letter to the editor
screening for cardiovascular disease in asymptomatic kidney transplant recipients improves outcomes. We agree with Malyszko et al. that ‘There are no definitive data at this time for or against screening for myocardial ischemia among kidney transplantation candidates who are free of active cardiac conditions.’1 We do not agree that detailed cardiac evaluation for the asymptomatic candidate has been proven to outweigh the risks of this evaluation, and renew our call for a randomized controlled trial to assess whether the current practice of screening is beneficial. 1.
2. 3.
4.
5.
Ma"yszko J, Bachorzewska-Gajewska H, Tomaszuk-Kazberuk A et al. Cardiovascular disease and kidney transplantation: evaluation of potential transplant recipient. Pol Arch Med Wewn 2014; 124: 608–616. Hart A, Weir MR, Kasiske BL. Cardiovascular risk assessment in kidney transplantation. Kidney Int 2015; 87: 527–534. Ma"yszko J, Bachorzewska-Gajewska H, Tomaszberuk A et al. Cardiovascular evaluation of potential transplant recipient: from non-US perspective. Kidney Int 2015; 87: 863. Authors/Task Force Members, Windecker S, Kolh P, Alfonso F et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35: 2541–2619. Fleisher LB, Brown J, Calkins K et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. J Am Coll Cardiol 2007; 50: e159–e242.
Allyson Hart1,2, Matthew R. Weir3 and Bertram L. Kasiske1,2 1
Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota, USA; 2School of Medicine, University of Minnesota, Minneapolis, MN, USA and 3Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA Correspondence: Allyson Hart, Department of Nephrology, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, Minnesota 55415, USA. E-mail: [email protected]
demonstrate that PCS in non-uremic concentrations is one of the metabolites associated with poor renal outcome. Does this mean that accelerated renal disease progression in diabetic nephropathy is due to toxic metabolites, including PCS? There are at least three other explanations to explain this observation. First, as renal clearance of PCS is mainly due to tubular secretion, high PCS levels may merely reflect renal proximal tubulopathy.2 Indeed, progressors presented with significantly higher albuminuria, which either may be a consequence or a cause of proximal tubulopathy. Second, PCS serum levels and urinary excretion rates are also substantially higher in diabetic versus nondiabetic chronic kidney disease patients (Meijers et al., CJASN 2010)3 and high PCS levels may contribute to insulin resistance, rendering the host more susceptible to development of more severe diabetes and its complications.4 Finally, high PCS may point to a disturbed and potentially deleterious gut microbial metabolism. As pharmacological (e.g., acarbose) and dietary interventions (e.g., fiber intake) may differentially affect microbial metabolism and PCS levels, they should be accounted for.5 Untargeted metabolomics will show us numerous intriguing associations. Even when in alignment with existing literature, such as for PCS, these associations may or may not point toward a causal relationship. As always, good science generates more questions. 1.
2. 3.
Kidney International (2015) 87, 863–864; doi:10.1038/ki.2014.422 4. 5.
The metabolomics grail: promising although not yet holy To the Editor: We read with interest the paper by Niewczas et al.,1 and would like to offer the following comments. Although the era of metabolome-wide association studies is still to arrive, the study by Niewczas et al.1 is a substantial step in this direction. Although p-cresyl sulfate (PCS) is a wellestablished nephro-vascular toxin, the authors are the first to
864
Niewczas MA, Sirich TL, Mathew AV et al. Uremic solutes and risk of endstage renal disease in type 2 diabetes: metabolomic study. Kidney Int 2014; 85: 1214–1224. Masereeuw R, Mutsaers HA, Toyohara T et al. The kidney and uremic toxin removal: glomerulus or tubule? Semin Nephrol 2014; 34: 191–208. Meijers BK, Claes K, Bammens B et al. p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin J Am Soc Nephrol 2010; 5: 1182–1189. Koppe L, Pillon NJ, Vella RE et al. p-Cresyl sulfate promotes insulin resistance associated with CKD. J Am Soc Nephrol 2013; 24: 88–99. Evenepoel P, Bammens B, Verbeke K et al. Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: a pilot study. Kidney Int 2006; 70: 192–198.
Ruben Poesen1, Pieter Evenepoel1 and Bjo¨ rn Meijers1 1 Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium Correspondence: Bjo¨ rn Meijers, Division of Internal Medicine, Department of Nephrology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: [email protected]
Kidney International (2015) 87, 864; doi:10.1038/ki.2014.396
Kidney International (2015) 87, 857–864
screening for cardiovascular disease in asymptomatic kidney transplant recipients improves outcomes. We agree with Malyszko et al. that ‘There are no definitive data at this time for or against screening for myocardial ischemia among kidney transplantation candidates who are free of active cardiac conditions.’1 We do not agree that detailed cardiac evaluation for the asymptomatic candidate has been proven to outweigh the risks of this evaluation, and renew our call for a randomized controlled trial to assess whether the current practice of screening is beneficial. 1.
2. 3.
4.
5.
Ma"yszko J, Bachorzewska-Gajewska H, Tomaszuk-Kazberuk A et al. Cardiovascular disease and kidney transplantation: evaluation of potential transplant recipient. Pol Arch Med Wewn 2014; 124: 608–616. Hart A, Weir MR, Kasiske BL. Cardiovascular risk assessment in kidney transplantation. Kidney Int 2015; 87: 527–534. Ma"yszko J, Bachorzewska-Gajewska H, Tomaszberuk A et al. Cardiovascular evaluation of potential transplant recipient: from non-US perspective. Kidney Int 2015; 87: 863. Authors/Task Force Members, Windecker S, Kolh P, Alfonso F et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014; 35: 2541–2619. Fleisher LB, Brown J, Calkins K et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery. J Am Coll Cardiol 2007; 50: e159–e242.
Allyson Hart1,2, Matthew R. Weir3 and Bertram L. Kasiske1,2 1
Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota, USA; 2School of Medicine, University of Minnesota, Minneapolis, MN, USA and 3Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA Correspondence: Allyson Hart, Department of Nephrology, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, Minnesota 55415, USA. E-mail: [email protected]
demonstrate that PCS in non-uremic concentrations is one of the metabolites associated with poor renal outcome. Does this mean that accelerated renal disease progression in diabetic nephropathy is due to toxic metabolites, including PCS? There are at least three other explanations to explain this observation. First, as renal clearance of PCS is mainly due to tubular secretion, high PCS levels may merely reflect renal proximal tubulopathy.2 Indeed, progressors presented with significantly higher albuminuria, which either may be a consequence or a cause of proximal tubulopathy. Second, PCS serum levels and urinary excretion rates are also substantially higher in diabetic versus nondiabetic chronic kidney disease patients (Meijers et al., CJASN 2010)3 and high PCS levels may contribute to insulin resistance, rendering the host more susceptible to development of more severe diabetes and its complications.4 Finally, high PCS may point to a disturbed and potentially deleterious gut microbial metabolism. As pharmacological (e.g., acarbose) and dietary interventions (e.g., fiber intake) may differentially affect microbial metabolism and PCS levels, they should be accounted for.5 Untargeted metabolomics will show us numerous intriguing associations. Even when in alignment with existing literature, such as for PCS, these associations may or may not point toward a causal relationship. As always, good science generates more questions. 1.
2. 3.
Kidney International (2015) 87, 863–864; doi:10.1038/ki.2014.422 4. 5.
The metabolomics grail: promising although not yet holy To the Editor: We read with interest the paper by Niewczas et al.,1 and would like to offer the following comments. Although the era of metabolome-wide association studies is still to arrive, the study by Niewczas et al.1 is a substantial step in this direction. Although p-cresyl sulfate (PCS) is a wellestablished nephro-vascular toxin, the authors are the first to
864
Niewczas MA, Sirich TL, Mathew AV et al. Uremic solutes and risk of endstage renal disease in type 2 diabetes: metabolomic study. Kidney Int 2014; 85: 1214–1224. Masereeuw R, Mutsaers HA, Toyohara T et al. The kidney and uremic toxin removal: glomerulus or tubule? Semin Nephrol 2014; 34: 191–208. Meijers BK, Claes K, Bammens B et al. p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin J Am Soc Nephrol 2010; 5: 1182–1189. Koppe L, Pillon NJ, Vella RE et al. p-Cresyl sulfate promotes insulin resistance associated with CKD. J Am Soc Nephrol 2013; 24: 88–99. Evenepoel P, Bammens B, Verbeke K et al. Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: a pilot study. Kidney Int 2006; 70: 192–198.
Ruben Poesen1, Pieter Evenepoel1 and Bjo¨ rn Meijers1 1 Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, Leuven, Belgium Correspondence: Bjo¨ rn Meijers, Division of Internal Medicine, Department of Nephrology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: [email protected]
Kidney International (2015) 87, 864; doi:10.1038/ki.2014.396
Kidney International (2015) 87, 857–864
