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Non-heart-beating donors for renal transplantation
CORRESPONDENCE
4
Consumer Products and the Environment. London: Department of Health, 2000: 66–67. Høyer AP, Jørgensen T, Brock JW, Grandjean P. Organochlorine exposure and breast cancer survival. J Clin Epidemiol 2000; 53: 323–30.
test for lactase activity and estimates of lactose and galactose intakes should be included in the investigation of cardiovascular disease in South Asians. Jeffrey J Segall 308 Cricklewood Lane, London NW2 2PX, UK 1
Cardiovascular disease in South Asians Sir—David Bell (Sept 23, p 1109)1 points out that in the study by Sonia Anand and colleagues2 features of insulin resistance were seen more frequently in South Asians. Bell believes a higher rate of insulin resistance in the South Asians would explain their higher prevalence of cardiovascular disease. This interpretation is inconsistent with reports of the absence of increased rates of coronary heart disease in other populations who have a high prevalence of non-insulin-dependent diabetes. These are Pima Indians (who also have a high prevalence of proven insulin resistance in non-diabetics), Sri Lankans, Afro-Caribbeans, and South African Bantu who all have a low prevalence of persistent lactase activity in adulthood (a genetic characteristic), associated with low intake of lactose from milk.3,4 Most South Asians in Anand and colleagues’ study originated from the northern Indian subcontinent,2 where the prevalence of adult lactase activity ranges from 67% to 100% and the intake of lactose from milk and lactose and galactose from yoghurt is high. By contrast, ethnic Chinese, who had the lowest rates of coronary heart disease, have a prevalence of adult lactase activity of only 6% and a low intake of milk.3,4 I suggest that insulin resistance in the South Asians whose intake of lactose was high and who had intestinal lactase in adulthood to hydrolyse it to glucose and galactose explains the higher rate of cardiovascular disease. Experimentally in healthy people, simultaneous absoption of glucose and galactose lowers the ensuing galactosaemia compared with that after absoption of galactose alone, possibly because insulin response to glucose speeds the rate of galactoase clearance. In insulin resistance, extrahepatic uptake of galactose might be increased because of hyperinsulinaemia and delayed uptake of glucose. Galactose glycation of arterial-wall proteins to which lipoprotein particles become attached could result.4 I believe that the breath-hydrogen
THE LANCET • Vol 356 • November 25, 2000
2
3
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Bell DSH. Cardiovascular disease in South Asians. Lancet 2000; 356: 1109. Anand SS, Salim Y, Vuksan V, et al. Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic Groups (SHARE). Lancet 2000; 356: 279–84. Segall JJ. Dietary lactose as a possible risk factor for ischaemic heart disease: review of epidemiology. Int J Cardiol 1994; 46: 197–207. Segall JJ. Epidemiological evidence for the link between dietary lactose and atherosclerosis. In: Colaco CALS, ed. The glycation hypothesis of atherosclerosis. Austin, Texas: Landes Bioscience, 1997: 186–209.
Non-heart-beating donors for renal transplantation Sir—Yves Vanrenterghem (Aug 12, p 528)1 advocates a cautious approach to the use of non-heart-beating donors (NHBDs). We are concerned by some of his conclusions, especially those relating to organ viability assessment. We agree that NHBD transplants have higher rates of delayed graft function than heart-beating-donor kidneys, and in some series, higher rates of primary non-function (kidneys that never function). We too are impressed by the decrease in the rate of primary non-function achieved in Newcastle after the introduction of viability testing.2 However, we differ in our interpretations of the above from Vanrenterghem in three ways. First, that delayed graft function can have adverse consequences for long-term transplant survival. Second, NHBD programmes are acceptable only with viability testing. Third, promotion of NHBDs would risk jeopardising well functioning donor programmes. Delayed graft function is associated with poor long-term results in heartbeating-donor transplants,3 not in NHBD transplants.4 The explanation for this difference is not clear. In animals, brain death induces peripheral organ dysfunction. Clinically this effect might adversely affect transplant outcome from brainstem-dead heartbeating donors, but not from NHBDs, which counterbalances the damage done by warm ischaemia. The example of the Newcastle experience, cited to justify the necessity
of viability testing, merits further scrutiny. Although the rate of primary non-function fell from 54% to 7% among NHBDs, caution must be exercised in attributing this striking improvement entirely to viability testing. The earlier group of only 11 transplants, effectively historical controls, might simply represent a learning curve. Also the viability tests used were not validated, since kidneys thought to be non-viable were discarded. There was also a learning curve in the Leicester NHBD programme, reflected in a rate of primary non-function of 17% over the first 4 years, then 3% over the next 4 years. The latter is not significantly different from heartbeating-donor transplants.5 Assessment of kidneys is subjective, done according to the adequacy of in-situ perfusion. The drawbacks of this method are that substantial experience is needed to judge viability, and, in erring on the side of caution, viable kidneys might be discarded. A sensitive and specific viability test could allow more organs to be transplanted. This conjecture is lent some weight by comparison of the proportion of kidneys transplanted per NHBD in the two centres, which have similar referral criteria and protocols. In Newcastle, 1·4 kidneys are transplanted per retrieval, compared with 0·5 in Leicester. Finally, we feel that NHBDs need to be promoted broadly if they are to have an impact on the transplant waiting list. In Maastricht and Leicester, around 25% of renal transplants are from NHBDs. We recognise that concerns over viability present a substantial obstacle to this aim, and, therefore, we would welcome the development of a reliable objective test of viability. *M S Metcalfe, M L Nicholson Transplant Division, University Department of Surgery, Leicester General Hospital NHS Trust, Leicester LE5 4WP, UK 1
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4
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Vanrenterghem Y. Cautious approach to use of non-heart-beating donors. Lancet 2000; 356: 528. Balpuri S, Buckley P, Snowdon C, et al. The trouble with kidneys derived from the nonheart-beating donor: a single centre experience. Transplantation 2000; 69: 842–46. Pirsch JD, Ploeg RJ, Gange S, et al. Determinants of graft survival after renal transplantation. Transplantation 1996; 61: 1581. Absalom H, White SA, Horsburgh T, et al. The influence of delayed graft function in recipients of conventional heart-beating donor kidneys. Ninth Congress of the European Society of Organ Transplantation, 1999, June, Oslo (abstr 75). Nicholson ML, Metcalfe MS, White SA, et al. A comparison of the results of renal transplantation from non-heart-beating, conventional cadaveric and living donors. Kidney Int (in press).
1853
For personal use only. Not to be reproduced without permission of The Lancet.
4
Consumer Products and the Environment. London: Department of Health, 2000: 66–67. Høyer AP, Jørgensen T, Brock JW, Grandjean P. Organochlorine exposure and breast cancer survival. J Clin Epidemiol 2000; 53: 323–30.
test for lactase activity and estimates of lactose and galactose intakes should be included in the investigation of cardiovascular disease in South Asians. Jeffrey J Segall 308 Cricklewood Lane, London NW2 2PX, UK 1
Cardiovascular disease in South Asians Sir—David Bell (Sept 23, p 1109)1 points out that in the study by Sonia Anand and colleagues2 features of insulin resistance were seen more frequently in South Asians. Bell believes a higher rate of insulin resistance in the South Asians would explain their higher prevalence of cardiovascular disease. This interpretation is inconsistent with reports of the absence of increased rates of coronary heart disease in other populations who have a high prevalence of non-insulin-dependent diabetes. These are Pima Indians (who also have a high prevalence of proven insulin resistance in non-diabetics), Sri Lankans, Afro-Caribbeans, and South African Bantu who all have a low prevalence of persistent lactase activity in adulthood (a genetic characteristic), associated with low intake of lactose from milk.3,4 Most South Asians in Anand and colleagues’ study originated from the northern Indian subcontinent,2 where the prevalence of adult lactase activity ranges from 67% to 100% and the intake of lactose from milk and lactose and galactose from yoghurt is high. By contrast, ethnic Chinese, who had the lowest rates of coronary heart disease, have a prevalence of adult lactase activity of only 6% and a low intake of milk.3,4 I suggest that insulin resistance in the South Asians whose intake of lactose was high and who had intestinal lactase in adulthood to hydrolyse it to glucose and galactose explains the higher rate of cardiovascular disease. Experimentally in healthy people, simultaneous absoption of glucose and galactose lowers the ensuing galactosaemia compared with that after absoption of galactose alone, possibly because insulin response to glucose speeds the rate of galactoase clearance. In insulin resistance, extrahepatic uptake of galactose might be increased because of hyperinsulinaemia and delayed uptake of glucose. Galactose glycation of arterial-wall proteins to which lipoprotein particles become attached could result.4 I believe that the breath-hydrogen
THE LANCET • Vol 356 • November 25, 2000
2
3
4
Bell DSH. Cardiovascular disease in South Asians. Lancet 2000; 356: 1109. Anand SS, Salim Y, Vuksan V, et al. Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic Groups (SHARE). Lancet 2000; 356: 279–84. Segall JJ. Dietary lactose as a possible risk factor for ischaemic heart disease: review of epidemiology. Int J Cardiol 1994; 46: 197–207. Segall JJ. Epidemiological evidence for the link between dietary lactose and atherosclerosis. In: Colaco CALS, ed. The glycation hypothesis of atherosclerosis. Austin, Texas: Landes Bioscience, 1997: 186–209.
Non-heart-beating donors for renal transplantation Sir—Yves Vanrenterghem (Aug 12, p 528)1 advocates a cautious approach to the use of non-heart-beating donors (NHBDs). We are concerned by some of his conclusions, especially those relating to organ viability assessment. We agree that NHBD transplants have higher rates of delayed graft function than heart-beating-donor kidneys, and in some series, higher rates of primary non-function (kidneys that never function). We too are impressed by the decrease in the rate of primary non-function achieved in Newcastle after the introduction of viability testing.2 However, we differ in our interpretations of the above from Vanrenterghem in three ways. First, that delayed graft function can have adverse consequences for long-term transplant survival. Second, NHBD programmes are acceptable only with viability testing. Third, promotion of NHBDs would risk jeopardising well functioning donor programmes. Delayed graft function is associated with poor long-term results in heartbeating-donor transplants,3 not in NHBD transplants.4 The explanation for this difference is not clear. In animals, brain death induces peripheral organ dysfunction. Clinically this effect might adversely affect transplant outcome from brainstem-dead heartbeating donors, but not from NHBDs, which counterbalances the damage done by warm ischaemia. The example of the Newcastle experience, cited to justify the necessity
of viability testing, merits further scrutiny. Although the rate of primary non-function fell from 54% to 7% among NHBDs, caution must be exercised in attributing this striking improvement entirely to viability testing. The earlier group of only 11 transplants, effectively historical controls, might simply represent a learning curve. Also the viability tests used were not validated, since kidneys thought to be non-viable were discarded. There was also a learning curve in the Leicester NHBD programme, reflected in a rate of primary non-function of 17% over the first 4 years, then 3% over the next 4 years. The latter is not significantly different from heartbeating-donor transplants.5 Assessment of kidneys is subjective, done according to the adequacy of in-situ perfusion. The drawbacks of this method are that substantial experience is needed to judge viability, and, in erring on the side of caution, viable kidneys might be discarded. A sensitive and specific viability test could allow more organs to be transplanted. This conjecture is lent some weight by comparison of the proportion of kidneys transplanted per NHBD in the two centres, which have similar referral criteria and protocols. In Newcastle, 1·4 kidneys are transplanted per retrieval, compared with 0·5 in Leicester. Finally, we feel that NHBDs need to be promoted broadly if they are to have an impact on the transplant waiting list. In Maastricht and Leicester, around 25% of renal transplants are from NHBDs. We recognise that concerns over viability present a substantial obstacle to this aim, and, therefore, we would welcome the development of a reliable objective test of viability. *M S Metcalfe, M L Nicholson Transplant Division, University Department of Surgery, Leicester General Hospital NHS Trust, Leicester LE5 4WP, UK 1
2
3
4
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Vanrenterghem Y. Cautious approach to use of non-heart-beating donors. Lancet 2000; 356: 528. Balpuri S, Buckley P, Snowdon C, et al. The trouble with kidneys derived from the nonheart-beating donor: a single centre experience. Transplantation 2000; 69: 842–46. Pirsch JD, Ploeg RJ, Gange S, et al. Determinants of graft survival after renal transplantation. Transplantation 1996; 61: 1581. Absalom H, White SA, Horsburgh T, et al. The influence of delayed graft function in recipients of conventional heart-beating donor kidneys. Ninth Congress of the European Society of Organ Transplantation, 1999, June, Oslo (abstr 75). Nicholson ML, Metcalfe MS, White SA, et al. A comparison of the results of renal transplantation from non-heart-beating, conventional cadaveric and living donors. Kidney Int (in press).
1853
For personal use only. Not to be reproduced without permission of The Lancet.