Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD Patients
Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and variable renal function decline that frequently leads to end-stage renal failure. With the advent of renoprotective treatment, there is renewed interest in noninvasive biomarkers to...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-06-01
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| Series: | Kidney International Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024919301160 |
| _version_ | 1811278660613701632 |
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| author | Shosha E.I. Dekker L. Renee Ruhaak Fred P.H.T.M. Romijn Esther Meijer Christa M. Cobbaert Johan W. de Fijter Darius Soonawala Joost P.H. Drenth Johan W. de Fijter Ron T. Gansevoort Dorien J.M. Peters Jack F. Wetzels Robert Zietse |
| author_facet | Shosha E.I. Dekker L. Renee Ruhaak Fred P.H.T.M. Romijn Esther Meijer Christa M. Cobbaert Johan W. de Fijter Darius Soonawala Joost P.H. Drenth Johan W. de Fijter Ron T. Gansevoort Dorien J.M. Peters Jack F. Wetzels Robert Zietse |
| author_sort | Shosha E.I. Dekker |
| collection | DOAJ |
| description | Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and variable renal function decline that frequently leads to end-stage renal failure. With the advent of renoprotective treatment, there is renewed interest in noninvasive biomarkers to help identify patients at risk of rapid disease progression at early stages. Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor–binding protein 7 (IGFBP7) have been validated as early markers of acute kidney injury. Because these markers are associated with tubular damage, we studied the performance of both markers in a cohort with chronic tubular pathology. We investigated whether these biomarkers may be useful to evaluate disease severity in ADPKD. Methods: In a cross-sectional analysis, we measured TIMP-2 and IGFBP7 in stored spot urine samples of patients with ADPKD with various stages of chronic kidney disease (CKD) and healthy controls by enzyme-linked immunosorbent assay. Renal function was estimated using the CKD–Epidemiology Collaboration equation. Patients were stratified according to the Kidney Disease Outcomes Quality Initiative classification for CKD. In a subset of patients, total kidney volume (TKV; using magnetic resonance imaging [MRI]) was measured. Results: In 296 patients with ADPKD (45.5 ± 11.5 years, 51.0% female, serum creatinine 106 [85–147] μmol/l), urine levels of TIMP-2 and IGFBP7 were not increased or tended to be lower as compared with 71 healthy controls (46.5 ± 18.5 years, 72.6% female). The levels did not differ across CKD stages, which remained so after correcting for urine creatinine or osmolality, and for age, sex, and urine protein in multivariable analyses. Conclusions: Urinary levels of TIMP-2 and IGFBP7 were not higher in patients with ADPKD, and did not correlate with disease severity. Keywords: ADPKD, chronic renal dysfunction, disease severity, insulin-like growth factor–binding protein 7, tissue inhibitor of metalloproteinases-2, urinary biomarkers |
| first_indexed | 2024-04-13T00:39:44Z |
| format | Article |
| id | doaj.art-6c2b04f4dfb84a14b998680513ff709f |
| institution | Directory Open Access Journal |
| issn | 2468-0249 |
| language | English |
| last_indexed | 2024-04-13T00:39:44Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj.art-6c2b04f4dfb84a14b998680513ff709f2022-12-22T03:10:11ZengElsevierKidney International Reports2468-02492019-06-0146833841Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD PatientsShosha E.I. Dekker0L. Renee Ruhaak1Fred P.H.T.M. Romijn2Esther Meijer3Christa M. Cobbaert4Johan W. de Fijter5Darius Soonawala6Joost P.H. DrenthJohan W. de FijterRon T. GansevoortDorien J.M. PetersJack F. WetzelsRobert ZietseDepartment of Nephrology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Nephrology, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Nephrology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Nephrology, Leiden University Medical Center, Leiden, the Netherlands; Department of Internal Medicine, Haga Teaching Hospital, The Hague, The Netherlands; Correspondence: Darius Soonawala, Department of Nephrology, Leiden University Medical Center (LUMC), P.O. Box 9600, 2300 RC Leiden, the Netherlands.Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation and variable renal function decline that frequently leads to end-stage renal failure. With the advent of renoprotective treatment, there is renewed interest in noninvasive biomarkers to help identify patients at risk of rapid disease progression at early stages. Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor–binding protein 7 (IGFBP7) have been validated as early markers of acute kidney injury. Because these markers are associated with tubular damage, we studied the performance of both markers in a cohort with chronic tubular pathology. We investigated whether these biomarkers may be useful to evaluate disease severity in ADPKD. Methods: In a cross-sectional analysis, we measured TIMP-2 and IGFBP7 in stored spot urine samples of patients with ADPKD with various stages of chronic kidney disease (CKD) and healthy controls by enzyme-linked immunosorbent assay. Renal function was estimated using the CKD–Epidemiology Collaboration equation. Patients were stratified according to the Kidney Disease Outcomes Quality Initiative classification for CKD. In a subset of patients, total kidney volume (TKV; using magnetic resonance imaging [MRI]) was measured. Results: In 296 patients with ADPKD (45.5 ± 11.5 years, 51.0% female, serum creatinine 106 [85–147] μmol/l), urine levels of TIMP-2 and IGFBP7 were not increased or tended to be lower as compared with 71 healthy controls (46.5 ± 18.5 years, 72.6% female). The levels did not differ across CKD stages, which remained so after correcting for urine creatinine or osmolality, and for age, sex, and urine protein in multivariable analyses. Conclusions: Urinary levels of TIMP-2 and IGFBP7 were not higher in patients with ADPKD, and did not correlate with disease severity. Keywords: ADPKD, chronic renal dysfunction, disease severity, insulin-like growth factor–binding protein 7, tissue inhibitor of metalloproteinases-2, urinary biomarkershttp://www.sciencedirect.com/science/article/pii/S2468024919301160 |
| spellingShingle | Shosha E.I. Dekker L. Renee Ruhaak Fred P.H.T.M. Romijn Esther Meijer Christa M. Cobbaert Johan W. de Fijter Darius Soonawala Joost P.H. Drenth Johan W. de Fijter Ron T. Gansevoort Dorien J.M. Peters Jack F. Wetzels Robert Zietse Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD Patients Kidney International Reports |
| title | Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD Patients |
| title_full | Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD Patients |
| title_fullStr | Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD Patients |
| title_full_unstemmed | Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD Patients |
| title_short | Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD Patients |
| title_sort | urinary tissue inhibitor of metalloproteinases 2 and insulin like growth factor binding protein 7 do not correlate with disease severity in adpkd patients |
| url | http://www.sciencedirect.com/science/article/pii/S2468024919301160 |
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