letter to the editor
http://www.kidney-international.org & 2013 International Society of Nephrology
Low body mass index in nutcracker phenomenon: an underrecognized condition To the Editor: We read with interest the nephrology image on ‘Physical finding of nutcracker phenomenon’ by Matsubara et al.1 They reported the case of a 16-year-old adolescent boy with orthostatic proteinuria, severe macrohematuria, and anemia, and the patient’s hematuria and anemia spontaneously improved after 6 months.1 They found a left varicocele by physical examination, which was caused by the nutcracker phenomenon.1 However, they did not describe other physical findings, such as height, weight, and body mass index (BMI), and the pathophysiology of spontaneous resolution of hematuria. We first reported that nutcracker phenomenon may be caused by thin body shape, such as a low BMI,2,3 and hematuria can be resolved by an improvement of nutcracker phenomenon in accordance with an increase in BMI during childhood.3 Our speculations have recently been proved by other authors, who showed that varicocele was less frequent in obese persons4 and showed a significant correlation between % visceral fat volume and superior mesenteric artery angle (R ¼ 0.30; Po0.001).5 Therefore, nutcracker phenomenon should be suspected in children or adolescents with hematuria or proteinuria, and varicocele, and physical characteristics such as a low BMI could give us an important clue to suspect nutcracker phenomenon.
resolution. We did not judge this increase as significant. In our case, however, slightly distended lumbar collateral vein was already found. Therefore, we speculated that the development of collateral veins caused the hemodynamic change of the left renal vein.2 Although we agree that patients with nutcracker phenomenon are usually lean, we could not conclude that the BMI of this patient was distinctly low on the basis of the Japanese Health Statistics. Further, the studies that they cited might be insufficient to support this hypothesis. Dr Nielsen et al.3 showed that varicocele was less frequent in obese men, which does not mean higher frequency of varicocele in lean men. Arthurs et al.4 pointed out the weak relationship between visceral fat and superior mesenteric artery angle; therefore, they doubted its clinical significance. For these reasons, we should be careful to use low BMI as a defined diagnostic clue of nutcracker phenomenon. A small case–control study suggested that varicocele could be useful for the diagnosis of nutcracker phenomenon.5 Since Drs Shin and Park1 already showed that the BMI in nutcracker patients was lower than that in control in case–control study, further evidence should be accumulated to show low BMI as a good diagnostic marker of nutcracker phenomenon. 1. 2. 3.
4. 1. 2.
3.
4. 5.
Matsubara T, Ogawa O, Yanagita M. Physical finding of nutcracker phenomenon. Kidney Int 2013; 83: 335. Shin JI, Park JM, Lee SM et al. Factors affecting spontaneous resolution of hematuria in childhood nutcracker syndrome. Pediatr Nephrol 2005; 20: 609–613. Shin JI, Park JM, Lee JS et al. Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children with hematuria. Eur J Pediatr 2007; 166: 399–404. Handel LN, Shetty R, Sigman M. The relationship between varicoceles and obesity. J Urol 2006; 176: 2138–2140. Arthurs OJ, Mehta U, Set PA. Nutcracker and SMA syndromes: What is the normal SMA angle in children? Eur J Radiol 2012; 81: e854–e861.
Se Jin Park1 and Jae Il Shin2 1
Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea and 2Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea Correspondence: Jae Il Shin, Department of Pediatrics, Yonsei University College of Medicine, Yonsei-ro 50, Seodaemun-gu, C.P.O. Box 8044, Seoul 120-752, Korea. E-mail: [email protected] Kidney International (2013) 84, 1287; doi:10.1038/ki.2013.376
The Authors Reply: We thank Drs Shin and Park for the interest in our report.1 The body mass index (BMI) of the patient was 18.4 kg/m2 at presentation and 19.0 kg/m2 at Kidney International (2013) 84, 1287–1288
5.
Shin JI, Park SJ. Low body mass index in nutcracker phenomenon: an underrecognized condition. Kidney Int 2013; 84: 1287. Bhimma R, Robbs J. Nutcracker. Lancet 2005; 365: 1280. Nielsen ME, Zderic S, Freedland SJ et al. Insight on pathogenesis of varicoceles: relationship of varicocele and body mass index. Urology 2006; 68: 392–396. Arthurs OJ, Set PA. Response to letter by Park & Shin–re: comment on: nutcracker and SMA syndrome. Eur J Radiol 2013; 82: 1035. Mohammadi A, Ghasemi-Rad M, Mladkova N et al. Varicocele and nutcracker syndrome: sonographic findings. J Ultrasound Med 2010; 29: 1153–1160.
Takeshi Matsubara1, Osamu Ogawa2 and Motoko Yanagita3 1 Department of Nephrology, Kyoto University, Kyoto, Japan; 2Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan and 3 Graduate School of Medicine, Kyoto University, Kyoto, Japan Correspondence: Takeshi Matsubara, Department of Nephrology, Kyoto University, 54 Shogoin Kawahara-cho, Kyoto 606-8507, Japan. E-mail: [email protected]
Kidney International (2013) 84, 1287; doi:10.1038/ki.2013.383
How does hemodiafiltration improve survival? To the Editor: Farrington and Davenport1 provide a scholarly account of the potential benefits of hemodiafiltration (HDF) over more standard hemodialysis (HD). Their summary of the three recent randomized controlled trials comparing HD and HDF is very informative. Some critical 1287
letter to the editor
remarks are in order. In particular, the results of the ESHOL trial cannot be taken as proof that ‘demonstrated improved all-cause mortality’ with HDF. If anything, ESHOL suggests benefits given the non-blinded study design and non-blinded end point adjudication of that trial that was financed by a company that started an intensive marketing campaign for HDF based on ESHOL, an obvious conflict of interest. Furthermore, the main differences of ESHOL to the CONTRAST and Turkish studies were not only the difference in convection volumes but also the woeful imbalance in baseline clinical characteristics. Namely, in ESHOL, the HD group was much sicker than the HDF group with higher age, more frequent history of diabetes, access via catheter in 13 vs. 7%, and only 79 patients being transferred to renal transplantation but 106 in the HDF group. These consistent imbalances in favor of the HDF group do not prove but are consistent with a defective randomization procedure in a trial with approximately 1000 participants. Such defective randomization cannot be healed with statistical adjustments. Subgroup data in the HDF groups of the above trials are compatible with a higher convection volume being beneficial, but are also compatible with patient conditions allowing higher volumes being beneficial, namely fistulas or grafts vs. catheter. The former dialysis access is usually associated with a lower mortality than the latter. It is entirely possible that HDF proffers definite advantages over standard HD, but that hypothesis awaits proof by appropriate trials.
and improved dialysis water quality were introduced, but, as high-flux dialysis results in internal diafiltration, it was unclear whether the reduction in the incidence and severity of dialysis amyloid was primarily due to the change in dialyzer flux or improved dialysis water quality. Hemodiafiltration is an extension of this principal delivering a much larger convective dose compared with that achievable with highflux dialysis. Uncontrolled observational studies suggested a survival benefit for hemodiafiltration, although these were confounded by center effects. Hemodiafiltration was initially reported to improve anemia, reduce systemic inflammation, and intra-dialytic hypotension. However, these benefits were not supported by later reports comparing hemodiafiltration with high-flux hemodialysis using ultrapure and cooled dialysis water.2,3 There have been four recent prospective randomized trials of hemodialfiltration. Secondary analysis of two of these trials suggested a survival benefit for patients receiving greater convective clearances. However, greater convective clearance depends primarily upon session time and reliable vascular access, permitting higher blood flows, and dialyzer choice. As such, healthier patients are generally more likely to receive greater convective clearances. The third trial, the ESOL study, observed increased survival benefit for hemodiafiltration, but, as we pointed out, the hemodiafiltration group was marginally younger, with fewer diabetics, lower co-morbidity scores, and significantly less catheter access,4 which may have combined to favor a survival bias. The results of the fourth trial are eagerly awaited.
1.
1.
Farrington K, Davenport A. The ESHOL study: hemodiafiltration improves survival—but how? Kidney Int 2013; 83: 979–981.
Johannes F. Mann1 1 Department of Nephrology and Hypertension, Ludwig Maximilians University, Schwabing General Hospital, Munchen, Germany Correspondence: Johannes F. Mann, Department of Nephrology and Hypertension, Ludwig Maximilians University, Schwabing General Hospital, Munchen 80804, Germany. E-mail: [email protected]
Kidney International (2013) 84, 1287–1288; doi:10.1038/ki.2013.388
The Author Replies: We thank Dr Mann for his comments.1 In the 1980s, dialysis amyloid became increasingly recognized as a complication of long-term dialysis. High-flux dialyzers
1288
2.
3.
4.
Mann J. How does haemodiafiltration improve patient survival? Kidney Int 2013; 84: 1287–1288. Oates T, Pinney JH, Davenport A. Haemodiafiltration versus high-flux haemodialysis: effects on phosphate control and erythropoietin response. Am J Nephrol 2011; 33: 70–75. Pinney JH, Oates T, Davenport A. Haemodiafiltration does not reduce the frequency of intradialytic hypotensive episodes when compared to cooled high-flux haemodialysis. Nephron Clin Pract 2011; 119: c138–c144. Farrington K, Davenport A. The ESHOL study: hemodiafiltration improves survival—but how? Kidney Int 2013; 83: 979–981.
Andrew Davenport1 1 UCL Center for Nephrology, Hampstead Campus, Royal Free and University College Medical School, London, UK Correspondence: Andrew Davenport, UCL Center for Nephrology, Hampstead Campus, Royal Free and University College Medical School, Pond Street, London NW3 2PF, UK. E-mail: [email protected]
Kidney International (2013) 84, 1288; doi:10.1038/ki.2013.390
Kidney International (2013) 84, 1287–1288
http://www.kidney-international.org & 2013 International Society of Nephrology
Low body mass index in nutcracker phenomenon: an underrecognized condition To the Editor: We read with interest the nephrology image on ‘Physical finding of nutcracker phenomenon’ by Matsubara et al.1 They reported the case of a 16-year-old adolescent boy with orthostatic proteinuria, severe macrohematuria, and anemia, and the patient’s hematuria and anemia spontaneously improved after 6 months.1 They found a left varicocele by physical examination, which was caused by the nutcracker phenomenon.1 However, they did not describe other physical findings, such as height, weight, and body mass index (BMI), and the pathophysiology of spontaneous resolution of hematuria. We first reported that nutcracker phenomenon may be caused by thin body shape, such as a low BMI,2,3 and hematuria can be resolved by an improvement of nutcracker phenomenon in accordance with an increase in BMI during childhood.3 Our speculations have recently been proved by other authors, who showed that varicocele was less frequent in obese persons4 and showed a significant correlation between % visceral fat volume and superior mesenteric artery angle (R ¼ 0.30; Po0.001).5 Therefore, nutcracker phenomenon should be suspected in children or adolescents with hematuria or proteinuria, and varicocele, and physical characteristics such as a low BMI could give us an important clue to suspect nutcracker phenomenon.
resolution. We did not judge this increase as significant. In our case, however, slightly distended lumbar collateral vein was already found. Therefore, we speculated that the development of collateral veins caused the hemodynamic change of the left renal vein.2 Although we agree that patients with nutcracker phenomenon are usually lean, we could not conclude that the BMI of this patient was distinctly low on the basis of the Japanese Health Statistics. Further, the studies that they cited might be insufficient to support this hypothesis. Dr Nielsen et al.3 showed that varicocele was less frequent in obese men, which does not mean higher frequency of varicocele in lean men. Arthurs et al.4 pointed out the weak relationship between visceral fat and superior mesenteric artery angle; therefore, they doubted its clinical significance. For these reasons, we should be careful to use low BMI as a defined diagnostic clue of nutcracker phenomenon. A small case–control study suggested that varicocele could be useful for the diagnosis of nutcracker phenomenon.5 Since Drs Shin and Park1 already showed that the BMI in nutcracker patients was lower than that in control in case–control study, further evidence should be accumulated to show low BMI as a good diagnostic marker of nutcracker phenomenon. 1. 2. 3.
4. 1. 2.
3.
4. 5.
Matsubara T, Ogawa O, Yanagita M. Physical finding of nutcracker phenomenon. Kidney Int 2013; 83: 335. Shin JI, Park JM, Lee SM et al. Factors affecting spontaneous resolution of hematuria in childhood nutcracker syndrome. Pediatr Nephrol 2005; 20: 609–613. Shin JI, Park JM, Lee JS et al. Effect of renal Doppler ultrasound on the detection of nutcracker syndrome in children with hematuria. Eur J Pediatr 2007; 166: 399–404. Handel LN, Shetty R, Sigman M. The relationship between varicoceles and obesity. J Urol 2006; 176: 2138–2140. Arthurs OJ, Mehta U, Set PA. Nutcracker and SMA syndromes: What is the normal SMA angle in children? Eur J Radiol 2012; 81: e854–e861.
Se Jin Park1 and Jae Il Shin2 1
Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea and 2Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea Correspondence: Jae Il Shin, Department of Pediatrics, Yonsei University College of Medicine, Yonsei-ro 50, Seodaemun-gu, C.P.O. Box 8044, Seoul 120-752, Korea. E-mail: [email protected] Kidney International (2013) 84, 1287; doi:10.1038/ki.2013.376
The Authors Reply: We thank Drs Shin and Park for the interest in our report.1 The body mass index (BMI) of the patient was 18.4 kg/m2 at presentation and 19.0 kg/m2 at Kidney International (2013) 84, 1287–1288
5.
Shin JI, Park SJ. Low body mass index in nutcracker phenomenon: an underrecognized condition. Kidney Int 2013; 84: 1287. Bhimma R, Robbs J. Nutcracker. Lancet 2005; 365: 1280. Nielsen ME, Zderic S, Freedland SJ et al. Insight on pathogenesis of varicoceles: relationship of varicocele and body mass index. Urology 2006; 68: 392–396. Arthurs OJ, Set PA. Response to letter by Park & Shin–re: comment on: nutcracker and SMA syndrome. Eur J Radiol 2013; 82: 1035. Mohammadi A, Ghasemi-Rad M, Mladkova N et al. Varicocele and nutcracker syndrome: sonographic findings. J Ultrasound Med 2010; 29: 1153–1160.
Takeshi Matsubara1, Osamu Ogawa2 and Motoko Yanagita3 1 Department of Nephrology, Kyoto University, Kyoto, Japan; 2Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan and 3 Graduate School of Medicine, Kyoto University, Kyoto, Japan Correspondence: Takeshi Matsubara, Department of Nephrology, Kyoto University, 54 Shogoin Kawahara-cho, Kyoto 606-8507, Japan. E-mail: [email protected]
Kidney International (2013) 84, 1287; doi:10.1038/ki.2013.383
How does hemodiafiltration improve survival? To the Editor: Farrington and Davenport1 provide a scholarly account of the potential benefits of hemodiafiltration (HDF) over more standard hemodialysis (HD). Their summary of the three recent randomized controlled trials comparing HD and HDF is very informative. Some critical 1287
letter to the editor
remarks are in order. In particular, the results of the ESHOL trial cannot be taken as proof that ‘demonstrated improved all-cause mortality’ with HDF. If anything, ESHOL suggests benefits given the non-blinded study design and non-blinded end point adjudication of that trial that was financed by a company that started an intensive marketing campaign for HDF based on ESHOL, an obvious conflict of interest. Furthermore, the main differences of ESHOL to the CONTRAST and Turkish studies were not only the difference in convection volumes but also the woeful imbalance in baseline clinical characteristics. Namely, in ESHOL, the HD group was much sicker than the HDF group with higher age, more frequent history of diabetes, access via catheter in 13 vs. 7%, and only 79 patients being transferred to renal transplantation but 106 in the HDF group. These consistent imbalances in favor of the HDF group do not prove but are consistent with a defective randomization procedure in a trial with approximately 1000 participants. Such defective randomization cannot be healed with statistical adjustments. Subgroup data in the HDF groups of the above trials are compatible with a higher convection volume being beneficial, but are also compatible with patient conditions allowing higher volumes being beneficial, namely fistulas or grafts vs. catheter. The former dialysis access is usually associated with a lower mortality than the latter. It is entirely possible that HDF proffers definite advantages over standard HD, but that hypothesis awaits proof by appropriate trials.
and improved dialysis water quality were introduced, but, as high-flux dialysis results in internal diafiltration, it was unclear whether the reduction in the incidence and severity of dialysis amyloid was primarily due to the change in dialyzer flux or improved dialysis water quality. Hemodiafiltration is an extension of this principal delivering a much larger convective dose compared with that achievable with highflux dialysis. Uncontrolled observational studies suggested a survival benefit for hemodiafiltration, although these were confounded by center effects. Hemodiafiltration was initially reported to improve anemia, reduce systemic inflammation, and intra-dialytic hypotension. However, these benefits were not supported by later reports comparing hemodiafiltration with high-flux hemodialysis using ultrapure and cooled dialysis water.2,3 There have been four recent prospective randomized trials of hemodialfiltration. Secondary analysis of two of these trials suggested a survival benefit for patients receiving greater convective clearances. However, greater convective clearance depends primarily upon session time and reliable vascular access, permitting higher blood flows, and dialyzer choice. As such, healthier patients are generally more likely to receive greater convective clearances. The third trial, the ESOL study, observed increased survival benefit for hemodiafiltration, but, as we pointed out, the hemodiafiltration group was marginally younger, with fewer diabetics, lower co-morbidity scores, and significantly less catheter access,4 which may have combined to favor a survival bias. The results of the fourth trial are eagerly awaited.
1.
1.
Farrington K, Davenport A. The ESHOL study: hemodiafiltration improves survival—but how? Kidney Int 2013; 83: 979–981.
Johannes F. Mann1 1 Department of Nephrology and Hypertension, Ludwig Maximilians University, Schwabing General Hospital, Munchen, Germany Correspondence: Johannes F. Mann, Department of Nephrology and Hypertension, Ludwig Maximilians University, Schwabing General Hospital, Munchen 80804, Germany. E-mail: [email protected]
Kidney International (2013) 84, 1287–1288; doi:10.1038/ki.2013.388
The Author Replies: We thank Dr Mann for his comments.1 In the 1980s, dialysis amyloid became increasingly recognized as a complication of long-term dialysis. High-flux dialyzers
1288
2.
3.
4.
Mann J. How does haemodiafiltration improve patient survival? Kidney Int 2013; 84: 1287–1288. Oates T, Pinney JH, Davenport A. Haemodiafiltration versus high-flux haemodialysis: effects on phosphate control and erythropoietin response. Am J Nephrol 2011; 33: 70–75. Pinney JH, Oates T, Davenport A. Haemodiafiltration does not reduce the frequency of intradialytic hypotensive episodes when compared to cooled high-flux haemodialysis. Nephron Clin Pract 2011; 119: c138–c144. Farrington K, Davenport A. The ESHOL study: hemodiafiltration improves survival—but how? Kidney Int 2013; 83: 979–981.
Andrew Davenport1 1 UCL Center for Nephrology, Hampstead Campus, Royal Free and University College Medical School, London, UK Correspondence: Andrew Davenport, UCL Center for Nephrology, Hampstead Campus, Royal Free and University College Medical School, Pond Street, London NW3 2PF, UK. E-mail: [email protected]
Kidney International (2013) 84, 1288; doi:10.1038/ki.2013.390
Kidney International (2013) 84, 1287–1288
