Abstract
The population of individuals with kidney failure requiring renal replacement therapy in the United States and around the world continues to grow. The optimal timing for the initiation of maintenance dialysis in patients with incident end-stage renal disease is currently unknown. Recently published clinical practice guidelines emphasize the importance of a patient-centered approach to dialysis decision making based primarily on the assessment of signs and symptoms attributable to kidney failure and the ability to medically manage complications of advanced kidney disease. Options for renal replacement therapy for patients with established chronic kidney failure include in-center hemodialysis, home hemodialysis, peritoneal dialysis, and kidney transplantation. Home dialysis modalities, including both peritoneal dialysis and home hemodialysis, have seen resurgent growth in the United States over the past decade, but remain underutilized.
Keywords
dialysis, end-stage renal disease, hemodialysis, initiation of dialysis, kidney failure, peritoneal dialysis, timing of dialysis, vascular access
Outline
Indications for Initiation of Dialysis in Chronic Kidney Disease, 287
Evolution of Clinical Practice Guidelines for Initiation of Dialysis, 287
Past Kidney Disease Outcomes Quality Initiative Recommendations for Timing of Initiation of Dialysis, 287
Initiation Dialysis Early and Late (IDEAL) Trial, 288
Current Kidney Disease Outcomes Quality Initiative Recommendations for Timing of Initiation of Dialysis, 288
Other Clinical Practice Guidelines for Timing of Initiation of Dialysis, 289
Trends in Timing of Initiation of Dialysis, 290
Preparation for Renal Replacement Therapy, 291
Timeliness of Nephrology Referral, 291
Predialysis Chronic Kidney Disease Education, 292
Timing of Dialysis Access Placement, 292
Timing of Referral for Kidney Transplant Evaluation, 292
Dialysis Modality Selection, 292
In-Center Dialysis Modalities, 293
Frequent in-Center Hemodialysis, 293
Home Dialysis Modalities, 293
Transplantation, 295
Conclusions, 295
Acknowledgments
Some data reported in this chapter have been supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. Dr. Rivara is supported in part by funding from the Extramural Grant Program (EGP) by Satellite Healthcare, a not-for-profit renal care provider.
Chronic kidney disease (CKD), defined as a reduction in the level of estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m 2 of body surface area, or by the presence of markers of structural or functional abnormalities of the kidney, affects a significant proportion of the population in the United States and across the globe. Globally it is estimated that the prevalence of CKD of all stages is approximately 13%, with the majority of this burden comprising individuals with CKD stages 3 through 5 (i.e., eGFR <60 mL/min/1.73 m 2 ). In the United States, the overall prevalence of CKD among the adult population is approximately 30 million individuals, and continues to grow annually. Among this group are >670,000 US individuals with kidney failure requiring treatment with renal replacement therapy (RRT), defined as either dialysis or kidney transplantation. Although from 2006 to 2012 the incidence rate for new cases of kidney failure requiring RRT, or end-stage renal disease (ESRD), leveled off for the first time in nearly two decades, the period from 2012 to 2014 again saw a rise in new ESRD cases. In 2014, the number of incident newly reported ESRD cases exceeded 120,000 for the first time. This included 106,097 individuals who initiated dialysis (either hemodialysis or peritoneal dialysis [PD]), and 3102 patients who received a preemptive kidney transplant. This growth in new ESRD cases has translated into a doubling of the prevalent dialysis population in the United States over the past 20 years. A recent report from the Global Burden of Disease project indicates that the growth in the provision of maintenance dialysis seen in the United States has been mirrored by similar growth in many other parts of the world, in particular in Australasia, Asia, and western Europe.
For patients with newly diagnosed kidney failure, the transition to RRT is a time characterized by exceptionally high risk for adverse outcomes. The mortality rate for patients with stage 5 CKD and ESRD approaches 20 per 100 patient-years, and the first 120 days after dialysis initiation represents the period of greatest risk, with an annualized mortality rate approaching 50%. In addition, the ESRD transition period is characterized by increased risks for other adverse patient-important outcomes, including high rates of hospitalization, heart failure exacerbations, and new strokes. Furthermore, ESRD care is extraordinarily costly to the US healthcare system. In 2012 spending for ESRD patients in the United States exceeded $28 billion, representing 5.6% of total Medicare costs, although the ESRD population represents <1% of the total Medicare population. For this plurality of reasons, optimizing the transition to ESRD care represents a critical challenge to the nephrology community, and one that encompasses timely and adequate preparation for RRT, as well as determining the appropriate timing for initiation of dialysis or kidney transplantation. In addition, optimizing the transition to ESRD also includes patient-centered modality selection and consideration of nondialytic conservative management of kidney failure. This chapter will review these important aspects of timing of RRT, selection of dialysis modalities, and transplantation for ESRD.
Indications for Initiation of Dialysis in Chronic Kidney Disease
Nephrologists have long agreed on a number of “absolute” indications for initiation of maintenance dialysis in patients with advanced CKD. These strong indications represent emergent life-threatening complications of kidney failure, and include electrolyte disturbances such as hyperkalemia refractory to medical management accompanied by electrocardiogram changes, severe metabolic acidosis, volume overload refractory to diuretic therapy and leading to respiratory compromise, and certain manifestations of the uremic syndrome including uremic pericarditis, uremic encephalopathy, or severe uremic nausea and vomiting. The vast majority of patients with incident end-stage kidney failure, however, do not initiate RRT due to one of these classic and life-threatending complications. Instead, the decision on the part of the nephrologist to recommend initiation of dialysis to a patient with advanced CKD is usually determined by a complex integration of clinical and laboratory data elements reflecting the fluid, electrolyte, hormonal, and metabolic abnormalities that develop as kidney function deteriorates. These elements include biochemical markers of filtration function such as serum creatinine and blood urea nitrogen concentrations, blood concentrations of other markers of uremia such as low blood hemoglobin, high serum phosphorus and parathyroid hormone concentrations, complications of fluid retention including hypertension and volume overload, and also includes assessment of physical examination signs and symptoms consistent with the uremic syndrome. In addition to the clinical manifestations of uremic stated previously, other frequent manifestations include fatigue, lethargy, anorexia, pruritis, sleep disturbances, bleeding diathesis associated with platelet dysfunction, memory impairment and other neurocognitive dysfunction, headaches, musculoskeletal pain, melanosis, muscle wasting, weight loss and protein-energy wasting (PEW), and sexual dysfunction.
Adding to the complexity regarding optimal timing of initiation of dialysis based on assessment of uremic complications is uncertainty about which signs and symptoms of advanced kidney disease consistently improve with the start of dialysis, and whether such improvement may vary based on patient demographic or clinical characteristics. A number of studies published over the past decade have indicated that patients undergoing maintenance dialysis suffer from a high prevalence and severity of residual physical, psychological, and emotional symptoms, and in many cases the symptom complex shares a high degree of similarity with the classic constituent components of the uremic syndrome. In addition, although it was previously thought the uremic symptom complex did not consistently manifest until late stage 4 or stage 5 CKD, more recent data have suggested that uremic symptoms may present at earlier stages of CKD. The central task of the nephrologist in assessing the optimal timing of initiation of dialysis for a patient with advanced CKD is to balance the risk for exposing the patient to complications of untreated kidney failure against the potential for harm from the dialysis procedure itself, along with the burden of dialysis therapy. Delaying the start of dialysis to too great a degree may lead to frequent hospital admissions or emergency department visits for uncontrolled hypertension, pulmonary edema, or hyperkalemia, or may lead to PEW, weight loss, and malnutrition. Conversely, initiation of dialysis at too early a stage may expose the patient unnecessarily to complications of dialysis therapy. Potential mechanisms of harm from dialysis include hemodynamic fluctuations leading to regional cardiac wall motion abnormalities, potentially arrhythmogenic electrolyte flux, oxidative stress, or risk for infection related to dialysis access. Finally, the significant and potentially adverse effect of daily or thrice-weekly dialysis treatments on patients’ ability to work, travel, socialize, and accomplish other activities of daily living cannot be overstated.
Evolution of Clinical Practice Guidelines for Initiation of Dialysis
Given the inherent limitations of the subjective assessment on the part of clinicians of the presence of components of the uremic syndrome in patients with advanced kidney disease, there has long been an interest on the part of the nephrology community in identifying less subjective and more standardized guidelines for the timing of initiation of maintenance dialysis. This interest and an underlying understanding of the importance of optimizing the transition to ESRD has led to the publication of numerous clinical practice guidelines for the timing of initiation of dialysis in patients with advanced CKD.
Past Kidney Disease Outcomes Quality Initiative Recommendations for Timing of Initiation of Dialysis
In the 1990s, in efforts to identify less subjective markers of uremia, a number of studies were carried out that highlighted the strong correlation between various markers of PEW and progression and outcomes of advanced CKD. These studies showed that not only did dietary protein intake decrease linearly with a decrease in native kidney creatinine clearance, but also that markers of PEW, such as serum albumin, at the time of dialysis initiation strongly predicted subsequent mortality risk. Furthermore, it was demonstrated that dietary protein intake increased significantly over the first 3 to 6 months after initiation of dialysis, presumed secondary to at least partial correction of uremic toxicity. These observations and others led to an early strong interest in objective measures of PEW as a complement to clinical assessment of uremia in timing initiation of maintenance dialysis in advanced CKD. In 1997 the Dialysis Outcomes Quality Initiative (DOQI, now Kidney Disease Outcomes Quality Initiative [KDOQI]), working group on dialysis adequacy released its first set of recommendations synthesizing many such observations about the association of advanced CKD with uremic PEW. In this early clinical practice guideline, the group recommended that patients with advanced CKD be advised to initiate some form of dialysis when the weekly renal Kt/V urea falls <2, unless either edema free body weight is stable or increased, the normalized protein catabolic ratio is ≥0.8 g/kg of body weight per day, or there is an absence of clinical signs or symptoms attributable to remia. This recommendation to assess patients’ native kidney weekly renal urea clearance as the primary criterion used to determine when to initiate dialysis was based on expert opinion, and corresponded to a threshold of eGFR of approximately 10.5 mL/min/1.73 m 2 . Nearly a decade later, in 2006, the KDOQI clinical practice guidelines for hemodialysis adequacy were updated to reflect a growing emphasis and understanding of the importance of focusing on patients’ symptoms and functional status in determination of the optimal timing for dialysis initiation among patients with advanced CKD. The 2006 KDOQI guideline update omitted discussion of calculation of the weekly renal Kt/V urea , reflecting contemporary changes in clinical nephrology that included widespread adoption of serum creatinine–based equations for estimation of glomerular filtration. Instead, the guideline stated that nephrologists should evaluate the benefits, risks, and disadvantages of initiation of RRT when patients reach stage 5 CKD, corresponding to an eGFR threshold of 15 mL/min/1.73 m 2 . Furthermore, the guideline recommended that certain clinical considerations or complications may prompt initiation of therapy before stage 5, including decline in functioning or patient well-being, gastrointestinal dysfunction, or weight loss/malnutrition.
Initiation Dialysis Early and Late (IDEAL) Trial
Although early clinical practice guidelines such as those written and published by KDOQI working group members provided recommendations to practicing nephrologists regarding thresholds of glomerular filtration at which to consider initiation of RRT, such recommendations were based on accumulated clinical experience and expert opinion of the members of the guideline committees rather than on the results of observational or interventional studies. During the first decade of the 21st century, numerous observational studies were conducted to investigate the association between eGFR at dialysis initiation with subsequent risk for adverse outcomes. The results of these studies consistently demonstrated that initiation of RRT at higher levels of GFR calculated using serum creatinine-based estimating equations were associated with higher mortality risk. In contrast, studies employing timed urea or creatinine clearances rather than serum creatinine–based estimating equations to calculate GFR demonstrated little to no association with mortality risk.
Given persistent uncertainty regarding the optimal timing for initiation of RRT in patients with advanced CKD, the results of the Initiation Dialysis Early and Late (IDEAL) trial, published in 2010, were welcomed by the nephrology community. The IDEAL study was the first (and to date only) large randomized trial to study the effect of estimated glomerular filtration function at the time of dialysis initiation with subsequent patient-centered outcomes such as mortality, hospitalization, and health-related quality of life (HRQoL). The IDEAL study was conducted between July 2000 and November 2008, and ultimately enrolled 828 adults with advanced CKD, defined as an eGFR (calculated by the Cockcroft-Gault method) of <15 mL/min/1.73 m 2 body surface area. Patients were recruited from 32 centers in Australia and New Zealand and were randomized to initiation of dialysis at eGFR of 10 to 15 mL/min/1.73 m 2 (“early start”) or eGFR of 5 to 7 mL/min/1.73 m 2 (“late start”). The median follow-up period was 3.6 years. Results of the primary analyses, published in a landmark paper in 2010, showed that there was no significant difference between the randomized groups in any clinically important outcome, including mortality, hospitalization risk, or cardiovascular events. A follow-up economic analysis of the IDEAL study demonstrated no significant difference in overall healthcare costs or HRQoL between the treatment groups.
The IDEAL trial, although groundbreaking and successful at bringing high-quality clinical trial data to bear on the question of the optimal time for initiation of maintenance dialysis in patients with advanced CKD, was not without a number of important limitations. Among patients randomized to the early-start group, approximately 20% initiated dialysis with eGFR <10 mL/min/1.73 m 2 . Conversely, among individuals assigned to the late-start group, 76% started dialysis with eGFR >7 mL/min/1.73 m 2 . The effect of these protocol deviations was that the difference in eGFR at the time of dialysis initiation between the two treatment groups was only 2.2 mL/min/1.73 m 2 , which some commentators have identified as a major contributor to the trial’s null results. In addition, participants in IDEAL were predominantly white and with lower burden of coexisting medical illnesses compared with the typical patient with ESRD in the United States, raising a concern about generalizability of the IDEAL trial findings. Finally, the majority of patients in early-start treatment group in IDEAL initiated dialysis with PD, making comparisons difficult with ESRD patients in the United States, where >90% of patients are treated with conventional in-center hemodialysis, and >80% initiate dialysis with a central venous catheter (CVC). Notwithstanding these limitations, in the few short years since its publication, the legacy of the IDEAL trial has profoundly influenced clinical nephrology practice and clinical practice guidelines regarding the timing and initiation of maintenance dialysis in patients with advanced CKD.
Current Kidney Disease Outcomes Quality Initiative Recommendations for Timing of Initiation of Dialysis
As previously stated, the influence of the results of the IDEAL trial was profound. The interpretation of the IDEAL results by many nephrologists and commentators was that among asymptomatic patients with advanced CKD without clinical appearance of uremia or its various complications, initiation of dialysis may be safely postponed until signs, symptoms, or complications of uremia are evident. What follows from this interpretation, but what is less commonly discussed, is that dialysis should not be delayed in patients in whom adverse effects from chronic kidney failure have appeared simply because the level of eGFR has not declined below a preconceived threshold. Further observational studies published since IDEAL using advanced statistical methods such as casual inference modeling with inverse probability weights and marginal structural models have confirmed the results of IDEAL through examination of existing clinical cohorts and demonstration that there is no significant survival impact of initiation of dialysis at higher versus lower eGFR.
The most recent iteration of the KDQOI guidelines for hemodialysis adequacy were published in 2015 and contain guidance for practicing nephrologists regarding the timing of dialysis initiation that reflect the message and lessons learned from IDEAL, as well as continued clinical experience and observational data from the past decade. These latest KDOQI guidelines recommend that rather than focusing on a specific level of kidney function, the decision to initiate maintenance dialysis should be based primarily on an assessment of attributable complications of kidney failure, including signs and symptoms of uremia, PEW, and development of metabolic or volume disturbances refractory to medical therapy ( Table 19.1 ). Although straightforward at first glance, the authors of this guidance statement acknowledge that the subjective assessment of signs and symptoms attributable to kidney disease can be quite challenging in patients with multiple coexisting illnesses, many of which may cause systemic symptoms that may mimic the quality and severity of those caused by kidney failure.
| Guideline | Statement |
|---|---|
| NKF-KDOQI (2015) | The decision to initiate maintenance dialysis in patients who choose to do so should be based primarily upon an assessment of signs and/or symptoms associated with uremia, evidence of protein-energy wasting, and the ability to safely manage metabolic abnormalities and/or volume overload with medical therapy rather than on a specific level of kidney function in the absence of such signs and symptoms. |
| Canadian Society of Nephrology (2014) | For adults (aged > 18 yr) with an eGFR of less than 15 mL/min/1.73 m 2 , we recommend an “intent-to-defer” over an “intent-to-start-early” approach for the initiation of chronic dialysis. With the intent-to-defer strategy, patients with an eGFR of less than 15 mL/min/1.73 m 2 are monitored closely by a nephrologist, and dialysis is initiated with the first onset of a clinical indication or a decline in the eGFR to 6 mL/min/1.73 m 2 or less, whichever of these should occur first. Clinical indications for the initiation of dialysis include the following: symptoms of uremia, fluid overload, refractory hyperkalemia or acidemia, or other conditions or symptoms that are likely to be ameliorated by dialysis. In the absence of these factors, the eGFR should not serve as a sole criterion for the initiation of dialysis unless it is 6 mL/min/1.73 m 2 or less. |
| ERA-EDTA/ERBP Advisory Board (2011) | In patients with a GFR <15 mL/min/1.73 m 2 , dialysis should be considered when there is one or more of the following: symptoms or signs of uremia, inability to control hydration status or blood pressure, or a progressive deterioration in nutritional status. It should be taken into account that the majority of patients will be symptomatic and need to start dialysis with GFR in the range 9–6 mL/min/1.73 m 2 . High-risk patients (e.g., diabetics and those whose renal function is deteriorating more rapidly than eGFR 4 mL/min/year) require particularly close supervision. Where close supervision is not feasible and in patients whose uremic symptoms may be difficult to detect, a planned start to dialysis while still asymptomatic may be preferred. Asymptomatic patients presenting with advanced CKD may benefit from a delay in starting dialysis in order to allow preparation, planning and permanent access creation rather than using temporary access. |
| KDIGO (2012) | We suggest that dialysis be initiated when one or more of the following are present: symptoms or signs attributable to kidney failure (serositis, acid-base or electrolyte abnormalities, pruritus), inability to control volume status or blood pressure, a progressive deterioration in nutritional status refractory to dietary intervention, or cognitive impairment. This often but not invariably occurs in the GFR range between 5 and 10 mL/min/1.73 m 2 . |
Other Clinical Practice Guidelines for Timing of Initiation of Dialysis
In addition to clinical practice guidelines published by the National Kidney Foundation (NKF) KDOQI working group on hemodialysis adequacy, numerous other guidelines have been published in recent years providing different perspectives and recommendations for clinicians facing the decision of when to recommend initiation of dialysis for their patients. The Kidney Disease Improving Global Outcomes (KDIGO) initiative released its own guideline in 2012 that, similar to the KDOQI guidance document, also endorses an approach to the timing of dialysis initiation that focuses on assessment of signs and symptoms attributable to kidney failure (see Table 19.1 ). Unlike KDOQI, the KDIGO guidance does identify a range of eGFR at which signs and symptoms of kidney failure are likely to appear (i.e., between 5 and 10 mL/min/1.73 m 2 ), but does not specifically recommend using this eGFR threshold as the basis for dialysis initiation. Similarly, the European Dialysis and Transplant Association updated its position statement in 2011 regarding timing of dialysis initiation, and although it provides a range of eGFR at which uremic symptoms are likely to appear, the guidance document specifically cautions against the use of eGFR as the primary guide to dialysis decision making (see Table 19.1 ). In contrast, the Canadian Association of Nephrology’s updated 2013 clinical practice guideline for timing the initiation of chronic dialysis identifies a threshold of 6 mL/min/1.73 m 2 as the absolute threshold below which dialysis should be initiated (see Table 19.1 ). This threshold was determined through consideration of the median eGFR targeted in the “late-start” arm of the IDEAL trial.
Trends in Timing of Initiation of Dialysis
From the mid-1990s through the end of the first decade of the 21st century, the mean eGFR at dialysis initiation for patients with incident ESRD in the United States rose steadily from 7.7 mL/min/1.73 m 2 to a peak of 11.2 mL/min/1.73 m 2 in 2009 ( Fig. 19.1 ). Evidence from population-based cohort studies in Canada and Europe has revealed a similar trend of increasing eGFR at dialysis initiation over that period outside of the United States as well. Although definitive evidence regarding the cause of these secular trends is lacking, there are multiple potential contributing factors. First, before the clinical trial results from IDEAL, conventional wisdom was that earlier use of dialytic clearance to complement native kidney clearance would provide enhanced clearance of uremic toxins that were associated with adverse cardiovascular outcomes, improved control of metabolic complications of advanced kidney disease, and further prevent hospitalizations related to volume overload as extracellular volume accumulated. The assumption was that such enhanced clearance and volume control would undoubtedly translate into improved patient-centered outcomes, such that earlier dialysis was indicated for most patients. Further potential contributing factors may have included changes in the demographic makeup of the ESRD population areound the world, implementation of automated reported of eGFR by laboratory facilities around the world, and changes in the predialysis practice characteristics such as duration of predialysis nephrology care and presence of a permanent dialysis access.
The year 2010 represented an inflection point in the secular trend of eGFR at dialysis initiation for patients with incident ESRD in the United States. From 2010 through 2014, the mean eGFR at dialysis initiation has decreased from 11.2 mL/min/1.73 m 2 to 10.2 mL/min/1.73 m 2 , its lowest point since 2004. Although representing a small absolute change in mean GFR, this fall marks a shift from the inexorable upward trend seen over the preceding two decades. Although data are limited, evidence from international data sources suggests that such recent shifts in practice have occurred outside the United States as well. The basis for these changing trends are uncertain and likely numerous, but have mirrored the publication and widespread dissemination of the results from the IDEAL trial as well as the revisions to clinical practice guidelines for timing of dialysis initiation that were discussed earlier in this chapter.
We recommend a patient-centered approach to dialysis initiation decision making that incorporates broad assessment of a patient’s clinical status including markers of metabolic and volume complications of advanced kidney disease, the presence of uremic signs and symptoms, as well as incorporation of patients’ values and preferences regarding RRT ( Fig. 19.2 ). Our recommendation is in line with the most recently revised KDOQI guidelines. Furthermore, we agree with the KDOQI guidelines that clinicians should avoid using a specific level of eGFR as a threshold for recommending that patients initiate dialysis. A reasonable approach is to defer initiation of dialysis until the development of signs and symptoms that could reasonably by attributed to kidney failure, and which would be likely to improve with the initiation of dialysis. It is important to recognize that such symptoms may not be overt, and patients may adapt to a lower level of functioning without conscious recognition of this adaptation. Similarly, patients may experience the effects of PEW leading to weight loss and malnutrition without recognition, and thus clinicians should be vigilant in frequent assessment of weight and functional capacity. To adopt this approach, patients must be seen and assessed by the clinician on a frequent and ongoing basis, and the principles of shared decision making should be employed to ensure that the decision of whether and when to start dialysis is patient- and family-centered.
Preparation for Renal Replacement Therapy
Timeliness of Nephrology Referral
A critical component of optimizing the transition from medical management of advanced kidney disease to the initiation of RRT is timely referral to a kidney specialist. Unfortunately, in the United States, available data show that only 30% of incident ESRD cases received care from a nephrologist before the onset of ESRD of >12 months. Nearly 25% of all patients with incident ESRD never saw a nephrologist before the initiation of RRT. Racial and ethnic disparities in late referral also are evident, with blacks and Hispanics less likely to have had pre-ESRD care than whites and non-Hispanic individuals. Late referral to a nephrologist has been found to be an independent risk factor for early death on dialysis, even after adjusting for demographic and healthcare utilization factors. Conversely, earlier nephrology referral has been associated with lower mortality and hospitalization, greater uptake of home dialysis modalities, lower utilization of CVCs at dialysis start, and better HRQoL. The KDIGO recommendations for referral of patients to specialist kidney care services for individuals with CKD include referral for an abrupt or sustained fall in GFR, eGFR <30 mL/min/1.73 m 2 , persistent albuminuria, or in whom the risk for kidney failure within 1 year is >10%. We recommend that early predialysis nephrology care be the goal for most individuals with stage 3 or greater CKD, in particular for individuals with evidence of progressive loss of kidney function,to allow adequate medical and psychosocial preparation for the initiation of RRT.
Predialysis Chronic Kidney Disease Education
Current KDOQI and KDIGO guidelines suggest that dialysis-related education should begin at stage 4 CKD, allowing adequate preparation for consideration of initiation of RRT once patients develop signs or symptoms consistent with kidney failure, generally when patients reach stage 5 CKD. Dialysis-related education should include dietary counseling, education regarding different RRT options including preemptive kidney transplantation, vascular or PD access options, and consideration of the psychosocial and medical effects on the patient of the transition to ESRD. We also recommend consideration of maximum conservative management without provision of dialysis. CKD patient education programs have been shown to be associated with greater objective and perceived kidney disease knowledge by patients, higher uptake of home dialysis modalities, better self-reported quality of life, and survival after dialysis initiation. CKD education initiatives empower patients, facilitate patient- and family-centered shared decision making, and embrace current national healthcare priorities for care to be patient-centered.
Timing of Dialysis Access Placement
The most recent NKF KDOQI clinical practice guidelines suggest that all patients should have a functional permanent access at the initiation of dialysis therapy. For hemodialysis, this means timely placement of an arteriovenous (AV) fistula or AV graft. For patients planning to initiate PD, this means timely placement of a PD catheter. Current recommendations are for an AV fistula to be placed at least 6 months before the anticipated start of hemodialysis, with the goal to allow adequate time for fistula maturation and the potential for access intervention and revision of necessary. An AV graft should be placed at least 6 weeks before the anticipated start of hemodialysis, although in many cases grafts can be used sooner than this conservative estimate. A PD catheter should ideally be placed at least 2 to 4 weeks before the anticipated need for initiation of dialysis to allow for adequate time for healing and to avoid the risk for pericatheter leaks. An alternative strategy for PD access is to implant a PD catheter far in advance of the anticipated need for dialysis, but instead of leaving a portion of catheter externalized, this portion is embedded under the skin in the subcutaneous space. When kidney function declines and the patient is felt to have a clinical need to initiate dialysis, this portion of the catheter is exeernalized through a small skin incision allowing immediate use of the catheter for full-volume PD exchanges. Studies have demonstrated that PD catheters can be embedded for prolonged periods and still result in functional dialysis access at the time the patient requires initiation of RRT.
Unfortunately, notwithstanding current clinical practice guideline recommendations, >80% of patients initiating hemodialysis in the United States were using a CVC rather than a permanent AV access, a figure that has remained steady for more than a decade. A large body of literature has demonstrated that the use of CVCs for dialysis access is associated with greater risk for adverse clinical outcomes, including higher risk for hospitalization, infection-related morbidity, cardiovascular events, and mortality. The United States and Canada have higher rates of catheter use at dialysis initiation than other industrialized countries, despite multiple vascular access initiatives implemented over the past two decades aimed at increasing the use of permanent AV access and decreasing the use of CVCs for dialysis access. Most notably, the Fistula First Breakthrough Initiative (FFBI) was jointly developed and implemented by the Centers for Medicare & Medicaid Services and the ESRD networks with the goal to encourage AV fistulas as the primary vascular access for ≥50% of all new patients initiating maintenance hemodialysis, and to reduce the prevalence of catheter use for >90 days to <10% of prevalent hemodialysis patients. However, recognition over the past 5 years that the proportion of incident ESRD patients using catheters for dialysis access remains persistently and unacceptably high has recently led to a shift in focus of the FFBI to include not only promotion of AV fistulas, but a coprimary aim of discouraging catheter use in both incident and prevalent hemodialysis patients. This shift has coincided with a growing literature suggesting that for particular subgroups of patients (in particular the elderly), AV graft outcomes may equal those achieved by patients using AV fistulas, in part due to the high rate of primary fistula maturation failure in these groups. Recently, the FFBI was the Fistula First Catheter Last (FFCL) Coalition as a symbol of its shifting focus. In contrast to the 2006 KDOQI guidelines for vascular access, the FFCL Coalition has recommended fistula placement ≤12 months before the anticipated need for hemodialysis initiation.
Timing of Referral for Kidney Transplant Evaluation
Preemptive kidney transplantation is considered the preferred method of RRT for the majority of patients, given the well-demonstrated improved morbidity, mortality, and patient-reported outcomes in transplant recipients compared with those undergoing dialysis. Wait times from listing to transplantation vary considerably in the United States based on patient characteristics and geography, and in some areas can approach 10 years. The median wait time nationally is approximately 4.5 years. Thus we believe that all patients with advanced kidney disease should be considered by their providers for early kidney transplant evaluation. Although there are a few agreed-upon absolute contraindications to kidney transplantation, such as active malignancy and severe active cardiovascular disease, inclusion and exclusion criteria for patients vary widely between transplant programs. Thus we believe that referral for transplant should be the default plan for most patients with advanced CKD. In general, all patients with stages 4 and 5 CKD (i.e., with eGFR <30 mL/min/1.73 m 2 ) are appropriate for referral. In some select cases of patients with rapidly progressive CKD, referral at even higher levels of eGFR may be appropriate.
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