- Email: [email protected]
Reply from the Authors
Letters to the Editor
Reply from the Authors We thank Szczech and Winston for their interest in our study and would like to clarify certain points. We concede to the possible biases recounted; however, the intent of our study was to evaluate the effect of angiotensinconverting enzyme inhibition (ACEI), not antiretroviral therapy (ARV) or highly active antiretrovrial therapy (HAART), on long-term renal survival in HIVAN. The survival benefit of ARV, and even more so of HAART, in human immunodeficiency virus infection is clear, but the effects on renal survival have yet to be established. In fact, in the referenced study by Szczech et al of more than 2000 HIV infected women, ARV monotherapy, ARV combination therapy, and HAART, all failed to affect the risk of renal failure [1]. This was also true when those with proteinuria were analyzed separately. In the article by Laradi et al referenced by Szczech and Winston, history of antiretroviral use was actually associated with worse patient survival, making conclusions regarding the effects of antiretrovirals on renal survival unattainable. Higher initial CD4 counts have consistently been shown in numerous studies, including our own, to be an independent variable associated with better renal outcomes. However, it does not necessarily follow that in HIVAN decreasing the HIV viral load or increasing the CD4 lymphocyte count will improve renal survival. This has been suggested by case reports [3, 4], but the issue needs to be addressed in larger prospective studies. While we prefer not to speculate on the role of ARV or HAART as a specific therapy for HIVAN, the authors would like to stress the importance of early diagnosis and intervention in HIVAN. There is compelling evidence that early initiation of ACE-I improves long-term renal survival in HIVAN. ALICE WEI, GODFREY C. BURNS, and BRENT A. WILLIAMS
New York, New York Correspondence to Alice Wei, Saint Vincents Hospital and Medical Center, Department of Medicine, MP-3B, 130 W. 12th Street, New York, NY 10011. E-mail: [email protected]
REFERENCES 1. SZCZECH LA, GANGE SJ, VAN DER HORST C, et al: Predictors of proteinuria and renal failure among women with HIV infection. Kidney Int 61:195–202, 2002 2. LARADI A, MALLET A, BEAUFILS H, et al: HIV-associated nephropathy: Outcome and prognosis factors. J Am Soc Nephrol 9:2327–2335, 1998 3. WINSTON JA, BRUGGEMAN LA, ROSS MD, et al: Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 344:1979–1984, 2001 4. WALI RK, DRACHENBERG CI, PAPADIMITRIOU JC, et al: HIV-1associated nephropathy and response to highly active antiretroviral therapy. Lancet 352:783–784, 1998
1115
Home nocturnal hemodialysis To the Editor: Home nocturnal hemodialysis (HND) has been an established form of treatment on a worldwide basis since its introduction in 1964 [1–4]. In its early days, many thought that it was superior to transplantation and was more cost effective than in center dialysis. Alas, the passage of time has not confirmed any of these earlier hopes. It is rarely practiced today for many reasons, including the increasing age and comorbidity of the endstage renal population being maintained on hemodialysis, although I still have one patient who has performed HND 4 times a week for 33 years [5]. Unless the increase in frequency of HND to 5 to 7 times per week can really be shown to be applicable on a large scale in less than highly motivated patients and staff, I doubt that the aspirations and claims of McFarlane et al [6] will stand the test of time more than our hopes and aspirations of 40 years ago. STANLEY SHALDON
Monaco, Monaco Correspondence to Stanley Shaldon, 25 Le Michelangelo, 7 Avenue des Papalins, Monaco 98000, Monaco. E-mail: stanley [email protected]
REFERENCES 1. SHALDON S: Overnight unattended home hemodialysis [letter]. Kidney Int 63:1957, 2003 2. SHALDON S: Panel contribution on experience with over-night haemodialysis in the home. Proc Working Conference on Chronic Dialysis at University of Washington, Seattle, University of Washington Press, 1964, pp 40 3. BAILLOD R, COMTY C, SHALDON S: Over-night haemodialysis in the home. Proc Eur Dial Transpl Assoc 2:99–104, 1965 4. SHALDON S: Independence in maintenance haemodialysis. Lancet 1:520–522, 1968 5. http://www.nephron.com/shaldon.html Accessed December 17, 2003 6. MCFARLANE PA, BAYOUMI AM, PIERRATOS A, REDELMEIER DA: The quality of life and cost utility of home nocturnal and conventional in-center hemodialysis. Kidney Int 64:1004–1011, 2003
Reply from the Authors We agree with Dr. Shaldon that long intermittent hemodialysis at home did not gain popularity in early days. However, we are more optimistic than Dr. Shaldon when considering more recent experiences [1]. The use of quotidian nocturnal hemodialysis is increasing. In Canada, the last few years have seen the start of at least four new home nocturnal hemodialysis programs, and the number of patients on the modality has doubled to more than 150. A similar number of patients are on nocturnal hemodialysis in the United States, and other programs exist in The Netherlands [2], Sweden [3], Germany, and Australia [4]. Furthermore, there are more than 300 patients primarily in the United States who are on long
1116
Letters to the Editor
intermittent hemodialysis either at home or in-center [5]. We think that the difference in experiences between the two eras relates to several factors. First, it has been demonstrated that many biochemical and clinical parameters including quality-of-life are improved by quotidian hemodialysis [6]. Second, as the number of programs offering quotidian hemodialysis has grown, the exposure of nephrologists and trainees to the method has increased, resulting in a larger pool of nephrologists capable of supervising these modalities. Third, the use of the buttonhole technique has helped resolve access difficulties inherent in daily hemodialysis. Fourth, industry interest has also increased, resulting in equipment that has simplified home hemodialysis techniques. Of course, the most important driver of growth has been patient interest, which has risen as patients have heard of others doing well on home-based hemodialysis. The full potential for growth in quotidian hemodialysis will not be realized until reimbursement issues have been resolved. Although we have demonstrated that a potential for cost savings at the global health care level, local funding for hemodialysis consumables and capital will need to be increased [7]. We believe that when the financial obstacles are removed and more patientfriendly hemodialysis machines become available, quotidian nocturnal and short-daily hemodialysis will become the modalities of choice for an even larger number of patients. PHIL MCFARLANE, ANDREAS PIERRATOS, AHMED BAYOUMI, and DON REDELMEIER
Toronto, Ontario, Canada Correspondence to Philip McFarlane, University of Toronto, 61 Queen St. E., 9th Floor, Toronto, Ontario M5C 2T2, Canada. E-mail: [email protected]
REFERENCES 1. PIERRATOS A: Daily hemodialysis: An update. Current Opinion in Nephrology & Hypertension. 11:165–171, 2002 2. KOOISTRA MP: Frequent prolonged home haemodialysis: Three old concepts, one modern solution. Nephrology Dialysis Transplantation 18:16–19, 2003 3. SIMONSEN O: Slow nocturnal dialysis (SND) as a rescue treatment for children and young patients with end stage renal failure. J Am Soc Nephrol 11:327A, 2000 4. AGAR JWM, SOMERVILLE CA, DWYER KM, et al: Nocturnal hemodialysis in Australia. Hemodialysis International 7:278–289, 2003 5. KURELLA M, HUNG A, TICHY M, HSU C, CHERTOW GM: Intermittent nocturnal in-center hemodialysis: UCSF-Mt Zion experience. J Am Soc Nephrol 13:410A, 2002 6. MCFARLANE PA, BAYOUMI AM, PIERRATOS A, REDELMEIER DA: The quality of life and cost utility of home nocturnal and conventional in-center hemodialysis. Kidney Int 64:1004–1011, 2003 7. MCFARLANE PA, PIERRATOS A, REDELMEIER DA: Cost savings of home nocturnal versus conventional in-center hemodialysis. Kidney Int 62:2216–2222, 2002
Components of the IGF system and not insulin itself are strongly associated with apoB100 kinetics in ESRD To the Editor: In our accompanying paper in this issue of Kidney International, insulin sensitivity tended to be lower both in end-stage renal disease (ESRD) and in peritoneal dialysis (PD) compared to controls. Additionally, apoB100 kinetics was not associated with indexes of insulin sensitivity. Insulin growth factors (IGFs) and the binding proteins (IGFBPs) are key regulators of fetal growth and development [1]. However, recently the IGF system has been associated with metabolic pathways that exhibit expression of a prodiabetic/proatherogenic phenotype [2]. Therefore, we aim to observe additional key pathways that may be involved in the origin of dyslipidemia in patients with ESRD. Plasma levels of IGF-1 (239 ± 12, 255 ± 44, 115 ± 12 ng/ mL), IGF-2 (658 ± 33, 765 ± 77, 470 ± 35 ng/mL), IGFBP1 (51 ± 9, 44 ± 6, 24 ± 5 lg/L), and IGFBP3 (4.0 ± 0.2, 5.5 ± 0.5, 2.1 ± 0.2 mg/L) are all significantly higher (P < 0.05) both in ESRD and PD compared with controls. Significant associations were found between parameters of the IGF system and apoB100 kinetics (Table 1). Strong negative associations for absolute synthesis rate (ASR) VLDL-2 apoB100, fractional catabolic rate (FCR) VLDL-2 apoB100, transfer to IDL apoB100 and IGF-1, IGF-2, and IGFBP3 were observed. In addition, ASR VLDL-1 apoB100 correlated positively with IGF-1 and IGFBP3. These results suggest a key role for circulating IGFs and IGFBPs involved in apoB100 kinetics. IGFBP3 appeared to be involved in all found associations. Indeed, IGFBP3 is bound in complex with either IGF-1 or IGF-2. IGFBP3 has intrinsic properties on nuclear receptors, and the uptake of IGFBP3 is facilitated by cholesterol in caveolins. Because insulin stimulates IGFBP3 synthesis [3], it may therefore be indirectly involved in these metabolic pathways. TH.B. TWICKLER, BERTHIL H.C.M.T. PRINSEN, and MONIQUE G.M. DE SAIN-VAN DER VELDEN
Utrecht, The Netherlands Correspondence to Monique G.M. de Sain-van der Velden, University Medical Center Utrecht, Department of Metabolic Diseases and Endocrinology HP KC 02.069.1, Lundlaan 6, Box 85090, 3508 AB Utrecht, The Netherlands. E-mail: [email protected]
Part of this work was financially supported by Pharmacia.
Reply from the Authors We thank Szczech and Winston for their interest in our study and would like to clarify certain points. We concede to the possible biases recounted; however, the intent of our study was to evaluate the effect of angiotensinconverting enzyme inhibition (ACEI), not antiretroviral therapy (ARV) or highly active antiretrovrial therapy (HAART), on long-term renal survival in HIVAN. The survival benefit of ARV, and even more so of HAART, in human immunodeficiency virus infection is clear, but the effects on renal survival have yet to be established. In fact, in the referenced study by Szczech et al of more than 2000 HIV infected women, ARV monotherapy, ARV combination therapy, and HAART, all failed to affect the risk of renal failure [1]. This was also true when those with proteinuria were analyzed separately. In the article by Laradi et al referenced by Szczech and Winston, history of antiretroviral use was actually associated with worse patient survival, making conclusions regarding the effects of antiretrovirals on renal survival unattainable. Higher initial CD4 counts have consistently been shown in numerous studies, including our own, to be an independent variable associated with better renal outcomes. However, it does not necessarily follow that in HIVAN decreasing the HIV viral load or increasing the CD4 lymphocyte count will improve renal survival. This has been suggested by case reports [3, 4], but the issue needs to be addressed in larger prospective studies. While we prefer not to speculate on the role of ARV or HAART as a specific therapy for HIVAN, the authors would like to stress the importance of early diagnosis and intervention in HIVAN. There is compelling evidence that early initiation of ACE-I improves long-term renal survival in HIVAN. ALICE WEI, GODFREY C. BURNS, and BRENT A. WILLIAMS
New York, New York Correspondence to Alice Wei, Saint Vincents Hospital and Medical Center, Department of Medicine, MP-3B, 130 W. 12th Street, New York, NY 10011. E-mail: [email protected]
REFERENCES 1. SZCZECH LA, GANGE SJ, VAN DER HORST C, et al: Predictors of proteinuria and renal failure among women with HIV infection. Kidney Int 61:195–202, 2002 2. LARADI A, MALLET A, BEAUFILS H, et al: HIV-associated nephropathy: Outcome and prognosis factors. J Am Soc Nephrol 9:2327–2335, 1998 3. WINSTON JA, BRUGGEMAN LA, ROSS MD, et al: Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 344:1979–1984, 2001 4. WALI RK, DRACHENBERG CI, PAPADIMITRIOU JC, et al: HIV-1associated nephropathy and response to highly active antiretroviral therapy. Lancet 352:783–784, 1998
1115
Home nocturnal hemodialysis To the Editor: Home nocturnal hemodialysis (HND) has been an established form of treatment on a worldwide basis since its introduction in 1964 [1–4]. In its early days, many thought that it was superior to transplantation and was more cost effective than in center dialysis. Alas, the passage of time has not confirmed any of these earlier hopes. It is rarely practiced today for many reasons, including the increasing age and comorbidity of the endstage renal population being maintained on hemodialysis, although I still have one patient who has performed HND 4 times a week for 33 years [5]. Unless the increase in frequency of HND to 5 to 7 times per week can really be shown to be applicable on a large scale in less than highly motivated patients and staff, I doubt that the aspirations and claims of McFarlane et al [6] will stand the test of time more than our hopes and aspirations of 40 years ago. STANLEY SHALDON
Monaco, Monaco Correspondence to Stanley Shaldon, 25 Le Michelangelo, 7 Avenue des Papalins, Monaco 98000, Monaco. E-mail: stanley [email protected]
REFERENCES 1. SHALDON S: Overnight unattended home hemodialysis [letter]. Kidney Int 63:1957, 2003 2. SHALDON S: Panel contribution on experience with over-night haemodialysis in the home. Proc Working Conference on Chronic Dialysis at University of Washington, Seattle, University of Washington Press, 1964, pp 40 3. BAILLOD R, COMTY C, SHALDON S: Over-night haemodialysis in the home. Proc Eur Dial Transpl Assoc 2:99–104, 1965 4. SHALDON S: Independence in maintenance haemodialysis. Lancet 1:520–522, 1968 5. http://www.nephron.com/shaldon.html Accessed December 17, 2003 6. MCFARLANE PA, BAYOUMI AM, PIERRATOS A, REDELMEIER DA: The quality of life and cost utility of home nocturnal and conventional in-center hemodialysis. Kidney Int 64:1004–1011, 2003
Reply from the Authors We agree with Dr. Shaldon that long intermittent hemodialysis at home did not gain popularity in early days. However, we are more optimistic than Dr. Shaldon when considering more recent experiences [1]. The use of quotidian nocturnal hemodialysis is increasing. In Canada, the last few years have seen the start of at least four new home nocturnal hemodialysis programs, and the number of patients on the modality has doubled to more than 150. A similar number of patients are on nocturnal hemodialysis in the United States, and other programs exist in The Netherlands [2], Sweden [3], Germany, and Australia [4]. Furthermore, there are more than 300 patients primarily in the United States who are on long
1116
Letters to the Editor
intermittent hemodialysis either at home or in-center [5]. We think that the difference in experiences between the two eras relates to several factors. First, it has been demonstrated that many biochemical and clinical parameters including quality-of-life are improved by quotidian hemodialysis [6]. Second, as the number of programs offering quotidian hemodialysis has grown, the exposure of nephrologists and trainees to the method has increased, resulting in a larger pool of nephrologists capable of supervising these modalities. Third, the use of the buttonhole technique has helped resolve access difficulties inherent in daily hemodialysis. Fourth, industry interest has also increased, resulting in equipment that has simplified home hemodialysis techniques. Of course, the most important driver of growth has been patient interest, which has risen as patients have heard of others doing well on home-based hemodialysis. The full potential for growth in quotidian hemodialysis will not be realized until reimbursement issues have been resolved. Although we have demonstrated that a potential for cost savings at the global health care level, local funding for hemodialysis consumables and capital will need to be increased [7]. We believe that when the financial obstacles are removed and more patientfriendly hemodialysis machines become available, quotidian nocturnal and short-daily hemodialysis will become the modalities of choice for an even larger number of patients. PHIL MCFARLANE, ANDREAS PIERRATOS, AHMED BAYOUMI, and DON REDELMEIER
Toronto, Ontario, Canada Correspondence to Philip McFarlane, University of Toronto, 61 Queen St. E., 9th Floor, Toronto, Ontario M5C 2T2, Canada. E-mail: [email protected]
REFERENCES 1. PIERRATOS A: Daily hemodialysis: An update. Current Opinion in Nephrology & Hypertension. 11:165–171, 2002 2. KOOISTRA MP: Frequent prolonged home haemodialysis: Three old concepts, one modern solution. Nephrology Dialysis Transplantation 18:16–19, 2003 3. SIMONSEN O: Slow nocturnal dialysis (SND) as a rescue treatment for children and young patients with end stage renal failure. J Am Soc Nephrol 11:327A, 2000 4. AGAR JWM, SOMERVILLE CA, DWYER KM, et al: Nocturnal hemodialysis in Australia. Hemodialysis International 7:278–289, 2003 5. KURELLA M, HUNG A, TICHY M, HSU C, CHERTOW GM: Intermittent nocturnal in-center hemodialysis: UCSF-Mt Zion experience. J Am Soc Nephrol 13:410A, 2002 6. MCFARLANE PA, BAYOUMI AM, PIERRATOS A, REDELMEIER DA: The quality of life and cost utility of home nocturnal and conventional in-center hemodialysis. Kidney Int 64:1004–1011, 2003 7. MCFARLANE PA, PIERRATOS A, REDELMEIER DA: Cost savings of home nocturnal versus conventional in-center hemodialysis. Kidney Int 62:2216–2222, 2002
Components of the IGF system and not insulin itself are strongly associated with apoB100 kinetics in ESRD To the Editor: In our accompanying paper in this issue of Kidney International, insulin sensitivity tended to be lower both in end-stage renal disease (ESRD) and in peritoneal dialysis (PD) compared to controls. Additionally, apoB100 kinetics was not associated with indexes of insulin sensitivity. Insulin growth factors (IGFs) and the binding proteins (IGFBPs) are key regulators of fetal growth and development [1]. However, recently the IGF system has been associated with metabolic pathways that exhibit expression of a prodiabetic/proatherogenic phenotype [2]. Therefore, we aim to observe additional key pathways that may be involved in the origin of dyslipidemia in patients with ESRD. Plasma levels of IGF-1 (239 ± 12, 255 ± 44, 115 ± 12 ng/ mL), IGF-2 (658 ± 33, 765 ± 77, 470 ± 35 ng/mL), IGFBP1 (51 ± 9, 44 ± 6, 24 ± 5 lg/L), and IGFBP3 (4.0 ± 0.2, 5.5 ± 0.5, 2.1 ± 0.2 mg/L) are all significantly higher (P < 0.05) both in ESRD and PD compared with controls. Significant associations were found between parameters of the IGF system and apoB100 kinetics (Table 1). Strong negative associations for absolute synthesis rate (ASR) VLDL-2 apoB100, fractional catabolic rate (FCR) VLDL-2 apoB100, transfer to IDL apoB100 and IGF-1, IGF-2, and IGFBP3 were observed. In addition, ASR VLDL-1 apoB100 correlated positively with IGF-1 and IGFBP3. These results suggest a key role for circulating IGFs and IGFBPs involved in apoB100 kinetics. IGFBP3 appeared to be involved in all found associations. Indeed, IGFBP3 is bound in complex with either IGF-1 or IGF-2. IGFBP3 has intrinsic properties on nuclear receptors, and the uptake of IGFBP3 is facilitated by cholesterol in caveolins. Because insulin stimulates IGFBP3 synthesis [3], it may therefore be indirectly involved in these metabolic pathways. TH.B. TWICKLER, BERTHIL H.C.M.T. PRINSEN, and MONIQUE G.M. DE SAIN-VAN DER VELDEN
Utrecht, The Netherlands Correspondence to Monique G.M. de Sain-van der Velden, University Medical Center Utrecht, Department of Metabolic Diseases and Endocrinology HP KC 02.069.1, Lundlaan 6, Box 85090, 3508 AB Utrecht, The Netherlands. E-mail: [email protected]
Part of this work was financially supported by Pharmacia.