Obesity and chronic kidney disease.

Obesity is associated with the early onset of glomerulomegaly, hemodynamic changes of a hyperfiltering kidney, and increased albuminuria, which are potentially reversible with weight loss. However, pathologic lesions of focal segmental glomerulosclerosis develop in experimental models of sustained obesity, and are observed in morbidly obese humans presenting with massive proteinuria. In addition, several observational, cross sectional and longitudinal studies document that obesity is as an independent risk factor for the onset, aggravated course, and poor outcomes of chronic kidney disease, even after adjustment for confounding co-morbidities including metabolic syndrome, diabetes and hypertension, the major causes of chronic kidney disease. Early dietary intervention to reduce weight, and where necessary bariatric surgery, should be considered in the management of overweight and obese chronic kidney disease (CKD) patients.

The artificial kidney: past, present, and future.

World War II can be taken as a turning point after which the introduction and development of several new diagnostic and therapeutic discoveries have revolutionized medicine and improved the expectancy of life for millions. Notable amongst those technological therapeutic achievements is that of the artificial kidney, first used successfully in the closing years of the war. As a result of the improvements that followed, the kidney was the first solid organ whose function could be replaced, at least partially, by a machine. What started then as exploratory efforts to sustain life evolved over the next few decades into life saving replacement therapy for millions worldwide. Chronic maintenance hemodialysis has certainly changed the prognosis of the otherwise fatal end stage kidney disease that had afflicted humans theretofore. Unfortunately, many of the challenges and problems that had to be overcome in making artificial kidney treatment available continue to plague end-stage kidney disease patients on maintenance hemodialysis. Concerted investigative efforts are currently underway to improve the replacement of kidney function with artificial kidneys that better mimic kidney function. This article reviews the beginnings, evolution, and current challenges of the artificial kidney.

Chronic kidney disease definition and classification: the quest for refinements.

The definition and staging of chronic kidney disease (CKD) have provided a unifying approach to CKD that has generated considerable new information on the epidemiology, course, outcomes, and burden of CKD. Eriksen and Ingebretsen propose a change in the current 3 months chronicity criterion of CKD. Whereas longer lengths of chronicity changed the number of patients in stages 3 and 4, mortality remained high in each of their new groupings. Essentially, CKD persisted and remained a risk multiplier of death.

Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes.

Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. There is now convincing evidence that CKD can be detected using simple laboratory tests, and that treatment can prevent or delay complications of decreased kidney function, slow the progression of kidney disease, and reduce the risk of cardiovascular disease (CVD). Translating these advances to simple and applicable public health measures must be adopted as a goal worldwide. Understanding the relationship between CKD and other chronic diseases is important to developing a public health policy to improve outcomes. The 2004 Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on 'Definition and Classification of Chronic Kidney Disease' represented an important endorsement of the Kidney Disease Outcome Quality Initiative definition and classification of CKD by the international community. The 2006 KDIGO Controversies Conference on CKD was convened to consider six major topics: (1) CKD classification, (2) CKD screening and surveillance, (3) public policy for CKD, (4) CVD and CVD risk factors as risk factors for development and progression of CKD, (5) association of CKD with chronic infections, and (6) association of CKD with cancer. This report contains the recommendations from the meeting. It has been reviewed by the conference participants and approved as position statement by the KDIGO Board of Directors. KDIGO will work in collaboration with international and national public health organizations to facilitate implementation of these recommendations.

The Kidney Disease: improving Global Outcomes website: comparison of guidelines as a tool for harmonization.

Chronic kidney disease (CKD) is a worldwide public health problem with significant comorbidity and mortality. Improving quality of life and survival of CKD patients necessitates a large number of preventive and therapeutic interventions. To resolve these issues several organizations have developed guidelines, which are difficult to compare comprehensively. The Kidney Disease: Improving Global Outcomes website at http://kdigo.org compares five major guidelines. The section 'compare guidelines' covers 41 topics distributed over five major subjects: (1) general clinics; (2) hemodialysis (HD); (3) vascular access for HD; (4) peritoneal dialysis; and (5) chemistries. The tables compare guideline recommendations and the evidence levels on which they are based, with direct links to each of the guidelines. These data show that the different guideline groups tend to propose similar targets, but that nuances in the guideline statements, their rationale, and grading of evidence levels present some discrepancies, although most guidelines are based on the same literature. We conclude that there is an urgent need to harmonize existing guidelines, and for a global initiative to avoid the parallel development of conflicting guidelines on the same topics. The tables displayed on the website offer a basis for structuring this process, a procedure which has recently been initiated by a body composed of the five guideline development groups.

Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Considerable variation in grading systems used to rate the strength of guideline recommendations and the quality of the supporting evidence in Nephrology highlights the need for a uniform, internationally accepted, rigorous system. In 2004, Kidney Disease: Improving Global Outcomes (KDIGO) commissioned a methods expert group to recommend an approach for grading in future nephrology guidelines. This position statement by KDIGO recommends adopting the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach for the grading of evidence and guidelines on interventions. The GRADE approach appraises systematic reviews of the benefits and harms of an intervention to determine its net health benefit. The system considers the design, quality, and quantity of studies as well as the consistency and directness of findings when grading the quality of evidence. The strength of the recommendation builds on the quality of the evidence and additional considerations including costs. Adaptations of the GRADE approach are presented to address some issues pertinent to the field of nephrology, including (1) the need to extrapolate from studies performed predominantly in patients without kidney disease, and (2) the need to use qualitative summaries of effects when it is not feasible to quantitatively summarize them. Further refinement of the system will be required for grading of evidence on questions other than those related to intervention effects, such as diagnostic accuracy and prognosis.

Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Disturbances in mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and are 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 based on bone biopsy. Kidney Disease: Improving Global Outcomes (KDIGO) sponsored a Controversies Conference on Renal Osteodystrophy to (1) develop a clear, clinically relevant, and internationally acceptable definition and classification system, (2) develop a consensus for bone biopsy evaluation and classification, and (3) evaluate laboratory and imaging markers for the clinical assessment of patients with CKD. It is recommended that (1) the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD, which can be further assessed by histomorphometry, and the results reported based on a unified classification system that includes parameters of turnover, mineralization, and volume, and (2) the term CKD-Mineral and Bone Disorder (CKD-MBD) be used to describe a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD, which is manifested by abnormalities in bone and mineral metabolism and/or extra-skeletal calcification. The international adoption of these recommendations will greatly enhance communication, facilitate clinical decision-making, and promote the evolution of evidence-based clinical practice guidelines worldwide.

The national epidemic of chronic kidney disease. What we know and what we can do.

The alarming increase in the incidence and mortality rate of end-stage renal disease (ESRD) over the past several years has prompted concerned physicians to ask why--and to ponder what can be done to ameliorate the situation. This article, the first in a seven-part series coordinated by the National Kidney Foundation, examines the factors surrounding the epidemic of chronic kidney disease and introduces readers to the organization's new clinical practice guidelines developed through its Kidney Disease Outcomes Quality Initiative. These recommendations emphasize early detection and treatment and offer a new avenue of communication between primary care physicians and nephrologists.

The importance of early treatment of the anaemia of chronic kidney disease.

The beneficial effects of treating the anaemia of dialysis-dependent patients with erythropoietin on the improvement of cardiac status, exercise capacity, cognitive function and quality of life are well established. Equally, if not more important is the reduction in morbidity and mortality that accompanies the treatment of anaemia with epoietin. These documented improvements in outcomes of care notwithstanding, mortality and morbidity due to cardiovascular disease (CVD) remain high in dialysis patients. Recent epidemiological evidence indicates that: (i) the prevalence of CVD is very high in patients at the start of dialysis; (ii) pre-existing CVD is the major risk factor for mortality and morbidity on dialysis; (iii) CVD begins early in the course of kidney disease, shows an inverse relationship to kidney function and increases in prevalence and severity with progression of kidney disease; and (iv) corrective measures, which take 3-5 years to show a favourable effect, must be instituted well before the initiation of dialysis. Hypertension and anaemia, which develop in the course of progressive reduction in kidney function, are the principal risk factors for the prevalence of left ventricular hypertrophy (LVH) in those with chronic kidney disease, and their treatment has been shown to arrest or reverse LVH in these individuals. Whereas the treatment of hypertension early in the course of kidney disease has been incorporated into clinical practice, there has been reluctance in the treatment of anaemia because of the possibility of worsening kidney function with epoietin, as shown in rats. There is now convincing evidence that epoietin has no potential adverse effect on kidney function in humans. While the most compelling reason for the early treatment of the anaemia of kidney disease is its beneficial effect on cardiovascular function, other documented potential benefits are improvements in exercise capacity, cognitive function and quality of life.

Design and statistical issues of the hemodialysis (HEMO) study.

The Hemodialysis Study is a multicenter clinical trial of hemodialysis prescriptions for patients with end stage renal disease. Participants from over 65 dialysis facilities associated with 15 clinical centers in the United States are randomized in a 2 x 2 factorial design to dialysis prescriptions targeted to a standard dose or a high dose, and to either low or high flux membranes. The primary outcome variable is mortality; major secondary outcomes are defined based on hospitalizations due to cardiovascular or infectious complications, and on the decline of serum albumin. The Outcome Committee, consisting of study investigators, uses a blinded review system to classify causes of death and hospitalizations related to the major secondary outcomes. The dialysis dose intervention is directed by the Data Coordinating Center using urea kinetic modeling programs that analyze results from dialysis treatments to monitor adherence to the study targets, adjust suggested dialysis prescriptions, and assist in trouble-shooting problems with the delivery of dialysis. The study design has adequate power to detect reductions in mortality rate equal to 25% of the projected baseline mortality rate for both of the interventions.

Methods used to evaluate the quality of evidence underlying the National Kidney Foundation-Dialysis Outcomes Quality Initiative Clinical Practice Guidelines: description, findings, and implications.

This report describes the approach the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) used to assess the strength of published evidence pertinent to individual NKF-DOQI Clinical Practice Guidelines, as well as the relationship between that approach and methods used by the US Preventive Services Task Force, the Cochrane Collaboration, and the Agency for Health Care Policy and Research to rate the quality and/or strength of evidence. We also present the results of an analysis of the strength of evidence underlying the NKF-DOQI Guidelines showing that one cannot infer the quality of evidence reported in a study (rated either on a 0-to-1 scale or categorically as excellent, very good, good, fair, or poor) simply by knowing the type of study design used (randomized trial, nonrandomized trial, natural experiment, cohort study, cross-sectional study, case-control study, case report). Issues related to assessment of the strength of evidence underlying a practice guideline opposed to that reported in an individual study are highlighted.

The dialysis outcomes quality initiative: history, impact, and prospects.

Rigorously developed clinical practice guidelines have the potential to improve patient outcomes. It is toward that end that the National Kidney Foundation (NKF) launched in March 1995 the Dialysis Outcome Quality Initiative (DOQI), an ambitious effort to develop evidence-based clinical practice guidelines for the care of patients with end-stage renal disease (ESRD). Independent, interdisciplinary work groups conducted a structured review of the content and methodologic rigor of all the published literature pertinent to four selected topics: hemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anemia. Following expert, organizational, and public review, the guidelines were issued in September and October 1997. An implementation plan that called for widespread dissemination of the guidelines and facilitation of adoption of them has resulted in their broad acceptance and Integration into quality improvement efforts. Additional guidelines on nutrition have recently been completed, while others on bone disease, hypertension, and hyperlipidemia are in various stages of planning or development. A major determinant of poor outcome of maintenance dialysis patients is the debilitated state of many individuals with ESRD at the time that they commence dialysis therapy. The recognition of this problem has stimulated an interest in extending the guidelines to management of patients with less severe renal insufficiency, well before they need renal replacement therapy; and to the early detection of renal insufficiency by a proteinuria and albuminuria risk assessment, detection, and elimination (PARADE) program. What started as an initiative to improve the quality of care of dialysis patients has evolved into a considerably expanded effort to making lives better for all individuals with any level of renal insufficiency.

Michelangelo: art, anatomy, and the kidney.

Michelangelo (1475-1564) had a life-long interest in anatomy that began with his participation in public dissections in his early teens, when he joined the court of Lorenzo de' Medici and was exposed to its physician-philosopher members. By the age of 18, he began to perform his own dissections. His early anatomic interests were revived later in life when he aspired to publish a book on anatomy for artists and to collaborate in the illustration of a medical anatomy text that was being prepared by the Paduan anatomist Realdo Colombo (1516-1559). His relationship with Colombo likely began when Colombo diagnosed and treated him for nephrolithiasis in 1549. He seems to have developed gouty arthritis in 1555, making the possibility of uric acid stones a distinct probability. Recurrent urinary stones until the end of his life are well documented in his correspondence, and available documents imply that he may have suffered from nephrolithiasis earlier in life. His terminal illness with symptoms of fluid overload suggests that he may have sustained obstructive nephropathy. That this may account for his interest in kidney function is evident in his poetry and drawings. Most impressive in this regard is the mantle of the Creator in his painting of the Separation of Land and Water in the Sistine Ceiling, which is in the shape of a bisected right kidney. His use of the renal outline in a scene representing the separation of solids (Land) from liquid (Water) suggests that Michelangelo was likely familiar with the anatomy and function of the kidney as it was understood at the time.

The kidney in ancient Egyptian medicine: where does it stand?

Driven by their deep-seated desire for eternal life in a healthy body, ancient Egyptians were one of the first civilizations to begin collecting and recording medical lore and medicinals that were effective for a healthy body. With its religious origins, medical care was initially provided by priests, but evolved over time into an independent discipline practiced by the swnw (sounou) or physician. What has been preserved of their knowledge in extant medical papyri reflects the great capacity of Egyptians for practical achievement in treating symptoms, but lacks the abstract thought that was to come with the advent of the more rational Greek medicine. The number of prescriptions and incantations for the management of urinary disorders (hematuria, retention, frequency, infection) and dropsy that are mentioned in extant medical papyri likely reflect the frequency with which these problems were encountered. Urine was thought to be formed in the region of the bladder, by a process considered akin to purification. Available studies on preserved mummies indicate that kidney disease was not uncommon. Whether a functional role of the kidney was appreciated at all is highly doubtful. On the other hand, the available evidence suggests an awareness of the kidney (ggt) to which was ascribed a mythological role that may well account for why the kidneys and the heart were the only organs not removed during the process of mummification.

Santorio Sanctorius (1561-1636) - founding father of metabolic balance studies.

The intellectual renaissance of the closing decades of the sixteenth century provided the fertile ground in which the budding spirit of scientific inquiry emerged in the seventeenth century. Direct observation, soon augmented by instrumentation that allowed for quantification and, therefore, verification, became the revelatory medium for the progress of the sciences. In medicine, progress depended on the application of the exact sciences of chemistry, mathematics and physics to the study of function. One of the medical luminaries of this early scientific revolution was Santorio Sanctorius (1561- 1636), whose principal contributions were his studies on insensible perspiration and his instrumental inventions. To study insensible perspiration, he designed a movable platform attached to a steelyard scale that allowed for the quantification of changes in body weight of subjects who partook in their daily activities on the platform. After years of self-experimentation, he applied his device to the study of patients. Unfortunately, his records are lost. What survives is a summary of his observations in a series of aphorisms published under the title of Ars de statica medicina, in 1614; 3 years after he was appointed Ordinary Professor of Theoretical Medicine in Padua. To enhance the bedside evaluation of patients, he also designed instruments to quantify the pulse, temperature, and environmental humidity. For his pioneering and detailed balance studies, Sanctorius clearly deserves the title of founding father of metabolic balance studies.