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Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

In Shakespeare’s King Lear, the impact of the storm on the heath on Lear is best explained in light of two obsolescent medieval cultural traditions that found positive value in wild nature, in contrast to the negative views common in early modern England. The forest laws help us understand the heath as a place, as well as the monarch’s relationship to that place. But for understanding the inner change in Lear, which is like that of the knight-hermits in medieval romance, we must turn to the cultural roots of the eremitical tradition in monastic spirituality, which, as Jacques Le Goff has argued, were transplanted from the deserts of Egypt to the forests of France and England. These two medieval cultural traditions, transposed into the play’s ancient pagan setting, provide essential help in understanding why a violent storm in a bleak landscape has such a strong presence in Shakespeare’s great tragedy.

BACKGROUND Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. METHODS We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). RESULTS Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P = 0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (−2.3 mm Hg; 95% CI, −4.4 to −0.2; P = 0.03). CONCLUSIONS Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.) abstr act

Introduction: The risk of dementia increases with increasing levels of hemoglobin A1c (HbA1c), a measure of average blood glucose. However the association between glucose peaks and dementia in persons with diabetes is unclear. 1,5-anhydroglucitol (1,5-AG) is a novel biomarker of glucose peaks, with low levels reflecting blood glucose concentrations that exceed the renal filtration threshold (~180 mg/dl) over the prior 7-10 days. Hypothesis: Glucose peaks, indicated by low levels of 1,5-AG, will be associated with higher risk of dementia, independent of HbA1c and other dementia risk factors. Methods: We conducted a prospective analysis of 1568 participants with diabetes from visit 2 (1990-1992) of the ARIC Study. Diabetes was defined based on self-reported physician diagnosis, diabetes medication use, or HbA1c ≥ 6.5%. Community surveillance of hospitalizations was used to identify incident dementia. Cases were defined as the first occurrence of a hospitalization with an ICD-9 code for dementia appearing in any position in the hospital discharge record. We used Cox regression to examine the association between 1,5-AG (modeled linearly) and incident dementia, adjusted for demographic and clinical risk factors, including HbA1c. Results: At baseline, the mean age was 58 years, 58% were female, 54% were white, and mean HbA1c was 8.1%. Over a median follow-up of 18 years, 158 participants had a hospitalization with an ICD-9 code of dementia. Each unit decrease in 1,5-AG increased the risk of dementia by 4% (HR=1.04, p-value=0.03, Figure). Associations were similar when 1,5-AG was modeled using linear splines. Conclusions: Short-term glucose peaks were associated with higher risk of dementia among adults with diabetes, independent of HbA1c and other dementia risk factors. More studies are needed to determine if targeting glucose peaks, in addition to average glucose, among persons with diabetes can reduce the risk of dementia.

Introduction: In current guidelines congestive heart failure (CHF) is an indication for renal artery stenting, however there is no data on the utility of stenting for the prevention of CHF. We sought to determine the effect of renal artery stenting in patients with atherosclerotic renal artery stenosis (ARAS) without a history of CHF. Hypothesis: In ARAS renal artery stenting does not prevent incident CHF in patients with no history of CHF. Design and method: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial is a prospective, international, multicenter clinical trial that randomized participants with ARAS, who received optimal medical therapy plus stenting versus no stenting. Optimal medical therapy included treating blood pressure and diabetes to goal, use of an angiotensin receptor-blocking drug, statin, and anti-platelet therapy. Glomerular filtration (eGFR) was estimated using the MDRD-GFR equation. Patients were followed for a median of 43 months (IQR, 31 to 55). Results: At enrollment, there were 795 out of 931 patients without a history of CHF, 395 were in the medical therapy group and 400 were in the medical therapy plus stenting group. In this group 117/795 had global renal ischemia. The rate of CHF admission (7% vs. 6%. p=0.74) and the pulmonary edema rate within those admitted for CHF were not different (82% vs. 64%, p=0.21). The rate of incident CHF was not different in patients with global renal ischemia and renal stenting did not prevent CHF events in this subgroup. Neither the composite event rate (35% vs. 34%, p=0.72), nor the rate of cardiovascular death (8% vs. 8%, p=0.96) differed between the two groups. At 3-year follow-up no differences were observed between medical therapy and medical therapy plus stenting for systolic blood pressure (SBP) (135±19 vs. 134±21 mmHg, p=0.74) or eGFR (56±22 vs. 55±23 ml/min, p=0.50). Conclusions: Renal artery stenting and optimal medical therapy, when compared to optimal medical therapy only, did not reduce the risk of CHF, or other cardio-renal events in patients that were enrolled without history of CHF in the CORAL trial.

Quand on lit The Winter’s Tale de Shakespeare à la lumière de ses allusions aux traditions culturelles grecques comme elles étaient comprises à la Renaissance, on se rend compte que les liens entre les personnages sont plus étroits que prévus. Si l’on se rappelle l’association entre l’ours et Artemis, protectrice de la faune sauvage et déesse de la fertilité, le lien entre l’ours et Hermione s’éclaircit. La transgression du loup, nommé Autolycus, offre une parodie de la louveté tyrannique de Léontès, ce qui aide le public à le comprendre et, peut-être, à lui pardonner. Par conséquent, ces deux personnages, qui ne sont pas essentiels à l’intrigue, sont en fait bien intégrés dans la pièce.

In the Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial, glycemic control with insulin-sensitization therapy was compared with insulin-provision therapy in patients with type 2 diabetes and coronary artery disease. This study examined differences in albumin excretion and renal function in the insulin-sensitization group versus the insulin-provision group over 5 years.In total, 1799 patients with measurements of creatinine and urine albumin/creatinine ratio at baseline and at least two follow-up visits were included. Management of BP, lipids, and lifestyle counseling was uniform. Progression of albuminuria was defined as doubling of baseline albumin/creatinine ratio to at least 100 mg/g or worsening of albumin/creatinine ratio status on two or more visits. Worsening renal function was defined as25% decline in estimated GFR and annualized decline of3 ml/min per 1.73 m(2) per year.By 6 months and thereafter, the mean glycated hemoglobin levels were lower in the insulin-sensitization group compared with the insulin-provision group (P0.002 for each time point; absolute difference=0.4%). Albumin/creatinine ratio increased over time in the insulin-sensitization group (P value for trend0.001) and was stable in the insulin-provision group. Risk for progression of albumin/creatinine ratio was higher in the insulin-sensitization group compared with the insulin-provision group (odds ratio, 1.59; 95% confidence interval, 1.25 to 2.02; P=0.02). Over 5 years, albumin/creatinine ratio increased from 11.5 (interquartile range=5.0-46.7) to 15.7 mg/g (interquartile range=6.2-55.4) in the insulin-sensitization group (P0.001) and from 12.1 (interquartile range=5.3-41.3) to 12.4 mg/g (interquartile range=5.8-50.6) in the insulin-provision group (P=0.21). Estimated GFR declined from 75.0±20.6 to 66.3±22.6 ml/min per 1.73 m(2) in the insulin-sensitization group (P0.001) and from 76.1±29.5 to 66.8±22.1 ml/min per 1.73 m(2) in the insulin-provision group (P0.001).Over 5 years, despite lower glycated hemoglobin levels, the insulin-sensitization treatment group had greater progression of albumin/creatinine ratio compared with the insulin-provision treatment group. Decline in estimated GFR was similar.

Impaired vitamin D metabolism may contribute to the development and progression of diabetic kidney disease.The aim of the study was to test associations of circulating vitamin D metabolites with risks of incident microalbuminuria, impaired glomerular filtration rate (GFR), and hypertension in type 1 diabetes.We performed a cohort study of 1193 participants in the Diabetes Control and Complications Trial (DCCT), a randomized clinical trial of intensive diabetes therapy, and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We measured plasma concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT and tested associations with incident microalbuminuria, impaired GFR, and hypertension over up to 16 yr of EDIC follow-up.At the time metabolites were measured, mean age was 32.4 yr; mean duration of diabetes, 7.5 yr; mean iothalamate GFR, 132.9 ml/min/1.73 m(2); and geometric mean albumin excretion rate, 11.8 mg/24 h. Over follow-up, 166 cases of microalbuminuria, 54 cases of impaired GFR, and 541 cases of hypertension were observed. Compared with 25(OH)D of at least 30 ng/ml, 25(OH)D below 20 ng/ml was associated with a 65% higher risk of microalbuminuria (95% confidence interval, 7 to 154%) in adjusted analyses. Low concentrations of 24,25-dihydroxyvitamin D, but not 1,25-dihydroxyvitamin D, were also associated with increased risk of microalbuminuria. No circulating vitamin D metabolite was associated with risk of impaired GFR or hypertension.Low plasma concentrations of 25(OH)D and 24,25-dihydroxyvitamin D are associated with increased risk of microalbuminuria in type 1 diabetes. In contrast, we did not find evidence linking impaired vitamin D metabolism to early GFR loss or the development of hypertension.

OBJECTIVE To determine the relationship between mean sensor glucose concentrations and hemoglobin A1c (HbA1c) values measured in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications laboratory at the University of Minnesota in a cohort of subjects with type 1 diabetes from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized trial. RESEARCH DESIGN AND METHODS Near-continuous glucose sensor data (≥4 days/week) were collected for 3 months before a central laboratory–measured HbA1c was performed for 252 subjects aged 8–74 years, the majority of whom had stable HbA1c values (77% within ±0.4% of the patient mean). RESULTS The slope (95% CI) for mean sensor glucose concentration (area under the curve) versus a centrally measured HbA1c was 24.4 mg/dL (22.0–26.7) for each 1% change in HbA1c, with an intercept of −16.2 mg/dL (−32.9 to 0.6). Although the slope did not vary with age or sex, there was substantial individual variability, with mean sensor glucose concentrations ranging from 128 to 187 mg/dL for an HbA1c of 6.9–7.1%. The root mean square of the errors between the actual mean sensor glucose concentration versus the value calculated using the regression equation was 14.3 mg/dL, whereas the median absolute difference was 10.1 mg/dL. CONCLUSIONS There is substantial individual variability between the measured versus calculated mean glucose concentrations. Consequently, estimated average glucose concentrations calculated from measured HbA1c values should be used with caution.

Background: Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and death or cardiovascular events among patients with stable coronary disease. Methods: We studied patients enrolled in the Prevention of Events with an ACE Inhibitor (PEACE) trial, in which patients with chronic stable coronary disease and preserved systolic function were randomized to trandolapril or placebo and followed for a median of 4.8 years. The urinary albumin to creatinine ratio (ACR) assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months) was related to estimated glomerular filtration rate (eGFR) and outcomes. Results: The majority of patients (73%) had a baseline albumin/creatinine ratio within the normal range. Independent of the eGFR and other baseline covariates, a higher albumin/creatinine ratio even within the normal range was associated with increased risks for all-cause mortality (p < 0.001) and cardiovascular death (p = 0.01). The effect of trandolapril therapy on outcomes was not significantly modified by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 ug/mg vs 14.6 ug/mg, p = 0.0002), after adjusting for baseline ACR, time between collections and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (HR per log ACR 1.74, 95% confidence intervals 1.08–2.82). Conclusions: Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality.

We reported strong relations between serum concentrations of persistent organic pollutants (POPs), especially organochlorine (OC) pesticides or nondioxin-like polychlorinated biphenyls (PCBs), and prevalence of diabetes in a U.S population with background exposure to POPs. Here, we investigated POPs and insulin resistance, a frequent pathogenic precursor of type 2 diabetes.Serum POPs and homeostasis model assessment of insulin resistance (HOMA-IR) were investigated cross-sectionally in 749 nondiabetic participants agedor = 20 years. Nineteen POPs in five subclasses were selected, detectable inor = 60% of participants.Among subclasses, OC pesticides were most strongly associated with HOMA-IR. Adjusted geometric means of HOMA were 3.27, 3.36, 3.48, and 3.85 (P for trend0.01) across quartiles of OC pesticides. The relationship strengthened with increasing HOMA-IR percentile: adjusted odds ratios comparing the highest versus lowest POPs quartile were 1.8 for beingor = 50th percentile of HOMA-IR, 4.4 for beingor = 75th percentile, and 7.5 for beingor = 90th percentile. Associations with elevated HOMA-IR appeared to be specific to oxychlordane and trans-nonachlor but also were found for two nondioxin-like PCBs. No HOMA-IR associations were seen in the other three POP subclasses. The association between OC pesticides and HOMA-IR tended to strengthen as waist circumference increased, with no apparent association in the lowest quartile of OC pesticide concentrations.These findings, coupled with those concerning diabetes prevalence, suggest that OC pesticides and nondioxin-like PCBs may be associated with type 2 diabetes risk by increasing insulin resistance, and POPs may interact with obesity to increase the risk of type 2 diabetes.

Low-level exposure to some persistent organic pollutants (POPs) has recently become a focus because of their possible link with the risk of diabetes.Cross-sectional associations of the serum concentrations of POPs with diabetes prevalence were investigated in 2,016 adult participants in the National Health and Nutrition Examination Survey 1999-2002. Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'-dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they were detectable inor=80% of participants.Compared with subjects with serum concentrations below the limit of detection, after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of all six POPs. When the participants were classified according to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7 (P for trend0.001). The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals.There were striking dose-response relations between serum concentrations of six selected POPs and the prevalence of diabetes. The strong graded association could offer a compelling challenge to future epidemiologic and toxicological research.

The Women's Angiographic Vitamin and Estrogen trial was a randomized, double-blind, placebo-controlled study designed to test the efficacy of estrogen replacement and antioxidant vitamins for preventing angiographic progression of coronary artery disease. Postmenopausal women with one or more angiographically documented coronary stenoses of 15-75% at baseline were assigned in a 2 x 2 factorial randomization to active hormone replacement therapy (conjugated estrogens for women who had had a hysterectomy or conjugated estrogens with medroxyprogesterone for women with intact uteri) or placebo and to active vitamins E and C or their placebos. Seven clinical centers, five in the United States and two in Canada, randomized 423 women between July 1997 and July 1999. Quantitative coronary angiography was performed at baseline and repeated after projected mean follow-up of 3 years.

International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes An International Expert Committee with members appointed by the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation was convened in 2008 to consider the current and future means of diagnosing diabetes in non pregnant individuals. The report of the International Expert Committee represents the consensus view of its members and not necessarily the view of the organizations that appointed them. The International Expert Committee hopes that its report will serve as a stimulus to the international community and professional organizations to consider the use of the A1C assay for the diagnosis of diabetes.

I syng of a mayden that is makeles, Kyng of alle kynges to here sone the ches. He cam also stylle ther his moder was As dewe in Aprylle that fallyt on the gras. He cam also stylle to his moderes bowr As dew in Aprille that fallyt on the flour. He cam also style ther his moder lay As dew in Aprille that fallyt on the spray. Moder and maydyn was never non but che -- Wel may swych a lady Godes moder be! 'I syng of a mayden' is one of the most widely read and most frequently commented on of the shorter Middle English poems. Derek Pearsall's remarks distil much of the scholarly discussion: A brain and a subtle ear has gone into the making of this poem ... celebrating the mystery of Christ's conception. Dew falling on grass, flower and spray (traditional imagery, deriving from OT texts such as Ps. 72:6) suggests case, grace and delicacy generally (not progressive stages of insemination). The emphasis on Mary's freedom of choice, at the moment of the Annunciation, is theologically strictly proper.1 In this essay I will concentrate on one of those images of `ease, grace, and delicacy', `dewe in Aprylle', and especially on its liturgical associations. My aim in doing so is not simply to give a clearer sense of the probable source of the image but, more importantly, to sketch a context within which the considerable artistry of this poem and the richness and complexity of its religious background may be more fully appreciated. It has been previously assumed that the poem's springtime imagery is for the most part derived from secular lyrics, especially secular love poetry, with the exception of the `dewe in Aprylle' which is related to an image in the Advent liturgy, celebrated, of course, in December, not in April.2 The liturgical text in question is from the Book of Isaiah xlv.8, rendered in the Douai Bible as `Drop down dew, ve heavens, from above, and let the clouds rain the just: let the earth be opened, and bud forth a saviour.'3 In the Saturn breviary's version of the Vulgate, the verse is rorate caeli desuper et nubes pluant justum:aperiatur terra et germinet Salvatorem'. Consideration of this passage does indeed enrich understanding of the dew image in 'I syng of a mayden'. In a number of medieval rites, however, `rotate caeli ...' not only occurs in the liturgy for Advent, as is still common, but in the liturgy for the Feast of the Annunciation as well.4 That the late-medieval English liturgical uses of York and Hereford, as well as the more widely known Sarum rite, used `rorate celi' for the Annunciation confirms its importance in understanding the dew image in 'I syng of a mayden', and, moreover, shows that the poem's natural imagery and religious context are much better integrated than had been realized. 'I syng of a mayden' is a very quiet and very beautiful meditation on the inward aspects of the Annunciation, on the immediate consequences of Mary's acceptance of Gabriel's message. (It may be of interest that in the manuscript this poem is immediately preceded by another that follows the biblical account of the Annunciation more literally, while the poem that comes after it, `Adam lay ibowndyn',5 reminds us of the need for the Incarnation and consequent Redemption, of the great benefit to humankind gained in the moment described in 'I syng of a mayden'.) There is a contrast in the poem between the deliberate choice of Mary to become the mother of Jesus and the inevitability implied by the natural imagery used to describe the working out of that choice. The natural images give a sense that what is happening is akin to the recurring processes of the renewal of nature, the formation of dew and the growth and blossoming of plants. On the one hand there is a 'mayden' exercising her free choice, and on the other there is a tremendous cosmic and metaphysical process with which she chooses to co-operate. Tact and delicacy, created at least in part by the natural images, predominate in this presentation of conception. …

INTRODUCTION: CHRONIC KIDNEY disease (CKD) is a worldwide public health issue. In the United States, there is a rising incidence and prevalence of kidney failure (Fig 1), with poor outcomes and high cost. The prevalence of earlier stages of CKD is approximately 100 times greater than the prevalence of kidney failure, affecting almost 11% of adults in the United States. There is growing evidence that some of the adverse outcomes of CKD can be prevented or delayed by preventive measures, early detection, and treatment. Hypertension is a cause and complication of CKD. Hypertension in CKD increases the risk of important adverse outcomes, including loss of kidney function and kidney failure, early development and accelerated progression of cardiovascular disease (CVD), and premature death. In the ongoing effort to improve outcomes of CKD, the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) appointed a Work Group and an Evidence Review Team in 2001 to develop clinical practice guidelines on hypertension and use of antihypertensive agents in CKD. During this same time, clinical practice guidelines on this topic relevant to CKD were also under development by other organizations, including the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the 2003 report of the American Diabetes Association (ADA) on the Treatment of Hypertension in Adults with Diabetes. The Work Group maintained contact with these organizations during development of these guidelines. The purpose of the Executive Summary is to provide a "stand-alone" summary of the background, scope, methods, and key recommendations, as well as the complete text of the guideline statements. Most tables and figures in the Executive Summary are taken from other sections of the document. BACKGROUND: Chronic Kidney Disease: Figure 2 is a conceptual model of CKD, which defines stages of CKD, as well as antecedent conditions, outcomes, risk factors for adverse outcomes, and actions to improve outcomes. CKD is defined as kidney damage, as confirmed by kidney biopsy or markers of damage, or glomerular filtration rate (GFR)

Introduction: Chronic kidney disease as a public health problem. Chronic kidney disease is a worldwide public health problem. In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. There is an even higher prevalence of earlier stages of chronic kidney disease. Increasing evidence, accrued in the past decades, indicates that the adverse outcomes of chronic kidney disease, such as kidney failure, cardiovascular disease, and premature death, can be prevented or delayed. Earlier stages of chronic kidney disease can be detected through laboratory testing. Treatment of earlier stages of chronic kidney disease is effective in slowing the progression toward kidney failure. Initiation of treatment for cardiovascular risk factors at earlier stages of chronic kidney disease should be effective in reducing cardiovascular disease events both before and after the onset of kidney failure. Unfortunately, chronic kidney disease is "under-diagnosed" and "under-treated" in the United States, resulting in lost opportunities for prevention. One reason is the lack of agreement on a definition and classification of stages in the progression of chronic kidney disease. A clinically applicable classification would be based on laboratory evaluation of the severity of kidney disease, association of level of kidney function with complications, and stratification of risks for loss of kidney function and development of cardiovascular disease. Charge to the K/DOQI work group on chronic kidney disease. In 2000, the National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (K/DOQI) Advisory Board approved development of clinical practice guidelines to define chronic kidney disease and to classify stages in the progression of chronic kidney disease. The Work Group charged with developing the guidelines consisted of experts in nephrology, pediatric nephrology, epidemiology, laboratory medicine, nutrition, social work, gerontology, and family medicine. An Evidence Review Team, consisting of nephrologists and methodologists, was responsible for assembling the evidence. Defining chronic kidney disease and classifying the stages of severity would provide a common language for communication among providers, patients and their families, investigators, and policy-makers and a framework for developing a public health approach to affect care and improve outcomes of chronic kidney disease. A uniform terminology would permit: 1. More reliable estimates of the prevalence of earlier stages of disease and of the population at increased risk for development of chronic kidney disease 2. Recommendations for laboratory testing to detect earlier stages and progression to later stages 3. Associations of stages with clinical manifestations of disease 4. Evaluation of factors associated with a high risk of progression from one stage to the next or of development of other adverse outcomes 5. Evaluation of treatments to slow progression or prevent other adverse outcomes. Clinical practice guidelines, clinical performance measures, and continuous quality improvement efforts could then be directed to stages of chronic kidney disease. The Work Group did not specifically address evaluation and treatment for chronic kidney disease. However, this guideline contains brief reference to diagnosis and clinical interventions and can serve as a "road map" linking other clinical practice guidelines and pointing out where other guidelines need to be developed. Eventually, K/DOQI will include interventional guidelines. The first three of these, on bone disease, dyslipidemia, and blood pressure management are currently under development. Other guidelines on cardiovascular disease in dialysis patients and kidney biopsy will be initiated in the Winter of 2001. This report contains a summary of background information available at the time the Work Group began its deliberations, the 15 guidelines and the accompanying rationale, suggestions for clinical performance measures, a clinical approach to chronic kidney disease using these guidelines, and appendices to describe methods for the review of evidence. The guidelines are based on a systematic review of the literature and the consensus of the Work Group. The guidelines have been reviewed by the K/DOQI Advisory Board, a large number of professional organizations and societies, selected experts, and interested members of the public and have been approved by the Board of Directors of the NKF. Framework. The Work Group defined "chronic kidney disease" to include conditions that affect the kidney, with the potential to cause either progressive loss of kidney function or complications resulting from decreased kidney function. Chronic kidney disease was thus defined as the presence of kidney damage or decreased level of kidney function for three months or more, irrespective of diagnosis. The target population includes individuals with chronic kidney disease or at increased risk of developing chronic kidney disease. The majority of topics focus on adults (age ≥18 years). Many of the same principles apply to children as well. In particular, the classification of stages of disease and principles of diagnostic testing are similar. A subcommittee of the Work Group examined issues related to children and participated in development of the first six guidelines of the present document. However, there are sufficient differences between adults and children in the association of GFR with signs and symptoms of uremia and in stratification of risk for adverse outcomes that these latter issues are addressed only for adults. A separate set of guidelines for children will have to be developed by a later Work Group. The target audience includes a wide range of individuals: those who have or are at increased risk of developing chronic kidney disease (the target population) and their families; health care professionals caring for the target population; manufacturers of instruments and diagnostic laboratories performing measurements of kidney function; agencies and institutions planning, providing or paying for the health care needs of the target population; and investigators studying chronic kidney disease. There will be only brief reference to clinical interventions, sufficient to provide a basis for other clinical practice guidelines relevant to the evaluation and management of chronic kidney disease. Subsequent K/DOQI clinical practice guidelines will be based on the framework developed here. Definition of chronic kidney disease. Why "Kidney"? The word "kidney" is of Middle English origin and is immediately understood by patients, their families, providers, health care professionals, and the lay public of native English speakers. On the other hand, "renal" and "nephrology," derived from Latin and Greek roots, respectively, commonly require interpretation and explanation. The Work Group and the NKF are committed to communicating in language that can be widely understood, hence the preferential use of "kidney" throughout these guidelines. The term "End-Stage Renal Disease" (ESRD) has been retained because of its administrative usage in the United States referring to patients treated by dialysis or transplantation, irrespective of their level of kidney function. Why Develop a New Classification? Currently, there is no uniform classification of the stages of chronic kidney disease. A review of textbooks and journal articles clearly demonstrates ambiguity and overlap in the meaning of current terms. The Work Group concluded that uniform definitions of terms and stages would improve communication between patients and providers, enhance public education, and promote dissemination of research results. In addition, it was believed that uniform definitions would enhance conduct of clinical research. Why Base a New Classification System on Severity of Disease? Adverse outcomes of kidney disease are based on the level of kidney function and risk of loss of function in the future. Chronic kidney disease tends to worsen over time. Therefore, the risk of adverse outcomes increases over time with disease severity. Many disciplines in medicine, including related specialties of hypertension, cardiovascular disease, diabetes, and transplantation, have adopted classification systems based on severity to guide clinical interventions, research, and professional and public education. Such a model is essential for any public health approach to disease. Why Classify Severity as the Level of GFR? The level of glomerular filtration rate (GFR) is widely accepted as the best overall measure of kidney function in health and disease. Providers and patients are familiar with the concept that "the kidney is like a filter." GFR is the best measure of the kidneys' ability to filter blood. In addition, expressing the level of kidney function on a continuous scale allows development of patient and public education programs that encourage individuals to "Know your number!" The term "GFR" is not intuitively evident to anyone. Rather, it is a learned term, which allows the ultimate expression of the complex functions of the kidney in one single numerical expression. Conversely, numbers are an intuitive concept and easily understandable by everyone.