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Cystatin C – A Fast and Reliable Biomarker for Glomerular Filtration Rate in Head and Neck Cancer Patients

Cystatin C – ein schneller und zuverlässiger Marker zur Bestimmung der glomerulären Filtrationsrate vor einer cisplatinhaltigen Chemotherapie bei Patienten mit Kopf-Hals-Tumoren

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Abstract

Purpose:

Determination of renal function is a prerequisite for planning therapy in cancer patients. Limitations of creatinine as marker for the glomerular filtration rate (GFR) led to the proposal of cystatin C as a more accurate biomarker especially in mild renal insufficiency or in patients with low muscle mass. We compared the accuracy of cystatin C- and creatinine-based equations to estimate GFR in head and neck cancer (HNC) patients receiving platinum-based radiochemotherapy.

Patients and Methods:

The study population consisted of 52 HNC patients (GFR range, 37–105 mL/min/1.73 m2 complemented by 17 patients with known renal insufficiency (GFR range, 10–60 mL/min/1.73 m2). Intraclass correlation coefficients were calculated between the reference method (51)Cr-EDTA clearance and estimated GFR by creatinine clearance and equations based on creatinine (Cockroft-Gault, modification of diet in renal disease (MDRD), Wright) or cystatin C (Larsson, Dade-Behring, Hoek). In addition, sensitivity and specificity to discriminate GFR > 60 mL/min/1.73 m2 were evaluated by receiver operating characteristic curve (ROC).

Results:

The highest correlation coefficients were found for the cystatin C-based estimates in comparison with creatinine-based estimates or creatinine clearance, even though Bland-Altman plots revealed GFR overestimation for all equations tested. The cystatin C-based Hoek formula exhibited the highest overall precision and accuracy. GFR of < 60 mL/min/1.73 m2 was assumed as a cut-off for chemotherapy. ROC analyses revealed the highest AUC to predict a GFR > 60 mL/min/1.73 m2 for the creatinine-based Wright formula, closely followed by the MDRD formula and cystatin C-based equations of Larsson, Dade-Behring, and Hoek.

Conclusion:

Cystatin C-based GFR estimates showed the overall strongest correlation to the reference method. Thus, we recommend cystatin C for GFR estimation in HNC patients as an alternative method to the estimated creatinine clearance in clinical practice.

Zusammenfassung

Zielsetzung:

Bei Tumorpatienten ist die exakte Bestimmung der Nierenfunktion eine wichtige Voraussetzung für die individuelle Therapieplanung. Die Aussagefähigkeit des Serumkreatinins als Marker der glomerulären Filtrationsrate (GFR) ist jedoch limitiert aufgrund seiner Abhängigkeit von der Muskelmasse sowie fehlendem Anstieg der Serumkonzentration bei einer GFR > 60 ml/ min/1,73 m2. Cystatin C wird als sensitiverer Parameter für das Vorliegen einer Niereninsuffizienz in den Frühstadien sowie bei Muskelschwachen Patienten diskutiert. In der vorliegenden Studie wurde die Präzision von Cystatin-C-basierten sowie Kreatinin-basierten Formeln zur Berechung der GFR in Kopf-Hals-Tumorpatienten verglichen.

Patienten und Methodik:

Die Studienkohorte bestand aus 52 Kopf-Hals-Tumorpatienten (GFR 37–105 mL/min/1,73 m2) sowie 17 Patienten mit bekannter Niereninsuffizienz Stadium 3–5 (GFR 10–60 mL/min/1,73 m2). Es wurde der Intra-Class-Correlation factor berechnet zwischen der Referenzmethode (51)Cr-EDTA-Clearance und der Kreatinin-Clearance, den Kreatinin-basierten Formeln (Cockroft-Gault, Modified Diet in Renal Disease, Wright) und den Cystatin-C-basierten Formeln (Larsson, Dade-Behring, Hoek) zur GFR-Berechnung. Zusätzlich ermittelten wir Sensitivität und Spezifität der verschiedenen Clearance-Bestimmungen zur Erkennung einer GFR > 60 ml/min/1,73 m2 mittels Receiver Operating Characteristic Curve (ROC).

Ergebnisse:

Die beste Korrelation zur Referenzmethode wurde für die Cystatin-C-basierten Formeln zur GFR-Bestimmung im Vergleich zu Kreatinin-basierten Formeln oder der Kreatinin-Clearance ermittelt. Jedoch zeigte der Bland-Altman-Plot, dass im Vergleich zur Referenzmethode alle Formeln – sowohl Cystatin-C- als auch Kreatinin-basiert – die Nierenfunktion überschätzen. Die höchste Genauigkeit und Präzision wurde bei der Hoek-Formel beobachtet. Da eine GFR < 60 ml/min/1,73 m2 häufig als Grenze angesehen wird zur Durchführung einer Chemotherapie, ermittelten wir die Präzision, mit der die verschiedenen GFR-Bestimmungen dies für den Einzelnen voraussagen konnten. Bei der ROC-Analyse zeigte die Kreatinin-basierte Formel nach Wright die höchste Area Under the Curve, dicht gefolgt von der Modified-Diet-in-Renal-Disease-Formel und den Cystatin-C-basierten Formeln nach Larsson, Dade-Behring und Hoek.

Schlussfolgerung:

Die Cystatin-C-basierten Formeln zur GFR-Berechnung zeigten insgesamt die beste Präzision und Korrelation zur Referenzmethode in Kopf-Hals-Tumorpatienten. Daher empfehlen wir Cystatin-C-basierte Formeln zur GFR-Berechnung im klinischen Alltag bei diesen Patienten.

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Author information

Author notes

  1. Matthias Peiper

    Present address: Department of General, Visceral and Trauma Surgery, Essen-Süd Hospital, Essen, Germany

Authors and Affiliations

  1. Department of Radiation Therapy and Radiation Oncology, University of Düsseldorf, Düsseldorf, Germany

    Edwin Bölke*, Stephan Gripp, Klaus Orth, Christiane Matuschek, Maximilian Pelzer, Guido Lammering, Rodrigo Mota, Peter Arne Gerber & Wilfried Budach*

  2. Department of Nephrology, University of Düsseldorf, Düsseldorf, Germany

    Gisela Schieren* & Lars Christian Rump

  3. Department of Clinical Chemistry, University of Ulm, Ulm, Germany

    Gerald Steinbach

  4. Department of Surgery, University of Düsseldorf, Düsseldorf, Germany

    Matthias Peiper

  5. Radiation Oncology, Maastro Clinic, Maastricht, The Netherlands

    Guido Lammering & Ruud Houben

  6. Department of Nuclear Medicine, University of Düsseldorf, Düsseldorf, Germany

    Christina Antke

  7. Department of Clinical Chemistry and Laboratory Diagnostics, University of Düsseldorf, Düsseldorf, Germany

    Derik Hermsen*

  8. Department of Otorhinolaryngology, Head and Neck Surgery, University of Essen, Essen, Germany

    Patrick Schuler & Thomas K. Hoffmann

  9. Department of Anesthesiology, State University of New York at Buffalo, Buffalo, NY, USA

    Ethelyn Rusnak

  10. Klinik für Strahlentherapie und Radiologische Onkologie, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany

    Edwin Bölke*

Authors
  1. Edwin Bölke*
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  2. Gisela Schieren*
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Correspondence to Edwin Bölke*.

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*Authors contributed equally to this work.

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Bölke*, E., Schieren*, G., Gripp, S. et al. Cystatin C – A Fast and Reliable Biomarker for Glomerular Filtration Rate in Head and Neck Cancer Patients. Strahlenther Onkol 187, 191–201 (2011). https://doi.org/10.1007/s00066-010-2203-5

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  • DOI: https://doi.org/10.1007/s00066-010-2203-5

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