Urinary Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor–Binding Protein 7 Do Not Correlate With Disease Severity in ADPKD Patients

Abstract

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