Correspondence

In Reply to ‘Creatinine-Based GFR Estimating Equations in Kidney Transplant Recipients’ and ‘Assessing Kidney Function in Transplant Recipients: Time to Work Together and Address the Most Relevant Questions’ We are pleased that Dr Delanaye1 and Drs Gill and Morris2 agree with our conclusions3 that the CKD-EPI and MDRD Study equations are more accurate than other creatinine-based equations in estimating glomerular filtration rate (GFR) in transplant recipients. We agree that the use of standardized creatinine level in these equations likely is an important factor contributing to their better performance. The BIS equation also uses standardized creatinine level, but was developed in a cohort with a mean age of 78 years, thus performing less well than the CKD-EPI and MDRD Study equations in those younger than 55 years and similarly to these equations in those 55 years or older (as shown in Fig S2 of our article3). Because most clinical laboratories are now using standardized creatinine assays, we would hope that guidelines would be updated to recommend using either the CKD-EPI or MDRD Study equations for reporting estimated GFR (eGFR) in transplant recipients. Although the 2 equations performed similarly in the entire cohort, the CKD-EPI equation is more accurate at higher GFRs and the MDRD Study equation is more accurate at lower GFRs (Fig S8 in our article).3 Because P30 (proportions of the subjects in whom absolute value of percent error [mGFR-eGFR/mGFR] is , or #30%) reflects percent errors, the magnitude of errors in the MDRD Study equation at higher eGFRs is larger than errors of the CKD-EPI equation at lower eGFRs. We acknowledge the limitation in accuracy of eGFR compared to measured GFR and the limited ability of GFR to detect kidney damage relevant for the early diagnosis of transplant rejection and other conditions. We agree that improving estimating equations and discovering kidney measures other than GFR to detect transplant damage are important research goals. Andrew S. Levey, MD1 Kamran Shaffi, MD2 Lesley A. Inker, MD1 1 Tufts Medical Center Boston, Massachusetts 2 University of New Mexico Albuquerque, New Mexico

Acknowledgements Financial Disclosure: The authors declare that they have no relevant financial interests.

References 1. Delanaye P. Creatinine-based GFR estimating equations in kidney transplant recipients. Am J Kidney Dis. 2014;64(5): 818. 2. Gill JS, Morris R. Time to work together and address the most relevant questions: comment on Shaffi et al. Am J Kidney Dis. 2014;64(5):818. 3. Shaffi K, Uhlig K, Perrone RD, et al. Performance of creatinine-based GFR estimating equations in solid-organ transplant recipients. Am J Kidney Dis. 2014;63(6):1007-1018. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.07.017

Am J Kidney Dis. 2014;64(5):817-820

Not All Convective Dialysis Therapies Are Equal To the Editor: With interest we read the systematic review of convective dialysis therapies by Nistor et al,1 which concluded that “in lowquality evidence, convective therapies had little or no effect on all-cause mortality.”1(p954) A meta-analysis is considered the highest evidence level, yet 3 recent meta-analyses of convective therapies showed different outcomes.1-3 Nistor et al1 compared hemodialysis to hemodiafiltration and acetate-free biofiltration, Susantitaphong et al2 analyzed low-flux hemodialysis in relation to high-flux hemodialysis and hemodiafiltration, and Mostavaya et al3 considered only randomized controlled trials in which online hemodiafiltration was compared to hemodialysis. Obviously, conclusions depend not only on data extraction and estimation of risk of bias, but also on the definition of convective therapies applied. In the mortality meta-analysis by Nistor et al,1 both an acetate-free biofiltration study and an offline hemodiafiltration study were included. However, these therapies can hardly be considered modern convective therapies because convection volumes of 8 L per session4 or 10-12 L per session5 are comparable to the amount of internal filtration in high-flux hemodialysis.6 Further, these convection volumes are completely different from those used in postdilution hemodiafiltration (17-23 L/session) or hemofiltration. After removing these studies, the relative risk for mortality becomes 0.82 (95% confidence interval, 0.72-0.93), which appears a better risk estimate. In our opinion, a statement on modern convective therapies should be based on randomized controlled trials of online convective treatments. Our second major concern is the absence of blinding for treatment assignment as an important risk of bias. In daily practice, blinding of patients and staff is impossible simply because patients are placed next to dialysis machines that are set and monitored by nursing staff. Muriel P.C. Grooteman, MD, PhD1 Peter J. Blankestijn, MD, PhD2 Menso J. Nubé, MD, PhD1 1 VU Medical Center, Amsterdam, the Netherlands 2 University Medical Center Utrecht, Utrecht, the Netherlands

Acknowledgements Financial Disclosure: Dr Grooteman reports receiving lecture fees from and research funded by Fresenius Medical Care BV, The Netherlands. Dr Blankestijn received research funding and speaker fees from Fresenius Medical Care BV, The Netherlands. Dr Nube reports research funding from Fresenius Medical Care BV, The Netherlands.

References 1. Nistor I, Palmer SC, Craig JC, et al. Convective versus diffusive dialysis therapies for chronic kidney failure: an updated systematic review of randomized controlled trials. Am J Kidney Dis. 2014;63:954-967. 2. Susantitaphong P, Siribamrungwong M, Jaber BL. Convective therapies versus low-flux hemodialysis for chronic kidney failure: a meta-analysis of randomized controlled trials. Nephrol Dial Transplant. 2013;28:2859-2874. 3. Mostovaya I, Blankestijn PJ, Bots ML, et al. Clinical evidence on hemodiafiltration: a systematic review and a metaanalysis. Semin Dial. 2014;27:119-127. 4. Tessitore N, Santoro A, Panzetta GO, et al. Acetate-free biofiltration reduces intradialytic hypotension: a European multicenter randomized controlled trial. Blood Purif. 2012;34:354-363. 819

Correspondence 5. Locatelli F, Mastrangelo F, Redaelli B, et al. Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters. The Italian Cooperative Dialysis Study Group. Kidney Int. 1996;50:1293-1302. 6. Ronco C, Brendolan A, Lupi A, et al. Effects of a reduced inner diameter of hollow fibers in hemodialyzers. Kidney Int. 2000;58:809-817. Nistor et al declined to respond. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.03.024

absolute terms, convective therapy might [emphasis added] prevent 25 cardiovascular deaths for every 1000 patients treated for 1 year, but has no significant effect on death overall.”1(p962) Moreover, in our view, the decision to solicit unpublished data for the meta-analysis from 10 past trials—unavailable to the reader for scrutiny—is in itself a breach of scientific candor. Ultimately, like most meta-analyses, the review by Nistor et al1 is not without its own methodologic limitations, which not only impair informed decision making but also may suppress therapy modality innovations that increase quality of patient care.2 Sudhir K. Bowry, MSc, PhD Christian Apel, BSc, MSc Bernard Canaud, MD, PhD Fresenius Medical Care GmbH Bad Homburg, Germany

Assessment of Clinical Evidence for Convective Dialysis Therapies To the Editor: Evidence-based medicine is the cornerstone for informed decision making in health care and policy. We take issue with aspects of the recent systematic review by Nistor et al1 of convective versus diffusive dialysis therapies. More than one-third of the studies assessed by the authors could be deemed inappropriate in terms of size under good clinical trial practices: of the 35 studies, 13 included 15 or fewer patients and 1 included only 5. Further, 5 trials are pre-2000, one of which is from 1987, when hemodiafiltration was in its technological infancy. Inexplicably, the Convective Transport Study (CONTRAST) was adjudged as having the least risk of bias of all studies, yet there is no mention of a violation of study protocol (not achieving target convective dose, which is decisive in providing the survival advantage) in almost two-thirds of the hemodiafiltration arm of patients. From a statistical standpoint, relative risks of cardiovascular mortality and hypotension were reduced significantly with convective therapies, but the authors downplay these data: “In

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Acknowledgements Financial Disclosure: The authors are employed by Fresenius Medical Care, which markets various dialysis therapy systems.

References 1. Nistor I, Palmer SC, Craig JC, et al. Convective versus diffusive dialysis therapies for chronic kidney failure: an updated systematic review of randomized controlled trials. Am J Kidney Dis. 2014;63(6):954-967. 2. Locatelli F. Comparison of hemodialysis, hemodiafiltration, and hemofiltration: systematic review or systematic error? Am J Kidney Dis. 2005;46(4):787-788. Nistor et al declined to respond. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.05.026

Am J Kidney Dis. 2014;64(5):817-820

Not all convective dialysis therapies are equal.

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