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Urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor–binding protein 7 do not correlate with disease severity in ADPKD patients
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 per-
formance 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 pa-
tients with ADPKD with various stages of chronic kidney disease ...Show moreIntroduction: 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 per-
formance 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 pa-
tients 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] mmol/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.
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- All authors
- Dekker, S.E.I.; Ruhaak, L.R.; Romijn, F.P.H.T.M.; Meijer, E.; Cobbaert, C.M.; Fijter, J.W. de; Soonawala, D.; DIPAK Consortium
- Date
- 2019-06-01
- Journal
- Kidney International Reports
- Volume
- 4
- Issue
- 6
- Pages
- 833 - 841