Dialysis & Transplantation最新文献

I had never felt more alive and inspired as I did the beautiful morning of January 1, 2011 when the Donate Life float made a right-hand turn onto Colorado Boulevard in Pasadena, Calif., for the 2011 Rose Parade. As I waived to the 51.9 million Americans watching on TV, millions of international viewers in 220 territories around the world, and the more than 700,000 people lining the streets, I was loving life and was so grateful to have the opportunity to show the country that organ donation is vital, that transplantation works, and the resilience and beauty of life. I was encouraging organ and tissue donation! I felt free, invincible and didn't have a care in the world.

I haven't had many moments in life like this—where I didn't have a care in the world. I feel as if I have an old soul and definitely had to grow up faster than most. My earliest memory as a little girl is from the age of five, when I had my first grand mal seizure. At ten years old, I had sky-high blood pressure of 160/140 and was diagnosed with one of the most common lifethreatening genetic diseases, polycystic kidney disease (PKD). I missed the first half of my eighth grade year because of scoliosis surgery: two Harrington rods were placed on either side of my spine. I battled cyst bleeds and onand-off hospital stays throughout high school. Two months into college, I had the worst cyst bleeding ever, which put me in the hospital for 11 months. During this time, the difficult decision was made to remove both of my kidneys (at 19 years old), and I was put on daily dialysis. In addition to all of this, I had a six-month bout of pancreatitis, more than 70 blood transfusions, 40 inches of scars, and emergency stomach surgery for a bleeding vessel and four bleeding ulcers. There was a point where my family was called down to Johns Hopkins because the doctors did not think I would make it through the next emergency surgery.

If only we knew how beautiful and rewarding my life would be. I pulled through that emergency surgery and my body held on for the next few months until I received just what I needed to survive, the gift of life from a dear family friend, Sally Robertson.

All of my health challenges and my transplant taught me that our bodies are stronger than we sometimes give them credit for, that when one embraces the journey one can surpass the boundaries of mind, body, and spirit, and that transplantation does not limit us; instead, it lets us live the most rewarding life possible.

Transplantation has a life-changing, domino effect on so many people, aside from the recipient. I love my transplanted kidney because it has given me life and the opportunity to help others improve their lives. In 2008, my award-winning biography, titled “My Favorite American,” was published. It's opened doors and enabled me to help educate the world about PKD and organ transplantation.

After my transplant, I developed a passion to raise awareness of PKD and organ dona

Citation: Mehrotra R, Chiu Y-W, Kalanatar-Zadeh K, et al. Similar out-comes with hemodialysis and peritoneal dialysis patients with end-stage renal disease. Arch Intern Med. 2010;171: 110-118.

Analysis: A scarcity of suitable donor organs for kidney transplantation necessitates that the majority of patients with end-stage renal disease (ESRD) must undergo some form of dialysis instead of or prior to transplantation. The two most common modalities of dialysis employed are in-center hemodi-alysis (HD) and home peritoneal dialy-sis (PD). Although peritoneal dialysis is associated with significantly lower costs, and despite the financial incen-tives from CMS, only 7% of dialysis patients use this modality. A number of reasons for this lack of acceptance have been postulated including the per-ception that peritoneal dialysis leads to poorer patient outcomes.

The perception that PD when com-pared with HD might lead to lower overall survival for ESRD patients requiring renal replacement therapy had emerged from epidemiologic observa-tions in the 1980 s and 1990 made from the U.S. Renal Data Systems (USRDS) database. The survival advantage for HD versus PD appeared to be greater for patients with certain clinical char-acteristics including for the elderly, the obese, for those with cardiovascular disease, and for those with diabetes. In 2002, Collins and colleagues report-ed that survival outcomes in elderly patients treated with peritoneal dialysis were significantly lower than in those treated with HD, even after adjustment.1 Stack and coworkers demonstrated in the USRDS cohort of patients initiated on dialysis in 1995-1997 that survival for those with patients with high BMI was better with hemodialysis than with PD.2 And more recently, Johnson and colleagues showed, using data from patients in Australia and New Zealand, an increased occurrence of cardiovas-cular events after one year of treat-ment with PD compared with HD.3 The CHOICE study demonstrated a significantly higher risk of death for patients undergoing PD versus HD only the second year of follow-up, even after adjustments. Furthermore, the risk of death was nearly twice as high in perito-neal dialysis patients with cardiovascu-lar disease versus the same population of patients receiving hemodialysis.4

Against these and other observa-tions are recent findings that suggest that in the current era that patient sur-vival with PD and HD are similar.5 The current studies attempt to overcome the limitations described previously with the earlier studies.6, 7, 8 These studies use methods that are increasingly employed in population-based studies of com-parative effectiveness. This study by Mehrotra and colleagues uses these advanced methods.

Validity and threats to validity: These authors used USRDS data to examine survival trends for new dialy-sis

Granulomatous interstitial nephritis (GIN) is an uncommon disorder, previously documented in the literature in asso-ciation with sarcoidosis, multiple medications, and infection. The coexistence of GIN and Crohn's disease has rarely been reported, and its true incidence is unknown. We describe a young female with Crohn's disease who was found to have an elevated serum creatinine with a normal urinalysis and autoimmune work-up. Kidney biopsy revealed granulomatous interstitial nephritis. She was treated with corticosteroids, cyclophosphamide, and mycophenolate mofetil. Her kidney function remains stable 2 years after diagnosis. This case report highlights the diagnosis and explores a novel treatment regimen.

For patients with end-stage renal disease who are not (yet) eligible for renal transplantation, treatment with dialy-sis is mandatory for survival. Home dialysis modalities (home hemodialysis or peritoneal dialysis) offer patients more flexibility compared with in-center treatment and have been advocated as the first choice in clinically stable patients. However, despite encouraging developments in dialysis systems that make the procedure easier, in many countries the proportion of patients using home dialysis, especially peritoneal dialysis, is decreasing. In Europe this decrease is most pronounced in the Netherlands and the United Kingdom. This evolution cannot be motivated by an inferiority of home dialysis modalities compared with in-center treatment, as all these modalities have been shown to generate similar results. Other, often non-medical, factors (such as reimbursement, social and logistic issues, and the experience of physicians and nurses with home dialysis) seem to be responsible for this development.

Aliskiren, amlodipine, and hydrochlorothiazide tablets (Amturnide), a triple-combi-nation antihypertensive, has been approved by the U.S. Food and Drug Administration (FDA) for patients who have failed treatment with any of the following types of drugs: direct-renin inhibitors, dihydropyridine cal-cium channel antagonists, and thiazide diuretics.1 It is available in the follow-ing mg dosage combinations of aliski-ren, amlodipine, and hydrochlorothia-zide, 150/5/12.5, 300/5/12.5, 300/5/25, 300/10/12.5, and 300/10/25.

Clonidine extended-release tab-lets and extended-release oral suspen-sion (Nexiclon XR) have been FDA-approved for treating hypertension.2 The tablets are available in 0.17- and 0.26-mg dosage strengths, and the extended-release oral suspension is available as 0.09 mg/mL clonidine base. The recommended initial start-ing dose is 0.17 mg once daily at bedtime, with a lower dose in the elderly.3, 4 Further increases of 0.09 mg may be made at weekly intervals if needed until the desired blood pres-sure-lowering response is achieved. For patients with renal impairment, slow up-titration is recommended to prevent dose-related adverse events. For patients with end-stage renal dis-ease (ESRD) on maintenance dialysis, the starting dose should be 0.09 mg daily with slow up-titration. Equivalent doses of clonidine XR and clonidine IR (Catapres and generics) can be seen in Table I.5

Fidaxomicin, an oral macrolide, is cur-rently being evaluated by the FDA as a treatment for Clostridium dif-ficile infection (CDI), also known as Clostridium difficile-associated dis-ease (CDAD).6 In January, the FDA accepted the New Drug Application (NDA) and set a Prescription Drug User Fee Act (PDUFA) goal date of May 30, 2011. The drug was also sub-mitted for review in Europe in July 2010. Oral tablets and a suspen-sion are being developed for elderly patients and intensive care unit patients who cannot swallow tablets. Clinical cure, lower recurrence rate, and global cure rate were obtained in clinical trials.

Linagliptin, an investigational oral dipeptidyl peptidase 4 (DPP-4) inhibi-tor, does not appear to be primarily excreted by the kidneys. Compared with the DPP-4 inhibitors that are already FDA-approved (sitagliptin and saxa-gliptin), renal impairment did not reduce the renal elimination of linagliptin. This agent is currently in Phase 3 clinical trials as monotherapy and combination therapy to manage type 2 diabetes mel-litus.7, 8

A thrice-weekly insulin, known as ultra-long-acting insulin degludec, is in Phase 3 clinical trials and has been compared in clinical trials with insulin glargine, with similar HbA1c-lowering effects.9 Patients included those who were previously treated with oral anti-diabetic agents (OADs) or basal insulin or OADs plus basal insulin. In clinical trials, insulin degludec was g

The aging dialysis population, with its decreasing functional status, the high mortality of end-stage renal disease (ESRD), and the rise of palliative medicine as a specialty have all served to promote the importance of end-of-life care for ESRD patients. Even though nephrologists have an increased understanding of the issues involved in ESRD end-of-life care, most individuals working in dialysis know of a case in which it felt as if “the dead were being dia-lyzed.” An increased effort to focus on palliative care issues in ESRD, especially advance care planning, may serve to reduce the frequency of such cases.

As this issue of D&T goes to press, the Centers for Medicare and Medicaid Services (CMS) has just declined to issue a change at this time to its payment policies for erythropoiesis-stimulating agents (ESAs) used to manage anemia in renal patients, citing insufficient data to determine risk of the drugs'usage, although it did find “emerging evidence for harm.” Spurred by several large, rigorous trials published over the past few years that link high hemoglobin levels to an increased risk of cardiovascular events and even mortality, CMS initially questioned whether the agency should subsidize a treatment with such a prominent downside and, if so, for which patients—everyone with renal disease? Dialysis and pre-dialysis patients? Transplant candidates and organ recipients? Currently, CMS coverage policies vary by region, with no national payment policy.The agency'sMarch 16th decision, ifmade final,will keep coverage decisions in the hands of regional contractors. A final decision is expected this June.

Two groups in particular are viewing the deliberations with apprehension. In one arena are the companies that make ESAs, most notably Johnson & Johnson, which makes epoetin alfa (Procrit), and Amgen, which also makes epoetin alfa (Epogen), and darbepoetin alfa (Aranesp). They maintain that ESAs improve patient outcomes and decrease the need for transfu-sions, an important issue for transplant candidates, as this can improve their eligibility for an organ by decreasing antibody production that results from exposure to tissue antigens on transferred cells.1 In 2009, ESAs used in the dialysis setting generated $2.8 billion for Amgen alone, with another $365 million coming from the pre-dialysis sector.And, as one industry observer points out, the pre-dialysis market is growing, while the end-stage renal disease (ESRD) market, which comprises most dialysis patients, is expected to remain flat. So restrictions on the use of ESAs in pre-dialysis settings could potentially have amuch greater impact than itmight at first appear.2

Theotherworriedgroupistherenalpatientsthemselves. ManyofthemviewESAs as essential to a decent quality of life, on or off dialysis, and fear that CMS's decision may interfere with their care. “To say, ‘We are not going to be in favor of any kind of therapy that brings hemoglobin up above a certain level’ is basically inserting a subjective decision into the conversation between the doctor and the patient on the best care,” says Paul Conway, vice president of theAmericanAssociationofKidney Patients(AAKP).Essentially,Conwaytells “The D&T Report,”CMSmay be trying to impose a standard that may not be in the patient's best interest or of the doctor's recommendation.

The use of ESAs has long been controversial. Along with their adverse effects, they are notoriously pricey, and the aggressive promotion of their use by the industry has raised some eyebrows. The National K

Cardiovascular disease is the leading cause of death among patients with chronic kidney disease (CKD) and the dialysis population. Approximately 26 million people in the United States are suffering from CKD, with disproportionately higher numbers among patients who have preexisting cardiovascular disease. Vascular abnormalities from hypertension, hyperlipidemia, hyperglycemia, and calcium and phosphate calcifications associated with renal disease rank high among risk factors for early and aggressive causes of accelerated atherosclerosis. It is well known that the risk of cardiovascular events is much higher in dialysis patients compared with the general population; Foly et al. documented that 25- to 35-year-old patients on dialysis are at the same risk of mortality from cardiovascular disease as someone at age 85 from the general population (Figure 1).1 Blood cholesterol reduction using HMG-CoA reductase inhibitors (statins) in people at risk of cardiovascular disease has been recommended. In regard to hyperlipidemia and the incidence of cardiovascular disease, most retrospective observations on patients with end-stage renal disease and on dialysis have shown no positive correlation between high cholesterol levels and increased rates of cardiovascular events. In fact, the opposite tendencies have been reported in dialysis patients. A large study with 1,167 HD patients showed that mortality actually increased with cholesterol levels < 140 mg/dL, compared with higher levels, up to 220 mg/dL.2 However, this study was not adjusted for disease severity or inflammatory stage associated with late-stage CKD.

In dialysis patients, most risk factors related to cardiovascular disease have a disconnect between observational studies and interventional studies. Although the effects of lowering low-density lipoprotein cholesterol (LDL-C) on the progression of renal disease or cardiovascular events are not fully understood, it is important to note that only one-fourth of dialysis patients die from acute myocardial infarction (MI). There are now three randomized, placebocontrolled studies of therapy with three different HMG-CoA reductase inhibitors (statins), all with negative results in the dialysis population (Table I).

The Deutsche Diabetes & Dialysis study (4D) was the first randomized study aimed at investigating the benefits of using a HMG-CoA reductase inhibitor (atorv-astatin) in patients on hemodialysis with type 2 diabetes mellitus.3 4D was a mul-ticenter, randomized, double-blind, pro-spective study of 1,255 (18-80 years old) type 2 diabetes mellitus patients receiv-ing maintenance hemodialysis for less than 2 years. The study was supported by the pharmaceutical industry, and patients were enrolled in 178 centers in Germany. Patients were excluded if the LDL-C was <80 or >190 mg/dL, serum triglycerides were >1,000 mg/dL, liver function tests were abnormal, or they had had a previous

Advances in the care of the child with moderate-to-severe chron-ic kidney disease (CKD stages 4/5) has resulted in a substantial improvement in patient survival over the past three decades.1, 2 Pediatric nephrolo-gists have recognized that superior medical outcomes, along with the necessary atten-tion directed to growth, development, and health-related quality of life (HRQOL) can only be achieved with a multidisci-plinary team of professionals including specialty nurses, surgeons, and dietitians, along with psychosocial support provided by social workers, psychologists, child life/play therapists, and, in some European centers, youth workers.3 Therefore, the care of children and adolescents with sig-nificantly impaired kidney function should be concentrated at clinical sites where the expertise and support counterbalance the travel time and distance factors that may at times be burdensome to affected families.4

A product of the successful management of CKD throughout childhood is the ultimate need for transition to adult-centered care, a topic of growing interest and action around the globe.5, 6 With the growth of adolescent medicine, the term “transition” was coined and defined in 1993 as the purposeful, planned process that addresses the medical, psychosocial, and educational/ vocational needs of adolescents with chron-ic physical and medical conditions as they move from child-centered to adult-oriented healthcare systems.7 Noteworthy is the fact that transition preparation is a process, and transfer to an adult unit should ideally only take place at the successful conclusion of the transition process. As part of that pro-cess, young people need to be increasingly involved in the management of their own care so that they develop the necessary self-management skills to cope with the changes that are sure to occur following their trans-fer to an adult center.

Of course, all of this often takes place on a backdrop of anxiety on the part of the patient, family, and both pediatric and adult-centered staff.8, 9 Pediatricians are regularly accused of spoiling their patients in the pediatric unit and being hesitant to let them go, and adult physicians are accused of giv-ing little attention to the transferred young adults and their unique needs. Consensus statements directed toward kidney trans-plant centers—settings with the greatest anxiety about “getting it right”—have been developed by expert panels to help guide transitions.10, 11

The general consensus between pediatric and adult clinicians is that transfer to an adult-centered program should take place when the adolescent/young adult is “mature enough,” in contrast to a specific age. This means that the decision must be individualized and should take into con-sideration pediatric-centric aspects of care (e.g., growth hormone therapy for g

In this issue of D&T, it is our privilege to introduce a new regular department that will feature content written by and specifically for nephrology fellows.

“From the Fellows” (p. 172) has been specifically designed to give fellows the opportunity to achieve scholarly research activity.1 The primary goal of this department is to continue to advance education regarding clinical concepts relating to the diagnosis, complications, and treatment of interesting and unique cases involving renal-replacement therapy or renal transplantation. We also aim to achieve scholarly activity, stimulate fellows to develop careers in academic medicine, and enhance the awareness of new clinical discovery and its application.

This venue for fellows in training to publish is unique. It offers an opportunity to facilitate collaboration between trainees, experienced clinicians, and physician scientists. D&T's wide circulation of 25,000 nephrologists, nephrology nurses, dialysis technicians, and allied health professionals will allow our fellows in training to showcase their work and contribute to the overall fund of medical knowledge and patient care.

By publishing their interesting or problematic case reports, brief reviews, and editorials and commentaries, we aim to provide a structured platform from which nephrology fellows can articulate and integrate the knowledge acquired from their day-to-day clinical encounters.

We welcomeBrahmVasudev,MDas section editor for this exciting new department. Dr.Vasudev is currently Assistant Professor of Medicine in the Division of Nephrology at the Medical College ofWisconsin in Milwaukee. He is also director of the institution's Nephrology Fellowship Program. We encourage you to work with your fellows to contribute to this new section, and look forward to their submissions.