested that patients are more likely to stick with ARBs than with ACE inhibitors when each were given as initial therapy, but "the magnitude of this difference is difficult to quantify," according to the report.
Although any differences in efficacy between the two drug classes are likely to be small, according to Matchar et al, pinning down such small differences might be worth the challenge of mounting a large long-term randomized study, given that small changes in blood pressure are known to have a substantial outcomes effect.
To heartwire Matchar said, "if there really is a marginal benefit to be had from, say, greater tolerability of ARBs compared with ACE inhibitors, then we really do need some [more definitive] head-to-head studies to show it."
"Encouraging" support for combination therapy in CKD
The other reported study provided "high-quality evidence" that monotherapy with ACE inhibitors or ARBs reduces proteinuria to comparable degrees in patients with CKD, regardless of the underlying cause of renal dysfunction. And, write the authors, led by Dr Regina Kunz (University Hospital, Basel, Switzerland), "evidence is encouraging that the combination of the two drugs is more effective, at usual doses, than either drug alone."
The group analyzed 49 RCTs that compared ARBs with ACE inhibitors, a combination of the two drug classes, placebo, or calcium-channel blockers and tracked microalbuminuria and proteinuria over at least four weeks in patients with CKD.
ARBs and ACE inhibitors were similarly effective at lowering proteinuria, ARBs were more effective than calcium-channel blockers, and a combination of ARBs and ACE inhibitors was more effective than either agent alone.
Ratio of means (95% CI)* for change in proteinuria, by randomized therapy, over two follow-up intervals
Randomized therapy
Over 1 - 4 mo
Over 5 - 12 mo
ARBs vs placebo
0.57 (0.47 - 0.68)
0.66 (0.63 - 0.69)
ARBs vs ACE-I
0.99 (0.92 - 1.05)
1.08 (0.96 - 1.22)
ARBs vs CCBs
0.69 (0.62 - 0.77)
0.62 (0.55 - 0.70)
ARB+ACE-I vs ARBs
0.76 (0.68 - 0.85)
0.75 (0.61 - 0.92)
ARB+ACE-I vs ACE-I
0.78 (0.72 - 0.84)
0.82 (0.67 - 1.01)
ACE-I = angiotensin-converting-enzyme inhibitor; ARB = angiotensin-receptor blocker; CCB = calcium-channel blocker*Ratio of means = ratio of the average treatment effect in the intervention group (either ARBs alone or in combination with ACE inhibitors) relative to the control group (placebo or single-drug comparator), with 95% CI
Only one-third of the reports included details on how adverse drug effects were assessed in the studies; according to the authors, few "presented adverse drug reactions in a structured manner that allowed us to make causal inferences," and 45 of the 49 studies "lacked quantitative data even on more common but less severe adverse drug reactions, prohibiting a reliable estimate of their incidence."
According to Parfrey, the editorialist, the findings from Kunz et al, along with those of the recent Irbesartan in the Management of PROteinuric patients at high risk for Vascular Events (IMPROVE) trial [4], suggest that "monotherapy with inhibitors of the renin-angiotensin system is sufficient for patients with early-stage renal disease and relatively low albumin excretion and that combination therapy is effective for patients with heavier proteinuria." However, he cautions, "for combination therapy, we have no safety data in chronic kidney disease, and we do not know the rates of progression of chronic kidney disease. . . . We need a large-scale, long-term, head-to-head, three-group RCT comparing monotherapy with ARBs or ACE inhibitors and with combination therapy involving both ARBs and ACE inhibitors."
The report by Matchar et al notes that coauthor Dr Douglas C McCrory (Duke Center for Clinical Health Policy Research) has received honoraria from AstraZeneca and coauthor Dr Gregory P Samsa (Duke Center for Clinical Health Policy Research) holds Pfizer stock or stock options. The article by Kunz et al says that "meetings, literature search, and statistical analysis were supported in part by Novartis" and that coauthor Dr Johannes F E Mann (Munich General Hospital, Germany) has received honoraria from Boehringer-Ingelheim, Novartis, and Aventis and grants from Aventis and Novartis.
Sources
Matchar DB, McCrory DC, Orlando LA, et al. Systematic review: Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med. 2008;148:16-29.
Kunz R, Friedrich C, Wolbers M, Mann JFE. Meta-analysis: Effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148:30-48.
Parfrey PS. Inhibitors of the renin angiotensin system: Proven benefits, unproven safety. Ann Intern Med. 2008; 48:76-77.
Bakris GL, Ruilope L, Locatelli F, et al. Treatment of microalbuminuria in hypertensive subjects with elevated cardiovascular risk: results of the IMPROVE trial. Kidney Int. 2007;72:879-885.

Guidelines Issued for Treatment of Anemia in Patients With Chronic Kidney Disease

Laurie Barclay
December 17, 2007 — Recommendations to treat anemia in patients with chronic kidney disease (CKD) in the primary care setting are reviewed in the December issue of the Southern Medical Journal. The report focuses on the association of anemia in CKD with diabetes, cardiovascular disease, and poor disease outcome, and provides practical guidelines for early recognition and management of this common but modifiable risk factor, including use of available agents to treat the anemia.
"Anemia is a common comorbidity associated with chronic kidney disease (CKD); it starts early in the course of the disease and worsens as renal function declines," writes Jan N. Basile, MD, from the Ralph H. Johnson Veterans Administration Medical Center and the Medical University of South Carolina in Charleston, South Carolina. "Anemia associated with declining kidney function is predominantly due to inadequate renal production of the hormone erythropoietin in response to low hemoglobin (Hb) levels, but regardless of the etiology, anemia in CKD results in fatigue, reduced exercise capacity, impaired cognitive and immune function, and reduced quality of life. Moreover, anemia of CKD significantly contributes to disease burden by causing or exacerbating existing comorbidities."
Anemia can be viewed as a risk multiplier in CKD, because patients with anemia vs those without anemia and with similar comorbidities have a significantly increased risk for death. Diabetes and hypertension are the 2 leading causes of CKD, and these conditions are typically first recognized and managed by the primary care clinician.
Thanks to the growing epidemic of diabetes and hypertension, the global prevalence of CKD is dramatically and rapidly increasing. Therefore, it is essential that the primary care clinician recognize CKD and the underlying risk factors, with adequate management of risk factors to delay progression to end-stage renal disease (ESRD) and to improve patient outcomes.
As kidney function worsens, erythropoietin production decreases, resulting in the frequent comorbidity of anemia with CKD. Another cause of anemia in CKD is iron deficiency, and potential contributing factors may include decreased red blood cell lifespan, chronic blood loss, secondary hyperparathyroidism, inflammation, nutritional (folate) deficiency, and buildup of uremic toxins and other inhibitors of erythropoiesis.
Anemia in CKD exacerbates the comorbidities of diabetes and hypertension, contributing to poor disease outcome and higher mortality, even in patients with only mild renal impairment. Poor cardiovascular outcomes occur frequently in patients with CKD, mandating continued research concerning the relationship between anemia correction in CKD and cardiovascular morbidity.
Fortunately, anemia is easy to diagnose and is usually highly responsive to therapy. The primary care clinician can easily perform an anemia evaluation and begin treatment, following management plans established in the National Kidney Foundation Kidney Disease Outcome Quality Initiative guidelines.
All patients with CKD, regardless of stage or cause, should be screened for anemia, which should be diagnosed and evaluated when Hb level is less than 12.0 g/dL in adult women and less than 13.5 g/dL in adult men. Assessment for anemia should include a complete blood count including Hb, mean corpuscular Hb (MCH), mean corpuscular volume (MCV), mean corpuscular Hb concentration (MCHC), white blood cell count and differential and platelet count, absolute reticulocyte count, serum ferritin level, and serum transferrin saturation (TSAT) level. Absolute iron deficiency is defined as a TSAT level of less than 20% and a serum ferritin level of less than 100 ng/mL; this must be corrected before starting therapy with erythropoiesis-stimulating agents (ESAs). Other possible causes of anemia should also be addressed before starting treatment with ESAs.
Oral administration for iron therapy is most convenient (at least 200 mg of elemental iron for most adult patients with CKD), but absorption is poor, sometimes requiring multiple smaller doses scheduled around mealtimes. Adverse effects may include nausea and vomiting. Some patients with CKD may require intravenous (IV) administration as iron dextran or iron sucrose. Rarely, patients may experience serious, life-threatening acute reactions to IV administration of iron.
According to current US guidelines, target Hb level in patients with CKD is 11 g/dL or more. Caution is warranted when Hb levels are intentionally maintained at more than 13 g/dL.
For patients with renal disease who undergo dialysis, ESAs are a cornerstone of treatment of anemia. However, evidence from recent studies suggests that earlier treatment of anemia in CKD may postpone the onset of ESRD and improve survival. Before initiation of dialysis, anemia of CKD is underrecognized and undertreated, although this is when normalization of anemia could have the most benefit on disease outcome. Timely treatment of anemia of CKD may improve disease outcomes, benefit quality of life, and potentially slow the progression of renal decline.
"Because of the enormous strain CKD places on the healthcare system, the burden of managing patients with, or at risk for CKD often falls upon the primary care physician," the study author writes. "An important part of the care of a CKD patient is the recognition and proper management of comorbidities to slow the progression of renal decline, and positively affect disease outcome."
Now that there are several classes of ESAs, treatment of anemia in CKD can be individualized based on specific patient needs. ESAs are available for subcutaneous administration, and there are extended dosing schedules that are more convenient for patients, thereby improving compliance.
Recombinant human erythropoietin (rHuEPO), first introduced in 1989, is effective and safe for decreasing morbidity and hospitalization costs while increasing patient quality of life. Epoetin alfa, or recombinant endogenous human erythropoietin, was first indicated for treatment of anemia in patients with CKD and renal failure. Darbepoetin alfa, an rHuEPO with 8 more sialic acid residues than epoetin alfa, has a lower binding affinity for the erythropoietin receptor than epoetin alfa but a 3-fold longer serum half-life and greater biologic activity. Two additional ESAs in development are continuous erythropoietin receptor activator and Hematide.
The recommended starting dose for epoetin alfa is 50 to 100 U/kg 3 times a week, but Hb can be increased and adequately maintained by dosing weekly or even every 2 to 4 weeks. For darbepoetin alfa, the recommended starting dose is 0.45 µg/kg once weekly, but target Hb may be achieved in some patients with 1 dose every 2 weeks.
ESA therapy may increase blood pressure, and it is therefore contraindicated in patients with uncontrolled hypertension. Rarely, patients treated with ESAs may develop antierythropoietin antibodies causing pure red cell aplasia. Antierythropoietin antibodies may make the anemia refractory to ESA therapy.
"Evidence suggests that ESA therapy can decrease the morbidity and mortality associated with CKD, slow the progression of renal disease, improve some aspects of CV function, reduce overall medical costs, and improve patient quality of life," the study author concludes. "This situation presents a critical opportunity for the primary care practitioner to recognize and manage anemia to both reduce renal risk factors and slow functional renal decline in the patient with CKD. Future studies will determine the optimal Hb level for outcome improvement in these individuals."
Dr. Basile had disclosed various financial relationships with the National Heart, Lung, and Blood Institute, Boehringer Ingelheim, Novartis, AstraZeneca, Merck, Abbott, Forest, GSK, Pfizer, and Sankyo.
South Med J. 2007;100:1200-1207.

Chronic Kidney Disease Increasing in the U.S.


BALTIMORE, Nov. 7 -- The estimated prevalence of chronic kidney disease in the U.S. has swelled over 10 years from 10% to 13%, according to a survey.
Action Points
Explain to interested patients that diabetes, hypertension, and obesity are risk factors for chronic kidney disease which in turn increases the risk of cardiovascular disease and kidney failure.
The increase has been partly fueled by an increase in diabetes, hypertension, and obesity, Josef Coresh, M.D., Ph.D., of Johns Hopkins, and colleagues, reported in the Nov. 7 issue of the Journal of the American Medical Association.
Rates of kidney failure leading to dialysis and transplantation in the U.S. have increased from 1988 to 2004, the researchers noted. Whether there has been a change in the prevalence of earlier stages of kidney disease during this period has been uncertain, the researchers said.
Chronic kidney disease is now recognized as a common condition that elevates the risk of cardiovascular disease as well as kidney failure, they said, although awareness of kidney disease in the general public is low. It is estimated that by 2015, there will be 136,000 patients with incident end-stage renal disease and a prevalence of 712,000 patients with kidney disease.
The investigators compared the prevalence, stages, and severity of chronic kidney disease in a cross-sectional analysis of two National Health and Nutrition Examination Surveys (NHANES 1988-1994 and NHANES 1999-2004). During the period between the surveys, the U.S. population became older and included a smaller proportion of non-Hispanic whites.
The nationally representative samples of noninstitutionalized Americans 20 or older included 15,488 in the earlier survey and 13,233 in the later survey.
Chronic kidney disease prevalence was determined by persistent albuminuria and decreased estimated glomerular filtration rate (GFR).
Persistence of microalbuminuria (>30 mg/g) was estimated from repeat-visit data in NHANES 1988-1994. The GFR was estimated using the abbreviated Modification of Diet in Renal Disease Study equation re-expressed to use standard serum creatinine.
The prevalence of both albuminuria and decreased GFR increased from 1988-1994 to 1999-2004, the researchers said.
The prevalence of chronic kidney disease stages one to four increased from 10.0% (95% confidence interval, 9.2%-10.9%) in 1988 to 1994 to 13.1% (95% CI: 12% to 14.1%) in 1999-2004 with a prevalence ratio of 1.3 (95% CI: 1.2 to 1.4).
The prevalence estimates of the four stages for chronic kidney disease in 1988-1994 and 1999-2004, respectively, were:
1.7% (95% CI: 1.3% to 2.2%) and 1.8% (95% CI: 1.4% to 2.3%) for stage 1.
2.7% (95% CI: 2.2% to 3.2%) and 3.2% (95% CI: 2.6% to 3.9%) for stage 2.
5.4% (95% CI: 4.9% to 6%) and 7.7% (95% CI: 7% to 8.4%) for stage 3.
0.21% (95% CI: 0.15% to 0.27%) and 0.35% (95% CI: 0.25% to 0.45%) for stage 4.
A higher prevalence of diagnosed diabetes and hypertension and higher body mass index (BMI) explained the entire increase in prevalence of albuminuria but only part of the increase in the prevalence of decreased glomerular filtration rate.
Estimation of GFR from serum creatinine has limited precision yet a change in mean serum creatinine accounted for some of the increased prevalence of chronic kidney disease, the investigators said.
Although the shift in age distribution was less pronounced in individuals older than 60 in whom kidney disease is more common, the prevalence of self-reported diabetes and hypertension increased. Similarly there was an increase in the mean BMI and the proportion of individuals who were overweight and obese, all risk factors for chronic kidney disease.
Overall, the increase of chronic kidney disease from 10% to 13.1% in the 10 years between surveys was largely attributed to the increase in obesity, diagnosed diabetes, and hypertension, and was only slightly explained by the aging of the population, the researchers said.
These increasing rates of diabetes and hypertension may lead to higher rates of complications and eventually kidney failure requiring dialysis or transplantation.
In fact, the age- and sex-adjusted incidence of end-stage renal disease in the U.S. increased 42% from 1991 to 2001. Even with progress in treating kidney failure, the growing prevalence of diabetes and the aging of the population will result in a progressive increase in the number of patients with kidney failure.
Earlier stages of kidney disease accounted for most of the individuals in this study, the researchers noted, but because these individuals have a higher risk of cardiovascular morbidity and mortality than their risk of kidney failure, management of cardiovascular risk factors in this group is also critical.
Study limitations included reliance on an estimation of GFR, rather than direct measurement. The persistence of albuminuria was also estimated from limited data and was assumed to be the same in different age and subgroups.
The high prevalence of chronic kidney disease overall, and particularly among older individuals and those with hypertension or diabetes, suggests that kidney disease needs to be a central part of future public health planning, the investigators concluded.
No financial disclosures were reported. The research for this study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Co-author Elizabeth Selvin Ph.D., was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases.
Primary source: Journal of the American Medical AssociationSource reference: Coresh J, et al "Prevalence of Chronic Kidney Disease in the United States"JAMA 2007; 298: 2038-2047.

Obesity Heightens Kidney Disease Risks

Thu Aug 16, 7:02 PM ET
THURSDAY, Aug. 16 (HealthDay News) -- Chronic kidney disease patients who are also obese are much more likely than normal-weight patients to have a condition called hyperparathyroidism, which raises their risk of heart problems and death, U.S. researchers say.
Hyperparathyroidism involves elevated levels of parathyroid hormone (PTH). Normally, parathyroid hormone plays an important role in maintaining normal bone structure. Elevated levels of the hormone can lead to bone abnormalities and increased risk of cardiovascular disease and death. Decreased kidney function is the main cause of hyperparathyroidism in chronic kidney disease patients.
This study of 496 patients with moderate to severe chronic kidney disease who were not yet on dialysis showed a significant association between obesity and hyperparathyroidism. As body mass increased, so did PTH levels, the researchers said.
"We knew that in people with normal kidney function obesity leads to impairment in vitamin D metabolism and elevated PTH levels, but this phenomenon was never studied in patients with chronic kidney disease," lead author Dr. Csaba P. Kovesdy, of Salem VA Medical Center in Salem, Va., said in a prepared statement.
"Since both obesity and hyperparathyroidism are very complex problems in chronic kidney disease, establishing an association between the two is important because of potential prognostic and therapeutic implications," Kovesdy said.
The study is published in the September issue of the Clinical Journal of the American Society of Nephrology.
More information
The American Academy of Family Physicians has more about chronic kidney disease.

Cardiovascular Disease Independently Increases Risk for Chronic Kidney Disease

June 18, 2007 — The vast pathophysiologic overlap between atherosclerotic cardiovascular (CV) disease and chronic kidney disease (CKD) may be increasingly appreciated but it remains less thoroughly studied than either condition alone. Two reports released this week do their parts toward changing that. One demonstrates strong independent relationships between CV disease and multiple measures of renal dysfunction among volunteer participants in a screening program for people with kidney-disease risk factors. The other portrays CV disease itself as a major independent risk factor for future renal functional decline and for CKD in a community-based population.
Together the studies highlight the intimate relationship between two broad disorders that, in some ways, are separated less by clinical and therapeutic issues than by the different hospital departments responsible for them.
An editorial on the 2 studies, published with them online June 11, 2007, by the Archives of Internal Medicine, casts CKD as both "cause and consequence" of CV disease and, in particular, asserts that "the presence of atherosclerotic CV disease should now be recognized as an independent risk factor for the development and progression of kidney disease."
The editorialists, nephrologists Drs Barry I Freedman and Thomas D DuBose Jr (Wake Forest University, Winston-Salem, NC), observe that the two disorders share risk factors and pathophysiology and note, for example, that "urinalysis provides a window into the systemic vasculature, since relatively small increases in urinary protein excretion appear to be surrogate markers for endothelial dysfunction and are an independent risk factor for systemic atherosclerosis. Reduced [glomerular filtration rate (GFR)] appears to pose a similar risk for cardiovascular disease."
Dr Daniel E Weiner (Tufts–New England Medical Center, Boston, MA), a coauthor of the report highlighting the increased risk of renal dysfunction and CKD when there is known CV disease — lauds both studies for calling attention to the links between the two disorders. "When you think of one, you should probably think of the other," he said to heartwire.
"In people with cardiovascular disease, we should screen for kidney disease. And when we find it, we should treat it," Weiner said. "If you stay on top of it, you can manage the progression of kidney disease fairly well, and for a lot of people who live long enough, you can really make a difference by slowing it down."
Screening could consist merely of serum-creatinine measurement to estimate GFR, "and you want to check the urine periodically to see if there's protein in it," Weiner said. Therapy would largely take after some forms of CV pharmacotherapy except, for example, "maybe you focus more on ACE inhibitors or angiotensin receptor blockers for blood pressure control," because those drugs can be renoprotective.
"As Good as We're Going to Get"
In his group's analysis, which Weiner called "probably about as good as we're going to get" to evidence that CV disease actually promotes CKD, 13,826 participants pooled from the Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS) were followed for a mean of 9.3 years. The increased renal risks associated with CV disease persisted "after adjusting for demographic and clinical characteristics and remained robust in multiple analyses using serum creatinine level and estimated GFR to assess kidney function," report the authors, led by Dr Essam F Elsayed (Tufts–New England Medical Center).
The pooled population, they write, represented patients from both longitudinal, community-based studies for whom long-term data were available, including complete demographics and both entry and final measurements of serum creatinine, and who didn't show evidence of imminent kidney failure.
About 13% of the participants had baseline CV disease, defined as a history of stroke, angina, claudication, TIA, PCI or CABG, or symptomatic or silent MI. The rate of kidney-function decline, defined as a serum creatinine increase of at least 0.4 mg/dL, for patients with or without CV disease was 7.2% and 3.3%, respectively (P < 0.001). When renal functional decline was defined as a drop in estimated GFR of at least 15 mL/min per 1.73 m2, the rates were nonsignificantly different at 34% and 32.5%, respectively. Outright CKD developed during follow-up in 2.3% of the population according to serum-creatinine criteria and 5.6% using a GFR-based definition.
Although several studies have evaluated epidemiological risk factors for progression of kidney disease, to our knowledge, this is the first community-based study that has demonstrated that CV disease is independently associated with kidney function decline and with development of kidney disease," according to the group.
"This well-executed study conclusively demonstrates that CV disease per se is independently associated with subsequent development of kidney disease and renal functional decline," write Freedman and DuBose in their editorial. "The effect of prevalent CV disease on the development and progression of kidney disease was heretofore unknown."
Three Markers of Renal Function and CV Risk
In the other analysis, based on the ongoing Kidney Early Evaluation Program (KEEP) of the National Kidney Foundation, a presence of CV disease was independently associated with its traditional risk markers but also with low hemoglobin levels, microalbuminuria (defined as > 30 mg/L) and CKD (estimated GFR < 60 mL/min per 1.73 m2). A combination of the kidney-related markers compounded the risk of CV disease and also predicted mortality.
The screened population consisted of 37,153 adult volunteers with diabetes, hypertension, or a family history of either or of kidney disease. About 8% had CV disease, defined as a self-reported history of "heart attack" or stroke, according to the authors, led by Dr Peter A McCullough (William Beaumont Hospital Royal Oak, MI).
nsurprisingly, current smoking (P < 0.001), diabetes (P < 0.001), higher body-mass index (P = 0.03), and hypertension (P < 0.001) were also significantly predictive of CV disease. But having at least a high-school education and being African American were significantly protective (P < 0.001 for both).
Compared to an absence of both CKD and CV disease, current CKD without CV disease about doubled the age-adjusted mortality risk (P = 0.05), CV disease without CKD tripled it (P = 0.003), and a presence of both disorders nearly quadrupled the risk, with a hazard ratio of 3.8 (P < 0.001).
Given that more than one-fourth of those in the study who had all three kidney-related risk factors also had CV disease, write McCullough et al, the findings "suggest that screening for CV disease would be of high yield among patients with these risk markers but who do not report any history of CV disease symptoms."
According to Freedman and DuBose, "When caring for individuals with preexisting CV disease and multiple CV-disease risk factors, primary care physicians and cardiologists should be vigilant in checking for the development and progression of CKD. Moreover, attention should be directed to the potential complications of kidney disease that may require consultation by a nephrologist." There is evidence, they write, that diabetes and hypertension often do not prompt primary-care physicians to screen for CKD. "It is reasonable to encourage screening for most patients in such high-risk groups."
Elsayed et al coauthor Dr Tobias Kurth (Brigham and Women's Hospital, Boston, MA) "has received research funding from... Bayer AG, McNeil Consumer & Specialty Pharmaceuticals, and Wyeth Consumer Healthcare. He is a consultant to i3 Drug Safety and received an honorarium from Organon for contributing to an expert panel." In the same study, partial financial support for the creation of the pooled database came from Amgen. Freedman reports that he is a consultant for and has received honoraria from Pfizer.
Arch Intern Med. 2007;167: 1113-1115, 1122-1129, 1130-1136.

Kidney Disease and Heart Disease Interact to No Good End

ROYAL OAK, Mich., June 12 -- Kidney disease and cardiovascular disease are intertwined risk factors, each contributing to the other, according to two studies.
Three markers of chronic kidney disease -- anemia, reduced glomerular filtration, and microalbuminuria -- were independently associated with heart disease, found Peter A. McCullough, M.D., of William Beaumont Hospital here, and colleagues,
When all three markers were present, approximately one-fourth of the patients had cardiovascular disease, they reported in the June 11 issue of the Archives of Internal Medicine.
Moreover, patients with a combination of all three markers had the lowest survival rate by the end of 30 months, about 93%, compared with any other individual marker group.
The relationship between chronic kidney disease and cardiovascular disease may be bi-directional, with impaired kidney function increasing the cardiovascular disease risk and vice versa, Dr. McCullough and colleagues wrote. However, most patients with chronic kidney disease die of complications from heart disease rather than of kidney failure, he added.
In a community-based population enrolled from 2000 to 2003, the researchers studied a cohort of 37,153 persons (mean age 52.9, 68.7% female) screened in the National Kidney Foundation's Kidney Early Evaluation Program.
A total of 1,835 (4.9%) had a self-reported history of myocardial infarction, 1,336 (3.6%) had a history of stroke, and 2,897 (7.8%) had a history of MI or stroke.
Participants, followed for a median of 16.0 months, were assessed for three markers of chronic kidney disease:
Glomerular filtration rates (eGFR) estimated on the basis of levels of blood creatinine; 30 to 59 mL/min per 173m3 ;
Anemia, determined by blood hemoglobin levels (12.8 g/dL or less);
Microalbuminuria, or protein albumin in the urine (30 mg/L or more).
Of the participants followed for a maximum of 47.5 months, 5,504 (14.8%) had eGFR rates of less than 60 mL/min per 173m3, a sign of declining kidney function. In addition, 4,588 (13.1%) had anemia, and 15,959 (49.5%) had microalbuminuria.
Multivariate, analysis controlling for age found that the following were independently associated with cardiovascular disease : male sex (odds ratio [OR], 1.64; P<0.001), smoking (OR, 1.73; P<0.001), body mass index (OR, 1.01; P=0.03), diabetes (OR, 1.66; P<0.001), hypertension (OR, 1.77; P<0.001).
Each of the three kidney markers was also independently associated with cardiovascular disease; estimated lower GFR (OR, 1.37; P=0.001), low hemoglobin level (OR, 1.45; P<0.001), and elevated microalbuminuria (OR, 1.28; P=0.01).
Survival analysis found that cardiovascular disease (OR, 3.02;
P=0.003), chronic kidney disease (OR, 1.98; P=0.05), and the combination (OR, 3.80; P<0.001) were independent predictors of mortality.
Persons with a combination of all three chronic kidney disease measures (anemia, microalbuminuria, and low glomerular filtration rates) had a threefold increased risk of death during the short follow-up period and the lowest survival of about 93% by the end of 30 months, the researchers reported.
Some explanations for how chronic kidney disease can worsen atherosclerosis and myocardial disease included uncontrolled confounding, or the effect of comorbidities that occur in kidney-disease patients, especially those who are older. Another explanation was therapeutic nihilism, meaning that kidney disease patients received fewer cardioprotective therapies, the researchers said.
Still other explanations, they suggested, included the possibility that excess treatment toxicities, or intolerances may limit use of certain therapies. It is also possible that a unique vascular pathology that occurs in chronic kidney disease may play a part.
The study limitations were those common to population screening studies. The glomerular filtration measurement may have misclassified patients, underestimating actual levels, especially since the numbers of individuals were small, leading to some unstable point estimates in that group.
Another shortcoming, the researchers noted, was the use of dipstick urine for microalbuminuria detection.
"These data suggest that screening for cardiovascular disease would be of high yield among patients with these risk markers but who do not report any history of cardiovascular disease symptoms," Dr. McCullough and his colleagues concluded.
In a related study in the same journal issue, Daniel E. Weiner, M.D., of Tufts-New England Medical Center in Boston, and colleagues, reported that the presence of cardiovascular disease in almost 13 % of the patients was associated with a decline in kidney function and a more than 50% increased risk of developing kidney disease, as measured by serum creatinine levels and eGFR.
The findings came from a study of 13,826 patients pooled in two large community-based studies, the Atherosclerosis risk in Communities Study and the Cardiovascular Health Study.
During a mean follow-up of about nine years, 520 patients (3.8%) had a decline in kidney function, defined by a serum creatinine level increase of at least 0.4 mg/dL, and 314 individuals (2.3%) developed kidney disease, the researchers reported.
Baseline cardiovascular disease among 1,728 patients (12.9%) with disease was associated with an increased risk of all outcomes (odds ratio, 1.70; CI, 1.36-2.13), an OR 1.75 (CI, 1.32-2.32) for serum creatinine level, and ORs of 1.28 and 1.54 for GFR reduction for decline in kidney function and development of kidney disease, respectively.
The data were pooled from two longitudinal, community-based, limited-access studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Patients were recruited from 1987 to 1990 and were followed-up at approximately three-year intervals for a mean 9.3 years.
Baseline cardiovascular disease was defined by stroke, angina, claudication, transient ischemic attack, coronary angioplasty or bypass, and recognized or silent MI.
Study outcomes included kidney function decline (increase in serum creatinine level of at least 0.4 mg/dL) and development of kidney disease (increase in serum creatinine level of at least 0.4 mg/dL in which the baseline serum creatinine level was less than 1.4 mg/dL in men and less than 1.2 mg/dL in women), and final serum creatinine that exceeded these levels.
Secondarily, kidney function decline was defined by a reduction in the estimated glomerular filtration rate.
Development of kidney disease was defined by an eGFR reduction of at least 15mL/min per 1.73m2 in which the baseline rate was at least 60 mL/min per 1.73m2 and the final GFR was below these levels.
Albuminuria was not measured in this the study.
Cardiovascular disease is independently associated with a decline in kidney function and with the development of kidney disease, Dr. Weiner and colleagues said.
Among the study's limitations the researchers noted is the fact that there is no accepted definition of kidney function decline, although the definition chosen for this study of at least 0.4 mg/dL likely exceeds the level that could be due to chance.
Furthermore, it is possible that many individuals may have been misclassified using the eGFR definition for kidney function decline, they said.
The present study, the researchers said, demonstrates that cardiovascular disease is independently associated with a decline in renal function and with the development of kidney disease.
The findings, they said, identify a population that might benefit from increased surveillance for cardiovascular risk factors and heightened awareness of the risk factors associated with kidney disease.
"Because these patients are mainly under the care of primary care physicians and cardiologists, it is important to draw attention to the increased risk of kidney disease in this population, with goals of preventing further progression, managing sequelae of kidney disease as they arise and adequately preparing individuals for kidney failure with timely nephrology referrals," the researchers concluded.
In an accompanying editorial, Barry I. Freedman, M.D., and Thomas D. DuBose Jr., M.D., of Wake Forest University in Winston-Salem, N.C., wrote that these two reports address the interactive effects of kidney disease and cardiovascular disease risk in more than 50,000 patients, "providing novel insights into the relationship between kidney disease and the vasculature."
The presence of atherosclerotic cardiovascular disease should now be recognized as an independent risk factor for developing kidney disease, and patients with both should be screened and treated accordingly, they said.
The chances for reducing the current high rates of chronic kidney disease and cardiovascular disease will be maximized when primary-care physicians, nephrologists, and cardiologists work in partnership to reduce and treat modifiable vascular disease risk factors, including those that are a consequence of kidney disease, Drs. Freedman and DuBose said.
In addition, they wrote, "the potential for achieving current treatment goals in individuals at risk for nephropathy and cardiovascular disease using a more focused approach promises greater reductions in future cardiovascular disease and end stage renal disease events."
No financial disclosures were reported by Dr. McCullough or his colleagues.
Tobias Kurth, M.D., a co-author of the Tufts study, reported research funding from the National Institutes of Health, Bayer AG, McNeil Consumer & Specialty Pharmaceuticals, and Wyeth Consumer Healthcare. He is a consultant to i3 Drug Safety and received an honorarium from Organon for contributing to an expert panel.
The Tufts study was supported by grants from the National Institutes of Health. Amgen provided partial support for the creation of the pooled database. The ARIC Study and the CHS are conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the individual study investigators.
Dr. Freedman, an editorial writer, reported that he is a paid consultant for and has received honoraria from Pfizer. Dr. Freedman's research cited in this editorial was supported in part by a Genetic Analysis of African American Hypertensive ESRD grant from the National Institutes of Diabetes, Digestive and Kidney Diseases. Additional source: Archives of Internal MedicineSource reference: McCullough PA, et al "Independent Components of Chronic Kidney Disease as a Cardiovascular Risk State" Arch Intern Med. 2007; 167:1122-1129. Additional source: Archives of Internal MedicineSource reference: Elsayed EF, et al "Cardiovascular Disease and Subsequent Kidney Disease" Arch Intern Med. 2007; 167: 1130-1136.
Freedman BI, DuBose, Jr. TD "Chronic Kidney Disease: Cause and Consequence of Cardiovascular Disease" Arch Intern Med. 2007; 167: 1113-1115

Nine-Question Survey Identifies Patients at Risk of Having Chronic Kidney Disease

The Screening for Occult Renal Disease (SCORED) questionnaire, which contains questions about demographic variables and health conditions, but does not require any laboratory test values, might be useful to identify individuals who are highly likely to have underlying chronic kidney disease (CKD).
This screening tool developed by researchers at the University of North Carolina School of Medicine in Chapel Hill and at Weill Medical College of Cornell University in New York is discussed in an article in the February 26 issue of the Archives of Internal Medicine.
Coauthor Abhijit V. Kshirsagar, MD, at the University of North Carolina told Medscape, "The main message is that CKD is very common; about 1 in 10 people may have it, but don't know they have it. Just asking these simple questions — about yourself if you are a lay person, or, asking your patient, if you are a clinician — will quickly help you determine who has a high chance of having kidney disease."

http://www.medscape.com/viewarticle/553095?rss