Transplantation

Abstract: 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.

Abstract: Background The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult. Methods We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Twenty-eight patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation...

Abstract: Background Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. Methods The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. Results Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and s...

Abstract: Background Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year. Methods Seven consecutive patients with type 1 diabetes and a history of severe hypoglycemia and metabolic instability underwent islet transplantation in conjunction with a glucocorticoid-free immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab. Islets were isolated by ductal perfusion with cold, purified collagenase, digested and purified in xenoprotein-free medium, and transplanted immediately by means of a percutaneous transhepatic portal embolization. Results All seven patients quickly attained sustained insulin independence after transplantation of a mean (±SD) islet mass of 11,547±1604 islet equivalents per kilogram of body weight (median follow-up, 11.9 months; range, 4.4 to 14.9). All recipients required islets from two donor pancreases, and one required a third transplant from tw...

Abstract: Background Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy Methods We performed a randomized, controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was Results Two hundred seven patients received captopril, and 202 placebo Serum creatinine concentrations doubled in 25 patients in the captopril group, as compared with 43 patients in the placebo group (P = 0007) The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole, 76 percent in the subgroup with a baseline serum creatinine concentration of 20 mg per deciliter (177 mumol per liter), 55 percent in the subgroup with a concentration of 15 mg per deciliter (133 mumol per liter), and 17 percent in the subgroup with a concentration of 10 mg per deciliter (884 mumol per liter) The mean (+/- SD) rate of decline in creatinine clearance was 11 +/- 21 percent per year in the captopril group and 17 +/- 20 percent per year in the placebo group (P = 003) Among the patients whose base-line serum creatinine concentration was > or = 15 mg per deciliter, creatinine clearance declined at a rate of 23 +/- 25 percent per year in the captopril group and at a rate of 37 +/- 25 percent per year in the placebo group (P = 001) Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death, dialysis, and transplantation that was independent of the small disparity in blood pressure between the groups Conclusions Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone