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Garabed Eknoyan

Publications and source records attributed to Garabed Eknoyan.

At least 37 records · Page 2Linked to original sources

On the central role of studies on the kidney in the recognition, conceptual evolution, and understanding of hypertension.

Elevated arterial pressure had long been surmised from the strength of the pulse. Its association with contracted kidneys and hypertrophied hearts was described by Richard Bright (1789-1858). Microscopic observations of the narrowed and obliterated vasculature initially observed in the kidneys of Bright's disease, and subsequently throughout the body, launched clinical research into hypertension. The description of these findings in the absence of symptoms of kidney disease led to the recognition of primary hypertension. Ultimately, the systematic recording of the blood pressure with a pneumatic cuff and mercury manometer established the significance of hypertension as a distinct disease entity. Subsequent experimental studies established the central role of the kidney in hypertension through the renin-angiotensin system and extracellular volume control. This finding provided the basis for the introduction of diuretics and angiotensin converting enzyme inhibitors, two of the most important and valuable antihypertertensive drugs now available. Thus, the study of kidney disease and function has played a pivotal role in the conceptual evolution of the understanding of hypertension as a disease, the identification of its mechanisms, and the development of clinically useful antihypertensive medications.

Glomerulonephritis↗

Emergence of the concept of cardiovascular disease.

Historically, the concept of cardiovascular disease is a recent and evolving concept. Well into the eighteenth century, cardiac and vascular diseases were little known and considered a rarity. Description of the circulation by William Harvey (1578-1657) in 1628 marks the beginning of the changes that ensued. However, knowledge was slow to accrue and not until the nineteenth century was the heart taken as a specific object of study. The description of end-stage kidney disease by Richard Bright (1789-1858) in 1827 launched studies of the vasculature, which were to lead to the recognition of hypertension and subsequent identification of the lesions of arteriosclerosis (1833) and atherosclerosis (1904) as diseases of the vasculature. Only between the two world wars did the full impact of these lesions on mortality and morbidity come to be finally recognized. Their study and therapy has defined much of the profound changes that affected twentieth century medicine.

Cardiology↗

Dialysis dose and the effect of gender and body size on outcome in the HEMO Study.

BACKGROUND: Gender and body size have been associated with survival in hemodialysis populations. In recent observational studies, overall mortality was similar in men and women and higher in small patients. The effect of dialysis dose in each of these subgroups has not been tested in a clinical trial. METHODS: The HEMO Study was a controlled trial of dialysis dose and membrane flux in 1846 hemodialysis patients followed up for 6.6 years in 15 centers throughout the United States. We examined the effect of dialysis dose on mortality and on selected secondary outcomes in subgroups of patients. RESULTS: Adjusting for age only, overall mortality was lower in patients with higher body weight (P < 0.001), higher body mass index (P < 0.001), and higher body water content determined by the Watson formula (Vw) (P < 0.001), but was not associated with gender (P= 0.27). The RR of mortality comparing the high dose with the standard dose group was related to gender (P= 0.014). Women randomized to the high dose had a lower mortality rate than women randomized to the standard dose (RR = 0.81, P= 0.02), while men randomized to the high dose had a nonsignificant trend for a higher mortality rate than men randomized to the standard dose (RR = 1.16, P= 0.16). Analysis of both genders combined showed no overall dose effect (R = 0.96, P= 0.52), as reported previously. Vw was greater than 35 L in 84% of men compared with 17% of women. However, the RR of mortality for the high versus standard dose remained lower in women than in men after adjustment for the interaction of dose with Vw or with other size parameters, including weight and body mass index. Conversely, the dose effect was not significantly related to size parameters after controlling for the relationship of the dose comparison with gender. CONCLUSION: The data suggest that mortality and morbidity might be reduced by increasing the dialysis dose above the current standard in women but not in men. This effect was not explained by differences between men and women in age, race, or in several indices of body size. Because multiple comparisons were considered in this analysis, the role of gender on the effect of dialysis dose is suggestive and invites further study.

Black People↗

The burden of kidney disease: improving global outcomes.

Chronic kidney disease (CKD) is a worldwide public health problem. There is an increasing incidence and prevalence of patients with kidney failure requiring replacement therapy, with poor outcomes and high cost. There is an even higher prevalence of patients in earlier stages of CKD, with adverse outcomes such as kidney failure, cardiovascular disease, and premature death. Patients at earlier stages of CKD can be detected through laboratory testing and their treatment is effective in slowing the progression to kidney failure and reducing cardiovascular events. The science and evidence-based care of these patients are universal and independent of their geographic location. There is a clear need to develop a uniform and global public health approach to the worldwide epidemic of CKD. It is to this end that a new initiative "Kidney Disease: Improving Global Outcomes" has been established. Its stated mission is "Improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration and integration of initiatives to develop and implement clinical practice guidelines."

Global Health↗

Emergence of the concept of endocrine function and endocrinology.

Endocrinology as a scientific discipline is relatively new. The term "hormone" was introduced in 1905, and "endocrinology" was introduced in 1909. However, its origins are ancient and rooted in the millennia-old practice of organotherapy, from its archaic religious beginnings, through early attempts to explain the integrated functions of the body by the philosophically sound but scientifically mysterious humors of Greek medicine, to its incorporation into the pharmacopoeias of the eighteenth century. The concept of internal secretions germinated in the anatomical discoveries of the Renaissance, which described ductless glands, and after the discovery of the circulation, came the suggestion of "internal secretions" into blood as organ "emanations which are useful to the body." The principal events that led to the emergence of endocrinology occurred in the latter half of the nineteenth century, from the experimental studies of Claude Bernard (1813-1878), the clinical observations of Thomas Addison (1793-1860), and the combined experimental and clinical studies of Brow-Sequard (1817-1894). The first decades of the twentieth century saw in sequence the isolation of crude organ extracts, their preparation as hormones in pure crystalline form, and their ultimate use in the cure of diseases that had haunted mankind thereto.

Endocrine Glands↗

National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

Chronic kidney disease is a worldwide public health problem with an increasing incidence and prevalence, poor outcomes, and high cost. Outcomes of chronic kidney disease include not only kidney failure but also complications of decreased kidney function and cardiovascular disease. Current evidence suggests that some of these adverse outcomes can be prevented or delayed by early detection and treatment. Unfortunately, chronic kidney disease is underdiagnosed and undertreated, in part as a result of lack of agreement on a definition and classification of its stages of progression. Recent clinical practice guidelines by the National Kidney Foundation 1) define chronic kidney disease and classify its stages, regardless of underlying cause, 2) evaluate laboratory measurements for the clinical assessment of kidney disease, 3) associate the level of kidney function with complications of chronic kidney disease, and 4) stratify the risk for loss of kidney function and development of cardiovascular disease. The guidelines were developed by using an approach based on the procedure outlined by the Agency for Healthcare Research and Quality. This paper presents the definition and five-stage classification system of chronic kidney disease and summarizes the major recommendations on early detection in adults. Recommendations include identifying persons at increased risk (those with diabetes, those with hypertension, those with a family history of chronic kidney disease, those older than 60 years of age, or those with U.S. racial or ethnic minority status), detecting kidney damage by measuring the albumin-creatinine ratio in untimed ("spot") urine specimens, and estimating the glomerular filtration rate from serum creatinine measurements by using prediction equations. Because of the high prevalence of early stages of chronic kidney disease in the general population (approximately 11% of adults), this information is particularly important for general internists and specialists.

Cardiovascular Diseases↗

Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder. National Kidney Foundation Carnitine Consensus Conference.

References are not cited within this report. However, they are included in the supplement to this issue of the American Journal of Kidney Diseases, which contains reports regarding each topic that was considered by the panel. These recommendations are not intended to be guidelines or standards of care. Instead, they have been developed to provide the best available information and expert opinion in decision-making for the clinician. The recommendations should not be considered as prescribing an exclusive course of management.

Anemia↗

Meeting the challenges of the new K/DOQI guidelines.

Substantial gains in the dialytic treatment of patients with end-stage renal disease have been made during the past several decades. However, inadequate attention has been given to the problem of chronic kidney disease (CKD) as a whole. CKD and its associated complications emerge years before patients develop kidney failure and become dialysis dependent. It now is evident that to improve dialysis outcomes, it is essential for practitioners to recognize the earlier stages of CKD, not only to retard disease progression, but also to prevent and treat its complications and comorbidities long before the need for dialysis arises. The recently published National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines identify the broad-based problem of CKD in the general population and introduce action plans that can be used at the different stages of CKD. This article discusses the process behind the development of the CKD guidelines and highlights the disease evaluation, classification, and stratification system provided by the guidelines. It is hoped that widespread implementation of these recommendations will increase the understanding of CKD among both providers and patients and eliminate many of the obstacles that nephrologists have faced in providing optimal care to dialysis patients in particular and to patients with CKD in general.

Anemia↗

Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.

BACKGROUND: Recently developed clinical practice guidelines and calibration of the Third National Health and Nutrition Examination Survey (NHANES III) serum creatinine assay provide a basis for estimating the prevalence and distribution of chronic kidney disease (CKD) in the United States using standardized criteria based on estimated glomerular filtration rate (GFR) and persistent albuminuria. METHODS: A nationally representative sample of 15,625 noninstitutionalized adults aged 20 years and older from the NHANES III was analyzed. Kidney function (GFR), kidney damage (albuminuria), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine level, spot urine albumin level, age, sex, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation and compared with the Cockcroft-Gault equation for creatinine clearance (CCr). RESULTS: The prevalence of CKD in the US adult population was 11% (19.2 million). By stage, an estimated 5.9 million individuals (3.3%) had stage 1 (persistent albuminuria with a normal GFR), 5.3 million (3.0%) had stage 2 (persistent albuminuria with a GFR of 60 to 89 mL/min/1.73 m(2)), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59 mL/min/1.73 m(2)), 400,000 individuals (0.2%) had stage 4 (GFR, 15 to 29 mL/min/1.73 m(2)), and 300,000 individuals (0.2%) had stage 5, or kidney failure. Aside from hypertension and diabetes, age is a key predictor of CKD, and 11% of individuals older than 65 years without hypertension or diabetes had stage 3 or worse CKD. Compared with GFR estimates, CCr estimates showed a steeper decline with age and were lower in non-Hispanic blacks. CONCLUSION: CKD is common and warrants improved detection and classification using standardized criteria to improve outcomes. Am J Kidney Dis 41:1-12.

Adult↗

The Armenian earthquake of 1988: a milestone in the evolution of nephrology.

A dreadful earthquake struck a densely populated region of Armenia on December 7, 1988. All principal determinants of structural damage and crush injury converged to magnify the dreadful outcomes of this otherwise modest earthquake, which registered 6.9 on the Richter scale. Two circumstantial events focused unprecedented world attention on this natural disaster. First, the news media, assembled to cover the historic visit of Mikhail Gorbachev to the United States, were suddenly deprived of the news they had gathered to cover when Gorbachev interrupted his visit to examine the disaster personally. As a result, the world news media channeled their collective force on covering the tragic events in Armenia. Second, an official Soviet request for dialysis assistance was delivered at the opening session of the annual meeting of the American Society of Nephrology in San Antonio on Sunday, December 11, 1988. As a result, the entire nephrology community was suddenly engulfed in the mounting worldwide enthusiasm to provide humanitarian aid. The subsequent efforts of the National Kidney Foundation and the International Society of Nephrology prompted the discipline to examine, evaluate, and establish a role for nephrologists in preparedness and response to natural disasters.

Acute Kidney Injury↗

Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO study.

Among the 1846 patients in the HEMO Study, chronic high-flux dialysis did not significantly affect the primary outcome of the all-cause mortality (ACM) rate or the main secondary composite outcomes, including the rates of first cardiac hospitalization or ACM, first infectious hospitalization or ACM, first 15% decrease in serum albumin levels or ACM, or all non-vascular access-related hospitalizations. The high-flux intervention, however, seemed to be associated with reduced risks of specific cardiac-related events. The relative risks (RR) for the high-flux arm, compared with the low-flux arm, were 0.80 [95% confidence interval (CI), 0.65 to 0.99] for cardiac death and 0.87 (95% CI, 0.76 to 1.00) for the composite of first cardiac hospitalization or cardiac death. Also, the effect of high-flux dialysis on ACM seemed to vary, depending on the duration of prior dialysis. This report presents secondary analyses to further explore the relationship between the flux intervention and the duration of dialysis with respect to various outcomes. The patients were stratified into a short-duration group and a long-duration group, on the basis of the mean duration of dialysis of 3.7 yr before randomization. In the subgroup that had been on dialysis for >3.7 yr, randomization to high-flux dialysis was associated with lower risks of ACM (RR, 0.68; 95% CI, 0.53 to 0.86; P = 0.001), the composite of first albumin level decrease or ACM (RR, 0.74; 95% CI, 0.60 to 0.91; P = 0.005), and cardiac deaths (RR, 0.63; 95% CI, 0.43 to 0.92; P = 0.016), compared with low-flux dialysis. No significant differences were observed in outcomes related to infection for either duration subgroup, however, and the trends for beneficial effects of high-flux dialysis on ACM rates were considerably weakened when the years of dialysis during the follow-up phase were combined with the prestudy years of dialysis in the analysis. For the subgroup of patients with <3.7 yr of dialysis before the study, assignment to high-flux dialysis had no significant effect on any of the examined clinical outcomes. These data suggest that high-flux dialysis might have a beneficial effect on cardiac outcomes. Because these results are derived from multiple statistical comparisons, however, they must be interpreted with caution. The subgroup results that demonstrate that patients with different durations of dialysis are affected differently by high-flux dialysis are interesting and require further study for confirmation.

Female↗

National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification.

OBJECTIVES: A series of new guidelines has been developed by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative to improve the detection and management of chronic kidney disease (CKD). In most instances of CKD, the earliest manifestations of the disorder may be identified by relatively simple tests. Unfortunately, CKD is often "underdiagnosed," in part because of the absence of a common definition of CKD and a classification of the stages in its progression. The Kidney Disease Outcomes Quality Initiative clinical practice guidelines for CKD evaluation, classification, and stratification provide a basis to remedy these deficits. The specific goals of the guidelines described in this review are to provide: 1) an overview of the clinical practice guidelines as they pertain to children and adolescents, 2) a simple classification of the stages of CKD, and 3) a practical approach to the laboratory assessment of kidney disease in children and adolescents. METHODS: The guidelines were developed as part of an evidence-based evaluation of CKD and its consequences in patients of all ages. The data that were used to generate the guidelines in this article were extracted from a structured analysis of articles that reported on children with CKD. RESULTS AND CONCLUSIONS: This review presents the definition and 5-stage classification system of CKD developed by the work group assigned to develop the guidelines, and summarizes the major recommendations regarding the early detection of CKD. Major emphasis is placed on the identification of children and adolescents with CKD by measuring the protein-to-creatinine ratio in spot urine specimens and by estimating the glomerular filtration rate from serum creatinine using prediction equations.

Adolescent↗

Effect of dialysis dose and membrane flux in maintenance hemodialysis.

BACKGROUND: The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain. METHODS: We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer. RESULTS: In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta2-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients. CONCLUSIONS: Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane.

Adult↗

Seasonal variations in clinical and laboratory variables among chronic hemodialysis patients.

Seasonal variations in BP among chronic hemodialysis patients have been reported. It was hypothesized that other characteristics of these patients might also vary with the seasons. Twenty-one clinical and laboratory variables were examined for seasonal variations among 1445 patients enrolled in the Hemodialysis Study, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. Mixed-effects models were applied to longitudinal changes (up to 45 mo) for individual patients for 19 of the 21 variables, which were measured at least twice each year, to determine the seasonal component of each variable. Seasonal variations in the other two variables, i.e., protein and energy intakes determined from annual dietary records, were assessed in cross-sectional comparisons of intakes of patients entering the study at different time points. Thirteen of the 21 variables examined demonstrated statistically significant (P < 0.01) seasonal components in their longitudinal variations. Predialysis blood urea nitrogen concentrations peaked in March, which coincided approximately with the peak protein catabolic rates, as well as protein and energy intakes (determined by dietary recall). Predialysis systolic and diastolic BP values were highest in winter and lowest in summer, corroborating previous reports. In addition, the lower predialysis BP values in summer were associated with higher outdoor temperatures and less interdialytic fluid gain. The mean predialysis hematocrit values were highest in July, which could not be attributed solely to the estimated changes in plasma volume. Seasonal variations in clinical and laboratory variables occur commonly among chronic hemodialysis patients. The reasons for most of these variations are not apparent and require further investigation. Nonetheless, failure to consider these variations might lead to biases in the interpretation of clinical studies. In addition, awareness of these variations might facilitate the interpretation of laboratory results and the clinical treatment of these patients.

Adult↗