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26.06.2023 | Original Article

Urinary TIMP-2*IGFBP-7 to diagnose acute kidney injury in children receiving cisplatin

verfasst von: Hayton Chui, Kelly R. McMahon, Shahrad Rod Rassekh, Kirk R. Schultz, Tom D. Blydt-Hansen, Cherry Mammen, Maury Pinsk, Geoffrey D. E. Cuvelier, Bruce C. Carleton, Ross T. Tsuyuki, Colin J. D. Ross, Prasad Devarajan, Louis Huynh, Mariya Yordanova, Frédérik Crépeau-Hubert, Stella Wang, Vedran Cockovski, Ana Palijan, Michael Zappitelli, for the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Research Study Group

Erschienen in: Pediatric Nephrology | Ausgabe 1/2024

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Abstract

Background

Cisplatin is associated with acute kidney injury (AKI) and electrolyte abnormalities. Urine tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7) may be early cisplatin-AKI biomarkers.

Methods

We conducted a 12-site prospective cohort study with pediatric patients treated with cisplatin (May 2013–December 2017). Blood and urine (measured for TIMP-2, IGFBP-7) were collected pre-cisplatin, 24-h post-cisplatin, and near hospital discharge during the first or second cisplatin cycle (early visit (EV)) and during second-to-last or last cisplatin cycle (late visit (LV)). Primary outcome: serum creatinine (SCr)-defined AKI (≥ stage 1).

Results

At EV (median (interquartile (IQR)) age: 6 (2–12) years; 78 (50%) female), 46/156 (29%) developed AKI; at LV, 22/127 (17%) experienced AKI. At EV, TIMP-2, IGFBP-7, and TIMP-2*IGFBP-7 pre-cisplatin infusion concentrations were significantly higher in participants with vs. those without AKI. At EV and LV, biomarker concentrations were significantly lower in participants with vs. those without AKI at post-infusion and near-hospital discharge. Biomarker values normalized to urine creatinine were higher in patients with AKI compared to without (LV post-infusion, median (IQR): TIMP-2*IGFBP-7: 0.28 (0.08–0.56) vs. 0.04 (0.02–0.12) (ng/mg creatinine)²/1000; P < .001). At EV, pre-infusion biomarker concentrations had the highest area under the curves (AUC) (range: 0.61–0.62) for AKI diagnosis; at LV, biomarkers measured post-infusion and near discharge yielded the highest AUCs (range: 0.64–0.70).

Conclusions

TIMP-2*IGFBP-7 were poor to modest at detecting AKI post-cisplatin. Additional studies are needed to determine whether raw biomarker values or biomarker values normalized to urinary creatinine are more strongly associated with patient outcomes.

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Oeffinger KC, Eshelman DA, Tomlinson GE, Buchanan GR, Foster BM (2000) Grading of late effects in young adult survivors of childhood cancer followed in an ambulatory adult setting. Cancer 88:1687–1695CrossRefPubMed

Bottomley SJ, Kassner E (2003) Late effects of childhood cancer therapy. J Pediatr Nurs 18:126–133CrossRefPubMed

Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, Friedman DL, Marina N, Hobbie W, Kadan-Lottick NS, Schwartz CL, Leisenring W, Robison LL, Childhood Cancer Survivor Study (2006) Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355:1572–1582CrossRefPubMed

Fujieda M, Matsunaga A, Hayashi A, Tauchi H, Chayama K, Sekine T (2009) Children’s toxicology from bench to bed--drug-induced renal injury (2): nephrotoxicity induced by cisplatin and ifosfamide in children. J Toxicol Sci 34(Suppl 2):SP251–S257

Ariceta G, Rodriguez-Soriano J, Vallo A, Navajas A (1997) Acute and chronic effects of cisplatin therapy on renal magnesium homeostasis. Med Pediatr Oncol 28:35–40CrossRefPubMed

Goren MP, Wright RK, Horowitz ME (1986) Cumulative renal tubular damage associated with cisplatin nephrotoxicity. Cancer Chemother Pharmacol 18:69–73CrossRefPubMed

McMahon KR, Harel-Sterling M, Pizzi M, Huynh L, Hessey E, Zappitelli M (2018) Long-term renal follow-up of children treated with cisplatin, carboplatin, or ifosfamide: a pilot study. Pediatr Nephrol 33:2311–2320CrossRefPubMed

Skinner R, Parry A, Price L, Cole M, Craft AW, Pearson AD (2009) Persistent nephrotoxicity during 10-year follow-up after cisplatin or carboplatin treatment in childhood: relevance of age and dose as risk factors. Eur J Cancer 45:3213–3219CrossRefPubMed

Skinner R, Pearson AD, Price L, Coulthard MG, Craft AW (1992) The influence of age on nephrotoxicity following chemotherapy in children. Br J Cancer 18:S30–S35

10.

Jones CA, McQuillan GM, Kusek JW, Eberhardt MS, Herman WH, Coresh J, Salive M, Jones CP, Agodoa LY (1998) Serum creatinine levels in the US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis 32:992–999CrossRefPubMed

11.

Dharnidharka VR, Kwon C, Stevens G (2002) Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis 40:221–226CrossRefPubMed

12.

Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, Davison DL, Feldkamp T, Forni LG, Gong MN, Gunnerson KJ, Haase M, Hackett J, Honore PM, Hoste EA, Joannes-Boyau O, Joannidis M, Kim P, Koyner JL, Laskowitz DT, Lissauer ME, Marx G, McCullough PA, Mullaney S, Ostermann M, Rimmele T, Shapiro NI, Shaw AD, Shi J, Sprague AM, Vincent JL, Vinsonneau C, Wagner L, Walker MG, Wilkerson RG, Zacharowski K, Kellum JA (2013) Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care 17:R25CrossRefPubMedPubMedCentral

13.

Meersch M, Schmidt C, Van Aken H, Rossaint J, Gorlich D, Stege D, Malec E, Januszewska K, Zarbock A (2014) Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery. PLoS One 9:e110865

14.

Bihorac A, Chawla LS, Shaw AD, Al-Khafaji A, Davison DL, Demuth GE, Fitzgerald R, Gong MN, Graham DD, Gunnerson K, Heung M, Jortani S, Kleerup E, Koyner JL, Krell K, Letourneau J, Lissauer M, Miner J, Nguyen HB, Ortega LM, Self WH, Sellman R, Shi J, Straseski J, Szalados JE, Wilber ST, Walker MG, Wilson J, Wunderink R, Zimmerman J, Kellum JA (2014) Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med 189:932–939CrossRefPubMed

15.

Hoste EA, McCullough PA, Kashani K, Chawla LS, Joannidis M, Shaw AD, Feldkamp T, Uettwiller-Geiger DL, McCarthy P, Shi J, Walker MG, Kellum JA (2014) Derivation and validation of cutoffs for clinical use of cell cycle arrest biomarkers. Nephrol Dial Transplant 29:2054–2061CrossRefPubMedPubMedCentral

16.

Schanz M, Hoferer A, Shi J, Alscher MD, Kimmel M (2017) Urinary TIMP2IGFBP7 for the prediction of platinum-induced acute renal injury. Int J Nephrol Renovasc Dis 10:175–181CrossRefPubMedPubMedCentral

17.

Chen J, Sun Y, Wang S, Dai X, Huang H, Bai Z, Li X, Wang J, Li Y (2019) The effectiveness of urinary TIMP-2 and IGFBP-7 in predicting acute kidney injury in critically ill neonates. Pediatr Res 87:1052–1059CrossRefPubMed

18.

Abitbol CL, Moxey-Mims M (2016) Chronic kidney disease: low birth weight and the global burden of kidney disease. Nat Rev Nephrol 12:199–200CrossRefPubMed

19.

Ronco C, Rizo-Topete L, Serrano-Soto M, Kashani K (2017) Pro: prevention of acute kidney injury: time for teamwork and new biomarkers. Nephrol Dial Transplant 32:408–413CrossRefPubMed

20.

Department of Health and Human Services (2014) US Food and Drug Administration. Letter to Astute Medical, Inc

21.

Yang Q-h, Liu D-w, Long Y, Liu H-z, Chai W-z, Wang X-T (2009) Acute renal failure during sepsis: potential role of cell cycle regulation. J Infect 58:459–464CrossRefPubMed

22.

Witzgall R, Brown D, Schwarz C, Bonventre JV (1994) Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Invest 93:2175–2188CrossRefPubMedPubMedCentral

23.

Rodier F, Campisi J, Bhaumik D (2007) Two faces of p53: aging and tumor suppression. Nucleic Acids Res 35:7475–7484CrossRefPubMedPubMedCentral

24.

McMahon KR, Rassekh SR, Schultz KR, Blydt-Hansen T, Cuvelier GDE, Mammen C, Pinsk M, Carleton BC, Tsuyuki RT, Ross CJD, Palijan A, Huynh L, Yordanova M, Crepeau-Hubert F, Wang S, Boyko D, Zappitelli M, Applying Biomarkers to Minimize Long-term Effects of Childhood/Adolescent Cancer Treatment Research Study Group (2020) Epidemiologic characteristics of acute kidney injury during cisplatin infusions in children treated for cancer. JAMA Netw Open 3:e203639CrossRefPubMedPubMedCentral

25.

McMahon KR, Rod Rassekh S, Schultz KR, Pinsk M, Blydt-Hansen T, Mammen C, Tsuyuki RT, Devarajan P, Cuvelier GD, Mitchell LG, Baruchel S, Palijan A, Carleton BC, Ross CJ, Zappitelli M, Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment Research Group (2017) Design and methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) nephrotoxicity study: a prospective observational cohort study. Can J Kidney Health Dis 4:2054358117690338CrossRefPubMedPubMedCentral

26.

McMahon KR, Chui H, Rassekh SR, Schultz KR, Blydt-Hansen TD, Mammen C, Pinsk M, Cuvelier GDE, Carleton BC, Tsuyuki RT, Ross CJD, Devarajan P, Huynh L, Yordanova M, Crepeau-Hubert F, Wang S, Cockovski V, Palijan A, Zappitelli M (2021) Urine neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 to detect pediatric cisplatin-associated acute kidney injury. Kidney 360(3):37–50. https://doi.org/10.34067/KID.0004802021

27.

Dong L, Ma Q, Bennett M, Devarajan P (2017) Urinary biomarkers of cell cycle arrest are delayed predictors of acute kidney injury after pediatric cardiopulmonary bypass. Pediatr Nephrol 32:2351–2360CrossRefPubMedPubMedCentral

28.

Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2:1–138

29.

Motwani SS, McMahon GM, Humphreys BD, Partridge AH, Waikar SS, Curhan GC (2018) Development and validation of a risk prediction model for acute kidney injury after the first course of cisplatin. J Clin Oncol 36:682–688CrossRefPubMedPubMedCentral

30.

(2010) Common terminology criteria for adverse events (CTCAE), Version 4.0. National Institutes of Health National Cancer Institute, pp 1–194

31.

DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845CrossRefPubMed

32.

Bojan M, Pieroni L, Semeraro M, Froissart M (2020) Cell-cycle arrest biomarkers: usefulness for cardiac surgery-related acute kidney injury in neonates and infants. Pediatr Crit Care Med 21:563–570

33.

Parikh CR, Devarajan P, Zappitelli M, Sint K, Thiessen-Philbrook H, Li S, Kim RW, Koyner JL, Coca SG, Edelstein CL, Shlipak MG, Garg AX, Krawczeski CD, TRIBE-AKI Consortium (2011) Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 22:1737–1747CrossRefPubMedPubMedCentral

34.

Parikh CR, Thiessen-Philbrook H, Garg AX, Kadiyala D, Shlipak MG, Koyner JL, Edelstein CL, Devarajan P, Patel UD, Zappitelli M, Krawczeski CD, Passik CS, Coca SG, TRIBE-AKI Consortium (2013) Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol 8:1079–1088CrossRefPubMedPubMedCentral

35.

Zappitelli M, Washburn KK, Arikan AA, Loftis L, Ma Q, Devarajan P, Parikh CR, Goldstein SL (2007) Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care 11:R84CrossRefPubMedPubMedCentral

36.

Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238CrossRefPubMed

37.

Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV (2008) Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 73:863–869CrossRefPubMed

38.

Goldstein SL (2010) Urinary kidney injury biomarkers and urine creatinine normalization: a false premise or not? Kidney Int 78:433–435CrossRefPubMed

39.

Ralib AM, Pickering JW, Shaw GM, Devarajan P, Edelstein CL, Bonventre JV, Endre ZH (2012) Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury. J Am Soc Nephrol 23:322–333CrossRefPubMed

40.

Toprak Z, Cebeci E, Helvaci SA, Toprak ID, Kutlu Y, Sakin A, Tukek T (2017) Cisplatin nephrotoxicity is not detected by urinary cell-cycle arrest biomarkers in lung cancer patients. Int Urol Nephrol 49:1041–1047CrossRefPubMed

41.

Westhoff JH, Tonshoff B, Waldherr S, Poschl J, Teufel U, Westhoff TH, Fichtner A (2015) Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) * insulin-like growth factor-binding protein 7 (IGFBP7) predicts adverse outcome in pediatric acute kidney injury. PLoS One 10:e0143628

42.

Bai Z, Fang F, Xu Z, Lu C, Wang X, Chen J, Pan J, Wang J, Li Y (2018) Serum and urine FGF23 and IGFBP-7 for the prediction of acute kidney injury in critically ill children. BMC Pediatr 18:192CrossRefPubMedPubMedCentral

43.

Gist KM, Goldstein SL, Wrona J, Alten JA, Basu RK, Cooper DS, Soranno DE, Duplantis J, Altmann C, Gao Z, Faubel S (2017) Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery. Pediatr Nephrol 32:1611–1619CrossRefPubMed

44.

Chui H, Caldwell J, Yordanova M, Cockovski V, Fredric D, Harel-Sterling M, Haasz M, Al-Ismaili Z, Pizzi M, Ma Q, Devarajan P, Goldstein SL, Zappitelli M (2020) Tubular injury and cell-cycle arrest biomarkers to predict acute kidney injury in noncritically ill children receiving aminoglycosides. Biomark Med 14:879–894CrossRefPubMedPubMedCentral

Titel: Urinary TIMP-2*IGFBP-7 to diagnose acute kidney injury in children receiving cisplatin
verfasst von: Hayton Chui
Kelly R. McMahon
Shahrad Rod Rassekh
Kirk R. Schultz
Tom D. Blydt-Hansen
Cherry Mammen
Maury Pinsk
Geoffrey D. E. Cuvelier
Bruce C. Carleton
Ross T. Tsuyuki
Colin J. D. Ross
Prasad Devarajan
Louis Huynh
Mariya Yordanova
Frédérik Crépeau-Hubert
Stella Wang
Vedran Cockovski
Ana Palijan
Michael Zappitelli
for the Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Research Study Group
Publikationsdatum: 26.06.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Nephrology / Ausgabe 1/2024
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-023-06007-8

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Urinary TIMP-2*IGFBP-7 to diagnose acute kidney injury in children receiving cisplatin