Correspondence

LETTERS TO THE EDITOR

Serum Cystatin C May Diagnose Rather ThanPredict Acute Kidney InjuryTo the Editor:

We read the recent meta-analysis by Zhang et al1 with concern.Recalculation of the main result (an area under the curve [AUC] of 0.96with a narrow confidence interval [0.95-0.97]) using the data providedshows an (un)weighted AUC of 0.8 regardless of whether the Liang et alstudy2 is included or not. The diagnostic odds ratio of 23.5 cannot berelated to the reportedAUC of 0.96.3

Even the recalculated AUC of 0.8 may not be reliable: 8 out of 15datasets provided in the third table do not match with any circle in thesecond figure of Zhang et al. One of the largest studies (Krawczeski etal4) and the study by Wald et al5 do not appear to be presented in thisfigure at all.

Additionally, only 11 out 15 studies provide paired sensitivity andspecificity. We, therefore, ask: which studies do the remaining 4circles in the second figure of Zhang et al refer to?An annotated figureshowing the corresponding circle for each of the 15 studies isnecessary for interpretation.

Further, we are concerned about study selection. The study byHaase et al6 showed that the value of early postsurgery serumcystatin C to predict acute kidney injury was in great part acarry-over effect from presurgery values in patients who subse-quently developed acute kidney injury.

Until such reassessment, we recommend caution interpretingthe findings of this meta-analysis.

Michael Haase, MD1

Rinaldo Bellomo, MD2

Anja Haase-Fielitz, PharmD1

1Otto-von-Guericke University MagdeburgMagdeburg, Germany

2Austin University HospitalMelbourne, Australia

AcknowledgementsFinancial Disclosure: Drs Haase and Bellomo have received

lecture fees from Abbott Diagnostics and Biosite/Alere Inc. Bothcompanies are involved in the development of NGAL assays to beapplied in clinical practice.

References1. Zhang Z, Lu B, Sheng X, Jin N. Cystatin C in prediction of

acute kidney injury: a systemic review and meta-analysis. Am JKidney Dis. 2011;58(3):356-365.

2. Liang XL, Shi W, Liu SX, et al. Prospective study of cystatinC for diagnosis of acute kidney injury after cardiac surgery. NanFang Yi Ke Da Xue Xue Bao. 2008;28(12):2154-2156.

3. Walter SD. Properties of the summary receiver operatingcharacteristic (SROC) curve for diagnostic test data. Stat Med.2002;21(9):1237-1256.

4. Krawczeski CD, Vandevoorde RG, Kathman T, et al. Serumcystatin C is an early predictive biomarker of acute kidney injuryafter pediatric cardiopulmonary bypass. Clin J Am Soc Nephrol.2010;5(9):1552-1557.

5. Wald R, Liangos O, Perianayagam MC, et al. Plasma cystatinC and acute kidney injury after cardiopulmonary bypass. Clin J AmSoc Nephrol. 2010;5(8):1373-1379.

6. Haase M, Bellomo R, Devarajan P, et al. Novel biomark-ers early predict the severity of acute kidney injury after cardiac

surgery in adults. Ann Thorac Surg. 2009;88(1):124-130.

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© 2012 by the National Kidney Foundation, Inc.doi:10.1053/j.ajkd.2011.07.028

In Reply to ‘Serum Cystatin C May Diagnose RatherThan Predict Acute Kidney Injury’

We thank Haase et al1 for their comments regarding our meta-analysis2 of the use of cystatin C in predicting acute kidney injury.

An area under the receiver operating characteristic curve (AUROC) of0.8 might be calculated using the sample size as the weight. However, inour study we used the standard error as the weight, which is an approachrecommended and validated by McClish.3 However, we concede thatbecause the test for heterogeneity was highly significant, a random effectsmodel would be more appropriate. Recalculating accordingly gives anestimate of 0.87 for the AUROC, instead of 0.96 as published in ourstudy. An Erratum notifying readers of this recalculated value is alsopublished in this issue.4

With respect to the comment regarding the diagnostic odds ratio,we acknowledge that the pooled diagnostic odds ratio is notdirectly related to a pooled AUROC.

As to the identity of circles shown in our article’s data figures, weextracted more than one set of data from a study if multiple measurementsof cystatin C were provided for different time points. Since this issue wasraised, we have learned that this methodology would only be appropriatein the case of independent subgroups; revised versions of the affectedfigures have been included in the Erratum.

With respect to the inclusion of the study by Haase et al,5 we concurthat presurgical kidney function is another determinant of acute kidneyinjury in patients who are undergoing cardiac bypass surgery.

Zhongheng Zhang, MDBaolong Lu, MD

Jinhua Municipal Central HospitalZhejiang, China

AcknowledgementsFinancial Disclosure: The authors declare that they have no

relevant financial interests.

References1. Haase M, Bellomo R, Haase-Fielitz A. Serum cystatin C may

diagnose rather than predict acute kidney injury. Am J Kidney Dis.2012;59(4):582.

2. Zhang Z, Lu B, Sheng X, Jin N. Cystatin C in prediction ofacute kidney injury: a systemic review and meta-analysis. Am JKidney Dis. 2011;58(3):356-365.

3. McClish DK. Combining and comparing area estimatesacross studies or strata. Med Decis Making. 1992;12(4):274-279.

4. No authors listed. Erratum regarding “Cystatin C in prediction ofacute kidney injury: a systematic review and meta-analysis” (Am JKidney Dis 2011; 58:356-365). Am J Kidney Dis. 2012;59(4):590-592.

5. Haase M, Bellomo R, Devarajan P, et al. Novel biomarkersearly predict the severity of acute kidney injury after cardiacsurgery in adults. Ann Thorac Surg. 2009;88(1):124-130.

© 2012 by the National Kidney Foundation, Inc.doi:10.1053/j.ajkd.2011.12.013

Secondary Capillary Leak Syndrome Related toPemetrexed ExposureTo the Editor:

We read the article by Glezerman et al1 with great interest. We would

like to report a patient who developed systemic capillary leak syndrome

Am J Kidney Dis. 2012;59(4):582-589