Use of cystatin C as a marker to detect renal insufficiency in head and neck cancer patients with cisplatin-based chemotherapy

e17048 Background: Knowledge of the usefulness of cystatin C measurement in the detection of chronic kidney disease in patients with head and neck cancer (HNC) is scant. The purpose of this study was to evaluate the ability of plasma cystatin C- and creatinine-based methods to predict glomerular filtration rate (GFR) and classify chronic kidney disease in HNC patients before receiving cisplatin based chemotherapy. Methods: The study population consisted of 43 HNC patients aged 39–76 years. Comparisons were made between measured plasma creatinine, cystatin C, creatinine clearance and GFR estimated by the Modification of Diet in Renal Disease (MDRD) formula. The plasma clearance of (51)Cr-EDTA served as a reference method. Results: The Pearson correlation coefficients between plasma clearance of (51)Cr-EDTA and the markers of GFR were calculated. The correlation coefficients were 0.765 for cystatin C, 0.688 for plasma creatinine, 0.585 for GFR values estimated by MDRD and 0.568 for plasma creatinine clearance. Conclusions: We recommend using cystatin C for the estimation of the GFR of HNC patients instead of solely creatinine or creatinine clearance in clinical practice. No significant financial relationships to disclose.

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Effects of GC4419 (avasopasem manganese) on chronic kidney disease in head and neck cancer patients treated with radiation and cisplatin.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.12071 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 12071-12071

Author(s):

Emily J. Steinbach ◽

Varun Monga ◽

Muhammad Furqan ◽

Douglas Earl Laux ◽

Diana Zepeda-Orozco ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Head And Neck Cancer ◽

Kidney Disease ◽

Head And Neck ◽

Kidney Function ◽

Neck Cancer ◽

Locally Advanced ◽

Male Population ◽

Comparator Group ◽

Platinum Based Chemotherapy

12071 Background: Nephrotoxicity is a major complication of platinum-based chemotherapy and ranges in incidence from 31-68%. The effects of platinum-based chemotherapeutics on long-term renal outcomes (chronic kidney disease, CKD) profoundly affect morbidity and mortality. Concurrent chemoradiotherapy (CRT) including cisplatin is standard for locally advanced squamous cell head and neck cancer (HNC) but is accompanied by the risk of CKD. In a randomized, multi-center, placebo-controlled Phase 2b trial ( NCT02508389 ) of GC4419 (avasopasem manganese) in HNC patients receiving CRT, avasopasem reduced the duration, incidence, and severity of severe oral mucositis (Anderson et al, JCO 2019). Avasopasem did not appear to alter the safety profile of CRT in that trial, including incidence of adverse events of kidney injury or azotemia. Methods: Pre- and post-treatment markers of kidney function including blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were retrospectively evaluated for a subset of 52 of the trial patients who received 3 cycles x 100 mg/m2 cisplatin plus placebo or 30 or 90 mg of avasopasem intravenously prior to RT, and 7 comparator patients who received the same CRT outside the study. Kidney function was evaluated between 3- and 24-months post-completion of cisplatin-radiation therapy by two-way analysis of variance (ANOVA) as defined by the Kidney Disease Improving Global Outcomes (KDIGO) CKD staging. Results: Baseline patient characteristics were skewed towards a male population but were balanced across all treatment arms with regards to baseline kidney function (comparator + placebo, n = 19; 30 mg GC4419, n = 18; 90 mg GC4419, n = 15). Treatment with 90 mg GC4419 demonstrated normal BUN values (10-20 mg/dL) at 3, 6, and 18 months and normal sCr values (0.6-1.2 mg/dL) between 3 and 24 months as compared to the placebo arm + comparator group, which exhibited statistically elevated BUN and sCr (p < 0.05). Treatment with 90 mg GC4419 also demonstrated significantly higher eGFR between 3 and 24 months post-chemoradiation (p < 0.05) compared to the placebo arm + comparator group. 90 mg GC4419 treatment significantly reduced the incidence of CKD compared to the placebo arm and comparator group, as determined by fold change in sCr values and eGFR measurements < 60 mL/min (stage G3a/b, G4, or G5 CKD). Conclusions: Avasopasem has the potential to reduce the incidence and severity of CKD in patients receiving cisplatin therapy. Clinical trial information: NCT02508389 .

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Use of cystatin C as a biomarker for glomerular filtration rate in patients with head and neck cancer receiving cisplatin-based chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.5592 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 5592-5592

Author(s):

E. Boelke ◽

G. Schieren ◽

W. Budach ◽

C. Matuschek ◽

M. Peiper ◽

...

Keyword(s):

Head And Neck Cancer ◽

Glomerular Filtration Rate ◽

Head And Neck ◽

Glomerular Filtration ◽

Cystatin C ◽

Neck Cancer ◽

Filtration Rate

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Genetic Variants as Predictive Markers for Ototoxicity and Nephrotoxicity in Patients with Locally Advanced Head and Neck Cancer Treated with Cisplatin-Containing Chemoradiotherapy (The PRONE Study)

Cancers ◽

10.3390/cancers11040551 ◽

2019 ◽

Vol 11 (4) ◽

pp. 551 ◽

Cited By ~ 3

Author(s):

Chantal M. Driessen ◽

Janneke C. Ham ◽

Maroeska te Loo ◽

Esther van Meerten ◽

Maurits van Lamoen ◽

...

Keyword(s):

Head And Neck Cancer ◽

Side Effects ◽

Creatinine Clearance ◽

Head And Neck ◽

Neck Cancer ◽

Genetic Variants ◽

Locally Advanced ◽

Added Value ◽

Advanced Head ◽

Patient Reported

Ototoxicity and nephrotoxicity are potentially irreversible side effects of chemoradiotherapy with cisplatin in locally advanced head and neck cancer (LAHNC) patients. Several predictive genetic variants have been described, but as yet none in LAHNC patients. The aim of this study is to investigate genetic variants as predictors for ototoxicity and nephrotoxicity in LAHNC patients treated with cisplatin-containing chemoradiotherapy. Our prospective cohort of 92 patients was genotyped for 10 genetic variants and evaluated for their association with cisplatin-induced ototoxicity (ACYP2, COMT, TPMT and WFS1) and nephrotoxicity (OCT2, MATE and XPD). Ototoxicity was determined by patient-reported complaints as well as tone audiometrical assessments. Nephrotoxicity was defined as a decrease of ≥25% in creatinine clearance during treatment compared to baseline. A significant association was observed between carriership of the A allele for rs1872328 in the ACYP2 gene and cisplatin-induced clinically determined ototoxicity (p = 0.019), and not for ototoxicity measured by tone audiometrical assessments (p = 0.449). Carriership of a T allele for rs316019 in the OCT2 gene was significantly associated with nephrotoxicity at any time during chemoradiotherapy (p = 0.022), but not with nephrotoxicity at the end of the chemoradiotherapy. In conclusion, we showed prospectively that in LAHNC patients genetic variants in ACYP2 are significantly associated with clinically determined ototoxicity. Validation studies are necessary to prove the added value for individualized treatments plans in these patients.

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CORRELATION OF RENOGRAM WITH CYSTATIN-C LEVELS AND CREATININE CLEARANCE IN MEASURING GLOMERULAR FILTRATION RATE

Majalah Kedokteran Andalas ◽

10.22338/mka.v38.i1.p1-6.2015 ◽

2015 ◽

Vol 38 (1) ◽

pp. 1

Author(s):

Aisyah Elliyanti ◽

Iskandar Iskandar ◽

Syaiful Azmi

Keyword(s):

Chronic Kidney Disease ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Creatinine Clearance ◽

Glomerular Filtration ◽

Cystatin C ◽

Filtration Rate ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Consecutive Stage

AbstrakRenogram 99mTc-DTPA (diethylenetriamine pentacetic acid) memiliki beberapa kelebihan dalam mengukur laju filtrasi glomerulus (LFG). Cystatin-c digunakan sebagai petanda biologik baru untuk memperkirakan LFG. Tujuan penelitian ini adalah untuk menentukan korelasi nilai LFG antara renogram dengan cystatin-c dan kliren kreatinin pada pasien dengan penyakit ginjal kronis (PGK). Subjek penelitian adalah pasien PGK stadium dua berdasarkan hasil estimasi LFG dengan rumus Cockroft-Gault. Pasien yang memenuhi kriteria diperiksa renogram, kadar kreatinin serum, cystatin-c dan klirens kreatinin.Rerata LFG dari 30 orang subjek yang diperiksa dengan renogram, cystatin-c, creatinine clearance, Cockroft-Gault’s formula berturut turut adalah 64.96 ml/min/1.73m2 (SD 28.047), 53.37 ml/min/1.73m2 (SD 21.29), 58.09 ml/min/1.73m2 (SD 35.45), 46.00 ml/min/1.73m2 (SD 12.06). Korelasi antara renogram dengan cystatin-c dengan nilai r = 0.585 dan p = 0.0007, antara renogram dengan klirens kreatinin dengan nilai r = 0.388 dan p = 0.03) dan antara renogram dengan rumus Cockroft-Gault’s dengan nilai r = -0.029 dan p=0.87. Pada penelitian ini didapatkan hasil korelasi yang lebih baik antara renogram dengan cystatin-c dari pada antara renogram dengan klirens kreatinin dan antara renogram dengan rumus Cockroft-Gault’s. Lebih lanjut, cystain-c merupakan alternatif yang lebih baik untuk memperkirakan LFG jika metode pemeriksaan LFG yang mendekati teknik pemeriksaan yang ideal tidak tersedia.AbstractRenogram using 99mTc-DTPA (diethylenetriamine pentacetic acid) has advantages in the measurement of glomerular filtration rate (GFR). Serum cystatin-c was recently projected to be the new marker of estimated GFR. The aim of this study is to establish correlation between GFRs, derived from renogram with cystatin-c levels and creatinine clearances in chronic kidney disease patients.We put to study thirty consecutive stage two of chronic kidney disease patients assigned based on GFR estimation by Cockroft-Gault’s formula, taking into account the serum creatinine. Cystatin-c and creatinine clearance were performed to determine of GFR and renogram was included in this study. A total of thirty subjects, the mean of GFRs were taken from renogram, cystatin-c, creatinine clearance, Cockroft-Gault’s formula were 64.96 ml/min/1.73m2 (SD 28.047), 53.37 ml/min/1.73m2 (SD 21.29), 58.09 ml/min/1.73m2 (SD 35.45), 46.00 ml/min/1.73m2 (SD 12.06) respectively. A correlation between renogram with cystatin-c (r = 0.585 and p = 0.0007) and renogram with creatinine clearance (r = 0.388 and p = 0.03) and renogram with Cockroft-Gault’s formula (r = -0.029 and p=0.87). This study has shown that a better correlation between renogram with cystatin-c than with creatinine clearance or Cockroft-Gault’s formula. Furthermore, cystain-c would be better alternative method incase having problems to obtain a closest ideal methods for GFR.

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Decrease of creatinine clearance rate with aging in patients with head and neck cancer in Japan

International Journal of Clinical Oncology ◽

10.1007/s10147-006-0635-9 ◽

2007 ◽

Vol 12 (2) ◽

pp. 120-124 ◽

Cited By ~ 11

Author(s):

Goshi Nishimura ◽

Mamoru Tsukuda ◽

Choichi Horiuchi ◽

Kenichi Satake ◽

Takafumi Yoshida ◽

...

Keyword(s):

Head And Neck Cancer ◽

Creatinine Clearance ◽

Head And Neck ◽

Neck Cancer ◽

Clearance Rate ◽

Creatinine Clearance Rate

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The Aqueous Extract from the Stem Bark of Garcinia lucida Vesque (Clusiaceae) Exhibits Cardioprotective and Nephroprotective Effects in Adenine-Induced Chronic Kidney Disease in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5581041 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Christelle Stéphanie Sonfack ◽

Elvine Pami Nguelefack-Mbuyo ◽

Jacquy Joyce Kojom ◽

Edwige Laure Lappa ◽

Fernande Petingmve Peyembouo ◽

...

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Creatinine Clearance ◽

Aqueous Extract ◽

Stem Bark ◽

Plasma Creatinine ◽

High Morbidity ◽

Bodyweight Loss

Chronic kidney disease (CKD) is a serious health problem with high morbidity and mortality, mainly attributable to cardiovascular risk. Garcinia lucida is traditionally used in Cameroon for the management of cardiovascular diseases. The aim of this study was to evaluate the cardioprotective and nephroprotective effects of the aqueous extract from the stem bark of G. lucida (AEGL). The in vitro antioxidant effect of AEGL was assessed at concentrations ranging 1–300 μg/mL against DPPH, lipid peroxidation, and AAPH-induced hemolysis. The reducing power and phenolic and flavonoids contents were also determined. CKD was induced by intraperitoneal bolus injection of adenine (50 mg/kg/day) for 4 consecutive weeks to male Wistar rats. AEGL (150 and 300 mg/kg/day) or captopril (20 mg/kg/day) was concomitantly administered with adenine per os. Bodyweight and blood pressure were monitored at baseline and weekly during the test. At the end of the experiment, plasma creatinine, urea, AST, and ALT were quantified. Proteinuria, creatinine excretion, and creatinine clearance were also assessed. The effect on GSH, CAT, and SOD activity was evaluated in cardiac and renal homogenates. Sections of the heart and kidney were stained with hematoxylin and eosin. AEGL exhibited a potent in vitro antioxidant activity and was shown to possess a large amount of phenolic compounds. Adenine alone increased blood pressure, cardiac and kidney mass, proteinuria, protein to creatinine ratio, plasma creatinine, AST, and urea levels ( p < 0.05 , 0.01, and 0.001). Besides, the bodyweight and creatinine clearance were significantly reduced ( p < 0.05 and p < 0.01 ). All these alterations were blunted by the plant extract, except the bodyweight loss. In addition, AEGL improved GSH levels and CAT and SOD activities. AEGL attenuated adenine-induced glomerular necrosis, tubular dilatation, and cardiac inflammation. AEGL exhibits cardioprotective and nephroprotective effects that may be ascribed to its antihypertensive and antioxidant activities.

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Improve optimal treatment in head and neck cancer patients (HNCA).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.30_suppl.227 ◽

2014 ◽

Vol 32 (30_suppl) ◽

pp. 227-227

Author(s):

Glenn Morris Mills ◽

Rebecca L. DeKay ◽

Srinivas S. Devarakonda ◽

Jennifer Nicholson ◽

Lee Ann Maranto ◽

...

Keyword(s):

Head And Neck Cancer ◽

Creatinine Clearance ◽

Head And Neck ◽

Neck Cancer ◽

Chart Review ◽

Speech Pathology ◽

Post Intervention ◽

Pareto Chart ◽

Peg Tube ◽

Practitioner Education

227 Background: Since 2011, 50% of HNCA patients receiving concurrent chemoradiation with Cisplatin (CIS/XRT) have not been able to complete their therapy per protocol (dose over time interval) leading to suboptimal therapy. Based on historical data, the non-completion rate for patients HNCA receiving radiation/ high dose Cisplatin was 15%. We aim to improve this in our patients. Methods: A chart review of patients on CIS/XRT conducted and, using a Pareto Chart, the data indicated Acute Kidney Iinjury as the major cause for failure of completion. Using methodology from ASCO’s Quality Training Program, a process map for patients on treatment was created and an Ishikawa diagram (cause and effect) assisted in pinpointing breaks in processes. A telephone survey of surviving patients further clarified inadequacies. Using the Plan, Do, Study, Act (PDSA) improvement cycle, inadequacies were identified. Results: Chart review showed that significant side effects from treatment began around the 2nd cycle of Cisplatin in spite of adequate IV hydration following chemotherapy. Inadequate documentation of dietary and speech pathology consultations, patient weight and serum creatinine levels during treatment were noted. Patients reported minimal PEG tube education and infrequent use of PEG tube for hydration. Analysis of post treatment weight and creatinine level revealed a significant change in creatinine clearance. Checking daily weights, speech pathology and dietary consult prior to initiation of therapy, added hydration instructions to EPIC PEG tube instruction sheet, and nurse practitioner education and follow-up in symptom management clinic were part of the PDSA cycle interventions. If 2lb. weight loss, patients were brought in for repeat lab and IV hydration. Conclusions: Patients with advanced head and neck cancer are frail and subject to acute toxicity from chemotherapy. Change in Creatinine Clearance is a sensitive measure of renal damage/likely predictor of non-completion. Post-intervention patients had fewer unplanned admissions leading to lower costs. PDSA helped identify inadequacies in our education and monitoring processes. More post intervention data are needed to determine if true improvement in patient outcomes exist.

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