Editorial Is Starting Hemodialysis on a Twice-Weekly Regimen a Valid Option? Related Article, p. 181
F
or several decades after its introduction, hemodialysis was performed only once or twice per week, often for long sessions (6-8 hours). When more efficient dialyzers and arteriovenous fistulas with high blood flows became available, the length of dialysis sessions was reduced and short dialysis (4 hours thrice weekly or 3 hours every other day) became standard. 1 In this issue of AJKD, Kalantar-Zadeh and colleagues2 revisit a theme advanced in 2013,3 advocating for randomized clinical trials to compare outcomes associated with initiating dialysis with twice-weekly versus thrice-weekly hemodialysis sessions. Although the thrice-weekly schedule is now current practice in many parts of the world, the authors support their thesis with opinions and some data which, taken together, seem appealing enough to consider a twice-weekly start. Before we embark on what probably will be complex clinical trials, some critical reflections should be considered. The arguments in favor of the twice-weekly approach mainly are based on results of incremental dialysis in peritoneal dialysis (PD). Several caveats should be noted. First, even in PD, the concept of incremental dialysis is not often practiced. Second, PD data should be extrapolated to hemodialysis with care, as PD removes uremic solutes on a continuous basis, with additional effects on uremic solute concentrations by as yet poorly defined mechanisms.4 Hemodialysis causes markedly more abrupt metabolic and hemodynamic shifts, which conceivably would be even more pronounced with twice-weekly therapy. Based on the assumption that an immediate thriceweekly start of dialysis is a cause of excess mortality, Kalantar-Zadeh et al hypothesize that the twiceweekly approach will reduce the unacceptably high early mortality among patients initiating hemodialysis.5 However, other factors may play a more prominent role, such as the high rate of catheter use in inadequately prepared late referrals,6 or the taking on of frail patients with congestive heart failure in a mostly unsuccessful attempt to reverse their underlying pathology. It is questionable how 2 instead of 3 dialysis sessions per week will improve the outcome of these patients. In addition, most, if not all, patients with the latter phenotype will fail the criteria for twice-weekly hemodialysis, as listed in Box 1 (adapted from the article by Kalantar-Zadeh et al2), resulting in a strong potential for bias by indication, a limitation probably already present in the few available small observational cohort studies on this Am J Kidney Dis. 2014;64(2):165-167
issue.7-9 Of note, one of the few studies comparing these 2 options in a US population9 shows better survival in prevalent twice-weekly starters, but not in incident dialysis patients, consistent with possible indication bias. Other data are derived from observational studies conducted in Asian populations.7,8 It might be risky to extrapolate these data all too enthusiastically to populations that are genetically, metabolically, and constitutionally different, or to countries with a divergent case mix, different therapeutic approaches, and different dietary habits. Finally, since it is accepted that the 3-day weekend interval in the current schedules is linked to increased mortality,10-12 it is unclear how reducing dialysis frequency to twice weekly and thus prolonging the interdialytic interval would improve outcomes. Preservation of residual kidney function, which is a key factor affecting survival of dialysis patients,13,14 is considered by Kalantar-Zadeh et al to be another major benefit of the twice-weekly start.2 However, data on the impact of start of treatment on residual kidney function are scarce in hemodialysis,6 and the most significant determinant of whether residual kidney function is preserved probably is a low ultrafiltration rate, and thus, the presence of low interdialytic weight gain.15 Kidney function does not decline at the same rate in all dialysis patients, and the decline may be faster in patients who are fluid overloaded at the initiation of dialysis; notably, these patients, according to the inclusion criteria of Box 1, have a much lower chance of receiving twice-weekly dialysis. In contrast, in those eligible for twice-weekly dialysis, kidney function might be preserved relatively well, irrespective of the dialysis regimen. Kalantar-Zadeh et al suggest that “incremental dialysis” could stop the dispute between supporters and opponents of early start of dialysis. In our opinion, this discussion has already been solved by the IDEAL (Initiating Dialysis Early and Late) trial,16 which demonstrated that patients should only start dialysis on clinical grounds17-19; again, the majority among the group of symptomatic patients will not fulfill the criteria in Box 1, and thus should not be considered candidates for twiceweekly start.
Address correspondence to Raymond Vanholder, MD, PhD, University Hospital, De Pintelaan 185, B9000 Ghent, Belgium. E-mail: [email protected] Ó 2014 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2014.06.003 165
Vanholder, Van Biesen, and Lameire Box 1. Proposed Criteria for Twice-Weekly Hemodialysis 1. Good residual kidney function with a urine output . 0.5 L/d 2. Limited fluid retention between 2 consecutive hemodialysis treatments with a fluid gain , 2.5 kg (or less than 5% of the ideal dry weight) without hemodialysis for 3-4 d 3. Limited or readily manageable cardiovascular or pulmonary symptoms without clinically significant fluid overloada 4. Suitable body size relative to residual kidney function; patients with larger body size may be suitable for twiceweekly hemodialysis if not hypercatabolic 5. Hyperkalemia (potassium . 5.5 mEq/L) is infrequent or readily manageable 6. Hyperphosphatemia (phosphate . 5.5 mg/dL) is infrequent or readily manageable 7. Good nutritional status without florid hypercatabolic state 8. Lack of profound anemia (hemoglobin . 8 g/dL) and appropriate responsiveness to anemia therapy 9. Infrequent hospitalization and easily manageable comorbid conditions 10. Satisfactory health-related quality of life Note: Adapted from Kalantar-Zadeh et al2 with permission of the National Kidney Foundation. The authors note that the proposed criteria are general rather than specific and should be refined for use in clinical trials and clinical decision making. a Lack of systolic dysfunction (ejection fraction . 40%) and no major coronary intervention over the previous 3 months.
Kalantar-Zadeh et al claim that twice-weekly dialysis may improve quality of life for those reluctant to travel and those with infirm family members or children needing their presence at home. This concept starts from the premise that in-center hemodialysis is the only option for such patients. In truth, homebased renal replacement therapy is the preferred option of patients and nephrologists,20,21 but is only hesitantly implemented, in most countries because of low reimbursement.22 Preemptive transplantation is another valid option. None of these, except PD, are mentioned as valid alternatives in the article by Kalantar-Zadeh et al. A second, even more unexpected, group of supposed beneficiaries mentioned are patients who are elderly or debilitated with cancer or other severe comorbid conditions. This suggestion conflicts with the criteria for being accepted into the twice-weekly regimen, as proposed by Kalantar-Zadeh et al in Box 1. Points 2, 3, and 9 of the treatment criteria allow only patients with limited fluid retention, limited cardiovascular or pulmonary symptoms and no clinically significant fluid overload, manageable comorbid conditions, and infrequent need for hospitalization. One may wonder how many older, debilitated patients will be fit enough to meet these strict inclusion criteria. The basic question may not be at how many sessions per week dialysis should be started in patients with this profile, but rather, whether 166
dialysis should be started at all, as conservative care may afford better quality of life. Kalantar-Zadeh et al argue that twice-weekly dialysis will result in improved cost-efficiency of dialysis. While this hypothesis remains to be proven, as inadequate dialysis might also result in more hospitalization and comorbid conditions, in our opinion, and extrapolating from the criteria for eligibility, the real target patient population for a twice-weekly dialysis start seems to be relatively young patients with few comorbid conditions. However, this population has become relatively rare in dialysis units in many parts of the world. Moreover, savings are strongly dependent on local health care and reimbursement policies, as twice-weekly dialysis only has a socioeconomic benefit for the community if dialysis is reimbursed on a per session rather than on a per week basis. In case of per week reimbursement, all financial benefit will go to the unit, at least if patient survival is preserved. The question can be raised, whether a randomized clinical trial on this issue is a real priority. All recent arguments for an ideal start of a long-term hemodialysis program, including those developed by Kalantar-Zadeh et al, seem to be more in favor of “smooth” renal replacement therapies, such as (home-based) nocturnal dialysis and PD. We wonder whether research questions on the outcome of intensity of dialysis and the impact of alternative dialysis strategies (nocturnal, daily short, PD, home hemodialysis, self-care) as compared to the traditional approaches, should not receive higher priority than the questions raised by Kalantar-Zadeh et al. Less frequent dialysis may also have advantages. As pointed out by Kalantar-Zadeh et al,2 recent analyses have shown the potential deleterious effect of more frequent dialysis on vascular access.23 However, this was only a trend in a secondary analysis of a randomized clinical trial, which in the primary analysis, demonstrated superiority of more frequent dialysis on 2 composites of hard and surrogate endpoints.23 Designing and launching randomized controlled trials to properly answer all questions raised in the article by Kalantar-Zadeh et al will require large patient populations with a broad array of socioeconomic and genetic backgrounds to ascertain generalizability. In our opinion, these studies, which will need to be years in duration, would consume impressive amounts of human and financial resources, with a low likelihood of delivering clear and definite answers on what to do in real life. In our opinion, the 1-year study proposed by Kalantar-Zadeh et al will be too short, potentially masking long-term negative effects of inefficient dialysis in healthier dialysis patients, who, according to the inclusion criteria for a twice-weekly start, would compose the majority of those enrolled. In conclusion, the randomized controlled trials evaluating starting with twice-weekly hemodialysis Am J Kidney Dis. 2014;64(2):165-167
Editorial
suggested by Kalantar-Zadeh et al will be difficult to perform because of the number needed to treat, may lead to less reliable conclusions if follow-up is kept short, and may still suffer from problems of generalizability. Although there are a number of potentially attractive elements associated with twice-weekly dialysis, we feel that limited resources are better directed elsewhere in improving dialysis care. Raymond Vanholder, MD, PhD Wim Van Biesen, MD, PhD Norbert Lameire, MD, PhD University Hospital Ghent, Belgium
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: Dr Vanholder has consulted for Baxter Healthcare, Gambro, and Bellco; and has received grant support from Baxter Healthcare, Bellco, Fresenius Medical Care, Gambro, Nippro, Amgen, Hoffman LaRoche, Astellas, and Sandoz. The remaining authors declare that they have no relevant financial interests.
REFERENCES 1. Cambi V, Savazzi G, Arisi L, et al. Short dialysis schedules (SDS)–finally ready to become routine? Proc Eur Dial Transplant Assoc. 1975;11:112-120. 2. Kalantar-Zadeh K, Unruh M, Zager PG, et al. Twice-weekly and incremental hemodialysis treatment for initiation of kidney replacement therapy. Am J Kidney Dis. 2014;64(2):181-186. 3. Rhee CM, Unruh M, Chen J, et al. Infrequent dialysis: a new paradigm for hemodialysis initiation. Semin Dial. 2013;26(6): 720-727. 4. Vanholder R, Meert N, Van Biesen W, et al. Why do patients on peritoneal dialysis have low blood levels of proteinbound solutes? Nat Clin Pract Nephrol. 2009;5(3):130-131. 5. Bradbury BD, Fissell RB, Albert JM, et al. Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Clin J Am Soc Nephrol. 2007;2(1):89-99. 6. Lukowsky LR, Kheifets L, Arah OA, et al. Patterns and predictors of early mortality in incident hemodialysis patients: new insights. Am J Nephrol. 2012;35(6):548-558. 7. Lin YF, Huang JW, Wu MS, et al. Comparison of residual renal function in patients undergoing twice-weekly versus three-timesweekly haemodialysis. Nephrology (Carlton). 2009;14(1):59-64. 8. Lin X, Yan Y, Ni Z, et al. Clinical outcome of twice-weekly hemodialysis patients in Shanghai. Blood Purif. 2012;33(1-3):66-72.
Am J Kidney Dis. 2014;64(2):165-167
9. Hanson JA, Hulbert-Shearon TE, Ojo AO, et al. Prescription of twice-weekly hemodialysis in the USA. Am J Nephrol. 1999;19(6):625-633. 10. Foley RN, Gilbertson DT, Murray T, et al. Long interdialytic interval and mortality among patients receiving hemodialysis. N Engl J Med. 2011;365(12):1099-1107. 11. Bleyer AJ, Hartman J, Brannon PC, et al. Characteristics of sudden death in hemodialysis patients. Kidney Int. 2006;69(12): 2268-2273. 12. Bleyer AJ, Russell GB, Satko SG. Sudden and cardiac death rates in hemodialysis patients. Kidney Int. 1999;55(4): 1553-1559. 13. Shafi T, Jaar BG, Plantinga LC, et al. Association of residual urine output with mortality, quality of life, and inflammation in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis. 2010;56(2):348-358. 14. van der Wal WM, Noordzij M, Dekker FW, et al. Full loss of residual renal function causes higher mortality in dialysis patients; findings from a marginal structural model. Nephrol Dial Transplant. 2011;26(9):2978-2983. 15. Bragg-Gresham JL, Fissell RB, Mason NA, et al. Diuretic use, residual renal function, and mortality among hemodialysis patients in the Dialysis Outcomes and Practice Pattern Study (DOPPS). Am J Kidney Dis. 2007;49(3):426-431. 16. 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. 17. Lameire N, Van Biesen W. The initiation of renalreplacement therapy—just-in-time delivery. N Engl J Med. 2010;363(7):678-680. 18. Rosansky SJ. Early dialysis initiation, a look from the rearview mirror to what’s ahead. Clin J Am Soc Nephrol. 2014;9(2):222-224. 19. Tattersall J, Dekker F, Heimburger O, et al. When to start dialysis: updated guidance following publication of the Initiating Dialysis Early and Late (IDEAL) study. Nephrol Dial Transplant. 2011;26(7):2082-2086. 20. Rubin HR, Fink NE, Plantinga LC, et al. Patient ratings of dialysis care with peritoneal dialysis vs hemodialysis. JAMA. 2004;291(6):697-703. 21. Jassal SV, Krishna G, Mallick NP, et al. Attitudes of British Isles nephrologists towards dialysis modality selection: a questionnaire study. Nephrol Dial Transplant. 2002;17(3): 474-477. 22. Vanholder R, Davenport A, Hannedouche T, et al. Reimbursement of dialysis: a comparison of seven countries. J Am Soc Nephrol. 2012;23(8):1291-1298. 23. 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.
167
F
or several decades after its introduction, hemodialysis was performed only once or twice per week, often for long sessions (6-8 hours). When more efficient dialyzers and arteriovenous fistulas with high blood flows became available, the length of dialysis sessions was reduced and short dialysis (4 hours thrice weekly or 3 hours every other day) became standard. 1 In this issue of AJKD, Kalantar-Zadeh and colleagues2 revisit a theme advanced in 2013,3 advocating for randomized clinical trials to compare outcomes associated with initiating dialysis with twice-weekly versus thrice-weekly hemodialysis sessions. Although the thrice-weekly schedule is now current practice in many parts of the world, the authors support their thesis with opinions and some data which, taken together, seem appealing enough to consider a twice-weekly start. Before we embark on what probably will be complex clinical trials, some critical reflections should be considered. The arguments in favor of the twice-weekly approach mainly are based on results of incremental dialysis in peritoneal dialysis (PD). Several caveats should be noted. First, even in PD, the concept of incremental dialysis is not often practiced. Second, PD data should be extrapolated to hemodialysis with care, as PD removes uremic solutes on a continuous basis, with additional effects on uremic solute concentrations by as yet poorly defined mechanisms.4 Hemodialysis causes markedly more abrupt metabolic and hemodynamic shifts, which conceivably would be even more pronounced with twice-weekly therapy. Based on the assumption that an immediate thriceweekly start of dialysis is a cause of excess mortality, Kalantar-Zadeh et al hypothesize that the twiceweekly approach will reduce the unacceptably high early mortality among patients initiating hemodialysis.5 However, other factors may play a more prominent role, such as the high rate of catheter use in inadequately prepared late referrals,6 or the taking on of frail patients with congestive heart failure in a mostly unsuccessful attempt to reverse their underlying pathology. It is questionable how 2 instead of 3 dialysis sessions per week will improve the outcome of these patients. In addition, most, if not all, patients with the latter phenotype will fail the criteria for twice-weekly hemodialysis, as listed in Box 1 (adapted from the article by Kalantar-Zadeh et al2), resulting in a strong potential for bias by indication, a limitation probably already present in the few available small observational cohort studies on this Am J Kidney Dis. 2014;64(2):165-167
issue.7-9 Of note, one of the few studies comparing these 2 options in a US population9 shows better survival in prevalent twice-weekly starters, but not in incident dialysis patients, consistent with possible indication bias. Other data are derived from observational studies conducted in Asian populations.7,8 It might be risky to extrapolate these data all too enthusiastically to populations that are genetically, metabolically, and constitutionally different, or to countries with a divergent case mix, different therapeutic approaches, and different dietary habits. Finally, since it is accepted that the 3-day weekend interval in the current schedules is linked to increased mortality,10-12 it is unclear how reducing dialysis frequency to twice weekly and thus prolonging the interdialytic interval would improve outcomes. Preservation of residual kidney function, which is a key factor affecting survival of dialysis patients,13,14 is considered by Kalantar-Zadeh et al to be another major benefit of the twice-weekly start.2 However, data on the impact of start of treatment on residual kidney function are scarce in hemodialysis,6 and the most significant determinant of whether residual kidney function is preserved probably is a low ultrafiltration rate, and thus, the presence of low interdialytic weight gain.15 Kidney function does not decline at the same rate in all dialysis patients, and the decline may be faster in patients who are fluid overloaded at the initiation of dialysis; notably, these patients, according to the inclusion criteria of Box 1, have a much lower chance of receiving twice-weekly dialysis. In contrast, in those eligible for twice-weekly dialysis, kidney function might be preserved relatively well, irrespective of the dialysis regimen. Kalantar-Zadeh et al suggest that “incremental dialysis” could stop the dispute between supporters and opponents of early start of dialysis. In our opinion, this discussion has already been solved by the IDEAL (Initiating Dialysis Early and Late) trial,16 which demonstrated that patients should only start dialysis on clinical grounds17-19; again, the majority among the group of symptomatic patients will not fulfill the criteria in Box 1, and thus should not be considered candidates for twiceweekly start.
Address correspondence to Raymond Vanholder, MD, PhD, University Hospital, De Pintelaan 185, B9000 Ghent, Belgium. E-mail: [email protected] Ó 2014 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2014.06.003 165
Vanholder, Van Biesen, and Lameire Box 1. Proposed Criteria for Twice-Weekly Hemodialysis 1. Good residual kidney function with a urine output . 0.5 L/d 2. Limited fluid retention between 2 consecutive hemodialysis treatments with a fluid gain , 2.5 kg (or less than 5% of the ideal dry weight) without hemodialysis for 3-4 d 3. Limited or readily manageable cardiovascular or pulmonary symptoms without clinically significant fluid overloada 4. Suitable body size relative to residual kidney function; patients with larger body size may be suitable for twiceweekly hemodialysis if not hypercatabolic 5. Hyperkalemia (potassium . 5.5 mEq/L) is infrequent or readily manageable 6. Hyperphosphatemia (phosphate . 5.5 mg/dL) is infrequent or readily manageable 7. Good nutritional status without florid hypercatabolic state 8. Lack of profound anemia (hemoglobin . 8 g/dL) and appropriate responsiveness to anemia therapy 9. Infrequent hospitalization and easily manageable comorbid conditions 10. Satisfactory health-related quality of life Note: Adapted from Kalantar-Zadeh et al2 with permission of the National Kidney Foundation. The authors note that the proposed criteria are general rather than specific and should be refined for use in clinical trials and clinical decision making. a Lack of systolic dysfunction (ejection fraction . 40%) and no major coronary intervention over the previous 3 months.
Kalantar-Zadeh et al claim that twice-weekly dialysis may improve quality of life for those reluctant to travel and those with infirm family members or children needing their presence at home. This concept starts from the premise that in-center hemodialysis is the only option for such patients. In truth, homebased renal replacement therapy is the preferred option of patients and nephrologists,20,21 but is only hesitantly implemented, in most countries because of low reimbursement.22 Preemptive transplantation is another valid option. None of these, except PD, are mentioned as valid alternatives in the article by Kalantar-Zadeh et al. A second, even more unexpected, group of supposed beneficiaries mentioned are patients who are elderly or debilitated with cancer or other severe comorbid conditions. This suggestion conflicts with the criteria for being accepted into the twice-weekly regimen, as proposed by Kalantar-Zadeh et al in Box 1. Points 2, 3, and 9 of the treatment criteria allow only patients with limited fluid retention, limited cardiovascular or pulmonary symptoms and no clinically significant fluid overload, manageable comorbid conditions, and infrequent need for hospitalization. One may wonder how many older, debilitated patients will be fit enough to meet these strict inclusion criteria. The basic question may not be at how many sessions per week dialysis should be started in patients with this profile, but rather, whether 166
dialysis should be started at all, as conservative care may afford better quality of life. Kalantar-Zadeh et al argue that twice-weekly dialysis will result in improved cost-efficiency of dialysis. While this hypothesis remains to be proven, as inadequate dialysis might also result in more hospitalization and comorbid conditions, in our opinion, and extrapolating from the criteria for eligibility, the real target patient population for a twice-weekly dialysis start seems to be relatively young patients with few comorbid conditions. However, this population has become relatively rare in dialysis units in many parts of the world. Moreover, savings are strongly dependent on local health care and reimbursement policies, as twice-weekly dialysis only has a socioeconomic benefit for the community if dialysis is reimbursed on a per session rather than on a per week basis. In case of per week reimbursement, all financial benefit will go to the unit, at least if patient survival is preserved. The question can be raised, whether a randomized clinical trial on this issue is a real priority. All recent arguments for an ideal start of a long-term hemodialysis program, including those developed by Kalantar-Zadeh et al, seem to be more in favor of “smooth” renal replacement therapies, such as (home-based) nocturnal dialysis and PD. We wonder whether research questions on the outcome of intensity of dialysis and the impact of alternative dialysis strategies (nocturnal, daily short, PD, home hemodialysis, self-care) as compared to the traditional approaches, should not receive higher priority than the questions raised by Kalantar-Zadeh et al. Less frequent dialysis may also have advantages. As pointed out by Kalantar-Zadeh et al,2 recent analyses have shown the potential deleterious effect of more frequent dialysis on vascular access.23 However, this was only a trend in a secondary analysis of a randomized clinical trial, which in the primary analysis, demonstrated superiority of more frequent dialysis on 2 composites of hard and surrogate endpoints.23 Designing and launching randomized controlled trials to properly answer all questions raised in the article by Kalantar-Zadeh et al will require large patient populations with a broad array of socioeconomic and genetic backgrounds to ascertain generalizability. In our opinion, these studies, which will need to be years in duration, would consume impressive amounts of human and financial resources, with a low likelihood of delivering clear and definite answers on what to do in real life. In our opinion, the 1-year study proposed by Kalantar-Zadeh et al will be too short, potentially masking long-term negative effects of inefficient dialysis in healthier dialysis patients, who, according to the inclusion criteria for a twice-weekly start, would compose the majority of those enrolled. In conclusion, the randomized controlled trials evaluating starting with twice-weekly hemodialysis Am J Kidney Dis. 2014;64(2):165-167
Editorial
suggested by Kalantar-Zadeh et al will be difficult to perform because of the number needed to treat, may lead to less reliable conclusions if follow-up is kept short, and may still suffer from problems of generalizability. Although there are a number of potentially attractive elements associated with twice-weekly dialysis, we feel that limited resources are better directed elsewhere in improving dialysis care. Raymond Vanholder, MD, PhD Wim Van Biesen, MD, PhD Norbert Lameire, MD, PhD University Hospital Ghent, Belgium
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: Dr Vanholder has consulted for Baxter Healthcare, Gambro, and Bellco; and has received grant support from Baxter Healthcare, Bellco, Fresenius Medical Care, Gambro, Nippro, Amgen, Hoffman LaRoche, Astellas, and Sandoz. The remaining authors declare that they have no relevant financial interests.
REFERENCES 1. Cambi V, Savazzi G, Arisi L, et al. Short dialysis schedules (SDS)–finally ready to become routine? Proc Eur Dial Transplant Assoc. 1975;11:112-120. 2. Kalantar-Zadeh K, Unruh M, Zager PG, et al. Twice-weekly and incremental hemodialysis treatment for initiation of kidney replacement therapy. Am J Kidney Dis. 2014;64(2):181-186. 3. Rhee CM, Unruh M, Chen J, et al. Infrequent dialysis: a new paradigm for hemodialysis initiation. Semin Dial. 2013;26(6): 720-727. 4. Vanholder R, Meert N, Van Biesen W, et al. Why do patients on peritoneal dialysis have low blood levels of proteinbound solutes? Nat Clin Pract Nephrol. 2009;5(3):130-131. 5. Bradbury BD, Fissell RB, Albert JM, et al. Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Clin J Am Soc Nephrol. 2007;2(1):89-99. 6. Lukowsky LR, Kheifets L, Arah OA, et al. Patterns and predictors of early mortality in incident hemodialysis patients: new insights. Am J Nephrol. 2012;35(6):548-558. 7. Lin YF, Huang JW, Wu MS, et al. Comparison of residual renal function in patients undergoing twice-weekly versus three-timesweekly haemodialysis. Nephrology (Carlton). 2009;14(1):59-64. 8. Lin X, Yan Y, Ni Z, et al. Clinical outcome of twice-weekly hemodialysis patients in Shanghai. Blood Purif. 2012;33(1-3):66-72.
Am J Kidney Dis. 2014;64(2):165-167
9. Hanson JA, Hulbert-Shearon TE, Ojo AO, et al. Prescription of twice-weekly hemodialysis in the USA. Am J Nephrol. 1999;19(6):625-633. 10. Foley RN, Gilbertson DT, Murray T, et al. Long interdialytic interval and mortality among patients receiving hemodialysis. N Engl J Med. 2011;365(12):1099-1107. 11. Bleyer AJ, Hartman J, Brannon PC, et al. Characteristics of sudden death in hemodialysis patients. Kidney Int. 2006;69(12): 2268-2273. 12. Bleyer AJ, Russell GB, Satko SG. Sudden and cardiac death rates in hemodialysis patients. Kidney Int. 1999;55(4): 1553-1559. 13. Shafi T, Jaar BG, Plantinga LC, et al. Association of residual urine output with mortality, quality of life, and inflammation in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis. 2010;56(2):348-358. 14. van der Wal WM, Noordzij M, Dekker FW, et al. Full loss of residual renal function causes higher mortality in dialysis patients; findings from a marginal structural model. Nephrol Dial Transplant. 2011;26(9):2978-2983. 15. Bragg-Gresham JL, Fissell RB, Mason NA, et al. Diuretic use, residual renal function, and mortality among hemodialysis patients in the Dialysis Outcomes and Practice Pattern Study (DOPPS). Am J Kidney Dis. 2007;49(3):426-431. 16. 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. 17. Lameire N, Van Biesen W. The initiation of renalreplacement therapy—just-in-time delivery. N Engl J Med. 2010;363(7):678-680. 18. Rosansky SJ. Early dialysis initiation, a look from the rearview mirror to what’s ahead. Clin J Am Soc Nephrol. 2014;9(2):222-224. 19. Tattersall J, Dekker F, Heimburger O, et al. When to start dialysis: updated guidance following publication of the Initiating Dialysis Early and Late (IDEAL) study. Nephrol Dial Transplant. 2011;26(7):2082-2086. 20. Rubin HR, Fink NE, Plantinga LC, et al. Patient ratings of dialysis care with peritoneal dialysis vs hemodialysis. JAMA. 2004;291(6):697-703. 21. Jassal SV, Krishna G, Mallick NP, et al. Attitudes of British Isles nephrologists towards dialysis modality selection: a questionnaire study. Nephrol Dial Transplant. 2002;17(3): 474-477. 22. Vanholder R, Davenport A, Hannedouche T, et al. Reimbursement of dialysis: a comparison of seven countries. J Am Soc Nephrol. 2012;23(8):1291-1298. 23. 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.
167
