Correspondence LETTERS TO THE EDITOR Hypotension and Frequent Hemodialysis: Clarification Requested Regarding the KDOQI Hemodialysis Adequacy Guideline 2015 Update To the Editor: The KDOQI (Kidney Disease Outcomes Quality Initiative) clinical practice guideline for hemodialysis adequacy lists more frequent hypotensive episodes as an adverse outcome of more frequent hemodialysis,1(p904) and this is repeated in guideline recommendation 2.2.1 The citation for this statement was the report on the FHN (Frequent Hemodialysis Network) Daily Trial.2 However, Table 4 of the FHN Trial Group article does not support that statement. Yes, there were numerically more episodes of hypotension (724 in the frequent hemodialysis group vs 470 in the conventional hemodialysis group); however, in the footnote to Table 4, the percentage of dialysis treatments with hypotension was 10.9% in the frequent hemodialysis group versus 13.6% in the conventional hemodialysis group (P 5 0.04).2 I ask the KDOQI Work Group authors to comment on the contradiction between the KDOQI guideline and the FHN Trial Group data. Ann Mancini, RN, MSN, FNP Baxter Healthcare Corporation
Acknowledgements Financial Disclosure: Ms Mancini is employed by Baxter Healthcare Corporation as a Medical Science Liaison.
References 1. National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update. Am J Kidney Dis. 2015;66(5):884-930. 2. FHN Trial Group; Chertow GM, Levin NW, Beck GJ, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2230. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.12.012
In Reply to ‘Hypotension and Frequent Hemodialysis: Clarification Requested Regarding the KDOQI Hemodialysis Adequacy Guideline 2015 Update’ We thank Ann Mancini for her careful review of the KDOQI hemodialysis adequacy guideline update.1 Although we do not believe guideline statement 2.2 is incorrect as published,2 we agree that a clearer explanation is needed. Mancini cites correctly the risk for intradialytic hypotension (IDH) in the FHN Daily Trial. Although the percent risk for IDH per treatment was slightly lower, the exposure to dialysis with a daily schedule was considerably higher because on average, patients randomly assigned to the “daily” schedule received dialysis 5 times per week. For this reason, if one assumes that an episode of IDH causes injury, the cumulative repetitive injury risk in patients randomly assigned to receive “daily” treatments was higher than for those randomly assigned to receive thrice-weekly dialysis. This was reflected by the higher number of total episodes of IDH in patients randomly assigned to receive frequent treatments in the Daily Trial.3 532
We appreciate that the sentence Ms Mancini flags on page 904 of the guideline update does not present this point clearly, and we have published an erratum to remove the inapplicable P value and clarify our intended meaning.4 As the updated wording in the erratum shows, what is important and consequential for each individual patient is the number of hypotensive episodes per unit of time. The risk is clearly higher for the frequently dialyzed patients (nearly 50% higher incidence per patient per year). This is the sense of guideline statement 2.2, which in our estimate emphasizes correctly the increased risk in frequently dialyzed patients. John Daugirdas, MD University of Illinois College of Medicine, Chicago, Illinois Thomas Depner, MD University of California, Davis, Sacramento, California
Acknowledgements Financial Disclosure: The authors declare that they have no relevant financial interests.
References 1. Mancini A. Hypotension and frequent hemodialysis: clarification requested regarding the KDOQI hemodialysis adequacy guideline 2015 update. Am J Kidney Dis. 2016;67(3):532. 2. National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update. Am J Kidney Dis. 2015;66(5):884-930. 3. FHN Trial Group; Chertow GM, Levin NW, Beck GJ, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2230. 4. No authors listed. Erratum regarding “KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update” (Am J Kidney Dis. 2015;66[5]:884-930). Am J Kidney Dis. 2016;67(3):534. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.12.013
Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome Due to a Mutation in CFH To the Editor: Dr Ardissino and colleagues1,2 recently reported on 16 patients with atypical hemolytic uremic syndrome (aHUS) who discontinued eculizumab treatment: 5 patients experienced relapse and 11 patients remained in stable remission. None of the patients in remission had a mutation in CFH, the gene encoding complement factor H, while 3 of the 5 patients with relapse harbored a CFH mutation. In light of these data, the authors discouraged discontinuation of eculizumab therapy in patients with CFH mutations. In another recent publication, Wetzels et al3 reported 3 patients with aHUS due to CFH mutations and discontinuation of eculizumab, with 1 patient experiencing relapse. The authors hypothesized that the location of the mutation within CFH might be critical and that patients with mutations in short consensus repeat (SCR) 19 and 20 of the gene are more prone to relapse. We describe a young girl presenting with aHUS at the age of 21 months who was treated with 2 doses of eculizumab (Fig 1). Genetic analysis revealed a novel heterozygous mutation in SCR19 of CFH that is predicted to produce a truncated protein due to the introduction of a premature stop codon at amino acid 1155 (p.Gly1155*). Segregation analysis revealed that this mutation was Am J Kidney Dis. 2016;67(3):532-533
Acknowledgements Financial Disclosure: Ms Mancini is employed by Baxter Healthcare Corporation as a Medical Science Liaison.
References 1. National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update. Am J Kidney Dis. 2015;66(5):884-930. 2. FHN Trial Group; Chertow GM, Levin NW, Beck GJ, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2230. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.12.012
In Reply to ‘Hypotension and Frequent Hemodialysis: Clarification Requested Regarding the KDOQI Hemodialysis Adequacy Guideline 2015 Update’ We thank Ann Mancini for her careful review of the KDOQI hemodialysis adequacy guideline update.1 Although we do not believe guideline statement 2.2 is incorrect as published,2 we agree that a clearer explanation is needed. Mancini cites correctly the risk for intradialytic hypotension (IDH) in the FHN Daily Trial. Although the percent risk for IDH per treatment was slightly lower, the exposure to dialysis with a daily schedule was considerably higher because on average, patients randomly assigned to the “daily” schedule received dialysis 5 times per week. For this reason, if one assumes that an episode of IDH causes injury, the cumulative repetitive injury risk in patients randomly assigned to receive “daily” treatments was higher than for those randomly assigned to receive thrice-weekly dialysis. This was reflected by the higher number of total episodes of IDH in patients randomly assigned to receive frequent treatments in the Daily Trial.3 532
We appreciate that the sentence Ms Mancini flags on page 904 of the guideline update does not present this point clearly, and we have published an erratum to remove the inapplicable P value and clarify our intended meaning.4 As the updated wording in the erratum shows, what is important and consequential for each individual patient is the number of hypotensive episodes per unit of time. The risk is clearly higher for the frequently dialyzed patients (nearly 50% higher incidence per patient per year). This is the sense of guideline statement 2.2, which in our estimate emphasizes correctly the increased risk in frequently dialyzed patients. John Daugirdas, MD University of Illinois College of Medicine, Chicago, Illinois Thomas Depner, MD University of California, Davis, Sacramento, California
Acknowledgements Financial Disclosure: The authors declare that they have no relevant financial interests.
References 1. Mancini A. Hypotension and frequent hemodialysis: clarification requested regarding the KDOQI hemodialysis adequacy guideline 2015 update. Am J Kidney Dis. 2016;67(3):532. 2. National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis adequacy: 2015 update. Am J Kidney Dis. 2015;66(5):884-930. 3. FHN Trial Group; Chertow GM, Levin NW, Beck GJ, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med. 2010;363(24):2287-2230. 4. No authors listed. Erratum regarding “KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update” (Am J Kidney Dis. 2015;66[5]:884-930). Am J Kidney Dis. 2016;67(3):534. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.12.013
Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome Due to a Mutation in CFH To the Editor: Dr Ardissino and colleagues1,2 recently reported on 16 patients with atypical hemolytic uremic syndrome (aHUS) who discontinued eculizumab treatment: 5 patients experienced relapse and 11 patients remained in stable remission. None of the patients in remission had a mutation in CFH, the gene encoding complement factor H, while 3 of the 5 patients with relapse harbored a CFH mutation. In light of these data, the authors discouraged discontinuation of eculizumab therapy in patients with CFH mutations. In another recent publication, Wetzels et al3 reported 3 patients with aHUS due to CFH mutations and discontinuation of eculizumab, with 1 patient experiencing relapse. The authors hypothesized that the location of the mutation within CFH might be critical and that patients with mutations in short consensus repeat (SCR) 19 and 20 of the gene are more prone to relapse. We describe a young girl presenting with aHUS at the age of 21 months who was treated with 2 doses of eculizumab (Fig 1). Genetic analysis revealed a novel heterozygous mutation in SCR19 of CFH that is predicted to produce a truncated protein due to the introduction of a premature stop codon at amino acid 1155 (p.Gly1155*). Segregation analysis revealed that this mutation was Am J Kidney Dis. 2016;67(3):532-533
