- Email: [email protected]
A wearable haemodialysis device
Correspondence
The CTSU has a policy of staff not accepting fees, honoraria, or consultancies. The CTSU is, however, involved in clinical trials of cholesterol modification therapy with funding from the UK Medical Research Council, the British Heart Foundation, and various companies (Merck, Schering, Solvay) as research grants to (and administered by) Oxford University.
*Sarah Lewington, Gary Whitlock, Robert Clarke, Paul Sherliker, Jonathan Emberson, Rory Collins, for the PSC collaborators [email protected] Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Richard Doll Building, University of Oxford, Oxford OX3 7LF, UK 1
2
3
4
5
The PROSPER Study Group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623–30. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267–78. Alsheikh AA, Maddukuri PV, Han H, Karas RH. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. J Am Coll Cardiol 2007; 50: 409–18. The Stroke Prevention by aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355: 549–59. Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 2007; 370: 1829–23.
The results of the meta-analysis by the Prospective Studies Collaboration (PSC)1 might be the best suggestion yet that the effect of lipid profiles on cardiovascular mortality is a surrogate for the independent effect of sedentary behaviour on this risk. Until now, evidence of the association between physical activity, lowered LDL cholesterol, and increased HDL cholesterol, and the accepted preventive role of overall energy expenditure on ischaemic heart disease has been potentially distorted by the usual attribution of a relative risk of 1 to the less active group, even though it might include people who are not physiologically sedentary. The PSC study sheds light on the ratio of total cholesterol to HDL cholesterol—the lipid-profile index that physical activwww.thelancet.com Vol 371 April 5, 2008
ity is most likely to affect—as the strongest predictor of ischaemic heart disease in all age-groups. Also, it reports independent effects of HDL and non-HDL cholesterol on ischaemic heart disease mortality, putatively representing the effect of practising an activity with sufficient intensity and frequency, and having an energy expenditure of any source, respectively. Much of the predictive value of the blood-cholesterol profile could therefore be physical activity patterns. The study of sedentary behaviour as a separate and not functionally opposite construct and its influence on cardiovascular risk, whether independent or not from its effect on biomarkers, would benefit from more attention.
the study [Xcorporeal] had no role in the design of the study and interview questions, data collection, data analysis, data interpretation, writing, or revising of the report“ with the fact that the second author, Victor Gura, “is a director of Xcorporeal Inc, and is their chief medical and scientific officer”. I declare that I have no conflict of interest.
Stanley Shaldon [email protected] 25 le Michelangelo, 7 Avenue des Papalins, Monaco 98000 1
2
We declare that we have no conflict of interest.
*Sophie Antoine-Jonville, Olivier Hue
3
[email protected] Laboratoire ACTES, Université des Antilles et de la Guyane, BP 250, 97157 Pointe-à-Pitre Cédex, Guadeloupe, France 1.
Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 2007; 370: 1829–39.
A wearable haemodialysis device Andrew Davenport and colleagues (Dec 15, p 2005)1 surprisingly do not mention conventional home haemodialysis as a way to increase the amount of treatment given to patients, given that overnight unattended home haemodialysis has been available in the UK since 1964.2,3 Davenport and colleagues prefer a new technique using outmoded, inefficient, and largely abandoned sorbent technology with charcoal, urease, and zirconium.1 The portability of this 5 kg belt can be limited by the dislocation of the blood access fistula needles. The removal of salt and water by “continuous ambulatory ultrafiltration”4 was first reported in 1980.5 Finally, I find it difficult to reconcile the declaration that “The sponsors of
3
4
Davenport A, Gura V, Ronco C, et al. A wearable haemodialysis device for patients with endstage renal failure: a pilot study. Lancet 2007; 370: 2005–10. Shaldon S. Experience to date with home hemodialysis. Proceedings of the Working Conference on Chronic Dialysis; Seattle, WA, USA; Dec 3–5, 1964. Seattle: University of Washington Press, 1964: 40–41. Baillod R, Comty C, Shaldon S. Over-night haemodialysis in the home. Proc Eur Dial Transplant Assoc 1965; 2: 99–109. Gura V, Ronco C, Nalesso F, et al. A wearable hemofilter for continuous ambulatory ultrafiltration. Kidney Int 2008; 73: 497–502. Shaldon S, Beau MC, Deschodt G, et al. Continuous ambulatory haemofiltration. Trans Am Soc Artif Intern Organs 1980; 26: 210–12.
Andrew Davenport and colleagues1 are to be congratulated on their technological achievement of producing a complete haemodialysis system that weighs only 5 kg. However, in their enthusiasm, and in that of Garabed Eknoyan (p 1977),2 they neglect the progress that has been achieved by chronic peritoneal dialysis. This technique can be used in about half of patients. It fulfils the requirements of continuous treatment and active participation of patient, and requires no anticoagulation. The additional weight burden for patients is only 2–3 kg. Where urea clearance is concerned, treatment with the wearable haemodialysis device for 8 h, 6 days per week will result in a weekly urea clearance corrected for total body water (Kt/Vurea) of 1·7/week, which fulfils the requirements of the European Best Practice Guidelines for Peritoneal Dialysis,3 but is much lower than the recommendations for haemodialysis. 1163
Correspondence
Science Photo Library
Many observational studies with corrections for case-mix4 and also one randomised controlled trial5 have shown that survival on peritoneal dialysis is superior to that on haemodialysis, at least during the first years of treatment, probably because of better preservation of residual renal function and fewer hypovolaemic episodes. Therefore, I consider it inappropriate to discuss the potential future role of the wearable haemodialysis device without even mentioning peritoneal dialysis and to publish (twice) a photograph of a happy-looking patient wearing a 5 kg girdle. Each dialysis modality can provide similar pictures and the patient involved does not necessarily receive the best dialysis treatment. Any modification of haemodialysis to make it more continuous should be welcomed, but such modifications should take the excellent results of modern peritoneal dialysis into account. I declare that I have no conflict of interest.
Raymond T Krediet [email protected] Division of Nephrology, Department of Medicine, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, Netherlands 1
2 3
4
5
Davenport A, Gura V, Ronco C, Beizai M, Ezon C, Rambod E. A wearable haemodialysis device for patients with end-stage renal failure: a pilot study. Lancet 2007; 370: 2005–10. Eknoyan G. Artificial kidneys: progress and promise. Lancet 2007; 370: 1977–78. European Best Practice Guidelines Working Group on Peritoneal Dialysis. European best practice guidelines for peritoneal dialysis. Nephrol Dial Transplant 2005; 20 (suppl 9): 1–27. Krediet RT, Boeschoten EW, Dekker FW. Why is the evidence favouring hemodialysis over peritoneal dialysis misleading? Semin Dial 2007; 20: 205–08. Korevaar JC, Feith GW, Dekker FW, et al. Effect of starting hemodialysis compared with peritoneal dialysis in patients new on dialysis treatment: a randomized controlled trial. Kidney Int 2002; 62: 1046–53.
Authors’ reply Stanley Shaldon and Rosemarie Baillod started a home haemodialysis programme based at the Royal Free Hospital in the UK, which grew and provided treatment to more than 90 patients at its peak in the 1970s. However, over time, the number 1164
of home haemodialysis patients treated by the Royal Free steadily declined to a nadir of just 11 last year. This is not because home haemodialysis is by any means an inferior treatment. It reflects changes, not only in patient demographics and increasing comorbidities, but also the development and provision of both main and satellite haemodialysis facilities within the UK. This downward trend in home haemodialysis is despite a policy statement from the National Institute for Health and Clinical Excellence (NICE) in 2002, which advocated home haemodialysis as an important treatment option for patients with chronic kidney disease (CKD).1 Although more than 100 000 patients are treated by peritoneal dialysis worldwide, there similarly has been a decline in the proportion of patients with CKD treated by peritoneal dialysis, particularly in the USA. Indeed, there is now a Canadian Government initiative to try to increase the proportion of patients treated by peritoneal dialysis in Ontario, where numbers have slipped down to around 18%, despite Toronto being one of the major pioneering centres behind the development of peritoneal dialysis.2 Thus, in both North America and Europe, most patients with CKD are treated by intermittent thrice weekly haemodialysis in a main hospital, and an ever-increasing number of satellite dialysis centres. Thus, as currently practised, haemodialysis is a very expensive treatment. In addition, owing to time constraints, and the intermittent nature of the therapy, several kilos of fluid often have to be removed over a relatively short period of time, potentially resulting in hypotension. A UK audit3 reported that some 15% or so of outpatient haemodialysis treatments were complicated by hypotension, requiring active fluid resuscitation. Furthermore, there is mounting evidence to show the benefits of daily haemodialysis. Unfortunately, there is currently no
logistical, practical, or economically feasible way to provide such therapy to most patients with CKD. To try to improve not only the quality of care delivered, but also patients’ quality of life, we have been working to develop wearable devices that would allow for an outpatientbased treatment for both chronic heart failure4 and end-stage kidney disease.5 As such we have recently reported our first pilot studies. Our pilot trial of the wearable artificial haemodialysis device was approved by the UK Medicines Health Regulatory Authority (MHRA), and as such the design of the trial, in terms of the number of patients, duration of therapy, and safety assessments was stipulated by the MHRA. Samples were analysed in the routine laboratories at the Royal Free Hospital, and as such the data were collected by the hospital laboratory data management system. Data were analysed by AD, who wrote the initial drafts. We wish to thank our sponsors, XCorporeal Inc and the Special Trustees of the Royal Free Hospital, who made this study possible. VG is chief medical and scientific officer to Xcorporeal Inc, Los Angeles, CA, USA.
*Andrew Davenport, Claudio Ronco, Victor Gura [email protected] Royal Free and University College Medical School, London NW3 2PF, UK (AD); Divisione de Nefrologia, Ospedale San Bortolo, Vicenza, Italy (CR); and Cedars Sinai Medical Center, University of California Los Angeles, Los Angeles, CA, USA (VG) 1
2
3
4
5
National Institute for Clinical Excellence. Guidance on home versus hospital haemodialysis for patients with end-stage renal failure. London: NICE, 2002. http://www. nice.org.uk/nicemedia/pdf/HvH_full_ guidance.pdf (accessed March 10, 2008). Oreopoulos DG, Coleman S, Doyle E. Reversing the decreasing peritoneal dialysis (PD) trend in Ontario: a government initiative to increase PD use in Ontario to 30% by 2010. Perit Dial Int 2007; 27: 489–95. Davenport A, Cox C, Thuraisingham R. Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension. Kidney Int 2008; 73: 759–64. Gura V, Ronco C, Nalesso F, et al. A wearable hemofilter for continuous ambulatory ultrafiltration. Kidney Int 2008; 73: 497–502. Davenport A, Gura V, Ronco C, Beizai M, Ezon C, Rambod E. A wearable haemodialysis device for patients with end-stage renal failure: a pilot study. Lancet 2007; 370: 2005–10.
www.thelancet.com Vol 371 April 5, 2008
The CTSU has a policy of staff not accepting fees, honoraria, or consultancies. The CTSU is, however, involved in clinical trials of cholesterol modification therapy with funding from the UK Medical Research Council, the British Heart Foundation, and various companies (Merck, Schering, Solvay) as research grants to (and administered by) Oxford University.
*Sarah Lewington, Gary Whitlock, Robert Clarke, Paul Sherliker, Jonathan Emberson, Rory Collins, for the PSC collaborators [email protected] Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Richard Doll Building, University of Oxford, Oxford OX3 7LF, UK 1
2
3
4
5
The PROSPER Study Group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360: 1623–30. Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267–78. Alsheikh AA, Maddukuri PV, Han H, Karas RH. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. J Am Coll Cardiol 2007; 50: 409–18. The Stroke Prevention by aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355: 549–59. Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 2007; 370: 1829–23.
The results of the meta-analysis by the Prospective Studies Collaboration (PSC)1 might be the best suggestion yet that the effect of lipid profiles on cardiovascular mortality is a surrogate for the independent effect of sedentary behaviour on this risk. Until now, evidence of the association between physical activity, lowered LDL cholesterol, and increased HDL cholesterol, and the accepted preventive role of overall energy expenditure on ischaemic heart disease has been potentially distorted by the usual attribution of a relative risk of 1 to the less active group, even though it might include people who are not physiologically sedentary. The PSC study sheds light on the ratio of total cholesterol to HDL cholesterol—the lipid-profile index that physical activwww.thelancet.com Vol 371 April 5, 2008
ity is most likely to affect—as the strongest predictor of ischaemic heart disease in all age-groups. Also, it reports independent effects of HDL and non-HDL cholesterol on ischaemic heart disease mortality, putatively representing the effect of practising an activity with sufficient intensity and frequency, and having an energy expenditure of any source, respectively. Much of the predictive value of the blood-cholesterol profile could therefore be physical activity patterns. The study of sedentary behaviour as a separate and not functionally opposite construct and its influence on cardiovascular risk, whether independent or not from its effect on biomarkers, would benefit from more attention.
the study [Xcorporeal] had no role in the design of the study and interview questions, data collection, data analysis, data interpretation, writing, or revising of the report“ with the fact that the second author, Victor Gura, “is a director of Xcorporeal Inc, and is their chief medical and scientific officer”. I declare that I have no conflict of interest.
Stanley Shaldon [email protected] 25 le Michelangelo, 7 Avenue des Papalins, Monaco 98000 1
2
We declare that we have no conflict of interest.
*Sophie Antoine-Jonville, Olivier Hue
3
[email protected] Laboratoire ACTES, Université des Antilles et de la Guyane, BP 250, 97157 Pointe-à-Pitre Cédex, Guadeloupe, France 1.
Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 2007; 370: 1829–39.
A wearable haemodialysis device Andrew Davenport and colleagues (Dec 15, p 2005)1 surprisingly do not mention conventional home haemodialysis as a way to increase the amount of treatment given to patients, given that overnight unattended home haemodialysis has been available in the UK since 1964.2,3 Davenport and colleagues prefer a new technique using outmoded, inefficient, and largely abandoned sorbent technology with charcoal, urease, and zirconium.1 The portability of this 5 kg belt can be limited by the dislocation of the blood access fistula needles. The removal of salt and water by “continuous ambulatory ultrafiltration”4 was first reported in 1980.5 Finally, I find it difficult to reconcile the declaration that “The sponsors of
3
4
Davenport A, Gura V, Ronco C, et al. A wearable haemodialysis device for patients with endstage renal failure: a pilot study. Lancet 2007; 370: 2005–10. Shaldon S. Experience to date with home hemodialysis. Proceedings of the Working Conference on Chronic Dialysis; Seattle, WA, USA; Dec 3–5, 1964. Seattle: University of Washington Press, 1964: 40–41. Baillod R, Comty C, Shaldon S. Over-night haemodialysis in the home. Proc Eur Dial Transplant Assoc 1965; 2: 99–109. Gura V, Ronco C, Nalesso F, et al. A wearable hemofilter for continuous ambulatory ultrafiltration. Kidney Int 2008; 73: 497–502. Shaldon S, Beau MC, Deschodt G, et al. Continuous ambulatory haemofiltration. Trans Am Soc Artif Intern Organs 1980; 26: 210–12.
Andrew Davenport and colleagues1 are to be congratulated on their technological achievement of producing a complete haemodialysis system that weighs only 5 kg. However, in their enthusiasm, and in that of Garabed Eknoyan (p 1977),2 they neglect the progress that has been achieved by chronic peritoneal dialysis. This technique can be used in about half of patients. It fulfils the requirements of continuous treatment and active participation of patient, and requires no anticoagulation. The additional weight burden for patients is only 2–3 kg. Where urea clearance is concerned, treatment with the wearable haemodialysis device for 8 h, 6 days per week will result in a weekly urea clearance corrected for total body water (Kt/Vurea) of 1·7/week, which fulfils the requirements of the European Best Practice Guidelines for Peritoneal Dialysis,3 but is much lower than the recommendations for haemodialysis. 1163
Correspondence
Science Photo Library
Many observational studies with corrections for case-mix4 and also one randomised controlled trial5 have shown that survival on peritoneal dialysis is superior to that on haemodialysis, at least during the first years of treatment, probably because of better preservation of residual renal function and fewer hypovolaemic episodes. Therefore, I consider it inappropriate to discuss the potential future role of the wearable haemodialysis device without even mentioning peritoneal dialysis and to publish (twice) a photograph of a happy-looking patient wearing a 5 kg girdle. Each dialysis modality can provide similar pictures and the patient involved does not necessarily receive the best dialysis treatment. Any modification of haemodialysis to make it more continuous should be welcomed, but such modifications should take the excellent results of modern peritoneal dialysis into account. I declare that I have no conflict of interest.
Raymond T Krediet [email protected] Division of Nephrology, Department of Medicine, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, Netherlands 1
2 3
4
5
Davenport A, Gura V, Ronco C, Beizai M, Ezon C, Rambod E. A wearable haemodialysis device for patients with end-stage renal failure: a pilot study. Lancet 2007; 370: 2005–10. Eknoyan G. Artificial kidneys: progress and promise. Lancet 2007; 370: 1977–78. European Best Practice Guidelines Working Group on Peritoneal Dialysis. European best practice guidelines for peritoneal dialysis. Nephrol Dial Transplant 2005; 20 (suppl 9): 1–27. Krediet RT, Boeschoten EW, Dekker FW. Why is the evidence favouring hemodialysis over peritoneal dialysis misleading? Semin Dial 2007; 20: 205–08. Korevaar JC, Feith GW, Dekker FW, et al. Effect of starting hemodialysis compared with peritoneal dialysis in patients new on dialysis treatment: a randomized controlled trial. Kidney Int 2002; 62: 1046–53.
Authors’ reply Stanley Shaldon and Rosemarie Baillod started a home haemodialysis programme based at the Royal Free Hospital in the UK, which grew and provided treatment to more than 90 patients at its peak in the 1970s. However, over time, the number 1164
of home haemodialysis patients treated by the Royal Free steadily declined to a nadir of just 11 last year. This is not because home haemodialysis is by any means an inferior treatment. It reflects changes, not only in patient demographics and increasing comorbidities, but also the development and provision of both main and satellite haemodialysis facilities within the UK. This downward trend in home haemodialysis is despite a policy statement from the National Institute for Health and Clinical Excellence (NICE) in 2002, which advocated home haemodialysis as an important treatment option for patients with chronic kidney disease (CKD).1 Although more than 100 000 patients are treated by peritoneal dialysis worldwide, there similarly has been a decline in the proportion of patients with CKD treated by peritoneal dialysis, particularly in the USA. Indeed, there is now a Canadian Government initiative to try to increase the proportion of patients treated by peritoneal dialysis in Ontario, where numbers have slipped down to around 18%, despite Toronto being one of the major pioneering centres behind the development of peritoneal dialysis.2 Thus, in both North America and Europe, most patients with CKD are treated by intermittent thrice weekly haemodialysis in a main hospital, and an ever-increasing number of satellite dialysis centres. Thus, as currently practised, haemodialysis is a very expensive treatment. In addition, owing to time constraints, and the intermittent nature of the therapy, several kilos of fluid often have to be removed over a relatively short period of time, potentially resulting in hypotension. A UK audit3 reported that some 15% or so of outpatient haemodialysis treatments were complicated by hypotension, requiring active fluid resuscitation. Furthermore, there is mounting evidence to show the benefits of daily haemodialysis. Unfortunately, there is currently no
logistical, practical, or economically feasible way to provide such therapy to most patients with CKD. To try to improve not only the quality of care delivered, but also patients’ quality of life, we have been working to develop wearable devices that would allow for an outpatientbased treatment for both chronic heart failure4 and end-stage kidney disease.5 As such we have recently reported our first pilot studies. Our pilot trial of the wearable artificial haemodialysis device was approved by the UK Medicines Health Regulatory Authority (MHRA), and as such the design of the trial, in terms of the number of patients, duration of therapy, and safety assessments was stipulated by the MHRA. Samples were analysed in the routine laboratories at the Royal Free Hospital, and as such the data were collected by the hospital laboratory data management system. Data were analysed by AD, who wrote the initial drafts. We wish to thank our sponsors, XCorporeal Inc and the Special Trustees of the Royal Free Hospital, who made this study possible. VG is chief medical and scientific officer to Xcorporeal Inc, Los Angeles, CA, USA.
*Andrew Davenport, Claudio Ronco, Victor Gura [email protected] Royal Free and University College Medical School, London NW3 2PF, UK (AD); Divisione de Nefrologia, Ospedale San Bortolo, Vicenza, Italy (CR); and Cedars Sinai Medical Center, University of California Los Angeles, Los Angeles, CA, USA (VG) 1
2
3
4
5
National Institute for Clinical Excellence. Guidance on home versus hospital haemodialysis for patients with end-stage renal failure. London: NICE, 2002. http://www. nice.org.uk/nicemedia/pdf/HvH_full_ guidance.pdf (accessed March 10, 2008). Oreopoulos DG, Coleman S, Doyle E. Reversing the decreasing peritoneal dialysis (PD) trend in Ontario: a government initiative to increase PD use in Ontario to 30% by 2010. Perit Dial Int 2007; 27: 489–95. Davenport A, Cox C, Thuraisingham R. Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension. Kidney Int 2008; 73: 759–64. Gura V, Ronco C, Nalesso F, et al. A wearable hemofilter for continuous ambulatory ultrafiltration. Kidney Int 2008; 73: 497–502. Davenport A, Gura V, Ronco C, Beizai M, Ezon C, Rambod E. A wearable haemodialysis device for patients with end-stage renal failure: a pilot study. Lancet 2007; 370: 2005–10.
www.thelancet.com Vol 371 April 5, 2008