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  NATURE REVIEWS  |   NEPHROLOGY    ADVANCE ONLINE PUBLICATION |   1 State University of New York Downstate Medical Center, Renal Division, 450 Clarkson Avenue, Box 52, Brooklyn, NY 11203, USA ( S. J. Saggi ). Division of Nephrology, University of Alabama at Birmingham, 1530 Third Avenue S, Birmingham, AL 35294, USA ( M. Allon ). University of Pittsburgh, 128 Hastings Street, Pittsburgh, PA 15206, USA ( J. Bernardini ). Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, 1124 W Carson Street, Torrance, CA 90502, USA ( K. Kalantar-Zadeh, R. Mehrotra ). American Society of Nephrology, 1510 H Street, NW, Suite 800, Washington, DC 20005, USA ( R. Shaffer ).Correspondence to: R. Mehrotra rmehrotra@ labiomed.org  Considerations in the optimal preparation of patients for dialysis Subodh J. Saggi, Michael Allon, Judith Bernardini, Kamyar Kalantar-Zadeh, Rachel Shaffer and Rajnish Mehrotra on behalf of the Dialysis Advisory Group of the American Society of Nephrology  Abstract  | Every year, more than 110,000 Americans are newly diagnosed with end-stage renal disease and in the overwhelming majority, maintenance dialysis therapy is initiated. However, most patients, having received no predialysis nephrology care or dietary counseling, are inadequately prepared for starting treatment; furthermore, the majority of patients do not have a functioning permanent dialysis access. Annualized mortality in the USA in the first 3 months after starting dialysis treatment is approximately 45%; this high rate is possibly in part due to inadequate preparation for renal replacement therapy. Data from the Dialysis Outcomes and Practice Patterns study suggest that similar challenges exist in many parts of the world. Implementation of strategies that mitigate the risk of adverse consequences when starting dialysis are urgently needed. In this Review we present a step-by-step approach to tackling inadequate patient preparation, which includes identifying individuals with chronic kidney disease (CKD) who are most likely to need dialysis in the future, referring patients for education, timely placement of dialysis access and timely initiation of dialysis therapy. Treatment with dialysis might not be appropriate for some patients with progressive CKD; these individuals can be optimally managed with nondialytic, maximum conservative management. Saggi, S. J. et al.   Nat. Rev. Nephrol . advance online publication 10 April 2012; doi:10.1038/nrneph.2012.66 Introduction In 2008, more than 110,000 Americans were started on maintenance dialysis, a life-saving therapy for patients with end-stage renal disease (ESRD). 1  Ideally, when patients begin renal replacement therapy (RRT), they should meet the following conditions: firstly, they should not require hospitalization for the management of untreated acute or chronic complications of uremia; secondly, they should have a thorough understanding of the different treatment options; and thirdly, they should have a functioning, permanent access for the dialysis therapy of their choice. 2 There is concern that a sizable proportion of patients in the USA are not adequately prepared for initiat-ing dialysis therapy. In 2008, 44% of patients received no predialysis nephrology care and only 25% had received ongoing care by a nephrologist for more than 12 months prior to initiating dialysis. 1  Despite the critical importance of lifestyle management (and the fact that reimburse ment is available for such counseling in the USA), fewer than 10% of patients receive dietary coun-seling prior to starting dialysis. 1  Furthermore, substan-tial numbers of patients newly diagnosed with ESRD are not offered alternatives to in-center hemodialysis (such as home dialysis or pre-emptive transplantation), even in the absence of medical contraindications. 3,4  More than 80% of patients in the USA initiate hemodialysis therapy with a central venous catheter (CVC); this type of access is associated with significantly higher rates of infectious complications, as well as more long-term non-infectious complications compared with a permanent  vascular access. 1,5–7  Inadequate preparation for dialysis in the USA can only partially be accounted for by delayed referral to nephrology specialists; however, as a consider-able number of patients who have received more than 1 year of specialist care prior to initiating dialysis are also inadequately prepared for this treatment. 1  In 2006, the annualized mortality in the first 3 months of starting dialysis for patients in the USA was approximately 45%, which was in part due to inadequate preparation of the patient for RRT. 8 The available data on dialysis preparation practices outside the USA are limited. Findings from studies per-formed in the 1980s and 1990s indicate a high rate of delayed referrals to a nephrologist in Europe, and con-temporary data from Canada also demonstrate a high incidence of suboptimal dialysis initiation. 9–12  Analyses from the Dialysis Outcomes and Practice Patterns Study (DOPPS) further highlight the international scope of this challenge. 13  One in five patients starting hemodialysis Competing interests M. Allon declares an association with the following company: CorMedix. J. Bernardini declares an association with the following company: Baxter. K. Kalantar-Zadeh declares an association with the following company: DaVita. R. Shaffer declares an association with the following organization: the American Society of Nephrology. R. Mehrotra declares an association with the following companies: Amgen, Baxter, DaVita, Genzyme, Mitsubishi Tanabe Pharma, NovaShunt AG, Reata Pharmaceuticals, Shire and Vifor Pharma. S. J. Saggi declares no competing interests. See the article online for full details of the relationships. REVIEWS © 2012 Macmillan Publishers Limited. All rights reserved  2   |  ADVANCE ONLINE PUBLICATION   www.nature.com/nrneph in DOPPS-participating countries (USA, Canada, UK, Belgium, Sweden, Germany, France, Spain, Italy, Japan, Australia and New Zealand) first see a nephrologist within 1 month of requiring dialysis. 13  Additionally, over one-half of patients in the UK, Sweden, Belgium and Canada start hemodialysis treatment with a CVC. 5  As such, a high prevalence of suboptimal initiation of dialysis treatment is not unique to the USA.In this Review we discuss the challenges associated with preparing patients for dialysis therapy and present a practical step-by-step approach to help bridge the gap in care and reduce the high mortality seen in the first few months of starting dialysis (Figure 1). In concert with continued efforts to slow disease progression and delay dialysis, the measures discussed in this Review should be implemented at appropriate times during the course of chronic kidney disease (CKD). The outlined approach is targeted primarily at practicing nephrolo-gists although individual components might be relevant to other specialists providing care to patients with CKD (such as internists, family practitioners, endocrinologists and geriatricians). Discussion of other areas of care in patients with CKD and ESRD (such as the management of high-risk pathology including diabetes mellitus and hypertension, treatment of anemia and provision of vac-cinations, and social support), although of importance, are beyond the scope of the Review. Step one: identify patients for RRT Renal replacement therapy An estimated 13% of adults in the USA have CKD, and approximately 700,000 have stage 4 CKD (glomerular filtration rate [GFR] 15–29 ml/min/1.73 m 2 ). 14  Long-term follow-up of population-based cohorts suggests that many individuals with CKD are unlikely to exhibit sufficient progressive decline in renal function to require dialysis. Over a 5-year follow-up of members of the Kaiser Permanente Northwest Division (a large, non-profit, group-model health maintenance organization, which provided comprehensive, prepaid medical cover-age to approximately one-fifth of the population of a US city), only 17% of patients with stage 4 CKD required dialysis but, notably, 45% of patients had died before requiring dialysis. 15  In contrast to the findings from this unselected cohort, in a study involving 4,231 Canadian Key points   ■ A large gap exists in care in transitioning patients with chronic kidney disease (CKD) to renal replacement therapy; a step-by-step approach is proposed to bridge this gap in care  ■ Demographic and clinical criteria can help identify those individuals with CKD who would benefit from early preparation for renal replacement therapy   ■ Iterative multidisciplinary patient education is the first step in preparing patients for dialysis and should offer decision support for selection of dialysis modality or maximum conservative care  ■ Dialysis access should be placed sufficiently early to preclude the need for central venous catheters  ■ The decision of when to start dialysis should be individualized based on uremic symptoms and/or the appearance of complications but should not be delayed until patient becomes too sick patients with stage 4 CKD who had been selected because they had been referred to nephrologists, only 7% of study participants died before needing dialysis, but 24% of patients were found to require dialysis support. 16  These data suggest that targeting all patients who have CKD with an estimated GFR (eGFR) below a certain thresh-old (<30 ml/min/1.73 m 2 ) for RRT preparation might be inappropriate. Instead, focusing on individuals who have at least one additional characteristic associated with a high probability of reaching ESRD, in addition to a low eGFR, would better identify those who would benefit from preparation for future dialysis (Box 1).With advancing age, the likelihood of dying prior to initiating dialysis far exceeds the likelihood of starting dialysis therapy. In a US population of veterans with CKD and a mean eGFR of 18 ml/min/1.73 m 2  at cohort entry, 67% of those aged 18–44 years initiated dialysis within 2 years and 22% died during this time. By con-trast, in the group of patients who were 85 years of age or older only 17% had initiated dialysis within 2 years, but 41% of this age group died during this time. 17  If all study participants had begun preparation for dialysis at cohort entry, the ratio of unnecessary to necessary dialy-sis access surgery would have been 0.5:1 for the group of patients aged 18–44 years, but 5:1 for those aged 85 years and older. Similar results have been demonstrated in several other cohort studies. 18–20  Patient age should, therefore, be an important consideration when decid-ing whether to begin preparation for RRT. Indeed, many elderly patients have stable reductions in eGFR and, in our opinion, only those individuals with progressive loss of renal function should be referred for planning RRT.Increasing albuminuria within each eGFR strata for CKD stages 1–5 is associated with a substantial increase Step one Identify patients with CKD highly likely to need dialysisor in selected cases nondialytic MCM Step two Begin preparation sufficiently early to mitigate need for CVCs;avoid cannulating upper extremity veins above the wrist Step three Provide CKD education and offer decision supportfor patients in selecting dialysis modality Step four Place hemodialysis vascular access at least 4–6 monthsprior to anticipated need for dialysis; perform early placement of embedded peritoneal dialysis catheters Step five Timely initiation of dialysis dictated primarily by patientsymptoms and/or early signs of uremic complications Figure 1 | A proposed step-by-step approach to help prepare patients for dialysis. Abbreviations: CKD, chronic kidney disease; CVCs, central venous catheters; MCM, maximum conservative management. REVIEWS © 2012 Macmillan Publishers Limited. All rights reserved  NATURE REVIEWS  |   NEPHROLOGY    ADVANCE ONLINE PUBLICATION |   3 in the risk of requirement for future dialysis. 21,22  Routine measurement of the albumin–creatinine ratio on spot urine samples could help physicians identify individuals with reduced eGFR who are more likely to have progres-sive CKD and, therefore, require referral to prepare for future RRT. Analyses of large patient cohorts also consis-tently identify high blood pressure, high levels of serum phosphorus, and/or low hemoglobin levels, as additional predictors of future dialysis requirement. 16,19 No single characteristic can reliably identify which individuals with advanced CKD are likely to progress to ESRD. It is important, therefore, that at every clini-cal encounter physicians consider each patient with advanced CKD with respect to the discussed characteris-tics using demographic, clinical and laboratory informa-tion (Box 1), and ensure that preparation for RRT begins sufficiently early for individuals likely to reach ESRD. Moreover, all patients with advanced CKD could benefit from patient education tailored to each individual’s probability of dialysis need in the future. Nondialytic maximum conservative management Although dialysis prolongs the lives of many individu-als with ESRD, the burden of RRT might not justify the potential benefits of treatment in certain patients, such as the elderly. 23  However, as illustrated by the North Thames Dialysis Study, judgment on the appropriateness for RRT should not depend solely upon chronological age but should instead be based on a composite assessment of the health and functional status of the individual. 24  Results from studies suggest that there are subgroups of patients who have a low likelihood of benefiting from dialysis therapies. 25–27  For example, initiating dialysis does not reverse the progressive decline in functional status of nursing home residents; rather, the decline in functional status seemingly accelerates after dialysis initation. 25  For certain individuals with advanced CKD, nondialytic, maximum conservative management (MCM) might, therefore, be superior to initiating dialysis; 26  this sugges-tion highlights the importance of considering the appro-priateness of dialysis for individuals with CKD early in the disease course. Assessment of disease management requires shared decision-making between patients, their family members, and the treating physicians. 27 Most of the data on the principles of management and outcomes of patients with advanced CKD who elect to have MCM are derived from the UK. 26,28,29  In most of the published studies to date, the life expectancy of patients with advanced CKD who choose MCM is shorter than that of patients with matching characteristics who choose RRT; the median life expectancy of patients with stage 5 CKD who forgo RRT has been reported to range from 14 months to 23 months. 20,26,28,29  However, the primary goal of care in patients who opt for MCM should be focused on symptom management to enhance quality of life and ensure patient comfort (Box 2). 26,30 In selected individuals, maximizing renoprotec-tive therapies can be an important component of MCM. Traditionally, renin–angiotensin–aldosterone system (RAAS) blockade has been used to slow CKD progression; however this intervention might be limited by hyperkalemia in individuals with advanced CKD. Furthermore, findings from a UK study demonstrated that discontinuing angiotensin-converting-enzyme (ACE) inhibitors and/or angiotensin-receptor blockers (ARBs) in patients with advanced CKD was associated with a significant increase in eGFR. 31  For these reasons, continued use of ACE inhibitors or ARBs should be peri-odically re-evaluated in individuals who choose MCM and, in fact, discontinuing drugs from these classes might facilitate patient management.Additional dietary interventions can be considered in certain patients who elect MCM. These interven-tions include: low-protein diets (0.6–0.8 g/kg daily); ketoanalog- supplemented very-low-protein diets; or nutritional supplements with low amounts of protein, phosphorus, and potassium. 32–34  A vegetarian diet might serve as another adjunct as it provides reduced amounts of protein and less digestible phosphorus, for example phytate-based phosphorus. 35  However, dietary restric-tions can be onerous and should be considered on an individual case-by-case basis. Correction of metabolic acidosis can also slow the decline in renal function. 36  Other therapies are in develop ment that may slow the decline of renal function, for example drugs that adsorb uremic toxins (such as indoxyl sulfate and oral anti-oxidants) and anti-inflammatory modulators (such as bardoxolone methyl). 37–39  Some patients who choose MCM might benefit from referral for hospice care, which can be provided either in the patient’s home or at a hospice facility. Step two: begin preparation for RRT Preparation for RRT should begin early enough in the course of CKD to allow time for patients to consider dif-ferent treatment options and to establish a permanent functioning access for the dialysis modality of choice. If pre-emptive living donor kidney transplantation is appropriate, the patient should undergo the proce-dure before they need temporary dialysis to minimize Box 1  | Characteristics associated with progression to ESRD   ■ Young age ■ Decline in renal function over time ■ Presence of albuminuria  ■ Presence of underlying primary renal disease (such as diabetic nephropathy, renovascular disease, or primary glomerular diseases)  ■ High blood pressure  ■ Development of CKD complications (such as increased serum phosphorus and/or decline in hemoglobin levels) Abbreviations: CKD, chronic kidney disease; ESRD, end-stage renal disease. Box 2  | Key elements of nondialytic maximum conservative management   ■ Interventions to slow rate of decline of native renal function  ■ Dietary counseling to prevent hyperkalemia  ■ Diuretics for management of hypervolemia  ■ Correct anemia to manage symptomatic fatigue and prevent blood transfusions  ■ Phosphate binders to relieve symptoms associated with hyperphosphatemia  ■ Referral for hospice care, if appropriate REVIEWS © 2012 Macmillan Publishers Limited. All rights reserved  4   |  ADVANCE ONLINE PUBLICATION   www.nature.com/nrneph morbidity resulting from dialysis access. In addition, allowing adequate time for patients to consider their options enables individuals who would be appropriate for MCM to consider this option as well. However, pre-emptive transplantation is uncommon, and limited evi-dence suggests that when given a choice most patients choose to have dialysis rather than MCM. 1,26  As such, the overwhelming majority of individuals who reach ESRD are likely to require maintenance dialysis and appropri-ate preparation should be incorporated early in their manage ment plan.In determining how early to begin preparation of patients for dialysis, it is useful to consider that in our experience it can take 1–3 months of iterative CKD edu-cation for patients to accept potential need for RRT, and also to decide which therapy best meets their expecta-tions and fits their lifestyle. Sufficient time should also be allocated for placement and maturation of dialysis access. The mean time for arteriovenous fistula maturation for patients in the USA is approximately 3 months, although shorter times (of approximately 1 month) have been reported in Europe and Japan. 40  Moreover, a substantial proportion of new fistulae fail to achieve suitability for dialysis treatment; therefore, the first vascular access should be placed sufficiently early to allow enough time to either revise the initial access, or for a second access to be placed and mature prior to initiation of dialysis. 31,32  In our opinion, therefore, preparation for RRT should begin about 9–12 months prior to the anticipated dialysis need. Of note, CKD progression rates can change over time making it challenging to precisely anticipate the need for dialysis. 41  In our opinion, it follows that educa-tion about CKD, dialysis therapies, dialysis access, and MCM should be initiated in individuals with an eGFR 20–30 ml/min/1.73 m 2 . Furthermore, in our opinion a vascular access should be placed in patients with an eGFR 15–20 ml/min/1.73 m 2 , in whom progression to ESRD seems likely.As most patients are likely to require hemodialysis at some stage of their disease, preservation of veins is a critical aspect of advanced planning. Most patients undergoing hemodialysis will require several arterio- venous fistulae or grafts in both upper extremities. To prevent the loss of available veins for dialysis access, can-nulation of veins above the wrist in either upper extrem-ity should be avoided. 42  Every effort should be made to limit phlebotomy and intravenous catheters to veins in the hand. Peripherally inserted central catheters (com-monly known as PICC lines) are particularly problematic as they can cause thrombosis of the upper arm veins in up to 38% of patients precluding future vascular access in the entire ipsilateral upper extremity; 43  avoiding these catheters in patients with CKD from early in the disease course is, therefore, of paramount importance. Step three: CKD education Although a paucity of clinical trials exists, a preponder-ance of other evidence demonstrates tangible benefits of CKD education. 44–50  Early patient education in those with CKD is shown to be highly effective when focused on health promotion, shared decision-making, and dis-cussion of treatment options. 45  In the only randomized, controlled trial on patient education that we are aware of, a one-on-one educational session followed by phone calls every 3 weeks significantly extended the time to requiring dialysis. 47   Post hoc  analyses from this clinical trial, as well as findings from other observational studies, demonstrate a variety of additional benefits from patient education, including the following: reduced patient anxiety; delay in dialysis need; reduced number of hos-pitalizations; reduced numbers of emergency room and physician visits; increased likelihood that the patient will remain employed in work and be more adherent to therapy; and reduced mortality. 46,48,49  Furthermore, results from several studies have demonstrated a substan-tially reduced need for CVCs following patient educa-tion. 49,50  Consequently, it is important to maximize these benefits by engaging patients in CKD education prior to planning dialysis access placement (Table 1).Patient education involves messengers, messages, receivers and a process. Before patient education can begin, the physician must initiate the discussion of what is often called breaking the bad news. 40,41  Patients do not want insensitive truth-telling but prefer for the truth to be told with support to assist them in decision-making. 51  It is estimated that it takes an average of five encounters before individuals actually understand the message; therefore, patient education on CKD should be iterative. 52  The initial message should be delivered in a private room that is free of interruptions, and preferably when the patient has a supportive friend or relative with them. 52–54  Communication of the bad news should be followed by formal CKD education, for which reimburse ment is now available in the USA for Medicare beneficiaries. 55 The curriculum for predialysis education should include psychosocial aspects and coping skills. 56  Components of successful CKD education programs have also included individualized and ongoing education throughout the course of the disease, tours of dialysis facilities, meeting patients who are undergoing treat-ment with different dialysis modalities, use of videos and written materials, and behavior-changing protocols with small-group problem-solving activities. 46,57,58  These and other strategies can be incorporated into any CKD education program (Table 1). The educator needs to possess skills in patient communication and to under-stand the nature of the patient’s barriers to receiving the information.Presenting treatment options to the patient is a major undertaking for the educator, and offering decision support is an important goal of successful CKD educa-tion. There is a large variability in the uptake of home dialysis options (peritoneal dialysis or hemodialysis) between centers, regions, and different countries. 1  Data from the USA indicate that the low uptake of peritoneal dialysis in the country does not reflect patient choice but is instead more often a reflection of the choice not being offered to patients by health-care providers. 3,4,59  Findings from numerous surveys show that most patients have no medical or psychosocial contraindications to in-center REVIEWS © 2012 Macmillan Publishers Limited. All rights reserved
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