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Biomedical subjects

Garabed Eknoyan

Publications and source records attributed to Garabed Eknoyan.

At least 19 recordsLinked to original sources
PubMed2007

Chronic kidney disease-mineral-bone disorder: a new paradigm.

Disturbances in mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and an important cause of morbidity, decreased quality of life, and extraskeletal calcification that have been associated with increased cardiovascular mortality. These disturbances have traditionally been termed renal osteodystrophy and classified on the basis of bone biopsy. Kidney Disease: Improving Global Outcomes (KDIGO) recently sponsored a Controversies Conference to evaluate this definition. The recommendations were that (1) the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD and (2) the term CKD-mineral and bone disorder (CKD-MBD) be used to describe the broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is manifested by an abnormality of any one or a combination of the following: laboratory-abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; bone-changes in bone turnover, mineralization, volume, linear growth, or strength; and calcification-vascular or other soft-tissue calcification. The pathogenesis and clinical manifestations of these components of CKD-MBD are described in detail in this issue of Advances in Chronic Kidney Disease.

Bone Diseases, Metabolic↗
PubMed2006

On the origin of genetics and beginnings of medical genetics of diseases of the kidney.

The twentieth century has been termed the century of the gene. Although the term "gene" was introduced in 1909, interest in reproduction and heredity has occupied humankind since its transition from hunter-gatherers to farmers and herders. Heredity, as it applies to diseases, began with Greek medicine. The humoral theory of the Hippocratic Corpus provided an etiological explanation for susceptibility of individuals to certain diseases well into the nineteenth century and was variously termed diathesis, temperament, and constitution. The application of the new probability math to quantify the hybridization of sweet peas by Gregor Mendel (1822-1884) in 1866 provided a scientific basis to inheritance, which had theretofore been an amalgam of scattered empirical observations. The near simultaneous publication of Origin of Species by Charles Darwin (1809-1882) in 1859 was a key catalyst in the transfer of what had been studies in plant biology into studies of populations and humans. The subsequent growth of genetics has been the outcome of interplay of technological breakthroughs in statistical analysis, cytology, biochemistry, physics, and computer science, coupled with the insightful analysis of workers in the field, several of whom have been the recipients of the Nobel Prize in medicine or chemistry since 1933. Application of these techniques to molecular biology and medical genetics is just beginning to yield insight into diseases of the kidney and provide visions of their likely therapies in the future.

Genetics, Medical↗
PubMed2006

A history of obesity, or how what was good became ugly and then bad.

Chronic food shortage and malnutrition have been the scourge of humankind from the dawn of history. The current worldwide epidemic of obesity, now recognized as a public health crisis, is barely a few decades old. Only after the technological advances of the eighteenth century did a gradual increase in food supply became available. The initial effect of these advances in improved public health and amount, quality, and variety of food was increased longevity and body size. These early favorable outcomes of technological advances notwithstanding, their incremental effect since the Second World War has been an overabundance of easily accessible food, coupled with reduced physical activity, that accounts for the recent increased prevalence of obesity. Obesity as a chronic disease with well-defined pathologic consequences is less than a century old. The scarcity of food throughout most of history had led to connotations that being fat was good, and that corpulence and increased "flesh" were desirable as reflected in the arts, literature, and medical opinion of the times. Only in the latter half of the nineteenth century did being fat begin to be stigmatized for aesthetic reasons, and in the twentieth century, its association with increased mortality was recognized. Whereas early reports listed obesity as a risk factor for mortality from "chronic nephritis," the subsequent recognition of the more common association of obesity with diabetes, hypertension, and heart disease altered the listings and questioned its being a risk factor for kidney disease. An enlarging body of evidence, accrued over the past decade, now indicates a direct association of obesity with chronic kidney disease and its outcomes.

Beauty↗
PubMed2006

Hemodialysis timing, survival, and cardiovascular outcomes in the Hemodialysis (HEMO) Study.

BACKGROUND: The timing of medical therapies has been shown to influence the outcomes and side effects of treatments for disease. This report examines the extent to which hemodialysis treatment time of day was associated with cardiovascular mortality and morbidity and all-cause mortality in a secondary analysis of the Hemodialysis Study. METHODS: Dialysis start time defined dialysis shift: morning beginning between 0400 and 0930 hours (n = 822); midday, between 0930 and 1530 hours (n = 851); and evening, between 1530 and 2200 hours (n = 172). Outcome measures included all-cause mortality, cardiac death, composite end point of all-cause mortality or first cardiac hospitalization, and composite end point of first cardiac hospitalization or cardiac death. RESULTS: Morning hemodialysis was associated with a lower likelihood of cardiovascular events compared with the evening shift in all-cause mortality or first cardiac hospitalization (evening versus morning, relative risk [RR], 1.29; 95% confidence interval [CI], 1.01 to 1.65; P = 0.043), as well as first cardiac hospitalization or cardiac death (evening versus morning, RR, 1.44; 95% CI, 1.11 to 1.89; P = 0.007). No differences were noted in the other 2 outcomes, and there was no statistically significant difference between the morning and midday shifts. Although crude mortality rates were greater in the midday compared with morning (RR, 1.21; 95% CI, 1.05 to 1.39; P = 0.008), this association was attenuated after adjustment (RR, 1.04; 95% CI, 0.89 to 1.22; P = 0.64). CONCLUSION: Making extensive adjustment for patient characteristics, this report does not support the association of lower all-cause mortality with morning hemodialysis or a particular benefit for older patients.

Cardiovascular Diseases↗
PubMed2005

Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study.

In the randomized Hemodialysis (HEMO) Study, chronic high-flux dialysis, as defined by higher beta-2 microglobulin (beta(2)M) clearance, compared with low-flux dialysis did not significantly alter all-cause mortality in the entire cohort but was associated with lower mortality in long-term dialysis patients. This analysis examined the determinants of serum beta(2)M levels and the associations of serum beta(2)M levels or dialyzer beta(2)M clearance with mortality. In a multivariable regression model that examined 1704 patients, baseline residual kidney urea clearance and dialyzer beta(2)M clearance were strong predictors of predialysis serum beta(2)M levels at 1 mo of follow-up, with regression coefficients of -7.21 (+/-0.69 SE) mg/L per ml/min per 35 L urea volume (P < 0.0001) and -1.94 (+/-0.30) mg/L per ml/min (P < 0.0001),respectively. In addition, black race and baseline years on dialysis correlated positively whereas age, diabetes, serum albumin, and body mass index correlated negatively with serum beta(2)M levels (P < 0.05). In time-dependent Cox regression models, mean cumulative predialysis serum beta(2)M levels but not dialyzer beta(2)M clearance were associated with all-cause mortality (relative risk = 1.11 per 10-mg/L increase in beta(2)M level; 95% confidence interval 1.05 to 1.19; P = 0.001), after adjustment for residual kidney urea clearance and number of prestudy years on dialysis. This association is supportive of the potential value of beta(2)M as a marker to guide chronic hemodialysis therapy.

Adult↗
PubMed2005

The kidneys in the Bible: what happened?

The kidneys, always used in the plural (kelayot), are mentioned more than 30 times in the Bible. In the Pentateuch, the kidneys are cited 11 times in the detailed instructions given for the sacrificial offering of animals at the altar. Whereas those instructions were for purification ceremonies at the Temple, sacrificial offerings were made subsequently in seeking divine intervention for the relief of medical problems. In the books of the Bible that follow the Pentateuch, mostly in Jeremiah and Psalms, the human kidneys are cited figuratively as the site of temperament, emotions, prudence, vigor, and wisdom. In five instances, they are mentioned as the organs examined by God to judge an individual. They are cited either before or after but always in conjunction with the heart as mirrors of the psyche of the person examined. There is also reference to the kidneys as the site of divine punishment for misdemeanors, committed or perceived, particularly in the book of Job, whose suffering and ailments are legendary. In the first vernacular versions of the Bible in English, the translators elected to use the term "reins" instead of kidneys in differentiating the metaphoric uses of human kidneys from that of their mention as anatomic organs of sacrificial animals burned at the altar. This initial effort at linguistic purity or gentility has progressed further in recent versions of the Bible, in which the reins are now replaced by the soul or the mind. The erosion may have begun in the centuries that followed the writing of the Bible, when recognition of the kidneys as excretory organs deprived them of the ancient aura of mysterious organs hidden deep in the body but accessible to the look of God. At approximately the same time, Greek analytical philosophy argued that the brain, which is never mentioned in the Bible, was the most divine and sacred part of the body. This argument gained ground in the past century, when the functions of the brain were elucidated, and ultimately established in the 1960s, when salvaging the kidneys for transplantation necessitated a change in the definition of death as irreversible brain function. It is ironic that advances in understanding kidney function and in nephrology that made kidney transplantation feasible may have contributed, albeit indirectly, to the gradual elimination of the metaphoric mention of human kidneys in the Bible.

Animals↗
PubMed2005

Association of achieved dialysis dose with mortality in the hemodialysis study: an example of "dose-targeting bias".

In the intention-to-treat analysis of the Hemodialysis Study, all-cause mortality did not differ significantly between the high versus standard hemodialysis dose groups. The association of mortality with delivered dose within each of the two randomized treatment groups was examined, and implications for observational studies were considered. Time-dependent Cox regression was used to relate the relative risk (RR) for mortality to the running mean of the achieved equilibrated Kt/V (eKt/V) over the preceding 4 mo. eKt/V was categorized by quintiles within each dose group. Analyses were controlled for case-mix factors and baseline anthropometric volume. Within each randomized dose group, mortality was elevated markedly when achieved eKt/V was in the lowest quintile (RR, 1.93; 95% confidence interval [CI], 1.40 to 2.66; P < 0.0001 in the standard-dose group; RR, 2.04; 95% CI, 1.50 to 2.76; P < 0.0001 in the high-dose group; RR relative to the middle quintiles). The mortality rate in the lowest eKt/V quintile of the high-dose group was higher than in the full standard-dose group (RR, 1.59; 95% CI, 1.29 to 1.96; P < 0.0001). Each 0.1 eKt/V unit below the group median was associated with a 58% higher mortality in the standard-dose group (P < 0.001) and a 37% higher mortality in the high-dose group (P < 0.001). The magnitude of these dose-mortality effects was seven- to 12-fold higher than the upper limit of the 95% CI from the intention-to-treat analysis. The effects were attenuated in lagged analyses but did not disappear. When dialysis dose is targeted closely, as under the controlled conditions of the Hemodialysis Study, patients with the lowest achieved dose relative to their target dose experience markedly increased mortality, to a degree that is not compatible with a biologic effect of dose. The possibility of similar (albeit smaller) biases should be considered when analyzing observational data sets relating mortality to achieved dose of dialysis.

Black People↗
PubMed2005

Emergence of quantification in clinical investigation and the quest for certainty in therapeutics: the road from Hammurabi to Kefauver.

Throughout most of history, medical knowledge was descriptive in nature and derived from the work of individual investigators of independent mind pursuing careful but often chance observations. Using deductive reasoning, these findings were then generalized, authoritatively presented, and dogmatically promulgated. This, coupled with firmly grounded principles of divine determinism, precluded any serious consideration of randomness, even when variations from recorded, but erroneous, statements were actually observed. Although probability remained an integral component of diagnosis and therapy, it was only as an attribute of opinion and not one supported by numbers. The gradual erosion of this edifice began during the scientific revolution of the seventeenth century that led to the burgeoning of the sciences basic to medicine. Although clinicians applauded these contributions, they failed to apply the inductive method of investigation to the study of disease or to therapy. The "numerical method" of Pierre Louis (1787-1872) first introduced systematic quantification into medicine during the first half of the nineteenth century. Analysis of quantifiable data found its principal application in epidemiology, which flourished during the second half of the nineteenth century. The subsequent adoption of probability calculus for the analysis of quantifiable data, during the first half of the twentieth century, refined the process further and led to the gradual emergence of medical statistics, with a distinct role in clinical research. The mathematical precision provided by quantification and statistical analysis established certainty in medicine and ultimately changed the conjectural art of clinical practice into a disciplined science founded on clinical investigation, the very basis of present-day, evidence-based medicine.

History, 15th Century↗
PubMed2005

A history of diabetes mellitus or how a disease of the kidneys evolved into a kidney disease.

Diabetes mellitus has a long history during which it was considered to be a disease of the kidneys well into the middle of the 19th century. Recognized in antiquity from its excessive urine output and described as a disease of the urinary tract, its clinical features and fatal outcome were quite accurately recorded by the 1st century ad . Galen (129-200) described it as a disease specific to the kidneys because of a weakness in their retentive faculties. The sweet taste of diabetic urine, which is described in ancient Indian texts and noted by Avicenna (980-1037) and Morgagni (1635-1683), was attributed to the passage of absorbed water and nutrients unchanged into the urine. In 1674, Thomas Willis (1621-1675) first differentiated diabetes from other causes of polyuria by the sweet taste (quasi melle) of diabetic urine and suggested that the sweetness first appears in the blood. A century later, Matthew Dobson (1732-1784) showed that the urine sweetness was because of sugar and was preceded and accompanied by sugar in the blood. Although diabetes then came to be ascribed to increased sugar in the blood, the presence of sugar in the urine continued to be attributed to the decreased retentive properties of the kidneys. The experimental production of diabetes in pancreatectomized dogs that could be reversed by subcutaneous pancreatic transplantation in 1889, and ultimate isolation of insulin in 1922 clearly established diabetes as an endocrine disease. The stage of diabetes as a disease of the kidneys was now over but that of diabetes as a cause of kidney disease was yet to come. Diabetes as a cause of end stage kidney disease was first described in 1936 and extensively documented shortly thereafter, whereas the evidence of its increasing prevalence as a cause of chronic kidney disease continues to accrue.

Diabetes Mellitus↗
PubMed2005

On the evolution of pediatrics and the emergence of pediatric nephrology.

Pediatrics is a relatively new discipline; it came into existence at the end of the nineteenth century, when the number practitioners of medicine interested in the study and teaching of pediatrics grew in proportion to research in diseases of children. The study of two childhood diseases was instrumental in the very emergence of nephrology. The first disease was diarrheal dehydration of infants, the study of which in the first decades of the twentieth century provided much of the body of knowledge of water and electrolyte metabolism that formed the foundations of renal physiology. The second disease was the nephrotic syndrome of children, the successful treatment of which became possible after the Second World War with the use of adrenal cortical tropic hormone and steroids. The prohibitive cost of obtaining these new miracle drugs then led to the foundation in 1948 of the Nephrosis Foundation, which became the National Kidney Foundation (NKF) in 1950-the first organization in the United States dedicated to the support and dissemination of knowledge on diseases of the kidney. The Scientific Advisory Board of the NKF was the nidus around which the discipline of nephrology then evolved and, after the availability of maintenance hemodialysis, flourished. Pediatric nephrology, which emerged from these beginnings, closes the circle that began with the emergence of nephrology from its foundations in pediatric studies of childhood diarrhea and treatment of the nephrotic syndrome.

Child↗
PubMed2005

Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD), and premature death. A simple definition and classification of kidney disease is necessary for international development and implementation of clinical practice guidelines. Kidney Disease: Improving Global Outcomes (KDIGO) conducted a survey and sponsored a controversies conference to (1) provide a clear understanding to both the nephrology and nonnephrology communities of the evidence base for the definition and classification recommended by Kidney Disease Quality Outcome Initiative (K/DOQI), (2) develop global consensus for the adoption of a simple definition and classification system, and (3) identify a collaborative research agenda and plan that would improve the evidence base and facilitate implementation of the definition and classification of CKD. The K/DOQI definition and classification were accepted, with clarifications. CKD is defined as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for 3 months or more, irrespective of cause. Kidney damage in many kidney diseases can be ascertained by the presence of albuminuria, defined as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens. GFR can be estimated from calibrated serum creatinine and estimating equations, such as the Modification of Diet in Renal Disease (MDRD) Study equation or the Cockcroft-Gault formula. Kidney disease severity is classified into five stages according to the level of GFR. Kidney disease treatment by dialysis and transplantation should be noted. Simple, uniform classifications of CKD by cause and by risks for kidney disease progression and CVD should be developed.

Albuminuria↗
PubMed2005

A new initiative in nephrology: 'Kidney disease: improving global outcomes'.

The burden of kidney disease: Improving global outcomes. Chronic kidney disease (CKD) is a worldwide public health problem with an increasing incidence and prevalence of patients requiring replacement therapy. 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 evidence-based care of these patients are universal and independent of their geographic location. This paper describes the 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. Some current and future activities of this initiative are described. They include among others modification of the classification of CKD, the development of guidelines on hepatitis C, the organisation of consensus conferences like on Renal Osteodystrophy, and the creation of a website allowing the comparison of the five main English language clinical practice guidelines in kidney disease worldwide.

Chronic Disease↗
PubMed2004

Clinical practice guidelines for chronic kidney disease in adults: Part II. Glomerular filtration rate, proteinuria, and other markers.

The Kidney Disease Outcome Quality Initiative of the National Kidney Foundation published clinical practice guidelines on chronic kidney disease in February 2002. Of the 15 guidelines, the first six are of greatest relevance to family physicians. Part II of this two-part review covers guidelines 4, 5, and 6. Glomerular filtration rate is the best overall indicator of kidney function. It is superior to the serum creatinine level, which varies with age, sex, and race and often does not reflect kidney function accurately. The glomerular filtration rate can be estimated using prediction equations that take into account the serum creatinine level and some or all of specific variables (age, sex, race, body size). In many patients, estimates of the glomerular filtration rate can replace 24-hour urine collections for creatinine clearance measurements. Urine dipsticks generally are acceptable for detecting proteinuria. To quantify proteinuria, the ratio of protein or albumin to creatinine in an untimed (spot) urine sample is an accurate alternative to measurement of protein excretion in a 24-hour urine collection. Patients with persistent proteinuria have chronic kidney disease. Other techniques for evaluating patients with chronic kidney disease include examination of urinary sediment, urine dipstick testing for red and white blood cells, and imaging studies of the kidneys (especially ultrasonography). These techniques also can help determine the underlying cause of chronic kidney disease. Family physicians should weigh the value of the National Kidney Foundation guidelines for their clinical practice based on the strength of evidence and perceived cost-effectiveness until additional evidence becomes available on the usefulness of the recommended quality indicators.

Adult↗
PubMed2004

The Dialysis Outcomes and Practice Patterns Study (DOPPS) and the Kidney Disease Outcomes Quality Initiative (K/DOQI): a cooperative initiative to improve outcomes for hemodialysis patients worldwide.

Two initiatives were launched in the closing years of the past century with the goal of improving the treatment outcomes of patients with kidney failure: the Kidney Disease Outcomes Quality Initiative, which formed expert panels to develop evidence-based clinical practice guidelines, and the Dialysis Outcomes and Practice Patterns Study (DOPPS), which now gathers data on practice patterns in dialysis facilities in 12 countries, including the United States. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) program was established to promote worldwide coordination and integration of initiatives to develop and implement clinical practice guidelines and provides new opportunities of cooperation with the international scope of the DOPPS. Collaboration between the DOPPS and KDIGO will lead to broader dissemination of relevant information to nephrologists, health care providers, and patients. Linking the DOPPS scope of work with the KDIGO goals will help develop continuous quality improvement programs and the provision of direct feedback to participating dialysis centers throughout the world. This will establish an essential component in the translation to clinical practice of evidence-based guidelines worldwide.

Evidence-Based Medicine↗