MO029: Urinary biomarkers in the progression of autosomal dominant polycystic kidney disease

Abstract

Abstract BACKGROUND AND AIMS Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease characterized by the formation and growth of renal cysts, affecting the decrease of renal function, which may lead to end-stage renal disease (ESRD). Due to the enormous intrafamilial phenotypic variability of ADPKD and since serum creatinine and glomerular filtration rate (GFR) have a limited ability to assess the disease and predict its progression at earlier stages, there is a need to find new biomarkers to predict disease progression. The α-glutathione s-transferase (GST-α) and haptoglobin (Hp) are produced mainly by the proximal convoluted tubule, and these enzymes are released into the urinary lumen in direct response to tubular damage. This study aims to evaluate the urine concentration of α-GST and Hp biomarkers at different stages of ADPKD progression and correlate the levels of urinary biomarkers α-GST and Hp with traditional markers of renal dysfunction. METHOD Twenty-five patients with ADPKD, mean age of 41.57 ± 14.43 years, mostly female (56.0%), diagnosed according to the Ravine criteria and with a follow-up of at least 60 months. Demographic, hemodynamic, urinary creatinine (UCr) and serum creatinine (SCr) data were collected in baseline (T0) and at the end of the follow-up period (T1). GFR was determined using the CKD-EPI formula, grouping patients into early stages (CKD1 and CKD2) and advanced stages (CKD3 to CKD5). Biomarkers were determined by the ELISA method and indexed to UCr in T1. In addition, α-GST was determinate in a control sample composed of 17 individuals without diagnosed kidney disease. Statistical analysis was performed by SPSS version 26 with a significant value of P < 0.05. RESULTS Comparing the means of SCr and GFR between T0 and T1 were observed a decrease of renal function during the follow-up period (P = 0.013 and P = .017, respectively). About 14.4% of patients were in an advanced stage of kidney disease in T1, compared with 4.8% in T0. ADPKD patients had increased values of α-GST in relation to the control group (P < 0.001), but no difference in the SCr was found. We also found a trend for higher levels of HP in advanced stages of CKD (P = 0.071). In ADPKD patients, direct correlations were observed between the variation of SCr during the follow-up with α-GST and Hp (r = 0.606, P = 0.048 and r = 0.738, P = 0.037, respectively). A trend to correlation was found between the levels of Hp and the Scr in T1 (r = P = 0.058). CONCLUSION The levels of α-GST and Hp are associated with renal damage and may be helpful in the early identification of the decline in renal function in ADPKD patients.