The 2015 update to the Kidney Disease Outcomes Quality Initiative clinical practice guidelines for hemodialysis adequacy explicitly recognizes that the ultimate goal of treatment for patients with advanced CKD is improvement in the quality of life with the prolongation of life often as an additional goal.1 The guidelines go on further to state that the purpose of dialysis is not solely prolongation of life but rather the promotion of living.
These statements resonate with a Australian study published in 2016 looking at the importance of various outcomes ranked by 12 separate patient and caregiver focus groups.2 Lifestyle and psychosocial outcomes constituted nine of the top 10 outcomes. Fatigue and energy level, resilience and coping, and the ability to travel were the top three outcomes of importance, with mortality being ranked 14th. Of the 33 outcomes that were identified in four or more of the focus groups, the traditionally measured biochemical outcomes of potassium, phosphate, calcium, parathyroid hormone, hemoglobin, and iron were all ranked in the bottom third. More recently, surveys conducted as part of the SONG initiative showed that patients prioritize outcomes differently than nephrology professionals (see the Patient Engagement section of this issue).
The KDOQI update offers recommendations and grading of evidence in five important areas based on literature published between 2000 and March 2014. They include
- timing of hemodialysis initiation
- frequent and long duration hemodialysis (including for the first time recommendations on home long HD)
- urea kinetics
- volume and blood pressure control
- new hemodialysis membranes
The grades for strength and quality of the recommendations and evidence are shown in Tables 1 and 2.
Timing of hemodialysis initiation
Guideline 1.1 Patients who reach CKD stage 4 (GFR, 30 mL/min/1.73 m2), including those who have imminent need for maintenance dialysis at the time of initial assessment, should receive education about kidney failure and options for its treatment, including kidney transplantation, peritoneal dialysis, HD in the home or in-center, and conservative treatment. Patients’ family members and caregivers also should be educated about treatment choices for kidney failure. (Not Graded)
Comments: It is notable that a large proportion of patients starting dialysis remain unaware of all possible options for their care despite decades of work on this issue. In the Comprehensive Dialysis Study, a special United States Renal Data System data collection effort, 41% of patients with ESRD reported that peritoneal dialysis was not discussed with them prior to beginning dialysis.3 In a subsequent study of dialysis patients in Southern California, 88% were not aware of the option of home hemodialysis.4 This represents a large area of opportunity to improve the current status quo.
Guideline 1.2 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. (Not Graded)
Comments: The update from the 2006 guidelines removes any suggested eGFR for dialysis initiation which was previously given as 15 ml/min/1.73m2 5 This change was largely based on the IDEAL trial published in 2010.6 The IDEAL trial randomized 828 patients to an early or late dialysis start strategy and provided evidence that an early start strategy did not offer any benefit in terms of quality of life or mortality. It was notable that more than 75% of patients assigned to the late start group started dialysis before reaching the target level of renal function primarily due to uremic symptoms, emphasizing the importance of close nephrology follow-up. Given the above, the Work Group favored an individualized approach to the timing of dialysis initiation, an area still within the “art” of our nephrology practice.
Frequent and long duration hemodialysis
In-center frequent HD
Guideline 2.1 We suggest that patients with end-stage renal disease be offered in-center, short frequent hemodialysis as an alternative to conventional in-center thrice weekly hemodialysis after considering individual patient preferences, the potential quality of life, and physiological benefits, and the risks of these therapies. (2C)
Guideline 2.2 We recommend that patients considering in-center short frequent hemodialysis be informed about the risks of this therapy, including a possible increase in vascular access procedures (1B) and the potential for hypotension during dialysis. (1C)
Comments: The above recommendations are largely based on the results of the Frequent Hemodialysis Network (FHN) trial which showed that 6x per week, in-center, short-frequent dialysis compared to 3x per week in-center conventional HD resulted in statistically significant improvements in health-related quality of life and reductions in left ventricular mass, intradialytic systolic BP, antihypertensive medications, serum phosphorus, and use of phosphate binders.7 This came at the expense of a statistically significant increased risk of vascular access repairs and an increase in intradialytic hypotensive episodes.
The Work Group did not review evidence concerning home dialysis techniques with lower dialysate flow rates, such as those employed by NxStage Medical and its SystemOne machine, and state that the above recommendations cannot be extrapolated to these therapies. As a practical matter, <10% of patients screened were eligible and agreed to participate in the FHN Daily trial, and adherence to 6 days per week in-center therapy during the 12-month trial period was moderate. At the end of the 1-year intervention period, 90% of patients randomized to daily HD reverted to 3 or 4 times per week HD. In practice, nephrologists will need to find flexible approaches to realize the benefits of frequent dialysis that work for patients and their families.
Home Long HD
Guideline 2.3 Consider home long hemodialysis (6-8 hours, 3 to 6 nights per week) for patients with end-stage kidney disease who prefer this therapy for lifestyle considerations. (Not Graded)
Guideline 2.4 We recommend that patients considering home long frequent hemodialysis be informed about the risks of this therapy, including possible increase in vascular access complications, potential for increased caregiver burden, and accelerated decline in residual kidney function. (1C)
Comments: Home hemodialysis offers a variety of potential benefits, including flexibility of schedule for work, life and travel, liberalization of diet, decreases in post dialysis recovery time, improvements in sleep quality, physical and emotional well-being, depressive symptom burden, and decreases in the number of antihypertensive and phosphorous binder drugs needed. The optimal way to prescribe home hemodialysis is unclear and patients who opt for longer or more frequent therapy to allow for various aspects of life should be aware of potential risks.
Guideline 2.5 During pregnancy, women with end-stage kidney disease should receive long frequent hemodialysis either in-center or at home, depending on convenience. (Not Graded)
Comments: It is extremely unlikely that we will ever see a randomized prospective trial of dialysis dose assessing outcomes for pregnant woman and their babies. As practicing nephrologists, we are left with observational evidence which associates improved live birth rates and higher birth weights with longer more frequent hemodialysis.
Measurement of dialysis: Urea kinetics
Guideline 3.1 We recommend a target single pool Kt/V (spKt/V) of 1.4 per hemodialysis session for patients treated thrice weekly, with a minimum delivered spKt/V of 1.2. (1B)
Guideline 3.2 In patients with significant residual native kidney function (Kru), the dose of hemodialysis may be reduced, provided Kru is measured periodically to avoid inadequate dialysis. (Not Graded)
Guideline 3.3 For hemodialysis schedules other than thrice weekly, we suggest a target standard Kt/V of 2.3 volumes per week with a minimum delivered dose of 2.1 using a method of calculation that includes the contributions of ultrafiltration and residual kidney function. (Not Graded)
Comments: Urea kinetic recommendations are largely unchanged from the 2006 guidelines. The ungraded recommendation to deliver a minimum standard Kt/V of 2.1 is slightly higher than the previous clinical practice guideline to deliver a standard Kt/V of 2.0 for hemodialysis schedules other than thrice weekly.
Volume and blood pressure control: Treatment time and ultrafiltration rate
Guideline 4.1 We recommend that patients with low residual kidney function (< 2 mL/min) undergoing thrice weekly hemodialysis be prescribed a bare minimum of 3 hours per session. (1D)
Guideline 4.1.1 Consider additional hemodialysis sessions or longer hemodialysis treatment times for patients with large weight gains, high ultrafiltration rates, poorly controlled blood pressure, difficulty achieving dry weight, or poor metabolic control (such as hyperphosphatemia, metabolic acidosis, and/or hyperkalemia). (Not Graded)
Comments: As adequacy is not solely confined to small solute clearance, the Work Group acknowledged that many patients require more than three hours to achieve optimal volume and metabolic control and suggested that sodium and water balance, interdialytic weight gain, hemodynamic stability during HD, BP control, overall metabolic control, Kru, patient preference, and health-related quality of life also be considered when making a decision regarding HD treatment time.
Regarding health-related quality of life, practicing nephrologists are very familiar with the patient report of prolonged periods of feeling wiped out after conventional 3x per week in-center dialysis. Published reports have noted post dialysis recovery times ranging between approximately 3.4 hours and 7.6 hours.8-11 In a recent study of 2,689 Satellite Healthcare in-center conventional hemodialysis patients, 29% reported a post- dialysis recovery time of 6 hours or longer with 20% reporting that it took them over 12 hours to recover.12 Interesting, this study also showed that fluid ultrafiltration rates above 13 ml/kg/hr were also associated with longer recovery times. Shortened post dialysis recovery times of approximately an hour or less have also been associated with longer and more frequent hemodialysis.10, 13
Guideline 4.2 We recommend both reducing dietary sodium intake as well as adequate sodium/water removal with hemodialysis to manage hypertension, hypervolemia, and left ventricular hypertrophy. (1B)
Guideline 4.2.1 Prescribe an ultrafiltration rate for each hemodialysis session that allows for an optimal balance among achieving euvolemia, adequate blood pressure control and solute clearance, while minimizing hemodynamic instability and intradialytic symptoms. (Not Graded)
Comments: Recent clinical evidence suggests that ultrafiltration rates above 13 ml/kg/hr are associated with increases in mortality.14-15 In recognition of this, ultrafiltration rates are a proposed QIP reporting measure in 2017 and have been incorporated into Satellite Healthcare Quality Management and Quality Focus reports. As mentioned above, higher ultrafiltration rates have been associated with longer post dialysis recovery times. Practical strategies to potentially lower ultrafiltration rates include longer and more frequent dialysis coupled with dietary and dialytic sodium reduction to lower thirst.
New hemodialysis membranes
Guideline 5.1 We recommend the use of biocompatible, either high or low flux hemodialysis membranes for intermittent hemodialysis. (1B)
Comments: This is unchanged from the 2006 guidelines.
The KDOQI Work Group acknowledges that in recent literature, adequacy of dialysis is sometimes confused with adequacy of other aspects of patient management, with the erroneous assumption that having achieved dialysis adequacy, the goal of dialysis has been accomplished. Humanizing dialysis implies that we do what matters most to our patients, which is to live as normal a life as possible with kidney disease. A critical component to achieve this is based on individualized prescription that limits adverse events, including fluid overload, intradialytic hypotension, and prolonged dialysis recovery time. Flexibility in prescribing using the best evidence available allows us to achieve this goal, and the 2015 Adequacy Guidelines provide an excellent evidence-based backdrop.
- National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update. Am J Kidney Dis. 2015;66(5):884-930.
- Urquhart-Secord, R. et al. Patient and caregiver priorities for outcomes in hemodialysis: An international nominal group technique study. Am J Kidney Dis, 2016.
- Kutner NG, Zhang R, Huang Y, Wasse H. Patient awareness and initiation of peritoneal dialysis. Arch Intern Med. 2011;171(2):119-124.
- Mehrotra R, Marsh D, Vonesh E, Peters V, Nissenson A. Patient education and access of ESRD patients to renal replacement therapies beyond in-center hemodialysis. Kidney Int. 2005;68(1):378-390.
- National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for 2006 Updates: Hemodialysis Adequacy, Peritoneal Dialysis Adequacy and Vascular Access. Am J Kidney Dis 48:S1-S322, 2006 (suppl 1).
- Cooper BA, Branley P, Bulfone L, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010;363(7):609-619.
- The FHN Trial Group. Prepared by Chertow GM, Levin NW, Beck GJ, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2300.
- Bossola M, Di Stasio E, Antocicco M et al. Variables associated with time of recovery after hemodialysis. J Nephrol 2013; 26: 787–792
- Lindsay RM, Heidenheim AP, Nesrallah G et al. London daily/ nocturnal hemodialysis study: minutes to recovery after a hemodialysis session: A simple health-related quality of life question that is reliable, valid, and sensitive to change. Clin J Am Soc Nephrol 2006; 1: 952–959
- Heidenheim AP, Muirhead N, Moist L et al. London daily/nocturnal hemodialysis study: patient quality of life on quotidian hemodialysis. Am J Kidney Dis 2003; 42(Supp. 1): 36–41
- Awuah KT, Afolalu BA, Hussein UT, Raducu RR, Bekui AM, Finkelstein FO. Time to recovery after a hemodialysis session: impact of selected variables. Clin Kidney J (2013) 6: 595–598
- Hussein W, Arramreddy R, Sun S, Reiterman M, Schiller B. Rapid fluid removal is associated with longer dialysis recovery time in conventional hemodialysis patients. American Society of Nephrology Annual Meeting Abstract 2015.
- Jaber BL, Lee Y, Collins AJ et al. Effect of daily hemodialysis on depressive symptoms and post-dialysis recovery time: interim report from the FREEDOM study. Amer J Kidney Dis 2010; 56: 531–539
- Flythe JE, Curhan GC, Brunelli SM. Disentangling the ultrafiltration rate-mortality association: the respective roles of session length and weight gain. Clin J Am Soc Nephrol. 2013;8(7): 1151-1161.
- Flythe JE, Kimmel SE, Brunelli SM. Rapid fluid removal during dialysis is associated with cardiovascular morbidity and mortality. Kidney Int. 2011;79(2):250-257.