Biomedical subjects
Publications and source records attributed to G Eknoyan.
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Hundreds of thousands of individuals are alive today because of the availability of dialysis for the treatment of patients with end-stage renal disease (ESRD). From the outset, it was evident that this was a costly therapy and would require specialized training. The federal government responded by providing financial support and medicine by establishing the discipline of nephrology to provide specialized training. As a result, the center stage that ESRD has come to occupy was dictated by a successful treatment in the purview of a new discipline by a model and well-intentioned, but restrictive, law that provided support only to the terminal stage of kidney disease. That this natural evolution was short-sighted has become a belated, but well-deserved, focus of attention. The care of chronic renal disease (CRD) patients cannot start after the onset of ESRD when renal replacement therapy is initiated but must be set into motion when renal failure first begins to exert its detrimental effects on the metabolic balance, function, and structure of the body. Attentive care is needed throughout the course of progressive renal failure, because once CRD begins to progress, there is an increasing number of detrimental consequences whose cumulative burden will exert its ravages on the body simultaneously with that of the ongoing loss of renal function. Consequently, the patient with CRD who presents in ESRD has already sustained considerable, often irreversible, loss of body function. Preventive measures to circumvent this eventuality are most effective, cost-efficient, and of greatest benefit when instituted early in the course of progressive CRD. This is probably truest of cardiovascular disease, which is the leading cause of mortality of patients on dialysis and following transplantation. The report of the National Kidney Foundation Task Force on Cardiovascular Disease in CRD is a first attempt to promulgate and provide evidence-based recommendations for this holistic approach to the care of patients with renal disease.
Both a bleeding diathesis and a tendency to hypercoagulability occur in the course of renal disease. More common and consistent in occurrence during the progression of renal failure to end-stage renal disease is the hemostatic defect. The principal cause of this abnormality is the uremic state and, as a rule, it is reversible following the institution of adequate renal replacement therapy and correction of the anemia with epoietin. By contrast, the tendency to hypercoagulability is usually encountered in patients with the nephrotic syndrome and shows a correlation to the degree of hypoalbuminemia, being more evident at serum albumin levels of < 2 g/dl. Although the coagulopathy is complex in pathogenesis, a defect in the fibrinolytic process plays a critical role in its development. A tendency to pro-thrombosis due to abnormal fibrinolysis has been identified also in patients on renal replacement therapy with continuous ambulatory peritoneal dialysis (CAPD). The observed coagulation abnormalities resemble those of the nephrotic syndrome. Although its etiology remains undefined, a role for the albumin losses in the peritoneal dialysate has been implicated in the prothrombotic state that occurs in some CAPD patients.
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BACKGROUND: The NKF-DOQI (National Kidney Foundation--Dialysis Outcomes Quality Initiative) began in March 1995 with the following objectives: To improve end-stage renal disease (ESRF) patient survival, to reduce patient morbidity, to increase efficiency of care, and to improve quality of life for ESRF patients. METHODS: The development of the NKF-DOQI Clinical Practice Guidelines focused on haemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anaemia. Principles guiding the methodology included scientific and methodological rigour, interdisciplinary approach, independence of the Work Groups, and an open review process. Unique features of this evidence-based guideline development process included the use of mock guidelines and rationales to guide the literature research, and an unprecedented three-stage review process. RESULTS: Work Groups reviewed more than 11,000 articles. A total of 114 clinical practice guidelines were developed by the Work Groups; these have been reviewed by more than 1200 professionals and patients. CONCLUSION: The NKF-DOQI Clinical Practice Guidelines has been a unifying effort for the entire renal community. The guidelines are an important step in the process of improving the quality of dialysis practice and improving ESRF patient outcomes. Priorities for implementation of the guidelines include education of ESRF professionals and patients, working with providers and insurers to encourage compliance, and follow-up evaluation of patient outcomes to quantify compliance results.
Rigorously developed clinical practice guidelines have the potential to change practice patterns to obtain improved patient outcomes. Toward that end, in March 1995 the National Kidney Foundation initiated the Dialysis Outcomes Quality Initiative, a comprehensive effort to create literature-based clinical practice guidelines in nephrology. Independent interdisciplinary work groups reviewed the available body of scientific literature on the following topics: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anemia. More than 11,000 papers were identified; of these approximately 1500 were found to be relevant, requiring formal structured review. Work groups formulated draft guidelines with supporting rationales that included the evidentiary basis for the recommendations. The draft guidelines were subjected to an unprecedented three-stage review process that involved more than 50 organizations from the renal community, including end-stage renal disease networks, patients dialysis providers, managed care organizations, and government. The finalized guidelines were issued in September 1997. Planned guideline implementation activities will focus on achieving the following: cooperation from the renal community; education of patients, clinicians, policy makers, and dialysis providers; information system tools to facilitate adoption of the guidelines; and evaluation strategies to determine whether practice patterns and outcome goals are achieved.
A pupil and then the successor of Vesalius to the Chair of Anatomy and Surgery at the University of Padua, Matteo Realdo Colombo (1516-1559) was equally consumed by the flame of scientific inquiry and recognition. His sole contribution to the literature, De Re Anatomica, was published after his death in 1559. In it, he correctly describes the position of the right kidney as lower than that of the left and provides the best description of the pulmonary circulation before that of William Harvey, who in his text duly acknowledged Colombo's contributions. In the concluding chapter, he establishes the beginnings of morbid anatomy in describing diseased organs. De Re Anatomica was widely used as a textbook of anatomy, being translated into English in 1578 and German in 1609. He came to be sufficiently well known to become physician to the Vatican. One of his best known patients was Michelangelo, with whom he vainly tried to collaborate in illustrating De Re Anatomica. A regrettable eventuality, which could have reversed the fortunes of Vesalius and Colombo in the annals of the history of medicine.
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The obvious disfigurement caused by clinically evident edema has been a matter of medical concern for ages. Most of the early writings on the subject (Sumerian, Babylonian, Egyptian, Greek) center on dropsy, its causes and management. While reference to the heart is made in the ancient texts, much of the focus is on the abdominal (ascitic) accumulation of fluid. The role of the heart and "dropsy of the chest" began to be differentiated and attract attention sometime by the end of the seventeenth century, and were well appreciated by the eighteenth century. By the beginning of the nineteenth century the reports of John Blackall and Richard Bright provided new insight by differentiating dropsy into that of cardiac and renal origins. The role of salt, initially measured and thought in terms of its anion chloride, began to be appreciated by the middle to late nineteenth century. Its mobilization, however, remained problematic. The "cure de dechloruration", which gained fame by the end of the nineteenth century, was not always a successful undertaking. The treatment of dropsy, which centered on augmenting secretions (diaphoretics, purgatives) or mechanical removal of body fluids (bleeding, leeching, lancing), remained a frustrating and chancy undertaking for much of the time that medicine has had to deal with it. Although mercury had been advocated as a diuretic in the sixteenth century, even the organic mercurials that were introduced after World War II were limited in their effectiveness. The discovery of sulfanilamide-induced sodium bicarbonate diuresis in the late 1940s was to provide the first step in the new age of clinically effective diuretics, which began in the 1950s with the introduction of chlorothiazide, the first orally effective agent to mobilize sodium chloride. The subsequent introduction of more potent diuretics was made possible by concurrent advances in renal physiology and the understanding of the sodium handling by the kidney.
The incidence and prevalence rates of end-stage renal disease (ESRD) in the United States continue to increase. In 1995, the incidence rate was 262 per million population, with a point prevalence rate of 975 per million population. The exact number of individuals with abnormal renal function but not yet at end stage is difficult to assess. Crude estimates suggest that approximately 0.4% of the U.S. population has serum creatinine values greater than 2.0 mg/dl. In some sub-populations, such as African Americans, the estimate is + as high as 1.0%. The rate of progression, likewise, is difficult to assess. In general, renal manifestations of certain systemic diseases such as diabetes mellitus and systemic lupus erythematosus, and those with significant proteinuria (usually greater that 3.0 g/24 hr) seem to have a more rapid progressive course to end stage. If intervention is expected to be successful in halting or slowing down progression, accurate assessment of the early manifestations of renal disease, structure, and function need to be established. Currently accepted methods of assessment of renal disease include measurement of renal function such as serum creatinine and glomerular filtration rate, measurement of proteinuria, assessment of tubular function, glomerular sieving and permselectivity, radiologic imaging techniques, and evaluation of histo-morphometry. Interventions that have been shown to slow progression include control of hypertension, and treatment modalities that reduce proteinuria, such as, the use of angiotensin converting enzyme inhibitors. Further clinical and basic science studies are needed to accurately define the important predictors of progression, and interventions that are effective in slowing or halting progression.
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A 55-year-old man with chronic inflammatory demyelinating polyradiculoneuropathy developed the nephrotic syndrome. Renal biopsy showed stage I membranous glomerulonephritis. Review of the literature revealed the association of these two rare syndromes, considered to be due to immunologic dysfunction, in two other cases, as well as several cases of the acute form of demyelinating peripheral polyradiculoneuropathy. The nephrotic syndrome appears to be persistent in the chronic form of the peripheral neuropathy but reversible in its acute form following immunosuppressive therapy. The possibility of a common immunopathogenesis in the association of membranous glomerulonephritis and inflammatory demyelinating peripheral neuropathies deserves further scrutiny.
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most valuable groups of available medications because of their effectiveness in relieving pain, particularly that associated with rheumatoid arthritis. They are also among the most commonly prescribed drugs and, because of their availability over-the-counter, they are among the most widely consumed agents, especially by elderly people. Older individuals are more predisposed to the renal adverse effects of NSAIDs, because of: (i) age-associated changes in renal function; (ii) the prevalence of comorbid conditions (congestive heart failure, hypertension, hepatic cirrhosis, renal insufficiency); and (iii) the pervasive use of concomitant drugs that affect kidney function (diuretics, antihypertensives). However, because the incidence of NSAID-induced acute renal failure (ARF) is relatively low, and because it occurs in an identifiable and therefore preventable setting, the benefits of limited NSAID use outweigh the risks of this adverse effect. Using NSAIDs for a restricted period of time at the lowest effective dosage, and informing patients of the conditions in which ARF can occur, should minimise the risk of this effect. If the use of an NSAID in a patient at potential risk of ARF is necessary, close monitoring of renal function should further reduce the already low risk:benefit ratio for this adverse effect.
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