Comment
Renal replacement therapy: how can we contain the costs?
www.thelancet.com Vol 383 May 24, 2014
low rates of living donation, and vice versa, while many countries have poor rates for both forms of transplantation. Measures such as pre-emptive donor-exchange programmes, fair reimbursement for living donors, increased retrieval of deceased-donor organs by implementation of presumed consent, and acceptance of expanded donation could all increase transplantation rates. Access to transplantation should be equally guaranteed to all valid candidates, while precluding commercial exploitation. All forms of dialysis outside hospital are more cost effective than is hospital-based dialysis,4 mainly because of reduced labour and transportation costs. Although preferred by patients6 and physicians,7 these modalities are for unclear reasons not always favourably reimbursed. However, fair financial compensation will propagate outside-hospital strategies only when accompanied by education of medical and paramedical professionals.8 Several systems offer extra reimbursement for highrisk patients. This policy could, however, stimulate enrolment of patients who might not benefit from treatment, such as the fast-growing group of frail elderly people. Generally, the gain in survival and quality of life from RRT is disappointing in this population.9,10 Although possibly leading to a complex debate about ethics, scoring systems could eventually help to select patients who might benefit most from RRT.11
See Editorial page 1782 See Comment pages 1785 and 1786
Science Photo Library
The final stages of failing kidney function (known as end-stage renal disease) jeopardise survival and quality of life, but can be countered therapeutically by renal replacement therapy (RRT). Kidney transplantation offers the best outcomes but is not always possible, and even suitable transplantation candidates are often confronted with long waiting times. The alternative is dialysis—either haemodialysis, whereby blood from the patient is rinsed by an artificial kidney, or peritoneal dialysis, whereby rinsing occurs via the intra-abdominal peritoneal membrane. Although RRT is lifesaving in patients with advanced kidney failure, its cost-utility (ie, the ratio of the percentage of the global population reached to the percentage of health-care budget absorbed, taking into account quality of life) remains low. Even in wealthy countries, the provision of RRT constitutes a heavy burden on health systems. In countries or regions where reimbursement of RRT per se is partial or even non-existent, RRT can ruin families who attempt to extend the lives of their relatives.1 Constraints on capital and human resources, combined with a rapidly escalating burden of chronic kidney disease, have forced almost all countries to revise the organisation and reimbursement of RRT. These attempts are, however, countered by a rising prevalence due to therapeutic improvements, treatment of older patients and those with comorbidities, and premature initiation of RRT. Appropriate patient selection and timing of dialysis initiation, essentially restricted to symptomatic patients, might thus bring socioeconomic benefits.2 The composite cost of dialysis is mainly made up by the treatment itself (including disposables, machines, accommodation, electricity, water, and nursing time) along with RRT-related medication, transportation, and indirect costs from complications, additional hospital admissions, and interventions.3 Reimbursement does not suggest true costs, and markedly differs between countries and strategies.4,5 Generally, transplantation has the highest costutility,5 but organ shortage and (despite availability of low-cost alternatives) cost of immunosuppressive drugs remain limiting factors. Countries with high rates of deceased-donor graft harvesting have
1783
Comment
Several countries have introduced bundling of expenses with both positive effects12 (ie, more rational prescriptions, and consultation among stakeholders) and negative effects13 (ie, cherry picking and favouring of cheaper therapies at the expense of quality). The clinical effects of bundling systems need further validation. Because of its substantial use of water, electricity, and plastics, dialysis is not favourable for the environment. More environmentally friendly solutions should be considered and might at the same time reduce costs— eg, through recycling of rejected reverse-osmosis water, or recirculation of spent dialysate. Although controversial, reuse can improve cost-effectiveness while reducing production of material waste, but safety should absolutely be guaranteed. Retardation of kidney disease progression might obviate the need for RRT, but necessitates timely identification of the patients at risk. Current risk markers (ie, estimated glomerular filtration rate and albuminuria) are not specific enough, resulting in a population selected for treatment greatly exceeding the patients who really benefit. Introduction of more appropriate markers would narrow the number needed to treat, but probably at the expense of the cost of the test method. Because chronic renal disease is associated with comorbidities such as obesity, diabetes, and hypertension, education about healthy lifestyles is probably more cost effective than is screening the global population to define the need for pharmacological intervention, and should become a primary goal. Screening itself should be focused on risk populations, such as those suffering from diabetes or hypertension, or with a history of familial kidney disease or kidney damage. Whatever the approach, screening and prevention policies might miss their target in the highest-risk groups (eg, people with little education), and could even result in a counterintuitive rise of RRT, by delaying rather than eliminating its need if more patients with chronic kidney disease survive until endstage disease is reached. Of note, some chronic kidney diseases, especially nondiabetic proteinuric nephropathies, can be stabilised by multipharmacological strategies, but at present this group represents only a small proportion of the patients with chronic kidney disease. Although these problems necessitate a cultural change in developed countries, the situation is even 1784
more precarious in developing countries, where therapies are only partly reimbursed or not reimbursed at all, transplantation is rare, and disposables are paid for in cash. This situation has a negative effect particularly on the implementation of peritoneal dialysis, because (as in many African countries) local production is non-existent, necessitating the importation of dialysis material. On the one hand, cheap labour might invalidate some of the therapeutic paradigms of developed countries, but, on the other, it might be counterbalanced by the scarcity of experienced professionals. In general, the focus should be shifted from expensive sophisticated treatment strategies, often without proven benefit, to approaches that can help large numbers of patients at acceptable cost. Expensive therapies should be reimbursed only when the evidence of their cost-utility is robust. Reimbursement strategies incentivising fair modality distribution, correct implementation of conservative care, and timely start of RRT can offer a scientifically and ethically correct solution with socioeconomic savings. A change in philosophy from market and hospital oriented nephrology to society and patient oriented nephrology is imperative to maintain sustainable treatment of advanced kidney disease for all patients at risk, with equity in access to all therapies for all classes of patients with chronic kidney disease, including the socially deprived. *Raymond Vanholder, Wim Van Biesen, Norbert Lameire Renal Division, Section of Internal Medicine, Ghent University Hospital, B9000 Ghent, Belgium (RV, WVB); and Ghent University Hospital, Ghent, Belgium (NL) [email protected] RV has received research grants from Fresenius Medical Care, Baxter Healthcare, Gambro, Roche, and Amgen; has received speaker honoraria from Amgen; and is President of the European Renal Association–European Dialysis and Transplant Asoociation. WVB has received research grants and speaker honoraria from Fresenius Medical Care, Baxter Healthcare, and Gambro. NL declares no competing interests. 1 2 3 4
5
Swanepoel CR, Wearne N, Okpechi IG. Nephrology in Africa—not yet uhuru. Nat Rev Nephrol 2013; 9: 610–22. Lameire N, Van Biesen W. The initiation of renal-replacement therapy— just-in-time delivery. N Engl J Med 2010; 363: 678–80. Icks A, Haastert B, GandjourA, et al. Costs of dialysis—a regional population-based analysis. Nephrol Dial Transplant 2010; 25: 1647–52. Vanholder R, Davenport A, Hannedouche T, et al. Reimbursement of dialysis: a comparison of seven countries. J Am Soc Nephrol 2012; 23: 1291–98. Laupacis A, Keown P, Pus N, et al. A study of the quality of life and cost-utility of renal transplantation. Kidney Int 1996; 50: 235–42.
www.thelancet.com Vol 383 May 24, 2014
Comment
6
7
8
9
Rubin HR, Fink NE, Plantinga LC, Sadler JH, Kliger AS, Powe NR. Patient ratings of dialysis care with peritoneal dialysis vs hemodialysis. JAMA 2004; 291: 697–703. Jassal SV, Krishna G, Mallick NP, Mendelssohn DC. Attitudes of British Isles nephrologists towards dialysis modality selection: a questionnaire study. Nephrol Dial Transplant 2002; 17: 474–77. Kleophas W, Reichel H. International study of health care organization and financing: development of renal replacement therapy in Germany. Int J Health Care Finance Econ 2007; 7: 185–200. Murtagh FE, Marsh JE, Donohoe P, Ekbal NJ, Sheerin NS, Harris FE. Dialysis or not? A comparative survival study of patients over 75 years with chronic kidney disease stage 5. Nephrol Dial Transplant 2007; 22: 1955–62.
10 11
12
13
Robinson BM, Zhang J, Morgenstern H, et al. Worldwide, mortality risk is high soon after initiation of hemodialysis. Kidney Int 2014; 85: 158–65. Couchoud C, Labeeuw M, Moranne O, et al. A clinical score to predict 6-month prognosis in elderly patients starting dialysis for end-stage renal disease. Nephrol Dial Transplant 2009; 24: 1553–61. Ponce P, Marcelli D, GuerreiroA, et al. Converting to a capitation system for dialysis payment—the Portuguese experience. Blood Purif 2012; 34: 313–24. Desai AA, Bolus R, Nissenson A, et al. Is there “cherry picking” in the ESRD Program? Perceptions from a dialysis provider survey. Clin J Am Soc Nephrol 2009; 4: 772–77.
Acute kidney injury is increasingly common in children admitted to hospital, with an incidence of almost 20% in children who require intensive care.1 Although the long-term effects of acute kidney injury continue to be debated,2 in the short-term it increases resource use, length of stay in hospital, and risk of death—all effects that become more pronounced in children who require renal replacement therapy.3,4 In The Lancet, Claudio Ronco and colleagues5 report the development of a new machine specifically designed to treat the smallest children in need of extracorporeal therapy, including children with acute kidney injury. Peritoneal dialysis is generally preferred to extracorporeal methods such as intermittent haemodialysis or continuous renal replacement therapy (CRRT) in neonates and young children who develop acute kidney injury or end-stage kidney disease that requires renal replacement therapy.6 The reasons for this preference are that peritoneal dialysis does not require large-diameter vascular access, can be haemodynamically less taxing than extracorporeal therapy, and is technically easier to do. However, some children are poor candidates for peritoneal dialysis, such as those with a history of abdominal surgery, severe anasarca, or who present with toxic ingestions or inborn errors of metabolism that require rapid solute removal.7,8 In the past few years, dialysis manufacturers have developed smaller filters for use in children receiving intermittent haemodialysis or CRRT. However, because the dialysis machines were designed for adult use, smaller children often need blood priming, which increases the risks of hypotension from bradykinin release and cardiac dysfunction secondary to chelation www.thelancet.com Vol 383 May 24, 2014
of calcium by the citrate anticoagulant used in banked blood.9 The high blood-flow requirements of adult machines also necessitate large-bore vascular access, which can be challenging to insert surgically and can permanently damage central vessels.10 There is a clear unmet technical need for paediatric-specific dialysis treatment. Ronco and colleagues5 describe their design, development, and testing of a new CRRT machine, named CARPEDIEM (Cardio-Renal Pediatric Dialysis Emergency Machine), specifically for use in neonates and infants. This work expands on the group’s previous experience doing continuous arteriovenous haemofiltration with a minifilter that they designed and used to treat four very young infants (younger than 12 days) with acute kidney injury.11 The investigators should be commended for their efforts in this important area and for their use of several collaborators, including non-profit funding support. Importantly, they report the first ever patient treated with their new machine, a neonate who developed oligoanuric acute kidney injury and several metabolic derangements secondary to severe haemorrhagic shock. The child survived the neonatal period, an outcome that would have been less likely just several years ago, without the new machine or improvements in overall neonatal care. In addition to having the capability to provide several forms of extracorporeal therapy (CRRT, plasmapheresis, and albumin dialysis), the small volume of the CARPEDIEM circuit does not require blood priming. The importance of limiting exposure to blood products, which decreases the risk of developing sensitising antibodies, should not be underestimated in children
Science Photo Library
Extracorporeal therapy for the smallest children
See Articles page 1807 See Comment pages 1783 and 1786
1785
Renal replacement therapy: how can we contain the costs?
www.thelancet.com Vol 383 May 24, 2014
low rates of living donation, and vice versa, while many countries have poor rates for both forms of transplantation. Measures such as pre-emptive donor-exchange programmes, fair reimbursement for living donors, increased retrieval of deceased-donor organs by implementation of presumed consent, and acceptance of expanded donation could all increase transplantation rates. Access to transplantation should be equally guaranteed to all valid candidates, while precluding commercial exploitation. All forms of dialysis outside hospital are more cost effective than is hospital-based dialysis,4 mainly because of reduced labour and transportation costs. Although preferred by patients6 and physicians,7 these modalities are for unclear reasons not always favourably reimbursed. However, fair financial compensation will propagate outside-hospital strategies only when accompanied by education of medical and paramedical professionals.8 Several systems offer extra reimbursement for highrisk patients. This policy could, however, stimulate enrolment of patients who might not benefit from treatment, such as the fast-growing group of frail elderly people. Generally, the gain in survival and quality of life from RRT is disappointing in this population.9,10 Although possibly leading to a complex debate about ethics, scoring systems could eventually help to select patients who might benefit most from RRT.11
See Editorial page 1782 See Comment pages 1785 and 1786
Science Photo Library
The final stages of failing kidney function (known as end-stage renal disease) jeopardise survival and quality of life, but can be countered therapeutically by renal replacement therapy (RRT). Kidney transplantation offers the best outcomes but is not always possible, and even suitable transplantation candidates are often confronted with long waiting times. The alternative is dialysis—either haemodialysis, whereby blood from the patient is rinsed by an artificial kidney, or peritoneal dialysis, whereby rinsing occurs via the intra-abdominal peritoneal membrane. Although RRT is lifesaving in patients with advanced kidney failure, its cost-utility (ie, the ratio of the percentage of the global population reached to the percentage of health-care budget absorbed, taking into account quality of life) remains low. Even in wealthy countries, the provision of RRT constitutes a heavy burden on health systems. In countries or regions where reimbursement of RRT per se is partial or even non-existent, RRT can ruin families who attempt to extend the lives of their relatives.1 Constraints on capital and human resources, combined with a rapidly escalating burden of chronic kidney disease, have forced almost all countries to revise the organisation and reimbursement of RRT. These attempts are, however, countered by a rising prevalence due to therapeutic improvements, treatment of older patients and those with comorbidities, and premature initiation of RRT. Appropriate patient selection and timing of dialysis initiation, essentially restricted to symptomatic patients, might thus bring socioeconomic benefits.2 The composite cost of dialysis is mainly made up by the treatment itself (including disposables, machines, accommodation, electricity, water, and nursing time) along with RRT-related medication, transportation, and indirect costs from complications, additional hospital admissions, and interventions.3 Reimbursement does not suggest true costs, and markedly differs between countries and strategies.4,5 Generally, transplantation has the highest costutility,5 but organ shortage and (despite availability of low-cost alternatives) cost of immunosuppressive drugs remain limiting factors. Countries with high rates of deceased-donor graft harvesting have
1783
Comment
Several countries have introduced bundling of expenses with both positive effects12 (ie, more rational prescriptions, and consultation among stakeholders) and negative effects13 (ie, cherry picking and favouring of cheaper therapies at the expense of quality). The clinical effects of bundling systems need further validation. Because of its substantial use of water, electricity, and plastics, dialysis is not favourable for the environment. More environmentally friendly solutions should be considered and might at the same time reduce costs— eg, through recycling of rejected reverse-osmosis water, or recirculation of spent dialysate. Although controversial, reuse can improve cost-effectiveness while reducing production of material waste, but safety should absolutely be guaranteed. Retardation of kidney disease progression might obviate the need for RRT, but necessitates timely identification of the patients at risk. Current risk markers (ie, estimated glomerular filtration rate and albuminuria) are not specific enough, resulting in a population selected for treatment greatly exceeding the patients who really benefit. Introduction of more appropriate markers would narrow the number needed to treat, but probably at the expense of the cost of the test method. Because chronic renal disease is associated with comorbidities such as obesity, diabetes, and hypertension, education about healthy lifestyles is probably more cost effective than is screening the global population to define the need for pharmacological intervention, and should become a primary goal. Screening itself should be focused on risk populations, such as those suffering from diabetes or hypertension, or with a history of familial kidney disease or kidney damage. Whatever the approach, screening and prevention policies might miss their target in the highest-risk groups (eg, people with little education), and could even result in a counterintuitive rise of RRT, by delaying rather than eliminating its need if more patients with chronic kidney disease survive until endstage disease is reached. Of note, some chronic kidney diseases, especially nondiabetic proteinuric nephropathies, can be stabilised by multipharmacological strategies, but at present this group represents only a small proportion of the patients with chronic kidney disease. Although these problems necessitate a cultural change in developed countries, the situation is even 1784
more precarious in developing countries, where therapies are only partly reimbursed or not reimbursed at all, transplantation is rare, and disposables are paid for in cash. This situation has a negative effect particularly on the implementation of peritoneal dialysis, because (as in many African countries) local production is non-existent, necessitating the importation of dialysis material. On the one hand, cheap labour might invalidate some of the therapeutic paradigms of developed countries, but, on the other, it might be counterbalanced by the scarcity of experienced professionals. In general, the focus should be shifted from expensive sophisticated treatment strategies, often without proven benefit, to approaches that can help large numbers of patients at acceptable cost. Expensive therapies should be reimbursed only when the evidence of their cost-utility is robust. Reimbursement strategies incentivising fair modality distribution, correct implementation of conservative care, and timely start of RRT can offer a scientifically and ethically correct solution with socioeconomic savings. A change in philosophy from market and hospital oriented nephrology to society and patient oriented nephrology is imperative to maintain sustainable treatment of advanced kidney disease for all patients at risk, with equity in access to all therapies for all classes of patients with chronic kidney disease, including the socially deprived. *Raymond Vanholder, Wim Van Biesen, Norbert Lameire Renal Division, Section of Internal Medicine, Ghent University Hospital, B9000 Ghent, Belgium (RV, WVB); and Ghent University Hospital, Ghent, Belgium (NL) [email protected] RV has received research grants from Fresenius Medical Care, Baxter Healthcare, Gambro, Roche, and Amgen; has received speaker honoraria from Amgen; and is President of the European Renal Association–European Dialysis and Transplant Asoociation. WVB has received research grants and speaker honoraria from Fresenius Medical Care, Baxter Healthcare, and Gambro. NL declares no competing interests. 1 2 3 4
5
Swanepoel CR, Wearne N, Okpechi IG. Nephrology in Africa—not yet uhuru. Nat Rev Nephrol 2013; 9: 610–22. Lameire N, Van Biesen W. The initiation of renal-replacement therapy— just-in-time delivery. N Engl J Med 2010; 363: 678–80. Icks A, Haastert B, GandjourA, et al. Costs of dialysis—a regional population-based analysis. Nephrol Dial Transplant 2010; 25: 1647–52. Vanholder R, Davenport A, Hannedouche T, et al. Reimbursement of dialysis: a comparison of seven countries. J Am Soc Nephrol 2012; 23: 1291–98. Laupacis A, Keown P, Pus N, et al. A study of the quality of life and cost-utility of renal transplantation. Kidney Int 1996; 50: 235–42.
www.thelancet.com Vol 383 May 24, 2014
Comment
6
7
8
9
Rubin HR, Fink NE, Plantinga LC, Sadler JH, Kliger AS, Powe NR. Patient ratings of dialysis care with peritoneal dialysis vs hemodialysis. JAMA 2004; 291: 697–703. Jassal SV, Krishna G, Mallick NP, Mendelssohn DC. Attitudes of British Isles nephrologists towards dialysis modality selection: a questionnaire study. Nephrol Dial Transplant 2002; 17: 474–77. Kleophas W, Reichel H. International study of health care organization and financing: development of renal replacement therapy in Germany. Int J Health Care Finance Econ 2007; 7: 185–200. Murtagh FE, Marsh JE, Donohoe P, Ekbal NJ, Sheerin NS, Harris FE. Dialysis or not? A comparative survival study of patients over 75 years with chronic kidney disease stage 5. Nephrol Dial Transplant 2007; 22: 1955–62.
10 11
12
13
Robinson BM, Zhang J, Morgenstern H, et al. Worldwide, mortality risk is high soon after initiation of hemodialysis. Kidney Int 2014; 85: 158–65. Couchoud C, Labeeuw M, Moranne O, et al. A clinical score to predict 6-month prognosis in elderly patients starting dialysis for end-stage renal disease. Nephrol Dial Transplant 2009; 24: 1553–61. Ponce P, Marcelli D, GuerreiroA, et al. Converting to a capitation system for dialysis payment—the Portuguese experience. Blood Purif 2012; 34: 313–24. Desai AA, Bolus R, Nissenson A, et al. Is there “cherry picking” in the ESRD Program? Perceptions from a dialysis provider survey. Clin J Am Soc Nephrol 2009; 4: 772–77.
Acute kidney injury is increasingly common in children admitted to hospital, with an incidence of almost 20% in children who require intensive care.1 Although the long-term effects of acute kidney injury continue to be debated,2 in the short-term it increases resource use, length of stay in hospital, and risk of death—all effects that become more pronounced in children who require renal replacement therapy.3,4 In The Lancet, Claudio Ronco and colleagues5 report the development of a new machine specifically designed to treat the smallest children in need of extracorporeal therapy, including children with acute kidney injury. Peritoneal dialysis is generally preferred to extracorporeal methods such as intermittent haemodialysis or continuous renal replacement therapy (CRRT) in neonates and young children who develop acute kidney injury or end-stage kidney disease that requires renal replacement therapy.6 The reasons for this preference are that peritoneal dialysis does not require large-diameter vascular access, can be haemodynamically less taxing than extracorporeal therapy, and is technically easier to do. However, some children are poor candidates for peritoneal dialysis, such as those with a history of abdominal surgery, severe anasarca, or who present with toxic ingestions or inborn errors of metabolism that require rapid solute removal.7,8 In the past few years, dialysis manufacturers have developed smaller filters for use in children receiving intermittent haemodialysis or CRRT. However, because the dialysis machines were designed for adult use, smaller children often need blood priming, which increases the risks of hypotension from bradykinin release and cardiac dysfunction secondary to chelation www.thelancet.com Vol 383 May 24, 2014
of calcium by the citrate anticoagulant used in banked blood.9 The high blood-flow requirements of adult machines also necessitate large-bore vascular access, which can be challenging to insert surgically and can permanently damage central vessels.10 There is a clear unmet technical need for paediatric-specific dialysis treatment. Ronco and colleagues5 describe their design, development, and testing of a new CRRT machine, named CARPEDIEM (Cardio-Renal Pediatric Dialysis Emergency Machine), specifically for use in neonates and infants. This work expands on the group’s previous experience doing continuous arteriovenous haemofiltration with a minifilter that they designed and used to treat four very young infants (younger than 12 days) with acute kidney injury.11 The investigators should be commended for their efforts in this important area and for their use of several collaborators, including non-profit funding support. Importantly, they report the first ever patient treated with their new machine, a neonate who developed oligoanuric acute kidney injury and several metabolic derangements secondary to severe haemorrhagic shock. The child survived the neonatal period, an outcome that would have been less likely just several years ago, without the new machine or improvements in overall neonatal care. In addition to having the capability to provide several forms of extracorporeal therapy (CRRT, plasmapheresis, and albumin dialysis), the small volume of the CARPEDIEM circuit does not require blood priming. The importance of limiting exposure to blood products, which decreases the risk of developing sensitising antibodies, should not be underestimated in children
Science Photo Library
Extracorporeal therapy for the smallest children
See Articles page 1807 See Comment pages 1783 and 1786
1785
